Neuropeptide Y is Elevated in Heart Failure and is an Independent Predictor of Outcomes

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Abstract
Aims: Neuropeptide Y (NPY) is the most abundant neuropeptide found in the heart and is released alongside norepinephrine following prolonged sympathetic activation, a process that is implicated in the pathophysiology of heart failure (HF). In patients with severely impaired left ventricular ejection fraction (LVEF) undergoing cardiac resynchronization therapy, higher levels of NPY measured in coronary sinus blood, are associated with poorer outcome. The aim was to examine the association of peripheral venous NPY levels and outcomes in a HF population with a range of LVEF, using a highly sensitive and specific assay. Methods and results: The association between NPY and the composite outcome of cardiovascular death or HF hospitalization, its components, and all-cause mortality was examined using Cox regression analyses among 833 patients using a threshold of elevated NPY identified through binary recursive partitioning adjusted for prognostic variables including estimated glomerular filtration rate (eGFR), ejection fraction and B-type natriuretic peptide (BNP). The mean value of NPY was 25.8 ± 18.2 pg/ml. Patients with high NPY levels (≥29 pg/ml) compared with low values were older (73 ± 10 vs. 71 ± 11 years), more often male (58.5% vs. 55.6%), had higher BNP levels (583 [261–1096] vs. 440 [227–829] pg/ml), lower eGFR (46.4 ± 13.9 vs. 52.4 ± 11.7 ml/min/1.73 m2), and were more often treated with diuretics. There was no associated risk of HF hospitalization with NPY levels ≥29 vs. <29 pg/ml. Higher NPY levels were associated with a greater risk of cardiovascular and all-cause death (adjusted hazard ratio 1.56 [95% confidence interval 1.21–2.10], p = 0.003 and 1.30 [1.04–1.62], p = 0.02, respectively). There was no associated risk of HF hospitalization with higher NPY levels. Conclusions: Peripherally measured NPY is an independent predictor of all-cause and cardiovascular death even after adjustment for other prognostic variables, including BNP.
Funding Information
  • British Heart Foundation Centre of Research Excellence (RE/18/6/34217)
  • British Heart Foundation Centre of Research Excellence (RE/13/1/30181)
  • British Heart Foundation (PG/13/17/30050)
  • British Heart Foundation Senior Clinical Research Fellowship (FS/SCRF/20/32005)
  • Vera Melrose Heart Failure Research Fund
  • British Heart Foundation (PG/13/17/30050)

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