Nonpharmacologic and pharmacologic alteration of high-density lipoprotein cholesterol: therapeutic approaches to prevention of atherosclerosis.
High-density lipoprotein (HDL) cholesterol, an independent coronary heart disease (CHD) risk factor, is inversely associated with CHD. Whether interventions to increase concentrations of HDL--particularly the HDL2, HDL3, and apolipoprotein A1 subfractions--will reduce the incidence of CHD in high-risk patients is thus an area of intense speculation. Both nonpharmacologic and pharmacologic regimens will raise HDL concentrations. Nonpharmacologic approaches include habitual high-level aerobic exercise and weight loss--both of these somewhat more effective in men than in women--cessation of cigarette smoking, and changing of dietary habits. A number of drugs have been found to elevate HDL cholesterol. These include the bile acid-binding resin cholestyramine, nicotinic acid, gemfibrozil, phenytoin, exogenous estrogens, and alcohol. Terbutaline has also been reported to raise HDL cholesterol. It is not yet known whether, and to what degree, pharmacologic and nonpharmacologic elevation of HDL cholesterol will retard or reverse the progression of atherosclerosis. Conversely, HDL cholesterol is lowered by a broad variety of drugs, including anabolic--androgenic steroids, exogenous progestins, and probucol, which are used therapeutically to reduce low-density lipoprotein (LDL) cholesterol. Some agents used to treat hypertension also reduce HDL cholesterol, especially thiazide diuretics and the beta blockers, with the possible exception of pindolol. In the antiadrenergic class of antihypertensive agents, reserpine and methyldopa lower HDL cholesterol, but the alpha blocker prazosin does not appear to affect HDL cholesterol. The alpha agonist guanabenz has no effect on HDL cholesterol, and the vasodilator carprazidil has been reported to raise HDL cholesterol. In light of these facts, investigations should be undertaken to determine whether the metabolic effects of antihypertensive agents blunt their beneficial effects on CHD.(ABSTRACT TRUNCATED AT 250 WORDS)
Glueck
C J
CJ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D001161:Arteriosclerosis / Q000517:prevention & control*; D001835:Body Weight; D008076:Cholesterol, HDL / Q000097:blood*; D004967:Estrogens / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D015248:Gemfibrozil; D009525:Niacin / Q000494:pharmacology; D010421:Pentanoic Acids / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D010809:Physical Fitness; D011743:Pyrimidines / Q000494:pharmacology; D012306:Risk; D012907:Smoking; D013726:Terbutaline / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D008076:Cholesterol, HDL; D004967:Estrogens; D010421:Pentanoic Acids; D011743:Pyrimidines; D014665:Vasodilator Agents; D009525:Niacin; D000431:Ethanol; D010672:Phenytoin; D013726:Terbutaline; C028934:carprazidil; D015248:Gemfibrozil