Klotho plasma levels are an independent predictorof mortality in women with acute coronary syndrome

Introduction Alterations in plasma levels of the components of the mineral metabolism (MM) system (calcidiol, fibroblast growth factor-23 [FGF23], phosphate, parathormone [PTH] and klotho) are related to cardiovascular diseases. However, gender differences of the whole MM system in patients with acute coronary syndrome (ACS) have not been reported so far. We have analysed the prognostic value of MM biomarkers in ACS patients, focusing on gender-specific outcomes. Methods We studied 1,230 patients with ACS. At baseline clinical data were collected and plasma levels of MM components were assessed. The primary outcome was a composite of acute ischaemic events, heart failure and all-cause mortality. Secondary outcomes included each component separately. Results 282 patients (22.9%) were female. At baseline, FGF23, PTH, phosphate, and klotho plasma levels were higher in women than in men, with no differences in calcidiol levels. After 5.44 (3.03-7.46) years of follow-up, the primary outcome occurred in 28.0% women and 23.5% men, and death in 10.6% and 9.4% respectively. At multivariate Cox regression analysis, FGF23 levels were independently associated with the incidence of the primary outcome in both, women (Hazard ratio [HR] 1.02 [95%CI:1.01-1.04];p=0.001) and men (HR 1.04 [1.00-1.03];p=0.016), in whom calcidiol levels were also an independent predictor of this outcome. Klotho (HR 0.80 [95%CI:0.67-0.96];p=0.019) and phosphate (HR=2.24 [95%CI: 1.11-4.50];p=0.025) were independent predictors of death in women, while calcidiol (HR=0.84 [95%CI0.72-0.98];p=0.024) and FGF23 levels (HR=1.02 [1.00-1.03];p=0.048) were predictors in men. The figure summarises the methodology used in our study, and the associations between the biomarkers analysed and outcomes during follow-up (in women and men separately). Conclusions Klotho levels are inversely and independently related to all-cause mortality after an ACS in women, but not in men. Furthermore, the MM profile in ACS patients differs in both genders. Future research should explore the underlying mechanisms of these associations.