Abstract-Certain hydroxymethylglutaryl coenzyme A reductase inhibitors, ie, statins, may cause vasodilation by restoring the endothelial dysfunction that frequently accompanies hypertension and hypercholesterolemia. Several studies have found that a blood pressure reduction is associated with the use of statins, but conclusive evidence from controlled trials is lacking. After an 8-week placebo and diet run-in period, 30 persons with moderate hypercholesterolemia and untreated hypertension (total cholesterol 6.29Ϯ0.52 mmol/L, systolic and diastolic blood pressure 149Ϯ6 and 97Ϯ2 mm Hg) were randomized in a double-blind manner to placebo or pravastatin (20 to 40 mg/d) in a crossover design. In 25 participants who completed the 32-week trial, pravastatin decreased total and LDL cholesterol (both Ϫ1.09 mmol/L, Pϭ0.001), systolic and diastolic blood pressure (Ϫ8 and Ϫ5 mm Hg, both Pϭ0.001), and pulse pressure (Ϫ3 mm Hg, Pϭ0.011) and blunted the blood pressure increase caused by the cold pressor test (Ϫ4 mm Hg, Pϭ0.005) compared with placebo. It also reduced the level of circulating endothelin-1 (Pϭ0.001). The blood pressure results were virtually unchanged in stratified analyses according to gender and age and in intention-to-treat analyses that included the 5 patients who dropped out of the study. When the participants were taking either placebo or pravastatin, blood pressure was not significantly correlated with total or LDL cholesterol or with circulating endothelin-1. Pravastatin decreases systolic, diastolic, and pulse pressures in persons with moderate hypercholesterolemia and hypertension. This antihypertensive effect may contribute to the documented health benefits of certain statins. (Hypertension. 1999;34:1281-1286.)Key Words: statins Ⅲ blood pressure Ⅲ cholesterol Ⅲ endothelin Ⅲ hypertension, essential Ⅲ hypercholesterolemia C ertain statins, or hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, are clinically proven to prevent coronary and cerebrovascular events in persons with increased plasma cholesterol levels. 1 In a large primary prevention trial, 2 it has been observed that compared with placebo, pravastatin can decrease the risk of cardiovascular events early after randomization. These findings suggest that in addition to the long-term prevention of atherosclerosis, other more immediate mechanisms might account for the clinical benefits of statins. 3 Several short-term studies have shown that statins can improve endothelial function and the endothelium-dependent arterial vasodilation that are typically altered in persons with increased plasma cholesterol levels. 4 -7 Hypercholesterolemia, endothelial dysfunction, and hypertension are frequently coexisting conditions, even in the absence of documented atherosclerotic lesions. 8 -11 Moreover, recent animal data indicate that the effect of pravastatin on the endothelium might be due in part to nonlipid effects. 12 In theory, by improving endothelial dysfunction, cholesterol reduction with statins may decrease blood pressure in persons wi...

Abstract-The basic requirement for declaring an association study positive is that the "hypertension-favoring" allele is more frequent in hypertensive cases than in normotensive controls. However, both positive and negative associations with hypertension have been found for the same polymorphism when studied in different populations. In the present study, we addressed the question of the possible cause(s) of this discrepancy among populations by using the ␣-adducin polymorphism as a paradigm. Four hundred ninety hypertensives and 176 normotensives enrolled in Sassari, Italy, and 468 hypertensives and 181 normotensives enrolled in Milano, Italy, were genotyped for the ␣-adducin Gly460Trp polymorphism. The blood pressure response to 2 months of hydrochlorothiazide therapy could be evaluated in 143 (85 in Sassari and 58 in Milano) hypertensives with and without the 460Trp ␣-adducin allele. The ␣-adducin 460Trp allele was not significantly more frequent in hypertensives in the Sassari population but was more frequent in hypertensives than in normotensives in Milano (Pϭ0.019). Basal plasma renin activity was lower and blood pressure fall after diuretic therapy more pronounced (PϽ0.01) in hypertensives carrying at least one 460Trp allele than in Gly460Gly homozygotes, irrespective of their membership in the Sassari or Milano cohort. The effect of ␣-adducin genotype in predicting basal plasma renin activity and blood pressure decrease with diuretic treatment is similar in Sassari and Milano, despite the lack of association of the ␣-adducin genotype with hypertension in Sassari. (Hypertension. 1999;34:649-654.)