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

TY - JOUR

T1 - Proenkephalin and prognosis in heart failure with preserved ejection fraction: a GREAT network study

AU - Kanagala, Prathap

AU - Squire, Iain B

AU - Jones, Donald J L

AU - Cao, Thong Huy

AU - Chan, Daniel C S

AU - McCann, Gerry

AU - Sandhu, Jatinderpal K

AU - Quinn, Paulene A

AU - McAdam, John

AU - Marsh, Anna-Marie

AU - Davies, Joan E

AU - Struck, Joachim

AU - Bergmann, Andreas

AU - Sabti, Zaid

AU - Twerenbold, Raphael

AU - Herrmann, Thomas

AU - Kozhuharov, Nikola

AU - Mueller, Christian

AU - Ng, Leong L

AU - GREAT (Global REsearch on Acute Conditions Team) Network

PY - 2019/8

Y1 - 2019/8

N2 - BACKGROUND: 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.METHODS: 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.RESULTS: 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' (rs 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).CONCLUSIONS: In HFpEF, PENK levels are related to BMI, and measures of diastolic dysfunction and are prognostic for all-cause mortality and heart failure rehospitalisation.

AB - BACKGROUND: 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.METHODS: 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.RESULTS: 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' (rs 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).CONCLUSIONS: In HFpEF, PENK levels are related to BMI, and measures of diastolic dysfunction and are prognostic for all-cause mortality and heart failure rehospitalisation.

KW - Aged

KW - Biomarkers/blood

KW - Cause of Death/trends

KW - Echocardiography, Doppler

KW - Enkephalins/blood

KW - Female

KW - Glomerular Filtration Rate/physiology

KW - Heart Failure/blood

KW - Heart Ventricles/diagnostic imaging

KW - Humans

KW - Magnetic Resonance Imaging, Cine

KW - Male

KW - Prognosis

KW - Protein Precursors/blood

KW - Stroke Volume/physiology

KW - Survival Rate/trends

KW - Switzerland/epidemiology

U2 - 10.1007/s00392-019-01424-y

DO - 10.1007/s00392-019-01424-y

M3 - SCORING: Journal article

C2 - 30767059

VL - 108

SP - 940

EP - 949

JO - CLIN RES CARDIOL

JF - CLIN RES CARDIOL

SN - 1861-0684

IS - 8

ER -