In an article to be published in The New England Journal of Medicine online Sept. 22, the Hopkins researchers report that existing strategies to prevent heart disease have not addressed the best means to raise HDL cholesterol and instead have focused heavily on lowering LDL cholesterol, which leads to plaque formation and narrowing of the arteries that can cause heart attack.
"We have reached a turning point in the prevention of coronary heart disease from an emphasis during the last 15 years on lowering LDL cholesterol levels to an emphasis in the next decade on raising levels of HDL cholesterol," says article lead author and cardiologist Roger Blumenthal, M.D., an associate professor and director of the Ciccarone Preventive Cardiology Center at The Johns Hopkins University School of Medicine and its Heart Institute.
According to Blumenthal, existing guidelines from the U. S. National Institutes of Health and its National Cholesterol Education Program primarily emphasize lowering LDL cholesterol to control blood lipid levels without considering the alternative of raising HDL cholesterol as the primary or even secondary goal.
However, Blumenthal notes that every single milligram per deciliter increase in HDL cholesterol lowers a person's risk of suffering a fatal heart attack by about 3 percent. Low levels of HDL cholesterol are known to increase overall risk of dying from heart disease and, specifically, to increase risk of arteries narrowing again after angioplasty surgery to clear them. Low levels of HDL cholesterol, he says, are defined as less than 40 milligrams per deciliter of blood in men and 50 milligrams per deciliter in women.
In the NEJM report, Blumenthal and fellow expert, nurse practitioner Dominique Ashen, Ph.D., C.R.N.P., an assistant professor at Hopkins' School of Nursing, provide a comprehensive review and summary of the 50 most significant research studies on how best to manage peoples' HDL-cholesterol levels through modification of lifestyle risk factors for developing heart disease and use of drug therapy.
In addition, the researchers support their summary findings with a concise table listing heart medications with guidelines about how and when the drugs - niacin, fibrates and statins, or various combinations - can be used to raise HDL cholesterol levels. Also provided in the table are details on the drugs' chemical properties, or mechanism of action, and possible side effects.
However, Blumenthal and Ashen point out that research to date has not yet clearly distinguished which reductions in risk from heart disease are due to drug gains in HDL levels or other direct effects on the arteries. "That has been responsible for delaying revisions to national guidelines on HDL cholesterol," Blumenthal says.
Using a recent patient case study from Hopkins involving a 41-year-old man with low levels of HDL cholesterol (28 milligrams per deciliter), the researchers reviewed how over a period of three years his HDL levels were raised to above normal by modifying his lifestyle risk factors. These modifications included making sure the patient engaged in regular exercise, ceased smoking, assumed control over his weight as measured by body mass index, limited alcohol intake, and monitored dietary fat intake. The patient lost nearly 50 pounds while undergoing treatment.
To raise HDL cholesterol levels, the researchers recommend a regular exercise program of brisk aerobic exercise for 30 minutes, several times per week, if not every day.
Quitting smoking, they point out, provides an average increase in HDL levels of 4 milligrams per deciliter. Aids such as drug therapy, nicotine replacement products and counseling can help patients quit.
Weight control is also highlighted as critical to raising HDL levels, with the researchers noting that every kilogram of weight lost raises a patient's HDL levels by an average 0.35 milligrams per deciliter. A reasonable weight loss goal, they suggest, for overweight or obese patients is 1 pound, or 0.45 kilograms, per week, with a target body mass index of less than 25.
Mild to moderate consumption of alcohol, no more than one to two drinks per day, they say, has been shown beneficial in raising HDL levels by an average of 4 milligrams per deciliter, irrespective of type of alcohol consumed. But the researchers caution that the potential risks here may outweigh the benefits in people with liver or addiction problems.
For dietary control, the researchers recommend a diet low in saturated fat and rich in the polyunsaturated fatty acids found in foods such as oils (olive, canola, soy and flaxseed), nuts (almonds, peanuts, walnuts and pecans), and cold-water fish (salmon and mackerel), and shellfish. Consumption of carbohydrates, they say, should be restricted because high glycemic products, such as processed cereals and breads, are associated with lower HDL levels.
In the report, the researchers cite niacin, also called nicotinic acid or vitamin B3, as the most effective medication for raising HDL cholesterol, leading to increases of 20 percent to 35 percent. Fibrate therapy is also effective, they say, producing an average increase of 10 percent to 25 percent. Statins are the least effective of the three drug classes, used primarily to reduce LDL cholesterol, raising HDL levels by 2 percent to 15 percent. When used in combination, low-dose statins and high-dose niacin have been shown to produce benefits of 21 percent to 26 percent.
"Our report offers people interim guidelines on how best to manage HDL cholesterol levels while awaiting the results of national clinical trials, which could prove more definitive," says Ashen, who was lead author of the article. "These guidelines also offer a good description of the problem posed by low levels of HDL cholesterol, along with details on how HDL cholesterol metabolism works in the body with LDL cholesterol.
"The guidelines should help physicians and nurses to manage their patients' blood lipid levels, including HDL cholesterol, with drug therapies currently available, and should help prepare them to manage future therapies, expected to be developed within the next five years, that focus on raising HDL-cholesterol levels."
Funding support for the researchers was provided by the Maryland Athletic Club & Wellness Center Charitable Foundation in Lutherville, Md.
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Journal
New England Journal of Medicine