Weight reduction and pharmacologic treatment in obese hypertensives

This study was conducted to evaluate the mechanisms of weight loss-induced blood pressure (BP) reduction focusing, in particular, on the contributions of sympathetic nervous system activity, fasting plasma insulin, and leptin to BP levels, and to delineate the additional influence of antihypertensiv e drug therapy. Each of five groups of obese hypertensives were treated wit h the long-acting calcium channel blocker (CCB) amlodipine, the angiotensin converting enzyme (ACE) inhibitor enalapril with or without a weight reduc tion program, or a weight reduction program alone. The goal BP was less tha n 140/90 mm Hg for the pharmacologic treatment groups. The weight reduction program groups with or without pharmacologic treatment were divided into t wo groups; weight loss groups who succeeded in weight reduction (greater th an or equal to 10%) and nonweight loss groups who failed in weight reductio n (< 10%) in the first 6 months. The final dose of CCB and ACE inhibitor were less in the combined pharmacol ogic and weight loss groups than in the pharmacologic treatment alone group s or in the pharmacologic and nonweight loss groups. In the weight reductio n groups regardless of pharmacologic treatment, the percent reductions from baseline in plasma insulin, leptin, and norepinephrine (NE) were greater i n the weight loss groups (greater than or equal to 10%) than in the nonweig ht loss groups (< 10%). The reductions in plasma NE, insulin, and leptin we re significantly greater and earlier in combined pharmacologic and weight l oss groups than in the pharmacologic treatment alone groups. In ACE inhibit or groups, the reductions in plasma NE, in insulin, and especially in lepti n were greater than the other groups. In the CCB alone group, reductions in insulin and leptin occurred. but there was no change in plasma NE. Reducti ons in insulin and leptin in CCB groups were less and occurred later than i n the ACE inhibitor groups or the weight reduction alone group. These results show that weight loss associated with favorable metabolic imp rovements and these improvements are amplified when combined with pharmacol ogic treatment. Therefore, weight loss should be regarded as an essential c omponent of any treatment program for obesity-related hypertension. A novel finding from this study is that ACE inhibition had a striking effect to lo wer plasma leptin. Suppression of sympathetic activity, insulinemia, and le ptinemia appeared to play a role in the BP reduction accompanying weight lo ss. (C) 2001 American Journal of Hypertension, Ltd.