Distinct vascular and metabolic effects of different classes of anti-hypertensive drugs

Background: ASCOT-BPLA study demonstrates that in hypertensive subjects, atenolol + bendroflumethiazide therapy is associated with higher incidence of adverse cardiovascular outcomes and developing diabetes than an amlodipine + perindopril regimen. This is not explained by changes in blood pressure alone. We hypothesized that distinct vascular and metabolic effects of anti-hypertensive drugs may explain these differential effects. Methods: Either placebo or one class of anti-hypertensive drug (atenolol 100 mg, amlodipine 10 mg, hydrochlorothiazide 50 mg, ramipril 10 mg, or candesartan 16 mg) was given daily during 8 weeks to 31 patients in each of 6 arms of a randomized, single-blind, placebo-controlled, parallel study. Results: Atenolol, amlodipine, and candesartan therapies significantly reduced systolic blood pressure when compared with ramipril (P < 0.05 by ANOVA). Atenolol and thiazide therapies increased triglycerides levels greater than ramipril or candesartan (P = 0.005 by ANOVA). Amlodipine significantly increased HDL cholesterol levels greater than atenolol (P = 0.011 by ANOVA). Ramipril and candesartan therapies improved FMD and increased adiponectin levels and insulin sensitivity to a greater extent than atenolol or thiazide therapies (P < 0.001 and P < 0.015 by ANOVA). Amlodipine therapy increased adiponectin levels greater than atenolol therapy (P < 0.05 by ANOVA). Ramipril, candesartan, and amlodipine therapies significantly decreased leptin levels to a greater extent when compared with atenolol or thiazide therapies (P < 0.001 by ANOVA). Amlodipine therapies significantly decreased resistin levels greater than ramipril or candesartan therapies (P = 0.001 by ANOVA). Conclusions: We observed differential effects of anti-hypertensive drugs on endothelial dysfunction and plasma adipocytokines.