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. 2015 Jan;65(1):45-53.
doi: 10.1161/HYPERTENSIONAHA.114.03936. Epub 2014 Nov 3.

Circulating aldosterone and natriuretic peptides in the general community: relationship to cardiorenal and metabolic disease

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Circulating aldosterone and natriuretic peptides in the general community: relationship to cardiorenal and metabolic disease

Alessia Buglioni et al. Hypertension. 2015 Jan.

Abstract

We sought to investigate the role of aldosterone as a mediator of disease and its relationship with the counter-regulatory natriuretic peptide (NP) system. We measured plasma aldosterone (n=1674; aged≥45 years old) in a random sample of the general population from Olmsted County, MN. In a multivariate logistic regression model, aldosterone analyzed as a continuous variable was associated with hypertension (odds ratio [OR]=1.75; 95% confidence interval [CI]=1.57-1.96; P<0.0001), obesity (OR=1.34; 95% CI=1.21-1.48; P<0.0001), chronic kidney disease (OR=1.39; 95% CI=1.22-1.60; P<0.0001), central obesity (OR=1.47; 95% CI=1.32-1.63; P<0.0001), metabolic syndrome (OR=1.41; 95% CI=1.26-1.58; P<0.0001), high triglycerides (OR=1.23; 95% CI=1.11-1.36; P<0.0001), concentric left ventricular hypertrophy (OR=1.22; 95% CI=1.09-1.38; P=0.0007), and atrial fibrillation (OR=1.24; 95% CI=1.01-1.53; P=0.04), after adjusting for age and sex. The associations with hypertension, central obesity, metabolic syndrome, triglycerides, and concentric left ventricular hypertrophy remained significant after further adjustment for body mass index, NPs, and renal function. Furthermore, aldosterone in the highest tertile correlated with lower NP levels and increased mortality. Importantly, most of these associations remained significant even after excluding subjects with aldosterone levels above the normal range. In conclusion, we report that aldosterone is associated with hypertension, chronic kidney disease, obesity, metabolic syndrome, concentric left ventricular hypertrophy, and lower NPs in the general community. Our data suggest that aldosterone, even within the normal range, may be a biomarker of cardiorenal and metabolic disease. Further studies are warranted to evaluate a therapeutic and preventive strategy to delay the onset and progression of disease, using mineralocorticoid antagonists or chronic NP administration in high-risk subjects identified by plasma aldosterone.

Keywords: aldosterone; biomarkers; chronic kidney disease; hypertension; natriuretic peptides; obesity.

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Conflict of interest statement

Conflicts of Interest/Disclosures: none.

Figures

Figure 1
Figure 1. Aldosterone Levels in the General Population
A) Aldosterone range in our entire cohort (overall); B) aldosterone according to tertiles; C) aldosterone distribution. x-axis= aldosterone levels, y-axis= % of subjects. The white bars indicate subjects with aldosterone levels in the 1st and 2nd tertiles; the blue bars indicate individuals in the 3rd tertile; the orange bars indicate subjects in the 3rd tertile with aldosterone levels above the normal range (n=95). The continuous line/arrow indicates the beginning of the 3rd tertile.
Figure 2
Figure 2. Kaplan-Meier Curve for Cumulative Incidence of All Cause-Death in the General Population
A) Aldosterone levels according to tertiles in the total population n=1674 (without excluding subjects with abnormal plasma aldosterone). 1st tertile (blue line) and 2nd tertile (red line) do not significantly correlate with an increased incidence of mortality. Aldosterone 3rd tertile (green line) is associated with an increased incidence of mortality (p=0.016). B) Aldosterone levels according to tertiles after excluding subjects with abnormal plasma aldosterone. Blue line (1st tertile), red line (2nd tertile), and green line (3rd tertile) do not significantly correlate with an increased incidence of mortality. Importantly, aldosterone abnormal levels (>16.2 ng/dL), orange line, were associated with a significant reduction in survival in the general community (p<0.001). Age, gender, BMI adjusted HR compared to 1st tertile: T2: 0.95 (0.70, 1.30), p=0.74; T3: 1.20 (0.90, 1.60), p=0.21; above normal range: 1.54 (1.03, 2.30), p=0.03. Follow-up results are truncated after 12-year. P-value (unadjusted log-rank test) significant when < 0.05.

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