title: The Association of Vitamin D Deficiency and Incident Frailty in Older Women: The Role of Cardiometabolic Diseases.
abstract: OBJECTIVE
  Evidence suggests vitamin D deficiency is associated with developing frailty. However, cardiometabolic factors are related to both conditions and may confound and/or mediate the vitamin D-frailty association. We aimed to determine the association of vitamin D concentration with incidence of frailty, and the role of cardiometabolic diseases (cardiovascular disease, diabetes, hyperlipidemia, hypertension) in this relationship.
  
  
  METHODS
  Prospective longitudinal cohort study (7 visits from 1994-2008).
  
  
  METHODS
  Baltimore, Maryland.
  
  
  METHODS
  Three hundred sixty-nine women from the Women's Health and Aging Study II aged 70-79 years, free of frailty at baseline.
  
  
  METHODS
  Serum circulating 25-hydroxyvitamin D (25[OH]D) concentration was assessed at baseline and categorized as: <10; 10-19.9; 20-29.9; and ≥30 ng/mL. Frailty incidence was determined based on presence of three or more criteria: weight loss, low physical activity, exhaustion, weakness, and slowness. Cardiometabolic diseases were ascertained at baseline. Analyses included Cox regression models adjusted for key covariates.
  
  
  RESULTS
  Incidence rate of frailty was 32.2 per 1,000 person-years in participants with 25(OH)D < 10 ng/mL, compared to 12.9 per 1,000 person-years in those with 25(OH)D ≥ 30 ng/mL (mean follow-up = 8.5 ± 3.7 years). In cumulative incidence analyses, those with lower 25(OH)D exhibited higher frailty incidence, though differences were non-significant (P = .057). In regression models adjusted for demographics, smoking, and season, 25(OH)D < 10 ng/mL (vs ≥30 ng/mL) was associated with nearly three-times greater frailty incidence (hazard ratio (HR) = 2.77, 95% CI = 1.14, 6.71, P = .02). After adjusting for BMI, the relationship of 25(OH)D < 10 ng/mL (vs ≥30 ng/mL) with incident frailty persisted, but was attenuated after further accounting for cardiometabolic diseases (HR = 2.29, 95% CI = 0.92, 5.69, P = .07).
  
  
  CONCLUSIONS
  Low serum vitamin D concentration is associated with incident frailty in older women; interestingly, the relationship is no longer significant after accounting for the presence of cardiometabolic diseases. Future studies should explore mechanisms to explain this relationship.
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, Maryland.|Center on Aging and Health, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Brian
authors.initials: B
authors.lastname: Buta
authors.affiliation: Department of Biostatistics, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Parichoy Pal
authors.initials: PP
authors.lastname: Choudhury
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, Maryland.|Center on Aging and Health, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Qian-Li
authors.initials: QL
authors.lastname: Xue
authors.affiliation: Benjamin Leon Center for Geriatric Research and Education and Department of Humanities, Health and Society, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida.
authors.forename: Paulo
authors.initials: P
authors.lastname: Chaves
authors.affiliation: Center on Aging and Health, Johns Hopkins University, Baltimore, Maryland.|Department of Biostatistics, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Karen
authors.initials: K
authors.lastname: Bandeen-Roche
authors.affiliation: Intramural Research Program, National Institute on Aging, Baltimore, Maryland.
authors.forename: Michelle
authors.initials: M
authors.lastname: Shardell
authors.affiliation: Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Semba
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, Maryland.|Center on Aging and Health, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Walston
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, Maryland.|Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.|Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Erin D
authors.initials: ED
authors.lastname: Michos
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, Maryland.|Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.|Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Appel
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.|Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Mara
authors.initials: M
authors.lastname: McAdams-DeMarco
authors.affiliation: Center on Aging and Health, Johns Hopkins University, Baltimore, Maryland.|Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.|Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Alden
authors.initials: A
authors.lastname: Gross
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, Maryland.|Center on Aging and Health, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Sevil
authors.initials: S
authors.lastname: Yasar
authors.affiliation: Intramural Research Program, National Institute on Aging, Baltimore, Maryland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.affiliation: Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Linda P
authors.initials: LP
authors.lastname: Fried
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, Maryland.|Center on Aging and Health, Johns Hopkins University, Baltimore, Maryland.|Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Rita Rastogi
authors.initials: RR
authors.lastname: Kalyani
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D016330:Frail Elderly / Q000706:statistics & numerical data*; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology; D006973:Hypertension / Q000453:epidemiology; D015994:Incidence; D008137:Longitudinal Studies; D008396:Maryland / Q000453:epidemiology; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000453:epidemiology*
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: aging; cardiometabolic diseases; frailty; vitamin D