We compared the effect on serum lipids of an alpha-blocker (prazosin) and a diuretic (hydrochlorothiazide) used as initial antihypertensive drug treatment for 102 men and women with less severe hypertension (average entry blood pressure, 148/97 mm Hg, with no major organ system damage). A two-center trial randomized patients to treatment with either prazosin or hydrochlorothiazide; the alternate drug was added if adequate blood pressure control was not achieved with the originally assigned drug, and patients were removed from any drug they were not able to tolerate. After an average of 40 weeks on the assigned drug regimen, a decline was observed in prazosin-treated patients in both serum total cholesterol (-9.3 mg/dl) and serum triglycerides (-33.9 mg/dl). In contrast, an increase in both these lipids was seen in hydrochlorothiazide-treated patients (+5.0 mg/dl for serum total cholesterol and +18.6 mg/dl for serum triglycerides). The net trial differences between the groups were 14.3 mg/dl for total cholesterol and 52.5 mg/dl for triglycerides, in favor of prazosin (p less than 0.001 for both comparisons). These differences in lipids between the two groups persisted into the second year of the trial (p less than 0.05). There were no significant differences between the drug groups in regard to the level of high density lipoprotein cholesterol or its subfractions or low density lipoprotein cholesterol. In patients who required a combination of the two drugs to achieve blood pressure control, the alpha-blocker diminished or eliminated the lipid-raising effects of the diuretic. Both drugs were similar in their ability to control the elevation of diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

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