Analysis of existing research studies on elevation of high-density lipoprotein cholesterol levels through modification of lifestyle risk factors and drug therapy can help physicians and patients better manage overall cholesterol profile, according to an article published online September 22nd by the New England Journal of Medicine.

Cardiology experts at Johns Hopkins analyzed the 50 most significant research studies to prepare the interim guidelines. Lead author Roger Blumenthal, MD, said “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.”

Blumenthal noted that every single milligram per deciliter increase in HDL cholesterol lowers a person’s risk for fatal myocardial infarction by about 3 percent. Low levels of HDL cholesterol are known to increase overall risk of death from heart disease and increase risk for restenosis after angioplasty. He said that low levels of HDL cholesterol are defined as less than 40 milligrams per deciliter of blood in men and 50 milligrams per deciliter in women.

The researchers supported 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, the authors also pointed 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 said.
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. Smoking cessation provides an average increase in HDL levels of 4 milligrams per deciliter.

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.

Other modifications were recommended for mild-to-moderate alcohol intake (weighed against risk for liver or dependence problems) and dietary control through a diet low in saturated fat and rich in polyunsaturated fatty acids found in foods such as oils (olive, canola, soy and flaxseed), nuts (almonds, peanuts, walnuts and pecans), cold-water fish (salmon and mackerel), and shellfish. Consumption of carbohydrates should be restricted because high glycemic products, such as processed cereals and breads, are associated with lower HDL levels.

In the report, the researchers cited niacin as the most effective medication for raising HDL cholesterol, leading to increases of 20 percent to 35 percent. Statins are the least effective, 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.”