LONG-TERM EFFECTS ON PLASMA-LIPIDS OF DIET AND DRUGS TO TREAT HYPERTENSION

Objective.-To compare long-term plasma lipid changes among 6 antihyper tensive treatment interventions for stage I (mild) hypertension. Desig n.-Multicenter, randomized, double-blind, parallel-group clinical tria l. Setting.-Four academic clinical research units in the United States . Participants.-A total of 902 men and women, aged 45 to 69 years, wit h stage I diastolic hypertension (diastolic blood pressure <100 mm Hg) , recruited from 11 914 persons screened in their communities. Interve ntions.-Participants were randomized to 1 of 6 treatment groups: (1) p lacebo, (2) beta-blocker (acebutolol), (3) calcium antagonist (amlodip ine), (4) diuretic (chlorthalidone), (5) alpha(1)-antagonist (doxazosi n), and (6) angiotensin-converting enzyme inhibitor (enalapril). All g roups received intensive lifestyle counseling to achieve weight loss, dietary sodium and alcohol reduction, and increased physical activity. Main Outcomes Measures.-Changes in plasma total cholesterol, high-den sity lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) chol esterol, and triglycerides from baseline to annual visits through 4 ye ars. Results.-Mean changes in all plasma lipids were favorable in all groups. The degree of weight loss with fat-modified diet and exercise was significantly related to favorable lipid changes. Significant diff erences (P<.01) among groups for average changes during follow-up in e ach lipid were observed. Decreases in plasma total cholesterol and LDL cholesterol were greater with doxazosin and acebutolol (for plasma to tal cholesterol, 0.36 and 0.30 mmol/L [13.8 and 11.7 mg/dL], respectiv ely), less with chlorthalidone and placebo (0.12 and 0.13 mmol/L [4.5 and 5.1 mg/dL], respectively). Decreases in triglycerides were greater with doxazosin and enalapril, least with acebutolol. Increases in HDL cholesterol were greater with enalapril and doxazosin, least with ace butolol. Significant relative increases in plasma total cholesterol wi th chlorthalidone compared with placebo at 12 months were no longer pr esent at 24 months and beyond, when mean plasma total cholesterol for the chlorthalidone group fell below baseline. Analyses of participants continuing to receive chlorthalidone throughout the 4 years of follow -up indicated this was not due solely to an increasing percentage of p articipants changing or discontinuing use of medication during follow- up. Conclusions.-Weight loss with a fat-modified diet plus increased e xercise produces favorable long-term effects on blood pressure and all plasma lipid fractions of adults with stage I hypertension; blood pre ssure reduction is enhanced to a similar degree by addition of a drug from any one of 5 classes of antihypertensive medication. These drugs differ quantitatively in influencing the degree of long-term favorable effects on blood lipids obtained with nutritional-hygienic treatment.