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 .