scholarly journals Plasma Soluble αKlotho, Serum Fibroblast Growth Factor 23, and Mobility Disability in Community-Dwelling Older Adults

2020 ◽  
Vol 4 (5) ◽  
Author(s):  
Michelle Shardell ◽  
David A Drew ◽  
Richard D Semba ◽  
Tamara B Harris ◽  
Peggy M Cawthon ◽  
...  
Keyword(s):  
Older Adults ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Community Dwelling ◽  
Fibroblast Growth ◽  
Mobility Disability ◽  
Body Composition Study ◽  
Health Aging ◽  
Community Dwelling Older Adults

Abstract Context αKlotho is a hormone and co-receptor for fibroblast growth factor 23 (FGF23), a hormone that downregulates active vitamin D synthesis and promotes phosphate excretion. Low αKlotho and high FGF23 occur in chronic kidney disease (CKD). Objective We aimed to assess the relationships of αKlotho and FGF23 with mobility disability in community-dwelling older adults. Design and Setting We estimated associations of plasma-soluble αKlotho and serum FGF23 concentrations with mobility disability over 6 years. Additional analyses was stratified by CKD. Participants Participants included 2751 adults (25.0% with CKD), aged 71 to 80 years, from the 1998 to 1999 Health, Aging, and Body Composition Study visit. Main Outcome Measures Walking disability and stair climb disability were defined as self-reported “a lot of difficulty” or an inability to walk a quarter mile and climb 10 stairs, respectively. Results Median (interquartile range [IQR]) serum FGF23 and plasma soluble αKlotho concentrations were 46.6 (36.7, 60.2) pg/mL and 630.4 (478.4, 816.0) pg/mL, respectively. After adjustment, higher αKlotho concentrations were associated with lower walking disability rates (Rate Ratio [RR] highest vs. lowest tertile = 0.74; 95% confidence interval l [CI] = 0.62, 0.89; P = 0.003). Higher FGF23 concentrations were associated with higher walking disability rates (RR highest vs. lowest tertile = 1.24; 95%CI = 1.03, 1.50; P = 0.005). Overall, higher αKlotho combined with lower FGF23 was associated with the lowest walking disability rates (P for interaction = 0.023). Stair climb disability findings were inconsistent. No interactions with CKD were statistically significant (P for interaction > 0.10). Conclusions Higher plasma soluble αKlotho and lower serum FGF23 concentrations were associated with lower walking disability rates in community-dwelling older adults, particularly those without CKD.

scholarly journals Fibroblast Growth Factor 23: A Biomarker of Kidney Function Decline

2018 ◽  
Vol 47 (4) ◽  
pp. 242-250 ◽  
Author(s):  
David A. Drew ◽  
Ronit Katz ◽  
Stephen Kritchevsky ◽  
Joachim H. Ix ◽  
Michael G. Shlipak ◽  
...  
Keyword(s):  
Older Adults ◽  
Vitamin D ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Kidney Function ◽  
Fibroblast Growth Factor 23 ◽  
Community Dwelling ◽  
Fibroblast Growth ◽  
Fgf 23 ◽  
Kidney Function Decline

Background: Fibroblast growth factor 23 (FGF-23) is a hormone that regulates phosphorus levels and vitamin D metabolism. Previous studies have shown FGF-23 to be a risk factor for incident end-stage renal disease; however, there are less data on the association of FGF-23 with earlier kidney-related outcomes. Methods: Serum FGF-23 was assayed using an intact ELISA assay in 2,496 participants of the Healthy Aging and Body Composition Study, a cohort of well-functioning older adults. Kidney function was estimated by assaying cystatin C at baseline and years 3 and 10. The associations between FGF-23 and decline in kidney function (defined by estimated glomerular filtration rate (eGFR) decline ≥30% or ≥3 mL/min/year) and incident chronic kidney disease (CKD; incident eGFR <60 mL/min/1.73 m2 and ≥1 mL/min/year decline) were evaluated. Models were adjusted for demographics, baseline eGFR, urine albumin/creatinine ratio, comorbidity, and serum calcium, phosphorus, 25(OH) vitamin D and parathyroid hormone. Results: The mean (SD) age was 75 (3) years, with 52% female and 38% black. There were 405 persons with 30% decline, 702 with >3 mL/min/year decline, and 536 with incident CKD. In fully adjusted continuous models, doubling of FGF-23 concentrations was not associated with kidney function decline (OR [95% CI] = 0.98 [0.82–1.19] for ≥30% decline and OR 1.17 [95% CI 1.00–1.37] for ≥3 mL/min/year decline), or incident CKD (incident rate ratio [IRR] 1.05 [95% CI 0.91–1.22]). In adjusted quartile analysis, the highest quartile of FGF-23 was significantly associated with incident CKD (IRR 1.27 [95% CI 1.02–1.58] for highest vs. lowest quartile). Conclusion: Higher FGF-23 concentrations were not consistently associated with decline in kidney function or incident CKD in community-dwelling older adults.

scholarly journals Fibroblast growth factor 23 and cognitive impairment: The health, aging, and body composition study

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243872
Author(s):  
David A. Drew ◽  
Ronit Katz ◽  
Stephen Kritchevsky ◽  
Joachim H. Ix ◽  
Michael Shlipak ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Body Composition Study ◽  
Composition Study ◽  
Fgf 23

Background Concentrations of fibroblast growth factor 23 (FGF-23), a hormone that regulates phosphorus and vitamin D metabolism, increase as kidney function declines. Excess fibroblast growth factor 23 may impact brain function through promotion of vascular disease or through direct effects on neuronal tissue. Methods In the Healthy Aging and Body Composition Study, a longitudinal observational cohort of well-functioning older adults, intact serum FGF-23 was assayed in 2,738 individuals. Cognitive function was assessed at baseline and longitudinally at years 3, 5, and 8 by administration of the Modified Mini Mental State Examination (3MSE), a test of global cognitive function, and the Digit Symbol Substitution Test (DSST), a test primarily of executive function. The associations between FGF-23 and baseline cognitive function and incident cognitive impairment were evaluated using logistic and Poisson regression respectively, and were adjusted for demographics, baseline estimated glomerular filtration rate (eGFR), urine albumin/creatinine ratio, comorbidity, and other measures of mineral metabolism including soluble klotho. Results The mean (SD) age was 74(3) years, with 51% female, and 39% black. The median (25th, 75th) FGF-23 concentration was 47 pg/mL (37, 60). Three hundred ninety-two individuals had prevalent cognitive impairment by the 3MSE and 461 by the DSST. There was no observed association between FGF-23 and baseline cognitive function for either cognitive test. There were 277 persons with incident cognitive impairment by 3MSE, and 333 persons with incident cognitive impairment by DSST. In fully adjusted models, each two-fold higher concentration of baseline FGF-23 was not associated with incident cognitive impairment by the 3MSE (IRR = 1.02[0.88, 1.19] fully adjusted model) or by the DSST (IRR = 0.98 [0.84, 1.15]. We saw no difference when analyses were stratified by eGFR greater than or less than 60 ml/min/1.73m2. Conclusion Intact FGF-23 was not associated with baseline cognitive function or incident cognitive impairment in this cohort well-functioning older adults.

scholarly journals Relationship of serum fibroblast growth factor 23 with cardiovascular disease in older community-dwelling women

2011 ◽  
Vol 165 (5) ◽  
pp. 797-803 ◽  
Author(s):  
Mansi Dalal ◽  
Kai Sun ◽  
Anne R Cappola ◽  
Luigi Ferrucci ◽  
Candace Crasto ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Elevated Serum ◽  
Community Dwelling ◽  
Fibroblast Growth ◽  
Multivariable Logistic Regression Model ◽  
Cross Sectional ◽  
The Relationship

ObjectiveAlthough fibroblast growth factor 23 (FGF23) has been implicated in the pathogenesis of cardiovascular disease, the relationship between FGF23 and cardiovascular disease has not been well characterized in the general population. The aim of this study was to determine whether serum FGF23 is independently associated with cardiovascular disease in older community-dwelling women.Design and methodsA cross-sectional design was used to examine the relationship between serum FGF23 and cardiovascular disease. The subjects consisted of a population-based sample of 659 women, aged 70–79 years, who participated in the Women's Health and Aging Studies in Baltimore, Maryland. Prevalent cardiovascular disease (coronary heart disease, stroke, congestive heart failure, and peripheral artery disease) was assessed through diagnostic algorithms and physician adjudication.ResultsOf the 659 women, 185 (28.1%) had cardiovascular disease. Median (25th, 75th percentile) intact serum FGF23 was 34.6 (25.2, 46.2) pg/ml. The prevalence of cardiovascular disease in the lowest, middle, and highest tertile of serum FGF23 was 22.6, 24.9, and 36.7% respectively (P=0.002). Serum log FGF23 was associated with cardiovascular disease (odds ratio per 1s.d.increase=1.23, 95% confidence interval 1.17, 1.30;P<0.0001) in a multivariable logistic regression model, adjusting for age, race, smoking, education, body mass index, cognition, diabetes, hypertension, physical activity, total cholesterol, high-density lipoprotein cholesterol, and renal function.ConclusionElevated serum FGF23 concentrations are independently associated with prevalent cardiovascular disease in older community-dwelling women. Further studies are needed to elucidate the potential biological mechanisms by which FGF23 may be involved in the pathogenesis of cardiovascular disease.

scholarly journals Persistent polypharmacy and fall injury risk: the Health, Aging and Body Composition Study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lingshu Xue ◽  
Robert M. Boudreau ◽  
Julie M. Donohue ◽  
Janice C. Zgibor ◽  
Zachary A. Marcum ◽  
...  
Keyword(s):  
Older Adults ◽  
Injury Risk ◽  
Clinic Visit ◽  
Community Dwelling ◽  
Fall Injuries ◽  
Fall Injury ◽  
Body Composition Study ◽  
Health Aging ◽  
Outpatient Settings ◽  
Community Dwelling Older Adults

Abstract Background Older adults receive treatment for fall injuries in both inpatient and outpatient settings. The effect of persistent polypharmacy (i.e. using multiple medications over a long period) on fall injuries is understudied, particularly for outpatient injuries. We examined the association between persistent polypharmacy and treated fall injury risk from inpatient and outpatient settings in community-dwelling older adults. Methods The Health, Aging and Body Composition Study included 1764 community-dwelling adults (age 73.6 ± 2.9 years; 52% women; 38% black) with Medicare Fee-For-Service (FFS) claims at or within 6 months after 1998/99 clinic visit. Incident fall injuries (N = 545 in 4.6 ± 2.9 years) were defined as the initial claim with an ICD-9 fall E-code and non-fracture injury, or fracture code with/without a fall code from 1998/99 clinic visit to 12/31/08. Those without fall injury (N = 1219) were followed for 8.1 ± 2.6 years. Stepwise Cox models of fall injury risk with a time-varying variable for persistent polypharmacy (defined as ≥6 prescription medications at the two most recent consecutive clinic visits) were adjusted for demographics, lifestyle characteristics, chronic conditions, and functional ability. Sensitivity analyses explored if persistent polypharmacy both with and without fall risk increasing drugs (FRID) use were similarly associated with fall injury risk. Results Among 1764 participants, 636 (36%) had persistent polypharmacy over the follow-up period, and 1128 (64%) did not. Fall injury incidence was 38 per 1000 person-years. Persistent polypharmacy increased fall injury risk (hazard ratio [HR]: 1.31 [1.06, 1.63]) after adjusting for covariates. Persistent polypharmacy with FRID use was associated with a 48% increase in fall injury risk (95%CI: 1.10, 2.00) vs. those who had non-persistent polypharmacy without FRID use. Risks for persistent polypharmacy without FRID use (HR: 1.22 [0.93, 1.60]) and non-persistent polypharmacy with FRID use (HR: 1.08 [0.77, 1.51]) did not significantly increase compared to non-persistent polypharmacy without FRID use. Conclusions Persistent polypharmacy, particularly combined with FRID use, was associated with increased risk for treated fall injuries from inpatient and outpatient settings. Clinicians may need to consider medication management for FRID and other fall prevention strategies in community-dwelling older adults with persistent polypharmacy to reduce fall injury risk.

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