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 2 intervention studies. In study 1 in hypertensive subjects, aldosterone was analyzed at baseline and after angiotensin II stimulation on both high- and low-sodium diets (1122 observations, 15% on statins for >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 and reduced salt sensitivity of blood pressure (both P<0.001). In study 2, aldosterone was measured in diabetic patients on a high-sodium diet, before and after angiotensin II 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 angiotensin II and a low-sodium diet in 2 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.

Keywords: adrenal cortex hormones; aldosterone; glucocorticoids; hypertension; sodium; statin.

Figure 1

Adjusted mean ± SD changes in aldosterone levels categorized by type of statins in hypertensive and diabetic subjects. HyperPATH: 1050 observations; Diabetes Trial: 143 observations.

Figure 2

Effects of acute statin treatment on aldosterone secretion in ex vivo mouse zona glomerulosa cells (ZG). Aldosterone levels were assessed in response to AngII 10-7 M or potassium (K+) 4.7 mM in the absence or presence of 3 different statins (all 10-5 M). Data represents means ± SD. *p<0.001 compared to AngII or K+; # P<0.001 compared between type of statin.