Abnormal Aldosterone Physiology and Cardiometabolic Risk Factors

Division of Endocrinology, Diabetes, and Hypertension.
Hypertension (Impact Factor: 6.48). 02/2013; 61(4). DOI: 10.1161/HYPERTENSIONAHA.111.00662
Source: PubMed

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.

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Available from: Claudio Ferri, Sep 29, 2015
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  • W Chen · F Li · C He · Y Zhu · W Tan
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    ABSTRACT: To conduct a meta-analysis of studies assessing abnormal glucose metabolism (AGM) prevalence among patients with primary aldosteronism (PA), calculating a combined pooled prevalence and summarizing metabolic parameters associated the pooled prevalence for comparative group. Four electronic databases (PubMed, EMBASE, Cochrane CENTRAL, and ISI-Web of Science) were systematically retrieved with no language and time restriction. Studies about elevated level of glucose metabolism in primary aldosteronism were included. Data were available in 16 studies. The pooled analysis revealed that the prevalence of elevated glucose in PA was 22.41 % (95 % CI 16.77-28.05 %), the retrospectively calculated prevalence was 31.20 % (95 % CI 15.81-46.60 %) for impaired fasting glucose, 26.19 % (95 % CI 15.17-37.21 %) for impaired glucose tolerance, 15.22 % (95 % CI 9.93-20.51 %) for diabetes mellitus. Prevalence of AGM in PA was higher than that in essential hypertension (OR = 1.55, 95 % CI 1.01-2.36, p = 0.04). From comparative groups, patients with primary aldosteronism had a lower level of insulin sensitivity indicators in comparison with normal group (p < 0.01). On the other hand, insulin resistance which presented by HOMA index was stronger in PA group than in normal control group (WMD = 0.41, 95 % CI 0.17, 0.65; p = 0.001), whereas it was weaker than that in EH group (WMD = -0.37, 95 % CI -0.62, -0.13; p = 0.003). There is a significant prevalence of elevated level of glucose metabolism in patients with PA. Awareness and treatment of this pre-diabetic or diabetic state are necessary.
    Irish Journal of Medical Science 08/2013; 183(2). DOI:10.1007/s11845-013-1007-x · 0.83 Impact Factor
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    ABSTRACT: Prehypertension is the category of blood pressure (BP) defined as systolic BP between 120 and 139 mmHg and diastolic BP between 85 and 89 mmHg. Prehypertension is a continuum to hypertension and is emerging as an important risk factor for cardiovascular disease. The definition of the cardiometabolic syndrome is a cluster of several risk factors such as abdominal obesity, prehypertension or hypertension, dyslipidemia and prediabetes. Prevention by lifestyle intervention and also treatment of individual components is recommended, given that most subjects with metabolic syndrome fall into the high-risk category. There are several studies with dietary approaches, which showed that these approaches helped in stopping the progression of hypertension and also improved the metabolic conditions. Several large trials are under way to study several antihypertensive drugs to delay the development of hypertension. Identifying early cardiovascular disease in asymptomatic individuals provides a better guide to the need for individualized preventive therapy than traditional risk factor assessment.
    Expert Review of Cardiovascular Therapy 12/2013; 11(12):1725-33. DOI:10.1586/14779072.2013.857272
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    ABSTRACT: Aging and abnormal aldosterone regulation are both associated with vascular disease. We hypothesized that aldosterone dysregulation influences the age-related risk of renal vascular and cardiovascular disease. We conducted an analysis of 562 subjects who underwent detailed investigations under conditions of liberal and restricted dietary sodium intake (1124 visits) in the General Clinical Research Center. Aldosterone regulation was characterized by the ratio of maximal suppression to stimulation (supine serum aldosterone on a liberal sodium diet divided by the same measure on a restricted sodium diet). We previously demonstrated that higher levels of this Sodium-modulated Aldosterone Suppression-Stimulation Index (SASSI) indicate greater aldosterone dysregulation. Renal plasma flow (RPF) was determined via p-aminohippurate clearance to assess basal renal hemodynamics and the renal vascular responses to dietary sodium manipulation and angiotensin II infusion. Cardiovascular risk was calculated using the Framingham Risk Score. In univariate linear regression, older age (β=-4.60; P<0.0001) and higher SASSI (β=-58.63; P=0.001) predicted lower RPF and a blunted RPF response to sodium loading and angiotensin II infusion. We observed a continuous, independent, multivariate-adjusted interaction between age and SASSI, where the inverse relationship between SASSI and RPF was most apparent with older age (P<0.05). Higher SASSI and lower RPF independently predicted higher Framingham Risk Score (P<0.0001) and together displayed an additive effect. Aldosterone regulation and age may interact to mediate renal vascular disease. Our findings suggest that the combination of aldosterone dysregulation and renal vascular dysfunction could additively increase the risk of future cardiovascular outcomes; therefore, aldosterone dysregulation may represent a modifiable mechanism of age-related vascular disease.
    Hypertension 03/2014; 63(6). DOI:10.1161/HYPERTENSIONAHA.114.03231 · 6.48 Impact Factor
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