Aims: 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.
Methods and results: 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.
Conclusion: Plasma renin concentration is associated with an increased risk for CV events in a community-based cohort not on antihypertensive medication.