Plasma renin activity predicts cardiovascular mortality in the Heart Outcomes Prevention Evaluation (HOPE) study

AIMS: Plasma renin activity (PRA) has been proposed as an independent predictor of cardiovascular (CV) risk, but there are limited data from large prospective studies, particularly in patients with stable vascular disease and/or diabetes, without heart failure. METHODS AND RESULTS: We evaluated the predictive value of PRA as a marker of CV events and mortality in a large population of patients with stable chronic vascular disease and/or diabetes and one CV risk factor. Baseline PRA was measured in 2913 patients enrolled in the Heart Outcomes Prevention Evaluation (HOPE) study. Subjects were followed for a median of 4.5 years. Compared with the referent lowest fifth, subjects in the highest fifth of the PRA distribution had a hazard ratio (HR) of 1.38 (95% confidence interval, 1.03-1.86; P = 0.03) for the composite of major vascular events, with an HR of 1.89 for CV death. These associations remained statistically significant after full adjustment for clinical characteristics, background use of β-blockers, diuretics, allocation to ramipril, in addition to inflammatory biomarkers, high-sensitivity C-reactive protein, and N-terminal pro-brain natriuretic peptide. CONCLUSION: High PRA is an independent predictor of major vascular events and mortality in a stable population of high-risk patients with atherosclerosis and/or diabetes. Although an increase in PRA could be a marker of more intense antihypertensive therapy, our results suggest that PRA may represent a risk marker and potential target for therapy in high-risk patients with atherosclerosis and/or diabetes.