4.7 Article

Abnormal Aldosterone Physiology and Cardiometabolic Risk Factors

Journal

HYPERTENSION
Volume 61, Issue 4, Pages 886-+

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.111.00662

Keywords

adrenal; aldosterone; metabolic syndrome; physiology; renin

Funding

  1. National Library of Medicine [U54LM008748]
  2. Harvard Clinical and Translational Science Center, from the National Center for Research Resources [UL1RR025758]
  3. Brigham and Women's Hospital, General Clinical Research Center, from the National Center for Research Resources [M01-RR02635]
  4. National Institute of Health [HL47651, HL59424, F32 NR013318, K24 HL103845, K23 HL111771-01]
  5. Specialized Center of Research (SCOR) in Molecular Genetics of Hypertension [P50HL055000]

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Abnormal aldosterone physiology has been implicated in the pathogenesis of cardiometabolic diseases. Single aldosterone measurements capture only a limited range of aldosterone physiology. New methods of characterizing aldosterone physiology may provide a more comprehensive understanding of its relationship with cardiometabolic disease. We evaluated whether novel indices of aldosterone responses to dietary sodium modulation, the sodium-modulated aldosterone suppression-stimulation index (SASSI for serum and SAUSSI for urine), could predict cardiometabolic risk factors. We performed cross-sectional analyses on 539 subjects studied on liberal and restricted sodium diets with serum and urinary aldosterone measurements. SASSI and SAUSSI were calculated as the ratio of aldosterone on liberal (maximally suppressed aldosterone) to the aldosterone on restricted (stimulated aldosterone) diets and associated with risk factors using adjusted regression models. Cardiometabolic risk factors associated with either impaired suppression of aldosterone on liberal diet, or impaired stimulation on restricted diet, or both; in all of these individual cases, these risk factors associated with higher SASSI or SAUSSI. In the context of abnormalities that constitute the metabolic syndrome, there was a strong positive association between the number of metabolic syndrome components (0-4) and both SASSI and SAUSSI (P<0.0001) that was independent of known aldosterone secretagogues (angiotensin II, corticotropin, potassium). SASSI and SAUSSI exhibited a high sensitivity in detecting normal individuals with zero metabolic syndrome components (86% for SASSI and 83% for SAUSSI). Assessing the physiological range of aldosterone responses may provide greater insights into adrenal pathophysiology. Dysregulated aldosterone physiology may contribute to, or result from, early cardiometabolic abnormalities. (Hypertension. 2013;61:886-893.) circle Online Data Supplement

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