Abstract 1134: Plasma Renin Activity is Associated With Increased Cardiovascular Events and Mortality in the HOPE Study
Background: Plasma Renin Activity (PRA) has been proposed as a potential biomarker of cardiovascular (CV) risk. However, this association remains controversial and has not been examined in a large clinical trial.
Methods and Results: We measured baseline PRA in 2913 high-risk patients with chronic stable vascular disease and/or diabetes enrolled in the Heart Outcomes Prevention Evaluation (HOPE) Study, and assessed its association with cardiovascular (CV) events and mortality over 4.5 years of follow-up using a Cox proportional hazards model. The age and sex adjusted hazard ratios (HR) for CV death, all-cause death and heart failure were 1.15 [1.00 –1.32] (p=0.04), 1.15 [1.03–1.27] (p=0.01), and 1.15 [1.03–1.29] (p=0.01) respectively (median PRA 0.82 ng/ml/hr). Furthermore, this relationship remained significant after adjusting for baseline use of beta-blocker therapy, and for allocation to ramipril or placebo. Compared to the referent lower fifth of the PRA distribution, patients in the upper fifth (>1.79 ng/ml/hr) had a substantially higher age and sex adjusted risk for major vascular events (CV death, myocardial infarction or stroke), CV death, all-cause death and heart failure, with HR of 1.49 [1.09 –2.04] (p=0.010), 2.02 [1.21–3.37] (p=0.007), 1.55 [1.10 –2.19] (p=0.01) and 1.56 [1.02–2.38] (p=0.04), respectively. These associations remained highly statistically significant after adjustment for a risk score shown to reliably discriminate risk in the HOPE study population and which considers age, gender, smoking status, hypertension, left ventricular hypertrophy, diabetes, prior stroke, peripheral vascular disease, coronary artery disease, and microalbuminuria. These associations remained statistically significant after adjustment for treatment with β-blockers and allocation to ramipril in the trial.
Conclusions: Elevated levels of PRA are associated with an increased risk of major CV events, CV death, all-cause death and heart failure in high-risk patients with stable chronic vascular disease and/or diabetes. PRA may thus represent a novel risk marker, and a potential target for therapy.