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Diuretics and  -Blockers Do Not Have Adverse Effects at 1 Year on Plasma Lipid and Lipoprotein Profiles in Men With Hypertension
M. Raj Lakshman, PhD;
Domenic J. Reda, MS;
Barry J. Materson, MD, MBA;
William C. Cushman, MD;
Edward D. Freis, MD;
for the Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents
Arch Intern Med. 1999;159:551-558.
Background Concern based on the reported short-term adverse effects of antihypertensive agents on plasma lipid and lipoprotein profiles (PLPPs) has complicated the therapy for hypertension.
Objective To compare the long-term (1-year) effects of 6 different antihypertensive drugs and placebo on PLPPs in a multicenter, randomized, double-blind, parallel-group clinical trial in 15 US Veterans Affairs medical centers.
Patients and Methods A total of 1292 ambulatory men, 21 years or older, with diastolic blood pressures (DBPs) ranging from 95 to 109 mm Hg taking placebo were randomized to receive placebo or 1 of 6 antihypertensive drugs: hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem, or prazosin. After drug titration, patients with a DBP of less than 90 mm Hg were followed up for 1 year. Plasma lipids and lipoprotein profiles were determined at baseline, after initial titration, and at 1 year.
Results After 8 weeks on a regimen of hydrochlorothiazide, increases of 3.3 mg/dL (0.09 mmol/L) in total cholesterol and 2.7 mg/dL in apolipoprotein B were significantly different (P .05) from decreases of 9.3 mg/dL in total cholesterol and 5.4 mg/dL in ApoB levels while receiving prazosin but not from placebo. Patients achieving positive DBP control using hydrochlorothiazide (responders) showed no adverse changes in PLPPs, whereas nonresponders exhibited increases in triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels. Plasma lipids and lipoprotein profiles did not change significantly among treatment groups after 1 year except for minor decreases in high-density lipoprotein 2 levels using hydrochlorothiazide, clonidine, and atenolol.
Conclusions None of these 6 antihypertensive drugs has any long-term adverse effects on PLPPs and, therefore, may be safely prescribed. Previously reported short-term adverse effects from using hydrochlorothiazide are limited to nonresponders.
From the Lipid Research Laboratory, Department of Veterans Affairs Medical Center, Washington, DC (Drs Lakshman and Freis); Cooperative Studies Program, Edward Hines Jr Veterans Affairs Medical Center, Chicago, Ill (Mr Reda); the Department of Medicine, University of Miami School of Medicine, Miami, Fla (Dr Materson); and the Preventive Medicine Section, Veterans Affairs Medical Center, Memphis, Tenn (Dr Cushman).
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