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Low Vitamin D and High Fibroblast Growth Factor 23 Serum Levels Associate with Infectious and Cardiac Deaths in the HEMO Study.
Chonchol, M, Greene, T, Zhang, Y, Hoofnagle, AN, Cheung, AK
Journal of the American Society of Nephrology : JASN. 2016;(1):227-37
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Abstract
Longitudinal studies testing the relationship between repeated measures of vitamin D or fibroblast growth factor 23 (FGF23) and infectious and cardiac hospitalizations and death in hemodialysis patients have not been reported. We examined the association between yearly 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and FGF23 serum levels and various clinical outcomes using time-dependent Cox regression models with repeated yearly measures and fixed-covariate Cox models with only baseline values after controlling for important clinical covariates in the HEMO study. During a median follow-up of 3 years, 582 of the 1340 participants died, and 499 and 514 participants had a hospitalization or death attributed to infectious and cardiac causes, respectively. Patients in the highest 25(OH)D quartile had the lowest risk of infectious events (hazard ratio [HR] 0.66 versus the lowest quartile; 95% confidence interval [95% CI], 0.49-0.89), cardiac events (HR, 0.71; 95% CI, 0.53-0.96), and all-cause mortality (HR, 0.46; 95% CI, 0.34-0.62) in time-dependent analyses. No significant associations of 1,25(OH)2D with clinical outcomes were observed in time-dependent or fixed-covariate Cox models. In contrast, the highest FGF23 quartile was associated with a higher risk of infectious events (HR, 1.57 versus the lowest quartile; 95% CI, 1.13-2.18), cardiac events (HR, 1.49; 95% CI, 1.06-2.08), and all-cause mortality (HR, 1.50; 95% CI, 1.07-2.12) in fixed-covariate Cox models. The addition of inflammation markers into the statistical models did not attenuate these associations. Thus, disordered mineral metabolism may affect outcomes in chronic hemodialysis patients.
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Circulating fibroblast growth factor 23 is associated with angiographic severity and extent of coronary artery disease.
Xiao, Y, Peng, C, Huang, W, Zhang, J, Xia, M, Zhang, Y, Ling, W
PloS one. 2013;(8):e72545
Abstract
OBJECTIVE Fibroblast growth factor 23 (FGF23) is a circulating regulator of phosphate and vitamin D metabolism and is associated with coronary artery calcification, and has been implicated in the pathogenesis of cardiovascular disease. The aim of this study was to determine whether circulating FGF23 concentration is independently associated with the severity and extent of coronary artery disease in patients undergoing coronary angiography. METHOD A cross-sectional design was used to examine the relationship between serum FGF23 and the severity and extent of coronary artery stenosis in 2076 patients undergoing coronary angiography (1263 male and 813 female, mean aged 62.5 years). Subgroup analyses were performed to assess the associations between FGF23 and coronary arterial plaque characteristics evaluated by intravascular ultrasound and 12-month incidence of target vessel revascularization (TVR) and target lesion revascularization (TLR). FINDINGS We found a stepwise increase of serum FGF23 concentrations in patients with mild, moderate, severe stenosis or with increased number of stenotic vessels compared with those without stenosis (P<0.001). Serum FGF23 concentration was positively correlated with stenosis scores as the global index of the severity and extent of coronary artery stenosis in both male and female (r = 0.315 and r = 0.291, P<0.001). In multiple regression analyses, serum FGF23 concentration was a significant determinant of the stenosis scores independent of other traditional risk factors (standardized β = 0.326, P<0.001). Furthermore, subgroup analyses found FGF23 was significantly associated with plaque and dense calcium volumes. Multiple logistic regression analyses showed that serum FGF23 levels were significantly independent predictors of TVR and TLR. CONCLUSIONS We report an independent association between circulating FGF23 concentration and the severity and extent of coronary artery stenosis in the coronary angiographic patients. Future studies are needed to elucidate the potential biological mechanisms and whether FGF23 is a modifiable cardiovascular risk factor.