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 <40% subgroup.
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.
- heart failure
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Contributors AA and GV: planning of the study, draft of the original paper; CPr and CPa: manuscript revision; ME, planning of the study, manuscript revision. ME and GV: responsible for the overall content as guarantors.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval This retrospective analysis conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the institutional review board (protocol number: 1437; approval date 25 May 2017).
Provenance and peer review Not commissioned; internally peer reviewed.
Data availability statement Data are available on reasonable request.
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