Norepinephrine, plasma renin activity and cardiovascular mortality in systolic heart failure

Objective We analysed the circulating levels and prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP), norepinephrine (NE), epinephrine (E), plasma renin activity (PRA) and aldosterone in patients with systolic heart failure (HF) receiving therapies that target the sympathetic system and the renin-angiotensin-aldosterone axis. Methods We retrieved data from consecutive HF outpatients with left ventricular ejection fraction (LVEF) <50% and available neurohormones, evaluated at a tertiary referral centre for HF from 1999 to 2016. Results Patients (n=1477) were aged 66 +/- 13 years, 75% were men, median LVEF was 32% (IQR 25-38), 77% had LVEF <40% and 44% ischaemic HF. At the time of sampling, 69% were on beta-blockers, 75% on ACE inhibitors/angiotensin receptor blockers and 48% on mineralocorticoid receptor antagonists vs 88%, 87% and 66%, respectively, after therapy optimisation. Median NT-proBNP, NE, E, PRA and aldosterone were 1441 ng/L, 494 ng/L, 30 ng/L, 1.2 ng/mL/hour and 130 ng/dL, respectively. Over a 4.8-year follow-up (2.4-8.2), 376 patients died from cardiovascular causes (26%). NT-proBNP and PRA predicted cardiovascular mortality after adjusting for all other univariable predictors. The risk of cardiovascular death increased by 8% or 7% per each doubling of PRA in 2 models considering therapies at the time of sampling or after therapy optimisation. PRA improved metrics of reclassification and discrimination, and independently predicted outcome even in the LVEF Conclusions In patients with HF with LVEF <50% or <40%, PRA shows independent prognostic significance from a model that includes NT-proBNP, and might represent an additive tool for risk stratification.