Proenkephalin and prognosis in heart failure with preserved ejection fraction: a GREAT network study.



Kanagala, Prathap ORCID: 0000-0001-6739-5607, Squire, Iain B, Jones, Donald JL ORCID: 0000-0001-6583-870X, Cao, Thong Huy ORCID: 0000-0002-6559-0836, Chan, Daniel CS, McCann, Gerry ORCID: 0000-0002-5542-8448, Sandhu, Jatinderpal K ORCID: 0000-0002-5612-274X, Quinn, Paulene A, McAdam, John, Marsh, Anna-Marie
et al (show 10 more authors) (2019) Proenkephalin and prognosis in heart failure with preserved ejection fraction: a GREAT network study. Clinical research in cardiology : official journal of the German Cardiac Society, 108 (8). pp. 940-949.

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Abstract

<h4>Background</h4>Proenkephalin (PENK), a stable endogenous opioid biomarker related to renal function, has prognostic utility in acute and chronic heart failure. We investigated the prognostic utility of PENK in heart failure with preserved ejection fraction (HFpEF), and its relationship to renal function, Body Mass Index (BMI), and imaging measures of diastolic dysfunction.<h4>Methods</h4>In this multicentre study, PENK was measured in 522 HFpEF patients (ejection fraction > 50%, 253 male, mean age 76.13 ± 10.73 years) and compared to 47 age and sex-matched controls. The primary endpoint was 2-years composite of all-cause mortality and/or heart failure rehospitalisation (HF). A subset (n = 163) received detailed imaging studies.<h4>Results</h4>PENK levels were raised in HFpEF (median [interquartile range] 88.9 [62.1-132.0]) compared to normal controls (56.3 [47.9-70.5]). PENK was correlated to urea, eGFR, Body Mass Index and E/e' (r<sub>s</sub> 0.635, - 0.741, - 0.275, 0.476, respectively, p < 0.0005). During 2 years follow-up 144 patients died and 220 had death/HF endpoints. Multivariable Cox regression models showed PENK independently predicted 2 year death/HF [hazard ratio (for 1 SD increment of log-transformed biomarker) HR 1.45 [95% CI 1.12-1.88, p = 0.005]], even after adjustment for troponin (HR 1.59 [1.14-2.20, p = 0.006]), and Body Mass Index (HR 1.63 [1.13-2.33, p = 0.009]). PENK showed no interaction with ejection fraction status for prediction of poor outcomes. Net reclassification analyses showed PENK significantly improved classification of death/HF outcomes for multivariable models containing natriuretic peptide, troponin and Body Mass Index (p < 0.05 for all).<h4>Conclusions</h4>In HFpEF, PENK levels are related to BMI, and measures of diastolic dysfunction and are prognostic for all-cause mortality and heart failure rehospitalisation.

Item Type: Article
Uncontrolled Keywords: GREAT (Global REsearch on Acute Conditions Team) Network, Heart Ventricles, Humans, Enkephalins, Protein Precursors, Magnetic Resonance Imaging, Cine, Echocardiography, Doppler, Stroke Volume, Glomerular Filtration Rate, Prognosis, Cause of Death, Survival Rate, Aged, Switzerland, Female, Male, Heart Failure, Biomarkers
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Clinical Directorate
Depositing User: Symplectic Admin
Date Deposited: 11 Jan 2022 15:56
Last Modified: 15 Mar 2024 20:16
DOI: 10.1007/s00392-019-01424-y
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3146263