An inverse association exists between high-density lipoprotein (HDL) cholesterol levels and coronary artery disease. Genetically determined high levels of HDL are associated with longevity and a decreased incidence of coronary artery disease. HDL levels appear to be predictive of coronary events, even in patients with cholesterol levels under 200 mg per dL (5.17 mmol per L). Rader reviewed the pathophysiology and management of low HDL levels.

HDL is a class of particles containing lipids (phospholipids, cholesterol and triglycerides) and proteins (apolipoproteins, enzymes and lipid transfer proteins). HDL particles may be subclassified based on lipid content and size. Small HDL particles promote movement of excess unesterified cholesterol from peripheral cells. This unesterified cholesterol is esterified on HDL and transferred to the liver.

Persons with the lowest HDL levels have the greatest decrease in coronary events when treated with gemfibrizil. Study calculations suggest that for every 1 percent increase in the HDL cholesterol level, the risk of having a coronary event decreased 3 percent.

Patients with low HDL cholesterol levels should undergo lifestyle counseling, including instruction about smoking cessation, weight reduction, exercise and proper diet, although very-low-fat diets may actually decrease HDL levels. Medical conditions associated with decreased HDL include type 2 diabetes (formerly known as non–insulin-dependent diabetes), chronic renal failure and chronic inflammatory conditions such as rheumatoid arthritis. Medications such as beta blockers, thiazide diuretics, androgens, progestins and probucol may also decrease HDL cholesterol levels. Oral estrogen therapy may bring about modest increases in HDL.

Reduction of hypertriglyceridemia is generally associated with an increase in HDL. Fibrates are probably the first choice of treatment in patients with significantly elevated triglyceride levels (near 500 mg per dL [5.64 mmol per L]). Fish oil can be an effective secondary agent in patients with severe hypertriglyceridemia who cannot tolerate fibrates or who do not have an adequate response to this medication. Niacin may be used in patients with moderate hypertriglyceridemia. High dosages of statins may be useful in patients with moderately elevated triglyceride levels but not in patients with severe elevations.

The author notes that treatment of patients with low HDL levels and normal triglyceride levels is more complex. Lovastatin can be used to lower low-density lipoprotein (LDL) cholesterol and decrease the number of cardiac events, but the HDL level will be minimally affected. Patients with acceptable levels of LDL and isolated low HDL levels may benefit from treatment with niacin or gemfibrizil.