Abstract

The renin-angiotensin system plays a central role in patients with established cardiovascular (CV) disease, but the prognostic effect of plasma renin in the community is unclear. The relationship between plasma renin concentration and CV events was studied in 6228 subjects who were enrolled in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study, and who were not using antihypertensive medication. Plasma renin concentration was measured using a direct automated immunochemiluminescent assay. The mean (± SD) age was 47(± 12) years, 49% were male; the mean follow-up was 10.5 years. The median (Q1-Q3) plasma renin was 17.6 (10.9-27.2) µIU/mL, and plasma aldosterone was 119 (93-153) ng/L. The primary outcome was a composite of fatal (n = 27) and non-fatal (n = 408) CV events. Adjusted for age and sex each doubling of plasma renin was associated with a hazard ratio (HR) for the primary outcome of 1.22 (95% CI: 1.04-1.43; P= 0.015). In a multivariable model, plasma renin showed a positive correlation with heart rate and male sex and a negative correlation with blood pressure, urinary sodium, glucose, and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) (adjusted R(2): 0.167, P< 0.001). After adjustment for covariates associated with plasma renin, the HR for reaching the primary outcome was 1.28 (95% CI: 1.09-1.49, P= 0.002). Plasma renin was associated with CV events regardless of blood pressure, but in subjects using antihypertensive medication this association was absent. Plasma renin concentration is associated with an increased risk for CV events in a community-based cohort not on antihypertensive medication.

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