Fibroblast growth factor-23, cardiovascular prognosis, and benefit of angiotensin-converting enzyme inhibition in stable ischemic heart disease.

Abstract

OBJECTIVES:

This study sought to test 2 hypotheses: 1) fibroblast growth factor (FGF)-23 identifies patients with stable ischemic heart disease (SIHD) at high risk of cardiovascular events independent of clinical factors, renal function, and established cardiovascular biomarkers; and 2) FGF-23 identifies patients who derive greater clinical benefit from angiotensin-converting enzyme 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 patients with SIHD are more sparse.

METHODS:

FGF-23 levels were measured in 3,627 patients with SIHD randomly assigned to trandolapril or placebo within the PEACE (Prevention of Events With Angiotensin-Converting Enzyme) trial and followed up for a median of 5.1 years.

RESULTS:

After adjustment for clinical risk predictors, left ventricular ejection fraction, markers of renal function, and established cardiovascular biomarkers, FGF-23 concentration was independently associated with an increased risk of cardiovascular death or heart failure among patients allocated to placebo (quartile 4 hazard ratio: 1.73; 95% confidence interval, 1.09 to 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 (hazard ratio: 0.45; 95% confidence interval: 0.28 to 0.72), whereas there was no clinical benefit in the remaining patients (hazard ratio: 1.07; 95% confidence interval: 0.75 to 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 patients with SIHD and identify patients who derive significant clinical benefit from angiotensin-converting enzyme inhibitor therapy regardless of renal function. (Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy [PEACE]: NCT00000558).

• Authors: Jacob A Udell, David A Morrow, Petr Jarolim, Sarah Sloan, Elaine B Hoffman, Thomas F O'Donnell, Amit N Vora, Torbjørn Omland, Scott D Solomon, Marc A Pfeffer, Eugene Braunwald, Marc S Sabatine
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 63 Issue 22 Pg. 2421-8 (Jun 10 2014) ISSN: 1558-3597 [Electronic] United States
• PMID: 24727254 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Biomarkers
• FGF23 protein, human
• Indoles
• trandolapril
• Fibroblast Growth Factors
• Fibroblast Growth Factor-23

Topics

• Aged
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Biomarkers (blood)
• Cardiovascular Diseases (etiology)
• Female
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors (blood)
• Humans
• Indoles (therapeutic use)
• Male
• Middle Aged
• Myocardial Ischemia (blood, complications, drug therapy)
• Prognosis
• Risk