Jenifer M. Brown, MD; Cassianne Robinson-Cohen, PhD; Miguel Angel Luque-Fernandez, MSc, MPH, PhD; Matthew A. Allison, MD, MPH; Rene Baudrand, MD; Joachim H. Ix, MD, MS; Bryan Kestenbaum, MD, MS; Ian H. de Boer, MD, MS; Anand Vaidya, MD, MMSc
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other funding agencies.
Acknowledgment: The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at www.mesa-nhlbi.org.
Financial Support: This research was supported by contracts HHSN268201500003I, N01 HC95159, N01 HC95160, N01 HC95161, N01 HC95162, N01 HC95163, N01 HC95164, N01 HC95165, N01 HC95166, N01 HC95167, N01 HC95168, N01 HC95169, R01 HL096875, R01 HL071739, and R01 HL072403 from the National Heart, Lung, and Blood Institute and by grants UL1-TR-000040 and UL1-TR-001079 from the National Coalition for Cancer Research. Dr. Vaidya was supported by the National Institutes of Diabetes and Digestive and Kidney Disease of the National Institutes of Health under award R01 DK107407, by the National Heart, Lung, and Blood Institute under award K23 HL111771, and by grant 2015085 from the Doris Duke Charitable Foundation. Dr. Baudrand was supported by grants 1150437, 1150327, 1160836, and 1160695 from Fondo Nacional de Desarrollo Científico y Tecnológico and grant 13CTI-21526 -P1 from Corporación de Fomento de la Producción de Chile.
Disclosures: Dr. Allison reports grants from the National Institutes of Health during the conduct of the study. Dr. Ix reports grants from the National Institute of Diabetes and Digestive and Kidney Diseases during the conduct of the study. Dr. de Boer reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study and grants from the National Institute of Diabetes and Digestive and Kidney Diseases, the American Diabetes Association, and JDRF; nonfinancial support from Medtronic and Abbott; and personal fees from Boehringer Ingelheim and Ironwood Pharmaceuticals outside the submitted work. Dr. Vaidya reports grants from the National Institutes of Health and the Doris Duke Charitable Foundation during the conduct of the study and personal fees from The Endocrine Society outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-0882.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: Available at www.mesa-nhlbi.org. Statistical code: Requests will be considered on a case-by-case basis by Dr. Vaidya (e-mail, firstname.lastname@example.org). Data set: Available with approvals from the MESA steering committee and local institutional ethics board(s).
Requests for Single Reprints: Anand Vaidya, MD, MMSc, Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, RFB, Boston, MA 02115; e-mail, email@example.com.
Current Author Addresses: Dr. Brown: Division of Cardiovascular Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115.
Dr. Robinson-Cohen: Division of Nephrology, Vanderbilt University, 1161 21st Avenue South, D-3100 Medical Center North, Nashville, TN 37232.
Dr. Luque-Fernandez: Department of Epidemiology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom.
Dr. Allison: Department of Family Medicine and Public Health, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093.
Dr. Baudrand: Department of Endocrinology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330074, Chile.
Dr. Ix: Division of Nephrology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093.
Drs. Kestenbaum and de Boer: Division of Nephrology, Department of Medicine, University of Washington, 410 9th Avenue, Seattle, WA 98104.
Dr. Vaidya: Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, RFB, Boston, MA 02115.
Author Contributions: Conception and design: J.M. Brown, C. Robinson-Cohen, M.A. Allison, R. Baudrand, A. Vaidya.
Analysis and interpretation of the data: J.M. Brown, C. Robinson-Cohen, M.A. Luque-Fernandez, M.A. Allison, R. Baudrand, J.H. Ix, B. Kestenbaum, I.H. de Boer, A. Vaidya.
Drafting of the article: J.M. Brown, C. Robinson-Cohen, R. Baudrand, A. Vaidya.
Critical revision of the article for important intellectual content: J.M. Brown, C. Robinson-Cohen, M.A. Allison, R. Baudrand, J.H. Ix, B. Kestenbaum, I.H. de Boer, A. Vaidya.
Final approval of the article: J.M. Brown, C. Robinson-Cohen, M.A. Luque-Fernandez, M.A. Allison, R. Baudrand, J.H. Ix, B. Kestenbaum, I.H. de Boer, A. Vaidya.
Provision of study materials or patients: J.H. Ix, I.H. de Boer.
Statistical expertise: C. Robinson-Cohen, M.A. Luque-Fernandez, R. Baudrand, J.H. Ix, A. Vaidya.
Obtaining of funding: M.A. Allison, I.H. de Boer, A. Vaidya.
Administrative, technical, or logistic support: A. Vaidya.
Collection and assembly of data: M.A. Allison.
Primary aldosteronism is recognized as a severe form of renin-independent aldosteronism that results in excessive mineralocorticoid receptor (MR) activation.
To investigate whether a spectrum of subclinical renin-independent aldosteronism that increases risk for hypertension exists among normotensive persons.
National community-based study.
850 untreated normotensive participants in MESA (Multi-Ethnic Study of Atherosclerosis) with measurements of serum aldosterone and plasma renin activity (PRA).
Longitudinal analyses investigated whether aldosterone concentrations, in the context of physiologic PRA phenotypes (suppressed, ≤0.50 µg/L per hour; indeterminate, 0.51 to 0.99 µg/L per hour; unsuppressed, ≥1.0 µg/L per hour), were associated with incident hypertension (defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or initiation of antihypertensive medications). Cross-sectional analyses investigated associations between aldosterone and MR activity, assessed via serum potassium and urinary fractional excretion of potassium.
A suppressed renin phenotype was associated with a higher rate of incident hypertension than other PRA phenotypes (incidence rates per 1000 person-years of follow-up: suppressed renin phenotype, 85.4 events [95% CI, 73.4 to 99.3 events]; indeterminate renin phenotype, 53.3 events [CI, 42.8 to 66.4 events]; unsuppressed renin phenotype, 54.5 events [CI, 41.8 to 71.0 events]). With renin suppression, higher aldosterone concentrations were independently associated with an increased risk for incident hypertension, whereas no association between aldosterone and hypertension was seen when renin was not suppressed. Higher aldosterone concentrations were associated with lower serum potassium and higher urinary excretion of potassium, but only when renin was suppressed.
Sodium and potassium were measured several years before renin and aldosterone.
Suppression of renin and higher aldosterone concentrations in the context of this renin suppression are associated with an increased risk for hypertension and possibly also with increased MR activity. These findings suggest a clinically relevant spectrum of subclinical primary aldosteronism (renin-independent aldosteronism) in normotension.
National Institutes of Health.
Brown JM, Robinson-Cohen C, Luque-Fernandez MA, Allison MA, Baudrand R, Ix JH, et al. The Spectrum of Subclinical Primary Aldosteronism and Incident Hypertension: A Cohort Study. Ann Intern Med. [Epub ahead of print 10 October 2017]167:630–641. doi: 10.7326/M17-0882
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Published: Ann Intern Med. 2017;167(9):630-641.
Published at www.annals.org on 10 October 2017
Adrenal Disorders, Cardiology, Coronary Risk Factors, Endocrine and Metabolism, Hypertension.
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