Growth differentiation factor-15 is associated with cardiovascular outcomes in patients with coronary artery disease

Abstract

Background: Growth differentiation factor-15 (GDF-15) is a marker of inflammation, oxidative stress and it is associated with adverse prognosis in cardiovascular disease. The aim of the present cohort study is to investigate the prognostic value of GDF-15 in patients with coronary artery disease (CAD) during long-term follow up. Methods: A total of 3641 consecutive patients with CAD were prospectively enrolled into the study and followed up for major adverse cardiovascular events (MACEs) and all-cause death up to 5.3-7.6 years. Plasma GDF-15 was measured and clinical data and long-term events were registered. The patients were subsequently divided into three groups by the levels of GDF-15 and the prognostic value of GDF-15 level with MACEs and all-cause death was evaluated. Results: After a median follow-up at 6.4 years later, 775 patients (event rate of 21%) had developed MACEs and 275 patients died (event rate of 7.55%). Kaplan-Meier analysis indicated that the patients with GDF-15 > 1800 ng/L were significantly associated with an increased risk of MACEs and all-cause death. Cox regression analysis indicated that GDF-15 > 1800 ng/L were independently associated with the composite of MACEs (HR 1.74; 95% CI 1.44-2.02; P < 0.001) and all-cause death (HR 2.04; 95% CI 1.57-2.61; P < 0.001). For MACEs, GDF-15 significantly improved the C-statistic (area under the curve, 0.583 [95% CI 0.559-0.606] to 0.628 [0.605-0.651]; P < 0.001), net reclassification index (0.578; P = 0.031), and integrated discrimination index (0.021; P = 0.027). For all-cause death, GDF-15 significantly improved the C-statistic (0.728 [95% CI 0.694-0.761] to 0.817 [0.781-0.846]; P < 0.001), net reclassification index (0.629; P = 0.001), and integrated discrimination index (0.035; P = 0.002). Conclusions: In the setting of CAD, GDF-15 is associated with long-term MACEs and all-cause death, and provides incremental prognostic value beyond traditional risks factors.

Emerging Biomarkers for Predicting Clinical Outcomes in Patients with Heart Disease

“…Growth differentiation factor 15 (GDF-15) belongs to the transforming growth factor-β (TGF-β) superfamily, previously known as the macrophage-inhibiting cytokine, which increases as a consequence of inflammation and oxidative stress [ 22 ]. Because atherosclerosis is an inflammatory process, it has been hypothesized that GDF-15 may be used as a valid marker of prognosis in patients with atherosclerosis-related CVD.…”

“…Because atherosclerosis is an inflammatory process, it has been hypothesized that GDF-15 may be used as a valid marker of prognosis in patients with atherosclerosis-related CVD. Recently, an observational cohort study evaluated the prognostic value of plasma GDF-15 in 3641 patients with CAD, who were followed up for 5.3–7.6 years [ 22 ]. In this study, elevated GDF-15 levels > 1800 ng/L were independently associated with the primary endpoint (composite of all-cause mortality, ACS, or unplanned coronary revascularization) and all-cause mortality [ 22 ].…”

From Classic to Modern Prognostic Biomarkers in Patients with Acute Myocardial Infarction

“…GDF-15 is increased in response to cardiac damage and the inflammatory process, thereby increasing the risk of an elevated cardiovascular event [ 177 ]. In the presence of an ACS, a single measurement of GDF-15 and concentrations greater than 1800 ng/L were linked to an elevated risk of all-cause mortality, MACEs and hospitalization for heart failure, but not subsequent readmission for MI [ 178 , 179 ]. Additionally, GDF-15 concentrations were assessed at baseline in 4330 patients, and the same cut-off value was linked to a twofold increase in the risk of CV death/HF [ 180 ].…”

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

“…Myocardial ischemia induced by coronary atherosclerosis or microcirculation dysfunction is tightly associated with heart structure and function. Several observational studies showed that GDF-15 concentration was continuously associated with the risk of coronary heart disease (33,34). Our data suggest that GDF-15 is a strong predictive factor of the mortality of CHF with ischemic etiology.…”