Abstract 3927: Comparative Effects of Ramipril and Candesartan on Plasma Leptin and Resistin Levels In the Treatment of Hypertensive Patients
Background: Cell culture study shows angiotensin II increases leptin secrestion. Leptin plays an important role in atherosclerotic lesion formation and progression. Resistin may serve as a link between insulin resistance to cardiovascular disease. However, the role of both in humans is unknown.
Methods: This was a randomized, double-blind, placebo-controlled cross-over trial with three treatment arms (each 2 months) and two washout periods (each 2 months). Thirty-four patients were given ramipril 10 mg and placebo, ramipril 10 mg and candesartan 16 mg, or candesartan 16 mg and placebo daily during each 2 month treatment period. Baseline mean body mass index was 25.24 Kg/m2.
Results:Ramipril, combined therapy, or candesartan significantly reduced blood pressure and increased plasma adiponectin levels after 2 months administration compared with baseline. However, combined therapy significantly reduced blood pressure and increased plasma adiponectin levels to a greater extent than ramipril or candesartan alone (P<0.001 for blood pressure and P=0.020 for adiponectin by ANOVA, respectively). Interestingly, only combined therapy significantly reduced plasma insulin levels and increased insulin sensitivity (determined by QUICKI) (P=0.001 and 0.002, respectively). Ramipril and candesartan tended to reduce plasma leptin levels by 11% and 5%, respectively, however, combined therapy significantly reduced plasma leptin levels relative to baseline measurements by 21% (P<0.001). The effect of combined therapy on leptin was significantly greater than ramipril or candesartan alone (P=0.042 by ANOVA). Surprisingly, ramipril, combined therapy, or candesartan increased plasma resistin levels relative to baseline measurements by 8%, 8%, and 12% (P=0.020, 0.151, and 0.015, respectively) with no significant differences among the three theapies (P=0.744 by ANOVA). Plasma resistin levels were not correlated with insulin sensitivity or body mass index.
Conclusions: Ramipril combined with candesartan increases plasma adiponectin and reduces leptin levels to a greater extent than monotherapy with either drug in hypertensive patients. Circulating resistin is unlikely to play a major role in insulin resistance in hypertensive patients.