Abstract Body (Do not enter title and authors here): Background: Dysregulated aldosterone is a modulator for the development and progression of cardio-renal-metabolic disease.
Aim: This study aimed to investigate the prognostic value of aldosterone plasma concentration in relation to incident cardiovascular disease (CVD) and mortality in a population-based cohort.
Methods: Participants from the population-based Gutenberg Health Study, a prospective cohort in Western Germany, underwent deep clinical phenotyping including venous blood sampling under standardized conditions. Quantification of baseline aldosterone concentration was performed using a chemiluminescent immunoassay (DiaSorin, Dietzenbach, Germany). Incident CVD was defined as the composite endpoint of incident coronary artery disease, atrial fibrillation, stroke, myocardial infarction and cardiac death. Mortality was assessed through regular verification of vital status via registration offices and death certificates from the mortality registry. Aldosterone concentrations were stratified by quartiles. Cox regression adjusted for age and sex was used to assess the association between aldosterone concentration and clinical outcomes. Based on an observed nonlinear U-shaped relationship, the lowest (Q1) and highest (Q4) quartiles were each compared against the middle quartiles (Q2-Q3).
Results: The analysis sample included n=14,756 individuals with aldosterone measurements with a mean±SD age of 55.0±11.1 years, of whom 49.3% were women. The median (interquartile range) plasma concentration of aldosterone was 7.51 ng/dL (5.62/10.10). Follow-up time for all-cause death was 15 years (n events=1,753), for cardiac death 10 years (n events=716) and for incident CVD 5 years (n events=759). Compared to the middle quartiles (Q2-Q3) of aldosterone, individuals in the lowest quartile (Q1) had a higher risk of all-cause death (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.03; 1.30, p=0.012), while the associations with cardiac death (HR 1.21, 95% CI 0.87; 1.68, p=0.26) and incident CVD (HR 0.96, 95% CI 0.81; 1.15, p=0.67) were not statistically significant. In contrast, those in the highest quartile (Q4) showed an increased risk of all-cause death (HR 1.46, 95% CI 1.31; 1.64, p<0.0001), cardiac death (HR 1.65, 95% CI 1.22; 2.24, p=0.0012), and incident CVD (HR 1.29, 95% CI 1.09; 1.53, p=0.004).
Conclusion: In this large population-based cohort, dysregulated plasma aldosterone was associated with an increased risk of mortality, cardiac death, and incident CVD.