The Impact of Statins on Aldosterone Production in Healthy Adults: A Randomized Controlled Study

Abstract Background Statins lower atherosclerotic cholesterol, but the cardiovascular benefit from treatment may extend beyond lipid management. Our group previously described in an observational study that individuals on statin therapy had 33% lower aldosterone (ALDO) than individuals not on statins, and this effect was greater in individuals taking a lipophilic statin (e.g. simvastatin) than a hydrophilic statin (e.g. pravastatin). Further, studies in isolated rodent adrenal zona glomerulosa cells demonstrated that statins lowered ALDO, and again lipophilic statins had a greater effect. We, therefore, tested the hypothesis that treatment with simvastatin would result in lower than treatment with pravastatin or placebo in a randomized controlled trial. Methods We conducted a 12-week, double-blind, randomized, placebo-controlled clinical trial among healthy adults ages with LDL-C > 70 mg/dL. Participants were randomized 1:1:1 to placebo, simvastatin 20 mg, or pravastatin 40 mg, stratified for sex. The study medication dose was doubled at Week 6 if the LDL-C decreased by less than 35% from screening values. We performed ALDO assessments at pre-treatment, 6-week, and 12-week post-treatment after 5 days on a controlled low sodium diet. Results Multivariate regression analysis controlling for sex, age, race, BMI, and pre-treatment angiotensin II (AngII)-stimulated ALDO showed no significant differences in the 12-week post-treatment AngII-stimulated ALDO between placebo and simvastatin (p-value 0.56; primary endpoint) nor between simvastatin and pravastatin (p-value 0.90; secondary endpoint). Conclusions Among healthy individuals on a low sodium diet, 12-week treatment with simvastatin or pravastatin did not alter ALDO responsiveness to AngII.