FitSugar

Know Your A, B, C's: Vitamin K

FitSugar — Tue, 13 Mar 2007 03:00:00 -0700

For a long time I was confused about Vitamin K - particularly its relationship to Special K the cereal. Plus, I wasn't really sure what the vitamin did for the human body. Basically I thought vitamins stopped at the letter E, so this one sounded fake. Then I had a baby and two seconds after she came out, she got a shot of vitamin K in her tiny little heel. OUCH!!!!
So I did some research; I wanted to know why the nice nurse was poking my baby with a needle so early in her little newborn life. I found out that Vitamin K is all about the blood, you need the vitamin to make clots. It is called Vitamin K since coagulation starts with a K in German (and maybe just because the name "Vitamin C" was already taken). It is given (how is that for a euphemism for injection?) to newborns to prevent bleeding problems related to birth trauma. Some folks also take it before surgery for the same reasons.

Another thing to note, Vitamin K is a fat soluble vitamin, so your body can store it in your fat. This is one reason why vitamin K deficiency is rare. Deficiency mainly occurs when the body can't properly absorb the vitamins from the intestinal tract, or from long term antibiotics use. The antibiotics kill the good bacteria (flora) that produce Vitamin K.

Vitamin K is abundant in leafy green vegetables such as spinach and lettuce, as well as kale, cabbage, cauliflower, broccoli, and brussel sprouts. It is also found in wheat bran (eat those whole grains), cereals (so maybe there is some Special K connection), cow's milk and other dairy products. The RDA for vitamin K for an adult woman is between 60 and 65 micrograms a day. Two tablespoons of parsley contains 153% of the recommended daily amount of Vitamin K.

Stroke

FitSugar — Wed, 08 Oct 2008 17:35:08 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Statin Drug Approved for Stroke Prevention

In 2007, the FDA approved the cholesterol drug atorvastatin (Lipitor) to reduce the risk of stroke in patients with heart disease.
High-dose atorvastatin may help reduce the risk of recurrent stroke in patients who have had a recent stroke or transient ischemic attack, according to a New England Journal of Medicine study.

Drug Warnings

In 2006, the FDA strengthened the warning label for the anticoagulant drug warfarin (Coumadin) to emphasize its bleeding risks. However, warfarin is still the gold standard treatment for most patients with atrial fibrillation.
Evidence suggests that people at risk for stroke should avoid taking non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil) and diclofenac (Cataflam). COX-2 inhibitors should only be used as a last resort for pain relief. Try non-drug treatments (physical therapy, hot/cold compresses) first.

Aspirin

In 2007, the American Heart Association (AHA) issued new heart disease prevention guidelines for women. The AHA recommends low-dose aspirin therapy for women over age 65 who are at risk for stroke.
The combination of aspirin and dipyridamole (Aggrenox) may be better than aspirin alone in preventing major stroke in patients who have had a minor stroke, suggests a Lancet study.

Diagnosis

Magnetic resonance imaging (MRI) is better than computed tomography (CT) in detecting whether stroke (especially ischemic stroke) has occurred, indicates an important Lancet study.

Surgery

Carotid endarterectomy appears to be superior to and safer than carotid angioplasty and stenting (CAS) for most patients with artery stenosis (narrowing) of over 60%, suggest several recent studies. Most experts recommend CAS only for patients who have severe stenosis (greater than 70%) and high surgical risk.

Rehabilitation

Constraint-induced movement therapy (CIMT) may help patients who have recently had a stroke regain use of a paralyzed arm. The technique involves repetitive motion exercises while restraining the less functional arm.

Introduction

Blood Flow Blockage. The brain receives about 25% of the body's oxygen, but it cannot store it. Brain cells require a constant supply of oxygen to stay healthy and function properly. Therefore, blood needs to be supplied continuously to the brain through two main arterial systems:

The carotid arteries come up through either side of the front of the neck. (To feel the pulse of a carotid artery, place your fingertips gently against either side of your neck, right under the jaw.)
The basilar artery forms at the base of the skull from the vertebral arteries, which run up along the spine, join, and come up through the rear of the neck.

The Circle of Willis is the joining area of several arteries at the bottom (inferior) side of the brain. At the Circle of Willis, the internal carotid arteries branch into smaller arteries that supply oxygenated blood to over 80% of the cerebrum.

A reduction of, or disruption in, blood flow to the brain is the primary cause of a stroke. Blockage for even a short period of time can be disastrous and cause brain damage or even death.

Click the icon to see an image of the brain.

A stroke is usually defined as two types:

Ischemic (caused by a blockage in an artery)
Hemorrhagic (caused by a tear in the artery's wall that produces bleeding in the brain)

The consequences of a stroke, the type of functions affected, and the severity, depend on where in the brain it has occurred and the extent of the damage.

Ischemic strokes are by far the more common type, causing over 80% of all strokes. Ischemia means the deficiency of oxygen in vital tissues. Ischemic strokes are caused by blood clots that are usually one of three types:

Thrombotic stroke
Embolic stroke
Lacunar stroke

Thrombotic or Large-Artery Stroke and Atherosclerosis. The thrombotic stroke accounts for about 60% of all strokes. It usually occurs when an artery to the brain is blocked by a thrombus (blood clot) that forms as the result of atherosclerosis (commonly known as hardening of the arteries). These strokes are also sometimes referred to as large-artery strokes. The process leading to thrombotic stroke is complex and occurs over time:

The arterial walls slowly thicken, harden, and narrow until blood flow is reduced, a condition known as stenosis.
These now abnormal arteries become vulnerable to injury. Such injuries signal the immune system to release white blood cells (particularly those called neutrophils and macrophages) at the site. This process is the first step in the inflammatory response, which may play a significant role in the stroke.
Macrophages literally "eat" foreign debris and become foamy cells that attach to smooth muscle cells of blood vessels, causing them to build up.
The immune system, sensing further harm, releases other factors called cytokines, which attract more white blood cells and perpetuate the whole cycle.

As these processes continue, blood flow slows. In addition, other events contribute to the coming stroke:

The injured inner walls fail to produce enough nitric oxide, a substance critical for maintaining blood vessel elasticity. The arteries become calcified and lose elasticity.
The arteries, now hardened and rigid, become susceptible to tearing. In this event, the thrombus (blood clot) forms.
The blood clot then blocks the already narrowed artery and shuts off oxygen to part of the brain. A stroke occurs.

Embolic Strokes and Atrial Fibrillation. An embolic stroke is usually caused by a dislodged blood clot that has traveled through the blood vessels (an embolus) until it becomes wedged in an artery. Embolic strokes account for about 25% of all strokes and may be due to various conditions:

In about 15% of embolic strokes, the blood clots originally form as a result of a rhythm disorder known as atrial fibrillation. This abnormal rhythm is a rapid quivering beat in the upper chambers of the heart (the atria). Because of the irregular pumping, some blood may remain in the heart chamber where it forms clots, which can then break off and travel to the brain as emboli.
Emboli can originate from blood clots that form at the site of artificial heart valves or as a result of heart valve disorders.
Emboli can also occur after a heart attack or in association with heart failure.
Rarely, emboli are formed from fat particles, tumor cells, or air bubbles that travel through the bloodstream.

Lacunar Strokes. Lacunar infarcts are a series of very tiny, ischemic strokes, which cause clumsiness, weakness, and emotional variability. They are actually a subtype of thrombotic stroke and constitute about 38% of this major group. In some populations, such as among Japanese, they are the most common stroke subtypes. They can also sometimes serve as warning signs for a major stroke.

Silent Brain Infarctions. Many elderly people have silent brain infarctions, small strokes that cause no apparent symptoms. They are detected in between 10 - 38% of elderly patients who undergo imaging tests for problems other than stroke. A 2002 study suggested that they double the risk for future stroke. They also may be major contributors to mental impairment in the elderly. Smokers and people with hypertension are at particular risk.

Transient ischemic attacks (TIAs) are mini-ischemic strokes, usually caused by tiny emboli (clots often formed of pieces of calcium and fatty plaque) that lodge in an artery to the brain. They typically break up quickly and dissolve but they do temporarily block the supply of blood to the brain. The mental or physical disturbances resulting from TIAs generally clear up in less than a day, with nearly all symptoms resolving in less than an hour.

However, experts now advise that a TIA should be taken very seriously and treated as aggressively as a stroke. Both stroke and TIA increase the risk for a subsequent stroke. Moreover, the risk for having another stroke can be as high as 40% within 5 years. The American Heart Association/American Stroke Association recommends these guidelines to prevent a second stroke after TIA:

Lifestyle changes.

Stop smoking
Limit alcohol
Increase exercise (30 minutes a day of moderate physical activity)
Lose excess weight (waist measurements should be no more than 35 inches for women and 40 inches for men; body mass index should be 18.5 - 24.9)

Drug treatments.

Drugs to control cholesterol, high blood pressure, and (for people with diabetes) high blood sugar levels
Antiplatelet therapy such aspirin, dipyridamole, or clopidogrel)

Surgery.

Carotid endarterectomy surgery or carotid artery stenting is recommended for patients with severe (70% or more) carotid stenosis (narrowing or blockage of one or both arteries in the neck)
Endarterectomy or stenting may also be appropriate for some patients with moderate stenosis (50 - 69%)
Endarterectomy and stents are not needed for patients with mild stenosis (less than 50%)

Over 15% of strokes occur from hemorrhage (sudden bleeding) in the brain. In a healthy brain, brain cells called neurons are protected from exposure to blood by the blood-brain barrier, a wall of tiny vessels and structural cells. In a hemorrhagic stroke, however, this barrier is broken.

Hemorrhagic strokes may be categorized by how and where they occur.

Parenchymal, or cerebral, hemorrhage strokes. These strokes occur within the brain and account for about 10% of all strokes. They are most often the result of hypertension exerting excessive pressure on arterial walls already damaged by atherosclerosis. Heart attack patients who have been given drugs to break up blood clots or blood-thinning drugs have a slightly elevated risk of this type of stroke.
Subarachnoid hemorrhagic strokes. This other major hemorrhagic stroke accounts for about 5% of all strokes. This kind of stroke occurs when a blood vessel on the surface of the brain bursts, leakign blood into the subarachnoid space, an area between the brain and the skull. They are usually caused by the rupture of an aneurysm, a weakening in the blood vessel wall, which is often an inherited trait.
Arteriovenous malformation (AVM) is an abnormal connection between arteries and veins. If it occurs in the brain and ruptures, it can also cause a hemorrhagic stroke.

Symptoms

People at risk and partners or caretakers of people at risk for stroke should be aware of the general symptoms. The stroke victim should get to the hospital as soon as possible after these warning signs appear. It is particularly important for people with migraines or frequent severe headaches to understand how to distinguish between their usual headaches and symptoms of stroke.

The American Stroke Association lists the following five warning signs of stroke. PEOPLE SHOULD IMMEDIATELY CALL FOR EMERGENCY ASSISTANCE IF THEY EXPERIENCE ANY OF THESE SYMPTOMS:

Sudden numbness or weakness of the face, arm or leg, especially on one side of the body
Sudden confusion, trouble speaking or understanding
Sudden trouble seeing in one or both eyes
Sudden trouble walking, dizziness, loss of balance or coordination
Sudden, severe headache with no known cause

Research indicates that patients receive faster treatment for stroke if they arrive by ambulance rather than coming to the emergency room on their own.

An easy way to remember the signs of stroke, and what to do, is by the acronym "F.A.S.T." If you think you or someone else is having a stroke, the National Stroke Association's F.A.S.T. test advises:

(F)ACE. Ask the person to smile. Check to see if one side of the face droops.
(A)RMS. Ask the person to raise both arms. See if one arm drifts downward.
(S)PEECH. Ask the person to repeat a simple sentence. Check to see if words are slurred and if the sentence is repeated correctly.
(T)IME. If a person shows any of these symptoms, time is essential. It is important to get to the hospital as quickly as possible. Call 9-1-1. Act FAST.

The symptoms of a transient ischemic attack (TIA) and early ischemic stroke are similar. In the case of a TIA, however, the symptoms should resolve within 24 hours. Symptoms depend on where the injury in the brain occurs. The origin of the stroke is usually either the carotid or basilar arteries.

The build-up of plaque in the internal carotid artery may lead to narrowing and irregularity of the artery's lumen, preventing proper blood flow to the brain. More commonly, as the narrowing worsens, pieces of plaque in the internal carotid artery can break free, travel to the brain, and block blood vessels that supply blood to the brain. This leads to stroke, with possible paralysis or other deficits.

Symptoms From Blockage in the Carotid Arteries. The carotid arteries stem off of the aorta (the primary artery leading from the heart) and lead up through the neck around the windpipe and on into the brain. When TIAs or stroke occur from blockage in the carotid artery, which they often do, symptoms may occur in either the retina of the eye or the cerebral hemisphere (the large top part of the brain).

Symptoms include the following:

When oxygen to the eye is reduced, people describe the visual effect as a shade being pulled down. People may develop poor night vision. About 35% of TIAs are associated with temporary lost vision in one eye. Although such events are risk factors for future stroke, they pose a lower risk for a stroke and its complications than more widespread TIA symptoms.
When the cerebral hemisphere is affected, a person can experience problems with speech and partial and temporary paralysis, drooping eyelid, tingling, and numbness, usually on one side of the body. The stroke victim may be unable to express thoughts verbally or to understand spoken words. If the stroke injuries are on the right side of the brain, the symptoms will develop on the left side of the body and vice versa.
Uncommonly, patients may experience seizures.

Symptoms From Blockage in the Basilar Artery. The other major site of trouble, the basilar artery, is formed at the base of the skull from the vertebral arteries, which run up along the spine and join at the back of the head. When stroke or TIAs occur here, both hemispheres of the brain may be affected so that symptoms occur on both sides of the body. The following symptoms may develop:

Temporarily dim, gray, blurry, or lost vision
Tingling or numbness in the mouth, cheeks, or gums
Headache, usually in the back of the head
Dizziness
Nausea and vomiting
Difficulty swallowing
Weakness in the arms and legs, sometimes causing a sudden fall

Such strokes usually occur in the brain stem, which can have profound affects on breathing, blood pressure, heart rate, and other vital functions, but does not affect thinking or language.

Speed of Symptom Onset. The speed of symptom onset of a major ischemic stroke may indicate its source:

If the stroke is caused by a large embolus (a clot that has traveled to an artery in the brain), the onset is sudden. Headache and seizures can occur within seconds of the blockage.
When thrombosis (a blood clot that has formed within the brain) causes the stroke, the onset usually occurs more gradually, over minutes to hours. On rare occasions it progresses over days to weeks.

Click the icon to see an image of carotid dissection.

Click the icon to see an image of stroke.

Cerebral Hemorrhage Symptoms. Symptoms of a cerebral, or parenchymal, hemorrhage typically begin very suddenly and evolve over several hours and include:

Headache
Nausea and vomiting
Altered mental states
Seizures

Subarachnoid Hemorrhage. When the hemorrhage is a subarachnoid type, warning signs may occur from the leaky blood vessel a few days to a month before the aneurysm fully develops and ruptures. Warning signs may include:

Abrupt headaches
Nausea and vomiting
Sensitivity to light
Various neurologic abnormalities. Seizures, for example, occur in about 8% of patients.

When the aneurysm ruptures, the stroke victim may experience:

A terrible headache
Neck stiffness
Vomiting
Altered states of consciousness
Eyes may become fixed in one direction or lose vision
Stupor, rigidity, and coma

Risk Factors

New or recurrent strokes affect about 700,000 Americans every year. Although incidence of stroke has increased, more people are surviving stroke, and the death rate is declining. While age is the major risk factor, people with stroke are likely to have more than one risk factor.

Older Adults. People most at risk for stroke are older adults, particularly those with high blood pressure, who are sedentary, overweight, smoke, or have diabetes. Older age is also linked with higher rates of post-stroke dementia.

Younger Adults. Younger people are not immune, however. About 28% of stroke victims are under age 65.

In most age groups except older adults, stroke is more common in men than in women. However, it kills more women than men, regardless of ethnic groups. It is not clear why women have a higher mortality rate from stroke. The arteries that lead to the brain may be more vulnerable to the effects of plaque build-up in women than in men.

In 2007, the American Heart Association released new heart disease prevention guidelines for women. The new guidelines recommend daily aspirin therapy (75 - 325 mg/day) to help prevent stroke in high-risk women over the age of 65. For older women with a lower stroke risk, the AHA recommends 81 mg of aspirin a day or 100 mg of aspirin every other day. Aspirin does not appear to provide much stroke protection benefit for women under the age of 65.

All minority groups, including Native Americans, Hispanics, and African-Americans, face a significantly higher risk for stroke and stroke death than Caucasians. The risk is also higher in Asian Americans, although stroke rates appear to be declining in this group. The differences in risk among all groups diminish as people age.

The greatest disparity in risk occurs in young adults. Younger African-Americans are two to three times more likely to experience a stroke than their Caucasian peers and four times more likely to die from one. They also face a higher risk for death from heart disease. African-Americans have a higher prevalence of diabetes and hypertension than other groups. However, studies suggest that socioeconomic factors also affect these differences.

People in the southeastern U.S. have had the highest risk for stroke in the country for some years; those at particular risk live in North Carolina, South Carolina, and Georgia. This risk may be shifting westward. High stroke rates are also occurring in the lower Mississippi valley and in Southern California. Socioeconomic differences do not fully explain these higher-risk areas.

Heart disease and stroke are closely tied for many reasons:

Patients with one condition often have risk factors for the other, such as high blood pressure, atherosclerosis (hardening of the arteries), and diabetes.
The risk of stroke increases during surgical procedures involving the coronary arteries, including coronary bypass operations and angioplasty. Coronary bypass poses the greater risk -- about 2 - 5%.
Anti-clotting drugs used for treatment of heart disease and heart attacks slightly increase the risk for hemorrhagic stroke.
A heart attack itself poses a high risk for stroke, which, according to a major 2002 study, is 2.5% in the first 6 months and 5% per year thereafter. In the study, patients with a higher risk (about 4%) for stroke within 6 months of a heart attack tended to be older (over age 75), African-American, or to have a history of a previous stroke, atrial fibrillation, hypertension, diabetes, or peripheral artery disease. Most people at high risk have more than one of these problems.

High Blood Pressure (Hypertension). High blood pressure (known medically as hypertension ) contributes to 70% of all strokes. Researchers have estimated that controlling blood pressure can prevent nearly 40% of strokes.

Two numbers are used to describe blood pressure phases and may affect stroke risk separately:

The systolic pressure (the higher and first number) is measured as the heart contracts to pump out the blood. Evidence suggests that elevated systolic pressure poses a significant danger for heart and stroke emergencies when diastolic is normal, a condition called isolated systolic hypertension. The wider the spread between the systolic and diastolic measurements, the greater the danger.
The diastolic pressure (the lower and second number) is measured as the heart relaxes to allow blood to refill the heart between beats. Abnormally higher diastolic pressure is a strong predictor of heart attack and stroke in most people with hypertension.
Stroke from Low Blood Pressure (Hypotension). Uncommonly, blood pressure that is too low can reduce oxygen supply to the brain and cause a stroke. This can occur from a heart attack, a major bleeding episode, an overwhelming infection, or rarely, from surgical anesthesia or from over-treatment of high blood pressure.

Hypertension is a disorder characterized by chronically high blood pressure. It must be monitored, treated, and controlled by medication, lifestyle changes, or a combination of both.

Click the icon to see an image of the risks of untreated hypertension.

Atrial Fibrillation. About one in six strokes are due to atrial fibrillation. This is a heart rhythm disorder in which the atria (the upper chambers in the heart) beat very quickly and nonrhythmically. The blood pools instead of being pumped out, increasing the risk for formation of blood clots that break loose and travel toward the brain. Atrial fibrillation poses a six-fold increased risk for stroke and may also pose a higher risk for complications after a stroke.

Atrial fibrillation is uncommon in people under 60 years old, but about 6% of adults over age 80 have this heart rhythm disorder. In this patient group, the risk for stroke may be higher or lower with the presence of other risk factors, including having heart failure, high blood pressure, diabetes, and a previous history of stroke, TIA, or rheumatic heart disease. More women than men have AF, but risk for stroke is higher in women with this condition than in men.

Patent Foramen Ovale. Patent foramen ovale (PFO) is a flap-like opening between chambers of the heart. The foramen ovale is always open during fetal development to enhance blood flow to the fetus. It then typically closes after birth when the lungs take over. However, evidence suggests that it remains open in up to 30% of adults. In such cases, blood moves backward (right to left) through this opening when pressure in the right chamber exceeds the left. Large PFOs are a major cause of stroke, particularly in younger adults. Treatments include anti-clotting drugs and procedures for closing the opening.

Atrial Septal Aneurysm. Atrial septal aneurysm is an inborn condition in which part of the atrium (one of the heart chambers) bulges out. Studies indicate that this may pose a slight risk for stroke in young people.

People who smoke a pack a day have almost two and a half times the risk for stroke as nonsmokers. Smoking increases both hemorrhagic and ischemic stroke risk. The risk for stroke may remain elevated for as long as 14 years after quitting, so the earlier one quits the better.

Heart disease and stroke are the leading causes of death in people with diabetes. Diabetes is a strong risk factor for ischemic stroke, perhaps because of accompanying risk factors, such as obesity and high blood pressure. Diabetes does not appear to increase the risk for hemorrhagic stroke. Diabetes is second only to high blood pressure as the main risk factor for stroke. The risk is highest for adults newly diagnosed with type 2 diabetes and patients with diabetes who are younger than age 55. African-Americans with diabetes are at even higher risk for stroke at a younger age.

Studies have also implicated insulin resistance, an important disease mechanism in type 2 diabetes, as an independent factor in the development of atherosclerosis and stroke. With this condition, insulin levels are normal to high, but the body is unable to use the insulin normally to metabolize blood sugar. The body compensates by raising the level of insulin, which in turn increases the risk for blood clots and reduces HDL levels (the beneficial form of cholesterol). Some studies have also reported a worse outcome in patients whose blood sugar levels are high at the time of a stroke.

Obesity may increase the risk for both ischemic and hemorrhagic stroke independently of other risk factors that often co-exist with excess weight, including insulin resistance and diabetes, high blood pressure, and unhealthy cholesterol level. Weight that is centered around the abdomen (the so-called apple shape) has a particularly high association with stroke, as it does for heart disease, in comparison to weight distributed around hips (pear-shape).

Obesity is particularly hazardous when it is one of the components of metabolic syndrome. This syndrome is diagnosed when three of the following conditions are present: abdominal obesity, low HDL cholesterol, high triglyceride levels, high blood pressure, and insulin resistance. Because metabolic syndrome is a pre-diabetic condition that is significantly associated with heart disease, people with this syndrome are at increased risk for stroke even before diabetes develops.

Although an unhealthy balance of cholesterol and other lipids (fatty compounds) plays a major role in heart disease, its role in stroke is less clear. Different lipids may have different effects:

Ischemic Stroke. The effects of high total cholesterol and LDL levels on stroke are not clear. One study suggested that the risk for ischemic stroke increases when total cholesterol is above 280 mg/dL. HDL (the so-called good cholesterol) may protect against ischemic stroke (although statins have little effect on HDL).

Hemorrhagic Stroke. HDL may reduce the risk for hemorrhagic stroke (bleeding in the brain). People with overall cholesterol levels below 180 mg/dL, however, may be at risk for hemorrhagic stroke, particularly if they also have high blood pressure. This is a far less common stroke, however, than ischemic stroke.

In any case, reducing cholesterol is extremely important in anyone with heart disease and abnormal lipid levels.

Genetics may be responsible for many of the causes of stroke. Studies indicate that a family history of stroke, particularly in one's father, is a strong risk factor for stroke.

Genetics and Subarachnoid Hemorrhage. Genetic factors account for between 7 - 20% of cases of subarachnoid hemorrhage. Ruptured aneurysms that occur in such patients tend to happen at an earlier age, are usually smaller, and are more apt to recur than in those without an inherited condition. A study of people who had suffered subarachnoid hemorrhages found that first-degree relatives of these stroke victims had a high lifetime risk of between 2 - 5%. Some experts recommend screening for aneurysms in people with more than one close relative who suffered a hemorrhagic stroke.

Inherited Disorders that Contribute to Stroke. Some cases of atrial fibrillation may be inherited. Genetic disorders that cause connective tissue disorders are also associated with stroke from hemorrhage; they include polycystic kidney disease, Ehlers-Danlos syndrome type IV, neurofibromatosis type 1, Marfan's syndrome, and moyamoya disease.

Specific Genetic Factors Under Investigation. Specific genetic factors are under investigation. They include:

Inherited deficiencies in protein factors C and S, which inhibit blood clotting, may be responsible for certain cases of stroke in young adults.
A genetic mutation in a factor V Leiden may be related to blood clotting risks.
People who have inherited a gene called apolipoprotein (Apo) E-4 may be at increased risk of stroke. This gene is also associated with Alzheimer's disease.

Stress. One survey revealed that men who had a more intense response to stressful situations, such as waiting in line or problems at work, were more likely to have strokes than those who did not report such distress. In some people, prolonged or frequent mental stress causes an exaggerated increase in blood pressure, which in turn can increase the risk for stroke.

Depression. Depression has also been linked to higher risk for stroke and lower stroke survival rates. In one study, patients with severe depression had a 73% higher risk for stroke, and those with moderate depression had a 25% higher risk than average. The risk for stroke in African-Americans with depression was 160% higher than average.

Studies indicate that migraine or severe headache may be a risk factor for stroke in both men and women, especially before age 50. Overall, between 2 - 3% of ischemic strokes occur in people with a history of migraine. However, in patients under age 45, about 15% of all strokes (and 30 - 60% of strokes in young women) are associated with a history of migraines, particularly migraine with aura. Some evidence suggests that some strokes in these cases may be due to excessive activation of the nervous system and the dehydration from vomiting that occurs during a severe migraine with aura.

The actual risk itself for migraineurs is low, however. In one study, women with migraines had a 2.7% risk of stroke, with the greatest risk between the ages of 45 - 65. Studies suggest specific risk factors for younger women with migraines, particularly those with auras, include taking high-estrogen oral contraceptives (OCs). (Whether progesterone-alone contraceptives carry any risk is unknown.) In migraineurs who take OCs, the risk increases with high blood pressure, smoking, or both.

Inflammation that occurs with various infections has been associated with stroke. One study found that patients hospitalized for stroke were three times more likely than patients without strokes to have recently been exposed to infections, usually mild ones in the respiratory tract.

Varicella Virus. Varicella zoster virus (the virus that causes chicken pox and shingles) has been associated with cerebral vasculitis, a condition in which blood vessels in the brain become inflamed. It is a very rare cause of stroke in children. The virus has also been associated with some cases of stroke in young adults.

Chlamydia Pneumonia. Some investigators suspect that some infections may produce inflammation in the arteries that can lead to stroke over time. (Similar work is underway in heart disease.) Researchers are particularly interested in Chlamydia pneumoniae, a non-bacterial organism that causes mild pneumonia in adults. Chronic infection has been linked with a higher risk for stroke, and evidence of the organism has been observed in thickened inner vessel walls of the carotid arteries in some studies. Chlamydia has also been linked to heart disease.

Periodontal Disease. A number of studies now strongly support an association between periodontal disease and cardiovascular disorders. According to a major analysis, periodontal (gum) disease is associated with a 20% higher risk for ischemic stroke and heart disease. The added risk may be even greater in adults under 65. Recent evidence points to the inflammatory response as the common element.

In 2007, the American Heart Association (AHA) issued a scientific statement encouraging doctors to change the way they prescribe pain relief medication for patients at risk for heart disease or stroke. The AHA recommends that at-risk patients first try non-drug methods of pain relief (physical therapy, exercise, weight loss to reduce stress on joints, and heat or cold therapy). If these methods don’t work, patients should take the lowest possible dose of acetaminophen (Tylenol) or aspirin. COX-2 inhibitors, such as celecoxib (Celebrex), should be the last resort.

In 2005, the FDA warned that all NSAIDs -- with the exception of aspirin -- carry heart risks. In particular, the NSAIDs ibuprofen (Advil, Motrin) and diclofenac (Cataflam, Voltaren) appear to carry increased risks for heart attack and stroke.

A number of medical or physical conditions may contribute to the risk for stroke:

Sleep apnea. This common disorder, in which the throat becomes obstructed during sleep, may contribute to the narrowing of the carotid artery, appearing to increase the risk for stroke three- to six-fold.
Pregnancy. Pregnancy carries a very small risk for stroke, mostly in women with pregnancy related high blood pressure and in those with cesarean delivery. The risk appears to be higher in the postpartum (post-delivery) period, perhaps because of the sudden change in circulation and hormone levels.
Anti-phospholipid antibodies. Nearly 40% of young people with strokes and 10% of all stroke patients have components of the immune system known as anti-phospholipid antibodies that increase the chance for blood clots.
Sickle-cell anemia. People with sickle-cell anemia are at risk for stroke at a young age.
Drug abuse, particularly with cocaine and, increasingly, methamphetamine, is a major factor in the incidence of stroke in young adults. Anabolic steroids, used for body-building and sports enhancement, also increase risk.

Timing. Like heart attack and sudden cardiac death, stroke appears to be more common in the morning hours, perhaps due to a temporary rise in blood pressure at that time. Various studies point to a higher risk for stroke on weekends, Mondays, and holidays. The risk for hemorrhagic stroke may also be higher in the winter, particularly in older people with high blood pressure.

Homocysteine and Vitamin B Deficiencies. Abnormally high blood levels of the amino acid homocysteine, which occur with deficiencies of vitamin B6, B12, and folic acid, may be linked to an increased risk of coronary artery disease and stroke.

Neck Manipulation. Some studies have reported a higher risk for stroke from injury to the carotid artery after neck manipulation by a chiropractor.

Prognosis

A stroke, the third leading cause of death in the U.S., is always serious. In 2004, over 150,000 Americans died of stroke with women accounting for 61% of these stroke deaths. The mortality rates are declining, however. Over 75% of patients survive a first stroke during the first year, and over half survive beyond 5 years.

People who suffer ischemic strokes have a much better chance for survival than those who experience hemorrhagic strokes. Among the ischemic stroke categories, the greatest dangers are posed by embolic strokes, followed by thrombotic and lacunar strokes. Hemorrhagic stroke not only destroys brain cells but also poses other complications, including increased pressure on the brain or spasms in the blood vessels, both of which can be very dangerous. Studies suggest, however, that survivors of hemorrhagic stroke have a greater chance for recovering function than those who suffer ischemic stroke.

Between 50 - 70% of people recover functional independence after a stroke. However, between 15 - 30% of those who survive either an ischemic or hemorrhage stroke suffer some permanent disability. On the encouraging side, one study reported that people who survived for many years after a stroke had a chance for independent living that was about the same as for their peers who had not suffered strokes. The stroke patients even appeared to be less depressed than the comparison group.

The National Institutes of Health (NIH) have devised a scoring system that helps predict the severity and outcome of the stroke by scoring 11 factors (levels of consciousness, gaze, visual fields, facial movement, motor functions in the arm and leg, coordination, sensory loss, problems with language, inability to articulate, and attention). Up to 70% of patients with ischemic strokes who score less than 10 have a favorable outlook after a year, while only 4 - 16% of patients do well if their score is more than 20.

The risk for recurring stroke is highest within the first few weeks and months. The risk is about 14% in the first year and about 5% thereafter, so preventive measures should be instituted as soon as possible. Some specific risk factors for early recurrence include:

Older age
Evidence of blocked arteries (a history of coronary artery disease, peripheral artery disease, ischemic stroke, or TIA)
Hemorrhagic or embolic stroke
Diabetes
Alcoholism
Valvular heart disease
Atrial fibrillation

Prevention

Forty percent of patients who have had a stroke or TIA will suffer a subsequent stroke within 5 years. In 2006, the American Heart Association/American Stroke Association released guidelines for preventing a second stroke. These guidelines recommend:

Quit Smoking. Also avoid exposure to second-hand smoke.

Maintain Weight. People should aim for a BMI index of 18.5 - 24.9. In people who are obese, reducing weight to this level can reduce the risk for stroke by 15% in men and 22% in women. Waist measurements should be no more than 35 inches for women and 40 inches for men.

Exercise. Everyone in normal health should engage in at least moderate physical activity for a minimum of 30 minutes on most -- if not all -- days of the week.

Limit alcohol. No more than 2 drinks a day for men and 1 drink a day for nonpregnant women.

Healthy Diet. Everyone should aim for a diet that contains a healthy balance of fruits, vegetables, grains, fish, nuts, legumes, poultry, lean meat, and low-fat dairy items. Avoid saturated fats and trans fatty acids.

Improve Cholesterol. People with at least two risk factors and a 10-year risk for heart disease or stroke of more than 20% should aim for LDL levels of less than 100 mg/dl. Raising HDL levels is important for people at risk for stroke. Statins are now used in most cases.

Keep Blood Pressure Low. People in normal health should aim for 139/89 mm Hg or less. Patients with certain health problems, such as diabetes, should aim lower.

Control Diabetes. People with diabetes should aim for fasting blood glucose levels of less than 110 mg/dl and hemoglobin A1C of less than 7%. Blood pressure goals should be 130/80 mm Hg or less.

Take Aspirin or Other Antiplatelet Therapy. People at high risk for heart disease should take a low-dose aspirin every day, unless they have medical reasons to avoid aspirin. (As an alternative to aspirin alone, your doctor may prescribe clopidogrel alone or aspirin plus extended release dipyridamole.) Aspirin may help to prevent strokes caused by blockage in the artery (ischemic stroke), but it may slightly increase the risk of strokes caused by bleeding in the brain (hemorrhagic stroke). The American Heart Association recommends aspirin therapy for women over age 65 who are at risk for stroke.

Control Atrial Fibrillation. People with atrial fibrillation should use anticoagulants to reduce their risk of blood clots. Carotid Endarterectomy Surgery or Stenting: Recommended for most symptomatic patients with neck artery stenosis (narrowing or blockage) of more than 70% and some patients with stenosis of 50 - 69%.

A healthy diet rich in fruits and vegetables and low in salt and saturated fats may significantly lower the risk for both ischemic and hemorrhagic stroke. For diet plans, the Mediterranean diet may be a particularly good choice for reducing the risk of stroke. [See In-Depth Report #43: Heart-healthy diet.]

Fruits and Vegetables. Studies suggest that people can protect their heart and circulation by eating plenty of fruits and vegetables. Eating at least five servings a day reduces blood pressure and protects against both heart attack and stroke. Important foods include most fruits (especially potassium-rich fruits including bananas, oranges, prunes, and cantaloupes) and vegetables (especially carrots, spinach, celery, alfalfa, mushrooms, lima beans, potatoes, avocados, broccoli). Vegetables, such as broccoli and kale, may be specifically protective against a first ischemic and possibly hemorrhagic stroke. Foods such as apples and tea, which are high in food chemicals called flavonoids, may also be very beneficial.

Whole Grains and Nuts. A 2000 study reported a lower incidence in stroke in women who had a high intake of whole-grain foods. Nuts may also be protective.

Calcium, Potassium, and Magnesium. Calcium, magnesium, and potassium serve as electrolytes in the body. They are important in controlling blood pressure and may also have protective effects against stroke:

Some evidence suggests that diets rich in potassium may protect against stroke by 22 - 40%, mostly by reducing blood pressure but also possibly because of other mechanisms. Low potassium levels may increase the risk for stroke in certain people.

A major study reported that calcium intake is associated with a lower risk for stroke in women, which supports an earlier study reporting a lower risk for stroke in men who drank more milk.

Magnesium deficiencies may increase the risk for atrial fibrillation. No evidence yet exists, however, that taking magnesium supplements is protective.

Salt Restriction. Although the effects of salt restriction are not entirely clear, a 2002 study indicated that even a modest reduction in salt intake for more than a month might reduce the risk of death from stroke by 14% in people with high blood pressure and 6% in people with normal blood pressure.

Fats and Oils. The effects of fats and oils on stroke are complex. One study indicated that middle-aged men without heart disease who had the highest intake of monounsaturated or saturated fat (but not polyunsaturated oils) also had the lowest risk for stroke. Monounsaturated oils, obtained in olive and canola oils, may have protective benefits against both heart disease and stroke. Saturated fats, found in animal products, are known risk factors for heart disease. Some studies suggest, however, that low intake of animal protein and saturated fat increases the risk of hemorrhagic stroke.

Other fat compounds that may be stroke protective are omega-3 fatty acids:

Alpha-linolenic acid is found in canola oil, soybeans, and walnuts. One particular benefit against stroke is its ability to help prevent the formation of blood clots.
Omega-3 fatty acids are categorized as docosahexaenoic (DHA) or eicosapentaneoic acids (EPA). They are found in oily fish and nutritional supplements. These compounds have anti-inflammatory and anti-blood clotting effects and may be significantly beneficial to the heart and reduce the risk for stroke. However, people who have implantable defibrillators should not take fish oil supplements because they may worsen heart rhythm problems.

In any case, consuming fish two or three times a week helps the heart.

Folic Acid and B Vitamins. Deficiencies in the B vitamins folate (known also as folic acid), B6, and B12 have been associated with a higher risk for heart disease in some studies. Such deficiencies produce higher blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure. Researchers have been studying whether vitamin B supplements can reduce homocysteine levels and, consequently, heart disease risks.

Several major 2006 studies indicated that while B vitamin supplements help lower homocysteine levels, they have no effect on heart disease outcomes. The studies, published in the New England Journal of Medicine, examined patients who had either recently had a heart attack or suffered from diabetes or heart disease. Results showed a similar number of heart attacks and strokes among patients who took folic acid and B6 and B12 vitamins and those who received placebo. And, the vitamins seemed to increase risks for patients who had undergone stenting. Some experts think that homocysteine may be a marker for heart disease rather than a cause of it.

Antioxidant Vitamins. The effects of antioxidant vitamins and carotenoids on stroke have been studied extensively. Most studies have found that these vitamins do not help protect against stroke. An important 2001 study reported no protection from stroke with vitamins A or E or beta carotene. A 2005 study in the Journal of the American Medical Association found that vitamin E definitely does not protect women from stroke or heart attack.

Smoking. Everyone should quit smoking.

Alcohol. Mild-to-moderate alcohol use (one to seven drinks a week) is associated with a significantly lower risk for ischemic stroke, although not hemorrhagic stroke. Heavy alcohol use, particularly a recent history of drinking, is associated with a higher risk of both ischemic and hemorrhagic stroke.

Coffee. In healthy people with normal blood pressure, drinking a couple of cups of coffee a day is unlikely to do any harm. Caffeine may actually have nerve-protecting properties that may help stroke survivors. Caffeine drinkers, however, might do better to choose tea, which may have beneficial nutrients, and people with existing hypertension should avoid caffeine altogether (since caffeine may increase the risk for stroke in this group).

Exercise helps reduce the risk of atherosclerosis, which can help reduce the risk of stroke. Experts recommend at least 30 minutes of exercise on most, if not all, days of the week.

Hypertension is a disorder characterized by chronically high blood pressure. It must be monitored, treated, and controlled by medication, lifestyle changes, or a combination of both.

Reducing blood pressure is essential in stroke prevention. Lifestyle measures such as exercise, weight loss, and healthy diets are important for everyone. Drug therapy is recommended for people with hypertension who cannot control their blood pressure through lifestyle changes. Many different types of drugs are used to control blood pressure. They include ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers, and diuretics. Some drugs, such as Hyzaar, combine an angiotensin receptor blocker with a diuretic to both treat high blood pressure and prevent stroke. [See In-Depth Report #14: High blood pressure.]

In 2004, the National Cholesterol Education Program issued updated recommendations on how to control cholesterol levels. These guidelines emphasize that patients should lower their LDL (“bad”) cholesterol and recommend that more people take LDL-lowering medication. Lowering LDL cholesterol and raising HDL (“good”) cholesterol can significantly reduce the risks of heart disease, including stroke.

Statins have become the most important LDL-lowering drugs. Brands include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). Research increasingly suggests that lowering LDL levels as much as possible is critical for preventing stroke and other heart disease problems. A major analysis of over 200 studies found that statins reduced the risk for heart problems by 60% and stroke by 17%. Another study of over 20,000 people with cerebrovascular disease found that patients who took statin therapy for 2 years reduced their risk of ischemic stroke by 25%.

Statins are proven to reduce the risk of stroke in people at increased risk for heart disease. Research suggests that they may also prevent stroke in patients without heart disease. However, current guidelines recommend that statins should be prescribed to patients without heart disease and with normal LDL levels only if diabetes and several heart disease risk factors are also present.

Researchers are also investigating whether statins might be beneficial in preventing a second stroke in patients who have suffered a stroke or transient ischemic attack (TIA). A study published in 2006 in the New England Journal of Medicine indicated that high-dose atorvastatin (Lipitor) therapy may help reduce the risk of stroke recurrence and other heart events for patients who have had a prior stroke or TIA. In 2006, the FDA expanded atorvastatin’s indications to include reducing the risk of fatal and non-fatal strokes in patients with heart disease

[See In-Depth Report #23: Cholesterol.]

Influenza vaccinations may protect patients with a history of heart attack or heart events. A 2002 study further suggested that flu shots might protect against stroke, although possibly not in patients older than age 75.

Treatment for atrial fibrillation always includes drugs (aspirin or warfarin) to prevent clots from forming. In addition to anticoagulants (blood thinners), other approaches may include:

Restoring or maintaining normal heart rhythm. This is accomplished with anti-arrhythmic drug, cardioversion procedures, or surgery to remove the defective area.
Controlling heart rate. Specific drugs are used for this approach.

Important studies report that controlling heart rate may be the preferable approach. In several studies, rhythm control offered no survival advantages and did not protect against ischemic stroke. Therapies aimed at controlling heart rate, furthermore, had fewer complications.

Drugs to Prevent Blood Clots

After a diagnosis of atrial fibrillation, warfarin (an anticoagulant) or aspirin (an antiplatelet) are essential to prevent blood clots. These drugs can reduce the risk for stroke by over 60% in patients with atrial fibrillation.

Warfarin (Coumadin) is the main anticoagulant (“blood thinner”) drug used to prevent strokes in high-risk patients with atrial fibrillation. Warfarin carries a risk for bleeding, but for most patients, warfarin’s benefits far outweigh its risks. The risk for bleeding is highest when warfarin therapy is first started, with higher doses, and with long periods of treatment. Patients at risk for bleeding are usually older and have a history of stomach bleeding and high blood pressure. It is important that patients who take warfarin have their blood checked regularly to make sure that it does not become “too thin.” Blood that is too thin increases the risk for bleeding, while blood that is “too thick” increases the risk for blood clots and stroke. Prothrombin time (PT) and international normalized ratio (INR) tests are used to monitor blood coagulation.
Aspirin is less effective than warfarin, but has a lower risk for bleeding. It is the preferred treatment for younger people with atrial fibrillation and for people who do not have other risk factors for stroke, such as high blood pressure or diabetes. Aspirin is also prescribed for higher risk patients who cannot tolerate anticoagulation therapy.
Researchers are investigating other drugs for preventing stroke and heart problems in patients with atrial fibrillation. These drugs include the antiplatelet medication clopidogrel (Plavix) and the angiotensin receptor blocker irbesartan (Avapro). Recent research indicates that anticoagulants such as warfarin (Coumadin) work better for atrial fibrillation patients than the combination of clopidogrel plus aspirin. Clinical trials are continuing to investigate whether clopidogrel alone is better than aspirin alone.

Restoring and Controlling Heart Rhythm

To initially restore heart rhythm, anti-arrhythmic drugs are usually tried first. If they fail to restore normal rhythm, cardioversion is often effective. (Some experts suggest trying cardioversion first to avoid side effects of the drugs.) Long-term maintenance therapy using anti-arrhythmic drugs may be required.

Electrical Cardioversion. Electrical cardioversion is mild shock therapy and is the current standard treatment used to restore normal heart rhythm. It is conducted as follows:

Anticoagulants (drugs used to prevent blood clotting) should be administered, if possible, at least 3 weeks before the procedure.
During the procedure, the patient must be conscious and, although sedated, can experience some pain from the procedure.

Although the stabilizing effect is usually only temporary, some evidence suggests that a series of cardioversion may succeed in maintaining normal rhythm in young healthy patients without the need for antiarrhythmic medications.

Low-energy implanted cardioverters (Atrioverter, Jewel AF) are being investigated for maintenance. Studies are promising.

Drugs Used for Maintaining Normal Heart Rhythm. For maintaining a stable rhythm, the following drugs may be used. The specific choices typically depend on whether or not the patient has existing heart disease:

For patients with no heart disease, the first choices include sotalol, flecainide, or propafenone, which are often used sequentially. If these fail, then amiodarone or a newer drug dofetilide (Tikosyn) may be tried. Others include ibutilide (Covert) and azimilide. If these drugs are not effective, other drugs tried include quinidine, procainamide, and disopyramide.
In patients with heart disease, amiodarone, dofetilide, or sotalol are commonly used depending on the cause of heart disease.

Amiodarone is more effective than most others and has been thought to be safer than many other similar drugs. Even in low doses, however, there is a high incidence of side effects, including thyroid disorders, neurologic, skin, and eye problems, and abnormally slow heart beats. Many of these drugs carry a small but significant increased risk, however, for a life-threatening arrhythmia called torsades de pointes. People with certain heart conditions should avoid these drugs.

Surgical Procedures for Complex AF. In some difficult cases, surgery may be recommended. The options and candidates depend on other complicating factors. The following are some examples:

AV node ablation involves severing the communication between the atria (the two upper chambers of the heart) and the ventricles (the two lower chambers). A pacemaker is then implanted just under the skin with electrodes leading to the ventricles. This approach is very effective, but it is irreversible and lifelong. Radiofrequency ablation may be an option in some patients.
A more aggressive procedure uses open chest surgery, in which a maze of cuts is made in the atria. As they heal, the scar tissue prevents the heart circuitry from misfiring. This technique controls atrial fibrillation in more than 90% of appropriate candidates. A new procedure is similar but less invasive.

Controlling Heart Rate

Drugs Used to Control Heart Rate. Beta-blockers or calcium channel blockers are used to control heart rate at the onset of atrial fibrillation. Digitalis, an older drug, is not used as often but can be effective in combination with the other drugs.

Diagnosis

Preventing a major stroke in people who experience transient ischemic attacks or small strokes requires determining the source of such attacks. A complete blood count, chest x-ray, and electrocardiogram are usually performed. Discouragingly, a 2001 study reported that over 30% of patients with TIA who called their primary care doctor were neither evaluated nor sent to the hospital within the month after a first event.

Examining the Carotid Artery. The doctor examines the carotid artery to determine if it is severely narrowed. If so, the patient is in danger of a major stroke. (The thickness of the carotid artery is also an important indicator for long-term risks for stroke, as well as heart disease and mortality rates in general.)

The doctor may use a number of approaches to determine the thickness of the artery:

An important clue to a blocked carotid artery is a bruit. This is a whooshing sound caused by blood flow turbulence in the narrowed artery. A doctor may be able to hear a bruit using a stethoscope. Occasionally, even a patient can hear the sound. The presence of a bruit, however, is not necessarily a sign of an impending stroke, nor does the absence of a bruit indicate an unblocked artery.
Carotid ultrasound is a very valuable tool for measuring the width of the artery. At this time, ultrasound is most useful in people between the ages of 40 and 60 years. Severely blocked carotid arteries may distort some measurements, so other tests may be required to confirm the results.
Measuring blood pressure to the eye may also be important in identifying problems in the carotid artery. If blood flow to the eye is reduced, it is likely that the carotid artery is severely narrowed.

Carotid duplex is an ultrasound procedure performed to assess blood flow through the carotid artery to the brain. High-frequency sound waves are directed from a hand-held transducer probe to the area. These waves "echo" off the arterial structures and produce a two-dimensional image on a monitor, which will make obstructions or narrowing of the arteries visible.

Imaging Techniques for TIAs. Several imaging techniques may identify small clots or other indicators of risk in the brain.

Identifying a Stroke Quickly. To save a patient's life, a fast diagnosis of both the presence and type of stroke is critical. Health professionals have devised different tests to help emergency workers quickly identify a person with stroke even before they reach the hospital. For example, an assessment tool called Face, Arms, Speech, Time (FAST) is highly accurate. It involves watching for the following signs:

(F)ACE. Ask the person to smile. Check to see if one side of the face droops.
(A)RMS. Ask the person to raise both arms. See if one arm drifts downward.
(S)PEECH. Ask the person to repeat a simple sentence. Check to see if words are slurred and if the sentence is repeated correctly.
(T)IME. If a person shows any of these symptoms, time is essential. It is important to get to the hospital as quickly as possible. Call 9-1-1. Act FAST.

Determining Ischemia Versus Hemorrhagic Stroke. Once a stroke has been identified, the next important step is to determine as quickly as possible whether it is hemorrhagic or ischemic. Clot-busting drug therapies can be life-saving for ischemic stroke patients, but they are effective only in the first 3 hours. In addition, they cause bleeding and can be lethal if the stroke is caused by a hemorrhage.

A computed tomography (CT) scan is essential for identifying or ruling out hemorrhagic strokes. The goal is to complete the CT examination and obtain and interpret the results within 45 minutes of arrival at the hospital. (An ultrasound technique called transcranial duplex sonography may be sensitive enough to differentiate between hemorrhagic and ischemic strokes if CT scans are not available.)

Certain factors suggest a hemorrhagic rather than ischemic stroke. They include specific symptoms (coma, vomiting, and severe headache), taking anticoagulants, very high systolic blood pressure, or high blood sugar levels in nondiabetics. However, such findings are not conclusive, and a CT scan or MRI is always needed.

Ruling Out Other Disorders. In most cases of stroke, the diagnosis is evident although a number of conditions may cause similar symptoms. These include seizures, infections that cause mental confusion, syncope (fainting), hypoglycemia, and brain tumors.

Magnetic Resonance Imaging (MRI). MRI uses a magnetic field to provide 3-dimensional images of the brain. In 2007, an important Lancet study of emergency room patients clearly indicated that MRI is superior to computed tomography (CT) in assessing whether a stroke has occurred. The MRI appears to work especially well for detecting ischemic stroke (stroke caused by blood clot). In the study, MRI accurately detected presence or absence of acute stroke in 80% of patients compared to 58% for CT. (Acute stroke included both ischemic and hemorrhagic types.) MRI detected acute ischemic stroke in 40% of patients compared to 10% for CT. In addition, MRI detected ischemic stroke within 3 hours of symptom onset (an important timeframe for delivering clotbuster drugs) in 46% of patients compared to only 7% for CT. Both MRI and CT performed similarly for detecting hemorrhagic stroke.

Computed Tomography. A computed tomography (CT) test uses x-ray images to take pictures of the skull and brain. Sometimes a dye is injected into a patient’s veins to enhance image contrast. Although research indicates that MRI is better in determining ischemic stroke, CT still may be useful in diagnosing hemorrhagic strokes.

Ultrasound. Ultrasound may be used in different circumstances. This imaging technique is painless and noninvasive.

Carotid ultrasound (also called Doppler or duplex sonography) can determine blockage in the carotid arteries that could lead to or be causing a stroke.
Transcranial duplex sonography can identify blockage in large arteries in stroke patients and to monitor the effects of thrombolytic therapy.

Cerebral Angiography. Cerebral angiography is an invasive procedure that may be used for patients with TIAs who require surgery. It can also detect aneurysms and monitor thrombolytic therapy. It requires the insertion of a catheter into the groin, which is then threaded up through the arteries to the base of the carotid artery. At this point a dye is injected, and x-rays, CTs, or MRI scans determine the location and extent of the narrowing, or stenosis, of the artery. In people with TIAs the risk of stroke itself increases using this technique, particularly in elderly people with diabetes.

Other Techniques. Other imaging tests, including positron-emission tomography (PET) and single photon-emission computed tomography (SPECT), may also help the doctor identify injuries caused by the stroke.

Electrocardiogram (ECG). A heart evaluation using an electrocardiogram (ECG) is important in any patient with a stroke or suspected stroke. An ECG records the electrical current in the heart muscle.

Echocardiogram. An echocardiogram uses ultrasound to view the chambers and valves of the heart. It is generally useful for stroke patients to identify blood clots or risk factors for blood clots that can travel to the brain and cause stroke. There two are types:

Transthoracic echocardiograms (TTE) view the heart through the chest. It is noninvasive and is the standard approach.
Transesophageal echocardiogram (TEE) examines the heart using an ultrasound tube that the patient literally swallows and passes down the throat. It is uncomfortable and requires sedation. It is typically used to obtain more accurate images of the heart if a TTE has suggested abnormalities, such as atrial fibrillation or patent foramen ovale (PFO).

Patients who have a TIA are at increased risk for a major stroke in the days and weeks that follow. The ABCD² score is a tool that helps doctors predict short-term stroke risk following a TIA. The ABCD² score assigns points for various factors:

Age (over 60 years)
Blood pressure (greater or equal to 140/90 mm Hg)
Clinical features (weakness on one side of the body; speech impairment without weakness
Duration of TIA symptoms (at least 60 minutes)
Diabetes

Based on the number of points, a doctor can identify whether a patient is at low, moderate, or high risk of having a subsequent stroke within 2 days after a TIA. Several 2006 and 2007 studies indicated that the ABCD² score works well in predicting stroke, and can help doctors better decide which patients require hospitalization and emergency care.

Blood Tests. Several blood tests may help predict the risk for a stroke and determine the severity and complications of an existing stroke.

Specific blood tests are important to determine clotting times, to check electrolytes (potassium, calcium, sodium), and to measure factors indicating liver or kidney problems. Kidney tests measure blood proteins that are filtered through the kidneys. These proteins include creatinine and blood urea nitrogen (BUN). A more recent type of kidney test measures the protein cystatin C. Recent research suggests that the cystatin C kidney test may be better at predicting cardiovascular risks in elderly patients.
Blood sugar (glucose) levels are measured. Hyperglycemia (high levels) may indicate a worse outcome for some strokes (although not hemorrhagic or lacunar strokes). Hypoglycemia (low levels) is a common complication of diabetes treatments, and its symptoms may mimic those of a stroke.
A new blood test, the PLAC test, was approved in 2005 to help diagnose people at increased risk for ischemic stroke. The PLAC test measures an enzyme called lipoprotein-associated phospholipase A2 (Lp-PLA2). Patients with high levels of this protein have twice the risk for ischemic stroke as patients with normal levels.

Examination of Spinal Fluid. If the CT scan is negative but the doctor still suspects a subarachnoid hemorrhagic stroke, a spinal tap may be performed. Spinal fluid containing significant amounts of blood will usually confirm a hemorrhagic stroke.

Managing a Stroke

Until recently, the treatment of stroke was restricted to basic life support at the time of the stroke and rehabilitation later. Now, however, treatments can be dramatically beneficial when administered as soon as possible after the onset of the stroke. It is critical to get to the hospital and be diagnosed as soon as possible. There are several steps in the initial assessment and management of a person with a stroke.

If significant symptoms appear in people at risk for stroke, calling 911 is critical (as opposed to calling the family doctor or trying to get the patient to the hospital by car). One study reported that patients who went to the emergency room in an ambulance had a much shorter delay in getting treatment than those who went on their own. Receiving treatment early is critical in reducing the damage from a stroke.

Important diagnostic and evaluation steps are needed for the optimal treatment of a stroke patient:

Determine Whether the Stroke Is Ischemic or Hemorrhagic. As soon as the patient enters the hospital, diagnostic tests, particularly a CT scan, should occur to determine whether the stroke is ischemic or hemorrhagic.

Determine The Need for Thrombolytic Drugs. If the stroke is ischemic, the next step is to determine if the patient would benefit from blood clot-busting drugs (called thrombolytics). The following factors can assist in making this decision:

Estimate the time of onset of the stroke. Time is critical in the decision-making process. Clot-buster drugs do not generally help if given more than 3 hours after stroke onset. Onset is when the patient first experiences any symptoms, even minor impairment. If the patient had a previous TIA that completely resolved before the stroke, however, onset is dated from when the more recent symptoms developed.
Tell the doctor if the patient has been taking any blood-thinning drugs.
Give the doctor a thorough history of any accompanying medical or physical condition and any recent event, such as surgery or injury, which might contribute to the condition.
CT scans will indicate if there are extensive early injuries, which might affect the decision to use these drugs.

The patient should receive treatment to support basic life functions and to reduce stress, pain, and agitation. The following steps are also very important:

Maintain Adequate Delivery of Oxygen. It is very important to maintain oxygen levels. In some cases, airway ventilation may be required. Supplemental oxygen may also be necessary for patients when tests suggest low blood levels of oxygen. Hyperbaric oxygen (which is oxygen administered under pressure) may help specific stroke patients, although it is not recommended for most patients, since there is some risk of significant adverse effects using this approach.

Managing Fever and Lowering Body Temperature (Hypothermia). Fever should be aggressively treated, since strong evidence suggests that its presence predicts a poorer outlook. Some evidence suggests that hypothermia -- reducing body temperature -- might protect nerve cells in stroke patients. Cooling is done through special cooling blankets, ventilators, or infusion of cool fluids. Unfortunately, severe side effects occur with even moderate hypothermia (86°F, 30°C), which can include pneumonia, blood clotting disorders, heart rhythm disturbances, and others.

Maintain Electrolytes. Maintaining a healthy electrolyte balance (the ratio of sodium, calcium, and potassium in the body's fluids) is critical.

Managing Blood Pressure. Managing blood pressure is essential and complicated. Patients with stroke and pressures above 220 (systolic) or 120 (diastolic) should be treated. Lowering blood pressure too quickly can be dangerous, however, in patients with both ischemic and hemorrhagic strokes. In general, experts do not advise aggressively lowering elevated pressures below 220/120 mm Hg in patients unless they have other conditions, such as a heart attack, that require pressure-lowering treatments. In patients who require thrombolytic drugs, blood pressure should cautiously be lowered to 185/110 mm Hg. In most cases, blood pressure declines when these patients become stabilized.

Managing Increased Brain Pressure. Hospital staff should watch carefully for increased pressure on the brain, which is a frequent complication of hemorrhagic strokes. It can also occur a few days after ischemic strokes. Early symptoms of increased brain pressure are drowsiness, confusion, lethargy, weakness, and headache. Medications such as mannitol may be given during a stroke to reduce pressure or the risk for it.

Keeping the top of the body higher than the lower part, such as by elevating the head of the bed, can reduce pressure in the brain and is standard practice for patients with ischemic stroke. However, this practice also lowers blood pressure in general, which may be dangerous for patients with massive stroke.

Monitoring the Heart. Heart attack and arrhythmias are potential complications of ischemic stroke. Patients must be monitored using electrocardiographic tracings.

Controlling Glucose Levels. Elevated blood sugar (glucose) levels can occur with severe stroke and may be a marker of serious trouble. In general, it is advisable to lower glucose levels that are about 300 mg/dL, usually with insulin. It is not clear, however, if glucose-lowering treatments offer any advantage. Excessive lowering of glucose levels can have damaging effects on the brain. Studies are underway to determine the best approach.

Medications

Intravenous Thrombolytics. Clot-busting (thrombolytic) drugs break up existing blood clots. They are among the important treatments for heart attacks, and are now also used for ischemic (not hemorrhagic) stroke. While research has confirmed that early treatment with thrombolytics can greatly increase a stroke patient's chances for recovery, their use has been limited due to the short treatment window (within 3 hours of onset of stroke symptoms). The standard thrombolytic drugs are tissue plasminogen activators (t-PAs). They include alteplase (Activase) and reteplase (Retavase).

The following steps are critical before administering these clot-buster drugs:

Before the thrombolytic is given, a CT scan must first confirm that the stroke is not hemorrhagic. If the stroke is ischemic, a CT scan can also suggest if injuries are very extensive, which might affect the use of thrombolytics.
Thrombolytics must be administered within 3 hours of a stroke to have any effect. According to a 2004 review of clinical trials, best results are achieved if patients are treated with 90 minutes of a stroke. Unfortunately, most stroke patients arrive at the hospital more than 3 hours after an attack and therefore are not eligible for treatment. There is some evidence that t-PA administered with 4 hours may also be effective, but more research needs to be conducted. These findings underscore the critical need for people to go to a hospital immediately if a stroke is suspected.

Thrombolytics carry a risk for hemorrhage, so they may not be appropriate for patients with existing risk factors for bleeding. They should not be used in patients who are experiencing seizures. The drug may be appropriate in more patients than previously thought, however, including older people, those with a history of stroke, and those with high blood pressure. Although older studies cited concern over the safety and effectiveness of t-PA, a 2004 review of clinical trial data found that patients who received t-PA were two times more likely to experience a favorable outcome than those who did not receive this treatment.

Intra-Arterial Thrombolytics. Researchers are investigating thrombolytics injected directly into an artery in the brain. Early studies suggest this approach may allow effective treatment up to 6 hours after a stroke and improve recovery in more patients. The risk for bleeding and hemorrhagic stroke is significantly increased, however.

Fibrin-Depleting Drugs. These drugs deplete the amount of fibrinogen in blood, which in turn reduces the "stickiness" in blood. Such drugs include ancrod and batroxobin (Defibrase), both derived from the venom of poisonous snakes. Some experts believe these drugs might be a possible alternative to thrombolytics. Studies suggest they may modestly reduce the risks for death and disability if given early on. As with all anti-clotting drugs, there is a higher risk for hemorrhage, but it appears to be slight.

Medications that prevent blood from clotting are used to prevent a recurring or second stroke. Anticlotting drugs include antiplatelets and anticoagulants.

Antiplatelet Drugs.Blood platelets are involved in blood clotting. Antiplatelets prevent clotting by blocking the accumulation of platelets. An antiplatelet drug -- most often aspirin -- is given within 48 hours of an ischemic stroke and continued in low doses as maintenance therapy. Studies suggest that antiplatelet therapy can reduce the risk for a second stroke by 25%.

Aspirin. Aspirin is recommended within 48 hours of a first ischemic stroke in doses of 50 - 325 mg. Daily low-dose aspirin may also help prevent a second ischemic stroke. Experts also recommend aspirin combined with the antiplatelet drug dipyridamole (Aggrenox). A 2006 study indicated that aspirin plus dipyridamole may be better than aspirin alone in preventing a heart attack or major stroke in patients who have had a minor ischemic stroke. Patients should not be given an aspirin until a diagnosis of ischemic or hemorrhagic stroke has been determined. Aspirin increases the risk for bleeding in patients with hemorrhagic stroke and can be dangerous.
Thienopyridines. Clopidogrel (Plavix) and ticlopidine (Ticlid) are antiplatelet drugs known as thienopyridines. (Clopidogrel is preferred over ticlopidine because of its better safety record.) Evidence suggests that clopidogrel plus aspirin is better than aspirin alone in reducing blood clots in patients who have carotid artery blockage (carotid stenosis). Other studies indicate that clopidogrel alone may be sufficient for patients who have had a recent ischemic stroke or TIA. A study of over 7,000 of these patients found that adding aspirin to clopidogrel therapy provided no additional benefit and increased the risk of bleeding; therefore, aspirin plus clopidogrel is not usually recommended for most patients who have had an ischemic stroke or TIA. Clopidogrel alone may also be better than aspirin alone in preventing a third stroke or heart attack in high-risk patients.
Glycoprotein IIB/IIIa Inhibitors. Glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors are sometimes administered intravenously in the hospital and include abciximab (ReoPro, Centocor), eptifibatide (Integrilin), tirofiban (Aggrastat), lotrafiban, and lamifiban. They are being investigated alone or as additions to thrombolytic (clot-busting) drugs.

Anticoagulants.Anticoagulants thin blood and may be useful under certain circumstances.

Warfarin. The anticoagulant warfarin (Coumadin) may not work as well as aspirin in preventing a second stroke in people who have partial artery blockage in the brain (intracranial stenosis). Warfarin is, however, very important in high-risk patients with atrial fibrillation. It may be useful in other situations, such as patients with patent foramen ovale (PFO), those whose stroke followed a heart attack, or in high-risk patients who cannot take antiplatelet drugs.
Heparin. Intravenous heparin, a potent anti-platelet drug, has been used for ischemic stroke since 1941. Although many doctors continue to use it, five out of six major studies have reported no clear protective benefits compared to aspirin with the use of standard heparin or any heparin-like drugs. They also pose a much higher risk for hemorrhagic stroke. Experts now recommend heparins only for preventing thromboembolism in stroke patients at risk for this condition.
Direct Thrombin Inhibitors (DTIs). Direct thrombin inhibitors are a more recent group of anti-coagulants. The first DTI is hirudin, a natural substance derived from the saliva of leeches. New forms include argatroban (Novastan), bivalirudin (Angiomax), danaparoid (Orgaran), lepirudin (Refludan), desirudin (Revasc), inogatran, and efegatran. Ximelagatran (Exanta) is new oral drug that is showing great promise for protection against stroke in patients with atrial fibrillation while posing a low risk for bleeding.

All anti-clotting drugs carry a risk for bleeding and a slightly increased risk for hemorrhagic stroke.

It is important that patients control their high blood pressure and LDL (“bad”) cholesterol levels. Various drugs, such as statins, diuretics, and ACE inhibitors, can manage these conditions. People with diabetes should also maintain tight control of their blood sugar levels.

Calcium Channel Blockers. Early administration of calcium channel blockers, such as nimodipine (Nimotop), can improve functional outcome. One of the most common and serious dangers after a subarachnoid hemorrhagic stroke is spasm of the blood vessels near the ruptured site, which closes off oxygen to the brain. Calcium causes contraction of the smooth muscles of the blood vessels; calcium channel blockers are drugs that relax the blood vessels. The drugs work best if they are administered within 6 hours of the stroke. Calcium channel blockers are not useful for ischemic strokes, although they can be used in combinations with blood pressure lowering drugs to prevent them.

Nerve-Protecting Drugs. More than 50 medications have been studied in clinical trials aimed at slowing or preventing the cascading process that destroys nerve cells after a stroke. Many investigative drugs are targeting the excitatory amino acids, such as glycine and glutamate, which are known to destroy nerve cells after a stroke. Although none to date have proven to have any significant benefits, some are showing promise. They include magnesium sulfate, citicoline, ebselen, piracetam, edaravone, albumin, erythropoietin, and NXY-059.

Investigative Drugs for Nerve Regeneration. Scientists used to think that when cells in the brain were destroyed, new ones could not grow to replace them. Researchers have now observed, however, that nerve regrowth (neurogenesis) can occur in the adult human brain. This exciting discovery opens the way for new drugs that might in the future stimulate nerve growth and repair damage done by many neurologic diseases, including stroke. For example, a 2002 study reported nerve regeneration in animals whose brains were treated with the drug inosine. More research is underway.

Surgery

Carotid endarterectomy is a surgical procedure that cleans out and opens up the narrowed carotid artery. It is used in patients at high risk for thrombotic ischemic strokes, which are caused by blockages in the internal carotid artery. It is also sometimes used after a stroke. In such cases, patients have reported improvements in vision, speech, swallowing, functioning of arms and legs, and general quality of life.

There is a risk of a heart attack or stroke from the procedure. Anyone undergoing this procedure should be sure their surgeon is experienced in recent techniques and that the medical center has complication rates of less than 6%. A 2000 study reported that older surgeons had a worse record than younger ones, possibly because they relied on residents or were less likely to adopt new procedures.

Procedure Description. The procedure generally is as follows:

The patient is usually given general anesthesia, although it has been reported that using local anesthetic is just as safe and reduces the cost of the procedure.
A bypass tube is put in place to transport blood around the blocked area during the procedure.
The surgeon scrapes away the plaque on the arterial wall.
The artery is sewn back together, and blood flow is restored.
The patient generally stays in the hospital for about 2 days. There is often a slight aching in the neck for about 2 weeks, and the patient should refrain as much as possible from turning the head during this period.

Endarterectomy is a surgical procedure removing plaque material from the lining of an artery.

Click the icon to see an illustrated series detailing surgery for unblocking carotid arteries.

Determining Who Should Have Surgery. Evidence strongly suggests that most patients with severe stenosis (over 70% of the carotid artery is obstructed) can benefit from either carotid endarterectomy or carotid artery stenting. An experienced surgeon with a good track record is essential. Patients with mild stenosis (less than 50% obstruction) should not have endarterectomy; these patients do better with medications even if they have symptoms. For patients with moderate stenosis (50 - 69%), the decision to perform surgery needs to be determined on an individual basis. When a carotid endarterectomy procedure is recommended, it should be performed within 2 weeks.

Carotid angioplasty and stenting (CAS) is being investigated as a less-invasive alternative to carotid endarterectomy. It is based on the same principles as angiography done for heart disease.

An extremely thin catheter tube is inserted into an artery in the groin.
It is threaded through the circulatory system until it reaches the blocked area in the carotid artery.
The doctor either breaks up the clot or inflates a tiny balloon against the blood vessel walls (angioplasty).
After temporarily inflating the balloon, the doctor typically leaves a circular wire mesh (stent) inside the vessel to keep it open.

This procedure carries a risk for an embolic stroke and other complications. At this time, it is being used in some centers as an alternative to endarterectomy in patients who cannot undergo endarterectomy, especially for patients with severe stenosis (blockage greater than 70%) and high surgical risk. Several studies published in 2006 suggested that CAS should be used only for patients with these types of conditions. One of these trials, EVA-3S, was stopped early because results clearly indicated a higher 30-day risk of death and stroke in patients who underwent CAS. Experts are waiting for results of further trials comparing stenting and endarterectomy.

Hemicraniectomy is surgical removal of a bone patch from the skull to relieve pressure. The bone is stored under sterile conditions and reimplanted a few months latter. It may have be a life-saving option for some patients with severe stroke that has resulted in swelling and injury to a large area in the brain. Studies are showing some benefits for high-risk patients, but more information is needed to determine specific conditions that will respond to this treatment.

Extracranial-intracranial (EC-IC) bypass has been under investigation for decades for ischemic stroke, but has had very mixed results, some extremely negative. With this procedure, a healthy artery in the scalp is rerouted to an area of the brain that was deprived of blood because of a blocked artery. This procedure is now sometimes used for patients with aneurysms. Some experts hope, however, that, in specific cases chosen via careful imaging and using the latest surgical techniques, EC-IC may prove to be helpful for some stroke patients.

Surgical Intervention of the Ruptured Aneurysms. In patients with subarachnoid hemorrhagic stroke, surgery to block off the aneurysm is usually recommended within a few days of the stroke. The standard procedure is to clip the aneurysm and stop bleeding. Alternative approaches are promising.

Surgical Intervention of Unruptured Aneurysms. If an unruptured aneurysm is detected, patients should discuss all options with their doctor, including surgical repair. Unruptured aneurysms occur in between 1 - 8% of the general population, however, and controversy exists over when to operate and on which patients.

In general, the decision rests on the size of the aneurysm, but uncertainty still exists. In one study, for example, the risk of rupture for aneurysms between 10 - 25 mm was quite low -- slightly less than 1% per year for both groups. Aneurysms over 25 mm, however, had a 6% chance of rupturing within a year. Studies have reported that in general, the risk for rupture is between .05 - 2% a year, but recent evidence suggests that the risks may be even less. In one study, even people with a history of subarachnoid hemorrhage had only a 0.5% annual risk for recurrence when aneurysms were small.

Aneurysms can often cause symptoms, however, even if they do not rupture. Patients should discuss their particular risk factors carefully with their doctors. Individuals with arteriovenous malformation, a condition caused by abnormal associations between arteries and veins, should be monitored for the development of an aneurysm.

Clipping the Aneurysm. The standard surgical procedure for treating a ruptured aneurysm is to place a clip across the neck of the aneurysm, which blocks off bleeding. It is usually performed within the first 3 days. Getting to the aneurysm is often extremely difficult. Deep cooling of the body to stop circulation may be used to allow more time for the operation. Procedures that remove large portions of the bone in the skull are being developed to allow fast access. There is a relatively high risk for newly formed aneurysms, particularly after 9 years. Patients may want to discuss follow-up angiography to detect any new aneurysms 9 - 10 years after the procedure.

Transcatheter Embolization for Sealing off the Aneurysm. Transcatheter embolization is a new technique for ruptured and unruptured aneurysms that is proving to be effective, although it is still investigational. The surgeon threads a thin tube through the artery leading to the aneurysm through which materials are passed to plug or obstruct the aneurysm. In one version of this procedure, the following occurs:

A tiny platinum coil is inserted through the tube and positioned into the aneurysm.
An electric charge is passed through the coil to form blood clots.
In this case, blood clots benefit the patient by using the coil as a scaffold and sealing off the aneurysm.

A 2002 study suggested it could be attempted safely in over 95% of patients with unruptured aneurysms. In the study, the procedure eliminated the aneurysm in nearly 90% of the patients. In small trials using the coil with a ruptured aneurysm, only 3.7% of patients suffered a second stroke after 7 months compared to the usual re-rupture rate of 30 - 40%.

Emergency Surgery for Hemorrhagic Strokes. Emergency surgery for a hemorrhagic stroke involves locating and removing large blood clots. In the past, such procedures had little effect on survival. Advances, however, are improving outcomes when surgery is performed very early.

Recovery

After a stroke, patients should take all necessary measures, including medications and lifestyle changes, to prevent another stroke. For those whose stroke was ischemic, aspirin, warfarin, or both will usually be prescribed.

Having a neurologist as the primary doctor after a stroke, rather than some other specialist or primary care doctor, significantly increases the chance for survival. Patients or their families should be persistent in requesting the best care possible during this important early period.

Receiving initial treatment at a stroke unit, instead of a general ward, plays a strong role for better long-term quality of life. Rehabilitation services aimed at patients living at home are also very effective in improving independence. Patients or their families should seek patient advocates or support associations to ensure they receive the right care.

In addition to problems brought on by neurologic damage, stroke patients are also at risk for other serious problems that reduce their chances for survival. They include:

Blood clots in the legs (deep vein thrombosis)
Pulmonary embolism (a blood clot that travels to the lungs)
Pneumonia
Widespread infection
Heart problems
Urinary tract infections (a catheter is sometimes used in the first 48 hours after stroke to help with urinary retention, but if it is left in longer it can cause urinary tract infections)

Measures should be taken to monitor and treat patients for these important problems.

In all, 90% of stroke survivors experience varying degrees of improvement after rehabilitation. The current cost-cutting climate generates pressure to send elderly patients who have had a stroke directly to a nursing home rather than a rehabilitation first. Not all patients, however, need or benefit from formal rehabilitation:

If the stroke is severe, intensive training would not be helpful.
If the stroke is mild, patients often improve on their own.

Positive factors that help predict good candidates for rehabilitation:

A patient should be able to sit up for at least an hour.
The patient should be able to learn and be aware.
Spasticity may be a good sign, because it indicates live nerve action.
Patients who are able to move their shoulders or fingers within the first 3 weeks after having a stroke are more likely to recover the use of their hands than patients who cannot perform these movements. The ability to feel light pressure on the affected hand, however, makes no difference for future hand movement.
Family members or close friends are available to be active participants in the rehabilitation process.

Factors that predict a poor response to rehabilitation:

Dysphagia (the inability to swallow) is associated with a higher mortality rate, possibly because of increased risk for infection and malnutrition. Dysphagic patients are given nutrition using a stomach tube or a feeding tube inserted down through the nose.
Incontinence.
The inability to recognize nonspeech sounds that occur right after a stroke.
A poor hand grip that is still present after 3 weeks is an indicator of severe problems.
Having had very severe seizures after the stroke.

Factors that do not rule out rehabilitation:

About 30% of patients experience aphasia (an impaired ability to speak). However, this disability does not necessarily affect the ability to think. Aphasia can also be temporary.
Although confusion is common among people who have had strokes, partial or even complete recovery is very possible.

Physical therapy should be started as soon as the patient is stable, as early as 2 days after the stroke. Some patients will experience the fastest recovery in the first few days, but many will continue to improve for about 6 months or longer. Because stroke affects different parts of the brain, specific approaches to managing rehabilitation vary widely among individual patients:

Exercise program. Recent guidelines from the Veteran’s Administration recommend that patients get back on their feet as soon as possible to prevent deep vein thrombosis. Patients should try to walk at least 50 feet a day. Assisted devices or bracing are sometimes used to help support the legs. Treadmill exercises can be very helpful for patients with mild-to-moderate dysfunction. Exercise should be tailored to the stroke survivor's physical condition and can include aerobic, strength, flexibility, and neuromuscular (coordination and balance) activities.
Retraining muscles. Stretching and range-of-motion exercises are used to help treat spastic muscles. They can also help patients regain function in a paralyzed arm. There are several approaches. The Bilateral Arm Training with Rhythmic Auditory Cueing (BATRAC) technique involves moving a bar with both arms in a sustained rhythmic pattern. A 2004 study in the Journal of the American Medical Association (JAMA) reported that BATRAC helped patients get back use of their paralyzed arm. Patients had a stroke at least 4 years before participating in the BATRAC study. Another technique, constraint-induced movement therapy (CIMT), involves doing a series of repetitive exercises while the less functional arm is restrained. Research published in 2006 in JAMA indicated that 2 weeks of CIMT can help patients regain arm function. Patients in the CIMT study had experienced a stroke within the prior 3 - 9 months.
Speech therapy and sign language. People who have had a stroke often have aphasia, a brain condition that makes it difficult to speak and understand language. Aphasia can come in many different forms. A person may be unable to speak at all, or just have difficulty saying the right word. Intense speech therapy after a stroke is important for recovery. Some experts recommend 9 hours a week of therapy for 3 months. A 2005 study indicated that a shorter period (3 hours a week for 10 days) also works well. Language skills improve the most when family and friends help reinforce the speech therapy lessons.
Biofeedback techniques combined with physical therapy. This combination has been beneficial in certain cases. Electrical stimulation of the throat, for example, may help patients with dysphagia recover their ability to swallow faster. Stimulation of the wrist and finger is also showing promise for improving motor capabilities.
Swallowing exercise. A promising study reported that swallowing improved when patients performed a simple exercise 3 times a day for 6 weeks. They lay flat and raised their heads three times, holding them up for 1 minute with a 1 minute rest in between. This was followed by 30 consecutive head lifts.
Attention training. Problems with attention are very common after strokes. Direct retraining teaches patients to perform specific tasks using repetitive drills in response to certain stimuli. (For example, they are told to press a buzzer each time they hear a specific number.) A variant of this approach trains patients to relearn real-life skills, such as driving, carrying on a conversation, or other daily tasks.
Occupational training. Occupational therapy is important and improves daily living activities and social participation.

Drug therapy can sometimes help relieve specific effects of stroke:

Dantrolene (Dantrium), tizanidine (Zanaflex), and baclofen (Lioresel) are used to treat spasticity.
Heparin, a blood-thinning drug, is used to prevent blood clots from forming in the veins of the legs (thrombosis).
Some patients experience constant hiccups, which can be very serious. Among the drugs used for this condition are chlorpromazine or baclofen.
Studies have reported that dextroamphetamine or methylphenidate (Ritalin), an amphetamine used in attention deficit disorder, may help patients recover speech and motor skills when combined with physical therapy.

Certain drugs commonly taken for conditions associated with stroke may actually slow recovery. They include drugs used for high blood pressure, including clonidine and prazosin, anticonvulsant drugs, the antipsychotic drug haloperidol, and anti-anxiety drugs such as benzodiazepines.

The Emotional State of the Patients. Strong motivation with the goal of independence after rehabilitation is important for recovery. Unfortunately, depression is very common after a stroke, both as a direct and indirect result of the stroke:

Strokes that affect the right hemisphere in the brain increase the risk for depression.
Patients can become depressed by the changes in their ability to function.
A peculiar stroke-induced condition, known as post-stroke crying or neurologic emotionalism, is a neurologic not a psychologic disorder.

If depression is prolonged, it can interfere with recovery. One study showed that people who suffered strokes and became depressed were three times more likely to die within 10 years than stroke victims who were not depressed. There is a significantly increased risk of suicide in patients with stroke, especially in women and those under age 60.

Antidepressants, particularly fluoxetine (Prozac) and similar so-called SSRI drugs, have been beneficial in relieving post-stroke crying as well as improving recovery in general and mood in particular. Antidepressants may also help restore mental abilities.

Some doctors also recommend tricyclic antidepressants, which include amitriptyline (Elavil) and nortriptyline (Pamelor). In one study nortriptyline (Pamelor) not only improved mood but also had positive effects on mental functioning, suggesting perhaps that some dementia associated with stroke may actually be due to depression. Tricyclics may also be useful for neurologic emotionalism.

Anxiety disorder is also common and debilitating. Some research indicates that many patients suffer from feelings identical to post-traumatic stress syndrome. The two disorders often overlap, but drug treatments for each differ and may offset the other.

Many drugs for psychologic disorders affect the central nervous system and can delay rehabilitation. Skilled professional help is needed to determine the most effective and safest treatments.

The Emotional State of the Caregiver. The caregiver's emotions and responses to the patient are critical. Patients do worse when caregivers are depressed, overprotective, or not knowledgeable about the stroke. Unfortunately, in one study, over half of the caregivers themselves were depressed, particularly if the stroke victims were left with dementia or abnormal behavior.

Resources

www.strokeassociation.org -- American Stroke Association
www.americanheart.org -- American Heart Association
www.stroke.org -- National Stroke Association
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.aphasia.org -- National Aphasia Association
www.aan.com -- American Academy of Neurology
www.strokecenter.org/trials -- Stroke Trials Directory

References

ACTIVE Writing Group on behalf of the ACTIVE Investigators; Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006 Jun 10;367(9526):1903-12.

Amarenco P, Bogousslavsky J, Callahan A 3rd, Goldstein LB, Hennerici M, Rudolph AE, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006 Aug 10;355(6):549-59.

Antman EM, Bennett JS, Daugherty A, Furberg C, Roberts H, Taubert KA. Use of nonsteroidal antiinflammatory drugs: an update for clinicians: a scientific statement from the American Heart Association. Circulation. 2007 Mar 27;115(12):1634-42. Epub 2007 Feb 26.

Chalela JA, Kidwell CS, Nentwich LM, Luby M, Butman JA, Demchuk AM, et al. Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison. Lancet. 2007 Jan 27;369(9558):293-8.

ESPRIT Study Group; Halkes PH, van Gijn J, Kappelle LJ, Koudstaal PJ, Algra A. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet. 2006 May 20;367(9523):1665-73.

Johnston SC, Rothwell PM, Nguyen-Huynh MN, Giles MF, Elkins JS, Bernstein AL, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet. 2007 Jan 27;369(9558):283-92.

Kurth T, Gaziano JM, Cook NR, Logroscino G, Diener HC, Buring JE. Migraine and risk of cardiovascular disease in women. JAMA. 2006 Jul 19;296(3):283-91.

Mas JL, Chatellier G, Beyssen B, Branchereau A, Moulin T, Becquemin JP, et al. Endarterectomy versus stenting in patients with symptomatic severe carotidstenosis. N Engl J Med. 2006 Oct 19;355(16):1660-71.

Mosca L, Banka CL, Benjamin EJ, Berra K, Bushnell C, Dolor RJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation. 2007 Mar 20;115(11):1481-501.

Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, et al. Heart disease and stroke statistics -- 2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007 Feb 6;115(5):e69-171. Epub 2006 Dec 28.

SPACE Collaborative Group; Ringleb PA, Allenberg J, Bruckmann H, Eckstein HH, Fraedrich G, et al. 30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial. Lancet. 2006 Oct 7;368(9543):1239-47.

Thavendiranathan P, Bagai A, Brookhart MA, Choudhry NK. Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006 Nov 27;166(21):2307-13.

Tsivgoulis G, Spengos K, Manta P, Karandreas N, Zambelis T, Zakopoulos N, et al. Validation of the ABCD score in identifying individuals at high early risk of stroke after a transient ischemic attack: a hospital-based case series study. Stroke. 2006 Dec;37(12):2892-7. Epub 2006 Oct 19.

Wolf SL, Winstein CJ, Miller JP, Taub E, Uswatte G, Morris D, et al. Effect of constraint-induced movement therapy on upper extremity function 3 to 9months after stroke: the EXCITE randomized clinical trial. JAMA. 2006 Nov 1;296(17):2095-104.

Review Date:
4/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

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adam.com

Coronary artery disease

FitSugar — Wed, 08 Oct 2008 17:35:07 -0700

In This Report

Highlights
Introduction
Prognosis
Risk Factors
Diagnosis
Managing Heart Disease
Anti-Clotting Medications...
Other Medications
Surgery
Coronary Artery Bypass Graf...
Angioplasty and Stents
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Angioplasty Versus Drugs

Angioplasty works no better than drug therapy (high blood pressure, cholesterol, anti-platelet, and other medication) in preventing heart attack and stroke in patients with stable coronary artery disease (CAD), according to an important New England Journal of Medicine study. Experts still recommend angioplasty for patients with unstable or severe CAD.

Stents

Stents coated with drugs may have a slightly higher risk of causing blood clots than bare metal stents, according to FDA meetings held in late 2006. Researchers still need to conduct more research before reaching final conclusions.
Drug-coated stents work well when they are used for patients with specific types of heart conditions, indicate several studies published in the New England Journal of Medicine. However, problems may develop when these stents are used for “off-label” purposes. Experts are also concerned that both bare metal and drug-coated stents may be used too frequently.
Patients who receive a drug-coated stent must take both aspirin and an anti-platelet thienopyridine drug (usually clopidogrel) for at least 1 year after the stent is inserted, advises an important statement from the American Heart Association. Patients who cannot take a thienopyridine drug should receive a bare metal stent instead of a drug-coated stent.

Anti-Bleeding Drugs for Coronary Artery Bypass Graft (CAGB)

Aprotinin (Trasylol), a drug used to control bleeding during CABG, is more dangerous than other types of anti-bleeding drugs, according to a 2007 study in the Journal of the American Medical Association. Many experts now recommend against its use.

Diagnosis

Blood tests for biomarkers do not provide much more predictive information than standard disease risk factors, suggest several recent studies. In a 2006 study published in the New England Journal of Medicine, researchers found that risk factors such as high blood pressure, high cholesterol, and diabetes are still the best methods for predicting the likelihood of heart disease and heart-related death.

Introduction

The heart is the human body's hardest working organ. Throughout life it continuously pumps blood enriched with oxygen and vital nutrients through a network of arteries to all parts of the body's tissues.

The external structures of the heart include the ventricles, atria, arteries, and veins. Arteries carry blood away from the heart while veins carry blood into the heart. The vessels colored blue indicate the transport of blood with relatively low content of oxygen and high content of carbon dioxide. The vessels colored red indicate the transport of blood with relatively high content of oxygen and low content of carbon dioxide.

In order to perform the difficult task of pumping blood to the rest of the body, the heart muscle itself needs a plentiful supply of oxygen-rich blood, which is provided through a network of coronary arteries. These arteries carry oxygen-rich blood to the heart's muscular walls (the myocardium).

Click the icon to see an image of the anterior heart arteries.

If blood flow to the myocardium is interrupted, an injury known as an infarct occurs. This is also known as myocardial infarction or, more commonly, a heart attack.

Click the icon to see an animation about coronary artery disease.

Coronary artery disease is the end result of a complex process called atherosclerosis (commonly called "hardening of the arteries"). This causes blockage of arteries (ischemia ) and prevents oxygen-rich blood from reaching the heart. There are many steps in the process leading to atherosclerosis, some not fully understood.

Click the icon to see an image of atherosclerosis.

Increasingly, however, researchers are studying the interactions between cholesterol and processes known as oxidation and the inflammatory response.

Cholesterol and Lipoproteins. The story begins with cholesterol and sphere-shaped bodies called lipoproteins that transport cholesterol.

Cholesterol is a white, crystalline substance that is found in all animal cells and in animal-based foods. It is critical for many functions, but under certain conditions cholesterol can have harmful effects.
The lipoproteins that transport cholesterol are referred to by their size. The most commonly known are low-density lipoproteins (LDL) and high density lipoproteins (HDL). LDL is often referred to as the "bad" cholesterol and HDL as the "good" cholesterol.

Click the icon to see an image of cholesterol inside an artery.

Oxidation. The damaging process called oxidation is an important trigger in the atherosclerosis story.

Oxidation is a chemical process in the body caused by the release of unstable particles known as oxygen-free radicals. It is one of the normal processes in the body, but under certain conditions (such as exposure to cigarette smoke or other environment stresses) these free radicals are overproduced.
In excess amounts, they can be very dangerous, causing damaging inflammation and even affecting genetic material in cells.
In heart disease, free radicals are released in artery linings and oxidize low-density lipoproteins (LDL). The oxidized LDL is the basis for cholesterol build-up on the artery walls and damage leading to heart disease.

Inflammatory Response. For the arteries to harden there must be a persistent reaction in the body that causes ongoing harm. Researchers now believe that this reaction is an immune process known as the inflammatory response. The following is one theory about how the inflammatory response contributes to heart disease:

The injuries to the arteries during oxidation signal the immune system to release white blood cells (particularly those called neutrophils and macrophages) at the site. These factors initiate the inflammatory response.
Macrophages literally "eat" foreign debris, in this case oxidized LDL cholesterol.
The process converts LDL cholesterol into foamy material that attaches to the smooth muscle cells of the arteries. The cholesterol becomes mushy and accumulates on artery walls.
Over time the cholesterol dries and forms a hard plaque, which causes further injury to the walls of the arteries.
In response to this additional harm, the immune system releases other factors called cytokines. These are powerful inflammatory molecules that attract more white blood cells and perpetuate the whole cycle, causing persistent injury to the arteries.

Click the icon to see an image of atherosclerosis.

Evidence is growing that the inflammatory response may be present not only in local plaques in single arteries but also throughout the arteries leading to the heart.

Blockage in the Arteries. Eventually these calcified (hardened) arteries become narrower (a condition known as stenosis).

As this narrowing and hardening process continues, blood flow slows and prevents sufficient oxygen-rich blood from reaching the heart.
Such oxygen deprivation in vital cells is called ischemia. When it affects the coronary arteries, it causes injury to the tissues of the heart.
Injured inner vessel walls also fail to produce enough nitric oxide, a substance critical for maintaining blood vessel elasticity. (Nitric oxide has complex effects and may increase inflammation in the arteries.)
These narrow and inelastic arteries not only slow down blood flow but also become vulnerable to injury and tears.

Click the icon to see an image of coronary artery blockage

The End Result: Heart Attack. Heart attack can occur as a result of one or two effects of atherosclerosis.

(1) If the artery becomes completely blocked and ischemia becomes so extensive that oxygen-bearing tissues around the heart die.

(2) If the plaque itself develops fissures or tears. Blood platelets adhere to the site to seal off the plaque, and a blood clot (thrombus) forms. A heart attack can then occur if the formed blood clot completely blocks the passage of oxygen-rich blood to the heart.

Click the icon to see an image of the developmental process of atherosclerosis.

Angina is the primary symptom of coronary artery disease and, in severe cases, of a heart attack. It is typically experienced as chest pain and occurs when the heart muscle does not get as much blood (hence as much oxygen) as it needs for a given level of work (ischemia). Angina is usually referred to as one of two states:

Click the icon to see an image about angina.

Stable Angina (which is predictable)
Unstable Angina (which is less predictable and a sign of a more serious situation)

Angina itself is not a disease. Much evidence indicates that onset of angina less than 48 hours before a heart attack may be protective, possibly by conditioning the heart to resist the damage resulting from the attack. Angina may be experienced in different ways and can be mild, moderate, or severe.

Click the icon to see an image of angina.

Specific factors are typically considered in determining whether symptoms indicate angina:

Quality of the pain. Angina pain is typically described by patients as squeezing, heavy, suffocating, or griplike. It is rarely described as stabbing or burning. Changing one's position or breathing in and out does not affect the pain. The intensity of the pain does not always relate to the severity of the medical problem. Some people may feel a crushing pain from mild ischemia, while others might experience only mild discomfort from severe ischemia. In some cases, the patient experiences shortness of breath, fatigue, or palpitations instead of pain. In others, the ischemia is entirely asymptomatic ("silent ischemia").
Duration. A typical angina attack lasts minutes. If it is more fleeting or lasts for hours, it is probably not angina.
Location. Pain is usually in the chest under the breast bone. It often radiates to the neck, jaw, or left shoulder and arm. Less commonly, patients report symptoms that radiate to the right arm or back.
Triggers of Angina. Angina is usually triggered by physical exertion, emotional stress, or exposure to cold.
Factors that Relieve Angina. Angina is usually relieved by rest or by taking nitroglycerine under the tongue.

Stable Angina. Stable angina is predictable chest pain. Although less serious than unstable angina, it can be extremely painful. It is usually relieved by rest and responds well to medical treatment (typically nitroglycerin). Any event that increases oxygen demand can cause an angina attack. Some typical triggers include:

Exercise
Cold weather
Emotional tension
Large meals

Angina attacks can occur at any time during the day, but most occur between 6 a.m. and noon.

Unstable Angina and Acute Coronary Syndrome. Unstable angina is a much more serious situation and is often an intermediate stage between stable angina and a heart attack, in which an artery leading to the heart (a coronary artery) becomes completely blocked. A patient is usually diagnosed with unstable angina under one or more of the following conditions:

Pain awakens a patient or occurs during rest.
A patient who has never experienced angina has severe or moderate pain during mild exertion (walking two level blocks or climbing one flight of stairs).
Stable angina has progressed in severity and frequency within a 2-month period, and medications are less effective in relieving its pain.

Unstable angina is now usually discussed as part of a condition called acute coronary syndrome (ACS). ACS also includes people with a condition called NSTEMI (non ST-segment elevation myocardial infarction) -- also referred to as non-Q wave heart attack. With NSTEMI, the blood tests suggest a developing heart attack. These conditions are less severe than heart attacks but may develop into full-blown attacks without aggressive treatment. [See In-Depth Report #12: Heart attack and acute coronary syndrome.]

Prinzmetal's Angina. A third type of angina, called variant or Prinzmetal's angina, is caused by a spasm of a coronary artery. It almost always occurs when the patient is at rest. About two-thirds of people with it have severe atherosclerosis in at least one major blood vessel. Irregular heartbeats are common, but the pain is generally relieved immediately with standard treatment.

Click the icon to see an image of a coronary artery spasm.

Silent Ischemia. Some people with severe coronary artery disease do not experience angina pain. This condition is known as silent ischemia, which some experts attribute to abnormal processing of heart pain by the brain. This is a dangerous condition because patients have no warning signs of heart disease. Some studies suggest that people with silent ischemia experience higher complication and mortality rates than those with angina pain. (Angina pain may actually protect the heart by conditioning it before a heart attack.)

Syndrome X. Syndrome X is a condition that occurs when patients have atypical angina chest pain. Their electrocardiograms are abnormal during a stress test, but they have no signs of blocked arteries. It is more likely to occur in women. Although it unclear what causes this condition, imaging tests suggest that Syndrome X may also be caused by ischemia, as is angina.

Prognosis

According to a 2007 report, nearly 16 million Americans have coronary artery disease. In the U.S., coronary artery disease is the leading killer of both men and women. In 2004, nearly 500,000 people died because of CAD. On the positive side, heart attack mortality rates have been declining. Half of men and 63% of women who die of heart disease do not have angina or other warning symptoms prior to their fatal attacks. Although at this time no tests can reliably predict whether a heart attack will occur, experts estimate that up to 30% of fatal attacks and many follow-up surgeries could be avoided with healthy lifestyle changes and by sticking to medical treatments. Two-thirds of patients who have suffered a first heart attack, however, do not take the necessary steps to prevent another.

The following syndromes suggest different degrees of severity among patients with heart disease.

Stable Angina. This condition can usually be managed with lifestyle measures and medications, such as low-dose aspirin. The more severe the angina, however, the greater the chance for progressing to a more serious condition.

Acute Coronary Syndromes (ACS). ACS includes severe and sudden heart conditions that require aggressive treatment but have not developed into a full-blown heart attack. ACS refers to either unstable angina or NSTEMI (non ST-segment elevation myocardial infarction). NSTEMI is also known as non Q-wave myocardial infarction.

Angina is a specific type of pain in the chest caused by inadequate blood flow through the blood vessels (coronary vessels) of the heart muscle (myocardium).

Unstable angina is potentially serious and chest pain is persistent, but blood tests do not show markers for heart attack.
With NSTEMI, the blood tests suggest a developing heart attack, but, most likely, injury in the arteries is less serious than with a full-blown heart attack.

Most discussions of the treatment of unstable angina now refer to acute coronary syndrome. Doctors use the presence of a number of factors to help predict which ACS patients are most at risk for developing a heart attack.

First, patients are categorized by whether they have a history of heart disease or risk factors for heart disease (such as diabetes, high blood pressure, peripheral artery disease) or other complicating conditions (such as lung disease, heart failure). The doctor also evaluates the severity of the angina. Other factors that pose a high risk for ACS include:

Age 65 years or older
Evidence of severe heart tissue injury
Having a lighter weight
Having a history of severe chronic angina
Having abnormal lung sounds called rales (a bubbling or crackling sound) on examination
ST-segment deviation
Having either very slow or very fast heat beats
Having very low blood pressure

Heart Attack. A full-blown heart attack occurs with severe damage to the heart, which blocks oxygen.

ANYONE WHO BELIEVES THEY ARE HAVING A HEART ATTACK SHOULD IMMEDIATELY CALL THE EMERGENCY MEDICAL SYSTEM (911 IN THE UNITED STATES).

People with known heart disease and any unusual chest pain or other symptoms of heart attack that do not clear up with medications should go to the hospital. The degree of pain and the specific symptoms before a heart attack vary greatly among individuals. Symptoms can be abrupt, gradual, or intermittent.

Chest Pain. People with heart disease or risk factors should be concerned about any chest pain, usually precipitated by exercise or stress, that interrupts normal activities and does not clear up after resting or taking angina medications. Chest symptoms might be experienced as follows:

Pain is typically felt as a crushing weight against the chest, accompanied by profuse sweating. The pain may radiate to the left shoulder and arm, the neck or jaw, and even infrequently to the right arm. The arm may be tingling or numb.
Some people may have only a tingling sensation or a sense of fullness, squeezing, or pressure in the chest.
In some patients with a history of heart disease, chest pain is mild. Such patients may have experienced unexplained fatigue, depression, and ill health within a month of a heart attack. Although chest pain is the classic symptom, it occurs in only about half of patients with a heart attack.

Other Common Symptoms.

Nausea, vomiting, and cold sweats
A feeling of indigestion or heartburn
Fainting
A great fear of impending death, a phenomena known as angor animi

Atypical Symptoms. Some studies suggest that nearly half of patients with heart attack do not have chest pain as the primary symptom. Common atypical symptoms of a heart attack include:

Shortness of breath
Cardiac arrest
Dizziness, weakness, and fainting
Abdominal pain

Patients most likely to have atypical symptoms are women and the very elderly (although they can certainly have classic heart attack symptoms as well).

In one study, 52% of elderly people with acute coronary syndrome had atypical symptoms that included shortness of breath, nausea, profuse sweating, pain in the arms, and fainting. Such symptoms were more likely to occur in people with personal or family history of heart disease.
Before a heart attack, women are more likely than men to be nauseous and experience pain high in the abdomen or chest. Their first symptom may be extreme fatigue after physical activity rather than chest pain. Chest pain in women is also more likely to be caused by non-heart problems than in men.

Symptoms That Are Less Likely to Indicate a Heart Attack. The following symptoms are less likely to be due to a heart attack:

Sharp pain brought on by lung movements or coughing
Pain that is mainly or only in the middle or lower abdomen
Pain that can be pinpointed with the top of one finger
Pain that can be reproduced by moving or pressing on the chest wall or arms
Pain that is constant and lasts for hours (although no one should wait hours if they suspect they are having a heart attack)
Pain that is very brief and lasts for a few seconds
Pain that spreads to the legs

However, the presence of these symptoms does not always rule out a serious heart event.

Chest pain is a very common symptom in the emergency room, but heart problems account for only 10 - 33% of all episodes.

The most common causes of chest pain are muscular and bone problems. Problems affecting the ribs and chest muscles include injured muscles, fractures, arthritis, spasms, and infections.

Other causes of chest pain include:

Anxiety attacks
Gastrointestinal disorders (gallstone attacks, peptic ulcer disease, hiatal hernia, heartburn)
Asthma
Spasm in the coronary artery
Abnormalities of the heart muscle
Rupture of the aorta
Collapsed lung
Acute inflammation of the heart
Blood clot in the lung
High thyroid levels (hyperthyroidism)
Anemia
Vasculitis (a group of disorders that cause inflammation of the blood vessels)
Exposure to high altitudes (rare)

Individuals who experience symptoms of a heart attack should take the following actions:

For angina patients, take one nitroglycerin dose either as an under-the-tongue tablet or in spray form at the onset of symptoms. Take another dose every 5 minutes up to three doses or when the pain is relieved, whichever comes first.
Call 911 or the local emergency number. This should be the first action taken if angina patients continue to experience chest pain after taking the full three doses of nitroglycerin. However, only 20% of heart attacks occur in patients with long-standing angina. Therefore, anyone who has heart disease or risk factors for it and experiences heart attack symptoms should contact emergency services.
The patient should chew an aspirin (250 - 500 mg) and be sure that emergency health providers are informed of this so an additional dose is not given.
Patients with chest pain should go immediately to the nearest emergency room, preferably traveling by ambulance. They should not drive themselves.

Click the icon to see an image about heart attack symptoms.

Click the icon to see another image about heart attack symptoms.

Risk Factors

Over 13 million Americans have had angina, a heart attack, or both. Each year, about 1.2 million people will experience a serious heart event. About 25% of all Americans have one or more risk factors for heart disease. Most risk factors for heart disease are related to lifestyle and environmental factors.

Over the past decades, heart disease rates declined in both men and women as they quit smoking and improved dietary habits. This rate, however, has stabilized in recent years, most likely because of the dramatic increase in obesity in the U.S. and other industrialized nations. There have also been minimal changes in other risk factors, including smoking, sedentary behavior, and blood pressure control. Some risk factors cannot be changed, including age, gender, and genetics. Nevertheless, their effects can still be modified with healthy lifestyle changes.

Heart disease may be prevented with a healthy diet and regular exercise, and by quitting smoking if you smoke. Follow your health care provider's recommendations for the treatment and prevention of heart disease.

The American Heart Association guidelines for preventing heart disease recommend:

Improve Cholesterol. People with at least two risk factors and a 10-year risk for heart disease or stroke of more than 20% should aim for LDL levels of less than 100 mg/dl. Statins are now used in more cases.

Keep Blood Pressure Low. People in normal health should have a blood pressure reading of 120/80 mm Hg or less. According to the latest guidelines, blood pressure readings of 120/80 are considered normal, readings of 140/90 or higher indicate hypertension, and readings in between the two are called pre-hypertension. Patients with diabetes or chronic kidney disease should maintain blood pressure readings of 130/80 mm Hg or less, while others should be no higher than 140/90 mm Hg.

Exercise. Everyone in normal health should engage in at least moderate physical activity for a minimum of 30 minutes on most, if not all, days of the week.

Healthy Diet. Everyone should aim for a diet that contains a healthy balance of fruits, vegetables, grains, fish, nuts, legumes, poultry, lean meat, and low-fat dairy items. Avoid saturated fats and trans-fatty acids.

Quit Smoking. Also avoid exposure to secondhand smoke.

Maintain Weight. People should aim for a BMI index of 18.5 - 24.9.

Taking Aspirin. People whose risk for heart disease within 10 years is 10% or more should take a low-dose aspirin every day, unless they have medical reasons to avoid aspirin.

Control Diabetes. People with diabetes should aim for fast blood glucose levels of less than 110 mg/dl and hemoglobin A1C or less than 7%.

Control Atrial Fibrillation. People with atrial fibrillation should use anticoagulants to reduce the risk for blood clots.

Age. About 85% of people who die from heart disease are over the age of 65.

Gender. Coronary artery disease and heart attacks are much more common in middle-aged men. Women have, on average, 10 - 15 more years of heart disease-free life than do men, but as women age, they catch up to men. Women, in fact, are more likely to have angina than men. Younger women with heart disease often do not have the same symptoms as their male counterparts and may be less likely to be diagnosed correctly. They are also more likely than men to die after a heart attack.

In 2007, the American Heart Association issued updated guidelines focusing on prevention of heart disease in women. The new guidelines recommend:

Healthy diet (fresh fruits and vegetables, low-fat dairy products, salt and saturated fat restrictions, alcohol moderation)
Eating oily fish (such as salmon) at least twice a week. Women with existing heart disease should consider taking fish oil supplements of 850 – 1,000 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DPA).
Increased physical activity (60 – 90 minutes, preferably 7 days a week)
Quitting smoking
Low-dose aspirin therapy for all women age 65 years and older who can safely take aspirin. High-risk women may require 75 – 325 mg / day; lower-risk women may benefit from 81 mg a day or 100 mg every other day.

Genetic Factors. Genetics are involved in increasing the likelihood of developing important risk factors such as diabetes and high blood pressure. For example, one genetic variant called apolipoprotein E4 (ApoE4) affects cholesterol levels, particularly those associated with heart disease.

Ethnicity. African-American women face the highest risk for death from heart disease, and their rate of heart attacks is increasing. (Mortality rates in men do not differ much by race.) Native American men have a lower risk for heart disease than Caucasian men, and Hispanics have the lowest risk for heart disease of all major American population groups.

African-Americans face a number of biologic and social dangers to their hearts.

They have a higher prevalence of diabetes and hypertension than do Caucasians.
They tend to have poorer diets, higher stress levels, and less access to health care.
All African-Americans risk discrimination in obtaining optimal treatments, but women may be at particular risk for unequal treatment. In one study in which female actors portrayed heart patients, African-American women were 60% less likely to receive aggressive (and expensive) diagnostic tests than African-American men or any Caucasians, even though they presented with similar symptoms.
While African-Americans comprise 13% of the U.S. population, African-Americans have comprised only 2 - 9% of subjects in most major research trials, so knowledge about their specific risks is limited.
Some African-Americans with coronary artery disease appear to have a genetic trait that increases the danger of triglycerides, which may be particularly hazardous for women.

Click the icon to see an image about ethnicity and heart disease risks.

Cholesterol. In spite of its bad press, cholesterol is an essential nutrient necessary for many cellular functions. However, when certain cholesterol levels rise in the blood, they can have dangerous consequences, depending on the type of cholesterol. Low-density lipoprotein (LDL) cholesterol is the "bad" cholesterol responsible for many heart problems. Triglycerides are another type of lipid (fat molecule) that can be bad for the heart. High-density lipoprotein (HDL) cholesterol is the "good" cholesterol that helps protect against heart disease. Doctors test for a "total cholesterol" profile that includes measurements for LDL, HDL, and triglycerides. The ratio of these lipids can affect heart disease risk.

For example, according to one study, men with total cholesterol levels over 240 mg/dl have a risk that is two to four times higher than men whose cholesterol is below 200. A number of studies have demonstrated that reducing LDL and total cholesterol levels and boosting high-density lipoprotein (HDL) levels can improve survival and prevent heart attacks in people with and without heart disease.

It is very difficult to measure LDL levels by themselves, but LDL levels can be reliably calculated by the Friedewald formula: LDL=TC-HDL-TG/5. (LDL=low-density lipoprotein; TC= total cholesterol; HDL=high-density lipoprotein; TG=triglycerides.)

Click the icon to see an image about serum cholesterol.

Cholesterol Goals. In 2004, the National Cholesterol Education Program updated its clinical practice guidelines. The new recommendations set lower treatment goals for LDL levels based on a patient's risk factors for heart disease.

These risk factors include:

Having a first-degree female relative diagnosed with heart disease before age 65 or a first-degree male relative diagnosed before age 55
Being male and over age 45 or female and over age 55
Cigarette smoking
Diabetes
High blood pressure
Metabolic syndrome (risk factors associated with obesity such as low HDL levels and high triglycerides

Having two or more of these risk factors indicates a greater than 20% chance of having a heart attack within 10 years.


Risk Level	Goal (d/L)	Optimal Goal(d/L)
Very High Risk	70	70
High Risk	100	70
Moderate Risk	130	100
Low Risk	160	130

LDL cholesterol, together with other risk factors for heart disease, is the best determinant for whether cholesterol therapy is needed and whether it is working properly. In particular, the new guidelines emphasize lower LDL levels and earlier treatment for people with coronary artery disease, or other forms of atherosclerosis, and diabetes.


Total Cholesterol Goals	LDL Goals	HDL Goals	Triglyceride Goals
Less than 200 mg/dL is desirable. Between 200 and 239 is borderline. Over 240 is high.	70 mg/dL or less is the new goal for very high-risk patients (recent heart attack; current active or unstable cardiovascular or cerebrovascular disease; or two multiple risk factors as defined above.) Below 100 mg/dl is optimal for everyone. It should be the goal for high-risk people including those with existing heart disease, diabetes, or two or more risk factors for heart disease; 70 mg/dL is an optimal goal for these individuals. 130 mg/dl or below for people with two or more risk factors; 100 mg/dL is the optimal goal. 160 mg/dl or less for people at less risk (one or zero risk factors); 130 mg/dL is the optimal goal. Anything over 160 is high with levels over 190 being very high. LDL levels over 190 require medication even with no other cardiac risk factors present.	Levels above 40 mg/dL are desirable; levels above 60 mg/DL are optimal.	Below 150 mg/dL is normal. 150-199 is borderline high. 200-499 is high. Over 500 is very high.
*Risk factors for heart disease include a family history of early heart problems before age 55 for men, before age 65 for women, smoking, high blood pressure, diabetes, being older (over 45 for men and 55 for women), and having HDL levels below 35 mg/dl. People with two or more of these risk factors may have a 10-year risk of heart attack that exceeds 20%, and may therefore need to aim for LDL levels of 100 mg/dL or below.

Other Lipids. Elevated levels of other fatty molecules (lipids) are also now thought to be important indicators of heart disease risk. Studies are finding an elevated risk for angina and first heart attacks in people with elevated levels of lipoprotein(a), or lp(a). This lipoprotein falls somewhere in density between HDL and LDL and may have some properties that increase the risk for blood clots. Some experts suggest, however, that high levels of lp(a) may merely be markers of late-stage atherosclerosis, not a cause.

[See In-Depth Report #23: Cholesterol; and In-Depth Report #43: Heart-healthy diet.]

High blood pressure, or hypertension, has long been a proven cause of coronary artery disease. Blood pressure is categorized as normal, prehypertensive, and hypertensive (which is further divided as Stage 1 or 2 according to severity). High blood pressure is generally considered to be a blood pressure reading greater than or equal to 140 mm Hg (systolic) or greater than or equal to 90 mm Hg (diastolic). Blood pressure readings in the prehypertension category (120 - 139 systolic or 80 - 89 diastolic) indicate an increased risk for developing hypertension. [See Table Blood Pressure Ranges.]

A normal blood pressure reading is 120/80 mm Hg or lower. Most people with high blood pressure should aim for a goal of below 140/90 mm Hg. Patients with certain health problems should aim lower (blood pressure in patients with kidney disease, heart failure, or diabetes should be equal to or lower than 130/80 mm Hg.)

Click the icon to see an image about hypertension.


Blood Pressure Category	Ranges for Most Adults (systolic/diastolic)
Normal Blood Pressure (systolic/diastolic)	Systolic below 120 mm Hg Diastolic below 80 mm Hg
Prehypertension (Formerly Classified as Normal to High-Normal Blood Pressure)	Systolic 120 to 139 mm Hg Diastolic 80 to 89 mm Hg (NOTE: 139/89 or below should be the minimum goal for everyone. People with diabetes or chronic kidney disease should strive for 130/80 or less.)
Mild Hypertension (Stage 1)	Systolic 140 to 159 mm Hg Diastolic 90 to 99 mm Hg
Moderate-to-Severe Hypertension (Stage 2)	Systolic over 160 mm Hg and/or Diastolic over 100 mm Hg
Note: If one of the measurements is in a higher category than the other, the higher measurement is usually used to determine the stage. For example, if systolic pressure is 165 (Stage 2) and diastolic is 92 (Stage 1), the patient would still be diagnosed with Stage 2 hypertension. A high systolic pressure should be a major focus of concern in most adults.

American obesity is at epidemic levels in all age groups. The effect of obesity on cholesterol levels is complex. Although obesity does not appear to be strongly associated with overall cholesterol levels, among obese individuals triglyceride levels are usually high while HDL (beneficial cholesterol) levels tend to be low, both risk factors for heart disease. Obesity has other effects (hypertension, increase in inflammation) that pose major risks to the heart.

Click the icon to see an image of childhood obesity.

Obesity is particularly hazardous when it is one of the components of the metabolic syndrome. This syndrome is diagnosed when three of the following are present: abdominal obesity, low HDL cholesterol, high triglyceride levels, high blood pressure, and insulin resistance. Metabolic syndrome is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. A 2002 study estimated that 24% of the population now has this condition. Obesity is highly linked with type 2 diabetes, and diabetes itself poses a significant risk for high cholesterol levels and heart disease.

Some obese patients with coronary artery disease may consider having bariatric surgery (stomach bypass) to lose excess weight. The weight lost after surgery can help improve blood pressure, cholesterol, blood sugar and other factors associated with CAD. A 2005 study reported that bariatric surgery is safe for patients with CAD who cannot lose weight with diet and exercise, which should always be tried first.

[See In-Depth Report #53: Weight control and diet.]

People who are sedentary are almost twice as likely to suffer heart attacks as are people who exercise regularly. Exercise has a number of effects that benefit the heart and circulation, including:

Improving cholesterol and lipid levels
Reducing inflammation in the arteries
Assisting weight loss programs
Helping to keep blood vessels flexible and open

Studies continue to show that physical activity and avoiding high-fat foods are the two most successful means of reaching and maintaining heart healthy levels of fitness and weight.

Experts have been attempting to define how much exercise is needed to produce heart benefits. In 2002, a well-conducted study on overweight adults confirmed previous research that reported beneficial changes in cholesterol and lipid levels even when people performed low amounts of moderate or high intensity exercise (walking or jogging 12 miles a week). However, more intense exercise is required to significantly change cholesterol levels, notably by increasing HDL (the so-called good cholesterol). Overweight people who have trouble losing pounds can still achieve considerable heart benefits by exercising. Resistance (weight) training has also been associated with heart protection. Exercises that train and strengthen the chest muscles may prove to be very important for patients with angina.

Click the icon to see an image about exercise.

Click the icon to see an image about hypertension and lifestyle changes.

Some studies suggest that for the greatest heart protection, it is not the duration of a single exercise session that counts but the total daily amount of energy expended. Therefore, the best way to exercise may be in multiple short bouts of intense exercise, which can be particularly helpful for older people.

Sudden strenuous exercise (such as snow shoveling and mowing lawns) puts many people at risk for angina and heart attack. Activities that involve raising the arms above the head may also be risky. Patients with angina should never exercise shortly after eating. People with risk factors for heart disease should seek medical clearance and a detailed exercise prescription. And all people, including healthy individuals, should listen carefully to their bodies for signs of distress as they exercise. [See In-Depth Report #29: Exercise.]

Heart disease and stroke are the leading causes of death in people with diabetes. People with diabetes are at risk for the following heart-risk conditions, and the more of these conditions they have, the worse the outlook.

High blood pressure (hypertension). Up to 75% of cardiovascular problems in people with diabetes may be due to hypertension.
Very unhealthy cholesterol and lipid balances (high triglyceride levels and lower HDL).
Blood clotting problems.
Impaired nerve function (neuropathy), which can also damage the heart. Some experts estimate that the mortality rates from neuropathy-related heart conditions range from 15 - 53%.

People with both diabetes and heart disease may have a higher risk for silent ischemia, a condition in which people have blocked arteries but do not experience the angina, the chest pain that signals heart disease. [See In-Depth Report #9: Diabetes - type 1; or In-Depth Report #60: Diabetes - type 2.]

Peripheral artery disease (PAD) occurs when atherosclerosis affects the extremities, particularly the feet and legs. The major risk factors for heart disease and stroke are also the most important risk factors for PAD. (The combination of such conditions with PAD also produces more severe forms of heart or circulatory disease.) Although signs of heart disease are detected in only 20 - 40% of patients with PAD after an initial diagnosis, studies suggest that when intense heart-diagnostics tests are performed, such as angiography or thallium stress tests, co-existing heart disease is detected in up to 90% of all PAD patients. [See In-Depth Report #102: Peripheral artery disease.]

Smokers in their 30s and 40s have a heart-attack rate that is five times higher than their nonsmoking peers. Cigarette smoking may be directly responsible for at least 20% of all deaths from heart disease, or about 120,000 deaths annually. Smoking cigars may increase the risk of early death from heart disease, although evidence is much stronger for cigarette smoking. Although heavy cigarette smokers are at greatest risk, a 2002 study suggested that people who smoke as few as three cigarettes a day are at higher risk for blood vessel abnormalities that endanger the heart. Regular exposure to passive smoke also increases the risk of heart disease in nonsmokers. [See In-Depth Report #41: Smoking.]

Eating habits can be protective or dangerous to the heart. Avoiding saturated fats and trans-fatty acids is particularly important for controlling cholesterol.

Diet plays an important role in the health of the heart. In 2006, the American Heart Association (AHA) issued revised diet and lifestyle recommendations. The current guidelines recommend:

Balance calorie intake and physical activity to achieve or maintain a healthy body weight. (Controlling weight, quitting smoking, and exercising regularly are essential companions of any diet program. Try to get at least 30 minutes, and preferably 60 – 90 minutes, of daily exercise.)
Consume a diet rich in a variety of vegetables and fruits. Vegetables and fruits that are deeply colored (spinach, carrots, peaches, berries) are especially recommended as they have the highest micronutrient content.
Choose whole-grain, high-fiber foods. These include fruits, vegetables, and legumes (beans). Good whole grain choices include whole wheat, oats/oatmeal, rye, barley, brown rice, buckwheat, bulgur, millet, and quinoa.
Consume fish, especially oily fish, at least twice a week (about 8 ounces/week). Oily fish such as salmon, mackerel, and sardines are rich in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Consumption of these fatty acids is linked to reduced risk of sudden death and death from coronary artery disease.
Limit daily intake of saturated fat (found mostly in animal products) to less than 7% of total calories, trans fat (found in hydrogenated fats, commercially baked products, and many fast foods) to less than 1% of total calories, and cholesterol (found in eggs, dairy products, meat, poultry, fish, shellfish) to less than 300 mg per day. Choose lean meats and vegetable alternatives (such as soy). Select fat-free and low-fat dairy products. Grill, bake, or broil fish, meat, and skinless poultry.
Use little or no salt in your foods. Reducing salt can lower blood pressure and decrease the risk of heart disease and heart failure.
Cut down on beverages and foods that contain added sugars (corn syrups, sucrose, glucose, fructose, maltrose, dextrose, concentrated fruit juice, honey.)
If you consume alcohol, do so in moderation. The AHA recommends limiting alcohol to no more than 2 drinks per day for men and 1 drink per day for women.

[See In-Depth Report #43: Heart-healthy diet.]

Stress. The effects of mental stress on heart disease are controversial. Stress can affect the heart when it activates the sympathetic nervous system (the automatic part of the nervous system that affects many organs, including the heart). Some studies suggest an association between acute stress and a higher risk for serious cardiac events, such as heart rhythm abnormalities and heart attacks, in people with heart disease. However, not all studies report strong evidence that stress has any effect on the heart, particularly in people without any history of heart disease. [See In-Depth Report #31: Stress.]

Depression. Depression increases the severity of heart attack and may even worsen a patient's response to medication for heart disease. Although people with heart disease may become depressed, this does not explain entirely the link between the two problems. Data suggest that depression itself may be a risk factor for heart disease as well as its increased severity.

A number of studies indicate that depression has biologic effects on the heart, including blood clotting and heart rate. One study, for example, reported an association between depression and a greater risk for death from heart problems even in people without a history of heart disease. Even mild depression, which includes feelings of hopelessness experienced over many years, may harm the heart. A 2007 study suggested that depressive symptoms (fatigue, loss of appetite) may be a sign of thickening arteries, the early stage of coronary artery disease. [See In-Depth Report #8: Depression.]

Benefits of Moderate Drinking. Several studies have found heart protection from moderate intake of alcohol (one or two glasses a day). Moderate alcohol consumption can help boost HDL levels. Alcohol may also prevent blood clots and inflammation. Although red wine is most often cited for healthful properties, any type of alcoholic beverage appears to have similar benefit.

Adverse Effects of Heavy Drinking. By contrast, heavy drinking harms the heart. In fact, heart disease is the leading cause of death in alcoholics. Evidence suggests that people who consume more than three drinks a day have abnormal blood clotting factors. Heavy alcohol consumption can raise blood pressure, and binge drinking may increase the risk for hemorrhagic stroke (caused by bleeding in the brain). Large doses of alcohol can trigger irregular heartbeats, which can be dangerous in people with existing heart disease.

Pregnant women and people who can't drink moderately should not drink at all.

Homocysteine and Vitamin B Deficiencies. Deficiencies in the B vitamins folate (known also as folic acid), B6, and B12 have been associated with a higher risk for heart disease in some studies. Such deficiencies produce higher blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure. Researchers have been studying whether vitamin B supplements can reduce homocysteine levels and, consequently, heart disease risks.

Several major 2006 studies indicated that while B vitamin supplements do help lower homocysteine levels, they have no effect on heart disease outcomes. The studies, published in the New England Journal of Medicine, examined patients who had either recently had a heart attack or suffered from diabetes or heart disease. Results showed a similar number of heart attacks and strokes among patients who took B vitamins and those who received placebo. Some experts think that homocysteine may be a marker for heart disease rather than a cause of it.

Click the icon to see the benefits of vitamin B.

Click the icon to see the food sources of vitamin B.

C-Reactive Protein. C-reactive protein is a product of the inflammatory process. Evidence increasingly suggests that high levels may predict future heart disease. It is not known if the protein plays any causal role or whether it is simply a marker for other factors in the disease process.

C. pneumoniae and Other Infectious Organisms. Some microorganisms and viruses have been under suspicion for triggering the inflammation and damage in the arteries that contribute to heart disease. The strongest evidence to date supports a possible role from Chlamydia (C.) pneumoniae (a non-bacterial organism that causes mild pneumonia in young adults). C. pneumoniae has been detected in plaques in the arteries of patients with heart disease. In some studies, evidence of previous infection has been associated with a higher risk for heart events.

Other studies also suggest that cytomegalovirus (CMV), a common virus, may have similar effects. Many people, however, have been infected with these organisms, and no clear association has been found with any of these infections.(H. pylori, the bacteria that causes peptic ulcers, has also been studied for heart effects, but evidence is very weak on any link.)

Erectile Dysfunction. Recent research suggests that erectile dysfunction may be a warning sign of coronary artery disease, even in men who are not considered at risk for the condition. Some studies indicate that men with erectile dysfunction have higher levels of C-reactive protein and more symptoms of atherosclerosis than men without erectile problems.

Periodontal Disease. A number of studies support an association between periodontal disease and cardiovascular disorders. According to a 2003 major analysis, periodontal (gum) disease is associated with a 20% higher risk for ischemic stroke and heart disease. (The added risk may be even higher in adults under 65.) Recent evidence is pointing to the inflammatory response as the common element.

Click the icon to see an image of gum disease.

Anemia. Anemia has adverse effects on the heart and increases the severity of cardiac conditions, including heart failure and heart attacks. A 2002 study suggested that anemia may even be a risk factor for heart disease itself. Blood transfusions after a heart attack improve survival rates in elderly patients who are anemic.

Iron Overload. An inherited disease called hemochromatosis, in which the intestinal tract absorbs too much iron from food, has been associated with atherosclerosis and heart attack. About 10% of Caucasians carry the gene for this condition. There is no strong evidence that excess iron levels in people without hemochromatosis can contribute to heart disease.

Sleep Apnea. Obstructive sleep apnea is a condition in which tissues in the upper throat collapse at intervals during sleep, thereby blocking the passage of air. It has been strongly associated with high blood pressure and obesity, but is also associated with heart disease and heart attacks, regardless of these risk factors. Some evidence suggests that obstructive apneas cause an increase in stiffness and inflammation in the arteries.

Some inborn or natural conditions are not risk factors themselves but have been associated with a higher incidence of heart disease or its consequences:

Factors Before Birth and In Infancy. Low weight at birth and in the womb has been associated with later heart disease in a few studies. Some suggest, however, that this may just reflect poor nutrition in the mother, which appears to affect life-long risk.

Seasonal Differences. More deaths from heart disease occur in December and January, and the fewest in the summertime. Although lower temperatures and snow shoveling may play a role in some cases, more winter deaths have been reported even in warm regions. Holiday stress or fewer daylight hours have been suggested as other reasons for these higher winter rates.

Physical Characteristics. Male pattern baldness, hair in the ear canals, and creased earlobes are associated with a higher risk for heart disease in Caucasian males.

Click the icon to see an image of an ear lobe crease.

Diagnosis

Many tests can diagnose possible heart disease. The choice of which (and how many) tests to perform depends on the patient's risk factors, history of heart problems, and current symptoms. Usually the tests begin with the simplest and may progress to more complicated ones.

Doctors routinely check for high blood pressure and unhealthy cholesterol levels in all older adults. Specific tests are also important in people who may have risk factors or symptoms of diabetes. Doctors may also test for homocysteine, the protein albumin, and blood clotting factors, especially fibrinogen.

An electrocardiogram (ECG) measures and records the electrical activity of the heart. Between 25 - 50% of people who suffer from angina or have silent ischemia, however, have normal ECG readings. The waves measured by the ECG correspond to the contraction and relaxation pattern of the different parts of the heart. Specific waves seen on an ECG are named with letters:

The electrocardiogram (ECG, EKG) is used extensively in the diagnosis of heart disease, from congenital heart disease in infants to myocardial infarction and myocarditis in adults. Several different types of electrocardiogram exist.

P. The P wave is associated with the contractions of the atria (the two chambers in the heart that receive blood from outside).
QRS. The QRS is a series of waves associated with ventricular contractions. (The ventricles are the two major pumping chambers in the heart.)
T and U. These waves follow the ventricular contractions.

The most important wave patterns in diagnosing and determining treatment for heart disease and heart attack are called ST elevations and Q waves.

A depressed or horizontal ST wave suggests some blockage and the presence of a heart disease, even if there is no angina present. (This finding, however, is not very accurate, particularly in women, and can occur without heart problems).
ST elevations and Q waves are the most important wave patterns in diagnosing and determining treatment for a heart attack. They suggest that an artery to the heart is blocked, and that the full thickness of the heart muscle is damaged. ST segment elevations do not always mean the patient has a heart attack. And, some heart attack patients do not have elevated ST segments. Other factors are important in making a diagnosis.

The primary value of exercise stress tests is not to detect coronary artery disease but to help determine the severity and predict the outcome of an existing heart condition. It is considered for the following people:

Patients with possible or probable angina and low or intermediate risk for adverse heart events.
Selected adults who do not have symptoms of heart disease but are at moderate risk to high risk for developing heart disease (a 10 - 20% chance within 10 years). Moreover, heart blockage without angina (silent ischemia) may suggest a more severe condition, at least in men.

Basic Procedure. A stress test (exercise tolerance test) monitors the patient's heart rhythms, blood pressure, and clinical status. It can tell how well the heart handles work and if parts of the heart have decreased blood supply. A typical stress test involves:

The patient walks on a treadmill or rides a stationary bicycle. Exercise continues until the heart is beating at least 85% of its maximum rate, until symptoms of heart trouble occur (changes in blood pressure, heart rhythm abnormalities, angina, fatigue), or the patient simply wants to stop.
For patients who cannot exercise, the doctor may administer dobutamine or arbutamine, which are drugs that simulate the stress of exercise.
An ECG is used to monitor heart rhythms during a stress test. (An echocardiogram or more advanced imaging technique may also be used to visualize the actions of the heart and blood flow.)

More than 25% of patients stop exercising before they reach their own maximum limits because of fear of a heart event. Patients should be reassured that the activities performed in the test under the guidance of a professional are safe.

Interpreting Results. To accurately assess heart problems, experts look at a number of findings derived from the ECG and other tools during exercise. They include:

Exercise capacity. This is a measure of a person's capacity to reach certain metabolic rates.
Heart rate and ST waves. On ECGs, doctors specifically look for abnormalities in part of the wave tracing called an ST segment. A certain type of ST segment depression may suggest the presence of heart disease. However, gender, drugs and other medical conditions can affect the ST segment. Using a measurement that adjusts the ST segment to heart rate improves accuracy.
Dukes Treadmill Score. This important score uses the number of minutes a patient can exercise and other factors that are present in patients with exercise-limiting angina.
Heart rate recovery.
Chronotropic index. This is the percentage of the heart-rate reserve that is used during the exercise. A result of 80% or less suggests a significant risk for serious heart problems in most patients.
Changes in systolic blood pressure.

Using these and other measures, doctors can determine risk fairly accurately, particularly for men of any age with chronic stable angina. The test has limitations, however, and some are significant. For example, a 2002 study indicated that in patients with suspected unstable angina the chances for a future adverse heart event remain high even if the exercise test shows low risk. In addition, for many reasons, the test is less accurate in women, and an echocardiogram may be a more accurate procedure for them. About 10% of patients, particularly younger people, will have false positive test results. In such cases, test results indicate abnormalities when there are no heart problems.

An echocardiogram is a noninvasive test that uses ultrasound images of the heart. This test is more expensive than an ECG, but it can be very valuable, particularly when used with a stress test, to detect the location and extent of heart muscle damage. It appears to be more accurate for women than ECG stress tests, but at this time it is not routinely recommended as a replacement for most women.

Computed tomography (CT) scans used alone or with ECG may be used to detect calcium deposits on the arterial walls, which are strong indicators of current and future coronary artery disease. The presence of calcium does not always signify narrowing of the arteries. But, the absence of calcification in the arteries indicates the patient has no risk for heart disease.

Advanced CT techniques are improving accuracy:

Click the icon to see an image of a CT scan.

Electron Beam Computed Tomography. Electron beam computed tomography (EBCT) is a CT technique that scans the heart so quickly that the motion of the heart appears frozen. This procedure identifies calcification and stratifies cardiac risk accurately.
Multidetector Computed Tomography. Another CT technique called multidetector computed tomography (MDCT) is able to take pictures of the entire heart in 1 millimeter slices in the time it takes for a patient to hold one breath. A 2006 study indicated that MDCT tends to have a high “false-positive” rate (indicating disease when it is not actually there), but for some patients the test may be helpful in ruling out coronary artery disease.

Some expert groups recommend CT scans in selected patients who have an intermediate risk (10 - 20% chance of heart disease within 10 years). For some of these patients, EBCT may be preferred over exercise stress testing, but most experts recommend a stress test as the main diagnostic tool. In general, the use of these expensive imaging tests is probably not very helpful for people at low or high risk. (For people with high risk, the additional information from these tests would not add much value.) More research is needed to determine the benefits of CT scanning in specific individuals.

Radionuclide procedures use imaging techniques and computer analyses to plot and detect the passage of radioactive tracers through the region of the heart. Such tracing elements are typically given intravenously. Radionuclide imaging is useful for diagnosing and determining:

Severity of unstable angina when less expensive diagnostic approaches are unavailable or unreliable
Severity of chronic coronary artery disease
Success of surgeries for coronary artery disease.
Whether a heart attack has occurred

Various imaging techniques may be used with radionuclide procedures, including:

Planar scintigraphy uses a special overhead camera and is the oldest scanning technique.
Single-photon emission computed tomography (SPECT) uses a camera that rotates around the patient and takes pictures of "slices" of the heart. It is more accurate than planar imaging in precisely locating problems in the arteries.
Positron-emission tomographic (PET) scanners employ multiple rings that surround the patients, which detect and record atomic particles (photons) that are emitted by the tracer elements (such as radioactive oxygen, nitrogen, or carbon). It is more expensive and less widely available than SPECT.

Myocardial Perfusion (Blood Flow) Imaging Test (also called the Thallium Stress Test). This radionuclide test is typically used with an exercise stress test to determine blood flow to the heart muscles. It is a reliable measure of severe heart events. It may be useful in determining the need for angiography if CT scans have detected calcification in the arteries. About a minute before the patient is ready to stop exercising, the doctor administers a radioactive tracer into the intravenous line. (Tracers include thallium, technetium, or sestamibi.) Immediately afterwards, the patient lies down for a heart scan, usually with a planar scintigraphy or with SPECT. If the scan detects damage, more images are taken 3 or 4 hours later. Damage due to a prior heart attack will persist when the heart scan is repeated. Injury caused by angina, however, will have resolved by that time.

Radionuclide Angiography. This is a technique for visualizing the chambers and major blood vessels of the heart. It uses an injected radioactive tracer and can be performed during exercise, at rest, or with use of stress-inducing drugs. It is an excellent test for assessing the heart's pumping action and for determining the severity of coronary artery disease. It is an alternative to echocardiograms in certain situations.

Click the icon to see an internal view of the heart.

Magnetic Resonance Angiography (MRA). MRA is a very promising noninvasive imaging technique that can provide three-dimensional images of the major arteries to the heart and identify disease with high accuracy. Experts believe this approach will eventually be a good alternative to angiography.

Click the icon to see an image of a MRI.

Angiography is an invasive test. It is used for patients who show strong evidence for severe obstruction on stress and other tests, and for patients with acute coronary syndrome.

A narrow tube is inserted into an artery, usually in the leg or arm, and then threaded up through the body to the coronary arteries.
A dye is injected into the tube, and an x-ray records the flow of dye through the arteries.
This process provides a map of the coronary circulation, revealing any blocked areas.

Click the icon to see an image of dye in the coronary artery.

Major complications include stroke, heart attacks, and kidney damage. These risks are very low (about 0.1%), however, if the procedure is done in an experienced medical center (one that performs at least 300 of these operations every year). Allergic reactions can also occur. The procedure is expensive, and between 10 - 30% of patients who have this procedure have normal results.

When heart cells become damaged, they release different enzymes and other molecules into the bloodstream. Elevated levels of such markers of heart damage in the blood or urine may help predict a heart attack in patients with severe chest pain and help determine treatment. Some of these factors include:

Troponins. The proteins cardiac troponin T and I are released when the heart muscle is damaged. Both are proving to be among the best diagnostic indications of heart attacks. They help to identify many individuals with ACS who might otherwise be misdiagnosed.
Creatine kinase myocardial band (CK-MB). CK-MB has been a standard marker, but the MB fraction is not as accurate as troponin levels, since elevated levels can appear in people without heart injury.
Myoglobin. Myoglobin is a protein found in heart muscles. It is released early in the injured heart, and it may be useful in combination with CK-MB and the troponins.
Newer biomarkers, including C-reactive protein (CRP), homocysteine, B-type natriuretic peptide (BNP), urinary albumin, and fibrinogen.

Several 2006 studies that evaluated how well biomarkers predict risk of heart events concluded that they do not provide much more useful information than standard risk factors (high blood pressure, unhealthy cholesterol levels, diabetes). At this time, most experts feel that these standard disease risk factors provide the best predictors of the likelihood of developing coronary artery disease, heart attack, or stroke.

Managing Heart Disease

The approach for managing any degree of coronary artery disease involves lifestyle changes. Depending on severity and individual conditions, patients may need one or more medications, surgery, or both.

Healthy diet, regular exercise and quitting smoking if you are a smoker may prevent heart disease. Follow your health care provider's recommendations for treatment and prevention of heart disease.

Experts have come up with a mnemonic device (ABCDE) for remembering 10 factors that are fundamental for management of stable angina and coronary artery disease:

A. Aspirin and anti-angina drugs

B. Blood pressure and beta-blockers

C. Cholesterol-lowering drugs (typically statins) and cigarettes (stopping)

D. Diet and diabetes control

E. Exercise and education

Unstable angina is now usually classified with non-Q myocardial infarction as acute coronary syndrome (ACS) in professional discussions of treatments. ACS usually requires more aggressive treatments, including surgery. [ACS is more fully discussed in In-Depth Report #12: Heart attack and acute coronary syndrome.]

Click the icon to see an image about angina.

Anti-Clotting Medications

Anti-clotting drugs that inhibit or break up blood clots are used at every stage of heart disease. They are generally classified as either antiplatelets or anticoagulants. All anti-clotting therapies carry the risk of bleeding, which can lead to dangerous situations, including stroke.

A thrombus is a blood clot that forms in a vessel and remains there. An embolism is a clot that travels from the site where it formed to another location in the body. Thrombi or emboli can lodge in a blood vessel and block the flow of blood in that location depriving tissues of normal blood flow and oxygen. This can result in damage, destruction (infarction), or even death of the tissues (necrosis) in that area.

Antiplatelet Drugs. These drugs prevent formation of blood platelets. Platelets are very small disc-shaped blood cells that are important for blood clotting.

Aspirin. Aspirin is an antiplatelet. It is the most common anti-clotting drug. Nearly anyone with existing heart disease or at risk for it is advised to take a low-dose aspirin every day.
Thienopyridines. Clopidogrel (Plavix) and ticlopidine (Ticlid) are thienopyridines, another type of anti-platelet drug.
Glycoprotein IIb/IIIa Inhibitors. These powerful blood-thinning drugs include abciximab (ReoPro, Centocor), eptifibatide (Integrilin), tirofiban (Aggrastat), and lamifiban. They are administered intravenously in the hospital and are used after angioplasty surgery and stent placement.

Click the icon to see an image about blood.

Anticoagulants. Anticoagulants help thin blood and include:

Heparin
Warfarin (Coumadin)
Direct thrombin inhibitors

Aspirin. Aspirin is known as a nonsteroidal anti-inflammatory drug (NSAID). It stops blood platelets, which are major clotting factors, from sticking together to form a blood clot. A daily low-dose aspirin (75 - 325 mg) is usually the first choice for preventing heart disease in high-risk individuals. Aspirin can prevent by 25 – 50% the risk of heart attacks and death in people with existing heart disease and a history of heart attack. It also reduces the risk for stroke. According to a 2006 review, aspirin works equally well for both men and women.

Click the icon to see an image about stomach ulcers.

Side effects from prolonged use of aspirin may include stomach ulcers and bleeding. (There may be a slight increased risk for bleeding-related strokes, which are very uncommon, however. Furthermore, this risk may be outweighed by protection against the more common type of stroke, which is caused by artery blockage.)

Clopidogreland Ticlopidine. Clopidogrel (Plavix) and ticlopidine (Ticlide) are anti-platelet drugs known as thienopyridines. When taken with aspirin, these drugs can significantly reduce the risk for heart attack and stroke in patients with acute coronary syndrome (unstable angina or early signs of heart attack). The combination of aspirin and a thienopyridine is essential for patients who have a drug-eluting stent. According to a 2007 American Heart Association advisory, patients who have a drug-eluting stent must take both aspirin and a thienopyridine for at least 1 year after the stent is inserted. Many experts recommend clopidogrel instead of ticlopidine because ticlopidine has been associated with dangerous blood disorders, particularly thrombocytopenia.

Clopidogrel is also recommended for patients who are undergoing angioplasty. For patients having coronary bypass surgery, it should be withheld for at least 5 -7 days prior to surgery because of a significant bleeding risk. Researchers are investigating whether clopidogrel and aspirin together are better than aspirin alone in reducing the risks following coronary bypass surgery. A 2006 study suggested that for some patients with heart disease, clopidogrel plus aspirin does not work better than aspirin alone for preventing a first heart attack or stroke.

Click the icon to see an image of the developmental process of atherosclerosis.

Click the icon to see an image about atherosclerosis.

Anticoagulants are drugs that prevent or delay blood coagulation and the formation of blood clots. Heparin has been the standard anticoagulant, but a number of drugs are now available that are proving to be better choices in many cases.

Standard (Unfractionated) Heparin. The heparin referred to as unfractionated heparin has been the standard for years and is used alone or in combination with aspirin for managing unstable angina. It is no longer the recommended first choice, however, for this patient group. It must be intravenously administered and monitored with frequent blood tests. The major complication is thrombocytopenia (a severe drop in platelets). This condition is extremely serious and can become life-threatening, particularly with bleeding in various body tissues. Alternatives include low-molecular weight heparin and direct thrombin inhibitors.

Low-Molecular Weight Heparin. Enoxaparin (Lovenox), dalteparin (Fragmin), tinzaparin (Innohep) are drugs known as low-molecular weight heparins (LMWHs). Many doctors now recommend these drugs over standard heparin for patients with unstable angina (unless bypass surgery is being planned). They have similar rates of survival, recurring angina, and bleeding as standard heparin. However, they pose lower risks for heart attack, repeat angioplasties, and thrombocytopenia. They require injections but do not require the ongoing monitoring that standard heparin does. Patients may even be able to self-administer LMWHs as people with diabetes do insulin.

Warfarin. Warfarin (Coumadin) is an oral anticoagulant. It prevents clots by inhibiting vitamin K. Warfarin is used with aspirin after a heart attack to prevent another one and to prevent blood clots in patients with atrial fibrillation. Warfarin is also proving to be more effective than aspirin for preventing heart attacks in patients with acute coronary syndromes. Warfarin therapy poses a dangerous risk for bleeding and blood coagulation must be monitored with frequent blood tests.

Direct Thrombin Inhibitors (DTIs). Direct thrombin inhibitors are a more recent group of anti-coagulants. The first DTI was hirudin, a natural substance derived from the saliva of leeches. New forms include argatroban (Novastan), bivalirudin (Angiomax), danaparoid (Orgaran), lepirudin (Refludan), desirudin (Revasc), and ximelagatran (Exanta). Many of these drugs are used along with warfarin and may be good options for patients who develop thrombocytopenia with heparin use. DTIs may prove to be superior to standard heparin for patients with acute coronary syndrome.

Other Medications

Nitrates have been used in the treatment of angina for over 100 years. These drugs release nitric oxide, thereby relaxing the smooth muscles in blood vessels. Many nitrate preparations are available. The most commonly used are nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate. Nitrates can be absorbed from the gastrointestinal tract (oral tablet), skin (ointment or patch), or from under the tongue (sublingual tablet or spray).

Rapid Acting Nitrates. Rapid-acting nitrates are used to treat acute attacks. Nitroglycerin is the most widely used drug for this purpose. It can be administered under the tongue (sublingually or as a spray) or pocketed between the upper lip and gum (buccally) and can relieve angina within minutes. The procedure for taking nitroglycerin during an attack is as follows:

At the onset of an angina attack, the patient administers one sublingual or buccal tablet or one metered dose of the spray.
If the pain is not relieved within 5 minutes the patient takes a second dose; a third can be taken after another 5 minutes if symptoms persist.
If pain continues after a total of three doses in 15 minutes, the patient should go immediately to the nearest emergency room.

Nitroglycerin is very volatile so its potency can be easily lost. Patients should take the following precautions:

Keep no more than 100 tablets on hand, stored in their original container.
When first opened, the cotton filler should be discarded, and the cap screwed on tightly immediately after each use.
A supply should always be kept close at hand in case of an attack, with the rest kept in a cool dry place.

Intermediate to Long-Term Nitrates. Sublingual tablets of isosorbide dinitrate have a somewhat slower onset of action than nitroglycerin and are useful for preventing exercise angina. Ointments, patches, and oral tablets are used for longer-term prevention of angina attacks:

Transdermal patches are applied in the morning to any hair- or injury-free area on the chest, back, stomach, thigh, or upper arm. Hands should be washed after each patch or ointment application, and sites of application should be rotated to avoid skin irritation.
Nitroglycerin ointment is applied by measuring out an even amount on an applicator paper and then placing, not rubbing or massaging, it on the chest, stomach, or thigh. Any ointment that remains from the previous application should be removed.

Long-acting forms may lose their effectiveness over time, so doctors generally schedule nitrate-free breaks to prevent tolerance. Some concern exists that nitrate-free periods might increase the risk for angina and adverse heart events. One large study, however, found no increased danger when patients used a nitroglycerine patch with scheduled breaks. The use of high blood pressure drugs known as ACE inhibitors may help prevent tolerance to nitrates.

Side Effects. Nitrates have many side effects, some of which can be serious.

Common side effects of nitrates include headaches, dizziness, nausea and vomiting, blurred vision, fast heartbeat, sweating, and flushing on the face and neck. Low blood pressure and dizziness can be relieved by lying down with the legs elevated. These effects are significantly worsened by alcohol, beta-blockers, calcium channel blockers, sildenafil (Viagra), and certain antidepressants. The doctor may prescribe medicines to lessen these side effects. Patients should contact their doctor if these side effects are persistent or severe.

Serious side effects requiring immediate medical help include fever, joint or chest pain, sore throat, skin rash (especially on the face), unusual bleeding or bruising, weight gain, and swelling of the ankles.

Withdrawal. Withdrawal from nitrates should be gradual. Abrupt termination may cause angina attacks.

Beta-blockers are useful for preventing angina attacks and reducing high blood pressure. They reduce the heart's oxygen demand by slowing the heart rate and lowering blood pressure. They are recognized for reducing deaths from heart disease and from heart surgeries, including angiography and coronary bypass. Beta-blockers are the drugs of choice for older patients with stable angina and may also be beneficial for people with silent ischemia. They are, however, less useful for the treatment of Prinzmetal’s angina. Beta-blockers are often prescribed along with other drugs such as nitrates, calcium channel blockers, or statins. A 2006 study suggested that beta-blockers and statins may help stabilize coronary artery disease and prevent the development of heart attacks.

Specific Beta-blockers. Beta-blockers include propranolol (Inderal), carvedilol (Coreg), bisoprolol (Zebeta), acebutolol (Sectral), atenolol (Tenormin), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol-XL), and esmolol (Brevibloc). A nasal spray form of propranolol appears to be very helpful in reducing exercise-induced angina attacks.

Side Effects. Beta-blocker side effects include fatigue, lethargy, vivid dreams and nightmares, depression, memory loss, and dizziness. They can lower HDL (“good”) cholesterol. Beta blockers are categorized as non-selective or selective. Non-selective beta blockers such as carvedilol and propranolol can narrow bronchial airways. These beta-blockers should not be used by patients with asthma, emphysema, or chronic bronchitis.

Patients should never abruptly stop taking these drugs. The sudden withdrawal of beta-blockers can rapidly increase heart rate and blood pressure. The doctor may advise a patient to slowly decrease the dose before stopping completely.

Calcium channel blockers reduce heart rate and slightly dilate the blood vessels of the heart, thereby decreasing oxygen demand and increasing oxygen supply. They also reduce blood pressure. CCBs vary chemically, however, and although some are helpful, others may even be dangerous for certain patients with angina.

Click the icon to see an image of the anterior heart arteries.

Long-acting nifedipine (Adalat, Procardia) and nisoldipine (Sular) and newer CCBs, such as amlodipine (Norvasc) and nicardipine (Cardene), may be beneficial for some patients with angina. They can be considered alone for patients who cannot tolerate beta-blockers, but may provide the best results when used in combination with a beta-blocker. Studies suggest that they reduce the need for repeat angioplasties. Their effects on other outcomes, including mortality rates and heart attack, are less clear.
Short-acting CCBs, including short-acting forms of verapamil, diltiazem, nifedipine, and nicardipine, are helpful for many patients with Prinzmetal's angina. However, short-acting forms of certain CCBs, such as nifedipine and nisoldipine, have been associated with severe and even dangerous side effects, including an increase in heart attacks and sudden death in some patients with unstable angina. They also increase the risk for adverse effects in patients with stable angina. Short-acting CCBs are, therefore, not used for stable or unstable angina.

There is no strong evidence that any calcium channel blockers improve survival rates. Overdose can cause dangerously low blood pressure and slow heart beats. Patients with heart failure have a higher risk for death with these drugs and should not take them. No one taking any calcium channel blocker should withdraw abruptly because such action could dangerously increase the risk of high blood pressure. Note: Grapefruit and Seville oranges boost the effects of CCBs, sometimes to toxic levels. (Regular oranges do not appear to pose any hazard.)

Angiotensin converting enzyme (ACE) inhibitors are important heart-protective drugs, particularly for people with diabetes and high blood pressure. They reduce the production of angiotensin, a chemical that causes arteries to narrow, and so are commonly used to lower blood pressure. They may also reduce risk for heart attack, stroke, complications of diabetes, and death in patients at high risk for heart disease.

ACE inhibitors include captopril (Capoten), ramipril (Altace), enalapril (Vasotec), quinapril (Accupril), benazepril (Lotensin), perindopril (Aceon), and lisinopril (Prinivil, Zestril).

Side Effects. Side effects of ACE inhibitors are uncommon but may include an irritating cough, excessive drops in blood pressure, and allergic reactions. In the past, doctors sometimes avoided giving aspirin to patients who were taking ACE inhibitors because the combination was believed to cause kidney problems. But, a 2005 study of patients with both coronary artery disease and heart failure found that taking aspirin and ACE inhibitord together is safe. The researchers also noted that taking aspirin with an ACE inhibitor can significantly reduce the risk of death for older patients with CAD and heart failure. [See In-Depth Report #14: High blood pressure.]

Statins are the most important of these drugs. Brands include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). A major analysis of over 200 studies found that statins reduced the risk for heart problems by 60% and stroke by 17%. A 2005 review found that the more that statins lower LDL, the more they reduce CAD and other heart disease risks.

An important 2006 study found that aggressive treatment with statins may have the potential to reverse coronary artery disease. In the study, rosuvastatin reduced fatty plaque in the arteries in addition to improving LDL and HDL cholesterol levels. However, a follow-up 2007 study of rosuvastatin indicated that while the drug slowed the rate of atherosclerotic progression, it did not reverse heart disease. Future studies will continue to investigate this issue.

Side effects of statins may include stomach upset, headaches, skin rashes, muscle aches, sexual dysfunction, drowsiness, dizziness, nausea, constipation, and peripheral neuropathy (numbness or tingling in the hands and feet).

The main safety concern with statins is an uncommon condition called myopathy, which can cause muscle and joint pain and possible muscle damage. Doctors will immediately stop statin therapy if myopathy occurs. Patients should talk to their doctor about any unusual muscle discomfort or weakness, or if their urine becomes brown-colored. Statins can also affect the liver, particularly at higher doses, so patients taking these drugs should receive regular liver function tests.

Click the icon to see an image of cholesterol.

Influenza Vaccinations (Flu Shots). Evidence suggests influenza vaccinations help protect against adverse heart events (including after heart surgeries), stroke, and death from all causes in the elderly. Still, studies suggest that only two-thirds of at risk people are vaccinated, mostly because of unwarranted fears of ineffectiveness or adverse effects.

Antibiotics. Researchers have investigated antibiotics for treating patients with heart disease and past infection of the bacteria Chlamydia pneumoniae. Results from several recent large-scale clinical trials suggest that antibiotic treatment provides no benefit in preventing heart attack or other cardiac events in patients with coronary artery disease. In addition, a 2006 study indicated that short-term treatment with the antibiotic clarithromycin may increase the risk for death in patients with coronary artery disease. While it is still possible that C. pneumoniae may play a role in triggering inflammatory responses associated with ACS, antibiotic therapy is no longer considered appropriate for treatment or prevention of heart disease.

Ranolazine (Ranexa) was approved in 2006 for treatment of chronic angina. It is recommended for patients who have not responded to other angina drugs. Ranolazine is taken in combination with amlodipine, beta blockers, or nitrates. The drug appears to work better in men than in women

Gene Therapy and Angiogenesis. Proteins known as growth factors are being investigated for their ability to grow new blood vessels for supplying oxygen to the heart. After promising small trials, two large studies of genetically engineered forms of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF [GenerX]) failed to detect any benefits. Studies on therapies that actually genetically encode these proteins are underway.

Testosterone Supplements. Some trials using testosterone supplements or patches have reported improved exercise-induced blood flow in the coronary arteries and improvement in angina in some cases. Supplements of this male hormone, however, may increase the risk for prostate cancer. Experts suggest that testosterone be used only in older men with significant deficiencies in testosterone.

Selective Estrogen-Receptor Modulators (SERMs). Selective estrogen-receptor modulators (SERMs), including raloxifene (Evista), have been designed to produce the benefits of estrogen without its risks. They are thought to act like estrogen in some tissues but behave like estrogen blockers (antiestrogens) in others. Raloxifene may have some heart benefits, although it poses a risk for deep vein blood clots, which may have long-term implications for patients with heart problems. A major study is underway to determine its effects on the heart.

Surgery

Surgery is usually recommended for patients who have:

Unstable angina that does not respond promptly to medical treatment
Severe recurrent episodes of angina that last more than 20 minutes
Acute coronary syndrome
Severe coronary artery disease (severe angina, multi-artery involvement, evidence of ischemia), particularly if abnormalities are evident in the left ventricle of the heart, the main pumping chamber

Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, resulting in narrowing and eventual impairment of blood flow. Severely restricted blood flow in the arteries to the heart muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

Researchers have been investigating whether surgery offers any advantages if used as an early treatment for mild angina. A major analysis in 2003 reported that the use of angioplasty in patients with mild heart blockage did not reduce the risk for heart attack or death over the long term. A landmark 2007 study found that angioplasty was no better than drug therapy for preventing heart attack and stroke in patients with stable coronary artery disease. (For more information, see Angioplasty and Stents.)

Two effective surgical procedures for heart patients are:

Coronary artery bypass grafting (commonly called bypass or CABG)
Percutaneous coronary intervention (commonly called angioplasty or PCI), usually with coronary artery stent placement

Click the icon to see an image about bypass grafting.

Each of these procedures is described below.

Studies have generally reported similar survival rates with either procedure. There are some differences, however, and decision often depends on individual conditions. Patients considering surgery should discuss all options and risks with their doctor. No surgical procedure cures coronary artery disease, and patients must continue to rigorously maintain a healthy lifestyle and any necessary medications. For some patients, lifestyle changes and medications may be able to control the disease without surgery or angioplasty.

Considerations for Choosing Angioplasty with Stent Placement. Angioplasty has the following advantages for most patients. It is:

Less invasive than bypass. (Although a minimally invasive variation of bypass surgery may reduce this distinction.)
Less expensive than bypass. (Although the postoperative need for more medications and the high risk for repeat procedures to reopen the artery may reduce the long-term difference in cost between the two procedures.)
Life-saving emergency procedure for many patients with heart attacks. (The use of bypass after a heart attack has much higher mortality rates than when it is used electively and its use is controversial in heart attack patients.)

It has the following disadvantages:

The blood vessels can close up again (restenosis) so that patients require additional procedures. (New blood thinning drugs, coronary stent coatings, and radiation treatments may help to significantly reduce restenosis rates. However, there is also some indication that stents, especially drug-eluting stents, may increase the risk for blood clots.)
It is not as appropriate as bypass for many patients with angina (people with diabetes, elderly patients, or those with multi-vessel blockage). Increasingly, however, angioplasty is proving to be as safe and as effective as bypass in many high-risk patients. Patients should be sure to discuss with their doctors the relevant risks and benefits of angioplasty and bypass.

Considerations for Choosing Bypass. Bypass is usually the appropriate procedure in patients with high-risk conditions, such as:

Multi-vessel blockage. (In one report comparing surgery to angioplasty in patients with two or three blocked vessels, the mortality rate 1 year after bypass was 0.8% and after angioplasty was 2.5%. About 80% of patients in the study were men.)
Diabetes. (Bypass produces significantly higher survival rates in these patients. Some experts believe angioplasty should rarely, if ever, be used in this population.)
Being elderly.
Certain structural features, such as a left main artery narrowed by 50% or more or a very long diseased portion of the artery.

Considerations for Women. Studies have reported higher mortality rates in women than in men after any heart surgery. Some experts theorize that on average women may be older and sicker when they have a heart operation. A 2002 study, however, suggested that when women with acute coronary syndromes are given the same aggressive and early treatment as men are, their survival rates are equal or even better.

In addition to angioplasty and bypass procedures, a number of other procedures are available or under investigation for coronary artery disease. They include:

Atherectomy
Myocardial Laser Revascularization
Enhanced External Counterpulsation (EECP)

Coronary Artery Bypass Graft Surgery

Coronary artery bypass graft surgery (CABG) is a good alternative to angioplasty for many patients, but it is very invasive. The surgery involves the following processes:

Click the icon to see an animation about CABG.

The chest is opened, and the blood is rerouted through a lung-heart machine.
The heart is stopped during the procedure.
Large blood vessels supply the grafts, which are used to reroute the blood. The blood vessel grafts are transplanted in front of and beyond the blocked arteries, so the blood flows through the new vessels around the blockage.
The standard grafts now use arteries taken from the chest wall. Studies are reporting that with such grafts arteries remain open in 90% of cases after 15 years.
In general, patients with triple bypass procedures stay in the hospital for 5 days. Those with one-vessel bypass may be able to go home in 3 days.

Click the icon to see an illustrated series detailing a heart bypass surgery.

In spite of the invasive nature of this procedure, elective bypass procedures produce better long-term survival rates than angioplasty, particularly in patients with diabetes and multi-vessel blockage. Overall mortality rates after this procedure range from 1% to slightly over 2%. The risk for stroke or heart attack after a bypass operation ranges from 1.3 - 5%. Finding a surgeon who performs at least 100 of the procedures a year helps reduce the risk for complications.

Blood clots may form in the new graft, closing it up or narrowing the treated vessel over time. Therapy with aspirin and other anti-clotting drugs help keep the graft open and working properly. For long-term prevention of closure, as well as for slowing progression of atherosclerosis, aggressive treatment with cholesterol-lowering drugs may be more beneficial than standard anti-clotting drugs.

Bleeding is also a potential complication of CABG. Anti-bleeding (also called hemorrhage-sparing) drugs are sometimes used to limit blood loss in patients who undergo this surgery. In 2006, concerns were raised about one of these drugs, aprotinin (Trasylol). Data suggested that aprotinin seriously increased the risks for kidney failure, heart failure, and stroke.

An important study, published in 2007 in the Journal of the American Medical Association, compared aprotinin with two anti-fibrinolytic drugs, aminocaproic acid (Amicar) and tranexamic acid (Cyklokapron), which are also used to control blood loss. The study of nearly 4,000 patients who had CABG found that over a 5-year period, the death rate for patients who took aprotinin was 21%, and patients had a 48% increased risk of dying. By comparison, the death rate was 16% for aminocaproic acid, 15% for tranexamic acid, and 13% for no anti-bleeding drug. Because aprotinin is more expensive as well as potentially more dangerous than other anti-bleeding drugs, experts are now recommending against its use in CABG.

Minimally invasive bypass (also called buttonhole or keyhole bypass) surgeries are exciting advances in basic bypass surgery. Studies indicate good success of these procedures for patients with disease in single vessels. They are also being investigated for multiple vessels.

One variation of minimally invasive bypass uses a four-inch incision. The surgeon works on the front of the heart while it is beating slowly. To date, there have been no differences in cardiac events or later mental complications between this so-called off-pump procedure and the standard bypass procedure.
In another variation, the heart is stopped, and the patient is put on a machine that reroutes the blood through a device that keeps it oxygenated. Fiberoptic scopes and instruments are passed through a number of finger-sized incisions. The surgeon works on all sides of the heart, guided by a video image from a tiny camera inserted through a 4-inch incision.
Some advanced heart centers now use robotic systems, which allow the surgeon to perform extremely delicate maneuvers on tiny vessels through pencil-size incisions. They are not yet used for the whole bypass process.

Eventually, minimally invasive bypass procedures may prove to be less expensive, require a shorter hospital stay, and have fewer complications than conventional coronary artery bypass surgery -- or even angioplasty. At this time, however, they are experimental procedures, performed in only a few medical centers for select candidates. Long term-success rates are unknown.

Angioplasty and Stents

Percutaneous coronary intervention (PCI), also called angioplasty, involves procedures such as percutaneous transluminal coronary angioplasty (PTCA) that help open the blocked artery.

Click the icon to see an animation about percutaneous transluminal coronary angioplasty.

A typical angioplasty procedure follows these steps:

The cardiologist threads a narrow catheter (a tube) containing a catheter into the blocked vessel.
The doctor opens the blocked vessel using balloon angioplasty, in which the surgeon passes a tiny deflated balloon through the catheter to the vessel.
The balloon is inflated to compress the plaque against the walls of the artery, flattening it out so that blood can once again flow through the blood vessel freely.
In order to keep the artery open afterwards, surgeons use a device called a coronary stent, an expandable metal mesh tube that is implanted during angioplasty at the site of the blockage. (In some cases, a stent may be used as the initial opening device instead of balloon angioplasty.)
Once in place, the stent pushes against the wall of the artery to keep it open.

Click the icon to see an animation about percutaneous transluminal coronary angioplasty.

Complications occur in about 10% of patients (about 80% within the first day). Outcomes are better in hospital settings with experienced teams and backup.

Click the icon to see an illustrated series detailing coronary artery balloon angioplasty surgery.

The most important long-term complication is reclosure (restenosis), which can lead to heart attack if not treated with a repeat procedure. Stenting and other advances have helped significantly in preventing reclosure and reducing heart attack rates. Nevertheless, a repeat procedure is still needed to restore the opening in 10 - 15% of procedures that use stents.

PCI (angioplasty) has been proven to help reduce the frequency of angina attacks. It is commonly recommended for patients who have critically blocked arteries or have already had a recent, acute heart attack. PCI can also help improve survival and prevent heart attacks in patients with acute coronary syndrome (ACS). However, doctors have been uncertain about angioplasty’s benefits for survival and heart attack prevention in lower-risk patients with stable coronary artery disease.

In 2007, a landmark study was published in the New England Journal of Medicine and presented at the 2007 meeting of the American College of Cardiology. The COURAGE study found that PCI works no better than standard heart medication (drugs to control blood pressure, lower cholesterol, and prevent blood clots) in preventing heart attack, stroke, and hospitalization in patients with stable coronary artery disease. Based on this study’s findings, experts are now recommending angioplasty only for patients who have severe heart disease. For patients with stable heart disease, drug therapy may be sufficient enough treatment and allow them to safely defer having surgery.

Angioplasty is less invasive than bypass surgery, requiring only one night in the hospital. Recuperation takes about a week. Chest pain after the procedure is very common and usually due to problems other than ischemia. Mild chest pain is even more common when a stent is used, possibly because the artery is stretched.

Reclosure of the artery during or shortly after angioplasty often occurs. A number of anti-clotting drugs are used to help prevent this.

Aspirin and the anti-platelet drug clopidogrel (Plavix) are often used to prevent reclosure during the procedure.
A high dose of the anticoagulant heparin is typically given before the operation.
Intravenous glycoprotein IIb/IIIa inhibitors, powerful drugs that block platelets, also prevent reclosure after stenting in many high-risk patients, and evidence now strongly suggests that they reduce rates of heart attack and death. Eptifibatide (Integrilin) and tirofiban (Aggrastat) are the standard drugs used during angioplasty. They may be most effective if administered during angioplasty, rather than beforehand.

All of these drugs pose a risk for bleeding complications.

Narrowing or reclosing of the artery (restenosis) can occur within a year of angioplasty or even longer in 15 - 60% of angioplasty patients. Coronary stents, anti-clotting drugs, and other advances have reduced these events significantly, but have not eliminated the problem. Theories for the cause of restenosis include:

The release of oxidants (damaging unstable particles) at the surgical site may cause injury and activate immune factors that produce cellular overgrowth in smooth muscles of the blood vessels.
Other activities, including scarring, may remodel and narrow the blood vessels. (This is most likely the reason for restenosis in patients with stents.)

Symptoms of restenosis include chest pain on exertion. (Heart attacks, however, do not usually occur with such events.) The narrowing of the artery in this case is not due to blood clots, so anti-clotting drugs are not useful. Restenosis usually requires a repeat operation. A number of approaches, mostly investigative, have been developed to prevent restenosis after angioplasty.

Drug-Coated Stents. Stents coated with the drugs sirolimus (Rapamune) or paclitaxel (Taxol) have been increasingly used in the last several years. Drug-eluting stents (as they are also called) can help prevent restenosis. However, because drug-eluting stents reduce arterial tissue growth, they can increase the risks of blood clots. In late 2006, the FDA held several meetings to discuss the increased risks of blood clots associated with drug-eluting stents. The committees found that drug-eluting stents do appear to have a small increased risk of blood clots compared to bare metal stents, but not enough research has been conducted to fully determine their risks for heart attack and death.

Five studies published in the New England Journal of Medicine in March 2007 indicated that drug-eluting stents are safe and effective for patients with coronary artery disease when they are used for FDA-approved indications. Problems have arisen when these stents are used for “off-label” purposes in patients with more complicated health problems. There is still some concern as to whether all stents (both bare metal and drug eluting) are used too frequently for patients who may be better served by drugs or bypass surgery.

In February 2007, the American Heart Association and other professional organization issued an extremely important joint advisory statement. The statement advises that all patients who have drug-eluting stents must continue to take aspirin and clopidogrel (or, rarely, ticlopidine) for at least 1 year after the stent is inserted to reduce the risk of blood clots. Clopidogrel and ticlopidine are thienopyridine drugs that, like aspirin, help prevent blood platelets from clumping together. It is very important that patients who have drug-eluting stents take both aspirin and a thienopyridine drug. If for some reason patients cannot take a thienopyridine drug, they should receive a bare metal stent instead of a drug-eluting stent.

Coronary Artery Brachytherapy. Radiation treatment called coronary artery brachytherapy (Gamma One, Beta-Cath) can slow the cell growth in the arteries that causes restenosis. With this approach, any blockage in the stent is first removed, and a tube with an inflatable balloon is inserted. The surgeon then implants a temporary device that delivers radiation. Brachytherapy has shown excellent results in preventing restenosis and significantly reducing heart events and improving survival. Brachytherapy is also showing promise in preventing restenosis in stented artery grafts that were put in place after bypass surgery and later failed. However, several 2006 studies in the Journal of the American Medical Association indicated that drug-coated stents may work better than brachytherapy in preventing restenosis in failed stents. In these studies, the drug-coated stents were inserted inside the original bare metal stents.

Medications. A number of medications are being studied for prevention of restenosis, although benefits to date have been modest. Other drugs under investigation include statins, various anti-clotting drugs, and B vitamins.

Other Procedures. Other procedures under investigation to keep the arteries open use ultrasound, "soft" x-rays, and cryotherapy (very low temperatures).

Other Treatments

Transmyocardial laser revascularization (TMLR) applies laser energy directly to areas in the heart where blockage has occurred, creating 10 - 50 tiny channels. TMLR is recommended for patients with severe angina who have not responded to surgical bypass or angioplasty procedures. TMLR is not suitable for patients who have severely damaged heart muscles. A variant called percutaneous transmyocardial laser revascularization uses a small laser (a holmium YAG laser), which is smaller than the device used in TMLR and does not require open chest surgery and a general anesthetic.

Patients report improved symptoms and exercise tolerance. Both procedures carry risks for serious complications, however, including some that can be life-threatening. It is not clear if either TMLR procedure improves survival, and, in one study, the quality of life afterwards was less than with standard heart surgeries.

A noninvasive technique called enhanced external counterpulsation (EECP) has been used successfully by over a million people in China. The technique uses an air pump that inflates and deflates pressurized cuffs around the legs, causing blood to be pushed into the heart.

EECP may help patients with angina who have not had pain relief from nitrate drugs and who do not qualify as candidates for bypass or angioplasty. In different studies, it has relieved angina in over 75% of patients who used it and reduced the need for medication. The benefits persist, and there is some evidence that it produces actual cellular changes that benefit the heart. In 2002, the FDA approved EECP for the treatment of heart failure but some insurance companies still consider its use “experimental” and will not pay for it. EECP is not recommended for patients with arrhythmia, serious heart valve problems, or peripheral artery disease.

Atherectomy procedures clear the narrowed arteries by using an approach called debulking. All of these procedures use a catheter (a thin tube) that is inserted into an artery (usually in the groin) and threaded up to the blockage. Devices are inserted through the tube to remove the plaque. They include:

Rotational atherectomy, which uses a tiny cutter spinning at 2,500 rpm
Extractional atherectomy, which "shaves" the plaque
Directional atherectomy, which slices the plaques

Although they are successful in opening arteries, they offer no advantages over standard angioplasty and are used only for special cases.

Resources

www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.americanheart.org -- American Heart Association
www.acc.org -- American College of Cardiology

References

Boden WE, O'Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, et al. Optimalmedical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007 Mar 26; [Epub ahead of print]

Crouse JR 3rd, Raichlen JS, Riley WA, Evans GW, Palmer MK, O'Leary DH, et al. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: the METEOR Trial. JAMA. 2007 Mar 28;297(12):1344-53. Epub 2007 Mar 25.

Eisenstein EL, Anstrom KJ, Kong DF, Shaw LK, Tuttle RH, Mark DB, et al. Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation. JAMA. 2007 Jan 10;297(2):159-68. Epub 2006 Dec 5.

Folsom AR, Chambless LE, Ballantyne CM, Coresh J, Heiss G, Wu KK, et al. An assessment of incremental coronary risk prediction using C-reactive protein and other novel risk markers: the atherosclerosis risk in communities study. Arch Intern Med. 2006 Jul 10;166(13):1368-73.

Garcia MJ, Lessick J, Hoffmann MH; CATSCAN Study Investigators. Accuracy of 16-row multidetector computed tomography for the assessment of coronary artery stenosis. JAMA. 2006 Jul 26;296(4):403-11.

Grines CL, Bonow RO, Casey DE Jr, Gardner TJ, Lockhart PB, Moliterno DJ, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulation. 2007 Feb 13;115(6):813-8. Epub 2007 Jan 15.

Kastrati A, Mehilli J, Pache J, Kaiser C, Valgimigli M, Kelbaek H, et al. Analysis of 14 trials comparing sirolimus-eluting stents with bare-metal stents. N Engl J Med. 2007 Mar 8;356(10):1030-9. Epub 2007 Feb 12.

Lagerqvist B, James SK, Stenestrand U, Lindback J, Nilsson T, Wallentin L; SCAAR Study Group. Long-term outcomes with drug-eluting stents versus bare-metal stents in Sweden. N Engl J Med. 2007 Mar 8;356(10):1009-19. Epub 2007 Feb 12.

Lloyd-Jones DM, Liu K, Tian L, Greenland P. Narrative review: Assessment of C-reactive protein in risk prediction for cardiovascular disease. Ann Intern Med. 2006 Jul 4;145(1):35-42.

Maisel WH. Unanswered questions--drug-eluting stents and the risk of late thrombosis. N Engl J Med. 2007 Mar 8;356(10):981-4. Epub 2007 Feb 12.

Mangano DT, Miao Y, Vuylsteke A, Tudor IC, Juneja R, Filipescu D, et al. Mortality associated with aprotinin during 5 years following coronary artery bypass graft surgery. JAMA. 2007 Feb 7;297(5):471-9.

Mangano DT, Tudor IC, Dietzel C; Multicenter Study of Perioperative Ischemia Research Group; Ischemia Research and Education Foundation. The risk associated with aprotinin in cardiac surgery. N Engl J Med. 2006 Jan 26;354(4):353-65.

Mauri L, Hsieh WH, Massaro JM, Ho KK, D'Agostino R, Cutlip DE. Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med. 2007 Mar 8;356(10):1020-9. Epub 2007 Feb 12.

Nicholls SJ, Tuzcu EM, Sipahi I, Grasso AW, Schoenhagen P, Hu T, et al. Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA. 2007 Feb 7;297(5):499-508.

Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, et al. Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007 Feb 6;115(5):e69-171. Epub 2006 Dec 28.

Spaulding C, Daemen J, Boersma E, Cutlip DE, Serruys PW. A pooled analysis of data comparing sirolimus-eluting stents with bare-metal stents. N Engl J Med. 2007 Mar 8;356(10):989-97. Epub 2007 Feb 12.

Stewart JC, Janicki DL, Muldoon MF, Sutton-Tyrrell K, Kamarck TW. Negative emotions and 3-year progression of subclinical atherosclerosis. Arch Gen Psychiatry. 2007 Feb;64(2):225-33.

Stone GW, Moses JW, Ellis SG, Schofer J, Dawkins KD, Morice MC, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med. 2007 Mar 8;356(10):998-1008. Epub 2007 Feb 12.

Wang TJ, Gona P, Larson MG, Tofler GH, Levy D, Newton-Cheh C, et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med. 2006 Dec 21;355(25):2631-9.

Review Date:
4/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Cirrhosis

FitSugar — Wed, 08 Oct 2008 17:35:41 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Complications
Diagnosis
Treatment
Lifestyle Changes
Abdominal Infections
Encephalopathy
Ascites
Bleeding Episodes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the Food and Drug Administration approved HepaGram B, an injectable immune globulin that can help prevent recurrence of hepatitis B following liver transplantation.

Primary Biliary Cirrhosis

Primary biliary cirrhosis is an autoimmune liver disease that increases the risk for liver cancer. According to a 2007 study, specific risk factors may help predict which patients with primary biliary cirrhosis are at particularly high risk of developing liver cancer. These risk factors include older age, being male, history of blood transfusion, and any signs of portal hypertension (high pressure of the blood in the portal vein, which leads to the liver) or cirrhosis.

Hepatitis C and Cirrhosis

Patients with cirrhosis who are infected with a particular hepatitis C genotype (1b) have a high risk of developing liver cancer, indicates a 2007 study. These patients should receive regular monitoring so that liver cancer can be detected in its earliest stages.
Interferon drug therapy can help reduce -- but not entirely eliminate -- the risk of liver cancer developing in patients with hepatitis C-related cirrhosis.

Hemochromatosis

Hemochromatosis, also called “iron overload,” is an iron disorder that increases the risk for cirrhosis. Hereditary hemochromatosis is one of the most common genetic diseases in the United States, and experts have debated whether all people should get screened for it. In 2006, the U.S. Preventive Services Task Force (USPSTF) released updated guidelines concerning hemochromatosis screening. The USPSTF does not recommend routine screening in the general population. However, people who have family histories of hemochromatosis, or who show signs or symptoms of this disorder, should get tested.

Encephalopathy

Lactulose, a drug that helps remove ammonia from the body, can help improve cognitive function and quality of life for people with hepatic encephalopathy, suggests a 2007 study. Hepatic encephalopathy, a complication of liver disease, affects the brain and nervous system.

Introduction

Cirrhosis is an irreversible result of various disorders that damage liver cells over time. Eventually, damage becomes so extensive that the normal structure of the liver is distorted and its function is impaired.

Cirrhosis is a chronic liver disease that causes damage to liver tissue, scarring of the liver (fibrosis - nodular regeneration), progressive decrease in liver function, excessive fluid in the abdomen (ascites), bleeding disorders (coagulopathy), increased pressure in the blood vessels (portal hypertension), and brain function disorders (hepatic encephalopathy). Excessive alcohol use is the leading cause of cirrhosis.

The disease process often takes the following path:

Scarring. The main damage in cirrhosis is triggered by scarring (fibrosis) that occurs from injuries due to alcohol, viruses, or other assaults. Normal clumps and form nodules around the scarred areas. The scar tissue and regenerated nodules act like small dams and alter the flow of blood and bile in and out of the liver.

Altered Blood and Bile Flow. The changes in blood and bile flow have significant consequences, with both the liver and other organs responding to the altered flow:

The spleen overproduces nitric oxide, a gas that causes blood vessels in the spleen to relax and open.
The small blood vessels and bile ducts in the liver itself, however, narrow (constrict). (Blood vessels in other organs, including the kidney, also narrow.)
Blood flow coming from the intestine into the liver is slowed by the narrow blood vessels. It backs up through the portal vein and seeks other routes.
New, abnormally twisted and swollen veins called varices form in the stomach and lower part of the esophagus in order to compensate for the backup blood.
Bile also builds up in the bloodstream, resulting in high levels of bilirubin, which causes a yellowish cast in the skin called jaundice.
Fluid buildup also occurs in the abdomen (called ascites), and swelling in the arms and legs is common.

Changes in Liver Size. The liver enlarges in the first phases of the disease. In advanced stages, the liver sometimes shrinks, a condition called postnecrotic cirrhosis.

The liver is the largest organ in the body. In the healthy adult, it weighs about 3 pounds. The liver is wedge-shaped, with the top part wider than the bottom. It is located immediately below the diaphragm and occupies the entire upper right quadrant of the abdomen.

Vital Functions. The liver performs over 500 vital functions. Damage to the liver can impair these and many other processes. Among them are the following:

Processing Healthful Nutrients. It processes all of the nutrients the body requires, including proteins, glucose, vitamins, and fats.

Bile Production. The liver produces bile, a green-colored fluid that helps the body absorb fats and fat-soluble vitamins. Bile is formed from bilirubin, a yellow-green pigment produced from the breakdown of hemoglobin, the oxygen-carrying component in red blood cells. Bile contains bile salts, fatty acids, cholesterol, and other substances. Bile travels from the liver to the gallbladder, where it is stored until after a meal. It is then secreted into the intestines where it helps digest fat.

Eliminating Toxins. One of the liver's major functions is to render harmless potentially toxic substances, including alcohol, ammonia, nicotine, drugs, and harmful by-products of digestion.

Recycling Blood. The liver and spleen removes old red blood cells from the blood. The iron contained in them is recycled in the bone marrow to make new red blood cells.

The Liver's Architecture. The vital processes the liver performs rely on well-organized liver architecture.

The Building Blocks. The basic building blocks of the liver are the following structures:

Bile ducts
Blood vessels
Working liver tissue (called the parenchyma)
Supportive (connective) tissue

The Architecture. The liver is a built on a framework of lobes:

The lobes. The liver is divided into two major lobes, a right and a smaller left, that are separated by tough, fibrous connective tissue.
The lobules. The liver's two major lobes contain about 100,000 smaller lobes, called lobules. Each lobule contains microscopic columns of liver cells and blood vessels. Bracing the corners of each lobule column are an artery and a vein that carry blood and a bile duct that drains bile.
The arteries and veins. The arteries bring oxygen-rich blood to nourish the liver cells. The veins supply the liver cells with blood containing the nutrients and toxins that the liver cells process. A central vein runs through each column and collects the processed blood from both sources. These veins join to form the hepatic vein.
The bile ducts. The bile ducts in the column corners collect bile draining from tiny canals around the liver cells. These ducts eventually join to form the large common bile duct that leads from the liver to the gallbladder.

The Liver's Blood Supply. The liver is rich in blood. It holds about a pint, or 13% of the body's supply. It is furnished with blood from two large vessels, the hepatic artery and the portal vein, and is drained of blood by the hepatic vein. (The word "hepatic" derives from the Latin word for liver.)

The hepatic artery. This artery supplies blood from the heart directly to the liver. This blood nourishes the liver.

The portal vein. The portal vein carries to the liver blood that has been circulating through the stomach, spleen, and intestine. The liver processes this blood, extracting nutrients and toxins.

The hepatic vein. This vein carries blood from the liver and connects to the inferior vena cava, a large vein that carries blood back to the heart.

Click the icon to see an image of the liver.

Causes

Several processes can lead to cirrhosis.

Alcoholism particularly endangers the liver. Alcoholic cirrhosis (also sometimes referred to as portal, Laennec's, nutritional, or micronodular cirrhosis) is the primary cause of cirrhosis in the U.S. It is estimated to be responsible for 44% of deaths from cirrhosis in North America. Some experts believe this estimate is low. One Canadian study found alcohol to be the major contributor in 80% of all cirrhosis deaths.

The relationship between alcohol and cirrhosis is generally as follows:

Alcohol is absorbed from the small intestine, and the blood carries it directly into the liver, where it becomes the preferred energy source.
In the liver, alcohol converts to toxic chemicals, such as acetaldehyde (AcH), which trigger the production of powerful immune factors called cytokines. These molecules in large amounts can cause inflammation and tissue injury. They are proving to be major culprits in the destructive process in the liver. AcH is particularly being researched because it plays a role in most actions of alcohol, including damaging effects on the liver that may lead to cirrhosis.
The injured liver eventually is unable to break down fatty acids, compounds that make up fat. Over time, then, fat accumulates, further impairing the liver's ability to absorb oxygen and increasing its susceptibility to injury. During the initial phase, the fat-laden liver becomes greatly enlarged, but it eventually shrinks as cirrhosis develops.

Chronic hepatitis, both hepatitis B and hepatitis C, is the second leading cause of cirrhosis. Chronic hepatitis C is the more dangerous form and accounts for one-third of all cirrhosis cases. About 5 - 20% of patients with chronic hepatitis C, and 5 - 10% of patients with chronic hepatitis B, eventually develop cirrhosis over the course of several decades. The longer a patient has had chronic hepatitis, the greater the risk for eventually developing cirrhosis. A 2005 study indicated that cirrhosis develops in 70% of patients who have had hepatitis C for more than 60 years.

The hepatitis virus can produce inflammation in liver cells, causing injury or destruction. If the condition is severe enough, the cell damage becomes progressive, building a layer of scar tissue over the liver. In advanced cases, as with alcoholic cirrhosis, the liver shrivels in size, a condition called postnecrotic or posthepatic cirrhosis.

Hepatitis C is a virus-caused liver inflammation which may lead to jaundice, fever, and cirrhosis. The people most at risk for contracting and spreading hepatitis C are those who share needles for injecting drugs and health care workers or emergency workers who may be exposed to contaminated blood.

Autoimmune liver diseases include autoimmune hepatitis and primary biliary cirrhosis. Like other autoimmune disorders, these conditions most likely develop because a genetically defective immune system attacks the body's own cells and organs. People who have one of these liver diseases also often have other autoimmune conditions, including systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, scleroderma, inflammatory bowel disease, glomerulonephritis, and hemolytic anemia.

Autoimmune Hepatitis. Autoimmune chronic hepatitis occurs when an abnormal immune response causes an attack on the liver cells. It accounts for about 20% of all chronic hepatitis cases. Autoimmune chronic hepatitis typically occurs in women age 20 - 40 who have other autoimmune diseases. Some research indicates that the postmenopausal period may be another peak in incidence of AIH among women. About 30% of patients are men, however, and in both genders there is often no relationship to another autoimmune disease. In general, no major risk factors have been discovered for this condition.

Suspects for triggering this hepatitis include the measles virus, a hepatitis virus, or the Epstein-Barr virus, which causes mononucleosis. It is also possible that a reaction to a drug or other toxin that affects the liver also triggers an autoimmune response in some people.

Click the icon to see an image of mononucleosis.

Primary Biliary Cirrhosis. Up to 95% of primary biliary cirrhosis (PBC) cases occur in women, usually around age 50. In people with PBC, the immune system attacks and destroys cells in the liver’s bile ducts. Like many autoimmune disorders, the causes of PBC are unknown. Recent research indicates the following risk factors:

Family history of PBC
Family history of Sjögren syndrome (another autoimmune disorder)
Individual history of urinary tract infections (UTI)
History of smoking
History of nail polish use
Hormone replacement therapy
Exposure to toxins from hazardous waste sites

This research suggests that environmental factors (chemicals, cigarette smoke) or infectious organisms (bacteria that causes UTI) may trigger PBC in patients who are genetically susceptible to the disease. Women who have never been pregnant appear less likely to develop PBC.

Nonalcoholic fatty liver disease (NAFLD) resembles alcoholic liver disease, but it occurs in people who do not drink a lot of alcohol. Obesity and type 2 diabetes are the two main causes of a fatty liver. Some evidence suggests that insulin resistance (the primary problem in type 2 diabetes) is a major factor in development of a fatty liver. A diet high in fatty foods may also be a risk factor, as dietary fat accumulates in the liver. Due to the recent rise in childhood obesity, NAFLD is increasingly occurring in children. In fact, NAFLD is now the most common liver disease in American children.

Nonalcoholic fatty liver disease can lead to nonalcoholic steatohepatitis (NASH). Liver inflammation and injury, as well as a fatty liver, characterize NASH. NASH occurs in about half of people with diabetes and up to 75% of obese people.

Nonalcoholic fatty liver disease is usually benign and very slowly progressive. But, in certain patients it can lead to cirrhosis, liver failure, or liver cancer. About 8 - 20% of people with nonalcoholic steatohepatitis go on to develop cirrhosis. A 2006 study indicated that NASH-related cirrhosis causes fewer deaths than cirrhosis that is caused by chronic hepatitis C. However, many patients with NASH have coronary artery disease and heart failure and have a high risk of dying from heart disease.

Weight reduction and diabetes and cholesterol management are the primary approaches to controlling these diseases.

Hemochromatosis is a disorder of iron metabolism. This disease interferes with the way the body normally gets rid of iron. People with hemochromatosis absorb too much more iron from the food that they eat. The iron overload accumulates in organs in the body. When excess iron deposits accumulate in the liver, they can cause cirrhosis.

There are two main forms of hemochromatosis:

Primary hemochromatosis, also called hereditary hemochromatosis, is an inherited genetic disease.
Secondary hemochromatosis results from other conditions, such as anemia and alcoholism.

Hereditary hemochromatosis is one of the most common genetic diseases, especially among Caucasians. About 1 in every 200 Americans carries the gene that causes this disease. Although experts do not recommend that everyone get screened for hemochromatosis, people who have a family history of this disease, or who show symptoms (joint pain, fatigue, abdominal pain), should get tested. Left untreated, hemochromatosis can lead to serious damage of the liver, heart, and pancreas.

Hemochromatosis is treated with phlebotomy, a procedure that involves removing about a pint of blood once or twice a week. Starting phlebotomy treatment before organ damage occurs can help prevent cirrhosis. If, however, cirrhosis has already developed, patients have a high risk for developing liver cancer even if iron levels are normalized.

Inherited Diseases. Cirrhosis can be caused by several inherited diseases, including:

Cystic fibrosis
Alpha-1 antitrypsin deficiency
Galactosemia
Glycogen storage diseases
Wilson's disease

Other Rare Causes. Rare causes of cirrhosis include:

Schistosomiasis, caused by a parasite found in the Far East, Africa, and South America.
Small intestine bypass surgery (rarely, if ever, performed anymore).
Long-term or high level exposure to certain chemicals and drugs can cause cirrhosis, including arsenic, methotrexate, and toxic doses of vitamin A.

Cancers that have metastasized to the liver, blood clots in the hepatic or portal vein, or obstructions in the bile duct can cause changes that resemble cirrhosis.

Risk Factors

Cirrhosis affects about 3 million Americans a year. However, because about 2.7 - 4 million people harbor hepatitis C, the rates of cirrhosis could dramatically increase over the next few years.

Only 10% of heavy drinkers develop advanced liver disease. Not eating when drinking and consuming a variety of alcoholic beverages are factors that increase the risk for liver damage. Still, the amount of alcohol consumed and the patterns of drinking are only weak predictions of risk. Other risk factors have been identified that may increase the danger to the liver:

Obesity is a major factor for all stages of liver disease.
Women develop liver disease at lower quantities of alcohol intake than men. The reason for this may be due to women's inability to metabolize alcohol as quickly as men, so it stays in the bloodstream longer.
Genetic factors that regulate the immune responses in the intestine also play a role in increasing the risk for liver injury from alcoholism.

Risk Factors for Developing Cirrhosis from Hepatitis C. Overall, between 10 - 15% of patients with chronic hepatitis C develop cirrhosis. The risk varies widely, however. The following conditions put people with hepatitis C at higher risk for liver damage:

Overall the risk for progression is highest in men -- particularly African-Americans -- who were older at the time of infection. The risk is much lower in women and children (2 - 4%).
Moderate-to-heavy alcohol users. (Even one or two alcoholic drinks a day increase the risk for liver injury in hepatitis C patients.)
Having a specific genetic type of the virus. There are six main genetic types and more than 90 subtypes, which can differ significantly in their effects and response to treatment. Genotype 1 is the most serious and is the cause of up to three quarters of the cases in the U.S. The other common forms are types 2 (15%) and 3 (7%), which pose less danger.
Co-infection with hepatitis B. Co-infection with B significantly affects the outcome of these patients and may be more common than previously believed. This co-condition may cause superinfections with very serious consequences, reduce these patients' responses to interferon therapy, and increase their risk of liver cancer. Patients with hepatitis C should be immunized against hepatitis B.
Co-infection with HIV.
A history of transfusions. (In one report, the risk in middle-aged patients with a history of transfusions was 20 - 30%).
Being diabetic and overweight, particularly if fat is distributed in the abdomen (an apple-shape). This condition poses a higher risk for nonalcoholic fatty liver disease (NASH), which in turn is apt to become scarred and cirrhotic.

Weight gain in the area of and above the waist (apple type) is more dangerous than weight gained around the hips and flank area (pear type). Fat cells in the upper body have different qualities than those found in hips and thighs.

Having large iron stores in the liver.
High exposure to toxic chemicals or environmental contaminants.

Because there are millions of Americans now infected with chronic hepatitis C, doctors have been justifiably concerned that there will be a significant number of cases of liver failure and liver cancer in the coming years. Computer analyses have suggested that mortality rates from hepatitis C-related cirrhosis or liver cancer will double or triple over the next 20 years. Fortunately, improved therapies may significantly reduce these discouraging estimates.

Researchers are working on developing a genetic test to identify patients with chronic hepatitis C who are most at risk of developing cirrhosis. In 2007, scientists announced they had made progress on a test that measures variations in seven genes to calculate a “Cirrhosis Risk Score.” The researchers hope that this experimental test may eventually help doctors decide which patients should receive early treatment with alpha-interferon and ribavirin.

Risk Factors for Developing Cirrhosis from Hepatitis B. The great majority of people with chronic persistent hepatitis B have a good long-term outlook. Between 5 - 10%, however, become carriers of the virus, and 5 - 10% of these individuals eventually develop cirrhosis. The addition of hepatitis D is a particular danger and increases the risk for cirrhosis. Seven genetic types of hepatitis B virus (designated A to G) have now been identified, which may help researchers determine the patients who may have a better outlook than others. Genotype C is the most common form and is more aggressive than genotype B, which also responds better to treatment.

Primary biliary cirrhosis accounts for only 0.6 - 2% of deaths from cirrhosis. In patients with chronic persistent autoimmune hepatitis, the outlook is very favorable, and survival rates are equal to the general population. If it becomes active, it must be treated. Left untreated, the 5-year survival rates of primary biliary cirrhosis are 50%.

Obesity increases the risk for nonalcoholic fatty liver disease (NAFLD), a condition that can lead to nonalcoholic steatohepatitis (NASH). Studies estimate that 8 - 20% of people with NASH eventually develop cirrhosis. A 2006 study found that people with NAFLD and elevated liver enzymes have a high risk of developing end-stage liver disease. People with NASH had an especially poor prognosis for survival. Losing weight is important for overweight people with NASH and may help to delay disease progression. A 2003 study of more than 11,000 patients indicated that obesity increases the risk of death from cirrhosis in people who drink little or no alcohol, but not among those who drink alcohol.

Symptoms

Many people experience few symptoms at the onset of cirrhosis.

Early symptoms include:

Fatigue and loss of energy.
Loss of appetite and nausea.
Spider angiomas may develop on the skin. These are pinhead-sized red spots from which tiny blood vessels radiate.

Patients in later stages may develop the following symptoms:

Jaundice. This yellowish cast to the skin and eyes occurs because the liver cannot process bilirubin for elimination from the body.

Jaundice is a condition produced when excess amounts of bilirubin circulating in the bloodstream dissolve in the subcutaneous fat (the layer of fat just beneath the skin), causing a yellowish appearance of the skin and the whites of the eyes. With the exception of normal newborn jaundice in the first week of life, all other jaundice indicates overload or damage to the liver, or inability to move bilirubin from the liver through the biliary tract to the gut.

The palms of the hands may be reddish and blotchy, a condition known as palmar erythema.
Loss of body hair.
Abnormalities in hormone-affected organs. In men with alcoholic cirrhosis, the testicles may atrophy, and their breasts may become swollen, sometimes painfully.
Ascites. A swollen belly is a sign of ascites, the most common major complication of cirrhosis, which occurs when fluid accumulates in the abdomen. Fever, abdominal pain, and tenderness when the belly is pressed indicate that the fluid is infected, but infection can occur without any symptoms.
Fluid buildup and swelling (edema) in legs.

People with primary biliary cirrhosis may have severe generalized itching and often develop small fatty yellow lumps called xanthomas on the eyelids, hands, and elbows. They may have an unpleasant condition called steatorrhea, in which the feces contain excessive fat, causing them to float and to be very foul smelling.

Click the icon to see an image of a xanthoma.

Complications

Cirrhosis is the eleventh leading cause of death by disease in the United States, killing more than 25,000 people each year. A damaged liver affects almost every bodily process, including the functions of the digestive, hormonal, and circulatory systems. The most serious complications are those associated with so-called decompensation, which occur when cirrhosis progresses. They include the following:

Bleeding and fluid buildup (ascites).
Infections.
Damage to the brain (encephalopathy). Impaired brain function occurs when the liver cannot detoxify harmful substances.

Liver cancer is also a long-term risk with cirrhosis.

Cirrhosis is irreversible, but the rate of progression can be very slow, depending on its cause and other factors. Five-year survival rates are about 85% and can be lower or higher depending on severity.

For example, alcoholics with cirrhosis who abstain can have a 5-year or more survival rate of as high as 85%. For those who continue drinking, the chance for living beyond 5 years is no higher than 60%.
In patients with hepatitis B or C, the 5-year survival rate after a diagnosis of cirrhosis is 71 - 85%.
About two-thirds of patients with primary biliary cirrhosis never develop symptoms and can have a normal lifespan. Once symptoms of liver damage, such as jaundice, occur, however, the average survival time declines. In one study of women diagnosed with primary biliary cirrhosis, about 36% developed symptoms over an 11-year period, and 11% either died or required liver transplantation.

Unfortunately, doctors are usually unable to determine when cirrhosis first occurred, which makes it difficult to determine prognosis.

In cirrhosis, liver cell damage slows down blood flow. This causes a backup of blood through the portal vein, a condition called portal hypertension. The effects of portal hypertension can be widespread and serious, including fluid buildup and bleeding.

Ascites and Fluid Buildup. Ascites is fluid buildup in the abdomen. It is uncomfortable and can reduce breathing function and urination. Ascites is usually caused by portal hypertension, but it can result from other conditions. Swelling can also occur in the arms, legs, and spleen. Although ascites itself is not fatal, it is a marker for severe progression. Once ascites occurs, only half of patients survive after 2 years. Some doctors refer to the phases of cirrhosis as preascitic and ascitic. Some doctors even believe that ascites signals the need for liver transplantation, particularly in alcoholic cirrhosis.

Variceal Bleeding. One of the most serious repercussions of portal hypertension is the development of varices, blood vessels that enlarge to provide an alternative pathway for blood diverted from the liver. In about two-thirds of patients, they form in esophagus. Varices pose a high risk for rupture and bleeding because of the following characteristics:

They are thin-walled.
They are often twisted.
They are subject to high pressure.
Internal bleeding from these varices (variceal bleeding) occurs in 20 - 30% of patients with cirrhosis. The risk of death from a single episode can reach 70%.

Bleeding commonly recurs within 2 weeks of the first episode, but after 6 weeks, the risk for recurrence is the same as for patients who have not had a bleeding event.

Factors that predict variceal bleeding include:

Ascites
Encephalopathy
Large veins

Factors that can increase the danger for a bleeding episode in high-risk individuals include the following:

Moderate-to-intense exercise
Bacterial infection
Certain times of the day. Eating increases portal pressure, and there is a greater risk for bleeding in the evening. A lesser but still significant risk occurs in the early morning.

It is important for patients to be screened for esophageal varices and treated with preventive beta blockers if they show signs of risk. Between 30 - 40% of patients with cirrhosis have bleeding. The risk of dying from this complication is 20 - 35%. Some doctors recommend that all newly diagnosed patients be screened using endoscopy. Screening should also be considered for all previously diagnosed patients who have not been screened but would benefit from preventive treatments.

Portal hypertension can cause several secondary complications, including kidney failure. Non-steroidal anti-inflammatory drugs, such as naproxen, may increase the risk for kidney failure.

Gastrointestinal bleeding can occur from abnormal blood clotting, which can be a result of a combination of complications associated with cirrhosis. They include vitamin K deficiencies and thrombocytopenia -- a drop in platelets (the blood cells that normally initiate the clotting process). Some research now suggests that thrombocytopenia itself may be associated with more advanced liver failure.

Bacterial infections are very common in advanced cirrhosis, and may even increase the risk for bleeding. Most bacterial infections, including those in the urinary, respiratory, or gastrointestinal tracts, develop when patients are in the hospital. Abdominal infections are a particular problem in cirrhosis and occur in up to 25% of patients with cirrhosis within a year of diagnosis.

Mental impairment is a common event in advanced cirrhosis. In severe cases, the disease causes encephalopathy (damage to the brain), with mental symptoms that range from confusion to coma and death. A combination of conditions associated with cirrhosis causes this serious complication:

Buildup in the blood of harmful intestinal toxins, particularly ammonia.
An imbalance of amino acids that affect the central nervous system.

Encephalopathy is often triggered by certain conditions, including:

Gastrointestinal bleeding
Constipation
Excessive dietary protein
Infection
Surgery
Dehydration

Alcoholics with cirrhosis are believed to be at higher risk for this complication than are nonalcoholic cirrhosis, but one study suggested that alcoholics simply tend to have more severe cirrhosis. Even minimal hepatic encephalopathy (MHE) can have detrimental effects on functional ability. One study suggested that MHE impairs the ability to safely drive a car, and that all patients with cirrhosis be tested for MHE.

Symptoms of Encephalopathy. Early symptoms of hepatic encephalopathy include forgetfulness, unresponsiveness, and trouble concentrating. Sudden changes in the patient's mental state, including agitation or confusion, may indicate an emergency condition. Other symptoms include bad fruity-smelling breath and tremor. Late stage symptoms of encephalopathy are stupor and eventually coma.

Hepatorenal syndrome occurs if the kidneys drastically reduce their own blood flow in response to the altered blood flow in the liver. It is a life-threatening complication of late-stage liver disease that occurs in patients with ascites. Symptoms include dark colored urine and a reduction in volume, yellowish skin, abdominal swelling, mental changes (delirium, confusion), jerking or coarse muscle movement, nausea, and vomiting.

People with cirrhosis have an increased risk for liver cancer. Hepatitis B and C themselves increase the risk for liver cancer, regardless of the presence of cirrhosis. Hepatitis B infection is the leading cause of liver cancer.

For hepatitis C-related cirrhosis, a 2007 study indicated that patients with cirrhosis who are infected with genotype 1b hepatitis C have a greater risk of developing liver cancer than patients infected with other types of hepatitis C genotypes. (Genotype 1 is the most common type of hepatitis C in the United States.)

People with primary biliary cirrhosis also face a high risk of liver cancer. According to a 2007 study, several factors can indicate the increased likelihood of developing liver cancer. These factors include older age, male gender, history of blood transfusion, and signs of portal hypertension or cirrhosis.

About 30% of patients with chronic liver disease develop osteoporosis (loss of bone density), which is twice the usual incidence. Patients with primary biliary cirrhosis have a particularly high risk for osteoporosis. Treating osteoporosis in patients with cirrhosis can be complicated. One study found that calcitriol (a form of vitamin D) is especially helpful in preventing bone loss in patients with cirrhosis.

Osteoporosis is a condition characterized by progressive loss of bone density, thinning of bone tissue, and increased vulnerability to fractures. Osteoporosis may result from disease, dietary or hormonal deficiency, or advanced age. Regular exercise and vitamin and mineral supplements may reduce and even reverse loss of bone density.

Nearly all patients with cirrhosis are insulin resistant. Insulin resistance is a primary feature in type 2 diabetes and occurs when the body is unable to use insulin. This hormone is important for delivering blood sugar and amino acids into cells and helps determine whether these nutrients will be burned for energy or stored for future use.

One study reported that nearly a quarter of patients with cirrhosis had gallstones.

Click the icon to see an image of gallstones.

They may also face a higher than average risk for certain abnormal heart rhythms. Peptic ulcers, sleep disorders, and respiratory problems are also more common in people with cirrhosis than in the general population.

Diagnosis

A physical examination may reveal the following in a patient with cirrhosis:

The cirrhotic liver is firm and often enlarged. The liver may feel rock-hard. (In advanced stages of cirrhosis, the liver may become small and shriveled.)
The left side can often be felt by the doctor when pressing on the abdomen.

If the abdomen is swollen, the doctor will check for ascites by tapping the flanks and listening for a dull thud and feeling the abdomen for a shifting wave of fluid.

Measuring Liver Enzymes (Aminotransferases). Enzymes known as aminotransferases, including aspartate (AST) and alanine (ALT), are released when the liver is damaged. Measurements of these enzymes, particularly ALT, are the least expensive and most noninvasive tests for determining severity of the underlying liver disease and monitoring treatment effectiveness. Enzyme levels vary, however, and are not always an accurate indicator of disease activity. (For example, they are not useful in detecting progression to cirrhosis.)

Radioimmunoassays. To identify a particular virus that may be causing hepatitis, blood tests called radioimmunoassays are performed. Typically, radioimmunoassays identify particular antibodies, which are molecules in the immune system that attack specific antigens. (Antigens are any molecules that the body considers threatening or dangerous, and can be targeted by antibodies.)

An antigen is a substance that can provoke an immune response. Typically antigens are substances not usually found in the body.

Some of these tests can pinpoint hepatitis antigens directly. These tests, however, have limitations:

There may not be enough antibodies for blood tests to detect for up to weeks or months after hepatitis develops. Blood tests that are taken too early, then, may miss these signs of infection.
Antibodies also persist after patients recover, so a positive antibody test can indicate a previous infection but does not necessarily determine if the infection is active.

The assays for individual hepatitis viruses may differ.

Polymerase Chain Reaction. In some cases of hepatitis C, a polymerase chain reaction (PCR), may be performed. A PCR is able to make multiple copies of the genetic material (the RNA) of the virus to the point where it is detectable.

Screening for Hepatitis C Virus. In 2004, the U.S. Preventive Services Task Force (USPSTF) recommended against routine screening for the hepatitis C infection in the general population due to low prevalence of the disease. In addition, it "found no evidence that screening for HCV infection in adults at high risk leads to improved long-term health outcomes" and found insufficient evidence to recommend for or against such screening. However, the USPSTF did advise testing in those with signs or symptoms of liver disease. The failure to recommend testing in the high-risk population goes against current recommendations made by the Centers for Disease Control and Prevention, the National Institutes of Health, and other professional organizations. In response to the study, published in the Annals of Internal Medicine, the American Association for the Study of Liver Diseases issued a statement saying that halting such screening would be a "terrible mistake with grave consequences," pointing out that the study itself underscored some key infection-related data that strongly emphasizes the need for screening in high-risk populations.

A liver biopsy is the only definite method for diagnosing cirrhosis. It also helps determine its cause, treatment possibilities, the extent of damage, and the long-term outlook. For example, hepatitis C patients who show no significant liver scarring when biopsied appear to have a low risk for cirrhosis.

The biopsy may be performed using various approaches, including:

Percutaneous Liver Biopsy. This approach uses a needle inserted through the abdomen to obtain a tissue sample from the liver. Various forms of needles are used, including those that use suction or those that cut out the tissue. If cirrhosis is suspected, a cutting needle is the better tool. This approach should not be used in patients with bleeding problems, and it must be used with caution in patients with ascites or severe obesity.

Click the icon to see an image of liver biopsy.

Transjugular Liver Biopsy. This approach uses a catheter (a thin tube) that is inserted in the jugular vein in the neck and threaded through the hepatic vein (which leads to the liver). A needle is passed through the tube, and a suction device collects liver samples. This procedure is risky but may be used for patients with severe ascites.
Laparoscopy. This procedure requires a small abdominal incision through which the doctor inserts a thin tube that contains small surgical instruments and a tiny camera to view the surface of the liver. This is generally reserved for staging cancer or for ascites with unknown causes.

Biopsies can be dangerous, so they cannot be performed on patients who have test results that indicate clotting problems, on those who have had previous liver biopsies, or who have ascites.

Certain blood tests are used to determine liver function. They include the following:

Serum albumin concentration. Serum albumin measures protein in the blood (low levels indicate poor liver function).
Prothrombin time (PT). The PT test measures in seconds the time it takes for blood clots to form (the longer it takes the greater the risk for bleeding).
Bilirubin. One of the most important factors indicative of liver damage is bilirubin, a red-yellow pigment that is normally metabolized in the liver and then excreted in the urine. In patients with hepatitis, the liver cannot process bilirubin, and blood levels of this substance rise, sometimes causing jaundice.

The results of these tests along with the presence of specific complications (ascites and encephalopathy) are used for calculating the Child-Pugh Classification. This is a staging system (A to C) that helps doctors determine the severity of cirrhosis.

Very high levels of serum alkaline phosphatase, an enzyme produced in the liver, and high levels of immune factors called mitochondrial antibodies are usually present in blood tests of patients with primary biliary blood cirrhosis. Bilirubin measurements appear to be important factors in determining its severity.

Fatty liver is suspected when a patient has elevated liver enzymes. The doctor will take imaging tests of the liver using ultrasound, computed tomography, or magnetic resonance imaging. A liver biopsy is the standard test for confirming a diagnosis of fatty liver disease and for distinguishing NAFLD from nonalcoholic steatohepatitis (NASH). Several studies in 2006 and 2007 suggested that a blood test for cytokeratin-18 (CK-18), a protein found in liver cells, may be an effective noninvasive approach for diagnosing NASH. Doctors hope that this simple blood test may eventually be able to replace liver biopsy.

Several imaging tests can be used to diagnose cirrhosis and its complications.

Imaging Techniques. Magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound are all imaging techniques that are useful in detecting and defining the extent of cirrhosis. Such tests can reveal ascites, an enlarged spleen, an irregular liver surface, reversed portal vein blood flow, and liver cancer. Sometimes they can even detect abnormally large blood vessels in the liver. In some cases, images from ultrasound and CT can be misinterpreted as cancer. MRI is most useful for ruling out or confirming cancer.

Click the icon to see an image of an MRI scan.

Click the icon to see an image of a CT scan.

Liver Scans. Sometimes liver scans are performed using a small radioactive tracer and a special camera that records information provided by the tracer as it passes through the liver:

Arteriography uses dye injected into the hepatic arteries that show up on x-ray.
Splenoportography uses dye injected into the spleen, which allows the doctor to measure portal vein pressure. This procedure is risky.

Hepatic vein wedge pressure involves insertion of a catheter into the hepatic veins. The blood pressure in the veins of the liver is then measured. The result is an indicator of portal vein pressure. If pressure is high, cirrhosis is likely. A low measurement is a favorable sign.

Endoscopy. Some doctors recommend endoscopy for patients newly diagnosed with mild-to-moderate cirrhosis in order to screen for esophageal varices. (These are abnormal blood vessels in the esophagus that increase the risk for bleeding). In this test, a fiber optic tube is inserted down the throat. The tube contains tiny cameras to view the inside of the esophagus, where varices are most likely to develop. Endoscopy is the only procedure for detecting varices, but it is not clear if screening for varices in patients without severe cirrhosis is any more beneficial than simply putting them immediately on preventive drugs -- whether or not varices have been identified.

Paracentesis. If ascites is present, paracentesis is performed to determine its cause. This procedure involves using a thin needle to withdraw fluid from the abdomen. The fluid is tested for different factors to determine the cause of ascites:

Bacteria cultures and white blood cell counts. (These are used to determine the presence of infection.)
Protein levels. Low levels of protein in the fluid plus a low white blood cell count suggest that cirrhosis is the cause of the ascites.

The appearance of the fluid is helpful in determining problems:

A cloudy fluid plus a high white blood cell count means an infection is present.
Bloody fluid suggests the presence of a tumor.

Screening for Liver Cancer. Patients with cirrhosis are usually screened for liver cancer using ultrasound and tests for a substance called alpha-fetoprotein (AFP). It is not known whether such screening has much impact on survival, because it is not very sensitive and has a high rate of false positives (suggesting the presence of cancer when it is not actually present). Screening is not necessary in patients without cirrhosis.

Treatment

The only treatment for alcoholic cirrhosis is to stop drinking. Individuals with alcoholic cirrhosis are typically malnourished and require increased calories and rigorous nutritional support, which can improve survival rates.

Interferons Alone and in Combination with Ribavirin. Pegylated interferon combined with ribavirin is the gold standard treatment for chronic hepatitis C in both adults and children. It achieves response rates of up to 50% for patients infected with HCV genotype 1 (the most common genotype form in the U.S.) and up to 80% for patients infected with genotypes 2 or 3. Interferon alone is usually reserved for patients who cannot tolerate ribavarin.

A 2005 clinical trial of patients with chronic hepatitis C and cirrhosis found that interferon treatment reduced the risk of liver cancer and significantly improved chance of survival. The study emphasizes the importance and substantial benefits of interferon therapy. A 2007 study of patients with hepatitis C-related cirrhosis also indicated that interferon therapy can help reduce the risk of liver cancer and overall risk of death from liver disease.

A number of natural and synthetic interferons are available:

Natural interferons include interferon alfa-2a (Intron) and interferon alfa-2b (Roferon).
Pegylated interferons (PegINF) are long-acting formulations of interferon. They include alfa-2b (Peg-Intron) or alfa-2a (Pegasys). These drugs are used in combination with ribavarin (Copegus, Rebetol).
Alfacon-1 (Infergen), also called consensus interferon, is a genetically modified interferon. A combination of alfacon-1 with ribavirin is proving to help some patients who had been resistant to ribavirin with interferon.

A 2005 study suggested that some patients with hepatitis C genotypes 2 or 3 may be able to benefit from a shorter course of combination treatment (12 weeks) than the standard 24-week treatment duration. A shorter treatment time may reduce the risk of side effects. However, a 2007 study in the New England Journal of Medicine found that 16 weeks of combination therapy in patients with these genotypes did not work as well as the 24-week regimen. Given the significant side effects associated with combination pegylated interferon and ribavarin treatment, particularly anemia, researchers are actively investigating how to identify which patients may be able to succeed with shorter treatment duration.

PegINF combinations are proving to slow progression of scarring, and have even achieved improvement in some patients who already have cirrhosis. Whether the combination treatment protects against future liver cancer is still unclear. (A higher total dose, rather than a longer duration of treatment, may be the critical factor for protection.)

Side Effects of Combination Treatment. The side effects of the combination include those of both interferon and ribavirin. Interferon side effects may occur more often in the combination treatment. Combination treatment side effects may include:

Anemia occurs in about 22% of patients who take combination treatment versus 1% who take interferon alone. This complication is reversible and usually stabilizes after 1 - 2 months of treatment. However, some patients may become so anemic that they have to stop the medication. Since anemia can worsen heart disease, patients with a history of significant heart problems should not be treated with ribavirin. Other nucleoside analogues are being investigated that may have a lower risk for anemia than ribavirin.
Flu-like symptoms, such as fever, headaches, and muscle aches, are the most common side effect.
Reduced white blood cell count.
Skin disorders, such as dry skin and rash.
Coughing and shortness of breath.
Gastrointestinal symptoms (nausea, indigestion, lack of appetite).
Emotional and psychological symptoms, such as severe sleep disturbances, depression, irritability, and anxiety.
Combination treatment in pregnant women poses a very high risk for birth defects.

The current drugs used for hepatitis C still do not meet the needs of all patients. They are expensive, have significant side effects, do not work in half the patients who take them, and are unsuitable in many others. Investigation is ongoing to find better solutions. Drugs showing promise include:

Albinterferon alfa-2b (Albuferon). This long-acting form of interferon-alfa may have fewer side effects and require less dosing than pegylated interferons. It is currently being tested in combination with ribavarin in Phase II trials for patients with genotype 1 chronic hepatitis C.
Thymosin Alpha 1 (Zadaxin), also called thymalfasin, is a synthetic version of a peptide derived from the thymus gland (which is responsible for maturation of immune factors called T-cells). It is being used for hepatitis B and is under investigation for hepatitis C in combination with interferon.
Celgosivir. Celgosivir is a new type of antiviral drug, which blocks alpha-glucosidase, an enzyme involved in viral replication. Celgosivir is being studied in combination with pegylated interferon alfa-2b and ribavirin. The drug is derived from the Australian chestnut tree.
Eltrombopag (Revolade). Thrombocytopenia, reduced production of blood platelets, is a condition that affects patients with hepatitis C and cirrhosis. Patients with thrombocytopenia cannot tolerate standard antiviral therapy. Researchers hope that eltrombopag, a drug that stimulates platelet production, may help normalize platelet levels so that they can start antiviral drug treatment.
Statins. Statin drugs are used for the treatment and management of cholesterol. Researchers are studying whether they may help improve liver enzyme levels in patients with hepatitis C.

Of interest are studies using phlebotomy (which is simply drawing blood) to reduce iron levels. In one study, maintenance therapy with this procedure reduced liver inflammation and possibly slowed progression of cirrhosis.

An ounce of prevention is worth a pound of cure, and the phrase resoundingly holds true in the case of hepatitis B. Today, a vaccine against hepatitis B is available. It can prevent hepatitis B and, therefore, also prevent liver cancer. The American Academy of Pediatrics and the Centers for Disease Control and Prevention currently recommend that all babies born in the United States receive a hepatitis B vaccine at birth.

Six drugs are currently approved in the United States for treatment of chronic hepatitis B:

Peginterferon alfa-2a (Pegasys)
Interferon-alfa-2b (Intron)
Adefovir (Hepsera)
Lamivudine (Epivir)
Entecavir (Baraclude)
Telbivudine (Tyzeka)

These drugs block the replication of hepatitis B in the body. Some also help boost the immune system. A doctor will decide which drug to prescribe based on a patient’s age, disease severity, and other factors. Each drug has various advantages and disadvantages in terms of cost, efficacy, side effects, and likelihood of drug resistance. A combination of drugs may also be prescribed.

Peginterferon alfa-2a. Peginterferon alfa-2a (Pegasys) was approved in 2005 for treatment of chronic hepatitis B. (Peginterferon is also called pegylated interferon.) The drug was previously approved in 2002 for treatment of chronic hepatitis C. Pegasys prevents the hepatitis B virus from replicating and also helps boost the immune system. It is given as a weekly injection. Peginterferon is sometimes prescribed in combination with lamivudine (Epivir).

Interferon Alpha. For many years, interferon alfa-2b (Intron) was the standard drug for hepatitis B. The drug is usually taken by injection every day for 16 weeks. (It does not appear to help hepatitis D.) Unfortunately, even in hepatitis B, the virus recurs in almost all cases, although this recurring mutation may be weaker than the original strain. Administering the drug for longer periods may produce sustained remission in more patients while still being safe. Interferon is also effective in eligible children, although long-term effects are unclear.

Lamivudine, Entecavir, and Telbivudine. These drugs are classified as nucleoside analogs. Lamivudine (Epivir or 3TC) is an antiretroviral drug that is used to treat human immunodeficiency virus (HIV) as well as hepatitis B. Studies suggest that lamivudine reduces viral count in over half of hepatitis B patients who take it as sole therapy for about a year. It is less expensive than interferon-alfa and has fewer side effects, but may not work as well as interferon-alfa for long-term therapy. A major problem with lamivudine is the development of mutated viral strains that become resistant to the drug, particularly in areas where the virus is common. About 20% of patients who take lamivudine develop drug resistance.

In 2005, the Food and Drug Administration (FDA) approved entecavir (Baraclude) for treatment of adults with chronic hepatitis B. In clinical trials, entecavir worked better than lamivudine for treating hepatitis B. Entecavir appears to have less risk of drug resistance than lamivudine. Studies also suggest that it may be a good alternative treatment for patients who have developed resistance to lamivudine. Questions have been raised about the drug’s possible cancer risks. Ongoing studies are evaluating this risk.

In 2006, the FDA approved telbivudine (Tyzeka), the newest nucleoside analog drug, for treatment of chronic hepatitis B.

Adefovir. Adefovir (Hepsera) belongs to a class of antiviral drugs called nucleotide analogs. (Nucleotides are related to nucleosides but have a slightly different chemical structure.) Nucleotide analogs block an enzyme involved in the replication of viruses. Adefovir costs more than lamivudine, but may be effective against lamivudine-resistant strains of hepatitis B. The drug must be taken on a long-term basis. A 2006 study indicated that when patients stopped taking adefovir after 48 weeks, the hepitatis B virus resumed replication. Patients who took the drug for a longer period (144 weeks) continued to benefit from treatment. Another 2006 study indicated that for some patients, adefovir remains effective for up to 5 years, although resistance occurs in about 20% of patients.

Drug Warnings. In 2004, the FDA issued two drug warnings for patients with hepatitis B. The HIV drug tenofovir (Viread) should not be used to treat patients with HIV who are co-infected with hepatitis Bas the drug may increase hepatitis severity. The lymphoma drug rituximab (Rituxan) may reactivate hepatitis B. Patients with lymphoma should be screened for hepatitis B. In 2007, the FDA revised the label for entecavir (Baraclude); patients who are co-infected with hepatitis Band HIV should take entecavir only if they are also taking antiviral HIV drugs.

Emtricitabine is a nucleoside analog drug used to treat HIV and AIDS. It is being investigated for chronic hepatitis B.
Pegylated interferon alfa-2b (Peg-Intron) and alfa-2a (Pegasys) are approved for treatment of chronic hepatitis C. They are being investigated alone and in combination with other drugs, such as ribavirin (Copegus, Rebetol), for treatment of hepatitis B. The combination of pegylated interferon and ribavirin is the standard treatment for hepatitis C.
Thymosin Alpha 1 (Zadaxin), also called thymalfasin, is a synthetic version of a substance derived from the thymus gland (which is responsible for maturation of immune factors called T-cells). It appears to be safe for hepatitis B patients when used alone or in combination with interferon. It is approved in many countries, but not the United States.

Ursodeoxycholic Acid (UDCA) and Drugs Used to Slow Progression. At this time no medication can cure primary biliary cirrhosis. Ursodiol, ursodeoxycholic acid (Actigall), or UDCA has been the standard drug used for primary biliary cirrhosis. Several studies have reported that it slows progression and helps prevent the need for liver transplantation.

It has no effect on symptoms, including itching and fatigue. Some drugs, such as colchicine, corticosteroids, or immunosuppressants, are being investigated for use in combination with UDCA. Long-term controlled trials are needed to determine the value of UDCA alone or with other drugs.

Drugs for Itching. Itching is a major problem with this disease. Cholestyramine, taken with meals, is the first choice for relieving itching. Several other drugs have been used or investigated, including low doses of the drug naltrexone and phototherapy.

Drugs for Impaired Fat Absorption. Because primary biliary cirrhosis affects fat absorption, patients may need high doses or injections of important fat-soluble vitamins, including K, D, A, and E.

Treatment of Nonalcoholic Fatty Liver Disease. Weight loss is the most important method for managing nonalcoholic fatty liver disease (NAFLD) and preventing progression to nonalcoholic steatohepatitis (NASH) and, eventually, cirrhosis. Diabetes and cholesterol control are also important. Investigators are studying whether various drugs used to treat type 2 diabetes may help treat NAFLD and NASH.

Other research is focusing on antioxidant vitamins, such as vitamin E.

In 2005, the National Institutes of Health launched two trials to study treatment of nonalcoholic fatty liver disease and nonalcoholic steatohepatitisin adults and children. Children with NAFLD will receive vitamin E, metformin, or placebo. In the adult trial, patients with NASH will receive vitamin E, pioglitazone, or placebo.

Secondary Biliary Cirrhosis. Secondary biliary cirrhosis caused by blockage in the bile ducts can be relieved by surgery.

Autoimmune Hepatitis. Autoimmune hepatitis is treated with the corticosteroid prednisone and also sometimes immunosuppressants, such as azathioprine (Imuran).

Hemochromatosis. For hemochromatosis, weekly bleedings (phlebotomies) may be performed until iron levels are normal, then repeated as needed. If treatment is given before cirrhosis develops, life expectancy may be normal.

Wilson's Disease. D-penicillamine is the drug most used for Wilson's disease.

There are no current safe and effective therapies for liver scarring (fibrosis). However, recent insights into the cellular and molecular mechanisms responsible for scarring have led to the development of specific, antifibrotic drugs that target the primary injury and inhibit abnormal cell mechanisms. Such drugs, now in very early testing, could one day help prevent or reduce the progression of liver scarring or the progression to liver cancer.

Liver transplantation may be indicated for the following:

Patients who have developed life-threatening cirrhosis and who have a life expectancy of more than 12 years.
Patients with liver cancer that has not spread beyond the liver.

Survival rates after transplantation are similar among those who have hepatitis B, hepatitis C, or alcoholic liver disease. Current 5-year survival rates after liver transplantation are about 75%. Patients also report improved quality of life and mental functioning after liver transplantation. Patients should seek medical centers that perform more than 50 transplants per year and produce better-than-average results.

Unfortunately, there are many more patients waiting for liver transplants than there are available organs. Fortunately, more procedures are now being performed using liver tissue from a living donor. In these cases, surgeons replace the patient’s diseased liver with a part of the liver taken from a donor. The donor’s liver regenerates to full size within a few weeks of surgery, and the recipient’s liver also regrows.

Transplantation surgery generally takes 4 - 12 hours to perform, and patients stay in the hospital for up to 3 weeks after the surgery. Most patients return to normal or near-normal activities 6 - 12 months following the transplant. For the rest of their lives, patients need to take immunosuppressive medication to prevent rejection.

Liver Transplantation in Patients with Hepatitis. One of the primary problems with many hepatitis patients is recurrence of the virus after transplantation.

One study of patients with hepatitis C reported 5-year risks of 80% for viral recurrence and 10% for cirrhosis. A 2004 study found that the hepatitis C virus recurs with more severity with liver donations from living donors than livers taken from cadavers.
Viral recurrence is also high in patients with hepatitis B. In 2007, the FDA approved HepaGram B, an immune globulin, to prevent recurrence of hepatitis B after transplantation. Patients need to receive HepaGram B injections on a lifelong basis.

Liver Transplantation in Autoimmune Liver Diseases. Patients who require transplantation for primary biliary cirrhosis are those who develop major complications of portal hypertension and liver failure or who have poor quality of life and short survival without the procedure. Survival rates after transplantation are excellent.

The outlook is also good for patients who have autoimmune hepatitis who require a transplant. Survival rates are about 90% after 1 year, and 70 - 80% after 5 years. Rejection usually occurs in those patients whose immune systems are very compromised.

Liver Transplantation in Alcoholism. There is considerable controversy over whether liver transplantation should be performed in alcoholics with cirrhosis who are unlikely to abstain. One French study reported no differences in survival, transplant rejection, and other indicators of success and failure after transplantation between alcoholics and non-alcoholics and between alcoholics who abstained and those who relapsed after the procedure.

Click the icon to see an illustrated series detailing a liver transplant.

Lifestyle Changes

A healthy lifestyle is particularly important for people with cirrhosis.

Healthy Foods. Because important antioxidant vitamins are depleted in the cirrhotic liver, patients should maintain a diet rich in fresh fruits, vegetables, and whole grains.

Coffee and Tea. Coffee appears to help lower the risk of cirrhosis, especially among heavy drinkers. A 2006 study indicated that people who drank 1 - 3 cups of coffee a day reduced their risk of alcoholic cirrhosis by 40%. Those who drank 4 or more cups reduced their risk by 80%. Researchers think that there is some ingredient in coffee (other than caffeine) that is responsible for this apparent protection. Studies on tea have been mixed. Some studies report that tea also lowers the risk of chronic liver disease, while others have found no effect.

Antioxidant Supplements. There is some preliminary laboratory evidence that various antioxidant supplements -- including vitamin E, selenium, and S-adenosylmethionine (SAMe) -- may help protect against liver damage and cirrhosis. Supplements, however, are not recommended for people with liver disease except with the advice of a doctor. Some vitamins, such as vitamins D and A, are metabolized in the liver and can be toxic.

Iron Restrictions. Elevated iron levels have been associated with cirrhosis from many causes. Patients should avoid iron-rich foods, such as red meats, liver, and iron-fortified cereals, and should avoid cooking with iron-coated cookware and utensils.

Supplemental Nutritional Products. Supplemental nutritional beverages may be helpful, particularly for patients with both alcoholism and cirrhosis. In one study, patients with both alcoholism and cirrhosis drank Ensure every day as a supplement to their regular diet. After 6 months they showed significant improvement in many signs of overall health compared to those who did not consume the beverage.

Vitamin B1 (Thiamine). Thiamine binds to iron and helps reduce iron load in the liver. One small study suggested it may be helpful for patients with chronic hepatitis B. It is not known if it has any benefit for cirrhosis. Pork is high in the vitamin, but more healthful sources include dried fortified cereals, oatmeal, corn, nuts, cauliflower, sunflower seeds and vitamin pills.

Like most vitamins, vitamin B1 may be obtained in the recommended amount with a well-balanced diet, including some enriched or fortified foods.

Omega-3 Fatty Acids. Some research suggests that supplements of omega-3 fatty acids (found in fish oil and evening primrose oil) may help protect the diseased liver.

Click the icon to see an image of omega-3 fatty acids.

Protein and Soy. High-quality dietary protein may be especially helpful for patients with ascites and for repairing muscle mass, but excessive protein loads may trigger encephalopathy. Protein solutions have been devised that provide beneficial amino acids without including those that increase this risk. There is no limit on vegetable proteins, such as those from soy.

Salt Restriction. Restricting salt consumption to less than 2,000 mg a day is particularly important for patients with ascites. The less salt the better.

Zinc. In some studies, taking zinc supplements have lowered ammonia levels in some patients who were zinc-deficient, a common problem in cirrhosis. Zinc replacement may reduce frequency and severity of muscle cramps and may even help protect against encephalopathy.

Fluid restriction is not usually necessary, but patients with severe ascites should discuss limiting fluid with their doctors.

Exercise increases the risk for portal pressure and variceal bleeding. One study reported that taking a beta-blocker may reduce this risk, although patients should discuss this with their doctor.

Infections can have a severe impact on the liver. Although most respiratory infections generally affect only the lungs, one small study suggested influenza may directly affect the liver in patients with cirrhosis and exacerbate the disease process. Researchers in the study advise annual flu shots for people with cirrhosis.

Patients should be aware that manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any herbal remedies or dietary supplements.

Among the natural substances being investigated for liver disease are ginseng, glycyrrhizin (a compound in licorice), catechin (found in green tea), SAMe, and silymarin (found in milk thistle).

Silymarin. Silymarin is a chemical found in the milk thistle herb. It is one of the most popular, and most studied, herbal remedies for liver disease. Some studies have indicated that silymarin may help improve liver enzyme levels. However, a 2005 review found that milk thistle did not help reduce deaths from liver disease caused by alcohol or hepatitis.

S-adenosylmethionine. S-adenosylmethionine (SAMe) is a chemical found in all parts of the body, which declines with age. It has been investigated for years in Europe for arthritis, depression, and liver disease. Some preliminary studies suggest it may provide some protection against liver damage and scarring and may improve survival rates in alcoholic patients with cirrhosis. It is very expensive, however, and as with all unregulated products, long-term side effects, drug interactions, and other factors are not fully known.

The following warnings are of particular importance for people with liver disease:

Kava kava (an herb used for anxiety and tension) can be toxic to the liver and cause severe hepatitis and even liver failure if taken excessively.

Abdominal Infections

Antibiotics are administered when fluid examination and tests for ascites indicate infection. For a first episode, the antibiotic cefotaxime is typically administered intravenously, requiring hospitalization. Treatment usually lasts 10 days, but research indicates that 5 days may be sufficient for certain patients. Some research indicates that the oral antibiotic ofloxacin may work as well with fewer complications, allowing patients to be treated at home.

In advanced cirrhosis, the risk for serious abdominal infection is high, and the antibiotic norfloxacin is often prescribed preventively against specific organisms that infect the abdominal cavity. One study reported, however, that patients who took norfloxacin became susceptible to Staphylococcal infections. Long-term treatments with norfloxacin or similar antibiotics may increase the risk for fungal infections after liver transplantation.

Encephalopathy

The first step in managing encephalopathy (damage to the brain) is to treat any precipitating cause, such as:

High ammonia levels
Bleeding
Low oxygen
Dehydration
Infection
Use of sedatives

Some studies indicate that manganese poisoning may be partially responsible for encephalopathy in cirrhosis. Studies are needed to determine if drugs that remove manganese improve this complication.

Ammonia is the leading toxin in causing encephalopathy related to cirrhosis. Mild encephalopathy is managed by directing therapy toward eliminating ammonia in the intestine:

The first step is to restrict animal protein, substituting meats and dairy products with vegetable protein, such as soy, and amino acid supplements.
Enemas, which clean out the intestine, may be effective.
Lactulose (Cephulac, Chronulac, Constulose, Duphalac, Enulose) and lactitol, known as disaccharides, help lower blood ammonia levels and have been shown to be effective in improving cognitive function and quality of life in people with mild encephalopathy.
Antibiotics, such as metronidazole, rifamycin, or neomycin, are effective in reducing levels of ammonia-producing bacteria in the intestine, although long-term use of these drugs can cause toxic side effects. Rifaximin (Xifaxan), another antibiotic, was approved in 2005 for treatment of hepatic encephalopathy.
L. acidophilus is the probiotic found in live culture yogurt. Researchers are studying whether L. acidophilus food or supplements can aid in improving liver and cognitive functions.
Researchers are investigating whether exercise can help remove ammonia from the body and improve encephalopathy.

Investigational Drugs. Certain drugs, such as rifaximin (Xifaxan) and flumazenil (Mazicon, Romazicon), are under investigation for treating encephalopathy. Flumazenil is typically administered to counteract the effects of sedatives.

Ascites

Nearly all patients with ascites (fluid accumulation in the abdomen) can benefit from the following measures:

Abstaining from alcohol. (Sometimes abstaining from alcohol is enough to improve this complication.)
Restricting salt.
Taking diuretics, usually spironolactone (Aldactone) and furosemide (Lasix). Previously, spironolactone was usually given alone, but experts now use it by itself only in patients with minimal fluid buildup. Patients should be monitored carefully for excessive and too-fluid loss, which can set off complications, including hypokalemia (dangerously low potassium levels), kidney failure, or encephalopathy. Weight loss from diuretics usually should not exceed 1 - 2 pounds per day, but there is no limit for patients with massive swelling.

Doctors often recommend bed rest for patients with ascites, but studies do not support its benefits. Restricting fluid is not usually necessary unless sodium levels in the blood are very low.

Patients with recurring ascites, or ascites that does not respond to standard diuretics after a month (refractory ascites), may require procedures to reduce fluid.

Large-Volume Paracentesis. Large-volume paracentesis is the current standard procedure and involves the following:

Large volumes of fluid are removed through a tube in the abdomen. Research indicates that 4 - 6 liters are usually effective and safe.
Albumin (protein) may be administered intravenously. This helps prevent a sudden drop in blood flow in the arteries. One study suggested that terlipressin, a drug that constricts blood vessels, may be as effective.
If the ascites does not respond to treatments, the patient may need paracentesis every 2 weeks or more frequently, and up to 10 liters may need to be removed.

Patients who need this procedure are probably not complying with dietary requirements.

Transjugular Intrahepatic Portosystemic Shunt. Studies have been mixed on whether transjugular intrahepatic portosystemic shunt (TIPS) improves survival without transplantation compared to large-volume paracentesis. An important 2003 study reported that although TIPS reduced the number of paracenteses, there was no improvement in survival rates. In addition, patients who were given TIPS had a higher risk for encephalopathy than those given large-volume paracentesis. In general, TIPS should be a second-line option for ascites that does not respond to diuretics.

Peritoneovenous Shunting. Peritoneovenous shunting is an older, more invasive, procedure involving insertion of a tube, or shunt, under the skin that routes the fluid from the abdomen into the jugular vein. The procedure can have serious complications, including infection, blood clots, encephalopathy, and rupture of blood vessels in the esophagus. It is now generally reserved for patients who are not candidates for repeat paracentesis or liver transplantation.

Hepatorenal syndrome can occur in patients with ascites. This is a life-threatening condition in which the kidneys fail in trying to compensate for altered blood flow in the liver. Studies suggest that terlipressin may be an effective treatment in combination with albumin for hepatorenal syndrome.

Researchers are testing certain drugs that may correct the imbalances in circulation that lead to portal hypertension and ascites. Of particular interest are drugs called nonpeptide vasopressin antagonists, also referred to as aquaretics. They may reverse the dilation in blood vessels that lead to salt and fluid retention.

The prognosis for patients with ascites is poor, even with intensive procedures. Liver transplantation should be considered for patients when ascites does not respond to treatments and when poor liver function or other complications, such as peritonitis or kidney failure, are present.

Bleeding Episodes

Preventing an Initial Bleeding Episode. About half of patients with mild-to-moderate cirrhosis have esophageal varices (enlarged veins in the esophagus). In such patients, the risk for bleeding within 2 years is as high as 35%. Bleeding is fatal in half of these patients. In general, experts recommend preventive drugs for such patients, even if they have not been screened with endoscopy -- the procedure needed to actually detect varices. Beta-blockers are the only medications to date that have some preventive effects, but others are under investigation.

Guidelines for Treating Bleeding Episodes. The doctor should first be certain that bleeding is caused by portal hypertension and ruptured varices and not by other conditions. For example, patients with cirrhosis are also at higher than average risk for bleeding peptic ulcers.

Saline or Ringers solution (a fluid and electrolyte replenisher) followed by red blood cells and plasma is administered immediately to replace lost blood.

The next step is to immediately achieve normal blood clotting (hemostasis) in order to stop the current bleeding episode and prevent early recurrence, which typically occurs 3 - 5 days after a bleeding episode.

In general it is a two-pronged approach using drugs and endoscopy procedures.

Drugs. Either octreotide or vasopressin are typically used to reduce portal pressure and blood flow.
Endoscopy. Endoscopy involves insertion of a thin tube containing a tiny camera followed by surgery to make repairs. Endoscopic sclerotherapy is the most common procedure. Emergency sclerotherapy is often used as first-line therapy for variceal bleeding, but a major 2002 analysis suggested that it is no more effective than drugs for stopping bleeding, and it has potentially serious adverse effects.

A combination of drugs and endoscopy is the best approach for stopping bleeding compared to endoscopy alone. It is not clear if there is any difference in long-term survival, however.

Prevent Bleeding Recurrence. Rebleeding is common after an episode. Beta-blocker drugs are typically used, although they are not effective for many patients.

Preventing Complications. The patient who is experiencing a bleeding episode is at high risk for other complications, including pneumonia, bacterial infections, and hepatic encephalopathy. Bacterial infections can also impair blood clotting. Preventive oral antibiotics are often problematic in these patients. One study suggested that intravenous ciprofloxacin may be helpful.

Beta-Blockers. Beta-blockers, typically propranolol (Inderal) or nadolol (Corgard), reduce the heart rate and can lower portal vein pressure in many patients and so reduce variceal bleeding. Carvedilol (Coreg), a newer drug, may be even more effective, but more research is needed. Beta-blockers are also used as a primary approach for prevention of recurring bleeding. Nevertheless, they fail to reduce portal pressure in nearly 40% of patients with cirrhosis. They may not be appropriate for patients with type 1 diabetes, asthma, emphysema, and chronic bronchitis. They must be taken for at least 2 years and most likely longer to sustain a survival advantage.

Other Drugs. Other drugs are being used or investigated, mostly in combination with beta-blockers, to reduce recurrence rates.

Isosorbide mononitrate is a nitrate, a type of drug commonly used for angina. Combinations with beta-blockers appear to prevent rebleeding more effectively than beta-blockers alone. It is not clear if the combination improves any other aspects of the disease. The nitrate may also be an alternative drug for patients who cannot tolerate beta-blockers. Studies have failed to show any survival advantage, however, when isosorbide mononitrate is used alone.
The diuretic spironolactone may be helpful in combination with a beta-blocker for reducing both ascites and rebleeding after an initial episode.
Angiotensin II receptor antagonists, including losartan (Cozaar), are being studied for lowering portal pressure.

Somatostatinand Similar Drugs. Somatostatin is a natural hormone that constricts blood vessels. This drug or synthetic derivatives (octreotide and vapreotide) may be more effective than the common procedure, endoscopic sclerotherapy, for controlling bleeding. No single drug is more effective than another. Their benefits for improving overall survival, however, are still uncertain, and a major analysis of current studies found no effects on survival rates with either octreotide or somatostatin.

Somatostatin, the natural hormone, controlled variceal bleeding in 87% of patients in one study, but it is short acting.
Octreotide (Sandostatin) is a derivative of somatostatin and is longer acting. It has largely replaced the older drug. It is very safe, even for heart patients, and has few serious side effects.
Vapreotide (Octastatin) also resembles somatostatin. One study concluded that a combination of vapreotide and endoscopic treatment is more effective than endoscopic treatment alone for controlling bleeding, but the combination therapy did not improve mortality rates at 42 days. The study suggested that these drugs should be taken for 5 days.

Vasoconstrictors. Vasoconstrictors narrow the blood vessels and reduce flow in the spleen. They are particularly effective when used with nitroglycerin.

Vasopressin (Pitressin) is the most commonly used vasoconstrictor. It poses a risk to the heart, however, and it is not clear whether it is actually helpful.
Terlipressin is a synthetic version of vasopressin that is proving to be as effective as sclerotherapy in controlling bleeding. It also lacks vasopressin's side effects and may prove to prolong survival and serve as a bridge for patients waiting for liver transplantation.

Endoscopic procedures use a tube inserted down through the esophagus, containing microcameras and tiny instruments. Endoscopy is used both to diagnose the disease and stop bleeding. The two standard procedures are band ligation and sclerotherapy. In general, a combination of drug therapies and an endoscopic procedure is the usual approach for preventing a bleeding recurrence.

Endoscopic Band Ligation. In endoscopic band ligation, latex bands are wrapped around the bleeding varices, shutting off the blood supply. It is the method of choice to control of bleeding and, in weekly sessions, to prevent rebleeding, because it has a lower risk for complications than sclerotherapy. Recurrence rates are higher with band ligation, however. Studies are mixed on whether weekly treatments with band ligation are any more effective in preventing rebleeding than beta-blockers plus isosorbide mononitrate. A combination of medications plus band ligation is under investigation.

Investigators are studying argon plasma coagulation (APC) after band ligation to prevent variceal recurrence and rebleeding. This procedure uses argon gas to deliver electric currents that coagulate and stop bleeding.

Endoscopic Sclerotherapy. Endoscopic sclerotherapy is only effective against bleeding in the esophagus. The endoscopic tube is inserted through the mouth. A sclerosant (a solution that toughens the tissue around the variceal blood vessels) is injected to stop the bleeding. The procedure is repeated over a period of 2 - 3 months. Repeat treatments appear to reduce rebleeding and death. Minor complications (usually ulcers in the mucus membranes) are common, and serious complications can occur (narrowing or perforation of the esophagus and leakage at the injection site.)

Balloon tamponade has been available for years, but it is now used only for bleeding that cannot be controlled by drugs or endoscopy. It uses a tube inserted through the nose and down through the esophagus until it reaches the upper part of the stomach. A balloon at the tube's end is inflated and positioned tightly against the esophageal wall. It is usually deflated in about 24 hours. Serious complications can occur, the most dangerous being rupture of the esophagus. Recurrence of bleeding is common.

Shunts are used for patients who are still bleeding in the esophagus after endoscopic sclerotherapy or who are bleeding in the stomach. Choices include the following:

Transjugular intrahepatic portosystemic shunt (TIPS)
A surgical shunt

Shunt operations usually eliminate variceal bleeding, but encephalopathy and shunt failure are frequent complications. Doctors do not recommend shunts as elective surgery for high-risk patients who are candidates for liver transplantation, since shunts make this operation more difficult.

Transjugular Intrahepatic Portosystemic Shunt.A transjugular intrahepatic portosystemic (or portal-systemic) shunt (TIPS) involves the following:

The patient only requires a local anesthetic and a sedative.
A long needle is inserted into the jugular vein in the neck and passed down through the vena cava, a large vein that conducts blood back to the heart. This serves to widen the vein.
The surgeon makes an incision in the hepatic vein in the liver and creates a connection to the portal vein.
A cylindrical wire-mesh stent is inserted into this connecting vein.
The stent now acts as a shunt, which reroutes blood around the scarred liver.

TIPS is a good choice for bleeding that is not controlled by endoscopy, particularly when it is performed shortly after a bleeding episode. It also reduces ascites.

It is not useful as the first choice for stopping an initial bleeding episode or for preventing rebleeding, however, since it poses a high risk for encephalopathy. This complication outweighs its benefits compared to endoscopy for initial treatment and to beta-blockers for preventing recurrence. Blockage or closure of the shunt can develop over time.

TIPS is generally recommended for only patients who:

Cannot tolerate sclerotherapy
Are unlikely or unable to comply with the repeated procedures necessary for sclerotherapy
Have poor blood circulation

Surgical Shunts. There are two types of surgical shunts:

A portal shunt, or portal systemic shunt. It was introduced in 1945 and was the first significant treatment for bleeding varices. It relieves pressure in the portal vein by surgically joining it to the inferior vena cava, a large vein that conducts blood back to the heart. It poses a high risk for encephalopathy and does not appear to improve survival, so is not used often.
A variation called the H-graft portacaval shunt is a partial shunt that is proving to be effective for treating bleeding. It controls bleeding in 90% of patients and has a lower encephalopathy rate than the complete portal shunt or TIPS. In fact, early studies report that it may have lower rates for transplantation and death than TIPS.
A distal splenorenal shunt (DSRS) preserves blood flow through the portal vein while relieving pressure on the varices by joining the left kidney vein to the splenic vein. (The splenic vein returns blood from the spleen and is one of two veins that form the portal vein.) Studies show that DSRS has similar mortality rates compared to the portal shunt but lower rates of encephalopathy afterwards. Patients with alcoholic cirrhosis fare worse with DSRS than nonalcoholic patients. It is probably best used as an elective operation in patients with good liver function who continue to bleed in spite of endoscopy.

Resources

www2.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.aasld.org -- American Association for the Study of Liver Diseases
www.liverfoundation.org -- American Liver Foundation
www.gastro.org -- American Gastrointestinal Association
www.cdc.gov/ncidod/diseases/hepatitis -- Centers for Disease Control and Prevention, Hepatitis
www.hepfi.org -- Hepatitis Foundation International
www.pbcers.org -- Primary Biliary Cirrhosis Organization
www.organdonor.org -- National Transplant Society
www.unos.org -- United Network for Organ Sharing
www.organdonor.gov -- US government organ donor site

References

Bruno S, Crosignani A, Maisonneuve P, Rossi S, Silini E, Mondelli MU. Hepatitis C virus genotype 1b as a major risk factor associated with hepatocellular carcinoma in patients with cirrhosis: A seventeen-year prospective cohort study. Hepatology. 2007 Aug 6; [Epub ahead of print]

Bruno S, Stroffolini T, Colombo M, Bollani S, Benvegnu L, Mazzella G, et al. Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: a retrospective study. Hepatology. 2007 Mar;45(3):579-87.

Ekstedt M, Franzen LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006 Oct;44(4):865-73.

Huang H, Shiffman ML, Friedman S, Venkatesh R, Bzowej N, Abar OT, et al. A 7 gene signature identifies the risk of developing cirrhosis in patients with chronic hepatitis C. Hepatology. 2007 Aug;46(2):297-306.

Prasad S, Dhiman RK, Duseja A, Chawla YK, Sharma A, Agarwal R. Lactulose improves cognitive functions and health-related quality of life inpatients with cirrhosis who have minimal hepatic encephalopathy. Hepatology. 2007 Mar;45(3):549-59.

Suzuki A, Lymp J, Donlinger J, Mendes F, Angulo P, Lindor K. Clinical predictors for hepatocellular carcinoma in patients with primary biliary cirrhosis. Clin Gastroenterol Hepatol. 2007 Feb;5(2):259-64. Epub 2006 Dec 15.

U.S. Preventive Services Task Force. Screening for hemochromatosis: recommendation statement. Ann Intern Med. 2006 Aug 1;145(3):204-8.

Whitlock EP, Garlitz BA, Harris EL, Beil TL, Smith PR. Screening for hereditary hemochromatosis: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2006 Aug 1;145(3):209-23.

Review Date:
8/31/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Benign prostatic hyperplasia

FitSugar — Wed, 08 Oct 2008 17:35:38 -0700

In This Report

Highlights
Introduction
Symptoms
Causes of Benign Prostatic ...
Causes of Lower Urinary Tra...
Risk Factors
Complications
Diagnostic Tests
Treatment
Lifestyle Changes
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Self-Management for Benign Prostatic Hyperplasia (BPH)

Men who receive training in lifestyle and behavioral approaches may be able to successfully manage BPH without drugs or surgery, suggests a 2007 study in the British Medical Journal. Men in the study were trained to self-manage their lower urinary tract symptoms (LUTS), a condition that often accompanies BPH. Self-management approaches included limiting daily fluid intake, avoiding caffeine and alcohol, and urinating at least once every 3 hours.

Diet and BPH

Eating lots of fruits and vegetables, especially those high in beta-carotene and vitamin C, may help protect against BPH, suggests a 2007 study in the American Journal of Clinical Nutrition. Another study, published in Urology, indicated that high consumption of cereal, bread, eggs, and poultry may increase the risk of BPH.

High Intake of Zinc Increases BPH Risk

High doses of zinc supplements may increase the risk for urinary problems, especially for men, indicates a 2007 study in the Journal of Urology. Patients in the study who took 80 mg/day of zinc were more likely to be hospitalized for urinary complications than those who did not take zinc. In general, the upper limit for zinc supplements should not exceed 40 mg/day.

Tamsulosin and Tolterodine Combination Treatment

For men with moderate-to-severe LUTS, including overactive bladder, a combination of tamsulosin (Flomax) and tolterodine (Detrol) works better than either drug alone, according to a study published in 2006 in the Journal of the American Medical Association.

Botox for BPH?

Botulinum toxin A (Botox) is being investigated as a treatment for BPH. In research presented at the 2007 meeting of the American Urological Association, men who had Botox injected into their prostate glands experienced symptom relief and improved quality of life for up to a year after treatment.

Introduction

Hyperplasia is a general medical term referring to excess cell replication. Benign prostatic hyperplasia (BPH), also called benign prostate hyperplasia, is a noncancerous growth of the prostate gland. It is the most common noncancerous form of cell growth in men and usually begins with microscopic nodules in younger men. BPH, however, is not a precancerous condition. Prostate cancer usually occurs in the outer area of the prostate, called the peripheral zone.

The prostate gland is an organ that surrounds the urinary urethra in men. It secretes fluid that mixes with sperm to make semen. The urethra carries urine from the bladder and sperm from the testes to the penis.

As BPH progresses, overgrowth occurs in the central area of the prostate, called the transition zone, which wraps around the urethra (the tube that carries urine through the penis). This pressure on the urethra can cause lower urinary symptoms that have been the basis for diagnosing BPH. In 2000, an expert committee suggested that the impact of such symptoms on quality of life, including sexual activity, is also important in assessment of the disease.

Click the icon to see an image of BPH.

Description of the Prostate Gland. The prostate gland is located between the bladder and the rectum and wraps around the urethra (the tube that carries urine through the penis). It is basically composed of three different cell types:

Glandular cells, which produce a milky fluid that liquefies semen.
Smooth muscle cells, which contract during sex and squeeze the fluid from the glandular cells into the urethra, where it mixes with sperm and other fluids to make semen. Molecules called alpha adrenergic receptors stimulate the muscle cells.
Stromal cells (which form the structure of the prostate).

Click the icon to see an image of the male reproductive anatomy.

The central area of the prostate that wraps around the urethra is called the transition zone. The entire prostate gland is surrounded by a dense, fibrous capsule.

Functions of the Prostate Gland. The prostate gland provides the following functions:

The glandular cells produce a milky fluid, and during sex the smooth muscles contract and squeeze this fluid into the urethra. Here, it mixes with sperm and other fluids to make semen.
The prostate also secretes another substance that may have antibacterial properties.
The prostate gland also contains an enzyme called 5 alpha-reductase that converts testosterone to dihydrotestosterone, another male hormone with a major impact on the prostate.

Changes During the Lifespan. The prostate gland undergoes many changes during the course of a man's life. At birth, the prostate is about the size of a pea. It grows only slightly until puberty, when it begins to enlarge rapidly. It reaches normal adult size and shape, about that of a walnut, when a man is in his early 20s. The gland generally remains stable until about the mid-40s, when, in most men, the prostate begins to grow again through a process of cell multiplication.

Hormonal changes also occur in the prostate gland. Testosterone levels fall while dihydrotestosterone remain at normal levels.

Symptoms

The symptoms commonly associated with BPH are collectively called lower urinary tract symptoms (LUTS). BPH is not always the cause of these symptoms. An enlarged prostate may be accompanied by few symptoms, while severe LUTS may be present with normal or even small prostates and are most likely due to other conditions. Many experts are now categorizing LUTS as either voiding or storage symptoms to help define the source of the problem.

Voiding symptoms, also referred to as obstructive symptoms, can be caused by an obstruction in the urinary tract. They are often due to BPH. Obstruction is the most serious complication of BPH and requires medical attention. Voiding symptoms include:

Weak or intermittent urinary stream
Straining when urinating
A hesitation before urine flow starts
A sense that the bladder has not emptied completely
Dribbling at the end of urination or leakage afterward
Painful urination
Hematuria (blood in the urine)

Storage symptoms, also referred to as irritative symptoms, include:

An increased frequency of urination, particularly at night
An urgent need to urinate
Bladder pain or irritation when urinating

Urine flows from the kidney through the ureters into the urinary bladder where it is temporarily stored. As the bladder becomes distended with urine, nerve impulses from the bladder signal the brain that it is full, giving the individual the urge to void. By voluntarily relaxing the sphincter muscle around the urethra, the bladder can be emptied of urine. Urine then flows out through the urethra.

The process of urination is more complicated than it appears:

It begins when waste fluids flow out of the kidneys into two long tubes called ureters.
The ureters empty into the bladder, which rests on top of the pelvic floor, a muscular structure similar to a sling running between the pubic bone and the base of the spine.
The brain regulates muscles in the urinary tract through a pathway of nerves. As the bladder fills to its capacity of 8 - 16 oz of fluid, the nerves send signals from the bladder to the brain that indicate how full the bladder is.
As the bladder swells, the muscles contract to prevent urination.
At the time of urination, the spinal cord initiates the voiding reflex. The detrusor muscles (which surround the bladder) contract, while the internal sphincter (a strong muscle encircling the neck of the bladder) relaxes.
When the internal sphincter is open, urine flows out of the bladder into the urethra (the tube that carries urine from the bladder out through the penis).

Causes of Benign Prostatic Hyperplasia

The causes of benign prostatic hyperplasia are not fully known. Several theories have been proposed to explain benign cell growth in older men.

Male Hormones. Androgens (male hormones) most likely play a role in prostate growth. The most important androgen is testosterone, which is produced throughout a man's lifetime. The prostate converts testosterone to a more powerful androgen, dihydrotestosterone (DHT). DHT stimulates cell growth in the tissue that lines the prostate gland (the glandular epithelium) and is the major cause of the rapid prostate enlargement that occurs between puberty and young adulthood. DHT is a prime suspect in prostate enlargement in later adulthood.

Estrogen. Some authorities believe that the female hormone estrogen may also play a role in BPH. (Some estrogen is always present in men.) As men age, testosterone levels drop, and the proportion of estrogen increases, possibly triggering prostate growth.

Another theory focuses on cells in a certain section of the gland that may become active late in life, signaling other prostate cells to replicate or causing them to be sensitive to growth-stimulating hormones.

This theory suggests that a process known as apoptosis, in which cells naturally self-destruct, goes awry and results in cell proliferation.

Some experts theorize that the blood vessels in the prostate gland may deteriorate as men age, causing abnormal blood flow and oxygen loss, which would stimulate cell growth. Such a theory is supported by the presence of heart and circulatory problems in many men with BPH.

Causes of Lower Urinary Tract Symptoms

Several structural or medical conditions, either independently or in conjunction with BPH, can cause lower urinary tract symptoms. In addition, prostate growth does not always explain symptoms normally attributed to BPH. Men with large prostates do not always have symptoms, and men with small or normal-sized prostates sometimes have symptoms that are more severe than in those with enlarged glands.

Abnormalities in the urinary tract can cause BPH-like symptoms in men with or without enlarged prostate glands. Such conditions can produce obstruction, impair or weaken the detrusor muscles surrounding the bladder, or cause other damage that impacts the urinary tract. They include:

Muscle contractions in the area where the bladder and urethra meet
A narrowing of the urethra
A weakened bladder
Overactivity in prostate muscles

The male and female urinary tracts are relatively the same except for the length of the urethra.

The process of aging weakens the detrusor muscles that surround the bladder, which causes the bladder to become unstable and lose capacity. Unstable detrusor muscles may also impair bladder storage capacity, which then produce irritative or storage symptoms. Studies also indicate that as men get older they may produce more urine at night, although the total daily output of urine is similar to that in middle-aged men. It is not fully known why this occurs.

Prostatitis is an inflammation of the prostate gland. It can be caused by bacterial infection, which is the easiest cause to diagnose. However, the most common form of prostatitis is nonbacterial.

Bacterial Prostatitis. A prostatitis infection can occur abruptly (acute) or be long-term (chronic). Chronic bacterial prostatitis (CBP) is often subtle and may persist for weeks or months with low-grade symptoms, including an urgent need to urinate, frequent urination, and the need to urinate at night. Pain may occur in the lower back or rectum, or it may develop after ejaculation. Because the prostate isn't swollen, doctors may mistake chronic prostatitis for BPH. A urine culture should always be taken, which, in the case of both acute and chronic bacterial prostatitis, will reveal bacteria and confirm a diagnosis. Antibiotics are required to treat CBP. Fluoroquinolones and trimethoprim-sulfamethoxazole (Bactrim, Septra) are particularly effective, but prolonged treatment may be necessary.

Nonbacterial Prostatitis. In nonbacterial prostatitis, inflammation occurs, but no bacteria are present. It is 8 times more common than bacterial prostatitis. The causes of nonbacterial prostatitis have not been determined. In one study, alfuzosin, an alpha-blocker drug that is used for BPH, provided some modest relief in patients with prostatitis and chronic pain. The routine use of drug therapy does not seem to help this condition. More research is needed.

Prostatodynia. Although it is considered a form of prostatitis, prostatodynia is a noninflammatory disorder characterized by prostate pain, but neither inflammation nor bacteria are present. The causes of prostatodynia are unknown.

Congestion of the prostate, sometimes called prostatosis, is a benign condition in which the prostate seems to be swollen by excess fluid. It can cause frequent, slow, or uncomfortable urination, but it responds well to a program of frequent ejaculation and sitz baths.

On occasion, prostate cancer can mimic BPH, since both conditions may cause obstruction of the urethra. Bladder cancer can sometimes cause urinary bleeding, frequency of urination, or a sense of urgency, also symptoms of BPH.

Click the icon to see an image of prostate cancer.

Several other conditions can impair the lower urinary tract, including tumors, reactions to medications, and spinal cord injuries. Diseases that affect the nervous system, such as diabetes, multiple sclerosis, and shingles, can desensitize the nerves so that they fail to sense fullness and do not trigger the contraction of the bladder.

Risk Factors

About 5.5 million American men have benign prostatic hyperplasia (BPH) that could warrant medical attention. Age is the major risk factor. BPH occurs in about 60% of men over 60 years of age and over 80% of men over age 80.

A family history of BPH appears to increase a man's chance of developing the condition. One study reported that men with BPH who had three or more family members with the condition had much larger prostate glands than men with BPH without such a family history.

Some evidence suggests a higher incidence of benign prostatic hyperplasia -- particularly fast-growing BPH -- in men with obesity, heart and circulatory diseases, and type 2 diabetes. Diabetes and hypertension, in any case, worsen urinary tract symptoms in men with BPH. In one study, diabetes adversely affected flow rates, although residual urine volumes were not significantly greater.

Complications

The progression of symptoms in benign prostatic hyperplasia (BPH) is typically very slow, and additional symptoms, when they occur, often come and go. Individual response to these symptoms also varies widely. Some men can tolerate very uncomfortable sensations of abnormal urination, while other men seek relief from mild symptoms. BPH does not appear to impair sexual function. Problems with urination, however, can be very distressing and severely affect quality of life in some cases.

Click the icon to see an animation about BPH.

Men are more apt to tolerate voiding symptoms (intermittent flow, hesitancy before urinating) and seek help for storage symptoms (urgency, frequency, urination at night). Voiding symptoms, however, may indicate an obstruction blocking the bladder, which if extensive can severely reduce urine flow and cause other complications, some serious.

Acute Urinary Retention. Sometimes a man is unaware of an obstruction until he suddenly cannot urinate at all. This condition is called acute urinary retention. It is a dangerous complication that can damage the kidneys and may require emergency surgery. In general, BPH progresses very slowly, and long-term urinary retention is very uncommon. Men with BPH at highest risk for this problem tend to be elderly and to have moderate-to-severe lower voiding symptoms. Taking anti-hypertensive drugs (except for diuretics) or antiarrhythmic drugs may also increase the risk.

Other Complications. Bladder obstruction can also cause bladder stones, blood in the urine, urinary tract infection, and incontinence. It may also increase the risk for chronic kidney disease. Unfortunately, no current tests can accurately predict which men are at higher risk for complications, although men with a weak urine stream and larger prostates are at higher risk for urinary retention.

Click the icon to see an image of prostate cancer.

Debate is ongoing over whether BPH and prostate cancer have any association. Both occur in men in the same age groups, and BPH causes prostate enlargement. Most evidence finds no significantly higher risk for prostate cancer in men with BPH. For one reason, the two conditions develop in different parts of the prostate:

BPH occurs in the inner transition zone, while
Cancer tends to develop in the peripheral outer zone

A 10-year study found no higher risk for prostate cancer in men with BPH. Unsuspected prostate cancer is detected during surgery in about 15% of BPH patients, but the risk of this slow-growing cancer is high in all older men. Some estimates suggest that up to a third of men over age 50 have at least microscopic prostate cancer.

Still, there is some evidence that men with fast-growing BPH may be at higher than average risk for prostate cancer. This prostate condition is also associated with obesity, heart disease, and diabetes. Some experts suspect that insulin resistance may be the common factor in all of these conditions, including prostate cancer.

Diagnostic Tests

An indexing tool called the International Prostate Symptoms Score (IPSS) can help evaluate the key lower urinary tract symptoms. As opposed to laboratory tests or other objective tests, this scoring system measures the patient's own experience. The higher the score, the more severe the conditions. It is useful for many reasons:

The patient's score on this test gives a highly accurate assessment of the effect of lower urinary tract symptoms on the quality of a man's life.
It is a reasonable basis from which the patient and doctor can discuss treatment options.
The index is also often used to gauge treatment outcomes and may be a better indicator of success than objective tests, such as the measurement of the prostate gland or the rate of urine flow.

Limitations. The IPSS is useful only as a measure of symptom severity, and has the following limitations:

Other conditions can produce similar scores, so the test is not used as a diagnostic tool for BPH.
The index does not include other urinary symptoms, such as dribbling and incontinence or sexual health, that are important for quality of life. At the very least, the patient should have a frank discussion with his doctor if such symptoms are present and affect his life.
It also does not reflect regional or ethnic differences that can vary the responses to these symptoms.


Symptoms over past month	Never	Less than 1 time in 5	Less than half the time	About half the time	More than half	Almost always
Sensation that the bladder is not empty after urinating	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Need to urinate within two hours of a previous urination	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Need to stop and start again several times while urinating	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Have a weak urinary stream	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Need to strain to urinate	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Number of times during the night awakened by the need to urinate	0 = None	1 = One time	2 = Twice	3 = three times	4 = four times	5 = five times or more
Circle appropriate number. Totals of 7 or less = mild symptoms; 8-19 = moderate; 20-35 = severe.

Other indexing systems, such as Symptom Problem Index (SPI) and the BPH Impact Index (BII), which gauge different quality-of-life and disease issues, are being used in addition to the IPSS to help assess the patient.

Digital Rectal Exam. The digital rectal exam is used to detect an enlarged prostate. The doctor inserts a gloved and lubricated finger into the patient's rectum and feels the prostate to estimate its size and to detect nodules or tenderness. The exam is quick and painless, but embarrassing for some, and far from infallible. The test helps rule out prostate cancer or problems with the muscles in the rectum that might be causing symptoms, but it generally underestimates the prostate's size. It is never the sole diagnostic tool for either BPH or prostate cancer.

Other Physical Examinations. The doctor will usually press on and manipulate (palpate) the abdomen and sides to detect signs of kidney or bladder abnormalities. The doctor will also check for signs of anemia or swelling in the legs and arms. Certain procedures that test reflexes, sensations, and motor response may be performed in the lower extremities to rule out possible neurologic causes of bladder dysfunction.

To determine whether the bladder is obstructed, an electronic test called uroflowmetry measures the speed of urine flow. The test cannot determine the cause of obstruction, which can be due not only to BPH but possibly also to problems in the urethra, weak bladder muscles, or other causes.

The patient is instructed not to urinate for several hours before the test and to drink plenty of fluids so he has a full bladder and a strong urge to urinate.
To perform this test, a patient urinates into a special toilet equipped with a uroflowmeter.
It is important that the patient remains still while urinating to help ensure accuracy, and that he urinates normally and does not exert strain to empty his bladder or attempt to retard his urine flow.
Many factors can affect urine flow (such as straining or holding back because of self-consciousness) so experts recommend then that the test be repeated at least twice.

Q[max]. The rate of urine flow is calculated as milliliters of urine passed per second (mL/s). At its peak, the flow rate measurement is recorded and referred to as the Q[max]. The higher the Q[max], the better the patient's flow rate. Men with a Q[max] of less than 12 mL/s have four times the risk for urinary retention than men with a stronger urinary flow.

The Q[max] measurement is sometimes used as the basis for determining the severity of obstruction and for judging the success of treatments. It is not very accurate, however, for several reasons:

Urine flow varies widely among individuals as well as from test to test.
The patient's age must be considered. Flow rate normally decreases as men age, so the Q[max] typically ranges from more than 25 mL/s in young men to less than 10 mL/s in elderly men.
The Q[max] level does not necessarily coincide with a patient's perceptions of the severity of his own symptoms.

A urinalysis can detect signs of bleeding or infection. A urinalysis involves a physical and chemical examination of urine. In addition, the urine is spun in a centrifuge to allow sediments containing blood cells, bacteria, and other particles to collect. This sediment is then examined under a microscope. Although urinary infection is uncommon in younger men, it occurs more frequently in older men, particularly those with BPH. A urinalysis also helps rule out bladder cancer.

To rule out prostatitis (infection or inflammation of the prostate gland), a simple test called the Pre and Post Massage Test (PPMT) is about 90% accurate. This test requires two cultures and microscopic examinations of urine samples, taken before and after massage of the prostate gland. To massage the prostate the doctor simply inserts a gloved finger into the rectum and presses several times on the prostate. The following results are indicated by findings on cultures after massage:

Category II prostatitis (Chronic bacterial). Bacteria are found on post-massage.
Category IIIA prostatitis (Inflammatory chronic pelvic pain syndrome). Leukocytes or other cells are found that indicate inflammation.
Category IIIB prostatitis (Noninflammatory chronic pelvic pain syndrome). No signs of inflammation or bacteria.

In men with symptoms, blood tests can measure a substance called serum creatinine, which is a marker for kidney trouble. Kidney problems exist in an average of 13.6% of BPH patients. Studies have reported rates as high as 30% and as low as 0.3%.

A PSA test measures the level of prostate-specific antigen (PSA) in the patient's blood. It is the standard screening test for prostate cancer. A PSA is recommended annually for all men over 50 years old and for men over age 40 who are at high risk for prostate cancer.

BPH itself can also raise PSA levels, but the test has generally been optional for men with suspected BPH. One 2000 study indicated that PSA levels may be good predictors of future prostate growth in men with BPH. In the study, men with the lowest PSA level groups (0.2 - 1.3 ng/mL) had prostate growth rates of only 0.7 mL per year while those in the high PSA groups (3.3 - 9.9) had growth rates of 3.3. mL per year. Other research has detected a specific molecular form of PSA, called BPSA because it may be a specific marker for BPH. Such findings could eventually lead to a shift from focusing on symptoms and flow rates for diagnosis to a more specific and possibly preventive approach.

Certain treatments for BPH, including the drug finasteride (Proscar) and the surgical procedure transurethral resection of the prostate (TURP), can reduce PSA levels and possibly mask the existence of prostate cancer.

A more recent test identifies so-called free PSA, which is found in lower levels when prostate cancer is present and in higher levels with benign prostate hyperplasia. This may be more accurate than total PSA, regardless of whether a man is taking finasteride or not.

One of the important tests for urinary incontinence is the postvoid residual urine volume (PVR), the amount of urine left after urination. Normally, about 50 mL or less of urine is left; more than 200 mL is a definite sign of abnormalities. Measurements in between require further tests. The most common method for measuring PVR is with a catheter, a soft tube that is inserted into the urethra within a few minutes of urination. PVR can also be measured using transabdominal ultrasonography.

Ultrasound of the prostate does not require a catheter and gives an accurate picture of the size and shape of the prostate gland. Ultrasound is very beneficial when planning surgery and determining treatment options and gauging their effectiveness. Ultrasound may also be used for detecting kidney damage, tumors, and bladder stones. Ultrasound tests of the prostate generally use one of two methods:

Transrectal ultrasonography (TRUS) uses a rectal probe for assessing the prostate. TRUS is significantly more accurate for determining prostate volume. It can sometimes detect cancer.
Transabdominal ultrasonography uses a device placed over the abdomen. It can give an accurate measure of postvoid residual urine and is less invasive and expensive than TRUS.

Filling cystometry, also called cystometrography, is usually used for patients who cannot urinate and in whom nerve damage or injury of the bladder is suspected. The test is used to determine the absence or presence of a condition called uninhibited detrusor contractions (UDC), which often occurs in men with storage urinary tract symptoms. The detrusor is the group of muscle fibers that cover the outside of the bladder. The test does not add much information to results from less invasive tests and is not used routinely.

A urethrocystoscopy, also called cystourethroscopy, may be performed in men diagnosed with BPH, particularly if they are surgical candidates or if other urinary tract problems are suspected. Such problems include blood in the urine, infection, interstitial cystitis, bladder cancer, or prior surgery or injury. The doctor can determine the presence of a number of structural problems, including enlargement of the prostate, obstruction of the urethra or neck of the bladder, anatomical abnormalities, or the presence of stones.

Procedure. In this procedure, a flexible or rigid fiberoptic tube (an endoscope) is inserted into the urethra to allow doctors to view the lower urinary tract.

Complication. The procedure is not without risks. Complications are uncommon but can include allergic response to the anesthetic, urinary tract infection, bleeding, and urine retention.

An x-ray called an intravenous excretory urography (IVU) is an invasive test that is used only when complications in the upper urinary tract, particularly in the kidney, are suspected. Alternatively, an abdominal ultrasound plus a normal x-ray may be as useful as IVU for most patients with suspected upper urinary tract problems.

Complications and Side Effects. If there is any danger of kidney failure, the test should not be performed, since it can exacerbate the condition. Severe side effects of the test occur in 0.1% of patients.

Some doctors believe that a number of men may be incorrectly diagnosed with BPH when they have interstitial cystitis (an inflammation of the bladder that may be associated with allergic or autoimmune response). The potassium sensitivity test is sometimes used to diagnose IC. Some experts believe this test missed too many IC patients, although a 2001 study concluded that a combination of potassium sensitivity and urodynamic tests is useful in distinguishing between BPH and interstitial cystitis.

Treatment

Because BPH rarely causes serious complications, men usually have a choice between treating it or opting for watchful waiting:

Watchful Waiting. Watchful waiting (also known as active surveillance) involves lifestyle changes and an annual examination. Even when choosing watchful waiting, an initial examination is critical to rule out other disorders.
Treatment Options. The primary goals of treatment for BPH are to improve urinary flow and to reduce symptoms. Many options are available. They include drug therapies, minimally invasive procedures, and major surgery.

The choice between watchful waiting and treatment usually depends on a number of factors, such as urine flow rates, prostate size, and PSA levels. Men with BPH who develop symptoms at around age 50 are more likely to need treatment within their lifetimes than older men. Unfortunately, there is no current way to determine who specifically might be at risk for serious problems and need early treatment.

The development of the International Prostate Symptoms Score (IPSS) has made the evaluation of symptoms somewhat easier. This scoring service serves as a benchmark for determining severity. The decision to treat or not to treat is typically based on the guidelines described below, but the ultimate choice is often guided primarily by a man's perception of his own symptoms.

Mild, or No, Symptoms. Men with mild, or no, symptoms (IPSS scores of 7 or below) usually choose watchful waiting even if their prostates are enlarged. BPH eventually progresses to the point of needing treatment in about 15% of men with mild symptoms who wait.

Moderate Symptoms. The choice is most difficult for men with moderate symptoms (scores between 8 - 19) and may simply depend on a man's ability to tolerate them. Some studies have reported that up to 40% of men with moderate symptoms eventually seek treatment, and a quarter require surgery. In a small percentage of patients, symptoms improve.

Severe Symptoms. Men with severe symptoms (scores over 20) nearly always choose treatment, although if their prostate glands are small or normal-sized, symptoms may improve.

If a man opts for treatment, there are several choices. Most experts recommend a staged approach as follows:

Mild Symptoms. Medications are the best choice for men with mild symptoms who decide to have their condition treated. There are two standard choices: alpha-blockers and anti-androgens, nearly always finasteride (Proscar). Specific conditions determine the choice, although most men take an alpha-blocker. Men with mild symptoms who choose surgery only experience minor improvement afterward but face the same risks as patients with more severe symptoms.
Moderate-Severe-Symptoms. Men with moderate-to-severe symptoms often respond to the same medications as men with mild symptoms. (Combinations of alpha-blockers and finasteride are under investigation.) Recent developments in drug therapy have reduced the number of surgical procedures needed and delayed their use. However, a quarter of men with moderate symptoms, and even more men with severe symptoms eventually need surgery. If a man chooses surgery, there are many choices. Transurethral resection of the prostate (TURP) is the standard procedure, but less invasive procedures, particularly those using heat or lasers to destroy prostate tissue, are gaining prominence.

Click the icon to see an illustrated series detailing transurethral resection of the prostate surgery.

The most common reason for choosing surgery is obstruction of the bladder outlet, which causes urinary retention. Surgery is also typically a reasonable option when BPH is clearly related to one or more of the following conditions:

Recurrent urinary tract infection.
Hematuria (blood in the urine). Studies have suggested that when hematuria is left untreated, two-thirds of patients continue to bleed and one third require surgery. The drug finasteride may help some men with this condition and should probably be tried before surgery.
Bladder stones.
Kidney problems.
Some experts believe that surgery might benefit patients for whom an early diagnosis of prostate cancer is important. Unsuspected prostate cancer is detected during surgery in about 15% of cases.

The greatest improvements resulting from surgery are usually increased urinary flow and reduced urine retention. In one study, men who chose surgery reported more worry and depression before the procedure, but afterward they had less depression and anxiety than those who had chosen medication. Often, however, the benefits of surgery are not permanent.

Lifestyle Changes

Certain lifestyle changes can help relieve symptoms and are particularly important for men who choose to avoid surgery or drug therapy. A 2007 study found that men who were educated on behavioral and lifestyle management of BPH were less likely to require surgery or drug therapy. Men should limit daily fluid intake to less than 2,000 mL (about 2 quarts) and, in particular, avoid alcohol and caffeine intake. Men should try to urinate at least once every 3 hours. “Double-voiding” may also be helpful -- after urinating, wait and try to urinate again. Cold weather and immobility may increase the risk for urine retention. Keeping warm and exercising may be useful. Stress reduction techniques may also help.

Studies have suggested the following:

Avoid fluids after your evening meal.
Coffee has been associated with a higher risk for BPH. Some evidence suggests that drinking green tea, however, may benefit the prostate.
Moderate alcohol consumption may be protective. (Heavy alcohol consumption, however, may increase the risk for lower urinary tract symptoms, and, in any case, is harmful.)
Genistein, a chemical found in soy, reduced the growth of BPH tissue in the laboratory. Although Asians have a low incidence of BPH and prostate cancer and also have diets rich in soy, it is not yet known if eating soy products will reduce the risk of BPH or improve any symptoms.
Fruits and vegetables rich in beta-carotene and vitamin C may help protect against BPH. Conversely, high consumption of cereals, bread, eggs, and poultry may increase the risk for BPH.
High doses of zinc supplements may increase the risk of BPH.

Decongestants and Antihistamines. Men with BPH should avoid, if possible, the many medications for colds and allergies that contain decongestants, such as pseudoephedrine (Sudafed). Such drugs, known as adrenergics, can exacerbate urinary symptoms by preventing muscles in the prostate and bladder neck from relaxing to allow urine to flow freely. Antihistamines, such as diphenhydramine (Benadryl), can also slow urine flow in some men with BPH.

Diuretics. Men who are taking diuretics, which increase urination, may want to talk to their doctor about reducing the dosage or switching to another drug. These are important drugs for many people with high blood pressure, with a proven track record for saving lives. No one should go off these medications without medical supervision.

Other Drugs. Other drugs that may worsen symptoms are certain antidepressants and drugs used to treat spasticity.

Some, but not all, research suggests that moderate exercise can reduce urinary tract problems associated with BPH.

Kegel (pelvic floor muscle) exercises, first developed to help women with childbirth, can also help men prevent urine leakage. They strengthen the pelvic floor muscles that both support the bladder and close the sphincter.

Performing the Exercises. Since the muscle is internal and sometimes hard to isolate, doctors often recommend practicing while urinating:

The patient is asked to contract the muscle until the flow of urine is slowed or stopped. He attempts to hold each contraction for 20 seconds.
He then releases the contraction.
In general, patients should perform 5 - 15 contractions, three to five times daily.

Medications

The two primary drug classes used for BPH are:

Alpha-blockers. These drugs relax smooth muscles, especially in the urinary tract and prostate. They include terazosin (Hytrin), doxazosin (Cardura), tamsulosin (Flomax), and alfuzosin (Uroxatral). Alpha-blockers help relieve BPH symptoms, but they do not reduce the size of the prostate. The can help improve urine flow and reduce risk of bladder obstruction. They are often the first choice, especially for men with smaller prostates.
5-alpha-reductase inhibitors. Finasteride (Proscar) and dutasteride (Avodart) block the conversion of testosterone to dihydrotestosterone, the male hormone that stimulates the prostate. These drugs are better for men with significantly enlarged prostates. In addition to relieving symptoms, they increase urinary flow and may even help shrink the prostate. However, patients may have to take these drugs for up to 6 - 12 months to achieve full benefits.

Because these two types of drugs work in different ways, researchers are investigating combinations of the two for selected patients. Results from the Medical Therapy of Prostatic Symptoms (MTOPS) trial, published in 2003, reported that a combination of doxazosin and finasteride delayed progression of BHP more effectively than either drug alone. The combination treatment may work best for high-risk patients with larger prostate glands and higher PSA readings. Many men, however, can control their condition with a single drug.

General Guidelines for Alpha-Blockers.Alpha-adrenergic antagonists, commonly called alpha-blockers, were originally used to treat high blood pressure. They are prescribed for BPH to relax smooth muscles in the prostate. The muscle cells in the prostate are stimulated by molecules called alpha adrenergic receptors. This can cause lower urinary tract symptoms.

Drugs that block these receptors relax the muscles in and around the prostate, increase urinary flow and improve symptoms, sometimes significantly. Improvement occurs within days to weeks. Because these drugs are short-acting, symptoms return very quickly once a man stops taking the medication. They neither affect PSA levels nor shrink the size of the prostate. Research also indicates that they may even promote a natural process called apoptosis, in which cells in the prostate gland self-destruct. Investigators are studying whether these drugs may help prevent the development of prostate cancer.

Alpha-blockers are prescribed for most men with BPH symptoms whose prostates are not significantly enlarged. Even men with moderately enlarged prostates might try alpha-blockers before more intense treatments because these drugs work fairly quickly, have no effect on sexual drive, and are the least expensive treatment for BPH. Some experts now recommend alpha-blockers as first-line treatment for patients with moderate-to-severe symptoms.

These drugs are generally referred to as either nonselective or selective alpha-blockers. Drugs in both categories are similar in effectiveness for reducing symptoms and improving urinary flow. There are some differences, however. Patients should discuss the appropriate alpha-blocker for their individual condition with their doctors.

Nonselective Alpha-Blockers. Nonselective alpha-blockers (also referred to as alpha-specific antagonists) include terazosin (Hytrin), doxazosin (Cardura), and alfuzosin (Uroxatral). Alfuzosin is the newest drug and can be taken once a day. They relax all smooth muscles, not only in the prostate but also those that surround any blood vessel in the body. These drugs work within a few weeks, are inexpensive, and produce long-lasting benefits. Alfuzosin begins to improve urine flow within hours.

Side Effects. Nonselective alpha-blockers can reduce blood pressure, which may cause dizziness, headache, rapid heartbeat, and fatigue. Orthostatic hypotension, a sudden drop in blood pressure when standing, can occur and increases the risk of falling. Taking the medication close to bedtime can help reduce these side effects. (Alfuzosin's extended-release formulation appears to pose a much lower risk than the other drugs.) Alpha-blockers can also cause headache, sore throat, and weakness. Nasal congestion occurs in about 2% of cases. Men may also experience a decreased ejaculate. (Impotence is not a common side effect of alpha-blockers, as it is with finasteride.)
Long-Term Effects. These drugs slow the progression of BPH but do not help prevent urinary retention.
Best Candidates. Nonselective alpha-blockers may be a good choice for many men with severe urinary problems and especially those with hypertension, high cholesterol levels, or both. However, alpha-blockers can exacerbate heart failure symptoms in men with this condition.

Selective Alpha-Blockers. Tamsulosin (Flomax) is the only selective alpha-blocker (sometimes called alpha1A-urospecific antagonists) approved for treatment of BPH. Naftopidil is a similar drug under investigation. These drugs target receptors that affect only the smooth muscles of the prostate. Tamsulosin seems to work as well as nonselective alpha-blockers. It is not clear if it reduces long-term complications of BPH.

Selective alpha-blockers appear to be very safe, even for years. Side effects are minimal. Most common ones include nasal congestion. The risk for low blood pressure and dizziness is lower than with the nonselective alpha-blockers. They may pose a higher risk for problems in ejaculation than nonselective alpha-blockers, but do not appear to cause impotence or reduce sexual drive as finasteride does. These drugs can interact with certain medications, including calcium channel blockers (particularly verapamil).

Researchers are studying the combination of tamsulosin and tolteridine (Detrol). Tolteridine is an anticholinerogic medication used to treat urinary incontinence. Tamsulosin targets the prostate while tamsulosin helps inhibit involuntary contractions of the bladder. A 2006 study in the Journal of the American Medical Association found that a combination of tolterodine and tamsulosin worked better than either drug alone for men with lower urinary tract symptoms (LUTS), including overactive bladder.

Specific Benefits. The prostate gland contains an enzyme called 5 alpha-reductase that converts testosterone to another androgen called dihydrotestosterone. Finasteride (Proscar) and dutasteride (Avodart), known as a 5-alpha-reductase inhibitors, block this enzyme and thus reduce dihydrotestosterone in the prostate.

Finasteride is not as effective as alpha-blockers in improving BPH and urinary tract symptoms, but it can be helpful. Follow-up studies have reported that the drug is safe and effective over the long-term. The 5 alpha-reductase inhibitors are perhaps most effective in reducing symptoms in men with large prostates. (Men with larger prostates and high PSA values may also benefit from combination therapy of finasteride and the alpha-blocker doxazosin.) In such cases, studies on finasteride also suggest it reduces the risk of acute urinary retention and the need for surgery. It also helps control bleeding in the urine that is related to BPH. A side benefit of finasteride is reduction of hair loss related to male hormones and in some cases hair growth in men with mild-to-moderate male pattern baldness.

Dutasteride (Avodart) is a newer drug that inhibits two types of the 5-alpha-reductase enzymes and achieves a more rapid suppression of dihydrotestosterone than finasteride. A 4-year study reported sustained improvements in urinary symptoms and prostate volume reduction. Comparison studies are needed to determine if the dual actions of dutasteride offer significant benefits over those of finasteride. Researchers are also investigating whether dutasteride can help prevent the development of prostate cancer.

Candidates. Some experts recommend 5-alpha-reductase inhibitors for men of any age who have all three of the following conditions:

Very large prostates (40 mL or larger)
Low urinary flow rates
Prostate enlargement related primarily to hormone-stimulated overgrowth of glandular tissue

Finasteride is also proving to be helpful for patients who have hematuria (blood in the urine) related to BPH.

Dosing. Finasteride and dutasteride are taken once a day. It may take as long as 6 - 12 months for a man to notice a change in symptoms.

Effects on PSA. Finasteride and dutasteride decrease prostate-specific antigen (PSA) levels, which are measured for screening prostate cancer. Lower PSA levels may mask the presence of the cancer. Doctors calculate PSA levels in men taking these drugs by doubling the PSA values. Studies confirm that this doubling equation helps provide an accurate measurement.

Side Effects. Finasteride has been associated with:

Sexual dysfunction, including low sexual drive and impotence, in about 6 - 19% of patients. Such problems appear to occur only during the first year of use and diminish over time in most men who take finasteride.
Reductions in energy.
Breast tenderness.
Possible weight loss in some men.

Other anti-androgens, including drugs known as gonadotropin-releasing hormone agonists, are effective against BPH, but they can reduce sexual drive and are much more likely to cause impotence. Flutamide is an anti-androgen that may be an alternative to surgery in certain patients with BPH who have physical or mental disorders.

Popular herbal treatments for BPH include:

Saw Palmetto. Saw palmetto is one of the most popular herbal remedies for BPH. It comes from the berry of the plant Serenoa repens. A major 2006 study in the New England Journal of Medicine found that saw palmetto had no benefit for treating BPH. The study enrolled 225 men with moderate-to-severe BPH. The men received either placebo or 160 mg of saw palmetto twice daily. After 1 year, there were no differences in symptom improvement between the placebo and saw palmetto groups.

Beta-Sitosterol. Beta-sitosterol preparations come from South African star grass, Hypoxis rooperi, and other plant species. Some studies have shown beta-sitosterol to improve urinary symptoms and flow. They may increase the risk for impotence, however.

Pygeum Africanum. The herbal Pygeum africanum is an extract from the bark of an African plum tree. In an analysis of 18 trials, the herb provided a moderate improvement in urinary symptoms compared to placebo. Side effects were mild. The studies were short in length, however.

Cernilton. Cernilton is prepared from rye grass pollen. Studies have been limited, but some suggest it may help improve symptoms, including nighttime urinary problems. Other studies have found no benefit.

Other popular herbs include nettle root extract (Urtica dioica) and pumpkin seed oil (Cucurbita peponis). There is no scientific evidence that any of these remedies help treat BPH.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Patients should check with their doctor before using any herbal remedies or dietary supplements.

Botulinum. Botulinum toxin A (Botox) injections, a common wrinkle treatment, cause small muscles to relax. This approach is now being investigated for treating many disorders that involve overexcited muscle activity, including BPH. Preliminary studies are showing promising results in improving urine flow and reducing urinary retention. Research, presented at the 2007 annual meeting of the American Urological Association, reported that men with BPH who had Botox injected directly into their prostate gland had symptom relief and improved quality of life for up to a year after treatment.

PDE5 Inhibitors. Phosphodiesterase-5 (PDE5) inhibitors can treat erectile dysfunction (ED). They include sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). Because lower urinary tract symptoms (LUTS) and ED often occur together in older men, researchers are investigating whether PDE5 inhibitors may help improve BPH symptoms. Research presented at the 2006 American Urological Association meeting suggested that sildenafil improves urinary symptoms in men who have both ED and LUTS. Another study indicated that a combination of sildenafil and the alpha-blocker alfusozin (Uroxatral) worked better for treating LUTS and ED than either drug alone.

Other Areas of Investigation. Researchers are looking at several different drugs for future BPH therapies. Most drugs being researched for BPH, such as arylpiperazines, target molecules in the prostate that may help suppress cell growth. Some efforts are focusing on drugs that affect the central nervous system or nerve fibers in the bladder and urethra to reduce urinary tract symptoms.

Other Treatments

Several surgical approaches are now available for treating BPH.

Invasive Procedures. The most effective surgical procedures, transurethral resection of the prostate (TURP) and open prostatectomy, are also the most invasive. They carry the highest risks for significant complications, including impotence and incontinence. Greater surgeon experience with TURP, however, has reduced complications and hospital stays. Because it is more effective than less invasive procedures, TURP remains the procedure of choice for many doctors. When considering invasive surgery, the patient should be sure his surgeon performs at least 50 of these procedures each year. The complication rates of the surgeon should be no higher than 1% for incontinence and 4% for impotence. Transurethral incision of the prostate (TUIP) is an alternative to TURP for men with smaller prostate glands.

Less Invasive Procedures. Minimally invasive procedures use some form of heat to destroy excess prostate tissue. The heat may be delivered by:

Radio frequency: transurethral needle ablation (TUNA)
Microwave: transurethral microwave thermotherapy (TUMT)
Electrical current: transurethral electrovaporization (TUVP)
Ultrasound: high-intensity focus ultrasound (HIFU)
Hot water: water-induced thermotherapy (WIT)
Laser: interstitial laser coagulation (ILC) and holmium laser enucleation of the prostate (HoLEP)

One laser procedure, photoselective vaporization (PVP), is typically done as an outpatient procedure. The patient goes home on the same day. However, there is no long-term data for this procedure.

None of the other minimally invasive procedures have proven superior to TURP to date, but they vary by complications. Some may be appropriate for certain patients, such as the following:

Younger men. (Many of the less invasive procedures carry a lower risk for impotence and incontinence than TURP, although the risk for TURP is not high.)
Debilitated elderly patients
Patients with severe medical conditions, including uncontrolled diabetes, cirrhosis, active alcoholism, psychosis, and serious lung, kidney, or heart disease
Men who are on blood-thinning drugs

Transurethral resection of the prostate (TURP) involves surgical removal of the inner portion of the prostate where BPH develops. It is the most common surgical procedure for BPH, although the number of procedures has dropped significantly over the past decades because of the availability of effective medications.

Click the icon to see an illustrated series detailing transurethral resection of the prostate surgery.

Procedure. TURP usually requires a 1 - 3 day hospital stay. The surgeon inserts a fiberoptic endoscope, which is a thin tube, into the urethra. No incision is needed. The surgeon uses the endoscope to cut away excess prostatic tissue, and water solutions are used to flush away the excised matter.

Risk of Water Intoxication. If the fluids used during TURP build up, water intoxication can develop, which can be serious. This condition is referred to as the transurethral resection (TUR) syndrome and includes abdominal cramps, nausea, vomiting, lethargy, and dizziness. Patients who undergo TURP for longer than 1 hour and those with larger prostate glands seem to be at greater risk for this complication. An irrigation system that uses a mechanical valve may reduce the risk.

Postoperative Catheterization. A Foley catheter generally remains in place for 3 - 5 days after surgery to allow urination. This device is a tube inserted through the opening of the penis to drain the urine into a bag. The catheter can cause bladder spasms that can be painful, but they eventually cease.

Some studies have suggested that in selected patients the catheter can safely be removed within 24 - 48 hours, allowing patients to go home earlier. Early catheter removal is not appropriate for patients with intense urine retention, signs of infection, bleeding, or other complications.

Recuperation. Urine flow is stronger almost immediately after most TURP procedures. After the catheter is removed, patients often experience some pain or sense of urgency as the urine passes over the surgical wound. These sensations gradually subside. Complete healing takes about 2 months. The following are some tips for hastening recovery and avoiding complications:

During recuperation at home, the patient should avoid driving, operating heavy equipment, lifting, sudden movements, and straining the muscles in the lower tracts, such as during a bowel movement.
Drinking 8 glasses of water a day after surgery is important to flush the bladder and help healing.
Foods that help prevent constipation, such as fruits and vegetables, are important. A laxative may be needed if constipation occurs.
Kegel exercises can help reduce incontinence. Performing three to four sets of 30 contractions daily is recommended. In one study, improvement due to Kegel exercises was significant within a month after surgery.

Postoperative Complications. Complications after TURP can be high, depending on the skill of the surgeon and other factors, but their incidence has decreased considerably over the past decades because of advances in surgical technique and more widespread expertise.

Bleeding. Some blood and small clots appear in the urine after surgery, and if the bladder is flushed with water, the urine may turn red. Such bleeding is normal. Occasionally, the scab on the surgical wound loosens, causing a sudden appearance of blood in the urine that can be alarming. Usually this stops after a rest, but the patient should notify the doctor at once if he is concerned about abnormal bleeding or clotting or has unusual feelings of discomfort. Rarely, hemorrhage may occur, requiring a transfusion.
Infection. Urinary tract infections occur in 5 - 10% of TURP patients. The risk is particularly high if a catheter is required. Antibiotics may be given to prevent infections, although often a doctor will choose to monitor a patient and administer antibiotics only if an infection is evident.
Incontinence. Temporary stress incontinence (urine leakage after activities such as sneezing, coughing, or lifting) occurs in most surgical patients. Urge incontinence is the involuntary loss of urine following an uncontrollable urge to urinate. About 2.1% of TURP patients experience stress incontinence, and nearly 2% have urge incontinence. In general, however, there is no significant risk for incontinence. [See In-Depth Report #50: Urinary incontinence.]
Sexual Dysfunction. Some men report certain sexual differences after the procedure, particularly low volume of fluid at ejaculation. Studies, however, do not report any significant risk for impotence. For most men who report this complication, sexual function returns in short order. (In some men it may take up to a year for complete recovery.) If potency was diminished before the operation, the procedure will not restore it. [See In-Depth Report #15: Erectile dysfunction.]
Retrograde Ejaculation and Low Semen. Many TURP patients report a lower volume of semen after the procedure. Between 66 - 75% of these patients experience retrograde ejaculation, in which semen is forced backward into the bladder instead of forward out of the urethra during orgasm. During most invasive procedures, the muscle that blocks off the bladder may be cut in order to widen the outlet. In such cases, the semen flows back through the wider opening rather than out of the penis. This condition can impair fertility and is of particular concern in younger men. Neither retrograde ejaculation nor the operation itself typically affects orgasm, although it takes many men some time to emotionally adjust to these conditions.
Low PSA Levels. PSA levels may be lowered after TURP, which might cause a doctor to miss a diagnosis of prostate cancer during routine screening.

Repeat Operations. Symptomatic relief is usually maintained for at least 15 years after surgery, but BPH may return or patients may need a second operation for other reasons. Up to 10% of TURP patients require a repeat operation within 10 years. In some cases, scarring in the bladder severe enough to cause obstruction occurs within a year of the procedure and may require transurethral incision (TUIP). More often, the urethra is scarred and narrows, but usually this condition can be corrected by a simple stretching procedure performed in the doctor's office.

In transurethral incision of the prostate (TUIP), the surgeon makes only one or two incisions in the prostate, causing the bladder neck and the prostate to spring open and reduce pressure on the urethra.

Candidates. TUIP is generally used only for men with minimally enlarged prostates (30 grams or less) who have obstruction of the neck of the bladder. Some experts believe TUIP is not performed enough and could benefit many patients, particularly those with severe medical conditions who are not good candidates for more invasive surgeries and men who want to lessen their risk for sterility.

Postoperative Complications. TUIP is less invasive than TURP, has a lower rate of the same complications, particularly retrograde ejaculation, and usually does not require a hospital stay. More studies are still needed, however, to determine whether they are comparative in long-term effectiveness.

In open prostatectomy, the enlarged prostate is removed through an open incision in the abdomen using standard surgical techniques. This is major surgery and requires a hospital stay of several days. Open prostatectomy is used only for severe cases, about 2 - 3% of BPH patients, when the prostate is severely enlarged, the bladder is damaged, or other serious problems exist. Up to 14% of patients require a second operation because of scarring. In making a decision about prostatectomy, it is essential that the doctor explains the consequences of a diminished sexual capacity that occurs after this procedure. When the situation of the patient does not constitute an emergency, prostatectomy should be considered a last resort if the patient still has an active sex life. Other complications are similar to those of TURP.

Click the icon to see an illustrated series detailing prostatectomy surgery.

Procedures. Laser technology is used for removal of prostate tissue. Laser procedures can usually be done as an outpatient procedure, and there is little risk for bleeding. Different procedures are used to provide different degrees of thermal cell destruction that range from coagulation to complete vaporization:

Interstitial laser coagulation (ILC) involves insertion of a scope through the prostate. A fiberoptic tip is threaded through the scope to direct a diode laser emission to targeted areas of the prostate. The coagulated tissue is naturally absorbed back into the body. Approved in 1998, this procedure is being performed less frequently as urologists turn to newer laser technologies (HoLEP, PVP).
Holmium laser enucleation of the prostate (HoLEP) is a newer technique that can actually cut and vaporize the tissue. Vaporization is effective immediately and also may pose lower risks for prolonged urinary retention and reoperation rates than coagulation. The Holmium laser is showing very good results with low complication rates in small studies, and trials have reported benefits lasting more than four years. (HoLEP is actually proving to be better than TURP or even open prostatectomy for removing very large prostate glands.)
Photoselective vaporization of the prostate (PVP) uses a potassium-titanyl-phosphate (KTP) laser ("green-light" laser) to vaporize prostate tissue. The procedure is virtually bloodless and may be a better option for men taking anticoagulant medication. Results from several recent clinical trials report sustained improvement up to 1 year after the procedure. More studies are needed to confirm long-term efficacy.

Complications. The laser procedure carries a lower risk for incontinence than TURP or TUVP, another minimally invasive procedure. Studies have been mixed on whether laser surgery poses any risk for sexual dysfunction. In one study, TURP had a lower risk for sexual dysfunction, although the risk from either procedure was very low and it wasn't clear that lasers had even been responsible for this complication. After laser procedures, and especially after coagulation, the prostate often temporarily enlarged and caused obstruction and irritation. Sometimes these symptoms were severe. Most men require a temporary catheter to drain urine after laser procedures. Newer laser procedures may significantly reduce these adverse effects.

Transurethral Microwave Thermotherapy (TUMT). Transurethral microwave thermotherapy (TUMT) delivers heat using microwave pulses to destroy prostate tissue. Studies have found that between 60 - 80% of men respond favorably to the treatment and the benefits seem to last. A 2001 study reported that it remained effective for at least 18 months and was superior over the long-term to the alpha-blocker drug terazosin. Improvement is not as complete as with TURP, but TUMT has fewer complications.

Candidates. TUMT may be beneficial for men with larger prostates and moderate to severe bladder obstruction, including those who require indwelling catheters. A 2000 study, for example, concluded that is was a safe and effective therapy for treatment of urinary retention. In general, the procedure should not be performed on men who have pacemakers, defibrillators, or any metal implants. One possible exception, the Targis System, was approved for use for patients with hip or penile implants that are located at least 1.5 inches from the urethra. Men who have had previous radiation therapy to the pelvic area are at higher risk for injuries from this procedure.
Procedure. A microwave antenna is inserted through the urethra with ultrasound used to position it accurately. The antenna is enclosed in a cooling tube to protect the lining of the urethra. Computer-generated microwaves pulse through the antenna to heat and destroy prostate tissue. When the temperature becomes too high, the computer shuts down the heat and resumes treatment when a safe level has been reached. The procedure takes 30 minutes to 2 hours, and the patient can go home immediately afterward. About 30% of patients experience some pain during the procedure. The patient should report any pain that appears to be unusually severe, however, since this could indicate improper application.
Complications. Swelling in the urinary tract often occurs later, which prevents urination and requires the use of a temporary catheter for about 3 days until the swelling subsides. There have also been reports of serious injuries to the penis and urethra from overheating due to improper application. It is important to note that TUMT does not significantly affect sexuality or cause incontinence or retrograde ejaculation, which are risks with some other prostate procedures.

Transurethral Needle Ablation. Transurethral needle ablation (TUNA) is a simple, safe, and relatively inexpensive procedure using needles to deliver high-frequency radio waves that heat and destroy prostate tissue. The procedure usually requires only a local anesthetic. One study reported that improvement was maintained in most patients after 2 years, although older men (over 70) had slightly worse symptoms and quality-of-life scores. Although small clinical studies have reported that TUNA is as effective as TURP, some experts believe that in actual medical practice TURP is still more effective.

Some studies have reported urinary retention, blood in the urine, retrograde ejaculation, and painful urination after the procedure, although in general TUNA has few or none of TURP's severe side effects. TUNA poses a very low to no risk for incontinence and impotence, and may be a good option for younger men.

Transurethral Electrovaporization. Transurethral electrovaporization (TUVP) uses high voltage electrical current delivered through a resectoscope to combine vaporization of prostate tissue and coagulation that seals the blood and lymph vessels around the area. Deprived of blood, the excess tissue dies and is sloughed off over time. Patients who have TUVP may be able to have their catheter removed within hours after the procedure compared to normal removal time of 3 - 5 days after TURP. A 5-year study reported that it was as effective as TURP over the long-term and had a similar complication rate.

Ultrasound. High-intensity focus ultrasound (HIFU) is a heat procedure under investigation that uses ultrasound to destroy specific prostate tissue. The principles are similar to transurethral microwave thermotherapy, but ultrasound techniques may destroy excess tissue without damaging other parts of the urethra.

Water-Induced Thermotherapy. A device called Thermoflex, which circulates heated water through a catheter to destroy prostatic tissue, has been approved for treating BPH. Another technique uses a balloon filled with hot water to destroy tissue around the urethra. Water-induced thermotherapy (WIT) does not require anesthesia and can be completed during a single outpatient visit.

Prostatic stents used for BPH are flexible mesh tubes that are inserted into the urethra. They are made of special alloys that do not cause reactions in the body. Typically, the insertion procedure takes only 15 minutes and requires only regional anesthetic and mild sedation. It usually requires minimal recuperation and no overnight hospital stay. Unfortunately, long-term studies are reporting high rates of dissatisfaction. Between 8 - 37% of the stents need to be removed later because of poor placement or complications, including irritation when urinating, urinary tract infections, and treatment failure. At this point stents seem to be best suited for high-risk surgical patients and those with a limited life expectancy. Stents composed of new materials and properties may increase their role.

Resources

www.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.urologyhealth.org -- American Urological Association

References

Bravi F, Bosetti C, Dal Maso L, Talamini R, Montella M, Negri E, et al. Food groups and risk of benign prostatic hyperplasia. Urology. 2006 Jan;67(1):73-9.

Johnson AR, Munoz A, Gottlieb JL, Jarrard DF. High dose zinc increases hospital admissions due to genitourinary complications. J Urol. 2007 Feb;177(2):639-43.

Kaplan SA, Roehrborn CG, Rovner ES, Carlsson M, Bavendam T, Guan Z. Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. JAMA. 2006 Nov 15;296(19):2319-28.

Rohrmann S, Giovannucci E, Willett WC, Platz EA. Fruit and vegetable consumption, intake of micronutrients, and benign prostatic hyperplasia in US men. Am. J. Clin. Nutr. 2007 Feb;85(2):523-9.

van der Meulen J, Brown CT, Yap T, Cromwell DA, Rixon L, Steed L, et al. Self management for men with lower urinary tract symptoms: randomised controlled trial. BMJ. 2007 Jan 6;334(7583):25. Epub 2006 Nov 21.

Review Date:
6/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Factor X assay

admin — Thu, 04 Sep 2008 19:14:08 -0700

Overview

Definition
How the test is performed
How to prepare for the test
How the test will feel
Why the test is performed
Normal Values
What abnormal results mean
What the risks are
Special considerations
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Factor X assay is a blood test to measure the activity of factor X -- one of the substances involved in coagulation (blood clotting).

How the test is performed

Blood is drawn from a vein, usually from the inside of the elbow or the back of the hand. The puncture site is cleaned with antiseptic. An elastic band is placed around the upper arm to apply pressure and cause the vein to swell with blood.

A needle is inserted into the vein, and the blood is collected in an air-tight vial or a syringe. During the procedure, the band is removed to restore circulation. Once the blood has been collected, the needle is removed, and the puncture site is covered to stop any bleeding.

In infants or young children, the area is cleansed with antiseptic and punctured with a sharp needle or a lancet. The blood may be collected in a pipette (small glass tube), on a slide, onto a test strip, or into a small container. A bandage may be applied to the puncture site if there is any bleeding.

How to prepare for the test

Your health care provider may ask you to stop taking certain medications.

How the test will feel

When the needle is inserted to draw blood, you may feel moderate pain, or only a prick or stinging sensation. Afterward, there may be some throbbing.

Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others.

Why the test is performed

This test may be used to detect the specific cause of excessive bleeding (decreased blood clotting).

Normal Values

A normal value is 50-200% of the laboratory control or reference value.

What abnormal results mean

Decreased factor X activity may indicate:

Congenital deficiency of factor X
Fat malabsorption
Heparin administration
Liver disease
Vitamin K deficiency
Warfarin administration

What the risks are

Excessive bleeding
Fainting or feeling light-headed
Hematoma (blood accumulating under the skin)
Infection (a slight risk any time the skin is broken)
Multiple punctures to locate veins

This test is most often performed on people who have bleeding problems. The risk of excessive bleeding is slightly greater than for people without bleeding problems.

Special considerations

When you bleed, the body launches a series of activities that help the blood clot. This is called the coagulation cascade. The process involves special proteins called coagulation factors. (Factor X is a coagulation factor.) Each factor's reaction triggers the next reaction. The final product of the coagulation cascade is the blood clot.

References

Schmaier AH, Thornburg CD, Pipe SW. Coagulation and Fibrinolysis. In: McPherson RA and Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods. 21st ed. Philadelphia, Pa.: W.B. Saunders; 2006.

Hoffman R, Benz Jr. EJ, Shattil SJ, et al., eds. Hematology: Basic Principles and Practice. 4th ed. Philladelphia, Pa: Churchill Livingston; 2005:1936-37.

Review Date: 2/26/2007

Reviewed By: William Matsui, MD, Assistant Professor of Oncology, Division of Hematologic Malignancies, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Source Doc: 1_003680

Factor IX assay

admin — Thu, 04 Sep 2008 19:14:07 -0700

Overview

Definition
Alternative Names
How the test is performed
How to prepare for the test
How the test will feel
Why the test is performed
Normal Values
What abnormal results mean
What the risks are
Special considerations
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Factor IX assay is a blood test that measures the activity of factor IX -- one of the substances involved in coagulation (blood clotting).

Alternative Names

Christmas factor assay; Serum factor IX

How the test is performed

How to prepare for the test

The health care provider may advise you to stop taking drugs that may affect the test.

How the test will feel

When the needle is inserted to draw blood, you may feel moderate pain, or only a prick or stinging sensation. Afterward, there may be some throbbing.

Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others.

Why the test is performed

This test is used to detect the specific cause of too much bleeding (decreased blood clotting).

Normal Values

A normal value is 50-200% of the laboratory control or reference value.

What abnormal results mean

Decreased factor IX activity may indicate:

Congenital deficiency of factor IX (hemophilia B)
Disseminated intravascular coagulation (DIC)
Fat malabsorption
Liver disease (such as cirrhosis)
Vitamin K deficiency
Warfarin administration

What the risks are

Excessive bleeding
Fainting or feeling light-headed
Hematoma (blood accumulating under the skin)
Infection (a slight risk any time the skin is broken)
Multiple punctures to locate veins

This test is most often performed on people who have bleeding problems. The risk of excessive bleeding is slightly greater than for people without bleeding problems.

Special considerations

When you bleed, the body launches a series of activities that help the blood clot. This is called the coagulation cascade. The process involves special proteins called coagulation factors. Each factor's reaction triggers the next reaction. The final product of the coagulation cascade is the blood clot.

References

Hoffman R, Benz Jr. EJ, Shattil SJ, et al., eds. Hematology: Basic Principles and Practice. 4th ed. Philladelphia, Pa: Churchill Livingston; 2005:1936-37.

A.D.A.M. Copyright

adam.com

Source Doc: 1_003679

Factor VII assay

admin — Thu, 04 Sep 2008 19:14:04 -0700

Overview

Definition
How the test is performed
How to prepare for the test
How the test will feel
Why the test is performed
Normal Values
What abnormal results mean
What the risks are
Special considerations
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Factor VII assay is a blood test to measure the activity of factor VII -- one of the substances needed for coagulation (blood clotting).

How the test is performed

How to prepare for the test

Your health care provider may ask you to stop taking certain medications.

How the test will feel

When the needle is inserted to draw blood, you may feel moderate pain, or only a prick or stinging sensation. Afterward, there may be some throbbing.

Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others.

Why the test is performed

This test is used to detect the specific cause of excessive bleeding (decreased blood clotting).

Normal Values

The normal value is 50-200% of the laboratory control or reference value.

What abnormal results mean

Decreased factor VII activity may be associated with:

Congenital deficiency of factor VII
Disseminated intravascular coagulation (DIC)
Fat malabsorption
Liver disease (such as cirrhosis)
Vitamin K deficiency
Warfarin administration

What the risks are

Excessive bleeding
Fainting or feeling light-headed
Hematoma (blood accumulating under the skin)
Infection (a slight risk any time the skin is broken)
Multiple punctures to locate veins

This test is most often performed on people who have bleeding problems. The risk of excessive bleeding is slightly greater than for people without bleeding problems.

Special considerations

When you bleed, the body launches a series of activities that help the blood clot. This is called the coagulation cascade. The process involves special proteins called coagulation factors. (Factor VII is a coagulation factor.) Each factor's reaction triggers the next reaction. The final product of the coagulation cascade is the blood clot.

References

McPherson RA and Pincus MR. Henry's Clinical Diagnosis and Management by Laboratory Methods. 21st ed. Philadelphia, Pa.: W.B. Saunders; 2006.

Hoffman R, Benz Jr. EJ, Shattil SJ, et al.. Hematology: Basic Principles and Practice. 4th ed. Philladelphia, Pa: Churchill Livingston; 2005:1937-38.

A.D.A.M. Copyright

adam.com

Source Doc: 1_003676

Factor V assay

admin — Thu, 04 Sep 2008 19:14:04 -0700

Overview

Definition
How the test is performed
How to prepare for the test
How the test will feel
Why the test is performed
Normal Values
What abnormal results mean
What the risks are
Special considerations
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Factor V assay is a blood test to measure the activity of factor V -- one of the substances involved in coagulation (blood clotting).

How the test is performed

How to prepare for the test

No special preparations are needed.

How the test will feel

When the needle is inserted to draw blood, you may feel moderate pain, or only a prick or stinging sensation. Afterward, there may be some throbbing.

Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others.

Why the test is performed

This test is used to detect the specific cause of too much bleeding (decreased blood clotting).

Normal Values

The value is normally 50-200% of the laboratory control or reference value.

What abnormal results mean

Decreased factor V activity may be related to:

Congenital (present at birth) deficiency of factor V
Disseminated intravascular coagulation (DIC)
Liver disease (such as cirrhosis)
Primary fibrinolysis

What the risks are

Excessive bleeding
Fainting or feeling light-headed
Hematoma (blood accumulating under the skin)
Infection (a slight risk any time the skin is broken)
Multiple punctures to locate veins

This test is most often performed on people who have bleeding problems. The risk of excessive bleeding is slightly greater than for people without bleeding problems.

Special considerations

When you bleed, the body launches a series of activities that help the blood clot. This is called the coagulation cascade. The process involves special proteins called coagulation factors. (Factor V is a coagulation factor.) Each factor's reaction triggers the next reaction. The final product of the coagulation cascade is the blood clot.

References

McPherson RA and Pincus MR. Henry's Clinical Diagnosis and Management by Laboratory Methods. 21st ed. Philadelphia, Pa.: WB Saunders; 2006.

Hoffman R, Benz Jr. EJ, Shattil SJ, et al. Hematology: Basic Principles and Pra ctice. 4th ed. Philladelphia, Pa: Churchill Livingston; 2005:1938.

A.D.A.M. Copyright

adam.com

Source Doc: 1_003675

Factor II assay

admin — Thu, 04 Sep 2008 19:14:03 -0700

Overview

Definition
Alternative Names
How the test is performed
How to prepare for the test
How the test will feel
Why the test is performed
Normal Values
What abnormal results mean
What the risks are
Special considerations
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Factor II assay is a test to measure the activity of factor II -- one of the substances involved in coagulation (blood clotting).

Alternative Names

Prothrombin

How the test is performed

How to prepare for the test

No special preparations are needed.

How the test will feel

When the needle is inserted to draw blood, you may feel moderate pain, or only a prick or stinging sensation. Afterward, there may be some throbbing.

Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others.

Why the test is performed

This test is used to detect the specific cause of too much bleeding (decreased blood clotting).

Normal Values

The value should be 50-200% of the laboratory control or reference value.

What abnormal results mean

Decreased factor II activity may be the result of:

Congenital (present at birth) deficiency of factor II
Fat malabsorption
Liver disease (such as cirrhosis)
Vitamin K deficiency
Taking warfarin

Additional conditions under which the test may be performed include disseminated intravascular coagulation (DIC)

What the risks are

Excessive bleeding
Fainting or feeling light-headed
Hematoma (blood accumulating under the skin)
Infection (a slight risk any time the skin is broken)
Multiple punctures to locate veins

This test is most often performed on people who have bleeding problems. The risk of excessive bleeding is slightly greater than for people without bleeding problems.

Special considerations

When you bleed, the body launches a series of activities that help the blood clot. This is called the coagulation cascade. The process involves special proteins called coagulation factors. (Factor II is a coagulation factor.) Each factor's reaction triggers the next reaction. The final product of the coagulation cascade is the blood clot.

References

McPherson RA and Pincus MR. Henry's Clinical Diagnosis and Management by Laboratory Methods. 21st ed. Philadelphia, Pa.: WB Saunders; 2006.

Hoffman R, Benz Jr. EJ, Shattil SJ, et al. Hematology: Basic Principles and Practice. 4th ed. Philladelphia, Pa: Churchill Livingston; 2005:2081-83.

A.D.A.M. Copyright

adam.com

Source Doc: 1_003674