Fibroblast Growth Factor‐23 and Frailty in Elderly Community‐Dwelling Individuals: The Cardiovascular Health Study

Abstract

Objectives Both fibroblast growth factor 23 (FGF-23) and frailty have been previously associated with components of bone mineral metabolism, chronic disease states, and mortality. We sought to evaluate whether FGF-23 is related to frailty and to characterize the nature of their joint association with mortality. Design Cross sectional analysis and Cox proportional hazards mortality analysis. Setting The Cardiovascular Health Study Participants 2,977 community dwelling individuals. Measurements The predictor was serum FGF-23 concentration (C-terminal ELISA assay) and the outcomes were frailty status (determined by frailty phenotype criteria of weight loss, weakness, exhaustion, slowness, and decreased physical activity) and mortality. Multinomial logistic regression was used to assess the cross-sectional association of FGF-23 with frailty and prefrailty, adjusting for demographics, cardiovascular disease and risk factors, and kidney markers. Proportional hazards regression was used to assess the association of FGF-23 and frailty with all-cause mortality. Results The mean age was 78 years (SD 4.7), 40% were male, 83% were Caucasian and mean eGFR was 64 ± 17 ml/min/1.73m2. The median FGF-23 value was 70.3 RU/mL [IQR 53.4–99.2]; 52% were prefrail and 13% were frail. After multivariate adjustment, each doubling in FGF-23 concentration was associated with 38% (95% CI 17–62%) higher odds of frailty vs. nonfrailty and 16% (3–30%) higher odds of prefrailty. FGF-23 (HR 1.16; 95% CI 1.10–1.23) and frailty (HR 1.82; 1.57–2.12) were independently associated with mortality, but neither association was meaningfully attenuated when adjusted for the other. Conclusion In a large cohort of older adults, higher FGF-23 was independently associated with prevalent frailty and pre-frailty. FGF-23 and frailty were independent and additive risk factors for mortality. FGF-23 may be a marker for functional outcomes.

Association of Fibroblast Growth Factor-23 (FGF-23) With Incident Frailty in HIV-Infected and HIV-Uninfected Individuals

“…25 With regards to the associations of FGF-23 with individual clinical presentations of frailty observed in our study, some, but not all, are consistent with those reported in the study by Beben and colleagues. 25 These differential observations across the two studies may arise from heterogeneity in study population composition, including age and co-morbidities.…”

“…Despite the importance of FGF-23 in bone mineral metabolism, its potential relationship with inflammation, and its observed association with age-related co-morbidities, only one study among elderly HIV-uninfected adults examined FGF-23’s association with frailty. 25 In this prior study, higher serum FGF-23 levels were associated with significantly higher odds of frailty. To our knowledge, no study has investigated this association in HIV-infected populations.…”

“…Our results are consistent with those of the only prior epidemiological study evaluating the link between FGF-23 and frailty. 25 In that community-based study of older adults (aged ~77 years), each doubling of FGF-23 levels was associated with 1.38-fold higher odds of frailty. 25 With regards to the associations of FGF-23 with individual clinical presentations of frailty observed in our study, some, but not all, are consistent with those reported in the study by Beben and colleagues.…”

Inverse Correlation Between Grip Strength and Serum Phosphorus: A Retrospective Observational Study in Japanese Elderly with Poorly Controlled Type 2 Diabetes

“…FGF23 and Klotho mainly maintain urinary phosphorus excretion; any depleted activity of these molecules leads not only to hyperphosphatemia, but also to premature aging [27]. A higher FGF23 level is independently related to the prevalence of frailty in the community-dwelling elderly, even after adjustment for bone mineral metabolic markers such as phosphorus, calcium, parathyroid hormone, and vitamin D. Thus, endo-organ resistance to FGF23 in patients with frailty has been suggested [28].…”

Alcoholism, Fibroblast Growth Factor 23 and Cardiovascular Risk

“…Other researchers have reported higher FGF-23 levels in patients with an obesity, especially visceral fat accumulation [29], suggesting an indirect relationship with cardiovascular risk in patients with intact renal function. Aditionally, it was shown that FGF-23 is a marker of frailty among community-dwelling individuals [30]. Also, FGF-23 is related with arterial stiffness in diabetic patients, independently on estimated glomerular fi ltration rate [31].…”