Growth Differentiation Factor 15 and Risk of Bleeding Events: The Atherosclerosis Risk in Communities Study

BACKGROUND: GDF15 (growth differentiation factor 15) is a potent predictor of bleeding in people with cardiovascular disease. However, whether GDF15 is associated with bleeding in individuals without a history of cardiovascular disease is unknown. METHODS AND RESULTS: The study population was from the ARIC (Atherosclerosis Risk in Communities) study. We studied the association of GDF15 with hospitalized bleeding events among 9205 participants (1993–1995) without prior bleeding and cardiovascular disease (mean age 60 years, 57% women, 21% Black). Plasma levels of GDF15 were measured in relative fluorescence units using DNA‐based aptamer technology. Bleeding was ascertained using discharge codes. We examined hazard ratios (HRs) of incident bleeding using Cox models and risk prediction with the addition of GDF15 to clinical predictors of bleeding. There were 1328 hospitalizations with bleeding during a median follow‐up of 22.5 years. The majority (76.5%) were because of gastrointestinal bleeding. The absolute incidence rate of bleeding per 1000 person‐years was 11.64 in the highest quartile of GDF15 versus 5.22 in the lowest quartile. The highest versus lowest quartile of GDF15 demonstrated an adjusted HR of 2.00 (95% CI, 1.69–2.35) for total bleeding. The findings were consistent when we examined bleeding as the primary discharge diagnosis. The addition of GDF15 to clinical predictors of bleeding improved the C‐statistic by 0.006 (0.002–0.011) from 0.684 to 0.690, P=0.008. CONCLUSIONS: Higher levels of GDF15 were associated with bleeding events and improved the risk prediction beyond clinical predictors in individuals without cardiovascular disease.