Growth Differentiation Factor-15 and Clinical Outcomes in Japanese Patients With Ischemic Heart Disease

BACKGROUND: Despite a reduction in the rate of thrombotic events, ischemic heart disease (IHD) remains a key medical problem associated with high major bleeding and mortality in Asian patients with IHD. Growth differentiation factor (GDF)-15, a stress-response cytokine belonging to the transforming growth factor beta superfamily, is reportedly associated with poor clinical outcomes in Western patients with IHD. However, the clinical significance of GDF-15 in Asian patients with IHD has not yet been fully elucidated. OBJECTIVES: The aim of the present study was to examine the impact of serum GDF-15 on clinical outcomes in Japanese patients with IHD. METHODS: Serum GDF-15 levels were evaluated in 632 consecutive patients with IHD. All patients were followed up for a median period of 2.8 years. The primary endpoint was the all-cause mortality rate. Secondary endpoints were major adverse cardiovascular events (MACE), heart failure (HF)–related rehospitalization, bleeding, and thrombotic events. RESULTS: Serum GDF-15 levels were elevated in acute coronary syndrome, severe coronary artery disease, and the major Japanese version of the high bleeding risk criteria. Multivariate Cox proportional hazards regression analysis demonstrated that GDF-15 was an independent predictor of all-cause mortality, MACE, HF-related rehospitalizations, and bleeding events after adjusting for confounding risk factors but not for thrombotic events. Adding GDF-15 to risk factors significantly improved the net reclassification index and integrated discrimination improvement for all-cause deaths, MACE, HF-related rehospitalization, and bleeding events. CONCLUSIONS: Serum GDF-15 could be a feasible marker for major bleeding and adverse clinical outcomes in Japanese patients with IHD.