Statin Use and Adrenal Aldosterone Production in Hypertensive and Diabetic Subjects

Abstract

Background—Statins substantially reduce cardiovascular mortality and appear to have beneficial effects independent of their lipid lowering properties. We evaluated the hypothesis that statin use may modulate the secretion of aldosterone, a well-known contributor to cardiovascular disease Methods and Results—We measured adrenal hormones in two intervention studies. In study 1 in hypertensive subjects, aldosterone was analyzed at baseline and after angiotensin-II stimulation (AngII) on both high (HS) and low sodium (LS) diets (1122 observations, 15% on statins > 3 months). Statin users had 33% lower aldosterone levels in adjusted models (p < 0.001). Cortisol was not modified by statins. In secondary analyses, the lowest aldosterone levels were seen with lipophilic statins and with higher doses. Statin users had lower blood pressure (BP) and reduced salt sensitivity of BP (p=0.001). In study 2, aldosterone was measured in diabetic patients on a HS diet, before and after AngII stimulation (143 observations, 79% statin users). Again, statin users had 26% lower aldosterone levels (p =0.006), particularly those using lipophilic statins. Ex vivo studies in rat adrenal glomerulosa cells confirmed that lipophilic statins acutely inhibited aldosterone, but not corticosterone, in response to different secretagogues Conclusions—Statin use among hypertensive and diabetic subjects was associated with lower aldosterone secretion in response to AngII and LS diet in two human intervention studies. This effect appeared to be most pronounced with lipophilic statins and higher doses. Future studies to evaluate whether aldosterone inhibition may partially explain the robust cardioprotective effects of statins are warranted