Aldosterone & Cardiometabolic Risk Factors

886 The renin–angiotensin–aldosterone system (RAAS) is a dynamic hormonal system. The manner in which the RAAS responds to physiological provocations, such as dietary sodium modulation, characterizes RAAS physiology and abnormalities in RAAS regulation may be associated with cardiometabolic diseases. This is highlighted in the literature that links aldosterone, using single cross-sectional measurements, with clinical outcomes and adverse cardiometabolic profiles. Improving the understanding of aldosterone dysregulation may provide insights into new avenues for the treatment and prevention of pathological conditions associated with altered adrenal physiology. Aldosterone dysregulation has been associated with cardiometabolic risk factors, and individual components of the metabolic syndrome (MetS) associate with higher aldosterone concentrations in human studies. These studies used single aldosterone measures as the predictor, rather than evaluating the dynamic physiology that regulates aldosterone responses and actions and has been previously correlated with cardiometabolic pathophysiology. For example, highsodium dietary interventions maximally suppress adrenal aldosterone secretion; the inability to suppress aldosterone in this setting has been associated with insulin resistance, dyslipidemia, obesity, and diabetes mellitus. In contrast, induction of a very restricted (RES) sodium balance, or the infusion of exogenous angiotensin II (AngII), stimulates adrenal aldosterone secretion; a blunted stimulation of aldosterone in these settings has also been associated with similar cardiometabolic abnormalities. Therefore, we speculated that the integration of aldosterone suppression and stimulation would provide an improved representation of aldosterone physiology in disease states that could offer new insights in the pathogenesis and treatment of cardiometabolic derangements. Abstract—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.) • Online Data Supplement