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A Meta-Analysis of Growth Differentiation Factor-15 and Prognosis in Chronic Heart Failure.

ABSTRACT: Background: Previous studies had reported increased circulating concentrations of growth differentiation factor-15 (GDF-15) in chronic heart failure (CHF), suggesting the potential prognostic significance of GDF-15 in this setting. To verify the relationship between the circulating GDF-15 levels and prognosis of CHF patients, we conducted an updated evidence-based meta-analysis. Methods: A comprehensive literature retrieval of PubMed, EMBASE, and Cochrane library was performed to collect the qualified studies that analyzed the prognostic value of GDF-15 in CHF from the inception of these online databases to September 25, 2021. The hazard ratio (HR) calculated for logGDF-15 of all-cause death and the related 95% confidence interval (CI) in multivariate analysis were used to measure the effect size. Additionally, subgroup analyses stratified by characteristics of the study participants were conducted for incremental evidence of GDF-15 in CHF with different clinical status. Results: A total of ten eligible studies involving 6,244 CHF patients were finally taken into the quantitative analysis. Results in the random-effects model indicated that there was an increased risk of 6% in all-cause mortality with a per 1LnU increase in baseline GDF-15 concentration (HR: 1.06, 95% CI: 1.03-1.10, P < 0.001). In stratified analyses, the association of GDF-15 with risk of all-cause mortality was found among chronic ischemic HF patients (HR:1.75, 95%CI: 1.24-2.48, P = 0.002), while the association was not found among chronic nonischemic HF patients (HR:1.01, 95%CI: 1.00-1.02, P = 0.219). Conclusion: The elevated GDF-15 is associated with an increased risk of all-cause mortality in CHF, especially, among CHF patients with ischemic etiology. The circulating GDF-15 might be a prognostic indicator in CHF patients. Registration Number: https://www.crd.york.ac.uk/PROSPERO; CRD42020210796.

SUBMITTER: Luo JW

PROVIDER: S-EPMC8602355 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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A Meta-Analysis of Growth Differentiation Factor-15 and Prognosis in Chronic Heart Failure.

Luo Jin-Wen JW Duan Wen-Hui WH Song Lei L Yu Yan-Qiao YQ Shi Da-Zhuo DZ

Frontiers in cardiovascular medicine 20211105

<b>Background:</b> Previous studies had reported increased circulating concentrations of growth differentiation factor-15 (GDF-15) in chronic heart failure (CHF), suggesting the potential prognostic significance of GDF-15 in this setting. To verify the relationship between the circulating GDF-15 levels and prognosis of CHF patients, we conducted an updated evidence-based meta-analysis. <b>Methods:</b> A comprehensive literature retrieval of PubMed, EMBASE, and Cochrane library was performed to c ...[more]

PMID: 34805295

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Project description:AimsHeart failure with preserved ejection fraction (HFpEF) continues to be an increasingly common health problem associated with a high mortality rate. Elevated levels of Growth differentiation factor-15 (GDF15) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are reportedly associated with poor clinical outcomes in a broad range of cardiovascular diseases. The aim of the present study was to examine the effect of the combined assessment of these markers on clinical outcomes in patients with HFpEF.MethodsThis study is the prospective observational study. We measured the serum levels of GDF15 and NT-proBNP in 643 patients (mean age 73 ± 12, 42% females). All patients were prospectively followed up for a median period of 1998 days. Total 132 HF-related events and 88 all-cause deaths occurred during the follow-up period.ResultsMultivariate Cox proportional hazards regression analysis demonstrated that both serum GDF15 and NT-proBNP levels were independently associated with HF-related events after adjustment for confounding risk factors (GDF15: hazard ratio, 1.72; 95% confidence interval, 1.35-2.19; P < 0.0001 and NT-proBNP: hazard ratio, 1.63; 95% confidence interval, 1.25-2.13; P = 0.0003). Serum GDF15 levels improved the prediction capacity for HF-related events (0.7405 vs. 0.7190; P = 0.0422), with a significant net reclassification index (0.2724) and integrated discrimination improvement (0.0246). The C indices of GDF15 for HF-related events and all-cause deaths were significantly larger than those of NT-proBNP in men (HF-related events: 0.7389 vs. 0.6721; P = 0.0393, and all-cause deaths: 0.6922 vs.0.6109; P = 0.0262) but not in women. The combination of GDF15 and NT-proBNP levels stratified patients with HFpEF, identifying those at a high risk for HF-related events and all-cause deaths.ConclusionsSerum GDF15 could be an additional prognostic information to NT-proBNP in patients with HFpEF. The prognostic abilities of serum GDF15 and NT-proBNP differed according to sex. These markers were the feasible markers for patients with HFpEF, identifying those at a high risk for HF-related events and all-cause deaths.

Project description:AimsEndothelial cell vascular endothelial growth factor receptor 2 (VEGFR-2) plays a pivotal role in angiogenesis, which induces physiological cardiomyocyte hypertrophy via paracrine signalling between endothelial cells and cardiomyocytes. We investigated whether a decrease in circulating soluble VEGFR-2 (sVEGFR-2) levels is associated with poor prognosis in patients with chronic heart failure (HF).Methods and resultsWe performed a multicentre prospective cohort study of 1024 consecutive patients with HF, who were admitted to hospitals due to acute decompensated HF and were stabilized after initial management. Serum levels of sVEGFR-2 were measured at discharge. Patients were followed up over 2 years. The outcomes were cardiovascular death, all-cause death, major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death and HF hospitalization, and HF hospitalization. The mean age of the patients was 75.5 (standard deviation, 12.6) years, and 57% were male. Patients with lower sVEGFR-2 levels were older and more likely to be female, and had greater proportions of atrial fibrillation and anaemia, and lower proportions of diabetes, dyslipidaemia, and HF with reduced ejection fraction (<40%). During the follow-up, 113 cardiovascular deaths, 211 all-cause deaths, 350 MACE, and 309 HF hospitalizations occurred. After adjustment for potential clinical confounders and established biomarkers [N-terminal B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin I, and high-sensitivity C-reactive protein], a low sVEGFR-2 level below the 25th percentile was significantly associated with cardiovascular death [hazard ratio (HR), 1.79; 95% confidence interval (CI), 1.16-2.74] and all-cause death (HR, 1.43; 95% CI, 1.04-1.94), but not with MACE (HR, 1.11; 95% CI, 0.86-1.43) or HF hospitalization (HR, 1.03; 95% CI, 0.78-1.35). The stratified analyses revealed that a low sVEGFR-2 level below the 25th percentile was significantly associated with cardiovascular death (HR, 1.76; 95% CI, 1.07-2.85) and all-cause death (HR, 1.49; 95% CI, 1.03-2.15) in the high-NT-proBNP group (above the median), but not in the low-NT-proBNP group. Notably, the patients with high-NT-proBNP and low-sVEGFR-2 (below the 25th percentile) had a 2.96-fold higher risk (95% CI, 1.56-5.85) for cardiovascular death and a 2.40-fold higher risk (95% CI, 1.52-3.83) for all-cause death compared with those with low-NT-proBNP and high-sVEGFR-2.ConclusionsA low sVEGFR-2 value was independently associated with cardiovascular death and all-cause death in patients with chronic HF. These associations were pronounced in those with high NT-proBNP levels.

Dataset Information

A Meta-Analysis of Growth Differentiation Factor-15 and Prognosis in Chronic Heart Failure.

Publications

A Meta-Analysis of Growth Differentiation Factor-15 and Prognosis in Chronic Heart Failure.

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