Treating Other Lipid Problems

Although most cholesterol treatment currently focuses on LDL, more attention is being paid to other blood lipids, particularly HDL and triglycerides. For example, the NCEP guidelines recommend aggressive treatment of elevated triglyceride levels. Experts don't always agree on when it is necessary to treat abnormal levels of these lipids, but current research is bringing some reasonable approaches to light.

What to Do About Low HDL

Low HDL levels often reflect a genetic abnormality, although they can also be pushed downward by a high blood level of triglycerides or by cigarette smoking, inactivity, hypertension, or a diet very high in carbohydrates or polyunsaturated fats. It is not uncommon to have a normal total cholesterol (below 200 mg/dL) in conjunction with low HDL; about 11% of men may have this lipid profile.

The Framingham Heart Study suggests that every 1 mg/dL decrease in HDL increases the risk of having a heart attack by 2%–3%. And the NCEP classifies an HDL level below 40 mg/dL as a risk factor — alongside cigarette smoking and high blood pressure — for developing heart disease.

For a long time, there was very little information to indicate whether raising HDL levels, a fairly tricky business, would lower the risk for heart disease. But in 1999 the long-awaited results of the VA-HIT (Veterans Affairs High-Density Lipoprotein Intervention Trial) were published. This study involved more than 2,500 men with low HDL, normal LDL, and pre-existing heart disease. It showed that participants who took the HDL-raising medication gemfibrozil for five years were significantly less likely to have heart attacks or die from heart disease. These results suggest that interventions that raise HDL may indeed make a difference, although it is possible that the benefits may have resulted from reductions in triglycerides, which also occurred among the men who took gemfibrozil.

Some people can raise their HDL level without drugs. Quitting smoking often leads to a gradual increase, as does adopting a diet that is low in the trans fats found in such products as stick margarine, fried foods, and commercial baked goods that contain partially hydrogenated oils. Exercise can raise HDL, as can moderate alcohol use, though health experts do not recommend that a nondrinker start drinking for this purpose (see "Alcohol and heart disease," below).

As yet, no drugs have been specifically designed to raise HDL, but both gemfibrozil and niacin cause modest increases. In VA-HIT, for example, patients taking gemfibrozil saw their HDL rise two points (from 32 mg/dL to 34 mg/dL, on average). Combining these treatments with LDL-lowering drugs is another option.

Although the following methods aren't ready for general use yet, they represent some exciting research that may lead to options for patients in the future.

CETP inhibitors. It's long been known that a protein called cholesterol ester transfer protein (CETP) plays a key role in determining HDL cholesterol levels. CETP helps exchange cholesterol between lipoproteins and can transfer it from HDL to the lower-density lipoproteins, LDL and VLDL. Individuals with a genetic mutation that causes loss of all CETP activity have very high levels of HDL cholesterol. They appear to be at lower risk of coronary disease. A small study in 2004 looked at whether a drug called torcetrapib, which blocks CETP from working, improves HDL cholesterol levels. The researchers found that the drug markedly raised HDL levels and lowered LDL levels when taken alone and also when taken in combination with a statin. The increases in HDL levels were much higher than can be achieved with existing lipid drugs. Studies now in progress will determine whether a CETP inhibitor can reduce heart disease. Results should be available early in 2007.

HDL-infusion therapy. A group of 40 people in a small Italian village led to the discovery of a rare type of HDL that seemed to protect against heart disease even when the levels of HDL were not very high. These people had a protein in their HDL, now called apo A-I Milano, that seemed to be better at stimulating the removal of cholesterol from plaques than did HDL containing the normal protein, called apo A-I. (You may remember news reports on apo A-I Milano calling it "Drano for the heart.")

Researchers tested whether a synthetic version of apo A-I Milano infused into the blood of people who didn't naturally have this protein would have the same effect. The small trial randomly assigned 47 people who had recently had heart attacks to receive either a placebo or a low or high dose of this chemical. Through ultrasounds of the arteries, researchers found that from the beginning to the end of the five-week trial, the plaque in the treatment groups shrank by 4%, while that of the placebo group grew by a small amount.

Although these are exciting results, bear in mind that this one small trial doesn't prove that infusions of this supercharged HDL will help prevent heart disease, or if it will even decrease plaque in a larger population of patients. But it does look very promising. Although FDA approval of this treatment may still be several years away, it is probable that people with heart disease who have low HDL levels could receive a similar treatment in a clinical trial much sooner.

How to Treat High Triglycerides

Studies indicate an association between elevated triglyceride levels and increased heart disease risk. In light of these findings, the NCEP guidelines recommend treating even borderline high triglyceride levels.

Elevated triglyceride levels (hypertriglyceridemia) may reflect two very different processes. Some people have an inherited tendency for high triglyceride levels. Some forms of familial hypertriglyceridemia do not seem to increase the risk of developing heart disease, assuming that the rest of the person's cholesterol profile is normal and there are no other risk factors. Other factors that may cause high triglyceride levels include obesity, alcohol abuse, a diet high in saturated fats, or illnesses such as poorly controlled diabetes, chronic kidney disease, or liver disease. Certain medications can also increase triglyceride levels, including estrogen-containing contraceptives, prednisone (a corticosteroid), thiazide diuretics, isotretinoin (Accutane), and some beta blockers.

The NCEP divides triglyceride levels into four categories (see Table 1). The treatment for high triglyceride levels depends on the cause of the elevation and its severity. For people who have borderline high (150–199 mg/dL) or high (200–499 mg/dL) triglycerides, the first goal of treatment is to bring LDLs to a healthy level. Look at Table 4 to find the appropriate LDL goal for your risk category and corresponding treatment recommendation.

Weight reduction and increased physical activity are an important part of treatment. The lifestyle changes that you can make to improve your triglyceride levels include losing weight, limiting alcohol to one drink a day, stopping smoking, and increasing your level of exercise. (As an added benefit, these interventions also lower LDL and raise HDL.) Dietary changes can also help reduce high levels of triglycerides. Such changes include limiting your daily calorie intake as well as the amount of fat and carbohydrate in your diet. Fish oil supplements may also help (see "Fish oil and heart disease," below).

For people with high or very high triglycerides (200 mg/dL or above) — as well as those with a combination of high LDL or a high risk for heart disease and borderline or higher triglycerides — lifestyle changes are generally accompanied by drug therapy. Drug therapies, in this case, include more aggressive LDL-lowering drugs or the use of nicotinic acid or a fibrate (gemfibrozil or fenofibrate).