Abstract 10291: Fibroblast Growth Factor (FGF)-23, Cardiovascular Prognosis, and Benefit of Angiotensin-Converting Enzyme Inhibition in Patients With Stable Coronary Artery Disease
Background: Fibroblast growth factor (FGF)-23 is an endocrine regulator of mineral metabolism. Higher levels of FGF-23 are associated with adverse cardiovascular events in patients with reduced renal function. Whether FGF-23 identifies high-risk patients independent of renal function and established cardiovascular biomarkers, and whether it identifies patients that derive greater clinical benefit from ACE inhibitor therapy, is unknown.
Methods: We measured FGF-23 levels in 3,627 patients with stable ischemic heart disease (SIHD) and preserved systolic function who were randomized to trandolapril or placebo within the Prevention of Events With Angiotensin-Converting Enzyme trial and followed for a median of 5.2 years.
Results: After adjustment for clinical risk predictors, left ventricular ejection fraction, markers of renal function, and established cardiovascular biomarkers, FGF-23 levels in the top quartile were independently associated with an increased risk of cardiovascular death or heart failure among patients allocated to placebo (HR, 1.72; 95% CI, 1.09-2.73; P=0.02) and significantly improved metrics of discrimination. Furthermore, among patients in the top quartile of FGF-23 levels, trandolapril significantly reduced the incidence of cardiovascular death or heart failure (HR, 0.45; 95% CI, 0.28-0.72), whereas there was no clinical benefit in the remaining patients (HR, 1.07; 95% CI, 0.75-1.52; P-interaction=0.0039). This interaction was independent of and additive to stratification based on renal function.
Conclusions: Elevated levels of FGF-23 are associated with cardiovascular death and incident heart failure in SIHD patients and identify patients who derive significant clinical benefit from ACE inhibitor therapy regardless of renal function.
- © 2013 by American Heart Association, Inc.