Study reviewed: Voight, B.J., et al. 2012. Plasma HDL cholesterol and risk of myocardial infarction: A mendelian randomization study. The Lancet, 380 (9841), 572–80.
Exercise professionals often inform clients that low-density lipoprotein cholesterol (LDL-C) is the “lousy,” or bad, cholesterol, while high-density lipoprotein cholesterol (HDL-C) is the “healthy,” or good, cholesterol.
Research finds a strong association between high levels of LDL-C and the buildup of arterial plaque that leads to cardiovascular disease, so exercise professionals need to keep talking about how exercise and lifestyle change can reduce LDL-C. Researchers have also noted that higher levels of HDL-C seem to negate or lessen the risk of cardiovascular disease. The standard advice for elevating “good” cholesterol is to exercise more, quit smoking and maintain a healthy weight.
A May 2012 article in The Lancet, led by Voight et al., found that a gene linked to elevated levels of HDL-C in the blood did not reduce the risk of one of cardiovascular disease’s most dangerous manifestations—the myocardial infarction, or heart attack. This column will review the function of cholesterol in the body, summarize the implications of the new Lancet study results and present consequential lifestyle changes that can lower LDL-C and reduce cardiovascular disease risk.
Cholesterol 101: The Good and the Bad
The body makes all the cholesterol it needs, but people get more of it from consuming animal products. Cholesterol is a building block for several body cell components, particularly cell membranes. It functions to make hormones and vitamin D, and helps in digestion. Cholesterol doesn’t mix well with blood, so it is circulated within particles called lipoproteins. Lipoproteins are made up of protein and fat, or lipids, and have different densities, or weights.
All lipoproteins transport fat molecules and cholesterol in the blood. From largest to smallest, they are categorized as chylomicrons, very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL). The main metabolic role of HDL, the “good” cholesterol, is to transfer cholesterol from plaque depots (called atherosclerotic plaque or atheromas) in blood vessels to the liver for excretion, a process scientists call reverse-cholesterol transport. An HDL particle has a cholesterol core surrounded by an outer shell of phospholipids (a 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.
Particles of LDL, the “bad” cholesterol, are formed as VLDLs deposit triglyceride in adipose (or body fat) sites, thus leaving the lipoprotein with more cholesterol. Some LDLs circulating through the bloodstream are absorbed in the walls of arteries and converted to an oxidized form. Oxidized LDL irritates the artery wall and can incite the body to release specialized proteins called cytokines. The cytokines attract white blood cells, which are inflammatory cells that try to protect arteries. These white blood cells convert to macrophages (which means “big eaters”) 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 become an atherosclerotic plaque called vulnerable plaque (because it is unstable). The constant contracting and stretching of an artery, especially from high blood pressure, can rupture the thin membrane covering the vulnerable plaque, releasing some of it into the blood. The body responds by forming a clot around the loose plaque and at the site of the rupture. Loose plaque can clog a blood vessel, causing a heart attack or stroke, while arterial plaque buildup impairs blood flow.
Overview of the Lancet Study
In this landmark study (actually two studies in one), Voight and a large group of international researchers conducted an investigation using a statistical technique called mendelian randomization. This mathematical tool allowed the researchers to test the hypothesis of whether certain biomarkers were actually causal in raising (in the case of LDL-C) or lowering (in the case of HDL-C) the risk of cardiovascular disease.
The study analyzed data from 19,139 cases of heart attacks (myocardial infarctions) and 50,812 myocardial infarction–free subjects from 30 different studies. With this data, researchers tested several subcomponents of an endothelial lipase gene (in LDL and HDL) to better determine its role in heart attacks. In this very sophisticated molecular biology study, the researchers’ analysis concluded that high plasma levels of LDL-C are consistently associated with high risk of heart attacks. 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 notion that raising HDL-C will uniformly translate into reductions in heart attack risk.
Bottom Line for Exercise Professionals
HDL is definitely a “scavenger” particle in blood that helps to remove atherosclerotic plaque. Its “reverse-transport” role in the body is a positive and healthy mechanism. In an email interview, Ralph LaForge, MS, president of the Accreditation Council for Clinical Lipidology, said that HDL-C is a “clear marker of CVD (cardiovascular disease) risk, but not particularly a target of therapy.”
LaForge said medical professionals are “not trying to determine ways of raising HDL-C” to reduce the risk of cardiovascular disease. Much more investigation is focused on reducing harmful LDL-C and VLDL-C. LaForge went on to say 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.
So while attempting complex therapies to elevate levels of “good” cholesterol may be misguided, there remains little doubt that targeted therapies to lower LDL-C should be encouraged because they are so effective at improving health and lowering cardiovascular disease risk.
- LDL of less than 100 milligrams per deciliter (mg/dL) is optimal.
- LDL of 100–129 mg/dL is near-optimal.
- LDL of 130–159 mg/dL is borderline high.
- LDL of 160–189 mg/dL is high.
- LDL of 190 mg/dL or more is very high.
Source: AHA 2012.
The U.S. Department of Health and Human Services’ Therapeutic Lifestyle Program (TLP) offers these guidelines for limiting the risks of high LDL-C:
Eat better. Decreasing (or keeping low) consumption of saturated fat (less than 7% of diet), trans fat and cholesterol (less than 200 milligrams [mg] per day) is a key factor because these are the leading causes of high blood cholesterol.
Lose weight. Excess weight has a tendency to elevate LDL-C and blood triglycerides. Losing excess weight is recommended when people 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 overweight; and a BMI of 30 or higher is obese.
Stay physically active. Adults should do at least 30 minutes of moderate-intensity physical activity on most, if not all, days of the week.
Consume soluble fiber. Eating foods full of soluble and insoluble fiber improves overall health. However, only soluble-fiber foods (such as oatmeal, pears, broccoli, prunes, lentils, kidney beans and lima beans) lower the risk of cardiovascular disease by reducing 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 dried beans and peas), vegetables and whole-grain foods.
Eat plant stanols and sterols. Plant stanols and sterols, from soybeans, can help prevent some LDL-C from being absorbed in the body.
Pass on the salt. Studies show that too much sodium may lead to elevated blood pressure, which may promote the deposition of LDL-C in the arteries. Limiting salt to ≤2,300 mg per day is best for heart health; more spices and herbs can be used to make food tastier.
Limit alcohol. Too much alcohol damages the heart and liver and may lead to high blood pressure. Women should limit alcohol consumption to one drink a day, men to two drinks.
Go for complex carbohydrates. Complex carbs such as cereals, pastas, fruits and vegetables are high in fiber and low in calories. People should limit their intake of simple carbohydrates such as candy, sweets and soft drinks, which are high in calories and low in nutrients.
Source: HHS 2005.
1. Is high LDL-C genetically determined?
Genetics only partially determines the amount of LDL-C the body makes and how fast it is removed.
2. Which gender tends to have higher cholesterol levels?
Before the age of 50, men tend to have higher cholesterol levels. After 50, because of menopause, women have higher cholesterol.
3. What are the major types of cholesterol-lowering drugs?
Statins lower LDL-C levels about 20%–55%—better than any other types of drugs. 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, but they do reduce the risk of heart attack and heart disease.
5. Does smoking affect cholesterol?
Yes, smoking tends to lower HDL-C and elevate blood triglycerides. Source: HHS 2005.
AHA (American Heart Association). 2012. What your cholesterol level means. www.heart.org/HEARTORG/Conditions/Cholesterol/AboutCholesterol/What-Your-Cholesterol-Levels-Mean_UCM_305562_Article.jsp; retrieved Aug. 23, 2012.
HHS (U.S. Department of Health and Human Services). 2005. Your guide to lowering your cholesterol with TLC. www.nhlbi.nih.gov/health/public/heart/chol/chol_tlc.pdf; retrieved Aug. 26, 2012.
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