Udell, J. A., Morrow, D. A., Jarolim, P., Sloan, S., Hoffman, E. B., O'Donnell, T. F., Vora, A. N., Omland, T., Solomon, S. D., Pfeffer, M. A., Braunwald, E., Sabatine, M. S. Fibroblast Growth Factor-23, Cardiovascular Prognosis, and Benefit of Angiotensin-Converting Enzyme Inhibition in Stable Ischemic Heart Disease J Am Coll Cardiol. 2014;NA(NA):NA.

OBJECTIVES: To test two hypotheses: 1) Fibroblast growth factor (FGF)-23 identifies patients with stable ischemic heart disease (SIHD) at high risk of cardiovascular events independent of renal function, clinical factors, and established cardiovascular biomarkers; and 2) FGF-23 identifies patients who derive greater clinical benefit from ACE inhibitor therapy.

BACKGROUND: FGF-23 is an endocrine regulator of mineral metabolism and markedly elevated levels are associated with cardiovascular events in patients with chronic kidney disease. Data in SIHD are more sparse.

METHODS: FGF-23 levels were measured in 3,627 SIHD patients randomized to trandolapril or placebo within the Prevention of Events With Angiotensin-Converting Enzyme (PEACE) 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, the top quartile FGF-23 concentration was independently associated with an increased risk of cardiovascular death or heart failure among patients allocated to placebo (HR, 1.73; 95% CI, 1.09-2.74; P=0.02) and significantly improved metrics of discrimination. Furthermore, among patients in the top quartile of FGF-23 levels, trandolapril significantly reduced cardiovascular death or incident 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. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov; Identifier: NCT00000558.