Abstract 12459: Fibroblast Growth Factor-23 and Incident Heart Failure With Reduced versus Preserved Ejection Fraction in the Multi Ethnic Study of Atherosclerosis

Abstract

Introduction: Higher FGF-23 levels are associated with incident heart failure (HF) in the Multi-Ethnic Study of Atherosclerosis. FGF-23 is also associated with left ventricular hypertrophy and diffuse myocardial fibrosis in experimental models. Whether FGF-23 association with HF is similar for reduced (HFrEF) and preserved (HFpEF) ejection fraction is not well established. Hypothesis: Higher FGF-23 levels are associated with increased risk of HFpEF. Methods: We studied 6,549 participants (mean age 62 ± 10 yrs, 53% women, mean eGFR of 81 ± 18 m,/min/1.53m 2 ) from the Multi-Ethnic Study of Atherosclerosis (MESA) who were free of cardiovascular disease at baseline (2000-2002). HF events were ascertained by an adjudication committee for a mean follow-up of 11.1 years. We classified HF events as HFrEF (ejection fraction (EF) <50%) or HFpEF (EF ≥50%) at the time of diagnosis. Cox proportional hazard regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association between baseline serum FGF-23 and incident HFrEF and HFpEF. Models were adjusted for age, sex, race/ethnicity, education, study site, smoking, diabetes, systolic blood pressure, use of antihypertensive medications, HDL-C, LDL-C, C-reactive protein, eGFR, and log urine albumin creatinine ratio. Results: A total of 227 HF events occurred during follow-up, of which 125 were classified as HFrEF. In the fully adjusted model, associations of FGF-23 with heart failure events tended to be stronger for HFpEF than for HFrEF (HR 2.1 vs. 1.5 per doubling of FGF-23; Table). However, these associations were not statistically distinguishable. Conclusion: FGF-23 association with HF is stronger for HFpEF than HFrEF in a population-based cohort. The qualitative difference in strength of associations of FGF-23 with HFpEF and HFrEF is consistent with experimental data demonstrating effects of recombinant FGF-23 on cardiac hypertrophic pathways.