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Norepinephrine, plasma renin activity and cardiovascular mortality in systolic heart failure
  1. Alberto Aimo1,2,
  2. Concetta Prontera1,
  3. Claudio Passino1,2,
  4. Michele Emdin1,2,
  5. Giuseppe Vergaro1,2
  1. 1 Fondazione Toscana Gabriele Monasterio, Pisa, Italy
  2. 2 Scuola Superiore Sant'Anna, Pisa, Italy
  1. Correspondence to Dr Alberto Aimo, Cardiology Department, University Hospital of Pisa, Pisa 56124, Italy; albertoaimo{at}


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
  • systolic
  • biomarkers

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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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.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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