Fibroblast growth factor 23, mineral metabolism and mortality among elderly men (Swedish MrOs)

Abstract

BackgroundFibroblast growth factor 23 (FGF23) is the earliest marker of disturbed mineral metabolism as renal function decreases. Its serum levels are associated with mortality in dialysis patients, persons with chronic kidney disease (CKD) and prevalent cardiovascular disease (CVD), and it is associated with atherosclerosis, endothelial dysfunction and left ventricular hypertrophy in the general population. The primary aim of this study is to examine the association between FGF23 and mortality, in relation to renal function in the community. A secondary aim is to examine the association between FGF23 and CVD related death.MethodsThe population-based cohort of MrOS Sweden included 3014 men (age 69–81 years). At inclusion intact FGF23, intact parathyroid hormone (PTH), 25 hydroxyl vitamin D (25D), calcium and phosphate were measured. Mortality data were collected after an average of 4.5 years follow-up. 352 deaths occurred, 132 of CVD. Association between FGF23 and mortality was analyzed in quartiles of FGF23. Kaplan-Meier curves and Log-rank test were used to examine time to events. Cox proportional hazards regression was used to examine the association between FGF23, in quartiles and as a continuous variable, with mortality. The associations were also analyzed in the sub-cohort with estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73 m2.ResultsThere was no association between FGF23 and all-cause mortality, Hazard ratio (HR) 95% confidence interval (CI): 1.02 (0.89-1.17). For CVD death the HR (95% CI) was 1.26 (0.99 - 1.59)/(1-SD) increase in log(10)FGF23 after adjustment for eGFR, and other confounders. In the sub-cohort with eGFR > 60 ml/min/1.73 m2 the HR (95% CI) for CVD death was 55% (13–111)/(1-SD) increase in log(10)FGF23.ConclusionsFGF23 is not associated with mortality of all-cause in elderly community living men, but there is a weak association with CVD death, even after adjustment for eGFR and the other confounders. The association with CVD death is noticeable only in the sub-cohort with preserved renal function.

FGF 23 and risk of all-cause mortality and cardiovascular events: A meta-analysis of prospective cohort studies

“…Our sensitivity analyses suggest that 2 studies [12,13] conducted only in male participants probably contributed to the heterogeneity. When these 2 studies were excluded, no statistical heterogeneity was found among the remaining 10 studies.…”

Fibroblast Growth Factor 23 Concentrations Reflect Sex Differences in Mineral Metabolism and Growth in Early Infancy

“…Values below the detection level (3 pg/ml) were recorded as 3.0 pg/ml for intact FGF23, and values exceeding the detection level (1,400 RU/ml) were recorded as 1,400 RU/ml for C-terminal FGF23. The coefficient of variation for intact FGF23 assay is <6% [25]. FGF23 analyses were performed in the Department of Medical Sciences, Uppsala University, Uppsala, Sweden.…”

FGF23 directly impairs endothelium-dependent vasorelaxation by increasing superoxide levels and reducing nitric oxide bioavailability

“…Elevated FGF23 levels are independently associated with endothelial dysfunction and arterial stiffness, which have been related to cardiovascular mortality (3,45,72,75). Therefore, we determined whether FGF23 alone could alter vascular function.…”

“…Fibroblast growth factor 23 (FGF23) is a hormone secreted by osteocytes that serves as an important regulator of serum phosphate and vitamin D via direct actions on the kidney and parathyroid (6,8). Recently, high circulating levels of FGF23 have been clinically associated with the development of CVD (3,9,33,47,55,72) especially during CKD where serum FGF23 is substantially increased 10-to 1,000-fold (30, 37). Nevertheless, despite these clinical associations, there have been relatively few studies to determine whether FGF23 directly induces cardiovascular pathologies or if it is simply a pathological marker.…”