Rene Baudrand1, Luminita H Pojoga2, Anand Vaidya2, Amanda E Garza2, Paul A Vöhringer2, Xavier Jeunemaitre2, Paul N Hopkins2, Tham M Yao2, Jonathan Williams2, Gail K Adler2, Gordon H Williams1. 1. From Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.B., L.H.P., A.V., A.E.G., T.M.Y., J.W., G.K.A., G.H.W.); Department of Endocrinology, School Of Medicine, Pontificia Universidad Catolica De Chile, Santiago, Chile (R.B.); Hospital Clinico, Facultad Medicina Universidad de Chile, Santiago, Chile and Tufts Medical Center, Tufts University School of Medicine, Boston, MA (P.A.V.); Centre Investigation Clinique, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Universite Paris Descartes, Paris, France (X.J.); and Cardiovascular Genetics Research, University of Utah School of Medicine Salt Lake City (P.N.H.). rbaudran@uc.cl gwilliams@partners.org. 2. From Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.B., L.H.P., A.V., A.E.G., T.M.Y., J.W., G.K.A., G.H.W.); Department of Endocrinology, School Of Medicine, Pontificia Universidad Catolica De Chile, Santiago, Chile (R.B.); Hospital Clinico, Facultad Medicina Universidad de Chile, Santiago, Chile and Tufts Medical Center, Tufts University School of Medicine, Boston, MA (P.A.V.); Centre Investigation Clinique, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Universite Paris Descartes, Paris, France (X.J.); and Cardiovascular Genetics Research, University of Utah School of Medicine Salt Lake City (P.N.H.).
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.
RCT Entities:
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 diabeticpatients 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.
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