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The Not-So-Good News About "Good" Choesterol
Len Kravitz, Ph.D.

Study reviewed: Voight, B.J. (2012). Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomization study. Published online May 17, 2012,, DOI:10.1016/S0140-6736(12)60312-2

One of the most common educational messages exercise professionals underscore to clients is that low density lipoprotein cholesterol (LDL-C) is the 'lousy' or 'bad cholesterol and high density lipoprotein cholesterol (HDL-C) is the 'healthy' or good cholesterol. The interpretation from the research is that high levels of LDL-C may lead to the buildup of arterial plaque and eventual cardiovascular disease. The evidence of this association appears to be quite strong. Thus, exercise professionals need to continue to talk about the positive role of exercise and lifestyle change to lower LDL-C. The understanding from observational studies with HDL-C has been that elevated levels of this 'good' cholesterol will have a reverse effect on cardiovascular disease. That is why it is referred to as a negative risk factor, because it supposedly negates or lessons the CVD risk. However, Voight and colleagues (2012) in their recently published article in Lancet online suggest the association of high HDL-C with CVD risk reduction is not accurate. This column will review the function of cholesterol in the body, the new Lancet study results, and present consequential lifestyle changes that can be made to lower LDL-C and cardiovascular disease risk.

Cholesterol 101: The Good and the Bad
The body makes all of the cholesterol it needs, however people get more of it from dietary consumption of animal products. It is a building block for several body cell components, particularly cell membranes. It functions to make hormones, vitamin D and helps in digestion. Cholesterol doesn't mix well with blood and is thus transported in the circulation within particles called lipoproteins. The lipoproteins are made up of protein and fat (i.e., lipids) and have different densities (or weight). Lipoproteins, which in order of size, largest to smallest, are chylomicrons, VLDL (very low density lipoproteins), IDL (intermediate density lipoproteins), LDL (low density lipoproteins), and HDL (high density lipoproteins), all transport fat molecules and cholesterol in the blood. Note, whenever the 'C' (for cholesterol) is behind the lipoprotein it refers to the measured value of that lipoprotein. HDL's main role in metabolism is to transfer cholesterol from plaque depots (called atherosclerotic plaque or atheromas) in blood vessels to the liver for excretion, which is called reverse cholesterol transport. The HDL particle is comprised of a cholesterol core surrounded by an outer shell of phospholipids (specific type of lipid attached to a phosphate group and nitrogen base) and apolipoproteins (proteins that bind to lipids). HDL particles are further classified into several subgroups

LDL particles are formed as VLDL deposit triglyceride in adipose sites, thus leaving the lipoprotein with more cholesterol. Some LDL circulating through the bloodstream will be absorbed in the walls of arteries and convert to a slightly different (i.e., oxidized) form. Oxidized LDL is an irritant to the artery wall and can lead to the release (by the body) of specialized proteins called cytokines. The cytokines attract white blood cells, which are inflammatory cells that try to protect the artery. These white blood cells convert to macrophages (which means 'big eater') and try to ingest the oxidized LDL particles on the artery wall. Sometimes the macrophages become so overloaded that they convert to foam cells, which eventually becomes atherosclerotic plaque called vulnerable plaque (because it is unstable). The constant contracting and stretching of the artery (especially from high blood pressure) may rupture the thin membrane covering the vulnerable plaque, releasing some plaque into the blood. The body responds by forming a clot around the loose plaque and where the rupture occurred. The loose plaque could clog a blood vessel, causing heart attack or stroke and the arterial plaque build up continues to impair blood flow.

Overview of the Lancet Study
In this landmark study (which was actually 2 studies in one) Voight and a rather large group of international researchers conducted an investigation using a statistical technique referred to as a mendelian randomisation. This mathematical tool allowed the researchers to test the hypothesis whether certain biomarkers were actually causal in raising (i.e. for LDL-C) or lowering (i.e. for HDL-C) the risk to CVD. Data were obtained and analyzed from 19, 139 cases of myocardial infarction and 50, 812 myocardial-infarction-free subjects from 30 different studies. With this data the researchers tested several subcomponents of an endothelial lipase gene (in LDL and HDL) to better determine its role in myocardial infarction. In this very sophisticated molecular biology study the researchers analysis concluded that high plasma levels of LDL-C are consistently associated with the risk of myocardial infarction (i.e., heart attack). However, with HDL-C the researchers found that some genetic mechanisms that raise plasma HDL-C do not seem to lower risk of myocardial infarction (as was once believed). Thus, the researchers findings refute the belief that raising HDL-C will uniformly translate into reductions in risk of myocardial infarction.

Application and Bottom Line Message to Exercise Professionals
HDL is definitely a 'scavenger' particle in blood that helps to remove atherosclerotic plaque from the blood. Its 'reverse transport' role in the body definitely is a very positive and healthy mechanism. According to Ralph Laforge (via email correspondence), Current President of the Accreditation Council for Clinical Lipidology, HDL-C is a “clear marker of CVD risk but not particularly a target of therapy”. Laforge states that medical professionals are “not trying to determine ways of raising HDL-C” to reduce CVD risk. Much more investigation is currently focused on lowering LDL-C and VLDL-C. Mr. Laforge continues that HDL is “far and away the most complex of all the lipoproteins”, suggesting there is much more to learn about its many functions in the human body.
Fortunately, the targeted therapies to lower LDL-C (Side Bar 1) are quite effective for improving health and lowering CVD risk and should be encouraged.

Side Bar 1. Introducing the Therapeutic Lifestyle Program (TLP)
The U.S. Department of Health and Human Services has introduced the following TLP to reduce the risks associated with high LDL-C
Dietary TLP: Decrease the amount of saturated (<7% of diet), trans fat and cholesterol (<200 mg) in the diet because these are the leading causes of high blood cholesterol.
Weight Loss TLP: Excess weight has a tendency to elevate LDL-C and blood triglycerides. Losing excess weight is recommended when persons are identified as overweight or obese via body mass index (BMI) assessment. A BMI of 18.5-24.9 indicates a normal weight; a BMI of 25-29.9 is over-weight; while a BMI of 30 or higher is obese.
Physical Activity TLP: Do at least 30 minutes of moderate-intensity physical activity on most, if not all days of the week.
Fiber Foods TLP: Eating foods full of soluble and insoluble fiber improve overall health. However, only soluble fiber foods (e.g., oatmeal, pears, broccoli, prunes, lentils, kidney beans, lima beans) lower the risk of cardiovascular disease because they reduce LDL-C. Soluble fiber dissolves into a viscous substance in the intestines that helps to block cholesterol absorption. Recommendations are to get 5-10 grams and preferably 10-25 grams of soluble fiber daily. Insoluble fiber, also called roughage is found in fruits (with the skins), legumes (such as dry beans and peas), vegetables and whole-grain foods.
Plant Stanols and Sterols TLP: Eat plant stanols and sterols, from soybean, as they also help to lower some LDL-C from being absorbed in the body.
Salt TLP: Studies show that too much sodium may lead to elevated blood pressure, which may promote the deposition of LDL-C in the arteries. Use more spices and herbs to make food tastier and limit salt to &Mac178;2,300 mg per day.
Alcohol TLP: Too much alcohol damages the heart and liver and may lead to high blood pressure. Limit alcohol consumption to one drink a day for women and two a day for men.
Carbohydrate TLP: Complex carbohydrates such as cereals, pastas, fruits and vegetables are high in fiber and low calories. Limit simple carbohydrates such as candy, sweets and soft drinks, which are high in calories and low in nutrients.
Source: US Department of Health and Human Services

Side Bar 2: What do the LDL-C Test Results Mean
LDL of less than 100 milligrams per deciliter (mg/dL) is optimal.
LDL of 100 to 129 mg/dL is near-optimal.
LDL between 130 and 159 mg/dL is borderline high.
LDL cholesterol between 160 and 189 mg/dL is high.
LDL of 190 mg/dL or more is very high.
Source: What Your Cholesterol Level Means. American Heart Association

Side Bar 3: Five Questions and Answers about Cholesterol
1) Is high LDL-C genetically determined?
The amount of LDL-C the body makes and how fast it is removed is only partially determined by genetics.
2) Which gender tends to have higher cholesterol levels?
Before the age of 50 yrs. men tend to have higher cholesterol levels. After 50 yrs women have higher cholesterol due to menopause.
3) What are the major types of cholesterol-lowering drugs?
Statins lower LDL-C levels better than any other types of drugs, about 20-55%. They do this by inhibiting the body from synthesizing cholesterol.
4) Do omega-3 fatty acids lower LDL-C?
Omega-3 fatty acids found in fish and some plants such as walnuts, flaxseed and soybean oils do not directly lower LDL-C, yet they do reduce the risk of heart attack and heart disease.
5) Does smoking affect cholesterol?
Yes, smoking tends to lower the HDL-C and elevate blood triglycerides
Source: US Department of Health and Human Services
Additional References:
US Department of Health and Human Services. NIH Publication No. 06-5235, December 2005.

What Your Cholesterol Level Means. American Heart Association
Retrieved: August 23, 2012

@bio:Len Kravitz, PhD, is the program coordinator of exercise science and a researcher at the University of New Mexico, where he won the Outstanding Teacher of the Year award. He has received the prestigious Can-Fit-Pro Lifetime Achievement Award and was chosen as the American Council on Exercise 2006 Fitness Educator of the Year.