Introduction: The mineral metabolism (MM) (vitamin D, phosphate, parathormone [PTH], and fibroblast growth factor-23 [FGF23]) is involved in cardiovascular (CV) damage and plasma levels of its components predict CV outcomes. Klotho is a co-receptor of FGF23 that has been associated with protective cardio-renal effects. However, its potential prognostic value in patients (pts) with coronary artery disease (CAD) remains unknown.
Hypothesis: Klotho plasma levels may have prognostic value or influence the predictive power of the components of MM in pts with CAD.
Methods: In 990 stable CAD pts we determined plasma levels of Klotho and the other components of MM along with clinical and analytic variables. The primary outcome (PO) was a composite of ischemic events (any acute coronary syndrome, stroke or transient ischemic attack), heart failure (HF), or death.
Results: Follow-up was 5.0±2.8 years. Age was 61.3±12.1 years and 76.3% pts were male, 63.7% had hypertension (HT), 23.9% had diabetes, and 60.1% hypercholesterolemia (HC). Glomerular filtration rate was 66.4±20.6 ml/min/1.73 m2. 194 pts developed the PO. Univariate Cox analysis showed a protective effect of Klotho (HR 0,925 [CI 0.861-0.993]; p=0.017) and calcidiol (25-hydroxy vitamin D) (HR 0.971 [CI 0.953-0.989]; p=0.001), while FGF-23 (HR 1.016 [CI 1.011-1.022]; p<0.001) and PTH (HR 1.099 [CI 1.070-1.130]; p<0.001) were directly associated with the PO and phosphate showed no significant association. At multivariate Cox regression analysis only FGF23 (HR 1.001 [CI 1.000-1.002]; p=0.009) and PTH (HR 1.006 [CI 1.003-1.010) p=0.001) were independent predictors of the PO, along with age, HT, HC, ejection fraction <40%, insulin treatment and no beta blocker use. This relation was driven by an increased risk of HF/death with no effect on the incidence of ischemic events. Pts were divided according to the median value of Klotho (569 pg/ml). While FGF23 remained independently associated with the PO in both groups, PTH predicted HF/death only in pts with Klotho≥569 pg/ml.
Conclusions: FGF23 and PTH levels are independent predictors of HF/death in CAD pts. However, PTH remained as a predictive factor only in pts with Klotho≥ median, while FGF23 predicted this end point independently of Klotho levels.