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Low levels of high-density lipoprotein cholesterol (HDL-C) are frequently encountered in patients with coronary artery disease (CAD), most often in combination with elevated triglycerides as part of a dysmetabolic syndrome. Although no large secondary prevention trials with statin therapy with special emphasis on low HDL-C have been performed, some guidance can be extracted from a number of post-hoc analyses on how to treat patients with low levels of HDL-C. In terms of risk reduction, statin therapy appears to be at least as effective in patients with low compared to normal HDL-C levels. Fibrate therapy seems only effective when low HDL-C coincides with a level of low-density lipoprotein cholesterol (LDL-C) in the low-normal range. Before considering combination therapy of statins with fibrates, much emphasis should be put on dietary changes, weight reduction, smoking cessation and regular exercise, since these measures are effective tools to raise HDL-C levels. Moreover, one should be aware of the fact that combination therapy of statins and fibrates is not evidence-based and confers some potential risk of myopathy. Future therapy options may include CETP (cholesterol ester transfer protein) inhibitors, but these agents are still in an experimental phase. As most patients with low HDL-C levels share features of the dysmetabolic syndrome, one could also consider a combination therapy of statins and ACE-inhibitors, since this combination is not only safe, but the individual preventive effects of these compounds appear to be cumulative.

New insights into low high-density lipoprotein cholesterol identify promising new directions for coronary heart disease prevention. The ATP-binding-cassette A1 gene has been identified as an important defect in genetic disorders of this lipid fraction. Recent studies indicate a benefit in treating patients with low levels of high-density lipoprotein cholesterol and suggest new clinical recommendations.

Dyslipidemias in patients with coronary heart disease confer a greater risk of ischemic cardiac events than comparable dyslipidemias in people free of disease. A major dyslipidemia can be diagnosed in more than 80% of patients with established premature coronary heart disease. These dyslipidemias constitute not only elevations of low-density lipoprotein cholesterol (hypercholesterolemia) but also indicate abnormalities in the metabolism of triglyceride-rich lipoproteins, high-density lipoproteins, and lipoprotein(a). Clinical trials have demonstrated that therapy to lower low-density lipoprotein levels can delay angiographic progression of coronary stenoses and reduce recurrent cardiac event rates. These clinical benefits from low-density lipoprotein cholesterol lowering may occur as early as 6 to 12 months after initiation of therapy. Intervention strategies for dyslipidemias are directed toward lowering the low-density lipoprotein cholesterol fraction to 90 to 100 mg/dl. This approach begins with dietary modification, weight loss, smoking cessation, and aerobic exercise. Patients with hypercholesterolemia refractory to nonpharmacologic intervention require lipid-lowering agents. The choice of lipid-lowering medications is influenced by concomitant abnormalities of lipoprotein metabolism, such as hypertriglyceridemia or hypoalphalipoproteinemia. Treatment of primary dyslipidemias other than hypercholesterolemia may be warranted in the presence of other cardiac risk factors; however, a broader spectrum of clinical trial data is needed to support or refute this contention.

Patients with insulin-dependent diabetes mellitus (IDDM) are at an increased risk for coronary heart disease. Factors that may enhance the risk include dyslipidemia, hypertension, and hyperglycemia. Until recently, the importance of dyslipidemia in IDDM was ignored because the prevalence of high cholesterol levels was similar to that in the nondiabetic population. However, unique abnormalities in the composition and metabolism of lipoproteins may occur in IDDM patients. Management of IDDM patients, therefore, should include control of dyslipidemia as well as control of hyperglycemia and hypertension. The therapeutic goals for serum cholesterol reduction in IDDM patients should be lower than that for nondiabetic patients, and the goals for children should be even lower than those for adults. Both very-low-density lipoprotein and low-density lipoprotein (LDL) levels should be the targets for therapeutic interventions and not just the LDL alone. Because of the unique features of dyslipidemia in IDDM patients, the therapeutic options may not be the same as that for nondiabetic patients. Hyperglycemia should be controlled by matching daily energy intake and activity with appropriately timed doses of insulin. The diets should be low in saturated fats and cholesterol. If dyslipidemia persists despite diet and hyperglycemia management, drug therapy may be initiated. For IDDM children > or = 10 years of age with elevated LDL-cholesterol levels, the first-line therapy should be bile acid sequestrants. For adults with IDDM, bile acid sequestrants also may be the drugs of choice, particularly for normotriglyceridemic patients. Nicotinic acid therapy should be avoided. Among other drugs, hydroxymethyl-glutaryl coenzyme A reductase inhibitors may be preferable for patients with elevated LDL cholesterol and borderline hypertriglyceridemia. Fibric acid derivatives should be used for markedly hypertriglyceridemic patients. The role of probucol for dyslipidemia in IDDM patients is not clear.