Growth differentiation factor 15

ABCHF

Original Article

Prognostic Value of Growth Differentiation Factor-15 in Heart Failure: A Systematic Review with Meta-Analysis

Lorena dos Santos Marreto Rimolo et al. Humberto Villacorta

Abstract

Background

Growth differentiation factor-15 (GDF-15) has emerged as a promising biomarker in heart failure (HF), reflecting multiple pathophysiological mechanisms, including inflammation, oxidative stress, and cardiac remodeling. However, evidence regarding its prognostic value remains inconsistent.

Objective

To systematically evaluate the association between circulating levels of GDF-15 and adverse clinical outcomes, including all-cause mortality and HF hospitalization.

Methods

A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. PubMed, Embase, Cochrane Library, and Web of Science were searched through April 2025. Studies reporting baseline levels of GDF-15 and adjusted hazard ratios (HRs) for mortality and/or HF hospitalization were included. Pooled HRs were calculated using a random-effects model (DerSimonian and Laird method). Statistical heterogeneity was assessed using Higgins’ I² statistic, and publication bias was evaluated using Egger’s test.

Results

Seven studies (n = 10,578 patients [mean age, 67 ± 11 years; 58% male]) met the inclusion criteria. Increased levels of GDF-15 were significantly associated with increased all-cause mortality (pooled HR, 2.72; 95% CI, 1.55-4.17; p < 0.001; I² = 49%) and HF hospitalization (HR, 2.43; 95% CI, 1.79-3.30; p < 0.001). Subgroup analyses demonstrated consistent associations across different HF phenotypes. Funnel plot assessment and Egger’s test (p = 0.12) showed no evidence of publication bias.

Conclusions

Higher circulating levels of GDF-15 are independently associated with increased risks of mortality and HF hospitalization. Incorporating GDF-15 into multimarker prognostic models may improve risk stratification and support earlier, more individualized management strategies in HF.

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ABCHF

Original Article

Local Inflammation May Underlie Cardiac Damage in Post-COVID-19 Period

Marcio Roberto Moraes de Carvalho et al. Natalia Fonseca Rosário Alice Ramos Carla Rodrigues do Amaral Azevedo … Mario Luiz Ribeiro Guilherme Schittine Bezerra Lomba Evelyn Maciel de Oliveira Rachel V. O’Neill de Souza Mauro Jorge Cabral Castro Jocemir Ronaldo Lugon

Abstract

Background

Some patients experience subclinical cardiovascular dysfunction after COVID-19, possibly driven by persistent inflammatory mechanisms that remain incompletely understood. NT-proBNP and GDF-15 have been proposed as biomarkers of myocardial stress and inflammation in this context.

Objectives

To investigate associations between NT-proBNP, GDF-15, inflammatory cytokines, and echocardiographic parameters in patients with Post-COVID-19 Condition (PCC).

Methods

This cross-sectional study included 78 adults followed in a university hospital cohort. Participants were stratified into elevated NT-proBNP (n = 39) and normal NT-proBNP (n = 39) groups. Clinical, laboratory, and echocardiographic variables were assessed, including PALS and RV-GLS. Serum GDF-15 and cytokines were quantified using a multiplex bead assay. ROC curve analysis evaluated the predictive value of GDF-15 for elevated NT-proBNP.

Results

Participants with elevated NT-proBNP had reduced PALS (28.5% vs. 36.7%; p < 0.05), and higher GDF-15 (median 368 vs. 219 pg/mL) and IL-1β levels (2.47 vs. 0.94 pg/mL; p < 0.05). GDF-15 ≥ 519 pg/mL predicted elevated NT-proBNP (AUC = 0.65). Individuals with elevated GDF-15 also showed worse RV-GLS (20.2% vs. 26.9%; p < 0.05) and higher IL-8 levels (p < 0.05).

Conclusions

NT-proBNP, GDF-15, and IL-1β identify subclinical myocardial dysfunction in PCC, supporting a pathophysiological model centered on persistent inflammation and early myocardial remodeling, distinct from classic ischemic pathways.

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ABC

Artigo Original

Growth-differentiation factor-15: a novel biomarker in patients with diastolic dysfunction?

Wilfried Dinh et al. Reiner Füth Mark Lankisch Georg Hess … Dietmar Zdunek Thomas Scheffold Frank Kramer Rolf Michael Klein Michael Coll Barroso Werner Nickl

BACKGROUND: Growth differentiation factor-15 (GDF-15), a stress-responsive transforming growth factor-ß-related cytokine, is elevated and independently related to an adverse prognosis in systolic heart failure. OBJECTIVE: This study aimed to investigate plasma levels of GDF-15 in patients with preclinical diastolic dysfunction or heart failure with normal ejection fraction (HFnEF). METHODS: We evaluated 119 patients with normal ejection fraction referred for an elective coronary angiography, 75 (63%) of whom had coronary artery disease. Subjects were classified as having either mild left ventricular diastolic dysfunction (LVDD grade I, n = 61), HFnEF (LVDD grade II or III, n = 38) or normal diastolic function (controls, n = 20). In a subgroup of 20 subjects, changes in cardiac output (CO) were measured by inert gas rebreathing (InnocorTM) in response to an orthostatic hemodynamic test. RESULTS: Growth differentiation factor-15 levels in HFnEF [median 1.08, interquartile range (0.88-1.30) ng/ml] were significantly higher than in controls [0.60 (0.50-0.71) ng/ml, p = 0.003] and in patients with LVDD grade I [0.78 (0.62-1.04) ng/ml, p < 0.001]. In addition, GDF-15 was significantly elevated in patients with LVDD grade I compared to controls (p = 0.003). Furthermore, GDF-15 was correlated with echocardiographic markers of diastolic dysfunction and was correlated with the magnitude of CO response to the change in body position from standing to supine (r = -0.67, p = 0.005). CONCLUSION: Growth differentiation factor-15 levels are elevated in subjects with HFnEF and can differentiate normal diastolic function from asymptomatic LVDD. In addition, GDF-15 is associated with a reduced cardiac output response in the orthostatic hemodynamic test.

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Prognostic Value of Growth Differentiation Factor-15 in Heart Failure: A Systematic Review with Meta-Analysis

Abstract

Background

Objective

Methods

Results

Conclusions

Local Inflammation May Underlie Cardiac Damage in Post-COVID-19 Period

Abstract

Background

Objectives

Methods

Results

Conclusions

Growth-differentiation factor-15: a novel biomarker in patients with diastolic dysfunction?

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Electronic Document Format (Vancouver)

Electronic Document Format (ABNT)

Electronic Document Format (APA)

Electronic Document Format (ISO)

Electronic Document Format (Vancouver)

Electronic Document Format (ABNT)

Electronic Document Format (APA)

Electronic Document Format (ISO)