Abstract
Background: Ischemic heart disease is the strongest risk factor for development of heart failure (HF). Growth-differentiation factor-15 (GDF-15) has been associated with future cardiovascular events in patients with heart failure but its association with incident heart failure in patients with stable ischemic heart disease is unknown. Methods: We measured serum GDF-15 and cardiac disease severity in 981 patients with stable ischemic heart disease who were recruited for the Heart and Soul Study between September 2000 and December 2002. Subsequent heart failure hospitalization was determined by chart review. Results: There were 164 HF hospitalizations over an average of 7.1 years of follow-up. HF hospitalization occurred in 31.4% (102/325) of participants with GDF-15 levels in the highest tertile vs. 3.7% (12/324) in those in the lowest tertile. Participants with GDF-15 levels in the highest tertile had a 3.4-fold higher rate of HF (HR, 3.41; 95% CI, 1.31-8.88; p=0.012) after adjustment for covariates. Each doubling in GDF-15 was associated with an increased risk of HF hospitalization (HR, 2.32; 95% CI, 1.82-3.00; p<0.001). This association persisted after extensive adjustment for covariates including comorbidities, cardiac disease severity, and left ventricular function, inflammatory markers, and adipokines (HR, 1.58; 95% CI, 1.02-2.45; p=0.04). Conclusions: Higher levels of GDF-15 predict HF hospitalizations in patients with stable ischemic heart disease. GDF-15 is an emerging biomarker which identifies patients at highest risk of developing heart failure.
Published Version
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