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The HDL Challenge.

The long-awaited update of the National Cholesterol Education Program guidelines continues to emphasize the importance of lowering low-density lipoprotein. But the report also contains new recommendations that call on physicians to be more aggressive in treating patients with diabetes or risk factors such as low levels of high-density lipoprotein. (See story on p. 1.)

Physicians have long tended to underestimate the importance of HDL in evaluating coronary artery disease (CAD) risk. But as to why low high-density lipoprotein is important and what exactly should be done about it, the new guidelines from the NCEP are somewhat limited.

The revised guidelines designate an HDL level below 40 mg/dL as a categorical risk factor for CAD, which is an improvement over the previous cutoff of 35 mg/dL. According to the guidelines, an attempt should be made to raise HDL above 40 mg/dL for both primary and secondary prevention of CAD-related events.

Many epidemiologic studies have shown that HDL levels are useful in evaluating CAD risk. The results are consistent in all racial and ethnic groups studied. The Framingham Heart Study found isolated low HDL levels in 75% of patients with CAD and a baseline cholesterol less than 200 mg/dL. Framingham also showed that an HDL level above 60 mg/dL becomes a "negative risk factor" that can offset elevations in low-density lipoprotein. It is estimated that for every 1 mg/dL elevation in serum HDL, men and women lower their CAD risk by 2%-3%.

HDL appears to confer cardioprotection through a variety of mechanisms, such as its ability to transport cholesterol from peripheral cells back to the liver or steroidogenic organs (reverse cholesterol transport), block LDL oxidation, reduce endothelial adhesion molecule expression, and potentiate prostacyclin production.

But raising low serum HDL levels can be quite challenging. Consistent with the NCEP recommendations, lifestyle modification should be front-line therapy Smoking cessation can increase HDL levels by up to 20%. Aerobic exercise and weight loss increase HDL levels and improve insulin resistance. Moderate alcohol intake can help. Discontinuation of drugs that lower HDL levels ([beta]-blockers, progestins, anabolic steroids) also should be considered.

The NCEP guidelines describe most pharmacologic interventions as inadequately "robust" for raising HDL, but three types of medication have established efficacy in patients with low HDL levels-and they are underutilized.

Fibrate therapy can reduce CAD risk and slow plaque progression in patients with low HDL levels, as shown in the Helsinki Heart Study and the Lopid Coronary Angiographic Trial (LOCAT), Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT), and Veterans Affairs High Density Lipoprotein Cholesterol Intervention Trial study group (VA-HIT). Fibrates are a good choice for low HDL, hypertriglyceridemia, and LDL below 140 mg/dL.

Statin therapy decreases CAD-related risk in patients with low HDL levels. This was shown in the Monitored Atherosclerosis Regression Study (MARS), the Air Force Coronary/Texas Atherosclerosis Prevention Study (AFCAPS/TexCAPS), and the Lipoprotein and Coronary Atherosclerosis Study (LCAS). Statins are generally viewed as weak HDL-elevating agents, but recent studies show that in patients with baseline HDL levels below 35mg/dL, statins can raise HDL levels by 12%-18%. In patients with low HDL, statins decrease CAD-related risk and slow plaque progression more than other lipid-lowering agents.

Niacin is the most potent of the medications available for increasing HDL levels. As shown in the Coronary Drug Project, niacin decreases risk for MI and stroke, but it required 14 years of follow-up to show a reduction in mortality The Cholesterol Lowering Atherosclerosis Study (CLAS) and Familial Atherosclerosis Treatment Study (FATS) showed that niacin slows plaque progression. Niacin therapy can be difficult to tolerate, but newer sustained-release preparations have better side-effect profiles.

The use of drug combinations (statin plus niacin, statin plus fibrate, or fibrate plus niacin) in patients with particularly low HDL or complex lipid profiles is becoming more common. Combination therapy improves lipid profiles beyond what single-agent therapy can achieve, but there are as yet no outcome trials using combination therapy Moreover, there is increased risk for hepatotoxicity and myopathy, though this has not yet been definitively quantified. Thus, combination therapy should be reserved for patients in whom the potential benefits outweigh the risks.

The preponderance of evidence favors treating low HDL aggressively Although HDL elevation can be challenging in many patients, any rise in serum HDL decreases the risk for CAD-related complications.

DR. PETER P. TOTH is clinical associate professor of family and community medicine at Southern Illinois University, Carbondale, and practices at the Sullivan (III.) Clinic.
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Publication:Family Practice News
Article Type:Brief Article
Geographic Code:1USA
Date:Jun 15, 2001
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