GROWTH DIFFERENTIATION FACTOR-15 IS AN INDEPENDENT PREDICTOR OF CARDIOVASCULAR DISEASE IN JAPANESE PATIENTS WITH CARDIOVASCULAR RISK FACTORS: THE J-HOP STUDY

Abstract

Objective: Growth differentiation factor-15 (GDF-15) is emerged as a novel biomarker to predict adverse outcomes in community-dwelling individuals and patients with cardiovascular (CV) disease. However, there is a paucity of information on the association between blood GDF-15 levels and adverse outcomes in outpatients with CV risk factors. In this study, we evaluated the prognostic value of GDF-15 in outpatients with CV risk factors and compared with those of other prognostic biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitive troponin T (hs-TnT). Design and method: We collected blood samples from 3,562 patients with CV risk factors in the J-HOP (Japan Morning Surge-Home Blood Pressure) study. Blood GDF-15 levels were determined by immunoassay analysis. During a mean follow-up period of 6.6 years, we recorded the incidence of adverse outcomes as follows: 1) cardiac events defined as ischemic heart disease and heart failure, 2) stroke events defined as ischemic stroke and cerebral hemorrhage, 3) all-cause death, and 4) cancer death. Patients were stratified according to tertiles of GDF-15. The association between GDF-15 and each outcome was evaluated by Cox-proportional hazard models adjusting for established risk factors and other biomarkers (hs-TnT and NT-proBNP). Results: We observed 141 (4.0%) cardiac events, 81 (2.3%) stroke events, and 155 (4.4%) death including 63 (1.8%) cancer death. Multivariate Cox regression model showed that patients in highest tertile of GDF-15 were independently and significantly associated with increased risk of stroke and death except for cardiac events [stroke events, hazard ratio (HR) 2.87, p = 0.008; all-cause death, HR 2.38, p = 0.007; cancer death, HR 2.48, p = 0.049; cardiac events; HR 1.07, p = 0.805, respectively] compared with lowest tertile after adjustment for established risk factors and other biomarkers. Furthermore, adding GDF-15 to the predictive models for stroke and death improved discrimination and reclassification more than adding other biomarkers to the models. Conclusions: In this study, GDF-15 predicts death and stroke except for cardiac events. Information of GDF-15 might be helpful when assessing the risk of death and stroke events in Japanese patients with CV risk factors.