Growth differentiation factor 15 and cardiovascular risk: individual patient meta-analysis

Abstract

Aims Levels of growth differentiation factor 15 (GDF-15), a cytokine secreted in response to cellular stress and inflammation, have been associated with multiple types of cardiovascular (CV) events. However, its comparative prognostic performance across different presentations of atherosclerotic cardiovascular disease (ASCVD) remains unknown. Methods and results An individual patient meta-analysis was performed using data pooled from eight trials including 53 486 patients. Baseline GDF-15 concentration was analyzed as a continuous variable and using established cutpoints (<1200 ng/L, 1200–1800 ng/L, > 1800 ng/L) to evaluate its prognostic performance for CV death/hospitalization for heart failure (HHF), major adverse cardiovascular events (MACE), and their components using Cox models adjusted for clinical variables and established CV biomarkers. Analyses were further stratified on ASCVD status: acute coronary syndrome (ACS), stabilized after recent ACS, and stable ASCVD. Overall, higher GDF-15 concentration was significantly and independently associated with an increased rate of CV death/HHF and MACE (P < 0.001 for each). However, while GDF-15 showed a robust and consistent independent association with CV death and HHF across all presentations of ASCVD, its prognostic association with future myocardial infarction (MI) and stroke only remained significant in patients stabilized after recent ACS or with stable ASCVD [hazard ratio (HR): 1.24, 95% confidence interval (CI): 1.17–1.31 and HR: 1.16, 95% CI: 1.05–1.28 for MI and stroke, respectively] and not in ACS (HR: 0.98, 95% CI: 0.90–1.06 and HR: 0.87, 95% CI: 0.39–1.92, respectively). Conclusion Growth differentiation factor 15 consistently adds prognostic information for CV death and HHF across the spectrum of ASCVD. GDF-15 also adds prognostic information for MI and stroke beyond clinical risk factors and cardiac biomarkers but not in the setting of ACS.

Growth Differentiation Factor 15 and Risk of Death in Haemodialysis Patients

“…Our data are in line with previous studies and with a recent large secondary patient-level analysis of eight randomized clinical trials across diferent forms of atherosclerotic cardiovascular disease, which observed a strong association between circulating GDF-15 and multiples types of cardiovascular events, including death and hospitalization for heart failure [3].…”

“…Today, GDF-15 is considered as a marker of integrated underlying cardiovascular disease burden with higher circulating levels being associated with the presence of atherosclerotic cardiovascular disease. Very recently, a large study across multiple populations with atherosclerotic cardiovascular disease showed that circulating GDF-15 is a robust biomarker for assessing the risk of cardiovascular events and death beyond established clinical factors and biomarkers [ 3 ].…”

FGF-21 and GDF-15 are increased in migraine and associated with the severity of migraine-related disability

“…Analogous circumstances are also encountered in other disease. A recent meta-analysis of individual patients showed that GDF-15 demonstrated a strong and consistent independent association with cardiovascular death and heart failure across all presentations of atherosclerotic cardiovascular disease [ 45 ]. In a longitudinally sampled cohort of patients with multiple sclerosis, mean GDF-15 concentrations may serve as a biomarker for disease stability [ 46 ].…”

Growth Differentiation Factor 15 Is Associated with Platelet Reactivity in Patients with Acute Coronary Syndrome

“…Our results suggest that GDF-15 may help to identify ACS patients at an increased bleeding risk who may benefit from a less aggressive antithrombotic treatment regimen following PCI. This is particularly important, as ACS patients’ bleeding events are associated with an increased risk of major adverse cardiac events (MACE) and death [ 32 , 33 , 34 , 35 ].…”