Elevated plasma renin activity predicts adverse outcome in chronic heart failure, independently of pharmacologic therapy: Data from the Valsartan heart failure trial (Val-HeFT)

Background: The prognostic value of plasma renin activity (PRA) in chronic heart failure (HF) has been assessed before the widespread use of angiotensin-converting enzyme inhibitors (ACEi) and beta-blockers, which exert opposite effects on renin secretion. We evaluated the association between PRA and outcome in patients with chronic HF treated with ACEi and beta-blockers. Methods and Results: PRA was measured in 4,291 patients from the Valsartan Heart Failure Trial (Val-HeFT). The prognostic performance of PRA in patients who were or were not taking ACEi or beta-blockers was evaluated by multivariable Cox models. PRA was elevated in patients on ACEi (median 5.85 [interquartile range (IQR) 1.82-17.83] ng/mL/h) compared with those not on ACEi (1.57 [0.74-4.15] ng/mL/h), and lower in those on beta-blockers (3.89 [1.17-12.61] ng/mL/h) than in those not on beta-blockers (6.21 [1.97-19.24] ng/mL/h). Lower systolic blood pressure, higher plasma aldosterone, and ACEi were associated with high PRA. Higher PRA was a strong and independent predictor of mortality in the whole population and in patients who were or were not treated with ACEi or beta-blockers. Conclusions: PRA is a powerful prognostic marker of death over a wide range of concentrations in patients with chronic HF. Prescription of ACEi and/or beta-blockers does not influence the relation between PRA and outcome.