PANTETHINE: A CRITICAL PLAYER IN A HEART_HEALTHY LIFESTYLE

A Healthy Blood Lipid Profile Goes Beyond "The Lower the Cholesterol, the Better"

Heart disease is the number one killer of Americans, accounting for more than 40 percent of all deaths in the United States. While heart disease is a broad term, it is used by doctors to describe atherosclerosis, the main cause of heart attacks and strokes. The National Cholesterol Education Program (NCEP), a division of the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) has just released the latest guidelines for identifying and managing risks for coronary heart disease (CHD). If you are like many health_conscious individuals, you may be willing to take several steps to prevent heart disease. You make healthy food choices, you exercise, and you probably take several supplements for your general health. However, you may be confused about what other steps you can take. You may wonder what role cholesterol and blood lipids play in cardiovascular health. You may wonder if you have any risk factors for heart disease, and what you can do in terms of prevention. If you have already been diagnosed with heart disease you may be wondering how you can supplement the program your doctor has given you.

Atherosclerosis results from the buildup of plaque along the walls of blood vessels. It begins when the lining of the vessel is damaged. Fat carrying proteins, called lipoproteins, attach themselves to the damaged surface, causing cholesterol to build up. The low density lipoproteins (LDL) start to break down, or oxidize, releasing free radicals, damaging nearby cells. The more LDL_cholesterol (LDL_C) in your blood, the more it can buildup on the blood vessels. This whole process sets off the immune system to try to repair the damaged site, sending in specialized white blood cells, called macrophages, which eat the LDL_C, however when they become full of LDL_C, they become useless foam cells, which contribute to the plaque formation. Chemical signals called growth factors are released, which cause fibrinogen (a sticky substance) to adhere to the plaque, attracting platelets. All these things together form a stiff plaque on the artery wall, and ultimately block the artery. Your blood flow can be reduced by 90% before you feel any symptoms, but then in is too late, CHD has occurred.

These plaques have the unfortunate propensity to break loose, causing strokes, heart attacks and other ischemic conditions, such as angina, poor kidney function, reduced eyesight, poor circulation in the legs (claudication). If in addition to poor lipids levels someone has other risk factors, such as hypertension (high blood pressure), or diabetes, then these events are accelerated. A heart attack (also called a myocardial infarction) is when something blocks the flow of blood to your heart – a clot, a spasm or an accumulation of plaque. A stroke is brain damage that occurs when blood flow to the brain is interrupted, either by a clot or when a blood vessel bursts. High blood pressure plays a crucial role in the development of heart disease and stroke. The higher the pressure the greater the stress on arteries, and the more rapid the buildup of plaque. For reasons that are not entirely known, diabetes also increases plaque formation.

When doctors order a lipid profile, they are measuring the levels of all the cholesterol in your blood, both good and bad. These include: Total Cholesterol (TC), Low density lipoprotein (LDL_C – also known as the bad "lousy" cholesterol), Very low density lipoprotein (VLDL_C _ another bad player, "very lousy"), High density lipoprotein (HDL_C – the good "healthy" cholesterol) and triglycerides (TG _ yet another bad player). They may order additional tests such as glucose, to test for diabetes, and homocysteine levels, as elevations of homocysteine are also implicated in heart disease.

When people talk about their "cholesterol level," they are usually referring to their total cholesterol. The assumption that many people make is simply "the lower, the better." In reality, a healthy lipid profile is more complicated than simply low cholesterol. Cholesterol is a natural substance found in your body. Your cells need a certain amount of cholesterol to make flexible, permeable membranes. Your liver usually makes all the cholesterol your body needs. The cholesterol you ingest in your diet provides excess amounts. Cholesterol travels from your liver into your circulation by hitching a ride on LDL. It is carried away from tissues and back to the liver aboard HDL. Perhaps even more important than the total cholesterol level is the ratio of good to bad cholesterol. High levels of HDL_C are cardioprotective. One well_known way to increase the level of HDL_C in the blood is to increase one's activity level. Conversely, elevated levels of LDL_C are associated with an increased risk of heart disease, as are elevated triglycerides.

We need a certain amount of HDL_C, because as discovered in the 1970's, it actually protects against the buildup of cholesterol plaques. It acts as a scavenger preventing plaques from adhering to vessel walls. Without these scavengers, or when the ratio of HDL_C to LDL_C is off, plaques can build causing atherosclerosis (or hardening of the arteries). An appropriate heart_healthy goal, then, goes beyond "low cholesterol." Instead, we need to focus on a healthy lipid profile, with appropriate ratios of HDL_C, LDL_C, and TG. Just as we should want to keep LDL_C and TG down to appropriate levels, we should also want to keep HDL_C up to an adequate level. The new definitions of normal, borderline and elevated cholesterol are more stringent than previously, which means that many more Americans will fall into "at risk" categories, with physicians recommending treatment. (For appropriate HDL and LDL levels, see "New Recommendations.)

Because heart disease claims more lives than any other condition in the United States (as well as other industrialized countries), the NHLBI is continually reviewing risk factors for heart disease in order to find more effective ways to prevent it. In this spirit, the NHLBI's National Cholesterol Education Program (NCEP) has established new guidelines for a healthy lipid profile. These guidelines establish LDL_C as the target for therapy, and define as normal an LDL_C level of 100 mg/dl or less (milligrams per deciliter of blood serum). The new guidelines identify levels of 100_129 mg/dl as "above optimal". Those of 130_159 mg/dl are still defined as "borderline high," and those at 160_189 mg/dl as high. Those above 190 mg/dl are considered very high. A healthy HDL_C level is defined as at least 40 mg/dl. Previous guidelines had identified 130 mg/dl as a borderline LDL_C level and 160 mg/dl as a high level. A desirable level of HDL_C was previously defined as at least 35 mg/dl. (See accompanying table.) For more information on the new NCEP cholesterol guidelines, you may want to visit this section of the NHLBI Web site: http://www.nhlbi.nih.gov/guidelines/cholesterol/atp_iii.htm

The NCEP guidelines also call for more aggressive monitoring of people with "borderline" LDL_C levels. A physician’s initial intervention for a person in the borderline category would typically be lifestyle modification. The number of Americans receiving recommendations increases from 52 to 65 million with the new guidelines. Lifestyle modifications designed to promote a healthy lipid profile include reduction of dietary fat, increase of soluble dietary fiber, and increase in physical activity, as well as weight loss and smoking cessation, if indicated.

As a result of the new recommendations, more people with borderline profiles may find their physicians recommending that they begin taking a cholesterol_lowering medication, in addition to lifestyle modifications. The new recommendations increase this number from 13 to 36 million Americans. The medications typically used to lower cholesterol belong to a drug category known as HMG CoA reductase inhibitors, or "statins," because they end with the suffix "_statin." Commonly used drugs in this category include atorvastatin (Lipitor), cerivastsin (Baycol), lovostatin (Mevacor), pravastatin (Pravachol), and simvastatin ( Zocor). Statins are typically prescribed with the goal of lowering LDL_C. They work by inhibiting cholesterol synthesis and increasing the number of LDL receptors in the liver. They also have a modest effect of increasing HDL_C, and lowering triglycerides (TG).

While statins have a clear benefit, they can also have adverse effects, a risk with any effective therapy. Common side effects include myositis (muscle inflammation), arthralgias (joint pains), GI upset and elevated liver function tests. Physicians typically obtain liver enzyme levels before starting a patient on a statin medication and monitor those levels throughout therapy. Because animal studies have shown an increase in birth defects, statins are not appropriate medications to take during pregnancy.

Additionally, there is some concern that statin medications deplete levels of certain natural substances that are beneficial, such as coenzyme Q_10 (CoQ10), a heart protective substance that is made in the liver. For this reason, many people on statin therapy often take supplements of CoQ10, as well.

If your physician is concerned about your lipid profile, you should be, too. There are several steps you may want to take before beginning statin therapy, or in addition. Anyone with an elevated LDL_C and an HDL_C that is less than optimal would be wise to make any and all lifestyle modifications that apply. As mentioned earlier, these include increasing fiber and reducing dietary fat, which would lower LDL_C, and increasing physical activity, which is known to raise HDL_C. If you smoke, you need to quit. If you have diabetes, tight glucose control can also aid your lipid profile.

While you will certainly benefit from a heart_healthy meal plan, it is wise to be skeptical of fad diets. They are often designed more for the benefit of the developer's pocketbook than for your health, and they often are too stringent for a reasonable person to follow for long. When perusing a diet, ask yourself, "Could I stay on this plan for the next five or ten years?" If the answer is "no," keep looking. In avoiding bad fats (animal fat and saturated plant fats – i.e. palm oil and trans fatty acids _ margarine) don’t be afraid of the good fats: nuts, fish and other sources of omega_3 fatty acids. These can help you to achieve a good lipid profile. Red wine is protective, as is red grape juice, because the flavinoids protect against the oxidative damage from LDL_C. Soy protein has also been shown to lower LDL_C.

Some supplements can lower cholesterol, too. As you probably know, niacin supplements (Vitamin B3) have been used since the 1950s, particularly for lowering triglycerides. While immediate_release niacin is associated with flushing, the likelihood of flushing is much less with sustained_release formulations, however the risk of liver toxicity increases with sustained release formulations. Other side effects are nausea, and difficulty with blood sugar control, making it less attractive for diabetics.

Whether vitamin E supplementation is beneficial is in question. Several recent studies have shown no relationship between vitamin E supplementation and the prevention of cardiovascular mortality. However, future studies that take into account the bioavailablility of Vitamin E and appropriate dosages may yield different results. It works because of its antioxidant protection. Since it is fat soluble, it is incorporated directly into the LDL_C molecule, helping prevent oxidative damage at the site of plaque formation.

Folic Acid (Vitamin B9) is known to lower homocysteine levels, as does vitamin B_12, vitamin B6 and Betaine. Since elevated homocysteine levels are associated with heart disease, and increased rate of atherosclerosis, it would be wise to include these in any heart healthy plan.

Garlic has also been shown to lower LDL_C and increase HDL_C. The sulfur_containing substances in garlic help inhibit HMG_CoA reductase. Garlic is best used as fresh garlic, as the preparations are somewhat ineffective. Prolonged cooking, and drying destroys the sulfur containing compounds that are thought to be beneficial. The equivalent of one clove per day is sufficient. Since garlic has some anti_thrombotic activity, it is not recommended for patients taking anticoagulants (i.e. Coumadin).