FitSugar

Recall: 286,000 Pounds of Meat and Poultry

FitSugar — Mon, 05 May 2008 08:15:00 -0700

If you're thinking about grilling this week or have a freezer packed with convenience foods, check your meat. Gourmet Boutique, a food company based in Queens, NY, is recalling 286,000 pounds of meat and poultry. The recall is voluntary and includes more than 30 types of fresh and frozen products produced by the company, which may be contaminated with the bacteria Listeria monocytogenes. The USDA reports that the contamination was discovered in sampling done by federal food safety inspectors and Florida agriculture officials.

The recall includes fresh meat and chicken salad produced between April 19 and 24, 2008. The frozen products were produced between Oct. 23, 2007 and April 23, 2008. Some of the products to look out for are Gourmet Boutique Curry Chicken Salad, Gourmet Boutique Turkey Club Twister, and Jan’s Buffalo Bob tortilla wrap sandwiches. Frozen foods include Archer Farms mini beef burritos, pulled-pork burritos, and chicken burritos.

There haven't been any cases of illness yet, but the bacteria could potentially cause Listeriosis, which involves a high fever, headache, and nausea. More seriously, people with weak immune systems could suffer from fatal infections. Consumers with questions about the recall can call Gourmet Boutique's recall hotline at (347) 887-0083.

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Yep, Another Beef Recall

FitSugar — Wed, 16 Jan 2008 13:30:00 -0800

The Rochester Meat Company of Minnesota has voluntarily recalled 188,000 pounds of ground-beef patties and other meat products because of an E. coli scare. Six illnesses were reported, one in California and five in Wisconsin. This dangerous strain of E. coli - O157:H7 - can be potentially deadly for the elderly, the very young, and those with weakened immune systems. It can cause bloody diarrhea and dehydration.

The beef was produced from Oct. 30 through Nov. 6, and was shipped nationwide for use in restaurants. For a complete list of recalled products, check out the USDA's website. If you have any questions about the recall, you can call the company's quality assurance manager at 507-529-4759.

Fit's Tip: If you think you may have consumed bad meat, call your doctor immediately.

Beef Recall Update

FitSugar — Mon, 01 Oct 2007 11:45:00 -0700

Last week I told you about yet another beef recall, and now I am here to tell you it has gone from bad to worse. Originally only 332,000 lbs of meat were recalled, but on Saturday, the Topps Meat Co. expanded its recall to include 21.7 million lbs of ground beef that may also be contaminated with e. Coli.

This Elizabeth, NJ based beef company's recall includes:

All Topps products with either a "sell by date" or "best if used by date" between Sept. 25, 2007 and Sept. 25, 2008. The date can be found on the package's back panel.
They also have a USDA establishment number of EST 9748.

The USDA suspended the grinding of raw products at the Topps plant after inspectors found inadequate safety measures there. Terrific.

So far three people have confirmed cases of e. Coli contamination and there are 22 other cases under investigation. Cases were found in Connecticut, Florida, Indiana, Maine, New Jersey, New York, Ohio and Pennsylvania. Check out the full list of recalled products here.

I don't know about you, but a salad is looking really good about now.

Must See Movie: Food, Inc.

FitSugar — Mon, 22 Jun 2009 09:00:00 -0700

With the amount of food recalls seeming to grown annually, it is easy to feel that our food system in the US is broken, and after watching the 94 minute documentary Food, Inc., you learn that it truly is.

From the opening shots of the supermarket, we begin to learn how corn and the fast food industry have changed the way Americans both grow and eat food. While the movie repeats many of the facts from Michael Pollan's informative book, In Defense of Food, the facts are just as interesting the second time around. Food, Inc. also delves deeper into the chemical giant Monsanto and its role in destroying the family farm from the seeds on up. Eric Schlosser, author of Fast Food Nation shares the narrator role with Pollan, and these two tear down the food industrial food system starting with corn and moving quickly to the meat industry. The film is peppered with interviews with farmers - chicken, corn, and soy - whose lives have been dramatically altered by multinational corporations' interest in commanding the food chain. The film is disturbing to say the least, but it ends with tales from Polyface farm, a family operation that makes food seem wholesome again. I left the theater charged up to make changes not only in my daily diet, but to petition the government to give power back to their regulatory arms, the USDA and FDA, to help keep our food supply safe. The Food, Inc. website has a petition to reauthorize the Child Nutrition Act. After watching this documentary, you may never look at food the same way again.

Check out the trailer after the break.

Yet Another Recall? Beef From Whole Foods

FitSugar — Mon, 11 Aug 2008 11:00:00 -0700

Sorry to spread the bad news, but we have yet another recall to deal with. Whole Foods voluntarily recalled more than 1.2 million pounds of ground beef that has come from Coleman Natural Beef's Nebraska Beef processing plant. It pains me to say it but E. coli strikes again. Over 31 illnesses in 12 US states and Canada have been linked to this contaminated meat, but officials have yet to name the states (not sure what's up with that). Apparently this recall comes after the same company recalled 5.3 million pounds of meat a month ago, that was linked to at least 49 cases of E. coli. Geez.

The beef in the 24 Whole Foods locations in Northern California are not involved, since their meat comes from Country Natural Beef in Oregon, a supplier not listed in the beef recall. Another chain, Fred Meyers, is also pulling meat from their shelves. The ground beef in question was sold between July 2 and Aug. 6. If you're concerned about the beef at your local Whole Foods or natural grocery store, it's best to contact the store directly.

The USDA is still investigating, so I'm sure more info will be coming. It's just so upsetting that these recalls continue to plague our food system. Does this latest recall inspire you to start eating veggie burgers?

Source

Beef Recalls: Caused by Chronic Staff Shortages?

FitSugar — Mon, 25 Feb 2008 14:45:00 -0800

I don't eat red meat all that often, but all these beef recalls make me scared to eat it at all. As consumers, we have the right to know what's causing these thousands of pounds of beef to be contaminated with E. coli bacteria. I wouldn't have guessed it, but it looks like it may have to do with lack of staff and inspectors at slaughterhouses.

When there aren't enough workers, there's no way to properly inspect every single animal. Fewer workers also mean that the ones who are working are less likely to follow the rules. When the Humane Society of the United States set up undercover cameras at the Westland/Hallmark Meat Co. (where beef was recently recalled), they discovered workers kicking and shoving sick and crippled cows, forcing them to stand by using electric prods and forklifts. Not only is this unquestionably cruel, but cows that are too sick to stand carry a higher risk for mad cow disease. Also, since they are lying in feces, they're more likely to carry E. coli and salmonella, too. Unfortunately it also boils down to money. If you have a cow that's "downed" and can't be used for meat, that's 300 pounds of beef the meat industry isn't getting paid for. Now I remember why I try to eat lower on the food chain.

So with all this said, it's believed that most consumers will shrug off beef recalls. So I was wondering, do recalls affect your decisions when buying or eating meat?

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Cholesterol

FitSugar — Wed, 08 Oct 2008 17:34:59 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New Guidelines for Children and Adolescents

In 2007, the American Heart Association (AHA) established new guidelines for assessing and treating high cholesterol in children and adolescents. According to the AHA’s scientific statement:

LDL (“bad") cholesterol goals for children should be 190 mg/dL or less for children without heart disease risk factors and 160 mg/dL or less for children with heart disease risk factors.
Children who are overweight or obese, as well as those with a family history of high cholesterol and heart disease, should get their cholesterol levels checked.
For overweight and obese children with cholesterol imbalances, diet changes and exercise should be tried before drug treatment. For children with cholesterol imbalances who have a family history of cholesterol and heart problems, statins are the best first-line drug therapy.

Herbs and Supplements

Garlic, whether raw or in supplement form, does not help lower LDL in patients with moderately high LDL levels, according to a 2007 Archives of Internal Medicine Study.
Policosanol, a dietary supplement derived from sugar cane, has no effect on cholesterol, indicates a 2006 Journal of the American Medical Association (JAMA) study.

Diet Plans

In a 2007 JAMA comparison study of four diet plans (Atkins, Ornish, Zone, and LEARN), the low-carbohydrate Atkins diet was best at raising HDL (“good cholesterol”) levels and lowering triglyceride levels, but did not affect LDL levels. The low-fat Ornish diet was best at lowering LDL levels.
The Mediterranean diet works better than a low-fat diet in quickly lowering cholesterol as well as blood pressure and blood sugar, suggests a 2006 Annals of Internal Medicine study.

Drug Research

In contrast to research findings released last year, rosuvastatin (Crestor) does not appear to reverse heart disease, according to a 2007 JAMA study. However, the statin drug did help slow the progression of arterial thickening.

Introduction

Lipids are the building blocks of the fats and fatty substances found in animals and plants. They are microscopic layered spheres of oil, which, in animals, are composed mainly of cholesterol, triglycerides, proteins (called lipoproteins), and phospholipids (molecules made up of phosphoric acid, fatty acids, and nitrogen). Lipids do not dissolve in water and are stored in the body to serve as sources of energy.

Cholesterol is a white, powdery substance that is found in all animal cells and in animal-based foods (not in plants). In spite of its bad press, cholesterol is an essential nutrient necessary for many functions, including:

Repairing cell membranes
Manufacturing vitamin D on the skin's surface
Producing hormones, such as estrogen and testosterone
Possibly helping cell connections in the brain that are important for learning and memory

Regardless of these benefits, when cholesterol levels rise in the blood, they can have dangerous consequences, depending on the type of cholesterol. Although the body acquires some cholesterol through diet, about two-thirds is manufactured in the liver, its production stimulated by saturated fat. Saturated fats are found in animal products, meat, and dairy products.

Saturated fats are found predominantly in animal products, such as meat and dairy products, and are strongly associated with higher cholesterol levels. Tropical oils -- such as palm, coconut, and coconut butter -- are also high in saturated fats.

Triglycerides are composed of fatty acid molecules. They are the basic chemicals contained in fats in both animals and plants.

Lipoproteins are protein spheres that transport cholesterol, triglyceride, or other lipid molecules through the bloodstream. Most of the information about the effects of cholesterol and triglyceride actually concerns lipoproteins.

Lipoproteins are categorized into five types according to size and density. They can be further defined by whether they carry cholesterol or triglycerides.

Cholesterol-Carrying Lipoproteins. These are the lipoproteins commonly referred to as cholesterol.

Low density lipoproteins (LDL). (Often called the "bad" cholesterol.)
High-density lipoproteins (HDL), the smallest and most dense. (Referred to as the "good" cholesterol.)

Triglyceride-Carrying Lipoproteins.

Intermediate density lipoproteins (IDL). They tend to carry triglycerides.
Very low density lipoproteins (VLDL). These tend to carry triglycerides.
Chylomicrons (largest in size and lowest in density).

Lipoprotein(a). Lipoprotein(a), or lp(a) has a size and density somewhere between LDL and HDL. The molecules carry a protein that may interfere with the body's ability to dissolve blood clots. Lipoprotein(a) is being investigated as a possible marker or cause of heart disease.

Remnant Lipoproteins. Remnant lipoproteins are byproducts of chylomicrons, very low-density lipoproteins (VLDL), or both. Some research indicates that high levels may be an important risk factor for coronary artery disease, particularly in patients who have otherwise normal cholesterol levels.

Reducing LDL and total cholesterol levels, while at the same time boosting HDL levels, can prevent heart attacks and death in all people (with or without heart disease). Reducing LDL is the primary goal of most cholesterol therapy.

Blood tests can easily measure both HDL and overall cholesterol levels. It is very difficult to measure LDL levels by themselves, but LDL levels can be reliably calculated by subtracting HDL and triglyceride levels from total cholesterol. The exact formula is:

LDL = TOTAL CHOLESTEROL - HDL - TRIGLYCERIDES/5.

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.

The 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)

Two or more of these risk factors increases by 20% the chance of having a heart attack within 10 years.

The LDL cholesterol level is one of the most important factors in determining whether a patient needs cholesterol therapy and whether the treatment 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.


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

The following chart summarizes all goals.


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 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 an optimal goal. 160 mg/dL or below for people at less risk (one or zero risk factors); 130 mg/dL is an optimal goal. Anything above 160 is high, with levels above 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.

Although current guidelines as described in the table are extremely useful, they do have pitfalls. For example, the following cholesterol levels pose some dilemmas:

Low LDL levels (protective) accompanied by low HDL, high triglycerides, or both (harmful)
High total cholesterol (harmful) accompanied by high HDL (protective)

Would individuals with these cholesterol balances be at high risk or low risk for developing heart disease? To resolve this dilemma, experts have devised a calculation for a risk ratio by dividing the total cholesterol by either total HDL or LDL. It is not clear at this point which ratio is a better predictor of heart disease, although the HDL ratio may be superior. Using this ratio, the following results indicate better to worse outlook:

The ideal ratio is 3.5 or below.
A ratio of 4.5 carries an average risk.
Ratios of 5 or higher are potentially dangerous.

For example, if a person has a high total cholesterol of 280 mg/dL but a high HDL level of 70 mg/dL, the risk ratio is 4, which actually carries a lower than average risk. The use of this ratio may predict coronary artery disease more accurately than using total cholesterol levels alone. Still, the primary goal of lipid-lowering therapy is reducing LDL levels. Evidence strongly suggests that the lower the LDL levels, the lower the risk for heart disease.

Cholesterol's Effect on the Heart

Coronary artery disease, commonly known as heart disease, is the leading cause of death in the U.S. and was responsible for nearly 500,000 deaths in 2003.

Atherosclerosis is a common disorder of the arteries. Fat, cholesterol, and other substances collect in the walls of arteries. Larger accumulations are called atheromas or plaque and can damage artery walls and block blood flow. Severely restricted blood flow in the heart muscle leads to symptoms such as chest pain.

As many as half of these deaths were probably due to unhealthy cholesterol and lipid levels. Strong evidence points to LDL as the villain and HDL as a hero in the process. The role of other lipids, notably triglycerides, is not entirely clear.

Unhealthy cholesterol, particularly low-density lipoprotein (LDL), forms a fatty substance called plaque, which builds up on the arterial walls. Smaller plaques remain soft, but older, larger plaques tend to develop fibrous caps with calcium deposits.

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

The long-term result is atherosclerosis, commonly called hardening of the arteries. The heart is endangered in two ways by this process:

Eventually these calcified and inelastic arteries become narrower (a condition known as stenosis). As this process continues, blood flow slows and prevents sufficient oxygen-rich blood from reaching the heart. This condition leads to angina (chest pain) and, in severe cases, to heart attack.

Click the icon to see an image of a heart attack.

Smaller unstable plaques may rupture, triggering the formation blood clots on their surface. The blood clots block the arteries and are important causes of heart attack.

This process is accelerated and enhanced by other risk factors, including high blood pressure, smoking, obesity, diabetes, and a sedentary life style. When more than one of these risk factors is present, the risk is compounded.

The effects of cholesterol on the heart may involve more than just the arteries. There is some evidence that unhealthy levels may affect the heart muscles and increase the risk for heart failure. High cholesterol levels may even reduce the protection that aspirin provides for people with heart disease.

On an encouraging note, mortality rates associated with coronary artery disease have declined dramatically during the past 30 years. Some experts estimate that about 30% of the decline is due to better cholesterol management and statin drugs.

Studies consistently report a higher risk for death from heart disease with high total cholesterol levels (200 mg/dL and higher). The higher the cholesterol, the greater the risk. One study reported that men with total cholesterol levels higher than 240 mg/dL had a risk nearly two to four times that of men whose cholesterol was below 200 mg/dL. On average, every time a person's cholesterol level drops by a point, the risk of heart disease drops by 2%.

The primary villain in the cholesterol story is low-density lipoprotein (LDL). In a major study, the lowest incidence in heart disease was found among people with the lowest LDL levels. Lowering LDL is the primary goal of cholesterol drug and lifestyle therapy.

Low-density lipoprotein (LDL) transports about 75% of the blood's cholesterol to the body's cells. It is normally harmless. However, if it is exposed to a process called oxidation, LDL can penetrate and interact dangerously with the walls of the artery, producing a harmful inflammatory response. Oxidation is a natural process in the body that occurs from chemical combinations with unstable molecules. These molecules are known as oxygen-free radicals or oxidants.

When LDL collects on arterial walls these oxidants are released from the wall membranes.
Oxidants are missing an electron and tend to bind with other molecules in the body, a process called oxidation.
When the oxidation process modifies LDL, it signals the immune system that a harmful molecule has appeared.

Inflammation and Plaque. In response to oxidized LDL, the body releases various immune factors aimed at protecting the damaged walls. Unfortunately, in excessive quantities they cause inflammation and promote further injury to the areas they target:

White blood cells and other factors gather and form a fatty substance called plaque. (Of interest in this process is an enzyme called lipoprotein-associated phospholipase A2, which binds to oxidized LDL. Studies report that this enzyme may play a major role in the release of plaque-forming inflammatory factors.)
Other immune factors also cause inflammation and injure the endothelium, the layer of cells that line blood vessels.

Click the icon to see an image of the cut section of an artery.

Immune factors that increase the risk for blood clots are also mobilized.
Oxidized LDL plays another dangerous role by reducing levels of nitric oxide, a chemical that helps relax the blood vessels and allow blood to flow freely.

High density lipoprotein (HDL) appears to benefit the body in two ways:

It removes cholesterol from the walls of the arteries and returns it to the liver.

Click the icon to see an image of the liver.

It helps prevent oxidation of LDL. HDL actually appears to have its own antioxidant properties.

HDL helps keep arteries open and reduces the risk for heart attack. High levels of high HDL (above 60 mg/dL) may be nearly as important for the heart as low levels of LDL. HDL levels below 40 mg/dL are considered to be harmful. In one study, for each 4 mg/dL decline in HDL levels there was a 10% increase in coronary artery disease.

Triglycerides are major troublemakers for the heart. They appear to interact with HDL cholesterol in such a way that HDL levels fall as triglyceride levels rise. Low HDL is known to be harmful to the heart.

The harmful imbalance of high triglycerides with low HDL levels is also associated with obesity (particularly around the abdomen), insulin resistance, and diabetes. Insulin is a hormone essential for regulating the storage and use of glucose (sugar) and amino acids (proteins) in the body. Insulin resistance occurs when there are normal levels of insulin but the body cannot use it. Insulin resistance increases the risk for developing type 2 diabetes, and it is also associated with metabolic syndrome. Both of these conditions increase the risk for heart disease.

Some evidence also suggests that high triglycerides pose other dangers, regardless of cholesterol levels. Triglycerides, for example, may be responsible for blood clots that form and block the arteries. High triglyceride levels are also associated with the inflammatory response -- the harmful effect of an overactive immune system that can cause considerable damage to cells and tissues, including the arteries.

Studies are finding an elevated risk for angina and first heart attacks in people with elevated levels of lipoprotein(a), also known as or lp(a). This lipoprotein falls somewhere between HDL and LDL in density 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. Because concentrations of lipoprotein(a) are usually inherited, they do not respond to dietary or lifestyle changes. At this time, few experts recommend drug treatments to reduce lp(a) levels. Older women, but not men, appear to be at greater risk for high lp(a) levels and their consequences.

Cholesterol's Effect on the Brain

Having adequate levels of HDL may be the most important lipid-related factor for preventing ischemic stroke, a type of stroke caused by blockage of the carotid arteries that carry blood to the brain. HDL may even reduce the risk for hemorrhagic stroke, a less common type of stroke caused by bleeding in the brain that is associated with low overall cholesterol levels.

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.

The effects of high total cholesterol and LDL levels on ischemic stroke are less clear. One study suggested that the risk for ischemic stroke increases when total cholesterol is above 280 mg/dL. A 2002 study suggested that high cholesterol poses a risk for stroke only when specific proteins associated with inflammation are present.

Evidence points to high cholesterol levels, along with high blood pressure and a family history of the disease, as independent risk factors for AD. A major research target for common factors between cholesterol levels and AD has been apolipoprotein E (ApoE). ApoE plays a role in the movement and distribution of cholesterol for repairing nerve cells during development and after injury. People who carry a variant of this gene (ApoE4) are at significantly higher risk for AD.

High cholesterol may pose a risk for Alzheimer's regardless of this genetic factor, however. Some studies report that cholesterol is important within the brain for cell communication and memory.

Risk Factors

About half of all American adults have total cholesterol levels over 200 mg/dL. Over 25% have been told by doctors that they have unhealthy levels. Total cholesterol levels have been declining over the last several decades, at least among middle-aged and older adults. This decline may be partly due to the increased use of statins and other lipid-lowering medications. However, total cholesterol levels are getting higher among younger adults (ages 25 – 34 years). The major risk factor for these high rates may be the Western lifestyle. The typical high-fat/low-fiber American diet coupled with sedentary habits is largely responsible for this unfortunate trend.

Men. Heart disease is the major cause of death in men. On average, men develop coronary artery disease 10 - 15 years earlier than women do and have a greater risk for dying of heart disease at a younger age. A 2006 study suggested that high total cholesterol may also contribute to the development of high blood pressure in men.

Women. Coronary artery disease is also the number one killer of women. Women between the ages of 20 and 34, and after menopause (around age 55), have higher cholesterol levels than men. Some evidence suggests that HDL levels may be more significant in women than in men. In one study, at total cholesterol levels above 200, women with HDL levels below 50 had a higher death rate than those with levels above 50, regardless of their LDL cholesterol levels. Women also appear to be more susceptible to the high-triglyceride low-HDL syndrome, which may be a particular risk factor for heart disease.

Children and Adolescents. Children who have abnormal cholesterol levels are at increased risk of developing heart disease later in life. However, it is difficult to distinguish “normal” cholesterol levels in children. Changes in cholesterol levels occur between the ages of 8 - 18, and vary between genders and population groups. Cholesterol levels tend to naturally rise sharply until puberty, then decrease sharply, and then rise again.

In 2007, the American Heart Association established general LDL goals for children that take into account these fluctuations. The association’s LDL goals are 190 mg/dL or less for children with no additional heart disease risk factors and 160 mg/dL or less for children with additional risk factors (such as family history of high cholesterol, heart disease, and diabetes).

It is also clear that children who are overweight are at higher risk for high triglycerides and low HDL, which may be directly related to later unhealthy cholesterol levels. Studies have confirmed that childhood LDL levels and body-mass index (BMI) are strongly associated with cardiovascular risk during adulthood. The American Heart Association recommends that children who are overweight and obese, as well as those with a family history of high cholesterol, undergo cholesterol screening. Overweight and obese children who have high cholesterol should also get tested for high blood pressure, diabetes, and other conditions associated with metabolic syndrome.

As in adults, the primary source of unhealthy cholesterol levels in children comes from diets high in unhealthy fats: Saturated fats (found mainly in animal and dairy products) and trans fatty acids (found in commercial food products). Over-consumption of unhealthy fats increases the risk for both obesity and heart disease.

Less common causes of unhealthy cholesterol levels in children include:

Low-birth weight (associated with low HDL levels)
Low thyroid levels (hypothyroidism)
Kidney or liver diseases
Homozygous familial hypercholesterolemia. This is an uncommon inherited condition that causes severe cholesterol imbalances and can result in very early heart disease.
Certain medications such as specific antiseizure drugs, corticosteroids, and isotretinoin (Accutane)

Young and Middle-Aged Adults. The strongest evidence of unhealthy cholesterol levels and heart disease is in adults over age 45. However, a 2006 analysis found that while total cholesterol levels are decreasing among older adults, they are increasing in those age 25 - 34 years. Research strongly suggests that the younger a person is when unhealthy cholesterol levels develop, the greater the chance for serious heart and blood vessel problems in the future. A 2006 study in the New England Journal of Medicine indicated that keeping LDL levels low from an early age can help prevent heart disease later in life. In one important study, young men (ages 16 - 34) who had cholesterol levels at or above 240 mg/dL had two to four times the risk of dying from heart attack or other cardiac problems than did men whose cholesterol was lower than 200 mg/dL. Young men without cholesterol problems had a higher life expectancy, by up to 8 years. Other studies have suggested similar risks from unhealthy cholesterol in young women as well.

Elderly Adults. About 85% of people who die from coronary artery disease are over the age of 65. Because high cholesterol is an important risk factor for heart disease, experts strongly recommend statin or other lipid-lowering therapy for elderly people with high cholesterol levels. Surveys indicate that total cholesterol levels have been declining in older people over the last few decades. Many experts believe this is due in part to increased use of statin drugs.

In the U.S., 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, obese individuals tend to have high triglyceride levels and low HDL levels. This combination is a risk factor for heart disease. Obesity also causes other effects (high blood pressure, increase in inflammation) that pose major risks to the heart.

Obesity is a particularly hazard when it is one of the components of the metabolic syndrome, formerly known as syndrome X. This syndrome consists of obesity marked by abdominal fat, unhealthy cholesterol 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. Many experts recommend that patients with metabolic syndrome should be aggressively treated with high-dose statin therapy to lower LDL levels.

Obesity is also strongly associated with type 2 diabetes, which itself poses a significant risk for high cholesterol levels and heart disease.

Low thyroid levels (hypothyroidism) are associated with unhealthy lipid levels. (Lipids are fat molecules). Specifically, people with hypothyroidism are at higher risk for high total and LDL cholesterol, triglycerides, and other lipids associated with heart disease. Treating the thyroid condition can significantly reduce cholesterol levels. Some experts suggest that patients with high cholesterol should be evaluated for thyroid function before they are given cholesterol-lowering drugs. Research is mixed on whether mild hypothyroidism (subclinical hypothyroidism) is associated with unhealthy cholesterol levels. [See In-Depth Report #38: Hypothyroidism.]

Hypothyroidism is a decreased activity of the thyroid gland which may affect all body functions. In this condition, the rate of metabolism slows, causing mental and physical sluggishness. The most severe form of hypothyroidism is myxedema, which is a medical emergency.

Genetics play a major role in determining a person's blood cholesterol levels. Children from families with a history of premature heart disease should be tested for cholesterol levels after they are 2 years old. Genes may influence whether a person has low HDL levels, high LDL levels, high triglycerides, or high levels of other lipoproteins, such as lipoprotein(a).

Some inherited disorders and genetic abnormalities have been identified:

Familial hypercholesterolemia causes dangerous increases in cholesterol. It may be more common than previously thought. One European study reported familial hypercholesterolemia in 1 out of every 400 people.
Familial lipoprotein lipase deficiency is a very rare disorder that causes depletion of lipoprotein lipase. This is an enzyme that appears to be important in the removal of lipoproteins that are rich in triglycerides. People who are deficient in it have high levels of cholesterol and fat in their blood. A very low-fat diet is essential and is an effective treatment for these individuals.
Several studies have found a genetic mutation affecting neuropeptide Y in people with high total cholesterol and LDL levels. Neuropeptide Y is a compound in the brain that regulates appetite.
Researchers have identified a gene called APOAV, which may help detect patients at risk for elevated levels of triglycerides.

Other medical conditions strongly associated with unhealthy cholesterol levels include:

Polycystic ovarian syndrome. Women with this disorder, particularly those who are obese, appear to be at increased risk for high triglyceride and low HDL levels. This risk may be due to higher levels of the male hormone testosterone in these women.

Click the icon to see an image of a polycystic ovary.

Kidney disease

Symptoms

There are no warning signs for high LDL cholesterol levels. When symptoms finally occur, they usually take the form of angina or heart attack in response to the buildup of atherosclerotic plaque in the patient's arteries. This is definitely a condition where it pays to invest in preventive medicine before dangerous complications occur.

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.

Diagnosis

A blood test for cholesterol should include the entire lipoprotein profile: LDL, total cholesterol, HDL, and triglycerides. It is very difficult to measure LDL levels by themselves, but LDL levels can be reliably calculated using total cholesterol and HDL levels.

To obtain a reliable cholesterol reading, experts advise:

Avoid strenuous exercise for 24 hours before the test.
Do not eat or drink anything but water for 12 hours beforehand.
If the test results are abnormal, a second test should be performed between 1 week and 2 months after the first test.

Home Tests. Tests are available for home use and in public locations, such as shopping malls and pharmacies. For example, the CholesTrak Test can be taken at home with results in 10 minutes, but it measures only total cholesterol. The BioSafe Cholesterol Panel Test is also a home test, but it needs to be sent to a laboratory. This test, however, is very accurate and provides a full lipid profile.

Certain blood tests for factors associated with inflammation in the arteries indicate a higher risk for heart disease, even in people without unhealthy lipids:

C-reactive protein (CRP). CRP is regulated by a very potent immune factor called interleukin-6. Elevated levels have been strongly associated with the inflammatory response and a higher risk for heart attack, even in people with normal cholesterol levels. CRP is also associated with high blood pressure, insulin resistance (the primary problem in type 2 diabetes), and obesity.
A high white blood cell count.
Elevated fibrinogen (a factor responsible for blood clotting).
Lipoprotein-associated phospholipase A2 may prove to be another marker for inflammation and heart disease. Studies suggest that it may play some causal role in coronary artery disease.

A new type of test measures cholesterol levels in the skin. High skin levels may indicate an increased risk for atherosclerosis and serious heart disease.

General Screening Recommendations. Experts groups differ slightly on when screening should start, but the following are generally accepted recommendations:

Periodic cholesterol testing in all adults starting at age 20. Adults with normal cholesterol levels do not need to have the test repeated for 5 years unless changes occur in lifestyle (including weight gain and diet). Adults with risk factors for heart disease or stroke should be rechecked every 2 years.
Selective screening of children who are at risk for high cholesterol and heart disease or familial hypercholesterolemia, which is genetically elevated cholesterol. Risk factors include having parents with total cholesterol levels greater than 240, or having a parent or grandparent who had symptomatic heart disease at age 55 or younger.
Patients already being treated for high cholesterol should be checked every 2 - 6 months.

Lifestyle Changes

Although most studies that prove that lowering cholesterol saves lives are done using drug therapy, the absolute mandate for improving cholesterol levels is to first make changes in lifestyle (both diet and exercise). Even when drugs are used, healthy diet and physical activity are critical companions.

Although there are many major dietary approaches for protecting health, experts generally agree on the following recommendations for heart protection:·

Choose fiber-rich food (whole grains, legumes, nuts) as the main source of carbohydrates, along with a high intake of fresh fruits and vegetables. Walnuts in particular have cholesterol-lowering properties and are a good source of antioxidants and alpha-linolenic acid.
Avoid saturated fats (found mostly in animal products) and trans fatty acids (found in hydrogenated fats and many commercial products and fast foods). Choose unsaturated fats (particularly omega-3 fatty acids found in vegetable and fish oils).
In selecting proteins, choose soy protein, poultry, and fish over meat. A 2006 study found that soy does not help improve cholesterol. However, experts still recommend it as a heart healthy food choice.
Controlling weight, quitting smoking, and exercising are essential companions of any diet program.

After embarking on any heart healthy diet, it generally takes an average of 3 - 6 months before any noticeable reduction in cholesterol occurs. However, some people see improved levels in as few as 4 weeks. An intensive program may be necessary to achieve significant improvements in cholesterol levels and to reduce heart risk factors.

Therapeutic Lifestyle Changes (TLC) from the National Cholesterol Education Program. Guidelines from the National Cholesterol Education Program include these recommendations for preventing and managing high cholesterol levels in adults:

Choose five or more servings of fresh fruits and vegetables and six or more servings of whole grains, legumes. Soluble fiber is preferred (from cereal grains, beans, peas, legumes, and many fruits and vegetables).
Fats can be up to 35% of daily calories, but no more than 7% should be from saturated fat. (People with high triglycerides, low HDL, or both may need a higher fat intake.) Choose fats containing unsaturated fatty acids (from vegetables, fish, legumes, and nuts). Choose margarines containing sterols or stanols (Benecol, Take Control). Avoid trans fatty acids found in commercial baked products.
Protein choices should be fat-free and low-fat milk products, fish, legumes, skinless poultry, and lean meats.
Limit dietary cholesterol intake to less than 200 mg per day.
Maintain healthy body weight and a healthy level of physical fitness.

Mediterranean Diet. The Mediterranean diet is rich in heart-healthy fiber and nutrients, including omega-3 fatty acids and antioxidants. The diet consists of fruits, vegetables, and unsaturated “good” fats, particularly olive oil. Olive oil has been associated with lower blood pressure, a lower risk for heart disease, and possible benefits for people with type 2 diabetes. Olive oil also contains polyphenol, which are phytochemicals that may help boost HDL levels.

A 2006 study that compared several types of Mediterranean diets to a low-fat diet found that Mediterranean diets were better at lowering blood pressure, cholesterol levels, and blood sugar levels after only 3 months. And, in research presented at the 2007 American College of Cardiology annual conference, the Mediterranean diet proved just as good as the American Heart Association low-fat diet for preventing recurrence of heart attack, stroke, or other heart events.

There are several variations to the Mediterranean diet but general recommendations include:

Limit red meats.
Drink one or two glasses of wine each day if alcohol is enjoyable and there are no reasons to restrict its use.
Limit dairy products.
Eat moderate amounts of fish and poultry. Fish is the diet’s main protein source. Some studies suggest that fish is the primary heart-protective ingredient in this diet.
Eat plenty of fresh fruits and vegetables, nuts, legumes, beans, and whole grains.
Season with garlic, onions, and herbs. Unfortunately, garlic does not appear to help lower cholesterol, but it may have other heart benefits. [See Herbs and Supplements in this section.]

Low-Carbohydrate Diets. The Atkins, South Beach, The Zone, and other diet restrict carbohydrate intake include. A 2006 review of low-carbohydrate diets found that they did help weight loss in the short term. However, while these diets appeared to lower triglyceride and raise HDL (“good”) cholesterol levels, they also raised overall and LDL (“bad”) cholesterol levels.

In contrast, a 2007 Journal of the American Medical Association study that compared four different low-carbohydrate and low-fat diet plans (Atkins, Zone, Ornish, and LEARN) found that the Atkins diet was best at raising HDL levels and reducing triglyciderides. In terms of LDL reduction, the low-fat Ornish diet produced the best improvements while the Atkins diet had no effect on LDL. The Atkins diet did result in better moderate weight loss (an average of 10 pounds over the course of a year versus 4 - 6 pounds for the other diet plans), which in itself may have accounted for the improved heart risk factors.

Glycemic Index. Low-carb diets -- such as South Beach, The Zone, and Sugar Busters -- rely on a concept called the "glycemic index," or GI, which ranks foods by how fast and how high they cause blood sugar levels to rise. Foods on the lowest end of the index take longer to digest. Slow digestion wards off hunger pains. It also helps stabilize insulin levels. Foods high on the glycemic index include bread, white potatoes, and pasta while low-glycemic foods include whole grains, fruit, lentils, and soybeans. (These low-glycemic foods are also important components of low-fat diet plans.) A 2006 study indicated that a high-protein, low-glycemic index diet can help produce better reductions in total and LDL cholesterol than a high-protein, high-glycemic index diet. Reducing glycemic load may also help to promote weight loss, especially for women.

Low Fat Diets. Dietary guidelines recommend keeping total fat intake to 20 - 30% of total daily calories, with saturated fat less than 10% of calories. Low-fat diets generally restrict fat intake to 20% or less of total daily calories. The Ornish program, which is recommended for some heart disease patients, limits fats even more drastically. It aims at reducing saturated fats as much as possible, restricting total fat to 10%, and increasing carbohydrates to 75% of calories. In 2006, the largest study to date on low-fat diets found that they did not help prevent heart disease or cancer. Women in the study reduced their fat consumption to 24 - 29% of total daily calories. Some critics say that the study did not do enough to distinguish between good types of fats (monounsaturated omega-3 polyunsaturated) and bad fats (saturated and trans fats).

The DASH Diet. The DASH diet (Dietary Approaches to Stop Hypertension) is proven to help lower blood pressure. Results are sometimes seen within a few weeks. Restricting sodium improves results. The diet appears to have antioxidant effects and may help lower LDL cholesterol levels, although beneficial HDL levels also decline. This diet is not only rich in important nutrients and fiber but also includes foods that contain far more electrolytes, potassium (4,700 mg/day), calcium (1,250 mg/day), and magnesium (500 mg/day) than are found in the average American diet.

A diet that is effective in lowering blood pressure is called Dietary Approaches to Stop Hypertension (DASH).

The DASH diet recommends:

Limit salt intake to no more than 2,300 mg a day (a maximum intake of 1,500 mg a day is an even better goal).
Reduce saturated fat to no more than 6% of daily calories and total fat to 27% of daily calories. (But, include dairy products that are non- or low-fat. Low-fat dairy products appear to be especially beneficial for lowering systolic blood pressure).
When choosing fats, select monounsaturated oils, such as olive or canola oils.
Choose whole grains over white flour or pasta products.
Choose fresh fruits and vegetables every day. Many of these foods are rich in potassium, fiber, or both which may help lower blood pressure.
Include nuts, seeds, or legumes (dried beans or peas) daily.
Choose modest amounts of protein (no more than 18% of total daily calories). Fish, skinless poultry, and soy products are the best protein sources.
Other daily nutrient goals in the DASH diet include limiting carbohydrates to 55% of daily calories and dietary cholesterol to 150 mg. Patients should try to get at least 30 g of daily fiber.

Slight changes to the DASH diet might help lower blood pressure even more, as well as improve cholesterol and lipid levels. Researchers reporting in the Journal of the American Medical Association and at the 2005 American Heart Association meeting said that replacing some carbohydrates in the DASH diet with more protein (from mostly plant sources) or monounsaturated fats may help reduce heart disease risk factors.

Calorie Restriction. Calorie restriction has been the cornerstone of weight-loss programs. Restricting calories in such cases also appears to have beneficial effects on cholesterol levels, including reducing LDL and triglycerides and increasing HDL levels. At this point, reducing calories and increasing exercise is still the best method for maintaining weight loss and preventing serious conditions, notably diabetes. A 2006 study reported that a low-calorie, but nutritionally balanced diet can help prevent an aging-associated change in heart function. Patients in the small study took in 1,400 - 2,000 calories a day for an average of 6 years.

The standard dietary recommendations for losing weight are the following:

As a rough rule of thumb, one pound of fat equals about 3,500 calories, so one could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss.
To determine the daily calorie requirements for specific individuals, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance, a 50-year-old moderately active woman who wants to maintain a weight of 135 pounds might require only 12 calories per pound (1,620 calories a day). A 25-year-old female athlete who wants to maintain the same weight might require 25 calories per pound 2,025 (calories a day).

Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Saturated fats (found in animal products) should be avoided.

Inactivity is one of the four major risk factors for coronary artery disease, on par with smoking, unhealthy cholesterol, and high blood pressure. In fact, studies suggest that people who change their diet in order to control cholesterol only achieve a lower risk for heart disease when they also follow a regular aerobic exercise program.

People who maintain an active lifestyle have a 45% lower risk of developing heart disease than sedentary people. Even moderate exercise reduces the risk of heart attack. One study of women found that just 1 hour of walking a week was associated with a lower risk for heart disease. The effects were similar even in women at high risk for developing heart disease.
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.
Burning at least 250 calories a day (the equivalent of about 45 minutes of brisk walking or 25 minutes of jogging) seems to offer the greatest protection against coronary artery disease, most likely because it raises HDL ("good cholesterol") levels. Moderate exercise has little effect on HDL.
Aerobic exercise helps to open up blood vessels and, in combination with a healthy diet, may improve blood-clotting factors.
Resistance (weight) training offers a complementary benefit to aerobics by reducing LDL ("bad cholesterol") levels.
Exercises that train and strengthen the chest muscles may prove to be very important for patients with angina.

Cigarette smoking lowers HDL and is directly responsible for approximately 20% of all deaths from heart disease. The importance of breaking this habit cannot be emphasized enough. Once a person quits smoking, HDL cholesterol levels rise within weeks or months to levels that are equal to their nonsmoking peers. Passive smoking also reduces HDL levels in people exposed to cigarette smoke.

A number of studies have found heart protection from moderate intake of alcohol (one or two glasses a day). Moderate amounts of alcohol help raise HDL levels. Although red wine is most often cited for healthful properties, any type of alcoholic beverage appears to have similar benefit. Pregnant women, anyone who cannot drink moderately, and people with liver disease should not drink at all.

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 a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

The following natural remedies are of interest for cholesterol control:

Garlic. Contrary to popular belief, garlic does not significantly reduce cholesterol, according to a 2007 Archives of Internal Medicine study. Researchers tested raw garlic and two types of garlic supplements in 192 patients with moderately high LDL levels. None of the forms of garlic had any effect on LDL levels. However, the researchers note that garlic may still help people with very high LDL levels and it may contain other heart-protective properties.

Policosonol. Policosanol is a nutritional supplement derived from sugar cane that has been promoted as having lipid-lowering benefits. In a randomized, placebo-controlled trial published in 2007 in the Archives of Internal Medicine, policosanol was no better than placebo in reducing LDL levels.

Treatment

In 2004, the National Cholesterol Education Program issued its latest recommendations for cholesterol control and management. These guidelines increase the number of Americans who should be taking LDL-lowering medication.

Starting Medications. Even modest lowering of high cholesterol levels, whether through drug therapy or lifestyle changes, reduces the risk of disability and death from heart disease. Most experts now focus on lowering LDL ("bad") cholesterol. Reducing LDL levels is particularly critical for patients with diabetes.

The doctor will start or consider medication when:

LDL cholesterol is 190 mg/dL or higher.
LDL cholesterol is 160 mg/dL or higher AND patient has one risk factor for heart disease.
LDL cholesterol is 130 mg/dL or higher AND patient has either diabetes or two other risk factors for heart disease.
LDL cholesterol is 100 mg/dL or higher AND patient has heart disease. (If patient has diabetes, even without heart disease, medication may be considered for an LDL cholesterol of 100 mg/dL.)
LDL cholesterol is greater than 70 mg/dL AND patient has had a recent heart attack or has known heart disease along with diabetes, current cigarette smoking, poorly controlled high blood pressure, or the metabolic syndrome (high triglycerides, low HDL, and obesity).

Risk factors for heart disease 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)

Recent studies have found that aggressive lipid lowering with high-dose statin therapy is more beneficial than standard statin therapy in patients with existing heart disease. The Pravastatin or Atorvastatin Evaluation and Infection Trial (PROVE-IT) and the Reversal of Atherosclerosis with Aggressive Lipid-Lowering trial (REVERSAL) compared the benefits of standard statin therapy (pravastatin, 40 mg) with intensive statin therapy (atorvastatin, 80 mg) in treating patients with heart disease.

Results from PROVE-IT demonstrated that for high-risk patients, intensive statin therapy is more effective than standard therapy in lowering LDL cholesterol and C-reactive protein (CRP) levels, and that CRP levels predict risk even when LDL cholesterol has been lowered substantially. The REVERSAL data suggest that intensive statin therapy produces greater reductions in LDL and CRP levels, and that the more that statins can lower LDL, the more effective they are in reducing the progression of atherosclerosis.

An important 2006 study found that aggressive treatment with rosuvastatin (Crestor):

Helped lower LDL to below guideline levels
Moderately increased HDL levels
Reduced fatty plaque in the arteries

Experts hoped that these results suggested that statin therapy might have the potential to reverse coronary atherosclerosis. 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 and to explore whether other statins have a similar positive effect on coronary artery disease. Rosuvastatin lowers LDL more than other statins, but it also carries greater risks for more serious side effects (see Adverse Effects section). Many experts believe that the more that LDL is reduced through statin therapy, the greater the reduction in risk for heart disease, heart attack, and stroke.

It is important to emphasize that cholesterol-lowering medications are used along with healthy lifestyle habits, not in place of them.

Choosing the Correct Lipid-Lowering Medication. Experts now recommend that drug treatments be tailored for raising or lowering specific lipids, depending on the patient's blood lipid picture:

Statins are now the standard drugs for most people who require LDL-lowering therapy. Bile-acid binding resins or niacin may be considered. If LDL goals are not achieved, combinations of a statin with a bile-acid resin or niacin should be considered.
Fibrates or niacin are beneficial for people who need to lower triglycerides and increase HDL.

Considerations for Children and Adolescents. In 2007, the American Heart Association (AHA) issued a scientific statement addressing the use of cholesterol drugs in children and adolescents. The AHA recommends that for children who are overweight or obese, lifestyle modifications (diet, exercise) are preferred over drug therapy and should be the first step in lowering cholesterol.

For children and adolescents who have high-risk cholesterol imbalances -- and have a family history of high cholesterol, heart attack, stroke, and diabetes -- the AHA now recommends statins as the first-line drug therapy.

Considerations for People with Diabetes. At this time, statins are recommended as the best drugs for improving cholesterol and lipid levels in people with diabetes. Studies suggest that they can reduce the risk for adverse heart events in people with diabetes, even if their cholesterol levels are normal or if their diabetes is mild. Furthermore, in one study, a statin was shown to reduce the risk of developing diabetes by 30% in people with high cholesterol. Fibrates may also be useful for people with type 2 diabetes. Niacin (nicotinic acid) has the best effect on the cholesterol profile of people with diabetes but it also increases blood sugar levels. One well-controlled study, however, found that people with diabetes who used niacin had little trouble with glucose control, and some experts believe it now may be used as an alternative to or in combination with statins.


	Effect on High LDL	Effect on Low HDL	Effect on High Triglycerides	Effect on Lp(a)
Statins	Decrease (18 - 55%)	Modest increase (5 - 15%)	Decrease (7 - 30%)	No change
Nicotinic acid (Niacin)	Modest decrease (5 - 25%) In combination with statins, may convert more dangerous LDL type to less dangerous.	Increase (15 - 35%) Drugs of choice for improving HDL levels	Decrease (20 - 50%) Drug of choice for lowering triglycerides	Decrease
Fibrates	Effect varies, but in general has little effect or modest decrease (5 - 20%)	Modest increase (6 - 20%)	Decrease (20 - 50%)	No change
Bile acid-binding resins	Decrease (15 - 30%)	Very modest increase (3 - 5%)	No change	No change

Statins are the most effective drugs for the treatment of high cholesterol, and may even prove important drugs for many people at risk for heart disease who have normal cholesterol levels. Statins inhibit the liver enzyme HMG-CoA reductase, which is used in the manufacturing of cholesterol. These drugs effectively reduce the risk of major coronary events, including first and second heart attacks, in both adult women and men of any age with unhealthy cholesterol levels. Experts estimate a 25 - 30% reduction in mortality rates when patients take statins after a heart attack. (Some believe the decrease may even be greater.) These drugs may also help improve the outcome in patients with heart disease who have had angioplasty.

Important studies have reported lower rates of heart attack, stroke, and mortality rates from all causes in statin users who were at high risk for heart disease, even if they had normal or low cholesterol levels. Benefits were similar in these people regardless of gender, age, or the presence of specific heart risk factors, such as diabetes or peripheral artery disease.

Brands. Statins are currently categorized into four groups:

So-called natural statins, including lovastatin (Mevacor, generics), pravastatin (Pravachol), and simvastatin (Zocor, generics). These are the most studied statins and have proven effectiveness and good safety record.
Synthetic statins include fluvastatin (Lescol) and atorvastatin (Lipitor). Studies using atorvastatin suggest they may reduce LDL more effectively than natural statins. In 2007, Lipitor was approved for additional indications to reduce the risk of heart attacks, strokes, certain types of heart surgery, hospitalization for heart failure, and chest pain in patients with heart disease. Lipitor is also approved for children.
The newer statins include rosuvastatin (Crestor), which was approved in 2003. Trial results have suggested that rosuvastatin is more effective in improving lipid profiles than atorvastatin, simvastatin, or pravastatin. However, like all statin drugs, rosuvastatin can cause serious side effects (see the Adverse Effects section in this report). The risks may be higher for Asian patients; this population should be started on the lowest rosuvastatin dose (5 mg).
Fixed-dose combination statins, which combine two drugs in one pill, first appeared on the market in 2004. Ezetimibe/simvastatin (Vytorin) combines two cholesterol medications that work in different ways. Simvastatin blocks cholesterol production in the liver, while ezetimibe (a non-statin cholesterol medication) blocks cholesterol absorption in the digestive tract. A 2005 study found that Vytorin was more effective than atorvastatin in lowering LDL and increasing HDL levels. Amlodipine/atorvastatin (Caduet) is a dual-therapy medication that combines the antihypertensive calcium channel blocker amlodipine with atorvastatin. It is used to treat simultaneously high blood pressure and high cholesterol.

Statins are generally administered once a day, typically in the evening because most cholesterol synthesis occurs between midnight and 3 a.m. (Atorvastatin and rosuvastatin, however, can be taken in the morning.) Statins are often prescribed along with other cholesterol-lowering drugs such as bile acid-binding resins, nicotinic acid (niacin), and fibrates.

Beneficial Effects on the Heart and Circulation.

Statins are particularly effective for lowering LDL levels. They also reduce triglycerides, apparently in direct proportion to their LDL-lowering effects. Statins also raise HDL levels, but to a lesser extent than other anti-cholesterol drugs. (The newer statins appear to produce more significant increases in HDL.) Evidence now strongly suggests that statins may offer other health benefits beyond lowering cholesterol:

Statins may improve the function of the endothelium (the lining of blood vessels), thereby improving blood flow. (This benefit apparently does not extend to people with diabetes.)
Statins appear to reduce inflammation in the arteries, which is now believed to be a major factor in blood vessel injury.
Some evidence suggests that statins may help prevent blood clotting, a major factor in heart attacks.

Beneficial Effects Outside the Heart. Studies also suggest that the benefits of statins go beyond the heart. At this time, nearly all studies on the following conditions have used natural statins:

Stroke. Statins may reduce the risk for ischemic stroke in high-risk patients with a wide range of cholesterol and lipid levels. (Ischemic strokes occur from blockage in the blood vessels that lead to the brain.) In 2003, statin therapy was shown to reduce both fatal and non-fatal stroke in patients with hypertension and at least three additional cardiovascular risk factors. A 2004 study of stroke patients found that those who were receiving statin therapy at the time of their stroke had more favorable long-term outcomes than patients who were not on statin therapy, suggesting that statin therapy may provide additional benefits to patients who develop stroke.
Diabetes. Statins may have a number of effects that are helpful for patients with diabetes, and may even prevent diabetes in some people with high cholesterol. Statins, however, do not appear to have any effect on blood vessel inflexibility in diabetes, which is an important risk factor for heart disease in these patients. A major 2003 study found that statin therapy helped prevent cardiovascular events including coronary death, heart attack, stroke, and the need for revascularization therapy in patients with diabetes, even in those who did not have high cholesterol levels or established coronary disease.
High Blood Pressure. In an important 2002 study, patients with high blood pressure but normal hMG-CoA reductase or slightly high cholesterol levels had fewer heart attacks and strokes when they took the statin atorvastatin. The study was stopped so all subjects could take statins. An earlier study showed similar benefits with the statin simvastatin.
Alzheimer's Disease. A number of studies have reported a significantly lower risk for Alzheimer's disease in people who take specific statins. Some evidence suggests they may even improve mental function in people without unhealthy cholesterol levels. Statins showing the greatest promise include lovastatin (Mevacor), pravastatin (Pravachol), and atorvastatin (Lipitor.) These statins appear to reduce levels of beta-amyloid. Other statins have not been associated with a lower risk for Alzheimer's. In fact, some researchers are concerned that certain statins that cross the blood-brain barrier may actually worsen Alzheimer's in people who already have it.
Kidney Disease. Statins may prove to protect against heart disease development in patients with mild kidney disorders. According to a 2004 study, statins may also help slow the progression of existing kidney disease.
Eye Disease. Studies are investigating whether statins can help prevent macular degeneration, an age-related eye disease that can lead to blindness. Research is still preliminary, and results have been mixed.

Macular degeneration is a disease of the retina that affects the macula in the back of the eye. The macula is important for clear central vision, allowing an individual to see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more common and is characterized by the thinning of the retina and drusen, small white deposits that form within the retina. The dry form of macular degeneration is usually mild. Wet macular degeneration can happen more quickly and be more serious. It occurs when vessels under the retinal layer hemorrhage and cause the retinal cells to die, creating blind spots or distorted vision in the central vision. The disease becomes increasingly common among people in each succeeding decade over 50.

Adverse Effects. The statins tend to be better tolerated than other cholesterol-lowering drugs. In many studies the side effects reported were nearly the same as those taking placebo. Side effects may include gastrointestinal discomfort, headaches, skin rashes, muscle aches, sexual dysfunction, drowsiness, dizziness, nausea, constipation, and peripheral neuropathy (numbness or tingling in the hands and feet).

The primary safety concern with statins has involved an uncommon condition called myopathy, which can cause muscle damage and in some cases, muscle and joint pain. A specific myopathy, called rhabdomyolysis, can lead to kidney failure. Reports of rhabdomyolysis prompted the recall of cerivastatin (Baycol) in 2001. The risk for myopathy/rhabdomyolysis is highest at higher doses and in older people (over 65 years), those with hyperthyroidism, and those with renal insufficiency (kidney disease). Both statins and fibrates carry a risk for myopathy. The combination of the two drugs increases this side effect. Some people who use a statin-fibrate combination withdraw from the regimen because of muscle discomfort.

In 2005, the FDA issued a public health advisory for rosuvastatin (Crestor), noting that this drug, like other statins, increased the risk for myopathy and rhabdomyolysis. The risks were greatest at the highest dose level (40 mg). The FDA advises that patients should not start therapy at this dose. In addition, the FDA reported the results of a post-marketing study that found that people of Asian heritage had twice the blood levels of the drug as Caucasians who had taken the same dose. Because of this difference in drug metabolism, the FDA advises that Asian Americans should start treatment at the lowest rosuvastatin dose (5 mg). In general, all statin therapy should start at a lower dose and be raised incrementally until healthy cholesterol levels are maintained. Patients should immediately tell their doctor about any unusual muscle discomfort or weakness, fever, nausea or vomiting, or darkening of urine color.

Statins can also affect the liver, particularly at higher doses, so patients should have periodic liver function tests. Statins should not be taken by anyone with liver problems or by women during pregnancy or breast-feeding. Similarly, high statin doses increase the risk for kidney failure, particularly for patients with other existing risk factors (diabetes, hypertension, atherosclerosis, history of heart failure).

Interactions with Drugs and Food. Statins may have some adverse interactions with other drugs, including other cholesterol-lowering medications. Among the drugs that increase the risk for adverse effects are cyclosporine, macrolide antibiotics, and certain antifungals. Patients should tell their doctors about any other medications they are taking. Grapefruit juice and Seville oranges may increase statin potency.

Brands. Nicotinic acid is the active compound found in niacin, or vitamin B3. It is the first choice for patients with low HDL levels. Brands include Niacor, Nicolar, and Slo-Niacin. An extended-release form (Niaspan), administered at bedtime, may have fewer side effects, including headaches and flushing, than rapidly-acting niacin drugs. Although niacin is available over the counter, the active form used for cholesterol is given in much higher doses and is available only by prescription. It is important to take this medication under a doctor's direction in order to ensure its safety and effectiveness.

Benefits. When used in high doses, it has the following benefits:

Raises HDL levels higher than other anti-cholesterol drugs
Reducing triglyceride levels very effectively
Lowers LDL-cholesterol and lipoprotein(a)
Costs less than other anti-cholesterol drugs

Combinations with other drugs, particularly statins, may add significant benefits.

Side Effects. Many patients do not like the side effects of the rapidly-absorbed form of nicotinic acid. About a quarter of patients who use rapid-acting forms of nicotinic acid stop taking them. The most common side effects are flushing of the face and neck, itching, headache, blurred vision, and dizziness. They usually occur between 5 minutes to hours after taking the drug and can last for minutes to, uncommonly, hours. The body does eventually become tolerant to these effects, and they generally subside.

The following may reduce flushing and itching:

Starting with low doses taken at mealtime and gradually working up to the prescribed dose.
Taking low-dose aspirin about 30 minutes before taking nicotinic acid. This may help prevent flushing.
Avoiding hot drinks.
Choosing an extended release form. (Even with this form, it is wise to gradually increase the bedtime dose over time and take a low-dose aspirin a half-hour beforehand.)

Stomach problems are common. Other side effects include dry skin and mucous membranes and darkening of the skin.

About 30% of patients who take niacin experience elevated levels in blood glucose, which can be a problem for people with diabetes. Niacin's effects on HDL and triglycerides, however, are especially suited for the lipid imbalances that are common in diabetes. And, some studies report that people with diabetes who use niacin have little trouble with blood sugar control.

Potentially Serious Complications. About 3 - 5% of people taking nicotinic acid develop liver problems, which disappear after the medication is discontinued. The extended form (Niaspan) appears to be safe for the liver, but people with chronic liver disease should not use any form of nicotinic acid. People with gout should also avoid nicotinic acid because it elevates uric acid.

Bile-acid binding resins work, as their name suggests, by binding to bile in the digestive tract. This reduces cholesterol in the following way:

Bile is made in the liver and is used as one of the body's primary manufacturing components.

Click the icon to see an image of the gallbladder.

Once the resins bind to bile in the digestive tract, the bile is excreted in feces.
As the resins eliminate bile from the body, the liver takes more cholesterol from the bloodstream in order to produce more bile.
As cholesterol is taken out of the bloodstream, LDL levels drop.

When used in combination with dietary control, LDL levels are reduced by 15 - 20%. Combinations with nicotinic acid are even more effective, with reductions of 40 - 60% observed.

Brands. The bile-acid binding resins and similar drugs include cholestyramine (Questran, Questran Light). They are commonly used in a powder that is dissolved in liquid. Colesevelam (Welchol) is available in tablet form.

Side Effects. None of these drugs poses major risks. Most, however, cause constipation, heartburn, gas, and other gastrointestinal problems, side effects that many people cannot tolerate. One study found that only half the standard dose of colestipol was needed when psyllium, (a soluble fiber supplement found in Metamucil, Fiberall, and Perdiem), was added to the drink. In addition, bloating and constipation were reduced. Colesevelam, a newer resin, appears to have significantly fewer of these side effects.

Bile-acting drugs may contribute to calcium loss and therefore increase the risk for osteoporosis. Over time, deficiencies of vitamins A, D, E, and K may occur, and vitamin supplements may be necessary.

Rarely, toxic effects on the liver have been reported. Patients with liver disorders should be monitored.

Drug Interactions. Bile-acid binding resins may also interfere with other medications, including digoxin (Lanoxin), warfarin, beta-blocker drugs, and a number of medications used to treat low blood sugar. In order to prevent drug interactions, other drugs should be taken 1 hour before or 4 - 6 hours after taking the bile acid-binding resins.

Brands. Fibrates (sometimes called fibric acid derivatives) break down the particles that make triglycerides. Gemfibrozil is the standard fibrate. It is usually taken twice a day, 30 minutes before breakfast and before the evening meal. Newer fibrates, including fenofibrate (Lofibra, Tricor, Triglide), may be more effective in lowering cholesterol than gemfibrozil.

Benefits. Most fibrates have been shown to lower the risk of heart attack. In a 2001 study, men with both low HDL and LDL levels had a slightly lower risk of stroke after taking gemfibrozil. Fibric acid derivatives, or fibrates, have the following effects on cholesterol, lipids, and other factors:

They are good choices for many patients who need to lower triglyceride levels and increase HDL but who cannot take drugs ordinarily used for these purposes, such as nicotinic acid. In one study gemfibrozil, the standard fibrate, reduced the risk for adverse heart events by 22%.
Fibrates can produce modest reductions in LDL levels, although not as effectively as statins or other drugs. LDL may actually increase in patients with very high triglycerides who take these drugs. (The newer fibrates are much more effective in lowering LDL than gemfibrozil.)
A study on bezafibrate suggested it might have anti-inflammatory effects in patients with high triglyceride levels. Inflammation in the blood vessels is now recognized as a major contributor to the process leading to heart disease. However, according to a 2004 study, patients with diabetes or impaired fasting glucose levels were less likely to benefit from bezafibrate.
A study on fenofibrate further suggested that it reduced certain clotting factors (another risk factor for heart disease) and also uric acid (a risk factor for gout). Another study, published in 2004, demonstrated that like bezafibrate, fenofibrate has significant anti-inflammatory properties in patients with high triglyceride levels.

Concerns. Fibrates do not appear to reduce mortality rates. In one study, people who took gemfibrozil had higher rates of death from other causes, including cancer. Some evidence suggests that fibrates may affect receptors involved in cancer development. However, a number of studies have found no higher incidence of cancer.

Side Effects. Side effects may include gastrointestinal discomfort, aching muscles, sensitivity to sunlight, and skin rashes. Fibrates have been known to cause gallstones, so people with gallbladder problems should not use these drugs.

Click the icon to see an image of gallstones in the gallbladder.

The drugs may cause abnormal heart rhythms and can affect the liver and kidney.

Drug Interactions. Fibrates interact with a number of drugs and substances including warfarin, some oral drugs used for diabetes, certain antibiotics, and grapefruit juice.

Ezetimibe (Zetia) blocks absorption of cholesterol that comes from food. Ezetimibe is usually prescribed alone or in combination with a statin. In 2004, the FDA approved Vytorin, which combines ezetimbe and the statin simvastatin into a single pill.

In 2006, the FDA approved the use of ezetimbe in combination with fenofibrate (Tricor) for reduction of total cholesterol and LDL in patients with mixed hyperglycemia (high LDL levels, high triglycerides, low HDL levels) whose cholesterol has not been adequately controlled through diet alone. Fenofibrate is a cholesterol drug that is used along with diet to reduce LDL and triglycerides.

CETP Inhibitors. Cholesteryl ester transfer protein (CETP) inhibitors, such as the experimental drug torcetrapib, are a new drug class that is being investigated for its effect on raising HDL ("good" cholesterol) levels while lowering LDL ("bad") cholesterol levels. Torcetrapib was the most widely studied of these drugs. However, in December 2006, the drug’s manufacturer abruptly stopped late-stage clinical trials after discovering that torcetrapib significantly increased blood pressure and risk of death.

Several studies published in 2007 in the New England Journal of Medicine revealed that while torcetrapib does greatly boost HDL levels (by 61% in one study) and lower LDL, it has no effect on arterial plaque. Scientists are trying to understand why this drug did not work. One theory is that torcetrapib may have increased the quantity of HDL, but not the quality. It is still not clear whether the failure of trocetrapib is specific to this drug or the entire CETP drug class. Given the current findings, it is also unclear whether research will continue on other CETP drugs.

Selective Estrogen-Receptor Modulators(SERMs). Selective estrogen-receptor modulators (SERMs) 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. They include tamoxifen (Nolvadex), raloxifene (Evista), and droloxifene. Any beneficial effects of the SERMs on cholesterol and the heart are still unclear. SERMs pose a risk for deep vein blood clots, which may have implications for people with heart problems. Longer studies are needed on possible risks and benefits.

Recombinant ApoA-I Milano. ApoA-I Milano is a type of HDL protein that is found in people with very low levels of HDL. A 2003 study showed that treating patients with a synthetic form of HDL, derived from ApoA-I Milano, caused a significant regression of atherosclerosis. Ongoing trials will evaluate whether this drug can prevent cardiovascular events such as heart attack or death.

Plasmapheresis and Familial Hypercholesterolemia. Plasmapheresis is a blood-filtering procedure that is used to dramatically reduce triglycerides and may also be used to remove LDL. The procedure may be beneficial for patients with severe hereditary forms of high cholesterol who do not respond to other therapies. Studies suggest, for example, that plasmapheresis is particularly useful for patients with familial hypercholesterolemia. The process takes about 3 hours. If not performed regularly, its benefits last only about 2 weeks. People using this procedure are still advised to maintain a healthy diet and continue to take any prescribed medications to control cholesterol.

Resources

www.nhlbi.nih.gov/about/ncep -- National Cholesterol Education Program
www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.acc.org -- American College of Cardiology
www.americanheart.org -- American Heart Association
www.eatright.org -- American Dietetic Association

References

Berthold HK, Unverdorben S, Degenhardt R, Bulitta M, Gouni-Berthold I. Effect of policosanol on lipid levels among patients with hypercholesterolemiaor combined hyperlipidemia: a randomized controlled trial. JAMA. 2006 May 17;295(19):2262-9.

Covas MI, Nyyssonen K, Poulsen HE, Kaikkonen J, Zunft HJ, Kiesewetter H, et al. The effect of polyphenols in olive oil on heart disease risk factors: a randomized trial. Ann Intern Med. 2006 Sep 5;145(5):333-41.

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 25; [Epub ahead of print]

Deedwania P, Barter P, Carmena R, Fruchart JC, Grundy SM, Haffner S, et al. Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome: analysis of the Treating to New Targets study. Lancet. 2006 Sep 9;368(9539):919-28.

Estruch R, Martinez-Gonzalez MA, Corella D, Salas-Salvado J, Ruiz-Gutierrez V, Covas MI, et al. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med. 2006 Jul 4;145(1):1-11.

Gardner CD, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR, et al. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA. 2007 Mar 7;297(9):969-77.

Gardner CD, Lawson LD, Block E, Chatterjee LM, Kiazand A, Balise RR, et al. Effect of raw garlic vs commercial garlic supplements on plasma lipid concentrations in adults with moderate hypercholesterolemia: a randomized clinical trial. Arch Intern Med. 2007 Feb 26;167(4):346-53.

Jolliffe CJ, Janssen I. Distribution of lipoproteins by age and gender in adolescents. Circulation. 2006 Sep 5;114(10):1056-62. Epub 2006 Aug 28.

Kastelein JJ, van Leuven SI, Burgess L, Evans GW, Kuivenhoven JA, Barter PJ, et al. Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. N Engl J Med. 2007 Mar 26; [Epub ahead of print]

McCrindle BW, Urbina EM, Dennison BA, Jacobson MS, Steinberger J, Rocchini AP, et al. Drug therapy of high-risk lipid abnormalities in children and adolescents. A scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, With the Council on Cardiovascular Nursing. Circulation. 2007 Mar 21; [Epub ahead of print]

McMillan-Price J, Petocz P, Atkinson F, O'Neill K, Samman S, Steinbeck K, et al. Comparison of 4 diets of varying glycemic load on weight loss and cardiovascular risk reduction in overweight and obese young adults: a randomized controlled trial. Arch Intern Med. 2006 Jul 24;166(14):1466-75.

Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT, et al. Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med. 2007 Mar 26; [Epub ahead of print]

Review Date:
7/23/2007
Reviewed By:
Alan Greene, MD, FAAP, Chief Medical Officer, A.D.A.M., Inc.; and Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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A.D.A.M. Copyright

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adam.com

Heart failure

FitSugar — Wed, 08 Oct 2008 17:35:10 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Complications
Diagnosis
Treatment
Medications
Surgery and Devices
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Permanent Implantable Heart Approved

In 2006, the FDA approved the first permanent artificial heart. The AbiCor is intended for patients who are not eligible for heart transplants and who are only expected to survive about a month without medical treatment. Patients who received the AbiCor have survived, on average, about 5 months.

Statin Drug Approved for Heart Failure

In 2006, the FDA approved the cholesterol drug atorvastatin (Lipitor) to reduce the risks of hospitalization for heart failure in patients with heart disease.

Drug Research

The investigational drug tolvaptan improved symptoms in patients hospitalized with severe heart failure and fluid build-up in the lungs, according to several 2007 Journal of the American Medical Association (JAMA) studies. However, the drug did not reduce the risks of re-hospitalization and death.

Preserved Versus Reduced Ejection Fraction

Heart failure with preserved left-ventricular ejection fraction (LVEF) is becoming more common, suggests several 2006 studies published in JAMA and the New England Journal of Medicine. Unfortunately, this type of heart failure is less well studied than reduced LVEF. Experts are urging that more studies be conducted to determine better treatment options for preserved LVEF. Both types of heart failure have high mortality rates.

Systolic Blood Pressure Predictor of Mortality

Patients who are admitted to the hospital with heart failure and low systolic blood pressure have a poorer chance of survival than patients admitted with high blood pressure, indicates a 2006 JAMA study.

Diet and Lifestyle Factors

Daily consumption of whole-grain breakfast cereals may reduce the risk for heart failure, suggests research presented at a 2007 American Heart Association conference on heart disease prevention.
A drink or two a day is associated with lower risk of heart failure, indicates a 2006 Journal of the American College of Cardiology study. However, heavy alcohol consumption can increase the risk for heart failure.

Introduction

To understand what occurs in heart failure, it is useful to be familiar with the anatomy of the heart and how it works. The heart is composed of two independent pumping systems, one on the right side, and the other on the left. Each has two chambers, an atrium and a ventricle. The ventricles are the major pumps in the heart.

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.

The Right Side of the Heart. The right system receives blood from the veins of the whole body. This is "used" blood, which is poor in oxygen and rich in carbon dioxide.

The right atrium is the first chamber that receives blood.
The chamber expands as its muscles relax to fill with blood that has returned from the body.
The blood enters a second muscular chamber called the right ventricle.
The right ventricle is one of the heart's two major pumps. Its function is to pump the blood into the lungs.
The lungs restore oxygen to the blood and exchange it with carbon dioxide, which is exhaled.

The Left Side of the Heart. The left system receives blood from the lungs. This blood is now oxygen rich.

The oxygen-rich blood returns through veins coming from the lungs (pulmonary veins) to the heart.
It is received from the lungs in the left atrium, the first chamber on the left side.
Here, it moves to the left ventricle, a powerful muscular chamber that pumps the blood back out to the body.
The left ventricle is the strongest of the heart's pumps. Its thicker muscles need to perform contractions powerful enough to force the blood to all parts of the body.
This strong contraction produces systolic blood pressure (the first and higher number in blood pressure measurement). The lower number ( diastolic blood pressure) is measured when the left ventricle relaxes to refill with blood between beats.
Blood leaves the heart through the ascending aorta, the major artery that feeds blood to the entire body.

The Valves. Valves are muscular flaps that open and close so blood will flow in the right direction. There are four valves in the heart:

The tricuspid regulates blood flow between the right atrium and the right ventricle.
The pulmonary valve opens to allow blood to flow from the right ventricle to the lungs.
The mitral valve regulates blood flow between the left atrium and the left ventricle.
The aortic valve allows blood to flow from the left ventricle to the ascending aorta.

Click the icon to see an image of the internal structures of the heart.

The Heart's Electrical System. The heartbeats are triggered and regulated by the conducting system, a network of specialized muscle cells that form an independent electrical system in the heart muscles. These cells are connected by channels that pass chemically caused electrical impulses.

Click the icon to see an image of the conduction system of the heart.

Heart failure is not a disease. It is a condition or process in which the heart is unable to pump enough blood to meet the needs of the body's tissues. The heart doesn't "fail" in the sense of ceasing to beat (as occurs during a heart attack). Rather, it weakens, usually over the course of months or years, so that it is unable to pump out all the blood that enters its chambers. As a result, fluids tend to build up in the lungs and tissues, causing congestion. This condition used to be called "congestive heart failure," but the name was officially changed to heart failure in 2005.

Ways the Heart Can Fail. Heart failure can occur in several ways:

The muscles of the heart pumps (ventricles) become thin and weakened. They stretch (dilate) to the extent that they cannot pump the blood with enough force to reach all the body's tissues.
The heart muscles stiffen or thicken. Here, they lose elasticity and cannot relax. Insufficient blood enters the chamber, so not enough blood is pumped out into the body to serve its needs.
Sometimes the valves of the heart are abnormal. (Valves open or close to control the flow of blood entering or leaving the heart). They may narrow, such as in aortic stenosis, causing a back up of blood, or they may close improperly so that blood leaks back into the heart. The mitral valve (which regulates blood flow between the two chambers on the left side of the heart) often becomes leaky in severe heart failure -- a condition called mitral regurgitation.

Click the icon to see an image of the valves of the heart.

The very mechanisms that the body uses to compensate for inefficient heart pumping can, over time, change the architecture of the heart (called remodeling) and finally lead to irreversible problems.

The specific effects of heart failure on the body depend on whether it occurs on the left or right side. Over time, however, in either form of heart failure, the organs in the body do not receive enough oxygen and nutrients, and the body's wastes are removed slowly. Eventually, vital systems break down.

Failure on the Left Side (Left-Ventricular Heart Failure). Failure on the left side of the heart is more common than failure on the right side. The failure can be a result of abnormal systolic (contraction) or diastolic (relaxation) action:

Systolic. Systolic heart failure is a pumping problem. In systolic failure, the heart muscles weaken and cannot pump enough blood throughout the body. The left ventricle is usually stretched (dilated). Fluid backs up and accumulates in the lungs (pulmonary edema). Systolic heart failure typically occurs in men between the ages of 50 - 70 years who have had a heart attack.
Diastolic. Diastolic heart failure is a filling problem. When the left ventricle muscle becomes stiff and cannot relax properly between heartbeats, the heart cannot fill fully with blood. When this happens, fluid entering the heart backs up. This causes the veins in the body and tissues surrounding the heart to swell and become congested. Patients with diastolic failure are typically women, overweight, and elderly, and have high blood pressure and diabetes.

Failure on the Right Side (Right-Ventricular Heart Failure). Failure on the right side of the heart is most often a result of failure on the left. Because the right ventricle receives blood from the veins, failure here causes the blood to back up. As a result, the veins in the body and tissues surrounding the heart to swell. This causes swelling in the feet, ankles, legs, and abdomen.

Ejection Fraction. To help determine the severity of left-sided heart failure, doctors use an ejection fraction (EF) calculation, also called a left-ventricular ejection fraction (LVEF). This is the percentage of the blood pumped out from the left ventricle during each heartbeat. An ejection fraction of 50 - 75% is considered normal. Patients with left-ventricular heart failure are classified as either having a preserved ejection fraction (greater than 50%) or a reduced ejection fraction (less than 50%).

In general, systolic heart failure has been thought to be associated with a reduced ejection fraction, whereas diastolic heart failure was associated with a preserved (normal) ejection fraction. However, several 2006 studies indicated that diastolic heart failure can occur regardless of the ejection fraction, although it is more common in patients with a preserved ejection fraction. Mortality rates among patients with reduced LVEF and preserved LVEF are similar.

Although reduced LVEF heart failure is better studied, and its treatment goals more clearly defined, several important 2006 studies suggest that preserved LVEF heart failure is becoming increasingly common. The studies, published in the Journal of the American Medical Association and the New England Journal of Medicine, indicated that patients with preserved LVEF heart failure are more likely to be female and older, and have a history of high blood pressure and atrial fibrillation (a disturbance in heart rhythm). Experts are now urging that more studies focus on patients with preserved LVEF so that better treatment options can be established.

Causes

Heart failure has many causes and can evolve in different ways.

It can be a direct, last-stage result of heart damage from one or more of several heart or circulation diseases.
It can occur over time as the heart tries to compensate for abnormalities caused by these conditions, a condition called remodeling.

In all cases, the weaker pumping action of the heart means that less blood is sent to the kidneys. The kidneys respond by retaining water and salt. This in turn increases edema (fluid buildup) in the body, which causes widespread damage.

Uncontrolled high blood pressure (hypertension) is also a major cause of heart failure even in the absence of a heart attack. In fact, about 75% of cases of heart failure start with hypertension. It generally develops as follows:

The heart muscles thicken to make up for increased blood pressure.
The force of the heart muscle contractions weaken over time, and the muscles have difficulty relaxing. This prevents the normal filling of the heart with blood.

[See In-Depth Report #14:High blood pressure.]

Hypertension is a disorder characterized by consistently high blood pressure. Generally, high blood pressure consists of systolic blood pressure (the "top" number, which represents the pressure generated when the heart beats) higher than 140, or diastolic blood pressure (the "bottom" number, which represents the pressure in the vessels when the heart is at rest) over 90.

Coronary artery disease is the end result of a complex process called atherosclerosis (commonly called "hardening of the arteries"). It is the most common cause of heart attack and involves the build-up of unhealthy cholesterol in the arteries, with inflammation and injury in the cells of the blood vessels. The arteries narrow and become brittle. Heart failure in such cases most often results from a pumping defect in the left side of the heart. [See In-Depth Report #3: Coronary artery disease and angina ; and In-Depth Report #23: Cholesterol.]

Click the icon to see an image of atherosclerosis.

People now often survive heart attacks, but eventually many develop heart failure from the physical damage done to the heart muscles by the attack. Ironically, heart attack recovery is probably one of the major factors in the dramatic increase in heart failure cases over the past decade. On an encouraging note, however, new therapies that are reducing the severity of heart attacks may help stabilize heart failure rates. [See In-Depth Report #12: Heart attack.]

The valves of the heart control the flow of blood leaving and entering the heart. Abnormalities can cause blood to back up or leak back into the heart.

Click the icon to see an image of the heart valves.

In the past, rheumatic fever, which scars the heart valves and prevents them from closing, was a major cause of death from heart failure. Fortunately, antibiotics have relegated this disease to a minor cause of heart failure. Birth defects may also cause abnormal valvular development. Although more children born with heart defects are now living to adulthood, they still face a higher than average risk for heart failure as they age.

Cardiomyopathy is disease that damages the heart muscles and leads to heart failure. There are several different types. Injury to the heart muscles may cause the heart muscles to thin out (dilate) or become too thick (become hypertrophic). In either case, the heart doesn't pump correctly.

Dilated Cardiomyopathy. Dilated cardiomyopathy involves an enlarged heart ventricle. The muscles thin out, reducing the pumping action, usually on the left side. Although this condition is associated with genetic factors, the direct cause often is not known. (This is called idiopathic dilated cardiomyopathy.) Research strongly indicates that viruses, such as Coxsackie virus, or other infections may be at the base of this condition. Experts think that an autoimmune response occurs in which infection-fighting antibodies attack a person's own proteins in the heart, mistaking them for foreign substances.

Click the icon to see an image of dilated cardiomyopathy.

Hypertrophic Cardiomyopathy. In hypertrophic cardiomyopathy, the heart muscles become thick and contract with difficulty. Some research indicates that this occurs because of a genetic defect that causes a loss of power in heart muscle cells and, subsequently, lower pumping strength. To compensate for this power loss, the heart muscle cells grow. This condition, rare in the general population, is often the cause of sudden death in young athletes.

Click the icon to see an image of hypertrophic cardiomyopathy.

High blood pressure, heart attacks, or other initial processes that impair the pumping actions of the heart trigger a number of hormonal and neurochemical mechanisms to correct imbalances in pressure and blood flow. Unfortunately, while these corrective responses help in the short term, they increase the work of the heart. The mechanisms are now viewed as major contributors to the end stages of heart failure. Some are described briefly in the following sections.

Remodeling. The heart responds to high blood pressure and overload by enlarging in order to increase blood input. This leads to structural damage called remodeling:

In order to accommodate the increased blood input, the heart muscle cells elongate. The muscular walls of the heart that they form become thinner and inefficient.
The muscle cells undergo other changes that result in calcium loss. Calcium is a mineral that is crucial for healthy heart contractions.
The thinner heart muscles and the impaired heart contractions further weaken the heart's pump.
Mitral valve regurgitation is a possible outcome of remodeling. The mitral valve regulates blood flow between the two chambers on the left side of the heart. In response to remodeling, the structural changes in the heart may distort the mitral valve so that the blood leaks backward into the left atrium of the heart instead of flowing out into the body's circulation.
These changes are generally irreversible, although heart pacemakers and certain drugs, including beta-blockers and ACE inhibitors, may reverse some of the remodeling in some patients.

Activation of the Sympathetic Nervous System. The sympathetic nervous system consists of the nerve cells that automatically govern and regulate the beating heart.

This nervous system responds to the failing heart pump by signaling the release of stress hormones, in particular a powerful one called norepinephrine.
These hormones flood the heart, causing it to beat even faster.
These rapid heart beats, although intended to accommodate the weakened pumping actions, only accelerate the damage.

The Renin-Angiotensin-Aldosterone System (RAAS). The renin-angiotensin-aldosterone system (RAAS) is a group of hormones that are responsible for the opening and narrowing of blood vessels and retention of fluids. They also affect cell development in the heart.

The RAAS hormones are called into action by the failing heart.
They respond to the lower blood volume of the weakened heart by constricting the blood vessels and retaining fluids and sodium.
The heart then works harder to pump blood through these narrowed vessels. Blood pressure, then, is forced to increase, which creates a vicious cycle.

Immune System Response. The immune system may also compound the damage. In response to injury in the heart muscle cells or in other parts of the body that occurs as the heart fails, the immune system releases factors intended to protect these areas.

In excess, however, they can cause inflammation and damage.

The most important of these factors are called cytokines. Active cytokines include tumor necrosis factor (TNF) and possibly interleukins 1 and 6.
High levels of these cytokines have been observed in patients with the most severe classes of heart failure.
They may play an important role in the process leading to remodeling. High levels of these cytokines may actually trigger muscle cell growth and enlargement of the heart.

Other Players. Other molecules or compounds have been identified that might play a positive or negative role in the process of the failing heart.

Natriuretic peptides are a family of compounds released to counterbalance the effects of RAAS. Atrial natriuretic peptide (ANP) is a specific member of this family that opens blood vessels and counteracts the sodium-retaining properties of aldosterone (one of the RAAS hormones). It is of particular interest to researchers looking for new treatments.
Endothelin is a powerful protein involved in blood vessel constriction, cell proliferation and build-up, and other negative effects on the heart.
Nitric oxide is important for blood vessel dilation and elasticity.

Symptoms

Many symptoms of heart failure result from the congestion that develops as fluid backs up into the lungs and leaks into the tissues. Other symptoms result from inadequate delivery of oxygen-rich blood to the body's tissues. Since heart failure can progress rapidly, it is essential to consult a doctor immediately if any of the following symptoms are detected.

Fatigue and shortness of breath (dyspnea) are the first symptoms. They are caused by fluid in the lungs. Patients typically report that they feel out of breath after mild exertion. It is unlike the breathlessness of angina, which feels like a heavy weight pressing on the chest.

Fluid retention. Patients may complain of leg or abdominal swelling.
Wheezing or cough. Patients may have asthma-like wheezing or a dry hacking cough that occurs a few hours after lying down, but then stops after the patient sits up.
Central sleep apnea. This disorder results when the brain fails to signal the muscles to breathe during sleep. It occurs in up to half of people with heart failure. Sleep apnea causes disordered breathing at night. If heart failure progresses, the apnea may be so acute that a person, unable to breathe, may awaken from sleep in panic.
Loss of muscle mass. Over time, patients may lose muscle weight due to low cardiac output.

Ultimately, fluid in the lungs may build up. This is called pulmonary edema. When this happens, symptoms become more severe.

In addition to shortness of breath, patients sometimes have a cough that produces a pinkish froth.
Patients may experience a bubbling sensation in the lungs and feel as if they are drowning.
Typically, the skin is clammy and pale, sometimes nearly blue. This is a life-threatening situation, and the patient must go immediately to an emergency room.

Fatigue. As with left-side heart failure, an early symptom of right-side (right-ventricular) failure is extreme tiredness.
Fluid accumulation. This first occurs in the feet, then the ankles and legs, and finally in the abdomen. The liver may also be enlarged.
Weight gain. Although appetites are often depressed, patients with heart failure gain weight because they retain salt and water.
Loss of muscle mass.

Risk Factors

Nearly 5 million Americans currently suffer from heart failure. About 550,000 new cases of heart failure are now diagnosed each year. In 1970 there were only 250,000 new cases, so the annual numbers have risen dramatically. Such numbers represent an increasingly older population. Although there has been a dramatic increase over the last several decades in the number of people who suffer from heart failure, survival rates have been improving greatly.

Coronary artery disease and high blood pressure are the main causes of heart failure. Other diseases that damage or weaken the heart muscle or heart valves can also cause heart failure. Heart failure is most common in people over age 65, African-Americans, and women.

Heart failure is the most common reason for hospitalization in the elderly, and as the population ages, the incidence of heart failure is rising dramatically. According to one report, it occurs at a rate of about 10 in 1,000 people after age 65. The positive implication is, however, that people are living longer with heart failure.

Men are at higher risk for heart failure than women, although the difference narrows with age. Women also have a better survival rate than men do when heart failure is caused by valvular heart disease, high blood pressure, or alcohol abuse. (Some studies indicate that this is because men may be more susceptible to the process of heart muscle-cell remodeling, a damaging effect of hypertension.)

The survival rates of women and men are more similar, however, when heart failure evolves from coronary artery disease or heart attack. Women are much more likely to develop heart failure after a heart attack than men. In such cases, some evidence suggests that the reasons for this may include less aggressive approach to treatment for the initial heart conditions.

African-Americans are at higher risk for heart failure than Caucasians, and studies have reported that they tend to do much worse. In a 2003 study, however, in which Caucasians and African-Americans had comparable treatment, African-Americans actually had lower 1-year mortality rates (with slightly higher rates of rehospitalizations). Some evidence suggests that African-Americans are more often likely than Caucasians to develop diastolic heart failure (a failure of the heart muscle to relax normally), which is often a precursor to systolic heart failure (impaired ability to pump blood). Caucasians tend to develop systolic heart failure first.

According to a 2006 New England Journal of Medicine study, people whose parents had heart failure have a greatly increased risk of developing heart failure, particularly left-ventricular systolic heart failure. Earlier studies have suggested that a family history of early heart failure caused by cardiomyopathies (diseases that damage the heart muscle) may also predispose people to the disease. Researchers are looking for changes in specific genes that might regulate systems involved in heart failure and so increase susceptibility in certain populations.

Chronic alcohol abuse can damage the heart muscles, can cause hypertension, and may prove to be one cause of idiopathic dilated cardiomyopathy. Moderate alcohol consumption, on the other hand (generally defined as 2 drinks a day for men and 1 drink for women), may protect against heart failure. Non-drinkers, though, are not advised to begin drinking.

Coronary artery disease. More than 60% of heart failure cases may be due to coronary artery disease and its risk factors (smoking, sedentary living, obesity).
Heart attack. The injured heart after an attack is at high risk for failure. The improved survival rates from heart attack over the past decades have actually been responsible for the dramatic increase in heart failure rates.
High blood pressure. Hypertension is a significant risk factor and is present in 75% of patients with heart failure.
Diabetes. People with diabetes are at high risk for heart failure, particularly if they also have coronary artery disease. Even blood sugar abnormalities that precede diabetes increase the risk.
Obesity. Obesity is associated with both hypertension and type 2 diabetes, conditions that place people at risk for heart failure. Evidence strongly suggests that obesity itself is a major risk factor for heart failure, particularly in women. In a major 2002 study, about 14% of heart failure cases in women and 11% in men could be attributed to obesity. Both overweight and obese women had a significantly higher than normal risk for heart failure. Only obesity led to a significant risk in men.
Valvular heart disease. Specific valvular conditions that are common in patients with heart failure include aortic stenosis and mitral regurgitation.
Severe emphysema. Chronic obstructive pulmonary disease is a major risk factor for right-side heart failure.

Emphysema is a lung disease involving damage to the air sacs (alveoli).There is progressive destruction of alveoli and the surrounding tissue that supports them. As the disease gets worse, large air cysts take the place of normal lung tissue. Air is trapped in the lungs.

Cardiomyopathies due to various causes, including birth defects, HIV infection, and other infections.
In rare cases, heart failure can occur in women around the time of childbirth, a condition called peripartum cardiomyopathy.

Click the icon to see an image of peripartum cardiomyopathy.

An overactive thyroid (hyperthyroidism) or underactive thyroid (hypothyroidism) can have severe effects on the heart and increase the risk for heart failure.
Amyloidosis. A starchy protein (amyloid) that builds up in tissues and organs can lead to heart failure.
Surviving childhood cancers. Survivors face a risk for developing heart failure in later years, particularly those treated with chemotherapies such as doxorubicin. Newer cancer advances may reduce this risk.
Acute myocarditis. This rare viral infection involves the heart muscle and can produce temporary but potentially life-threatening heart failure.

Long-term use of anabolic steroids (male hormones used to build muscle mass) increases the risk for heart failure. The drug itraconazole (Sporanox), used to treat skin, nail, or other fungal infections, has been linked to heart failure. In 2006, the FDA warned that the cancer drug imatinib (Gleevec) has been associated with heart failure cases. Most patients who took imatinib and developed heart failure had a history of diabetes, high blood pressure, or heart disease.

Complications

At least 20% of hospitalizations in older adults are due to heart failure. For people over age 65, it is the number one cause of death, with nearly 290,000 people dying from this disease each year. Nevertheless, although heart failure produces very high mortality rates, treatment advances in hypertension, heart surgeries, and heart pacemakers are improving survival rates.

The most serious and life-threatening complications of heart failure are:

Arrhythmias (irregular beatings of the heart)
Acute pulmonary edema (fluid in the lungs)

Left-side heart failure tends to be more severe than right-side heart failure, particularly when it is associated with the following conditions:

Coronary artery disease
HIV infection
Amyloidosis (a metabolic disorder than can lead to organ failure)
Chemotherapy that uses the drug doxorubicin

The outlook is better in patients with left-side heart failure associated with:

Idiopathic cardiomyopathy (the cause is unknown)
Heart failure due to childbirth

Weight Issues. If patients with heart failure are overweight to begin with, their condition tends to be more severe. Once heart failure develops, however, an important indicator of a worsening condition is the occurrence of cardiac cachexia, which is unintentional rapid weight loss (a loss of at least 7.5% of normal weight within 6 months).

Impaired Kidney Function. Heart failure weakens the heart’s ability to pump blood. This can affect other parts of the body including the kidneys (which in turn can lead to fluid build-up). Decreased kidney function is common in patients with heart failure, both as a complication of heart failure and as a complication of other diseases associated with heart failure (such as diabetes). Studies suggest that in patients with heart failure, impaired kidney function increases the risks for heart complications including hospitalization and death.

Congestion (Fluid Buildup). In left-sided heart failure, fluid builds up first in the lungs. Later, as right-sided heart failure develops, fluid builds up in the legs, feet, and abdomen. According to one study, patients with severe symptoms who had congestion (fluid buildup) had poorer survival rates than those without fluid build up. Two-year survival rates were 87% in those who were congestion-free compared to 41 - 67% in patients with various signs of congestion (such as swelling, difficulty breathing when lying down, and weight gain from fluid buildup). Fluid buildup is treated with lifestyle measures, such as reducing salt in the diet, as well as drugs, such as diuretics. Sometimes, for hospitalized patients, an ultrafiltration device is used to remove excess water and salt from the body (see Surgery and Devices).

Atrial Fibrillation. This abnormal rhythm is a rapid quivering beat in the upper chambers of the heart. It is a major cause of stroke and very dangerous in people with heart failure.

Left Bundle Branch Block. Left bundle-branch block is an abnormality in electrical conduction in the heart. It develops in about 30% of patients with heart failure and is a major risk factor for serious adverse heart events.

Systolic Blood Pressure. An important 2006 study indicated that patients who arrive at the hospital with heart failure and low systolic blood pressure have a poorer prognosis than those who arrive with high systolic blood pressure. Researchers think that high systolic blood pressure may be a signal for unique clinical characteristics.

Sleep Apnea. With this disorder, a person stops breathing during the night, perhaps hundreds of times, usually for periods of 10 seconds or longer. It is a very strong risk factor for heart failure, and patients with apnea have a higher mortality rate than those who do not.

Depression. The presence of depression indicates a poorer outlook for the heart. Studies indicate that depression may have adverse biologic effects on the immune and nervous systems, blood clotting, blood pressure, blood vessels, and heart rhythms.

Seasonal and Daily Patterns. Studies have shown that more emergency room visits and higher mortality rates occur during winter months and on Mondays in patients with heart failure. One factor in this higher risk may be sudden and strenuous exertion, particularly snow-shoveling, which is associated with a risk for heart attack in people with heart problems.

Diagnosis

Doctors can often make a preliminary diagnosis of heart failure by medical history and careful physical examination.

The medical history risks for heart failure include:

High blood pressure
Diabetes
Poor cholesterol levels
Heart or peripheral vascular disease
Sleep apnea
Thyroid problems
Obesity
Lifestyle factors (smoking, alcohol use)

The following physical signs, along with medical history, strongly suggest heart failure:

Enlarged heart
Irregular heart sounds
Abnormal sounds in the lungs
Swelling or tenderness of the liver
Fluid retention in legs and abdomen
Elevation of pressure in the veins of the neck

Both blood and urine tests are used to check for problems with the liver and kidneys and to detect signs of diabetes. Lab tests can measure:

Cholesterol and lipid levels
Blood sugar (glucose)
Red blood cell count (to rule out anemia)
Blood sugar levels
Thyroid function

Urine tests can be used to assess the presence of a protein called albumin. Albumin in the urine is usually a sign of kidney disease, but even tiny amounts (microalbumin) signal an increased risk for heart failure in people with and without diabetes.

The exercise stress test measures heart rate, blood pressure, and oxygen consumption while a patient is performing physically, usually walking on a treadmill. It is an important diagnostic component in determining heart failure symptoms. Doctors also use exercise tests to gauge long-term outlook and the effects of particular treatments.

An electrocardiogram (ECG) cannot diagnose heart failure, but it can indicate underlying heart problems. It is sometimes called an EKG. The test is simple and painless to perform. It may be used to diagnose:

Enlargement of the heart muscle, which may help to determine long-term outlook
The presence of coronary artery disease
Abnormal cardiac rhythms. A rhythm pattern called a prolonged QT interval, for example, might predict people with heart failure who are at risk for severe complications and would need more aggressive therapies.

The major benefit of an ECG is that it can help determine which patients do not need an echocardiogram, a more accurate (but more expensive) diagnostic test.

The electrocardiogram (ECG, EKG) is used extensively to diagnose heart disease, from congenital heart disease in infants to myocardial infarction and myocarditis in adults. There are several different types of electrocardiograms.

The best diagnostic test for heart failure is echocardiography. Echocardiography is a noninvasive, entirely safe test that uses ultrasound to image the heart as it is beating. Cardiac ultrasounds provide the following information:

Accurate indications of valve function
The amount of blood flow through the heart's chambers
The location of the failure and where it has occurred

Doctors use information from the echocardiogram for calculating the ejection fraction (how much blood is pumped out during each heartbeat), which is important for determining the severity of heart failure.

Radionuclide Ventriculography. Radionuclide ventriculography is an imaging technique that uses a tiny amount of radioactive material (called a trace element). The substance is injected into a patient. As it passes through the bloodstream it is picked up on x-rays. This is a very important imaging technique for patients with heart failure. It is very sensitive in revealing heart enlargement or evidence of fluid accumulation around the heart and lungs. It is typically used in concert with angiography.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) scans that use contrast dyes to improve resolution are proving helpful for identifying patients with irreversible heart damage. Damage appears as very bright areas on the scan.

Doctors may recommend angiography if they suspect that blockage of the arteries is contributing to heart failure. This procedure is invasive.

A thin tube called a catheter is inserted into one of the large arteries in the arm or leg.
It is gently guided through the artery until it reaches the heart.
The catheter measures internal blood pressure at various locations, giving the doctor a comprehensive picture of the extent and nature of the heart failure.
Dye is then injected through the tube into the heart.
X-rays called angiograms are taken as the dye moves through the heart and arteries.
These images help locate problems in the heart's pumping action or blockage in the arteries.

Major complications of angiography are rare (about 0.1%) but can occur. They include stroke, heart attacks, and kidney damage. The more experienced the medical center in this procedure, the lower the risk.

Click the icon to see an image of cardiac catheterization.

Researchers are looking for biologic factors (called biomarkers) that will confirm a diagnosis or suggest a better or worse prognosis. Many are under investigation.

Tumor Necrosis Factor. Elevated levels of tumor necrosis factor (TNF) may be a very strong and accurate predictor of a poor outlook. This immune substance is known to be a potent substance in the inflammatory process.

Natriuretic Peptides. Natriuretic peptides are substances that help regulate salt and water balance in the body. Levels of these peptides increase as heart failure symptoms worsen. Blood tests for brain natriuretic peptide (BNP) are now used to help diagnose heart failure. There are two types of BNP tests: The enzyme-linked immunosorbent assay (ELISA) and the radioimmunosorbent assay (RIA). Research from 2006 suggested that the ELISA test may be more accurate, but it is also more expensive.

BNP testing can be very helpful in correctly diagnosing heart failure in patients who come to the emergency room complaining of shortness of breath (dyspnea). A 2006 study indicated that this test can also help predict which patients with dyspnea are at greatest risk of dying within a year from heart failure.

Brain Metabolites. High levels of a compound called N-acetylaspartate, generated as a byproduct of chemical processes in the brain, may indicate a poor outlook.

Treatment

Guidelines for evaluating the severity of heart failure and determining treatments use a staging system that is similar to the one used for major cancers:

Stage A: Patients are at high risk for heart failure, but there is no evidence of structural damage to the heart. Risk factors include high blood pressure, heart diseases, diabetes, obesity, metabolic syndrome, and previous use of medications that damage the heart (such as some chemotherapy).
Stage B: Patients have a structural heart abnormality but no symptoms of heart failure. Abnormalities include left ventricular hypertrophy and low ejection fraction, asymptomatic valvular heart disease, and a previous heart attack.
Stage C: Patients have a structural abnormality and current or previous symptoms of heart failure, including shortness of breath, fatigue, and difficulty exercising.
Stage D: Patients have end-stage symptoms that do not respond to standard treatments.

According to expert guidelines, the first step in managing heart failure is to treat the primary conditions causing or complicating heart failure. These include:

Coronary artery disease. Treatment includes a healthy diet, exercise, smoking cessation, medications, and, possibly, bypass or angioplasty. [See In-Depth Report #3: Coronary artery disease and angina.]
Cholesterol and lipid problems. Treatments include lifestyle management and medications, especially statins. [See In-Depth Report #23: Cholesterol.]
High blood pressure. A normal systolic blood pressure is considered below 120 mm Hg, and a normal diastolic blood pressure is below 80 mm Hg. Patients with diabetes or chronic kidney disease should maintain blood pressure readings of 130/80 or less, while other patients with high blood pressure should aim for readings no higher than 140/90. Effective reduction of blood pressure reduces the risk of heart failure by 30 - 50%. [See In-Depth Report #14: High blood pressure.]
Diabetes. Treating diabetes is extremely important for reducing the risk for heart disease. ACE inhibitors are especially beneficial, particularly for people with diabetes. Recent research suggests that metformin, a drug used to treat diabetes, may also help prevent heart failure. [See In-Depth Report #60: Diabetes - type 2; and In-Depth Report #9: Diabetes - type 1.]
Valvular abnormalities such as aortic stenosis and mitral regurgitation. Surgery may be required.
Abnormal health rhythms (arrhythmias). Ventricular assisted devices, notably biventricular pacers (BVPs), are proving to be important in preventing hospitalizations for patients with these conditions.
Anemia. Giving erythropoietin (EPO) and iron injections to patients with heart failure and underlying anemia not only reverses the anemia, but may markedly improve heart symptoms as well. [See In-Depth Report #57: Anemia.]
Thyroid function. Various medications are used to treat overactive thyroid (hyperthyroidism) or underactive thyroid (hypothyroidism). [See In-Depth Report #38: Hypothyroidism.]
Sleep apnea. Continuous positive airway pressure (CPAP) is an effective treatment for sleep apnea. CPAP may help reduce systolic blood pressure and improve left ventricular systolic function. [See In-Depth Report#65:Sleep apnea.]

Click the icon to see an image of CPAP treatment.

Treatments for patients with Stage B risk for heart failure include all of the treatments recommended in Stage A. In addition, the following types of drugs and devices may be recommended for some patients. These include:

Angiotensin-converting enzyme (ACE) inhibitors for patients with a recent or past history of heart attack. Also for patients who have not had a heart attack if they have a low left ventricular ejection fraction (LVEF) and no heart failure symptoms. A reduced LVEF indicates that the heart’s left ventricle is not pumping blood efficiently.
Beta blockers for patients with a recent or past history of heart attack. Also for patients who have not had a heart attack but who do have reduced LVEF without heart failure symptoms.
Angiotensin-receptor blockers (ARBs) for patients who have had a heart attack or have low LVEF, but who cannot take ACE inhibitors.
Implantable defibrillators for patients who have weakened heart pumps (ischemic cardiomyopathy), who had a heart attack more than 40 days prior, and who have low LVEF.

Treat conditions as recommended in Stage A plus:

Restrict dietary salt. Lowering salt in the diet can help diuretics work better.
ACE inhibitors, beta blockers, and diuretics are recommended for most patients.
ARBs are recommended for patients who cannot tolerate ACE inhibitors.
Aldosterone inhibitors or digitalis may be used for some patients.
A hydralazine and nitrate combination (BiDil) may be used for African-American patients who are taking an ACE inhibitor and beta blocker and who still have heart failure symptoms.
Avoid drugs that can worsen heart failure symptoms. These include nonsteroidal anti-inflammatory drugs (NSAIDs), most calcium channel blockers, and most drugs used to treat irregular heart rhythms (arrhythmia).
Exercise training for appropriate patients.
Biventricular pacemakers and implantable defibrillators for some patients.

Treatment includes appropriate measures used for Stages A, B, and C plus:

Heart transplantation referral for appropriate patients.
Left-ventricular assist devices (LVADs) as permanent therapy for patients who are not candidates for heart transplants. LVADs are surgically implanted to help pump blood through the body.
Hospice and end-of-life care information for patients and families.

Medications

Many different medications are used in the treatment of heart failure. They include:

Angiotensin-converting enzyme (ACE) inhibitors
Angiotensin-receptor blockers (ARBs)
Beta blockers
Diuretics
Aldosterone blockers
Digitalis
Hydralazine and nitrates
Statins
Nesiritide (Natrecor)
Aspirin

Angiotensin-converting enzyme (ACE) inhibitors are among the most important drugs for treating patients with heart failure. ACE inhibitors open blood vessels and decrease the workload of the heart. They are used to treat high blood pressure but can also help improve heart and lung muscle function. Major studies suggest that ACE inhibitors may reduce the risk of death, heart attack, and hospital admissions by 28% in patients with existing heart failure.

ACE inhibitors are particularly important for patients with diabetes. A large study reported that patients with diabetes who took these drugs had fewer heart attacks and lower overall mortality rates than patients who took other types of high blood pressure medications. ACE inhibitors may also help slow progression of kidney disease, in addition to controlling blood pressure.

Doctors sometimes avoid giving aspirin to patients who are taking ACE inhibitors due to concerns that this drug combination can cause kidney problems. A 2005 study of patients with both coronary artery disease and heart failure indicated that an aspirin and ACE inhibitor combination is not harmful, and that aspirin can significantly reduce mortality risk for these patients.

Choosing an ACE inhibitor. ACE inhibitors treat Stage A high-risk conditions such as high blood pressure, heart disease, and diabetic nerve disorders (neuropathy). They also treat Stage B patients who have had a heart attack or who have left ventricular systolic disorder, and Stage C patients with heart failure. Specific brands and stages include:

Benazepril (Lotrel) -- (Stage A)
Captopril (Capoten) -- (Stages A, B, C)
Enalapril (Vasotec) -- (Stages A, B, C)
Fosinopril (Monopril) -- (Stages A, C)
Lisinopril (Prinivil, Zestril) -- (Stages A, B, C)
Moexipril (Univasc) -- (Stage A)
Perindopril (Aceon) -- (Stage A)
Quinapril (Accupril) -- (Stages A, C)
Ramipril (Altace) -- (Stages A, B, C)
Trandolapril (Mavik) -- (Stages A, B, C)

Side Effects of ACE Inhibitors:

Low blood pressure is the main side effect of ACE inhibitors. This can be severe in some patients, especially at the start of therapy.
Irritating cough is a common side effect, which some people find intolerable. Although all ACE inhibitors can have this side effect, sometimes switching to another brand will reduce this symptom.
Although ACE inhibitors can protect against kidney disease, they also increase potassium retention in the kidneys. This increases the risk for cardiac arrest if potassium levels become too high. Because of this action, they are not generally given with potassium-sparing diuretics or potassium supplements.
A rare but severe side effect is granulocytopenia, which is an extreme reduction in infection-fighting white blood cells.
In very rare cases, patients suffer a sudden and severe allergic reaction called angioedema that causes swelling in the eyes and mouth and may close off the throat.

Patients who have difficulty tolerating ACE inhibitor side effects are usually switched to an angiotensin-receptor blocker (ARB).

ARBs, also known as angiotensin II receptor antagonists, are similar to ACE inhibitors in their ability to open blood vessels and lower blood pressure. They may have fewer or less-severe side effects than ACE inhibitors, especially coughing, and are sometimes prescribed as an alternative to ACE inhibitors. Some patients with heart failure take an ACE inhibitor along with an ARB.

Brands and Indications. ARBs are used to treat Stage A high-risk conditions such as high blood pressure and diabetic nerve disorders (neuropathy). They are also used to treat Stage B patients who have had a heart attack or who have left ventricular systolic disorder, and Stage C patients with heart failure. Specific brands, and the stage of heart failure they are used for, are listed below.

Candesartan (Atacand) -- (Stages A, C)
Eprosartan (Teveten) -- (Stage A)
Irbesartan (Avapro) -- (Stage A)
Losartan (Cozaar) -- (Stages A, B)
Olmesartan (Benicar) -- (Stage A)
Telmisartan (Micardis) -- (Stage A)
Valsartan (Diovan) -- (Stages A, B, C)

Common Side Effects

Low blood pressure
Dizziness and lightheadedness
Raised potassium levels
Drowsiness

Beta blockers are almost always used in combination with other drugs, such as ACE inhibitors and diuretics. They help slow heart rate and lower blood pressure. Research presented at the 2006 American College of Cardiology meeting indicated that beta-blockers are an important treatment for most patients with left ventricular heart failure. Data from the study found that the beta blocker carvedilol (Coreg) significantly lowered the risk of death or rehospitalization within 3 - 6 months after hospital discharge.

Beta blockers can help patients with heart failure by:

Treating high blood pressure, angina, arrhythmias, and preventing heart attack in high-risk patients.
Preventing left ventricular remodeling in patients with enlarged heart chambers and weakened heart muscles (dilated cardiomyopathy), and in those who have suffered a first heart attack.
Blocking inflammatory immune factors called cytokines, including tumor necrosis factor (TNF). TNF may play a key role in the process leading to heart failure.
Preventing norepinephrine (adrenaline) from binding to heart cells. Elevated levels of norepinephrine, a stress hormone, can overstimulate the failing heart and are associated with severe heart failure.

Brands and Indications. Beta blockers treat Stage A high blood pressure. They are also treat Stage B patients (both those who have had a heart attack and those who have not had a heart attack but who have heart damage). Recent guidelines identify three drugs best for treating Stage C patients with heart failure. Specific brands and stages include:

Acebutolol (Sectral) -- (Stage A)
Atenolol (Tenormin) -- (Stages A, B)
Betaxolol (Kerlone) -- (Stage A)
Bisoprolol (Zebeta) -- (Stages A, C)
Cartelol (Cartrol) -- (Stage A)
Carvedilol (Coreg) -- (Stages A, B, C)
Labetalol (Trandate) -- (Stage A)
Metoprolol succinate (Toprol XL) -- (Stages A, C)
Metoprolol tartrate (Lopressor) -- (Stages A, B)
Nadolol (Corgard) -- (Stage A)
Penbutolol (Levatol) -- (Stage A)
Pindolol (Visken) -- (Stage A)
Propranolol (Inderal) -- (Stages A, B)
Timolol (Blocadren, Timolide) -- (Stages A, B)

Beta Blocker Concerns

Do not abruptly stop taking these drugs. The sudden withdrawal of beta blockers can rapidly increase heart rate and blood pressure. Your doctor may want you to slowly decrease the dose before stopping completely.
Beta blockers are categorized as non-selective or selective. Non-selective beta blockers such as carvedilol and propranolol can narrow bronchial airways. Patients with asthma, emphysema, or chronic bronchitis should not use these beta blockers.
Beta blockers can lower HDL (“good”) cholesterol.
These drugs can hide warning signs of low blood sugar (hypoglycemia) in patients with diabetes.
Beta blockers are usually used in combination with ACE inhibitors, but the two drugs are not started at the same time. Research presented at the 2005 European Society of Cardiology meeting indicates that either a beta blocker or an ACE inhibitor can be prescribed at first, and the other drug added on later.

Common Side Effects

Fatigue and lethargy
Vivid dreams and nightmares
Depression
Memory loss
Dizziness and lightheadedness
Reduced ability to exercise
Coldness in extremities (legs, toes, arms, hands)

Check with your doctor about any side effects. Do not stop taking these drugs on your own.

Diuretics cause the kidneys to rid the body of excess salt and water. Fluid retention is a major symptom of heart failure. Aggressive use of diuretics can help eliminate excess body fluids, while reducing hospitalizations and improving exercise capacity. These drugs are also important to help prevent heart failure in patients with high blood pressure. In addition, certain diuretics, notably spironolactone (Aldactone), block aldosterone, a hormone involved in heart failure. This drug class is beneficial for patients in late stages of heart failure (Stages C and D).

Diuretic Types and Brands. Diuretics come in many brands and are generally inexpensive. Some need to be taken once a day, some twice a day. Treatment is usually started at a low dose and gradually increased. Diuretics are virtually always used in combination with other drugs, especially ACE inhibitors and beta blockers. There are three main types of diuretics:

Potassium-sparing diuretics. These include amiloride (Midamor), spironolactone (Aldactone), and triamterene (Dyrenium).
Thiazide diuretics. These include chlorothiazide (Diuril), chlorthalidone (Hygroton), indapamide (Lozol), hydrochlorothiazide (Esidrix, HydroDiuril), and metolazone (Mykrox, Zaroxolyn).
Loop diuretics. Because loop diuretics act faster than other diuretics it is important to avoid dehydration and potassium loss. Loop diuretics include bumentanide (Bumex), furosemide (Lasix), and torsemide (Demadex).

Problems with Diuretics. Loop and thiazide diuretics deplete the body's supply of potassium, which, if left untreated, increases the risk for arrhythmias. Arrhythmias are heart rhythm disturbances that can, in rare instances, lead to cardiac arrest. In such cases, doctors will prescribe lower doses of the current diuretic, recommend potassium supplements, or use potassium-sparing diuretics either alone or in combination with a thiazide. Potassium-sparing drugs have their own risks, which include dangerously high levels of potassium in people with existing elevated levels of potassium or in those with damaged kidneys. However, all diuretics are generally more beneficial than harmful.

Common Side Effects

Fatigue
Depression and irritability
Urinary incontinence
Reduced sexual drive

Aldosterone is a hormone that is critical in controlling the body's balance of salt and water. Excessive levels may play important roles in hypertension and heart failure. Drugs that block aldosterone are prescribed for some patients with Stage C heart failure.

Spironolactone (Aldactone, Spirinol) is both a potassium-sparing diuretic and an aldosterone blocker. A major study of patients with heart failure found that spironolactone reduced death rate by 30%. Like all medications for heart failure, it must be used with care; elevated potassium levels are a potential risk of therapy.
Eplerenone (Inspra), a newer aldosterone blocker, has been specifically approved for treatment of heart failure. It is prescribed for patients who have heart failure following a heart attack. Its actions are similar to potassium-sparing diuretics and, like these drugs, it poses some risk for high potassium levels.

Digitalis is derived from the foxglove plant. It has been used to treat heart disease since the 1700s. Digoxin (Lanoxin) is the most commonly prescribed digitalis preparation. Digoxin decreases heart size and reduces certain heart rhythm disturbances (arrhythmias).

Unfortunately, digitalis does not reduce mortality rates, although it does reduce hospitalizations and worsening of heart failure. Controversy has been ongoing for more than 100 years over whether the benefits of digitalis outweigh its risks and adverse effects.

Digitalis may be useful for patients with left-ventricular systolic dysfunction who do not respond to other drugs (diuretics, ACE inhibitors). It is also used for patients who have atrial fibrillation.

Digitalis does not appear to help patients with left-ventricular diastolic heart failure. It may be harmful in patients with right-ventricular heart failure and those who stop taking digoxin after using it in combination with ACE inhibitors.

Side Effects and Problems. While digitalis is generally a safe drug, it can have toxic side effects due to overdose or other accompanying conditions. The most serious side effects are arrhythmias (abnormal heart rhythms that can be life-threatening). Early signs of toxicity may be irregular heartbeat, nausea and vomiting, stomach pain, fatigue, visual disturbances (such as yellow vision, seeing halos around lights, flickering or flashing of lights), and emotional and mental disturbances.

Many factors increase the chance for side effects.

Advanced age
Low blood potassium levels (which may be caused by diuretics)
Hypothyroidism
Anemia
Valvular heart disease
Impaired kidney function

Digitalis also interacts with many other drugs, including quinidine, amiodarone, verapamil, flecainide, amiloride, and propafenone.

A blood test that monitors drug levels in patients taking the drug can limit the rate of toxicity to about 2%. For most patients with mild-to-moderate heart failure, low-dose digoxin may be as effective as higher doses. If side effects are mild, patients should still consider continuing with digitalis if they experience other benefits.

Hydralazine and nitrates are two older drugs that help relax arteries and veins, thereby reducing the heart's workload and allowing more blood to reach the tissues. In 2005, the FDA approved BiDil, a drug that combines isosorbide dinitrate and hydralazine. BiDil is approved to specifically treat heart failure in African-Americans. African-Americans have a particularly high risk for heart failure. BiDil is the first drug approved for a specific racial group. The Food and Drug Administration (FDA) based its approval on a landmark 2004 study published in the New England Journal of Medicine, which showed that African-Americans who took the drug were 43% more likely to survive heart failure than patients who took placebo. Some experts suggest that BiDil could also benefit other racial groups.

Statins are important drugs used to lower cholesterol and to prevent heart disease leading to heart failure. These drugs include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). In 2007, the FDA approved atorvastatin to reduce the risks for hospitalization for heart failure in patients with heart disease.

In a 2006 Journal of the American Medical Association study, patients with heart failure who began taking a statin drug had a 24% lower relative risk of death and a 21% lower relative risk of hospitalization for heart failure than patient who did not take a statin. Statins appeared to help these patients regardless of whether or not they had co-existing coronary heart disease.

Aspirin is a type of non-steroid anti-inflammatory (NSAID). A 2005 study in the Journal of the American College of Cardiology indicated that aspirin is important for preventing heart failure death in patients with heart disease, and can safely be used with ACE inhibitors. However, some research has suggested that NSAIDs may increase the risk of heart failure for patients with a history of heart disease, especially when used in combination with ACE inhibitors or diuretics. Patients with heart disease should ask their doctor which NSAIDs are right for them.

Nesiritide treats patients who have arrived at a hospital with decompensated heart failure. Decompensated heart failure is a life-threatening condition in which the heart fails over the course of minutes or a few days, often as the result of a heart attack or sudden and severe heart valve problems. However, nesiritide may cause serious kidney damage.

In 2005, the FDA released recommendations from an expert panel concerning the appropriate and inappropriate use of nesiritide. The panel emphasized that nesiritide should be used to treat only patients with decompensated heart failure who have shortness of breath (dyspnea) and trouble breathing. The drug should not be a replacement for diuretics.

Despite these warnings, some doctors have prescribed nesiritide “off-label” to treat patients with severe heart failure outside of a hospital setting. Research presented at the 2007 American College of Cardiology annual conference criticized this practice by demonstrating that nesiritide plus standard treatment does not reduce the risk of heart- or kidney-related death or hospitalization. In addition, the research suggested some concerns about nesiritide’s overall safety.

Tolvaptan. Tolvaptan is an investigational drug that is being studied in combination with standard therapy for treatment of heart failure. It is especially being investigated for acute decompensated heart failure, a type of heart failure categorized by fluid build-up in the lungs (pulmonary edema) for which there are few available treatments. In patients hospitalized with heart failure, tolvaptan plus standard drugs improved breathing problems (dyspnea) and reduced fluid accumulation (edema) and body weight, according to two studies published in 2007 in the Journal of the American Medical Association. However, the drug did not appear to reduce the risk of re-hospitalization or death.

Levosimendan. Levosimendan is an experimental inotropic drug that is being investigated as a treatment for severely ill patients with heart failure. It belongs to a new class of drugs called calcium sensitizers that may help improve heart contractions and blood flow. Clinical trials suggest that levosimendan may improve survival in patients hospitalized for heart failure. The drug also appears to reduce levels of BNP (brain natriuretic peptide), a chemical marker for heart failure severity.

Prograf. Tacrolimus (Prograf) was approved in 2006 to help prevent organ rejection in patients who have received a heart transplant. The drug suppresses the immune system. Patients who receive this drug are at increased risk of developing lymphoma (a cancer of the immune system).

Surgery and Devices

Revascularization surgery helps to restore blood flow to the heart. It can treat blocked arteries in patients with coronary artery disease and may help selected patients with heart failure. Surgery types include coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI). CABG is a traditional type of open heart surgery. PCI, also called angioplasty, uses a catheter to inflate a balloon inside the artery. A metal stent may also be inserted during a PCI procedure. [See In-Depth Report#03:Coronary artery disease.]

A 2006 study suggested that early treatment with revascularization surgery may be particularly important for patients with systolic heart failure, a condition that occurs when the heart does not pump out enough blood. This condition has a very high death rate. Researchers found that CABG or PCI surgery halved the risk of dying compared to standard drug therapy. Patients in the study first underwent a positron emission tomography (PET) test to determine if they would be good candidates for surgery.

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

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

In appropriate patients, mitral valve surgery may significantly reduce the severity of heart failure. In a study of 92 patients with late-stage heart failure and faulty valves, reconstruction of the heart's mitral valve drastically improved heart function.

An experimental mesh "heart sock" is being investigated as an adjunct to mitral valve repair surgery. Research presented at the 2004 American Heart Association Scientific Sessions suggested that the device reduced the progression of heart failure and halved the need for transplant surgery. The "sock" helps realign the shape of the heart and improve heart function. To date, it has been tested in patients with dilated cardiomyopathy.

Ventricular Remodeling. Ventricular remodeling (also called partial left ventriculectomy or the Batista procedure, after its inventor) may allow some patients with dilated cardiomyopathy to avoid a heart transplant.

The procedure involves the following:

The surgeon first performs ventriculectomy, which is the removal of a section of healthy heart muscle weighing about 3 ounces.
The surgeon then reshapes the heart to a more normal size and form.
Any faulty heart valves are repaired.

Ventricular remodeling is still relatively new, and mortality rates are very high. Studies on long-term improvement are mixed. More research is needed to target the patients who would most benefit.

Patients who suffer from severe heart failure and whose symptoms do not improve with drug therapy or mechanical assistance may be candidates for heart transplantation. Some 3,600 people are awaiting a transplant, although only about 2,000 operations are performed each year.

The most important factor for heart transplant eligibility is overall health. Chronological age is less important. Most heart transplant candidates are between the ages of 50 – 64 years. About 72% of transplant patients are male, and 70% are white.

While the risks of this procedure are high, the 1-year survival rate is about 86% for men and 84% for women. The 3-year survival rate is 78% for men and 75% for women. Five years after a heart transplant, about 71% of men and 67% of women remain alive. In general, the highest risk factors for death 3 or more years after a transplant operation are coronary artery disease and the adverse effects (infection and certain cancers) of immunosuppressive drugs used in the procedure. The rejection rates in older people appear to be similar to those of younger patients.

In 2004, the FDA approved a temporary artificial heart (Syncardia) intended to keep patients alive in the hospital while they waited for a heart transplant. In 2006, the FDA approved the first permanent implantable artificial heart (AbiCor). The AbiCor is available only for patients who are not eligible for a heart transplant and who are not expected to live more than a month without medical treatment. The device requires a large chest cavity, which means that most women will not be eligible for it. Of the 14 men who have received the AbiCor, the average survival was less than 5 months after surgery. Only one patient was discharged from the hospital. The device’s manufacturer is working on a new model that it hopes will extend survival by as long as 5 years.

A growing array of heart devices and machines are changing the face of heart failure treatment. They have gained widespread acceptance for use as a bridge to transplant in patients who are on medications but still have severe symptoms and are awaiting a donor heart. Increasingly, though, doctors are exploring the possibility that such devices may be satisfactory treatments themselves, forestalling the need for a transplant altogether in some patients.

Ventricular Assist Devices (VADs). Ventricular assist devices are machines that help improve pumping actions. Several models with slightly different features are in use or under investigation. Some include the following:

Left ventricular assist device (LVAD) are used for patients whose heartbeat has slowed dangerously (a condition called bradycardia) to help take over the pumping action of the failing heart. Studies suggest that in some people the use of an LVAD may allow some of the damaged heart muscle to heal, perhaps even helping some patients avoid heart transplants. These devices are also being studied in combination with drug therapy to help recover heart function and improve patients’ chances for survival. Until recently, these machines required remaining in the hospital. Smaller battery-powered LVAD units, however, are allowing many patients to leave the hospital and are proving to be effective bridges to heart transplants in adults. The HeartMate, for example, a portable LVAD about the size of a portable CD player (2 in. by 4 in.), is implanted in the upper abdomen. The implanted device plugs into an external power base, which is used when the patient is at rest to recharge the battery and provide continuous power.
Fully implanted miniature artificial pumps that assist the heart (not replace it) are also being tested. The DeBakey ventricular assist device (VAD) for example, is a tiny heart pump that weighs less than 4 ounces. It has been approved in Europe and is being tested in the United States. The Jarvik 2000 heart pump is also showing promise.
The intra-aortic balloon pump (IABP) is helpful for maintaining heart function in people with left-side failure waiting for transplants and in those who develop a sudden and severe deterioration of heart function. The IABP is an implanted thin balloon that is usually inserted into the artery in the leg and threaded up to the aorta leading from the heart. Its pumping action is generated by inflating and deflating the balloon at certain rates. Usually, it is used only for short periods, but some studies indicate that patients may be able to use it safely for somewhat longer periods (an average duration of 23 days in one study).

There are risks involved with many of these devices, including bleeding, blood clots, and right-side heart failure. Infections are a particular hazard.

Pacers (Pacemakers). Pacers, or pacemakers, help regulate the heart’s beating action, especially when the heart beats too slowly. Biventricular pacers (BVPs) are a special type of pacemaker used for patients with heart failure. Because BVPs help the heart’s left and right chambers beat together, this treatment is called cardiac resynchronization therapy (CST). BVPs may particularly help heart failure patients who have left bundle branch block, a condition in which the electrical impulses in the heart do not follow their normal pattern. In general, BVPs are recommended for patients with moderate-to-severe heart failure. A small 2006 study suggested that a defibrillator may be better suited for patients with moderate heart failure, while indicating a BVP might be best for patients with severe heart failure.

Implantable Cardioverter-Defibrillators. Devices called implantable cardioverter-defibrillators (ICDs), which are sometimes combined with pacemakers, work well for preventing arrhythmias (abnormal heart rhythms) in heart failure patients. Studies have also found them effective in preventing sudden death from severe rhythm disturbances in patients with weakened hearts from previous arrhythmias and in patients with genetic hypertrophic cardiomyopathy. Patients who have an ICD should avoid taking fish oil supplements. A 2005 Journal of the American Medical Association study found that omega-3 fatty acid supplements may increase the risk of rapid heart beat (ventricular tachycardia) or irregular heart rhythm (ventricular fibrillation) in some of these patients.

ICDs have many benefits, and recent expert guidelines recommend that they be used in more patients with heart failure. However, in June 2005, certain ICD models and biventricular pacemaker-defibrillators were recalled by the manufacturer because of a circuitry flaw that prevents the devices from delivering therapeutic electrical shocks when needed. The problem may result in patient death. Although the FDA did not make any specific recommendations, the agency encourages patients who may have such a device to ask their doctor if they should have it removed or replaced.

In April 2006, two studies published in the Journal of the American Medical Association evaluated data concerning the safety and reliability of implantable pacemakers and defibrillators. The studies found that from 1990 – 2002, pacemakers became increasingly reliable. From 1998 – 2002, ICDs had a significantly higher rate of malfunction than pacemakers, although the reliability of ICDs appeared to improve from 2003 – 2004.

In October 2006, the U.S. Heart Rhythm Society issued recommendations for doctors, manufacturers, and the FDA to help improve communication concerning performance and recalls of ICDs and pacemakers. Experts stress that the chance of an ICD or pacemaker saving a person’s life far outweigh the possible risks of these devices failing.

Ultrafiltration devices are used in hospitals to pump excess water and salt from the body. Catheters are inserted into several of the patient’s veins. The catheters are connected to a blood filter device. Blood is withdrawn through one of the catheters and filtered in the device to remove excess fluid. The filtered blood is then returned to the patient through another catheter. A 2006 study reported that ultrafiltration devices may work better than diuretic drugs for patients with acute decompensated heart failure (ADHF). ADHF is heart failure that has rapidly deteriorated so that patients require immediate hospitalization.

Lifestyle Changes

Between 30 - 47% of patients who require hospitalization for heart failure are back in the hospital within 6 months. Many people return because of lifestyle factors such as poor diet, failure to comply with medications, and social isolation.

In one study, elderly people who had no emotional support at home had triple the risk of a heart attack after hospitalization for heart failure than those who did have such support. (Women had eight times the risk.) In another study, the greatest risk factor for death and readmission to the hospital after a first hospitalization was being single, regardless of the health of the patient at discharge. A third study confirmed that a strong marriage predicted long-term survival. Evidence continues to mount that programs that offer intensive follow-up to ensure that the patient complies with lifestyle changes and medication regimens at home are reducing rehospitalization rates and improving survival. Patients without available rehabilitation programs should seek support from local and national heart associations and groups.

Patients should weigh themselves each morning and keep a record. Any changes are important:

A sudden increase in weight of more than 2 - 3 pounds may indicate fluid accumulation and should prompt an immediate call to the doctor.
Rapid wasting weight loss over a few months is a very serious sign and may indicate the need for surgical intervention.

Whole Grains. Evidence suggests that daily consumption of whole grain foods may help prevent heart failure. In research presented at a 2007 American Heart Association conference, people who ate whole-grain breakfast cereals seven or more times a week had a 28% lower risk of developing heart failure than those who never ate these cereals.

Mediterranean Diet. Evidence suggests that the Mediterranean diet helps protect the heart and may even reduce the risk for heart failure after a first heart attack. The diet emphasizes whole grains, fish, olive oil, garlic, and moderate daily intake of wine. There are several variations to the Mediterranean diet but general recommendations include:

Limit red meats.
Limit dairy products.
Eat moderate amounts of fish and poultry. Fish is the diet’s main protein source. Some studies suggest that fish is the primary heart-protective ingredient in this diet. However, patients who have an implantable defibrillator should not take fish oil supplements. A 2005 study suggested that these supplements may worsen heart rhythm problems in some patients.
Eat plenty of fresh fruits and vegetables, nuts, legumes, beans, and whole grains.
Daily glass or two of wine. Light-to-moderate alcohol use may reduce the risk for heart failure, (but heavy alcohol consumption is a risk factor).
Plenty of fresh fruits and vegetables, as well as nuts, legumes, beans, and whole grains.

DASH Diet. The Dietary Approaches to Stop Hypertension (DASH) diet is an important lifestyle step in managing blood pressure. It may also be useful for many patients with heart failure. This diet is not only rich in important nutrients and fiber but also includes foods that contain two and a half times the amounts of electrolytes, potassium, calcium, and magnesium found in the average American diet.

Potassium-rich foods, which are important for patients with heart failure, include bananas, oranges, prunes, cantaloupes, carrots, spinach, celery, alfalfa, mushrooms, lima beans, potatoes, avocados, and broccoli. However, patients who take potassium-sparing diuretics or ACE inhibitors, and those with kidney dysfunction, may have to restrict their potassium intake.

The DASH diet is rich in whole grains and fresh fruits and vegetables. It stresses avoiding saturated fats, as any healthy diet does, although it includes calcium-rich dairy products that are non- or low-fat. When choosing fats, the diet recommends monounsaturated oils such as olive or canola oil.

Salt Restriction. People with high blood pressure are generally urged to restrict salt, although certain people may be more susceptible to its effects. For example, a high intake of salt may be an independent risk factor for the development of heart failure in people who are overweight. All patients with heart failure should limit their salt intake, and in severe cases, very stringent salt restriction may be necessary. Patients should not add salt to their cooking and their meals. They should also avoid foods high in sodium. These salty foods include ham, bacon, hot dogs, lunch meats, prepared snack foods, dry cereal, cheese, canned soups, soy sauce, and condiments. Some patients may need to reduce their water intake as well. People with high cholesterol levels or diabetes require additional dietary precautions. [See In-Depth Report #43: Heart-healthy diet. ]

People with heart failure used to be discouraged from exercising. Now, experts think that exercise, when performed under medical supervision, is extremely important for many patients with stable conditions. Studies have reported that patients with stable conditions who engage in regular moderate exercise (three times a week) experience a better quality of life and lower mortality rates than those who do not exercise.

The following guidelines are critical:

Experts warn that exercise is not appropriate for all patients with heart failure. If you have heart failure, always consult your doctor before starting an exercise program.
People who are approved for, but not used to, exercise should start with 5 - 15 minutes of easy exercise with frequent breaks. Although the goal is to build up to 30 - 45 minutes of walking, swimming, or low-impact aerobic exercises three to five times every week, even shorter times spent exercising are useful.

Studies report benefits from specific exercises:

Progressive strength training may be particularly useful for patients with heart failure since it strengthens muscles, which commonly deteriorate in this disorder. Strength training typically uses light weights, weight machines, or even the body's weight (leg raises or sit-ups, for example). Even performing daily handgrip exercises can improve blood flow through the arteries.
Patients who exercise regularly using supervised treadmill and stationary-bicycle exercises can increase their exercise capacity by 14 - 36%. In one study, patients as old as 91 years increased their oxygen consumption significantly after 6 months of supervised treadmill and stationary bicycle exercises. Exercising the legs may help correct problems in heart muscles. In one study, patients who did leg extension exercises for 8 weeks had higher levels of an enzyme involved in forming new blood vessels. Exercise has also been associated with reduced inflammation in blood vessels.
Dancing may be a fun and beneficial alternative to standard aerobic exercise, according to research presented at the 2006 annual meeting of the American Heart Association. In a study of patients with stable chronic heart failure, dancing helped improve cardiopulmonary fitness, arterial elasticity, and quality of life. Patients in the study danced fast and slow waltzes for 21 minutes, three times a week.

Bed rest may be required in cases of severe heart failure. To reduce congestion in the lungs, the patient's upper body should be elevated. For most patients, resting in an armchair is better than lying in bed. Relaxing and contracting leg muscles is important to prevent clots. As the patient improves, a doctor will progressively recommend more activity.

Experts have traditionally recommended that people with heart failure avoid warm baths, which can increase the heart rate. Some studies now report that carefully controlled bathing for short periods may not be harmful and may actually be beneficial, reducing irregular heart beats and increasing cardiac output and ejection fraction. Warm water may behave like a vasodilating drug, opening up the vessels gently and improving circulation. In clinical trials, patients sat in warm water or a dry sauna for 10 minutes, with their bodies tilted at a 45 degree angle.

Warning Note: Prolonged periods in hot or even warm conditions can be dangerous. Any patient with heart failure should consult their doctor first, not bathe unaccompanied, and be sure that the temperature does not go above 106° Fahrenheit for water bathing or 140° Fahrenheit for dry saunas.

Stress reduction techniques, such as meditation and relaxation response methods, may have direct physical benefits for lowering stress hormones. These hormones include cortisol, which suppresses the immune system, and norepinephrine (also known as adrenaline), the chemical messenger associated with heart dysfunction.

Patients with heart failure may resort to alternative remedies. Such remedies are often ineffective and may have severe or toxic effects. Of particular note for patients with heart failure is an interaction between St. John's wort (an herbal medicine used for depression) and digoxin (a heart drug). St. John's wort can significantly interfere with this drug.

Arginine. Some evidence suggests that arginine (also called L-arginine) may have some benefit. This amino acid appears to reduce endothelin, a protein that causes blood vessel constriction and is found in high amounts in patients with heart failure. It can have adverse effects, however, including gastrointestinal problems. It can also lower blood pressure and change levels of certain chemicals and electrolytes in the body. It may increase the risk for bleeding. Some people have an allergic reaction to it, which in same cases may be severe. It may worsen asthma.

Coenzyme Q10 and Vitamin E. Small studies have suggested that coenzyme Q10 (CoQ10) may help patients with heart failure, particularly when combined with vitamin E. CoQ10 is a vitamin-like substance found in organ meats and soybean oil. More recent studies, however, have found that CoQ10 and vitamin E do not help the heart or prevent heart disease. According to a 2005 Journal of the American Medical Association study, vitamin E supplements can actually increase the risk of heart failure, especially for patients with diabetes or vascular diseases.

Crataegus Extract. An herbal remedy, Crataegus Extract WS1442, which is made from the leaves of the Crataegus tree, may have antioxidant properties that can help patients with heart failure. In a study presented at the 2007 American College of Cardiology annual meeting, over 2,000 patients with severe heart failure were randomized to receive either Crataegus Extract or placebo (plus standard drug treatment) for 2 years. The researchers noted a 20% reduction in heart-related deaths among patients who received the extract, and suggested that the herb extended patients’ lives by 4 months during the first 18 months of the study.

Other Vitamins and Supplements. A wide variety of other vitamins (thiamin, B6, and C), minerals (calcium, magnesium, zinc, manganese, copper, selenium), nutritional supplements (carnitine, creatine), and herbal remedies (hawthorn) have been proposed as treatments for heart failure. None have been adequately tested. There is no evidence that a particular vitamin or supplement can cure heart failure. In any case, vitamins are best consumed through the food sources contained in a healthy diet.

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. Always check with your doctor before using any herbal remedies or dietary supplements.

Resources

www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.americanheart.org -- American Heart Association
www.acc.org -- American College of Cardiology
www.hfsa.org -- Heart Failure Society of America
www.heartfailure.org -- Heart Failure Online
www.unos.org -- United Network for Organ Sharing
www.organdonor.org -- National Transplant Society
www.organdonor.gov -- US government organ donor site

References

Ahmed A, Rich MW, Fleg JL, Zile MR, Young JB, Kitzman DW, et al. Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation. 2006 Aug 1;114(5):397-403.

Battaglia M, Pewsner D, Juni P, Egger M, Bucher HC, Bachmann LM. Accuracy of B-type natriuretic peptide tests to exclude congestive heart failure: systematic review of test accuracy studies. Arch Intern Med. 2006 May 22;166(10):1073-80.

Bhatia RS, Tu JV, Lee DS, Austin PC, Fang J, Haouzi A, et al. Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med. 2006 Jul 20;355(3):260-9.

Birks EJ, Tansley PD, Hardy J, George RS, Bowles CT, Burke M, et al. Left ventricular assist device and drug therapy for the reversal of heart failure. N Engl J Med. 2006 Nov 2;355(18):1873-84.

Bryson CL, Mukamal KJ, Mittleman MA, Fried LP, Hirsch CH, Kitzman DW, et al. The association of alcohol consumption and incident heart failure: the Cardiovascular Health Study. J Am Coll Cardiol. 2006 Jul 18;48(2):305-11.

Bursi F, Weston SA, Redfield MM, Jacobsen SJ, Pakhomov S, Nkomo VT, et al. Systolic and diastolic heart failure in the community. JAMA. 2006 Nov 8;296(18):2209-16.

Carlson MD, Wilkoff BL, Maisel WH, Carlson MD, Ellenbogen KA, Saxon LA, et al. Recommendations from the Heart Rhythm Society Task Force on Device Performance Policies and Guidelines Endorsed by the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) and the International Coalition of Pacing and Electrophysiology Organizations (COPE). Heart Rhythm. 2006 Oct;3(10):1250-73.

Davis BR, Piller LB, Cutler JA, Furberg C, Dunn K, Franklin S, et al. Role of diuretics in the prevention of heart failure: the Antihypertensive andLipid-Lowering Treatment to Prevent Heart Attack Trial. Circulation. 2006 May 9;113(18):2201-10. Epub 2006 May 1.

Gheorghiade M, Abraham WT, Albert NM, Greenberg BH, O'Connor CM, She L, et al. Systolic blood pressure at admission, clinical characteristics, and outcomes inpatients hospitalized with acute heart failure. JAMA. 2006 Nov 8;296(18):2217-26.

Gheorghiade M, Konstam MA, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heartfFailure: the EVEREST clinical status trials. JAMA. 2007 Mar 25; [Epub ahead of print]

Go AS, Lee WY, Yang J, Lo JC, Gurwitz JH. Statin therapy and risks for death and hospitalization in chronic heart failure. JAMA. 2006 Nov 1;296(17):2105-11.

Hildebrandt P. Systolic and nonsystolic heart failure: equally serious threats. JAMA. 2006 Nov 8;296(18):2259-60.

Konstam MA, Gheorghiade M, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. 2007 Mar 25; [Epub ahead of print]

Lee DS, Pencina MJ, Benjamin EJ, Wang TJ, Levy D, O'Donnell CJ, et al. Association of parental heart failure with risk of heart failure in offspring. N Engl J Med. 2006 Jul 13;355(2):138-47.Maisel WH. Pacemaker and ICD generator reliability: meta-analysis of device registries. JAMA. 2006 Apr 26;295(16):1929-34.

Maisel WH, Moynahan M, Zuckerman BD, Gross TP, Tovar OH, Tillman DB, et al. Pacemaker and ICD generator malfunctions: analysis of Food and Drug Administration annual reports. JAMA. 2006 Apr 26;295(16):1901-6.

Mueller C, Laule-Kilian K, Schindler C, Klima T, Frana B, Rodriguez D, et al. Cost-effectiveness of B-type natriuretic peptide testing in patients with acute dyspnea. Arch Intern Med. 2006 May 22;166(10):1081-7.

Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006 Jul 20;355(3):251-9.

Review Date:
4/11/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Alzheimer's disease

FitSugar — Wed, 08 Oct 2008 17:35:13 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Prevention
Symptoms
Diagnosis
Medications
Stages
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Alzheimer’s Disease Toll Increasing

More than 5 million Americans now have Alzheimer’s disease, and the number could increase to 16 million by mid-century, according to a 2007 report from the Alzheimer’s Association.

New Drug Indication

In 2006, the FDA expanded the use of donepezil (Aricept) to include treatment of people with severe dementia associated with Alzheimer’s disease. Donepezil was previously approved only for people with mild-to-moderate dementia.

Managing Psychotic and Behavioral Symptoms

Newer antipsychotic drugs are no better than placebo for controlling psychosis, aggression, and agitation in patients with Alzheimer’s disease, indicates an important study in the New England Journal of Medicine. In addition, these drugs can cause severe side effects and have been associated with increased death rate.
Non-drug approaches, such as behavioral techniques and bright light boxes, may be helpful for these patients, suggests an Archives of Internal Medicine study.

Brain Exercises Prevent Mental Decline

Cognitive training exercises that help boost memory, reasoning, and processing speed may help slow mental decline and improve functional abilities in older adults, indicates a Journal of the American Medical Association study.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Do Not Prevent Alzheimer’s

The NSAIDs naproxen (Aleve) and celecoxib (Celebrex) do not protect against Alzheimer’s disease, indicates a data analysis from a large-scale U.S. National Institutes of Health (NIH) clinical trial.

Docosahexaenoic Acid (DHA) for Alzheimer’s Prevention

DHA, an omega-3 fatty acid found in some types of fish, may lower the risk for dementia and Alzheimer’s disease as well as delay its progression. However, researchers are uncertain whether DHA dietary supplements provide the same benefits as food sources (salmon, mackerel, and other types of fatty fish). In 2007, the NIH announced the launch of a national clinical trial to evaluate whether DHA can slow cognitive and functional decline in people with mild-to-moderate Alzheimer’s disease.

Support for Caregivers

Intensive programs that combine counseling, support groups, and problem-solving techniques can dramatically improve caregivers’ quality of life and may help delay patients’ transfers to nursing homes, several recent studies suggest.

Introduction

Alzheimer's disease (AD) is a degenerative disease of the brain from which there is no recovery. The disease slowly attacks nerve cells in all parts of the cortex of the brain and some surrounding structures, thereby impairing a person's abilities to govern emotions, recognize errors and patterns, coordinate movement, and remember. Ultimately, a person with AD loses all memory and mental functioning.

The major areas of the brain have one or more specific functions.

Causes

Researchers are finding specific biologic factors involved with Alzheimer's disease. Various environmental and genetic players appear to contribute to or trigger the process by which these factors destroy nerve cells leading to this disease.

Imaging techniques in patients with Alzheimer's disease have found significant loss of cells and volume in the regions of the brain devoted to memory and higher mental functioning. Important abnormalities have specifically been observed during biopsies:

Twisted nerve cell fibers, known as neurofibrillary tangles
A sticky protein, beta amyloid

Other factors also play a role.

Click the icon to see an animation about Alzheimer's disease.

The Effects of Neurofibrillary Tangles and Beta Amyloid in Alzheimer's Disease. These biologic factors appear to be involved in the development Alzheimer's disease in the following ways:

Neurofibrillary tangles are the damaged remains of microtubules, the support structure that allows the flow of nutrients through the neurons (nerve cells). A key component in these tangled fibers is an abnormal form of the tau protein, which in its healthy version helps in the assembly of the microtubule structure. The defective tau, however, appears to block the actions of the normal version.
Beta Amyloid (also called A beta) is the second significant finding. This insoluble protein accumulates and forms sticky patches called neuritic plaque, which are found surrounded by the debris of dying nerve cells in the brains of Alzheimer's victims.
Amyloid precursor protein (APP) is a large nerve-protecting protein that is the source of beta amyloid. In Alzheimer's certain enzymes, particularly those called gamma-secretases, snip APP into beta amyloid pieces. This process is controlled by factors called presenilin proteins. (Genetic abnormalities that affect either APP or presenilin proteins occur in some inherited cases of early-onset Alzheimer's.)
High levels of beta amyloid are associated with reduced levels of the neurotransmitter acetylcholine. (Neurotransmitters are chemical messengers in the brain.) Acetylcholine is part of the cholinergic system, which is essential for memory and learning and is progressively destroyed in Alzheimer's disease.
Beta amyloid may also disrupt channels that carry sodium, potassium, and calcium. These elements serve the brain as ions, producing electric charges that must fire regularly in order for signals to pass from one nerve cell to another. If the channels that carry ions are damaged, an imbalance can interfere with nerve function and signal transmission.

Click the icon to see an image of amyloidosis.

Other Proteins. Researchers have now identified other important proteins in the areas of the brain affected by Alzheimer's disease.

ERAB (endoplasmic-reticulum associated binding protein) appears to combine with beta amyloid, which in turn attracts new beta amyloid from outside the cells. High amounts of ERAB may also enhance the nerve-destructive power of beta amyloid.
AMY plaques resemble beta amyloid so closely that researchers were able to detect them only with the use of highly sophisticated techniques.
Elevated levels of a protein called prostate apoptosis response-4 (Par-4) may cause nerve cells to self-destruct.

Researchers are also attempting to discover why beta amyloid is so toxic to nerve cells. Some researchers are focusing on two processes in the body that may be involved with Alzheimer's disease: oxidation and the inflammatory process. There is some evidence that such events can begin decades before Alzheimer's disease actually develops. One scenario for their role in Alzheimer's is as follows:

The Role of Oxidation.

As beta amyloid breaks down it releases unstable chemicals called oxygen-free radicals. Once released, oxygen-free radicals bind to other molecules through a process called oxidation.
Oxidation is the result of many common chemical processes in the body, but when oxidants are overproduced, they can cause severe damage in cells and tissue, including even affecting genetic material in cells (its DNA). Oxidation is known to play a role in many serious diseases, including coronary artery disease and cancers, and experts believe it may also contribute to Alzheimer's.

The Inflammatory Response.

One result of oxidation is the marshaling of immune factors to repair the cellular injuries it produces. Overproduction of some of these factors, however, produces the so-called inflammatory response, in which the immune process itself can actually damage the body's own cells themselves.
Principle immune cells in the brain are called macrophage/microglia (M phi). In the healthy brain, they play an important protective role against invading organisms. However, when they are activated by beta amyloid oxidation, they release toxic molecules called cytokines, which are known to cause harm. For example, significantly high levels of interleukin-6, a specific cytokine, have been detected in people with Alzheimer's.
Other inflammatory factors of specific interest in Alzheimer's research are the enzyme cyclooxygenase (COX) and its products called prostaglandins. Excess amounts of these factors may increase levels of glutamate. Glutamate is an amino acid that excites nerves and, when overproduced, is a powerful nerve-cell killer.
The inflammatory process has also been associated with the release of soluble toxins called amyloid beta-derived diffusible ligands, which some investigators believe may prove to key players in the destructive process.

Major research targets in Alzheimer's disease are the factors responsible for beta amyloid build-up and concentration in certain people and not in others. Genetic factors are believed to play a role in many cases. In 2003, the National Institute on Aging (NIA) launched the ambitious AD Genetics Initiative, a 3-year national project to bank genetic material from families who have at least two members with late-onset Alzheimer's.

The ApoE Gene and Late-Onset Alzheimer's. The major target in genetic research on late-onset Alzheimer's disease (called LOAD) has been apolipoprotein E (ApoE), which plays a role in the movement and distribution of cholesterol for repairing nerve cells during development and after injury.

The gene for ApoE comes in three major types:

ApoE4. Studies have reported the greatest deposits of beta amyloid in people with ApoE4, which is now believed to be a major risk factor for late-onset Alzheimer's. Some evidence suggests that the ApoE protein removes beta amyloid but the ApoE4 variant does so less efficiently than other ApoE types. (ApoE4 has also been studied for years as a risk factor for heart disease.)
ApoE3 and ApoE2. Fewer beta amyloid deposits have been observed in people with the ApoE3, and the fewest deposits have been observed in people with ApoE2, which may actually be protective.

People inherit a copy of one type from each parent, but Alzheimer's disease is not inevitable even in people with two copies of the ApoE4 gene. Reports vary widely in estimating the extent of risk:

People without ApoE4 have an estimated risk of between 9 - 20% for developing Alzheimer's by age 85.
In people with one copy of the gene, the risk is between 25 - 60%.
In people with two copies, the risk ranges from 50 - 90%. (Only 2% of the population carries two copies of the ApoE4 gene.)

Some researchers suspect that some specific variation of the ApoE4 gene or combinations with other genes are critical for the disease, since many people who carry the ApoE4 exhibit no signs of Alzheimer's. For example, evidence suggests that genetic factors play a role in a common subtype of late-onset Alzheimer's disease that also includes psychosis. An important 2002 genetic study has identified certain genetic linkages associated with ApoE4 that appear to play a strong role in this subtype.

Other Genetic Factors in Late-Onset Alzheimer's. Most people with late-onset Alzheimer's disease do not carry the ApoE4 gene. Increasingly, researchers believe that many cases of late-onset Alzheimer's result from a combination of genetic factors that participate in the process of producing or degrading beta amyloid. Some under investigation include:

Researchers are targeting chromosomes 9, 10, and 12 as possible locations for genetic factors involved with Alzheimer's disease. (The ApoE4 gene is on chromosome 19.) In 2005, researchers announced that mutations linked to the ubiquilin 1 (UBQLN1) gene, located on chromosome 9, might be associated with increased risk for late-onset Alzheimer's disease.
Researchers have detected mutations in the proteins amyloid precursor protein (APP) and ubiquitin-B (Ubi-B), which may account for some cases of late- and early-onset Alzheimer's. Such mutations are not inherited, however, but appear to be genetic mistakes that occur during transcription, the coding process in which DNA establishes the pattern for the production of its proteins and other molecules.
In 2007, researchers identified mutations in the SORL1 gene as a possible factor in late-onset Alzheimer’s disease. Researchers think that variations in this gene may contribute to amyloid plaque formation in Alzheimer’s disease.

Genetic Factors for Early-Onset Alzheimer's. Scientists are coming closer to identifying defective genes responsible for early-onset Alzheimer's, an uncommon, but extremely aggressive form of the disease.

Mutations in genes known as presenilin-1 (PS1) and presenilin-2 (PS2) account for most cases of early-onset inherited Alzheimer's disease. The defective genes appear to accelerate beta amyloid plaque formation and apoptosis, a natural process by which cells self-destruct.
Genetic mutations in the genes that control amyloid precursor protein (APP) are also being targeted as causes of early-onset Alzheimer's. The genetic disease Down syndrome, for example, overproduces beta-amyloid precursor protein (APP), the source of beta amyloid, and almost always leads to early Alzheimer's. Other APP mutations are being identified.

Researchers are also investigating environmental factors (infections, metals, industrial and other toxins) that may trigger oxidation, inflammation, and the disease process, particularly in people with a genetic susceptibility to Alzheimer's.

Infectious Organisms. Slow, infectious viruses cause a number of other degenerative neurologic diseases, such as kuru and Creutzfeldt-Jakob disease.

Click the icon to see an image of Creutzfeldt-Jakob disease.

Although no specific virus has been linked to Alzheimer's, some researchers theorize that people with a genetic susceptibility to Alzheimer's may be vulnerable to the actions of certain viruses, particularly under circumstances when the immune system may be weakened.

Metals. Some laboratory studies have reported excessive amounts of metal ions such as zinc, copper in the brain of people with Alzheimer's disease. Such ions may possibly change the chemical architecture of normal beta amyloid, making it more harmful. A mildly acidic environment appears to be important in the process that binds these metals to beta amyloid. Experts observe that such conditions (acidic environment and higher levels of zinc and copper) commonly occur as part of the inflammatory response to local injury.

Electromagnetic Fields. Some studies on people exposed to intense electromagnetic fields (EMF) have reported a higher incidence of Alzheimer's. However, the association between EMF and Alzheimer's is very weak.

Risk Factors

Alzheimer's disease is the seventh leading cause of death in American adults. It affects about 5 million Americans and 8 million more people worldwide. According to the U.S. Alzheimer’s Association, 1 in 8 people age 65 and older, and nearly 1 in 2 people over age 85, have Alzheimer’s disease.

Age is the greatest risk factor for Alzheimer's disease. The number of cases of Alzheimer's disease doubles every 5 years in people over 65. By age 85, almost half of all people are afflicted. People with the disease survive, on average, half as long as similarly aged adults without the disease.

With the increasing numbers of aging adults, unless effective methods for prevention and treatment are developed, Alzheimer's disease will reach epidemic proportions, afflicting about 16 million Americans within 50 years. Evidence points to older age, high blood pressure, cholesterol levels, and a family history of the disease as the most important risk factors for Alzheimer's disease.

Several studies have reported that women have a much higher risk for Alzheimer's disease than men. If there is a gender difference, it is likely to be due estrogen, the primary female hormone, which appears to have properties that protect against the memory loss and lower mental functioning associated with normal aging. Such actions include blocking production of beta amyloid, offering antioxidant protection, and regulating blood sugar (glucose) levels in the brain. The drop in estrogen levels after menopause may explain a higher risk for Alzheimer's disease in older women than in men. (Testosterone, the male hormone, converts to estrogen, which may help protect men.) Studies have been mixed, however, on the association between the decline in natural estrogen levels and mental functioning in older women.

People with a family history of the disease are at higher than average risk for Alzheimer's disease. Researchers are identifying important genetic factors, notably the ApoE4 gene, that may be responsible for late- and early-onset cases.

Dietary and other cultural factors that increase the risk for hypertension and unhealthy cholesterol levels may also play a role. For example, a study of Japanese men showed that their risk increased if they emigrated to America. And the disease is much less common in West Africa than in African-Americans, who share the same or higher risk with Caucasians in America.

High blood pressure and unhealthy cholesterol levels -- the same important risk factors for heart disease and stroke -- may also be risk factors for Alzheimer's disease. In fact, they appear to be more important than ApoE4, the genetic factor most commonly associated with Alzheimer's disease.

Blood pressure is the force applied against the walls of the arteries as the heart pumps blood through the body. The pressure is determined by the force and amount of blood pumped and the size and flexibility of the arteries.

High Blood Pressure. Studies have reported an association between Alzheimer's disease and systolic hypertension (the higher and first number in blood pressure measurement). High blood pressure can cause problems with the vascular system, which is responsible for delivering blood to the brain. Recent research suggests that some types of blood pressure medication may lower Alzheimer's risk.

High Cholesterol Levels. Research indicates an association between high cholesterol levels and Alzheimer's disease in some people. One theory is that cholesterol regulates the processing and accumulation of amyloid beta-protein.

Click the icon to see an image of cholesterol.

Stroke. High blood pressure and heart disease can increase the risk for stroke. For people who have Alzheimer’s disease or mild cognitive impairment, stroke can increase the decline of cognitive function and accelerate dementia.

Diabetes. Patients with diabetes often have high blood pressure, lipid imbalances, and circulatory disorders that affect the heart and vascular system, which in turn increases the risk for Alzheimer’s. In patients who do not have other risk factors for Alzheimer’s, diabetes itself may increase risk. Research also suggests that diabetes can increase the risk for mild cognitive impairment, a condition that often precedes Alzheimer’s disease.

High Homocysteine Levels. Homocysteine is an amino acid that has been identified as a modest risk factor in heart disease. It has also been associated with a higher risk for Alzheimer's disease. High levels are general due to deficiencies of the B vitamins B6, B12, and folate. Such vitamins are also related to nerve protection. Researchers theorize that homocysteine impairs the ability of DNA to repair nerve cells. The weakened cells are then more vulnerable to the harmful effects of oxidized beta amyloid.

Nearly all patients who inherit Down syndrome develop changes in the brain that resemble Alzheimer's if they live into their 40s, although onset varies and can occur as late as age 70. Women under the age of 35, but not older mothers, who give birth to children with Down syndrome are also at much higher risk for Alzheimer's.

Lower Education and Economic Groups. A number of studies have reported either a higher risk for Alzheimer's disease in people with less education or a lower risk for Alzheimer's disease in those who remain mentally active. Some experts speculate that learning itself may stimulate more neurons to grow and thus create a larger reserve in the brain so that it takes longer for brain cells to be destroyed. Some evidence suggests that early malnutrition, which is more likely to occur in lower income and educational groups, has been associated with smaller brains and with Alzheimer's disease in old age. Low-birth weight can cause problems in growth factors that could affect both mental and physical health later on in adulthood.

Small Head Size. The size of the skull is fixed by age 7. Brain size approximates the head size until old age, when it begins to shrink. Some evidence has reported an association between small head size (and therefore less brain volume) and Alzheimer's disease, possibly because people who start with larger brains can sustain more injury over time. For example, a 2002 study indicated that it was reduction in overall brain volume, not specific regions, that contributed to mental impairment in older healthy adults. Another study reported that people who had small heads plus the ApoE4 gene had 14 times the risk for Alzheimer's disease than those without this combination. Nevertheless, other studies have found no association between a small head size and Alzheimer's disease.

Some experts suggest that the relationship observed in other research may simply be due to social and economic factors, such as malnutrition or low birth weight, which have been associated with both Alzheimer's disease and small head size. Small head size independent of other factors, they argue, does not pose a higher risk for either Alzheimer's disease or low intelligence

Depression. There is a significant overlap between depression and dementia in the elderly. In fact depression itself is often an early symptom of Alzheimer's disease. In a 2002 study of Catholic nuns, for each of four depressive symptoms, the risk for developing Alzheimer's disease increased by an additional 19%. For example, for a woman with four depressive symptoms the risk increased by 76%. Some evidence suggests that there may even be common genetic factors in people who have both early depression and Alzheimer's disease.

Head Injury. Some studies have found an association between serious head injuries in early adulthood and the development of Alzheimer's. It is not yet known if such injuries directly cause Alzheimer's or simply accelerate the disease in people who are already susceptible to it.

Prevention

Although there is no strong evidence that any lifestyle change can prevent Alzheimer's disease, studies suggest that certain behaviors may help protect against mental decline. In particular, medications and lifestyle choices that protect the heart may be of specific importance. Various preventive drugs are under investigation, including antioxidant and anti-inflammatory therapies.

In 2004, the National Institutes of Health (NIH) halted a large clinical trial that was investigating the use of anti-inflammatory drugs in preventing Alzheimer's disease. While prior data had confirmed that NSAIDs were not effective in treating AD, research continued to explore these drugs' potential preventive benefits.

The Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT) was launched in 2001 to investigate whether long-term use of naproxen (Aleve) or celecoxib (Celebrex) could decrease the risk of developing AD. The trial was based on the premise that because inflammation is known to be involved in the process of Alzheimer’s disease, anti-inflammatory drugs may help to prevent it. The NIH suspended this trial due to evidence that the NSAID naproxen was associated with increased incidence of cardiovascular and cerebrovascular events among participants. No adverse effects appeared during this trial for the COX-2 inhibitor celecoxib. However, heart safety concerns about this drug had been raised in other trials, and investigators did not believe that celecoxib's potential benefits outweighed its risks.

Since 2004, the ADAPT investigators have continued to monitor the trial’s participants to see if these treatments had any effect in changing their risk for Alzheimer’s. In an update analysis of ADAPT data published in 2007, the researchers announced that neither naproxen nor celecoxib appear to reduce the risk for Alzheimer’s.

The same lifestyle and medical choices that reduce risk factors for heart disease and diabetes are important for reducing the risk for Alzheimer's disease. And, experts believe that treating high blood pressure and diabetes may help slow the progression of Alzheimer’s disease. The following are some heart-protective medications that may also protect the brain.

Blood Pressure Drugs. Because high blood pressure is associated with increased risk of Alzheimer’s, researchers have been studying whether blood pressure medication can reduce this risk. In a 2006 study of patients who took high blood pressure drugs, researchers found that potassium-sparing diuretics reduced the risk of developing Alzheimer’s by 70%. Beta-blockers and certain calcium channel blockers also helped to a lesser extent. ACE inhibitors appeared to offer no protection.

Statins. Statins are common drugs used to lower cholesterol levels. In past years, a number of studies reported a significantly lower risk for Alzheimer's disease in patients who took statins. However, newer studies have failed to prove that statins can help prevent Alzheimer's disease. In these recent studies, large numbers of elderly people had their dementia evaluated at baseline and then monitored over several years. The results indicated that statin use did not predict onset of AD. In the meantime, the NIH is conducting a clinical trial to investigate whether simvastatin can slow the progression of AD.

Hormone Replacement Therapy. Hormone replacement therapy (HRT) has been studied for years for health effects after menopause, including its effect on mental decline. A number of studies, including a major 2003 analysis, have found no differences in mental performance and no protection from Alzheimer's disease in women taking HRT compared to non-users. The 2003 trial, called the Women's Health Initiative Memory Study (WHIMS), enrolled 4,500 women over 65 years of age. The WHIMS study showed that older postmenopausal women who took combination HRT (estrogen plus progestin) had twice the risk of developing dementia than similarly aged women who received placebo pills. In addition to increasing the risk for dementia (including Alzheimer's disease), combination HRT failed to prevent the development of mild cognitive impairment. Based on these results, the researchers from the National Institute on Aging (NIA) recommended against prescribing combination hormone therapy to older women for maintaining or improving cognitive function. The NIA continued to research whether estrogen-only therapy could prevent or delay the onset of Alzheimer's disease. Results released in 2004 indicated that women ages 65 years and older who took estrogen-only HRT had a slightly increased risk of developing dementia.

Testosterone. Some testosterone converts to estrogen, which may be why older men appear to have a lower risk for Alzheimer's disease than older women. Animal studies have suggested that testosterone may help reduce levels of beta amyloid. There is also some evidence that low testosterone levels may be a particular risk factor in men with the ApoE4 gene. Some experts believe that giving testosterone to elderly men, and combinations of testosterone and estrogen to older women, may prove to be protective. Side effects of testosterone in women include increased body hair, acne, fluid retention, anxiety, and depression. Long term benefits or serious adverse effects are unknown.

DHEA. Dehydroepiandrosterone (DHEA) is a male-like hormone in the body that declines with age. Some evidence suggests that it may help reduce mental decline in older women, but not in older men. Studies are under way. The hormone may, however, reduce HDL (the so-called good cholesterol) when taken in higher doses. While its effect on cancer-cell growth is unknown, some evidence indicates that high levels may increase cancer risk. In any case, DHEA is not regulated, and brands vary widely in their content.

Because Alzheimer's disease rates vary among different populations, investigators are researching how diet can help in prevention. Caloric intake itself may play a role in brain health. In one study on animals, restricting calories below normal (but above starvation levels) helped prevent age-related nerve degeneration. However, in patients with existing Alzheimer's, weight loss is a strong indicator of mental decline.

Fats and Oils. Some studies suggest an association between fat and Alzheimer's disease:

In China and Nigeria, where fat intake is low, the risk of developing Alzheimer's is 1% at age of 65 compared to 5% in the U.S.
A study in the Netherlands reported an association between dementia and diets high in total fat, saturated fat, and cholesterol.
A number of studies suggest that a high-fat high-calorie diet in people who carry the ApoE4 gene may confer a particularly high risk. For example, in one study, adults who carried the ApoE4 gene and whose diet consisted of 40% fat calories had 29 times the risk for Alzheimer's compared to non-ApoE4 carriers on the same high-fat diet.

The recommended dietary goal is to limit total fat intake to 25 - 35% of total daily calories. But not all fats are alike. Unhealthy fats include saturated fats (contained in animal products such as meat) and trans-fatty acids (contained in fast foods and commercially baked products). The American Heart Association recommends limiting saturated fat intake to less than 7% of total daily calories and trans-fatty acid intake to less than 1% of total daily calories.

It is best to replace saturated fats and trans-fatty acids with unsaturated fats from plant and fish oils. Omega-3 fatty acids are excellent sources of unsaturated fats. Plant sources of omega-3 fatty acids include canola oil, soybeans, flaxseed, and certain types of nuts such as walnuts. For fish sources, salmon, mackerel, sardines, lake trout, herring, and albacore tuna are especially high in marine omega-3 fatty acids. For heart health, and possibly brain health, experts recommend eating these types of fish at least twice a week.

Two types of omega-3 fatty acids are found in fish oils: Docosahexaenoic acid (DHA) and eicosapentaneoic acid (EPA). Researchers are particularly interested in the role that DHA may play in Alzheimer’s disease prevention. DHA has been linked to many brain cell functions, and appears to have particular importance for aging brains. Studies indicate that people who have higher blood levels of DHA have a much lower risk of developing dementia and Alzheimer’s disease.

Although evidence suggests that consuming DHA-rich foods later in life helps to increase DHA levels in the brain, it is unclear whether dietary supplements can provide similar benefits. A 2007 study indicated that omega-3 fatty acid supplements may help slow cognitive decline in some patients with very mild Alzheimer’s disease, but that the supplements have little effect for advanced stages of the disease. In 2007, the U.S. National Institutes of Health launched a large-scale clinical trial to evaluate whether DHA supplements can slow the progression of cognitive and functional decline in people with mild-to-moderate Alzheimer’s disease.

Mediterranean diet is an eating plan that has specific heart-health benefits. It is rich in fiber and nutrients, including omega-3 fatty acids and antioxidant vitamins. The diet emphasizes fish, fruits, vegetables, and monounsaturated (“good”) fats, particularly olive and canola oils. A 2006 study suggested that the Mediterranean diet may also be good for the brain. In the study, patients who strictly followed the diet had a 40% lower risk of developing Alzheimer’s disease than patients who ate a conventional American diet. Other studies also indicate the Mediterranean diet is associated with a lower risk for Alzheimer’s.

Omega-3 fatty acids, found plentifully in oily fish and flaxseed and canola oils, are beneficial to people afflicted with IBD (inflammatory bowel disease).

Fruits and Vegetables. According to several studies, eating plenty of darkly colored fruits and vegetables may slow brain aging. Blueberries, which are very rich in antioxidants, are of particular interest. A 2006 study of over 3,000 elderly adults found that consumption of vegetables (especially green leafy vegetables) helped reduce the rate of cognitive decline, but fruit intake had no effect.

Alcohol. Some studies have suggested that moderate intake of alcohol (one or two drinks a day) may protect the aging brain, possibly by releasing acetylcholine, the chemical in the brain that is deficient in Alzheimer's disease. Not all studies have been positive. In any case, heavy alcohol consumption offers no protection and is dangerous.

Folate and Vitamin B12. Some studies suggest that deficiencies of vitamins B6, B12, and folate (folic acid) may be a risk factor for Alzheimer' diseases. Deficiencies in these vitamins can increase homocysteine levels, which some research associates with a higher risk for Alzheimer's disease. Foods containing folate include avocados, bananas, oranges, asparagus, green leafy vegetables, and dried beans. In the United States and some other countries, grain and cereal products are fortified with folate. B12 is found only in animal, dairy, and fish products. B6 is found in a variety of foods, including fortified cereals, beans, meat, fish, and some fruits and vegetables.

Click the icon to see an image of vitamin B12 sources.

Click the icon to see an image of folate sources.

Research is still inconclusive and conflicting about whether increased consumption of folate, through food or dietary supplements, can help prevent Alzheimer’s disease or slow its progression. A small 2006 study of healthy older adults, published in the New England Journal of Medicine, found that supplements containing folate, vitamin B12, and vitamin B6 did not help improve cognitive performance. A 2007 Lancet study indicated that folic acid supplements may help slow cognitive decline. People in the Lancet study took 800 mcg of folic acid daily, which is twice the recommended daily allowance of 400 mcg. However, this study was conducted in the Netherlands, where people tend to get less folate in their daily diets than in the United States.

Another 2007 study found that elderly people who consumed folate from both diet and supplement sources had a reduced risk for Alzheimer’s disease. Neither diet alone nor supplements alone affected Alzheimer’s risk; only the combination of the two produced an effect. The study also indicated that vitamins B6 and B12 do not affect Alzheimer’s risk.

Antioxidant Supplements. Much research on Alzheimer's disease has indicated that oxidation (release of damaging unstable particles) may play an important role in the disease process. Some reports, including a large 2002 population study, have suggested that vitamin E intake, from food or supplements, may protect against mental decline. Other studies suggest that vitamin E protects only those who carried the ApoE4 gene. Most of the evidence finding any benefits from other antioxidants comes from using a combination of antioxidant vitamins, such as vitamins C and E, but not from using them separately. However, there is no strong evidence of protection to date from using antioxidant supplements.

Physical Exercise. Studies indicate that exercise may help prevent the development of Alzheimer’s disease and other forms of dementia. A 2006 study found that older adults (65 years and older) who exercised three times a week reduced their risk for Alzheimer’s by about 40%. Exercise in the study included walking, hiking, aerobics, calisthenics, swimming, water aerobics, weight training, and stretching.

Mental Exercise. Cognitive training that includes exercises to stimulate memory, reasoning, and mental processing speed may help improve both mental ability and daily functioning. In an important 2006 study in the Journal of the American Mental Association, older community-dwelling adults who received cognitive training showed reductions in cognitive decline. In addition, they were better able to handle daily living tasks -- such as performing housework, managing money, and preparing meals -- than people who did not receive the training. The benefits of cognitive training lasted for up to 5 years afterwards. Other studies indicate that participating in intellectually engaging activity -- such as doing crossword puzzles or learning a new language -- may help reduce the risk of Alzheimer’s disease.

Social Interaction. Social interaction is also important for maintaining emotional health as well as keeping the mind active and energized. A 2007 study indicated that adults who are lonely have twice the risk of developing Alzheimer’s dementia as those who are not socially isolated.

Symptoms

The early symptoms of Alzheimer's disease (AD) may be overlooked because they resemble signs of natural aging. Older adults who begin to notice a persistent mild memory loss of recent events may have a condition called mild cognitive impairment (MCI). MCI is now believed to be a significant sign of early-stage Alzheimer's in older people. Studies now suggest that older individuals who experience such mild memory abnormalities can later develop Alzheimer's disease.

Early symptoms of Alzheimer's disease may include:

Forgetfulness (particularly of recent events or information)
Loss of concentration (having trouble planning or completing familiar tasks, difficulty with abstract thinking such as simple arithmetic problems)
Language problems (forgetting the names of objects, mixing up words, difficulty completing sentences)
Confusion about time and place (difficulty recognizing familiar neighborhoods or remembering how you arrived at a location, confusion about months or seasons )
Impaired judgment (dressing inappropriately or making poor financial decisions)
Impaired movement and coordination (slowing of movements, halting gait, reduced sense of balance)
Mood and behavior changes (rapid mood swings, emotional outbursts, personality changes, increased fear or suspicion)
Apathy and depression (loss of interest in activities, increased sleeping, sitting in front of the television for long periods of time)

Diagnosis

A definitive test to diagnose Alzheimer's disease, even in patients showing signs of dementia, has not yet been developed. A number of expert groups have developed criteria to help diagnose Alzheimer's disease and rule out other disorders. A diagnosis often involves answering questions about the patient:

Do psychological tests indicate dementia?
Does the patient have deficits in two or more areas of mental functioning (such as language, motor skills, and perceptions)?
Has memory and mental functions gotten progressively worse?
Is consciousness disturbed? (It is not in Alzheimer's disease.)
Is the patient over age 40?
Are other medical or physical conditions present that could account for the same symptoms?
Are daily activity impaired or has the behavior changed?
Is there a family history of Alzheimer's disease?
Are there other symptoms, such as depression, insomnia, incontinence, delusions, hallucinations, dramatic verbal, emotional or physical outbursts, sexual disorders, and weight loss?

Other steps involved in making a decision include laboratory tests (EEG and possibly tests to rule out other diseases) and psychological testing to determine the presence of dementia.

Although some memory impairment occurs in many people as they age, only some of these people develop Alzheimer's disease. Many similar symptoms can occur in healthy older individuals from other conditions associated with aging:

Fatigue
Grief or depression
Illness
Vision or hearing loss
The use of alcohol or certain medications
Simply the burden of too many details to remember at once

The first step in diagnosing Alzheimer's disease is to rule out other conditions that might cause memory loss or dementia. There are a number of causes for dementia in the elderly besides Alzheimer's disease:

Vascular dementia (abnormalities in the vessels that carry blood to the brain)
Lewy bodies variant (LBV), also called dementia with Lewy bodies
Parkinson's disease
Frontotemporal dementia

Experts believe that 60% of cases of dementia are due to Alzheimer's, 15% to vascular injuries, and the rest are a mixture of the two or caused by other factors.

Vascular Dementia. Vascular dementia is primarily caused by either multi-infarct dementia (multiple small strokes) or Binswanger's disease (which affects tiny arteries in the midbrain). One major analysis suggested that patients with vascular dementia have better long-term verbal memory than patients with Alzheimer's disease, but poorer executive function (less ability to integrate and organize).

Lewy Bodies Variant. Lewy bodies are abnormalities found in the brains of patients with both Parkinson's disease and Alzheimer's. They can also be present in the absence of either disease; in such cases, the condition is called Lewy bodies variant (LBV). In all cases, the presence of Lewy bodies is highly associated with dementia. LBV was defined in 1997, and some experts believe it may be responsible for about 20% of people who have been diagnosed with Alzheimer's. They can be difficult to distinguish. Compared to Alzheimer's disease patients, those with LBV may be more likely to have hallucinations and delusions early on, to walk with a stoop (similar to Parkinson's disease), to have more fluctuating attention problems, and to perform better than Alzheimer's disease patients on verbal recall but less well with organizing objects.

Parkinson's Disease. Dementia is about six times more common in the elderly Parkinson patient than in the average older adult. It is most likely to occur in older patients who have had major depression. Unlike in Alzheimer's, language is not usually affected in Parkinson's related dementia. Visual hallucinations occur in about a third of people on long-term medications.

Parkinson's disease is a slowly progressive disorder that affects movement, muscle control, and balance. Part of the disease process develops as cells are destroyed in certain parts of the brain stem, particularly the crescent-shaped cell mass known as the substantia nigra. Nerve cells in the substantia nigra send out fibers to tissue located in both sides of the brain. There the cells release essential neurotransmitters that help control movement and coordination.

Frontotemporal Dementia (FTD). Once considered rare, FTD is now considered to be the second most common cause of early-onset dementia. People who develop this condition tend to be in their mid-fifties although it can develop later on. It results in greater behavioral impairment (apathy, reduced empathy, poor self-care, unrestrained behavior) than with Alzheimer's disease. It may also be marked by speech problems and early incontinence. Brain imaging scans can help diagnose this problem.

Other Conditions that Cause Similar Symptoms. Some elderly people have a condition called mild cognitive impairment, which involves more severe memory loss than normal but no other symptoms of Alzheimer's. A number of conditions, including many medications, can produce symptoms similar to Alzheimer's:

Severe depression
Drug abuse
Thyroid disease
Severe vitamin B12 deficiency
Blood clots
Hydrocephalus (excessive accumulation of spinal fluid in the brain)
Syphilis
Huntington's disease
Creutzfeldt-Jakob disease
Brain tumors

It is important that the doctor recognize any treatable conditions that might be causing symptoms or worsening existing dementia caused by Alzheimer's or vascular abnormalities.

A number of psychological tests are used or being developed to assess difficulties in attention, perception, and memory and problem-solving, social, and language skills. Experts are researching specific tests that may help identify early on people with mild memory impairment who are at high risk for Alzheimer's disease.

Two commonly used tests that are very useful in identifying individuals who may be at risk for Alzheimer's are the Mini-Mental State Exam (MMSE) and the Mattis Dementia Rating Scale. Still, these tests have limitations.
A clock drawing test is also a good test for Alzheimer's disease. The patient is given a piece of paper with a circle on it and is first asked to write the numbers in the face of a clock and then to show "10 minutes after 11." The score is based on spacing between the numbers and the positions of the hands.

Electroencephalography (EEG) traces brain-wave activity; in some patients with Alzheimer's disease this test reveals "slow waves." EEG data helps distinguish a potential patient with Alzheimer's disease from a patient with severe depression, whose brain waves are normal.

Imaging tests include magnetic resonance imaging (MRI), positron-emission tomography (PET), and single photon emission computed tomography (SPECT). These tests are sometimes used to rule out other disorders, such as multi-infarct dementia, stroke, blood clots, and tumors. Research is being conducted to determine if these tests can help to confirm a diagnosis of Alzheimer's disease and improve understanding of disease progression. Researchers hope that imaging tests may also be able to provide diagnoses of Alzheimer’s disease while it is still in its early stages.

In 2006, scientists developed a new imaging molecule called FDDNP that they hope will enable earlier detection of Alzheimer’s disease. Research also continues on Pittsburgh compound B, a tracer molecule used in PET brain scans to highlight beta-amyloid protein deposits. Results from all this research may help to define potential drug targets and aid in the development of new Alzheimer's drugs.

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

In 2005, the National Institute of Aging, in collaboration with industry partners, launched the $60 million Alzheimer's Disease Neuroimaging Initiative (ADNI). This landmark 5-year clinical trial, which will be conducted at 50 sites throughout the United States and Canada, will investigate whether neuroimaging techniques, such as MRI and PET scans, can be combined with biomarkers and neuropsychological tests to measure the progression of AD and mild cognitive impairment. In 2004, the U.S. Medicare system expanded insurance coverage of PET scans for eligible beneficiaries who meet specific diagnostic criteria for both Alzheimer's disease and fronto-temporal dementia. Medicare also covers the costs for patients enrolled in its agency-approved imaging clinical trials.

Blood Tests. Blood tests are currently used to check for anemia and other disorders that can produce dementia symptoms. Investigators are researching serum biomarkers, such as the iron transport protein p97, that might help detect the presence of Alzheimer's disease.

Cerebrospinal Fluid Test. Scientists are developing new nanotechnology screening methods that may eventually be used to identify Alzheimer's disease while it is still in its earliest stages and before plaque deposits accumulate. In 2005, a research team announced it had used a bio-barcode assay to detect tiny amounts of a protein called amyloid-beta-derived diffusable ligand (ADDL) in cerebrospinal fluid. ADDLs may be involved in cognitive decline and are a potential biomarker for early stage Alzheimer's disease. Tests for other proteins are also being developed.

Odor Test. Investigators are also using the impairment of smell in Alzheimer's disease to develop tests that require patients to distinguish between odors.

Once a diagnosis has been made, some experts observe that certain factors at the time of diagnosis indicate a higher risk for a more rapid decline:

Older age
Being male
The presence of high blood pressure
Signs of loss of motor control and coordination
Tremor
Social withdrawal
Loss of appetite and severe weight loss
Accompanying sensory problems, such as hearing loss and a decline in reading ability
General physical debility

Medications

Most drugs used to treat Alzheimer's, and those under investigation, are aimed at slowing progression. There are no cures to date. In addition, the improvements from some of these drugs may be so modest that even the patients and their families are not aware of them. Even in these cases, however, the drugs may delay the need for admission to nursing homes.

There are currently two drug classes that have been approved by the U.S. Food and Drug Administration (FDA) to treat the cognitive symptoms of Alzheimer's disease:

Cholinesterase inhibitors (generally used to treat mild-to-moderate Alzheimer's; donepezil is also approved for treatment of severe dementia )
N-methyl-D-aspartate (NMDA) receptor antagonists (used to treat moderate-to-severe Alzheimer's)

Cholinesterase inhibitors are designed to protect the cholinergic system, which is essential for memory and learning and is progressively destroyed in Alzheimer's. These drugs work by preventing the breakdown of the brain chemical acetylcholine and are recommended for the treatment of mild-to-moderate Alzheimer's. The first cholinesterase inhibitor, tacrine, was approved in 1993 but is rarely prescribed today due to safety concerns. The three most commonly prescribed cholinesterase inhibitors are donepezil (approved in 1996), rivastigmine (approved in 2000), and galantamine (approved in 2001).

Cholinesterase inhibitors may increase the risk for gastrointestinal bleeding or ulcers, and patients should be cautious about using these medicines with NSAIDs (which can also cause gastric irritation). Common side effects of cholinesterase inhibitors, especially when taken at higher doses, may include nausea, vomiting, diarrhea, and upset stomach.

Donepezil. Donepezil (Aricept) is the only Alzheimer’s drug approved for all stages of dementia, from mild to severe. It is taken once a day and has only modest benefits, but it does help slow loss of function and reduce caregiver burden. It works equally in patients with or without the ApoE4 gene. Several trials, including an important 2005 New England Journal of Medicine (NEJM) study, have found that donepezil may have short-term benefits for patients with mild cognitive impairment by delaying progression to AD. In the NEJM study, donepezil slowed progression during the first year of therapy, but demonstrated no benefits by the conclusion of the 3-year trial. Studies also suggest that donepezil may help improve behavior and memory in patients with moderate-to-severe Alzheimer’s when it is given in combination with memantine (Namenda).
Rivastigmine. Rivastigmine (Exelon) targets two enzymes: Acetylcholinesterase and butyrylcholinesterase. It is taken as a pill twice a day. (The FDA approved a skin patch version of the drug in 2007.) Rivastigmine may be particularly helpful for patients with rapidly progressing disease. It has slowed or slightly improved disease status even in patients with advanced disease. Rivastigmine may cause significantly more side effects than donepezil, including nausea, vomiting, and headache.
Galantamine (Razadyne). Galantamine not only protects the cholinergic system but also acts on nicotine receptors, which are also depleted during Alzheimer's. Studies report that it improves daily living, behavior, and mental functioning, including in patients with mild to advanced-moderate Alzheimer's disease and those with a mix of Alzheimer's disease and vascular dementia. Some studies have suggested that the effects of galantamine may persist for a year or longer and even strengthen over time. In 2005, the name of galantamine was changed from Reminyl to Razadyne.
Tacrine. Tacrine (Cognex) was the first cholinergic protective drug. It needs to be taken four times a day, has only modest benefits, and has no benefits for patients who carry the ApoE4 gene. In high doses, it can also injure the liver. In general, newer cholinergic protective drugs that do not pose as great a risk for the liver are now used for Alzheimer's.

About half of patients with mild-to-moderate disease show slight improvement with these drugs. Comparative studies have reported little differences in effectiveness among them. All drugs have gastrointestinal side effects, including nausea. Of note, some of the drugs often used in elderly Alzheimer's disease patients are known as anticholinergics and may offset the effects of the Alzheimer's disease pro-cholinergic drugs. Such drugs include antihistamines, antipsychotic drugs, and some anti-incontinence drugs.

In any case, the benefits of these drugs are far from dramatic. In fact, many experts have reservations about developing any additional drugs that affect the cholinergic system since, at best, they only slow progression and do not appear to affect the basic destructive disease process. When patients go off the drugs, the deterioration continues. In 2005, the United Kingdom’s National Institute for Clinical Excellence (NICE) recommended against the use of donepezil, rivastigmine, galantamine, and memantine for Alzheimer’s disease treatment. The agency contended that the costs of these drugs outweigh their modest benefits.

Memantine (Namenda) is approved for treatment of moderate-to-severe Alzheimer’s disease. (Most cholinesterase inhibitors are used to treat mild-to-moderate stages of the disease.) By blocking NDMA receptors, memantine protects against the overstimulation of glutamate, an amino acid that excites nerves and, in excess, is a powerful nerve-cell killer.

Memantine is prescribed either alone or in combination with donepezil. Studies indicate that memantine may help improve cognitive function and delay the progression of Alzheimer’s disease for up to 1 year. Side effects are generally mild but may include dizziness, drowsiness, or fainting.

In one study of effects on moderate-to-severe Alzheimer's, patients who received memantine showed a small but statistically significant benefit in cognitive function and performance of daily abilities compared with those patients who were given placebo. In a 2004 study, memantine was added to the drug regimen of patients with moderate-to-severe Alzheimer's who had taken donepezil for at least 6 months. In comparison to patients who took only donepezil, patients who received the combination donepezil-memantine therapy showed a greater improvement in measures of cognitive function, activities of daily living, and behavior parameters. A 2006 study indicated that memantine combined with donepezil may help reduce behavior problems -- such as agitation, aggression, and irritability -- and improve disturbances in appetite and eating.

Although cholinesterase inhibitors and memantine are the best available medications for Alzheimer's, their benefits are, unfortunately, quite modest. More effective methods of prevention and treatment are urgently needed.

There has been considerable controversy over whether NSAIDs may help in the treatment of Alzheimer's disease. As inflammation is involved in the destruction of brain cells, it has been suggested that anti-inflammatory drugs might be able to halt this process and thus slow the progression of the disease. In a rigorous 2003 study, patients with mild-to-moderate Alzheimer's were randomized to receive either naproxen (Aleve) or rofecoxib (Vioxx) or placebo. After 12 months of treatment, patients in the anti-inflammatory groups did not show any difference in cognitive improvement compared to those patients who received placebo.

Results from another large study, published in 2004, also failed to demonstrate improvement in cognitive function for patients with mild-to-moderate Alzheimer's who were treated with rofecoxib. Since the completion of these studies, rofecoxib was withdrawn from the market, and the NIH suspended a clinical study assessing naproxen’s preventive benefits (see Nonsteroidal Anti-Inflammatory Drugs as Prevention). As mentioned earlier, patients should be cautious about taking NSAIDs in combination with cholinesterase inhibitors as they may increase the risk of gastrointestinal bleeding.

Nicotine enhances the actions of the cholinergic system (which is depleted in Alzheimer's disease) and is known to improve concentration and memory in the short term. Some studies have suggested that nicotine may protect nerve cells and help prevent the formation of beta amyloid. One study indicated that nicotine might help protect against Alzheimer's disease in carriers, but not noncarriers, of the ApoE4 gene. Another reported improvement in verbal recall and word retrieval in healthy relatives of Alzheimer's disease patients who wore a low-dose nicotine patch. Research to date, however, has found no strong evidence of improvement in Alzheimer's disease patients with nicotine replacement methods. No one should smoke to prevent or treat Alzheimer's disease.

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. Always check with your doctor before using any herbal remedy or dietary supplement.

Ginkgo Biloba. Ginkgo biloba is a common herb that has antioxidant properties and appears to increase blood flow to the brain. A 2002 study of healthy people who took over-the-counter ginkgo for 6 weeks reported no improvements in memory or mental function. Studies are reporting that a ginkgo biloba extract, called Egb 761, may slightly improve the memory of patients with mild to moderate Alzheimer's disease. The herb poses a small increased risk for bleeding, which may be hazardous in combination with other blood-thinning medications, such as warfarin or high-doses of vitamin E.

Turmeric. Studies suggest that circumin, a compound found in the spice turmeric, has properties that may protect against the Alzheimer's disease process.

Melatonin. Melatonin, a natural hormone involved in sleep regulation, is of interest to researchers. It is an antioxidant, may break down beta amyloid, and is able to pass through the blood-brain barrier. Deficiencies have been observed in patients with Alzheimer's disease. A number of studies (but not all) report that melatonin may improve sleep habits in these patients. Some studies reported slower progression of mental impairment.

A number of drugs are being investigated for treatment and prevention of Alzheimer's disease. Intense areas of research are focusing on drugs that prevent beta amyloid build-up, its toxic effects on nerve cells, or other mechanisms of the disease process. Promising research in late-stage clinical trials include.

Tramiprosate (Alzhemed) is an experimental drug designed to prevent beta-amyloid accumulation in the brain.
Flurizan (MPC-7869) may help reduce amyloid plaque development. It is currently being studied in Phase III trials for adults with mild Alzheimer’s disease.
Rosiglitazone XR (Avandia) is an extended-release formulation of a drug used to treat type 2 diabetes. Its anti-inflammatory properties are being studied as a treatment for patients with mild-to-moderate Alzheimer’s who do not carry the APOE-e4 gene. Phase III results have been promising, but this drug has been linked to increased risk for heart attack deaths in patients with diabetes. In 2007, a panel of experts from the Food and Drug Administration (FDA) agreed the drug increases the risk of heart attacks -- but concluded it should remain on the market. The panel did, however, recommend the FDA require rosiglitazone's maker to add warnings to the drug's label. Patients or caregivers of patients who take rosiglitazone, especially those who have heart disease or who are at high risk for heart attack, should discuss their treatment options with their doctors.
Dimebon is an antihistamine, which researchers think may help prevent brain cell death. The drug is currently in Phase II trials.
Antioxidants such as vitamin E and selenium are being investigated for their preventive effects. Antioxidant treatment trials include curcumin (the yellow pigment found in turmeric spice) and a combination trial with fish oil and alpha-lipoic acid.

Depression. Major depression with dementia that occurs in elderly people may be an early sign of Alzheimer's. In such cases, it precedes Alzheimer's by 2 years or less. (It is, in fact, sometimes difficult to differentiate major depression from early-stage Alzheimer's disease.) Antidepressants known as selective serotonin reuptake inhibitors (SSRIs), including fluoxetine (Prozac) and sertraline (Zoloft), may be effective in relieving depression, irritability, and restlessness associated with Alzheimer's in some patients.

Apathy. Depression is often confused with apathy. An apathetic patient lacks emotions, motivation, interest, and enthusiasm while a depressed patient is generally very sad, tearful, and hopeless. According to one study, apathy is more common than depression in patients with Alzheimer's disease. It responds to stimulants, such as methylphenidate (Ritalin), rather than antidepressants.

Psychosis. Antipsychotic drugs are used to treat verbally or physically aggressive behavior and hallucinations. Because older antipsychotic drugs, such as haloperidol (Haldol), have severe side effects, most doctors now prescribe newer atypical antipsychotics, such as risperidone (Risperdal) or olanzapine (Zyprexa).

However, these newer antipsychotic drugs still can cause serious side effects, including confusion, sleepiness, and Parkinsonian-like symptoms. In addition, studies indicate that their safety risks may outweigh any possible benefits. A 2005 study showed that these drugs produce a slightly increased rate of death in patients with Alzheimer’s disease or dementia. In addition, several studies from 2006 and 2007 published in the New England Journal of Medicine suggested that atypical antipsychotics work no better than placebo in controlling psychosis, aggression, and agitation in patients with Alzheimer’s.

Most experts now recommend that doctors delay prescribing antipsychotic medication unless absolutely necessary. They recommend first trying behavioral treatments and controlling changes in the patient’s environment and routine. Anti-seizure drugs, such as carbamazepine (Tegretol) or valproate (Depakote), can also sometimes treat agitation and other psychotic symptoms. Non-drug treatments, such as bright light boxes, are also showing promise for managing psychotic and behavioral symptoms.

Disturbed Sleep. Patients with Alzheimer's disease commonly experience disturbances in their sleep/wake cycles. Moderately short-acting sleeping drugs, such as temazepam (Restoril), zolpidem (Ambien), or zaleplon (Sonata), or sedating antidepressants, such as trazodone (Desyrel, Molipaxin), may be useful in managing insomnia. Some research suggests that exposure to brighter-than-normal artificial light during the day for patients with normal vision may help reset wake/sleep cycles and prevent nighttime wandering and sleeplessness. Trials on melatonin, a natural hormone that helps trigger sleep at night, are in progress.

Stages

The lifespan of patients with Alzheimer's is generally reduced, although a patient may live anywhere from 3 - 20 years after diagnosis. The final phase of the disease may last from a few months to several years, during which time the patient becomes increasingly immobile and dysfunctional. Caregivers should understand the phases of this illness in order to help determine their own capacities for dealing with this painfully sad disease.

Telling the Patient. Often doctors will not tell patients that they have Alzheimer's. If a patient expresses a need to know the truth, it should be disclosed. Both the caregiver and the patient can then begin to address issues that can be controlled, such as access to support groups and drug research.

Mood and Emotional Behavior. Patients display abrupt mood swings, and many become aggressive and angry. Some of this erratic behavior is caused by chemical changes in the brain. But it may also be due to the experience of losing knowledge and understanding of one's surroundings, causing fear and frustration that patients can no longer express verbally.

The following recommendations for caregivers may help soothe patients and avoid agitation:

Keep environmental distractions and noise at a minimum if possible. (Even normal noises, such as people talking outside a room, may seem threatening and trigger agitation or aggression.)
Speak clearly. Most experts recommend speaking slowly to a patient with Alzheimer's disease, but some caregivers report that patients respond better to clear, quickly spoken, short sentences that they can more easily remember.
Use a combination of facial expressions, voice tones, and words for communicating emotions. (One study suggested that patients may have difficulty in recognizing the meaning of facial expressions, particularly those signaling sadness, surprise, and disgust.)
Limit choices (such as clothing selection).
Offer diversions, such as a snack or car ride, if the patient starts shouting or exhibiting other disruptive behavior.
Simply touching and talking may also help.
Maintain as natural an attitude as possible. Patients with Alzheimer's disease can be highly sensitive to the caregiver's underlying emotions and react negatively to patronization or signals of anger and frustration.
Showing movies or videos of family members and events from the patient's past may be comforting.

Although much attention is given to the negative emotions of patients with Alzheimer's disease, some patients become extremely gentle, retaining an ability to laugh at themselves or appreciate simple visual jokes even after their verbal abilities have disappeared. Some patients may seem to be in a drug-like or "mystical" state, focusing on the present experience as their past and future slip away. Encouraging and even enjoying such states may bring some comfort to a caregiver.

There is no single Alzheimer's personality, just as there is no single human personality. All patients must be treated as the individuals they continue to be, even after their social self has vanished.

Appearance and Cleanliness. For the caregiver, grooming the patient may be an alienating experience. For one thing, many patients resist bathing or taking a shower. Some spouses find that showering with their afflicted mate can solve the problem for a while. Often patients with Alzheimer's disease lose their sense of color and design and will put on odd or mismatched clothing. It is important to maintain a sense of humor and perspective and to learn which battles are worth fighting and which ones are best abandoned.

Driving. As soon as Alzheimer's is diagnosed, the patient should be prevented from driving. One study found that more than half of elderly people involved in fatal accidents had some degree of neurologic damage.

Wandering. A potentially dangerous trait is the patient's tendency to wander. At the point the patient develops this tendency, many caregivers feel it is time to seek out nursing homes or other protective institutions for their loved ones. For those who remain at home, the following precautions are recommended:

Locks should be installed outside the door, which the caregiver can open, but the patient cannot.
Alarms may be installed at exits.
A daily exercise program should be implemented, which may help tire the patient. One study showed that walking 30 minutes, three times a day, also improved communication.
The caregiver should contact organizations, such as Alzheimer's Association or Medic Alert, for identification supplies and procedures that help locate patients who wander away from home and become lost.
Some experts are discussing the benefits versus the ethics of electronic tagging, which would emit a radio signal or alarm that allows the patient to be tracked using a detector.

Speech Problems. Some evidence suggests that speech therapy combined with Alzheimer's disease medications may be helpful for maintaining verbal skills patients with mild symptoms.

Sexuality. In many cases, the patient becomes uninhibited sexually. At the same time, the patient's physical deterioration and receding capacity to recognize the spouse as a known and loved individual can make sexual activity unattractive for the caregiving spouse. Other patients may lose interest in sex. If sexual issues are a problem, they should be discussed openly with the doctor. Ways should be found to maintain non-sexual physical affection that can bring comfort to both the patient and the spouse.

Patients with Alzheimer's disease need 24-hour a day attention. Even if the caregiver has the resources to keep the patient at home during later stages of the disease, outside help is still essential. If available, home visits by a health profession can have a favorable impact on survival and delay the need for a nursing home. Medicare now covers many Alzheimer's services, and patients should be able to stay at home longer than previously.

Incontinence. A patient's incontinence is generally devastating to the caregiver and a primary reason why many caregivers decide to seek nursing home placement when the patient reaches this stage. When the patient first shows signs of incontinence, the doctor should make sure that it is not caused by an infection. Urinary incontinence may be controlled for some time by trying to monitor times of liquid intake, feeding, and urinating. Once a schedule has been established, the caregiver may be able to anticipate incontinent episodes and get the patient to the toilet before they occur.

Immobility and Pain. As the disease progresses, patients become immobile, literally forgetting how to move. Eventually, they become almost entirely wheelchair-bound or bedridden. Bedsores can be a major problem. Sheets must be kept clean, dry, and free of food. The patient's skin should be washed frequently, gently blotted thoroughly dry, and moisturizers applied. The patient should be moved every 2 hours and the feet kept raised with pillows or pads. Exercises should be administered to the legs and arms to keep them flexible.

Dehydration. Dehydration can become a problem. It is essential to encourage fluid intake equal to 8 glasses of water daily. Coffee and tea are diuretics and will deplete fluid.

Eating Problems. Weight loss and the gradual inability to swallow are two major related problems in late-stage Alzheimer's and are associated with an increased risk of death. Weight gain, however, is linked to a lower risk of dying. The patient can be fed through a feeding syringe, or the caregiver can encourage chewing action by pushing gently on the bottom of the patient's chin and on the lips. The caregiver should offer the patient foods of different consistency and flavor. Because choking is a danger, the caregiver should learn to administer the Heimlich maneuver, which may be taught by the local Red Cross. In very late stages, some caregivers choose feeding tubes for the patient. They should be aware that feeding tubes have no measurable impact on survival.

About 80% of patients with Alzheimer's disease are cared for by family members, who often lack adequate support, finances, or training for this difficult job. Few diseases disrupt patients and their families so completely or for so long a period of time as Alzheimer's. The patient's family endures two separate losses and grieves twice:

First, they must grieve for the ongoing disappearance of the personality they recognize. Dealing with the patient throughout the course of the disease is like Alice's fall down the rabbit hole into Wonderland. No sooner has the caregiver grappled with one set of problems, when the patient's further deterioration creates new and more intractable ones.
Finally, the caregiver must grieve the actual death of the person.

Often, caregivers themselves begin to show signs of mental disorder or ill health. Depression, empathy, exhaustion, guilt, and anger can play havoc with even a healthy individual faced with the care of a loved one suffering from Alzheimer's.

Fortunately, research shows that intensive support services can greatly improve caretakers’ quality of life and make it easier for them to continue caring for patients in their homes. In a 2006 study, caregivers who received individual and family counseling, telephone counseling, support groups, and stress management and problem-solving techniques reported reduced rates of depression and improved self-confidence compared with those who received only written educational materials. Another 2006 study indicated that improving caregivers’ access to counseling and support services can help delay nursing home placement of patients. National and local Alzheimer's associations can provide important support and other services.

A point comes when the most devoted caregiver will probably need to institutionalize the patient. That point is determined not only by the caregiver's emotional endurance, but also by their physical strength and stamina, as a patient typically takes on the random, undisciplined behavior of a very young child. Financial considerations in finding a nursing home are often paramount, but the kind of care is equally important. Although fully half of all nursing home patients suffer from Alzheimer's, not all nursing homes have programs specifically designed for them. Some institutions may claim that they do, but often they simply group patients together without offering any special programs. If a caregiver manages to find a facility that offers good services, it may be located far from home, making visits difficult. The caregiver must then decide whether superior care at a distant institution is worth seeing the patient less frequently. When the patient's illness becomes terminal, a hospice program may be another option.

1. Although I cannot control the disease process, I need to remember I can control many aspects of how it affects my relative.

2. I need to take care of myself so that I can continue doing the things that are most important.

3. I need to simplify my lifestyle so that my time and energy are available for things that are really important at this time.

4. I need to cultivate the gift of allowing others to help me, because caring for my relative is too big a job to be done by one person.

5. I need to take one day at a time rather than worry about what may or may not happen in the future.

6. I need to structure my day because a consistent schedule makes life easier for me and my relative.

7. I need to have a sense of humor because laughter helps to put things in a more positive perspective.

8. I need to remember that my relative is not being difficult on purpose; rather their behavior and emotions are distorted by the illness.

9. I need to focus on and enjoy what my relative can still do rather than constantly lament over what is gone.

10. I need to increasingly depend upon other relationships for love and support.

11. I need to frequently remind myself that I am doing the best that I can at this very moment.

12. I need to draw upon the Higher Power, which I believe is available to me.

Source: The American Journal of Alzheimer's Care and Related Disorders & Research, Nov/Dec 1989

Resources

www.alzheimers.org -- Alzheimer's Disease Education and Referral Center
www.alz.org -- Alzheimer's Association
www.alzforum.org -- Alzheimer's Research Forum
www.alzfdn.org -- Alzheimer's Foundation of America
www.alz.co.uk -- Alzheimer's Disease International
www.nia.nih.gov -- National Institute on Aging
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.aan.com -- American Academy of Neurology
www.medicalert.org -- Medic Alert
www.ahaf.org -- American Health Assistance Foundation
www.clinicaltrials.gov -- Find clinical trials
www.medicare.gov/NHCompare/Home.asp -- Find a nursing home

References

ADAPT Research Group, Lyketsos CG, Breitner JC, Green RC, Martin BK, Meinert C, et al. Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial. Neurology. 2007 May 22;68(21):1800-8. Epub 2007 Apr 25.

Akomolafe A, Beiser A, Meigs JB, Au R, Green RC, Farrer LA, et al. Diabetes mellitus and risk of developing Alzheimer disease: results from the Framingham Study. Arch Neurol. 2006 Nov;63(11):1551-5.

Ayalon L, Gum AM, Feliciano L, Arean PA. Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in patients with dementia: a systematic review. Arch Intern Med. 2006 Nov 13;166(20):2182-8.

Belle SH, Burgio L, Burns R, Coon D, Czaja SJ, Gallagher-Thompson D, et al. Enhancing the quality of life of dementia caregivers from different ethnic or racial groups: a randomized, controlled trial. Ann Intern Med. 2006 Nov 21;145(10):727-38.

Cummings JL, Schneider E, Tariot PN, Graham SM; Memantine MEM-MD-02 Study Group. Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment. Neurology. 2006 Jul 11;67(1):57-63.

Durga J, van Boxtel MP, Schouten EG, Kok FJ, Jolles J, Katan MB, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet. 2007 Jan 20;369(9557):208-16.

Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-Irving G, et al. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol. 2006 Oct;63(10):1402-8.

Gamaldo A, Moghekar A, Kilada S, Resnick SM, Zonderman AB, O'Brien R. Effect of a clinical stroke on the risk of dementia in a prospective cohort. Neurology. 2006 Oct 24;67(:1363-9.

Luchsinger JA, Reitz C, Patel B, Tang MX, Manly JJ, Mayeux R. Relation of diabetes to mild cognitive impairment. Arch Neurol. 2007 Apr;64(4):570-5.

Luchsinger JA, Tang MX, Miller J, Green R, Mayeux R. Relation of higher folate intake to lower risk of Alzheimer disease in the elderly. Arch Neurol. 2007 Jan;64(1):86-92.

McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med. 2006 Jun 29;354(26):2764-72.

Mittelman MS, Haley WE, Clay OJ, Roth DL. Improving caregiver well-being delays nursing home placement of patients with Alzheimer disease. Neurology. 2006 Nov 14;67(9):1592-9.

Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS. Associations of vegetable and fruit consumption with age-related cognitive change. Neurology. 2006 Oct 24;67(:1370-6.

Regan C, Katona C, Walker Z, Hooper J, Donovan J, Livingston G. Relationship of vascular risk to the progression of Alzheimer disease. Neurology. 2006 Oct 24;67(:1357-62.

Rogaeva E, Meng Y, Lee JH, Gu Y, Kawarai T, Zou F, et al. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat Genet. 2007 Feb;39(2):168-77. Epub 2007 Jan 14.

Scarmeas N, Stern Y, Mayeux R, Luchsinger JA. Mediterranean diet, Alzheimer disease, and vascular mediation. Arch Neurol. 2006 Dec;63(12):1709-17. Epub 2006 Oct 9.

Schaefer EJ, Bongard V, Beiser AS, Lamon-Fava S, Robins SJ, Au R, et al. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Arch Neurol. 2006 Nov;63(11):1545-50.

Schneider JA, Arvanitakis Z, Bang W, Bennett DA. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology. 2007 Jun 13; [Epub ahead of print]

Schneider LS, Tariot PN, Dagerman KS, Davis SM, Hsiao JK, Ismail MS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med. 2006 Oct 12;355(15):1525-38.

Small GW, Kepe V, Ercoli LM, Siddarth P, Bookheimer SY, Miller KJ, et al. PET of brain amyloid and tau in mild cognitive impairment. N Engl J Med. 2006 Dec 21;355(25):2652-63.

Willis SL, Tennstedt SL, Marsiske M, Ball K, Elias J, Koepke KM, et al. Long-term effects of cognitive training on everyday functional outcomes in older adults. JAMA. 2006 Dec 20;296(23):2805-14.

Wilson RS, Krueger KR, Arnold SE, Schneider JA, Kelly JF, Barnes LL, et al. Loneliness and risk of Alzheimer disease. Arch Gen Psychiatry. 2007 Feb;64(2):234-40.

Review Date:
7/31/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

More Beef Recalls!

FitSugar — Mon, 26 Nov 2007 11:45:00 -0800

I'm sorry to have to tell you that another recall on ground beef has been issued, this time by a Wisconsin company called American Foods Group.

Ninety-six thousand pounds of beef were voluntarily recalled after two people became ill, possibly from E.coli. These cases are being investigated by the Illinois Department of Health. The meat was sold in seven states including Indiana, Kentucky, Maryland, Ohio, Tennessee, Wisconsin, and Virginia.

The meat was produced on Oct. 10 and labeled with "Est. 18076" inside the USDA mark of inspection. If you have questions about the recall, check out the USDA's Web site or call the toll-free USDA Meat and Poultry Hotline at 1-888-MPHotline (1-888-674-6854).

Is it just me, or are these constant recalls making you scared to eat?

Source