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Canadian Journal of Cardiology

Growth Differentiation Factor-15 Is a Useful Prognostic Marker in Patients With Heart Failure With Preserved Ejection Fraction

Published:December 20, 2013DOI:https://doi.org/10.1016/j.cjca.2013.12.010

      Abstract

      Background

      Circulating growth differentiation factor 15 (GDF-15) levels correlate with heart mass and fibrosis; however, little is known about its value in predicting the prognosis of patients with heart failure with preserved ejection fraction (HFpEF).

      Methods

      We measured serum GDF-15 levels in 149 consecutive patients with left ventricular diastolic dysfunction (LVDD) and normal LV ejection fraction (>50%) and followed them for cardiovascular events. LVDD was defined according to the European Society of Cardiology guidelines.

      Results

      The New York Heart Association functional class and circulating B-type natriuretic peptide (BNP) levels were significantly higher in the high–GDF-15 group (n = 75; greater than or equal to the median value [3694 pg/mL]) than in the low–GDF-15 group (n = 74). Patients were divided into HFpEF and LVDD groups according to the presence or absence of HF. Serum GDF-15 levels were significantly higher in the HFpEF group (n = 73) than in the LVDD group (n = 76) (median, 4215 [interquartile range, 3382-5287] vs 3091 [interquartile range, 2487-4217 pg/mL]; P < 0.0001). Kaplan-Meier curve analysis showed a significantly higher probability of cardiovascular events in the high–GDF-15 group than in the low–GDF-15 group for data of all patients (log-rank test P = 0.006) and data of patients in the HFpEF group only (P = 0.014). Multivariate Cox hazard analysis identified age (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.87-0.98; P = 0.008), atrial fibrillation (HR, 7.95; 95% CI, 1.98-31.85, P = 0.003), lnBNP (HR, 3.37; 95% CI, 1.73-6.55; P < 0.0001), and GDF-15 (ln[GDF-15]) (HR, 4.74; 95% CI, 1.26-17.88, P = 0.022) as independent predictors of primary end points.

      Conclusions

      GDF-15 is a potentially useful prognostic biomarker in patients with HFpEF.

      Résumé

      Introduction

      Les concentrations circulantes du GDF-15 (growth differenciation factor 15) corrèlent avec la masse cardiaque et la fibrose. Cependant, on en connaît peu sur sa valeur pour prédire le pronostic des patients ayant une insuffisance cardiaque à fraction d’éjection préservée (IC-FEP).

      Méthodes

      Nous avons mesuré les concentrations sériques du GDF-15 de 149 patients consécutifs ayant une dysfonction diastolique du ventricule gauche (DDVG) et une fraction d’éjection du VG normale (> 50 %), et avons suivi les événements cardiovasculaires subis. Le DDVG a été défini selon les lignes directrices de la Société européenne de cardiologie.

      Résultats

      La classification fonctionnelle et les concentrations circulantes du peptide natriurétique de type B (PNB) selon la New York Heart Association ont été significativement plus élevées dans le groupe ayant un GDF-15 élevé (n = 75; plus grand ou égal à la valeur médiane [3694 pg/ml]) que dans le groupe ayant un GDF-15 faible (n = 74). Les patients ont été divisés en deux groupes : le groupe ayant une IC-FEP et le groupe ayant un DDVG selon la présence ou l’absence d’IC. Les concentrations sériques du GDF-15 ont été significativement plus élevées dans le groupe ayant une IC-FEP (n = 73) que dans le groupe ayant un DDVG (n = 76) (médiane, 4215 [intervalle interquartile, 3382-5287] vs 3091 [intervalle interquartile, 2487-4217 pg/ml]; P < 0,0001). L’analyse de la courbe de Kaplan-Meier a montré une probabilité significativement plus élevée d’événements cardiovasculaires dans le groupe du GDF-15 élevé que dans le groupe du GDF-15 faible quant aux données de tous les patients (test logarithmique par rangs P = 0,006) et aux données des patients du groupe IC-FEP seul (P = 0,014). L’analyse multivariée selon le modèle de Cox a déterminé l’âge (rapport de risque [RR], 0,92; intervalle de confiance [IC] à 95 %, 0,87-0,98; P = 0,008), la fibrillation auriculaire (RR, 7,95; IC à 95 %, 1,98-31,85, P = 0,003), le lnBNP (RR, 3,37; IC à 95 %, 1,73-6,55; P < 0,0001) et le GDF-15 (ln[GDF-15]) (RR, 4,74; IC à 95 %, 1,26-17,88, P = 0,022) comme des prédicteurs de critères de jugement principaux.

      Conclusions

      Le GDF-15 est un biomarqueur pronostique potentiellement utile chez les patients ayant une IC-FEP.
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