Effects of alpha- and beta-blocker antihypertensive therapy on blood lipids: a multicenter trial.
Since reports that increased high-density lipoprotein cholesterol levels are a negative risk factor for ischemic heart disease, high-density lipoprotein cholesterol has become an important parameter to evaluate. We have shown that hypertensive patients have normal plasma high-density lipoprotein cholesterol levels, that these are higher in women than in men, and that they are significantly decreased in patients with coronary heart disease. Recently, studies have shown that the beta blocker propranolol unfavorably decreases high-density lipoprotein cholesterol levels and increases triglycerides, whereas the selective alpha 1-blocker prazosin increases high-density lipoprotein cholesterol and decreases triglycerides. A randomized 12-week multicenter trial was conducted to clarify the effects of prazosin and propranolol on serum lipids in essential hypertensive patients (WHO I, II, and III without severe end-organ damage) with blood pressures of at least 160 mm Hg systolic and 95 mm Hg diastolic after a minimum of four weeks treatment with trichlormethiazide (or an equivalent diuretic). Both drugs showed equally good antihypertensive effects. After 12 weeks of therapy, patients receiving prazosin (0.5 mg three times a day, titrated to a maximum dose of 12 mg per day) showed no change in high-density lipoprotein cholesterol, a significant decrease in triglycerides (169 to 129 mg/dl, p less than 0.001) and an increase in lecithin cholesterol acyltransferase (73 to 83 mg/dl). However, the opposite trend was apparent in patients receiving propranolol (10 mg three times a day, titrated to a maximum dose of 120 mg per day); there were decreases in high-density lipoprotein cholesterol, increases in triglycerides, and decreases in lecithin cholesterol acyltransferase, although these changes were not statistically significant. We postulate that the mechanism by which triglyceride is decreased during prazosin therapy is via activation of lipoprotein lipase, which results in a decrease in very low-density lipoprotein, and ultimately triglyceride. Conversely, the increase in lecithin cholesterol acyltransferase seen with prazosin is thought to be related to an increase in the activity of the high-density lipoprotein-lecithin cholesterol acyltransferase cycle, low-density lipoprotein pathway, and very low-density lipoprotein/high-density lipoprotein pathway, which results in elevated high-density lipoprotein cholesterol levels. In hypertensive patients receiving diuretics, prazosin and propranolol have opposing effects on lipid metabolism with prazosin having the more favorable profile.
D000293:Adolescent; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000097:blood*; D002986:Clinical Trials as Topic; D004041:Dietary Fats / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007564:Japan; D008297:Male; D008875:Middle Aged; D011224:Prazosin / Q000627:therapeutic use; D011433:Propranolol / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004041:Dietary Fats; D014280:Triglycerides; D002784:Cholesterol; D011433:Propranolol; D011224:Prazosin