Dataset Information

Fibroblast Growth Factor 23 and Exercise Capacity in Heart Failure with Preserved Ejection Fraction.

ABSTRACT:

Background

Heart failure with preserved ejection fraction (HFpEF) is characterized by left ventricular hypertrophy and decreased exercise capacity. Fibroblast growth factor 23 (FGF23), a hormone involved in phosphate, vitamin D, and iron homeostasis, is linked to left ventricular hypertrophy and HF. We measured c-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels and examined their associations with exercise capacity in patients with HFpEF.

Methods and results

Using multivariable linear regression and linear mixed models, we studied the associations of cFGF23 and iFGF23 with baseline and mean weekly change over 24 weeks in peak oxygen consumption and 6-minute walk distance in individuals enrolled in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF trial. Our study population included 172 individuals with available plasma for cFGF23 and iFGF23 measurements. Median (25th-75th percentile) baseline cFGF23 and iFGF23 levels were 208.7 RU/mL (132.1-379.5 RU/mL) and 90.3 pg/mL (68.6-128.5 pg/mL), respectively. After adjustment for cardiovascular disease and hematologic and kidney parameters, higher cFGF23 was independently associated with a lower peak oxygen consumption at baseline. Higher iFGF23 was independently associated with shorter 6-minute walk distance at baseline. No significant associations were appreciated with the longitudinal outcomes.

Conclusions

In patients with HFpEF, higher FGF23 levels are independently associated with decreased exercise capacity at baseline.

SUBMITTER: Ghuman J

PROVIDER: S-EPMC7914143 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Fibroblast Growth Factor 23 and Exercise Capacity in Heart Failure with Preserved Ejection Fraction.

Ghuman Jasleen J Cai Xuan X Patel Ravi B RB Khan Sadiya S SS Hecktman Jonathan J Redfield Margaret M MM Lewis Gregory G Shah Sanjiv J SJ Wolf Myles M Isakova Tamara T Mehta Rupal R

Journal of cardiac failure 20201007 3

<h4>Background</h4>Heart failure with preserved ejection fraction (HFpEF) is characterized by left ventricular hypertrophy and decreased exercise capacity. Fibroblast growth factor 23 (FGF23), a hormone involved in phosphate, vitamin D, and iron homeostasis, is linked to left ventricular hypertrophy and HF. We measured c-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels and examined their associations with exercise capacity in patients with HFpEF.<h4>Methods and results</h4>Using multivar ...[more]

PMID: 33035687

Similar Datasets

Project description:AimsThis 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.Methods and resultsWe 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.ConclusionsPlasma 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.

Project description:AimsBesides regulating calcium-phosphate metabolism, fibroblast growth factor 23 (FGF-23) has been associated with incident heart failure (HF) and left ventricular hypertrophy. However, data about FGF-23 in HF and preserved ejection fraction (HFpEF) remain limited. The aim of this study was to assess the association between FGF-23 levels, clinical and imaging characteristics, particularly diffuse myocardial fibrosis, and prognosis in HFpEF patients.Methods and resultsWe prospectively included 143 consecutive HFpEF patients (78 ± 8 years, 61% female patients) and 31 controls of similar age and gender (75 ± 6 years, 61% female patients). All subjects underwent a complete two-dimensional echocardiography and cardiac magnetic resonance with extracellular volume (ECV) assessment by T1 mapping. FGF-23 was measured at baseline. Among the patients, differences in clinical and imaging characteristics across tertiles of FGF-23 levels were analysed with a trend test across the ordered groups. Patients were followed over time for a primary endpoint of all-cause mortality and first HF hospitalization and a secondary endpoint of all-cause mortality. Median FGF-23 was significantly higher in HFpEF patients compared with controls of similar age and gender (247 [115; 548] RU/mL vs. 61 [51; 68] RU/mL, P < 0.001). Among HFpEF patients, higher FGF-23 levels were associated with female sex, higher incidence of atrial fibrillation, lower haemoglobin, worse renal function, and higher N terminal pro brain natriuretic peptide levels (P for trend < 0.05 for all). Regarding imaging characteristics, patients with higher FGF-23 levels had greater left atrial volumes, worse right ventricular systolic function, and more fibrosis estimated by ECV (P for trend < 0.05 for all). FGF-23 was moderately correlated with ECV (r = 0.46, P < 0.001). Over a mean follow-up of 30 ± 8 months, 43 patients (31%) died and 69 patients (49%) were hospitalized for HF. A total of 87 patients (62%) reached the primary composite endpoint of all-cause mortality and/or first HF hospitalization. In multivariate Cox regression analysis for the primary endpoint, FGF-23 (HR: 3.44 [2.01; 5.90], P < 0.001) and E wave velocities (HR: 1.01 [1.00; 1.02], P = 0.034) were independent predictors of the primary composite endpoint. In multivariate Cox regression analysis for the secondary endpoint, ferritin (HR: 1.02 [1.01; 1.03], P < 0.001), FGF-23 (HR: 2.85 [1.26; 6.44], P = 0.012), and ECV (HR: 1.26 [1.03; 1.23], P = 0.008) were independent predictors of all-cause mortality.ConclusionsFibroblast growth factor 23 (FGF-23) levels were significantly higher in HFpEF patients compared with controls of similar age and gender. FGF-23 was correlated with fibrosis evaluated by ECV. High levels of FGF-23 were significantly associated with signs of disease severity such as worse renal function, larger left atrial volumes, and right ventricular dysfunction. Moreover, FGF-23 was a strong predictor of poor outcome (mortality and first HF hospitalization).

Project description:BackgroundInorganic nitrate (NO3(-)), abundant in certain vegetables, is converted to nitrite by bacteria in the oral cavity. Nitrite can be converted to nitric oxide in the setting of hypoxia. We tested the hypothesis that NO3(-) supplementation improves exercise capacity in heart failure with preserved ejection fraction via specific adaptations to exercise.Methods and resultsSeventeen subjects participated in this randomized, double-blind, crossover study comparing a single dose of NO3-rich beetroot juice (NO3(-), 12.9 mmol) with an identical nitrate-depleted placebo. Subjects performed supine-cycle maximal-effort cardiopulmonary exercise tests, with measurements of cardiac output and skeletal muscle oxygenation. We also assessed skeletal muscle oxidative function. Study end points included exercise efficiency (total work/total oxygen consumed), peak VO2, total work performed, vasodilatory reserve, forearm mitochondrial oxidative function, and augmentation index (a marker of arterial wave reflections, measured via radial arterial tonometry). Supplementation increased plasma nitric oxide metabolites (median, 326 versus 10 μmol/L; P=0.0003), peak VO2 (12.6±3.7 versus 11.6±3.1 mL O2·min(-1)·kg(-1); P=0.005), and total work performed (55.6±35.3 versus 49.2±28.9 kJ; P=0.04). However, efficiency was unchanged. NO3(-) led to greater reductions in systemic vascular resistance (-42.4±16.6% versus -31.8±20.3%; P=0.03) and increases in cardiac output (121.2±59.9% versus 88.7±53.3%; P=0.006) with exercise. NO3(-) reduced aortic augmentation index (132.2±16.7% versus 141.4±21.9%; P=0.03) and tended to improve mitochondrial oxidative function.ConclusionsNO3(-) increased exercise capacity in heart failure with preserved ejection fraction by targeting peripheral abnormalities. Efficiency did not change as a result of parallel increases in total work and VO2. NO3(-) increased exercise vasodilatory and cardiac output reserves. NO3(-) also reduced arterial wave reflections, which are linked to left ventricular diastolic dysfunction and remodeling.Clinical trial registration urlwww.clinicaltrials.gov. Unique identifier: NCT01919177.

Dataset Information

Fibroblast Growth Factor 23 and Exercise Capacity in Heart Failure with Preserved Ejection Fraction.

Background

Methods and results

Conclusions

Publications

Fibroblast Growth Factor 23 and Exercise Capacity in Heart Failure with Preserved Ejection Fraction.

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