title: 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.
  
  
  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.
authors.affiliation: 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.
authors.forename: Rene
authors.initials: R
authors.lastname: Baudrand
authors.affiliation: 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.).
authors.forename: Luminita H
authors.initials: LH
authors.lastname: Pojoga
authors.affiliation: 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.).
authors.forename: Anand
authors.initials: A
authors.lastname: Vaidya
authors.affiliation: 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.).
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Garza
authors.affiliation: 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.).
authors.forename: Paul A
authors.initials: PA
authors.lastname: Vöhringer
authors.affiliation: 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.).
authors.forename: Xavier
authors.initials: X
authors.lastname: Jeunemaitre
authors.affiliation: 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.).
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hopkins
authors.affiliation: 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.).
authors.forename: Tham M
authors.initials: TM
authors.lastname: Yao
authors.affiliation: 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.).
authors.forename: Jonathan
authors.initials: J
authors.lastname: Williams
authors.affiliation: 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.).
authors.forename: Gail K
authors.initials: GK
authors.lastname: Adler
authors.affiliation: 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.
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Williams
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D003920:Diabetes Mellitus; D004039:Diet, Sodium-Restricted / Q000379:methods; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000097:blood* / Q000175:diagnosis* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000450:Aldosterone
keywords: adrenal cortex hormones; aldosterone; glucocorticoids; hypertension; sodium; statin