Ask the Doctor

Should low HDL get more attention?

(This article was first printed in the April 2005 issue of the Harvard Heart Letter. For more information or to order, please go to http://www.health.harvard.edu/heart.)

Q. My doctor is focused on keeping my LDL in a good range, but she doesn’t seem too concerned that my HDL is on the low side. Shouldn’t it get the same attention?

A. You are asking about one of the important unanswered questions in cardiology. I believe we have enough information, though, to support a more intense focus on HDL.

Interest in boosting HDL (good cholesterol) is growing. New agents for raising HDL are being tested. But you needn’t wait for them — you can make lifestyle changes or try one of the HDL-raising medications that have been available for years.

Exercise and physical activity raise HDL and do many other wonderful things for the heart, bones, muscles, and psyche, so I suggest starting there. Alcohol in moderation (no more than one drink a day for women, one to two for men) also raises HDL. The trans fats found in hard margarines, many baked goods, and fried fast foods lower HDL. Avoiding them and eating unsaturated fats instead can positively affect HDL. So can losing weight.

The two main classes of HDL-elevating drugs are fibrates and niacin. Fibrates include gemfibrozil (Lopid) and fenofibrate (TriCor). They raise HDL about 4 mg/dL; they also lower total cholesterol, LDL, and triglycerides. Together, these changes reduce the risk of cardiac problems by about 25%. The drawback is that about one in three people who take a fibrate have side effects. The most common are an upset stomach, gas, diarrhea, or a rash. Less common problems include liver and muscle damage.

Niacin is the other main medication for improving HDL, with an average increase of 7 mg/dL, along with a decent reduction in LDL. As with fibrates, side effects are common, especially with immediate-release niacin. Most people taking it experience flushing, an uncomfortable feeling of heat, itching, or tingling in the skin. With the newer sustained-release preparation, only about 25% of people report flushing. Other side effects can include gastrointestinal, muscle, and liver problems.

As bothersome as the side effects of fibrates and niacin can be, a variety of tactics can minimize them. Many people learn to take these medications without problems.

Combinations may work even better. In a small study of retired military men with low HDL, triple-drug therapy with niacin, gemfibrozil, and cholestyramine boosted HDL by an average of 36%.

Side effects are one reason why doctors love pushing statins to reduce LDL — the rates of side effects are much lower with statins, and both patient and doctor can declare victory by pointing to lower and lower LDL levels. The war against heart disease still hasn’t been won, though, so many doctors add on HDL-raising therapy to the statins their patients are already taking.

Just over the horizon are treatments that might lead to far greater increases in HDL. Weekly infusions with a synthetic form of HDL called Apo A-I Milano reduce atherosclerotic plaque size by 4.2% — in just five weeks! Also in the pipeline are drugs and a vaccine that inhibit cholesteryl ester transfer protein, which works against HDL in the body.

Five or 10 years from now, many doctors will probably use some sort of new HDL-raising treatment. But we shouldn’t wait — we need to use the effective strategies we already know about.

Every 1% increase in HDL is associated with a 1%–3% reduction in heart attack risk. So if your LDL is already down, keep after your doctor to focus on your low HDL.

— Thomas H. Lee, M.D.,
Editor in Chief, Harvard Heart Letter