Fibroblast-growth-factor-23 in heart failure with preserved ejection fraction: relation to exercise capacity and outcomes

Kanagala, Prathap ORCID: 0000-0001-6739-5607, Arnold, Jayanth R, Khan, Jamal N, Singh, Anvesha, Gulsin, Gaurav S, Eltayeb, Mohamed, Gupta, Pankaj, Squire, Iain B, McCann, Gerry P and Ng, Leong L (2020) Fibroblast-growth-factor-23 in heart failure with preserved ejection fraction: relation to exercise capacity and outcomes. ESC HEART FAILURE, 7 (6). pp. 4089-4099.

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Official URL: http://dx.doi.org/10.1002/ehf2.13020

Abstract

<h4>Aims</h4>This study aimed to assess plasma fibroblast growth factor 23 (FGF23) in patients with heart failure with preserved ejection fraction (HFpEF) and its relation to inflammation, renal function, clinical and imaging characteristics, exercise capacity, and prognosis.<h4>Methods and results</h4>We performed a prospective, observational study of 172 age-matched and sex-matched subjects (HFpEF n = 130; controls n = 42, age 73 ± 9, female 50%) who underwent plasma biomarker sampling, echocardiography, cardiac magnetic resonance imaging, and 6 min walk testing (6MWT). The primary endpoint was the composite of all-cause death or HF hospitalization. FGF23 was higher in HFpEF compared with controls (62 [42-105] vs. 34 [22-41] pg/mL, P < 0.0001). In HFpEF, FGF23 correlated with greater symptom burden (New York Heart Association class: r = 0.308), poorer exercise capacity (6MWT distance: r = -0.345), and plasma biomarkers reflecting inflammation (highly sensitive C-reactive protein: r = 0.207, myeloperoxidase: r = 0.311), bone metabolism (osteoprotegerin: r = 0.446), renal dysfunction (urea: r = 0.267, creatinine: r = 0.351, estimated glomerular filtration rate: r = -0.367), and echocardiographic E/e' (r = 0.298); P < 0.05. Following multivariable linear regression modelling, FGF23 remained independently associated with shorter 6MWT distance (P = 0.012) in addition to age, body mass index, and lower haemoglobin. During follow-up (median 1428 days), there were 61 composite events (21 deaths, 40 HF hospitalizations) in patients with HFpEF. In multivariable Cox regression analysis, FGF23 [adjusted hazard ratio (HR) 1.665; 95% confidence interval (CI) (1.284-2.160; P < 0.0001)], B-type natriuretic peptide (HR 1.433; CI 1.053-1.951; P = 0.022), and prior HF hospitalization (HR 2.058; CI 1.074-3.942; P = 0.030) were independent predictors of the composite endpoint.<h4>Conclusions</h4>Plasma FGF23 is higher in HFpEF compared with age-matched and sex-matched controls and is strongly associated with exercise incapacity and prognosis. FGF23 correlates with plasma markers of inflammation and renal impairment.

Item Type:	Article
Uncontrolled Keywords:	FGF23, Bone, Exercise capacity, Heart failure with preserved ejection fraction, Inflammation, Prognosis
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Clinical Directorate
Depositing User:	Symplectic Admin
Date Deposited:	16 Mar 2021 09:18
Last Modified:	18 Jan 2023 22:56
DOI:	10.1002/ehf2.13020
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3117361