Brian Buta1,2, Parichoy Pal Choudhury3, Qian-Li Xue1,2, Paulo Chaves4, Karen Bandeen-Roche2,3, Michelle Shardell5, Richard D Semba6, Jeremy Walston1,2, Erin D Michos1,7,8, Lawrence J Appel1,7,8, Mara McAdams-DeMarco7,9, Alden Gross2,7,8, Sevil Yasar1,2, Luigi Ferrucci5, Linda P Fried10, Rita Rastogi Kalyani1,2,8. 1. Department of Medicine, Johns Hopkins University, Baltimore, Maryland. 2. Center on Aging and Health, Johns Hopkins University, Baltimore, Maryland. 3. Department of Biostatistics, Johns Hopkins University, Baltimore, Maryland. 4. 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. 5. Intramural Research Program, National Institute on Aging, Baltimore, Maryland. 6. Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland. 7. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 8. Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland. 9. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. 10. Mailman School of Public Health, Columbia University, New York, New York.
Abstract
OBJECTIVES: 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. DESIGN: Prospective longitudinal cohort study (7 visits from 1994-2008). SETTING: Baltimore, Maryland. PARTICIPANTS: Three hundred sixty-nine women from the Women's Health and Aging Study II aged 70-79 years, free of frailty at baseline. MEASUREMENTS: 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). CONCLUSION: 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.
OBJECTIVES: 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. DESIGN: Prospective longitudinal cohort study (7 visits from 1994-2008). SETTING: Baltimore, Maryland. PARTICIPANTS: Three hundred sixty-nine women from the Women's Health and Aging Study II aged 70-79 years, free of frailty at baseline. MEASUREMENTS: 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). CONCLUSION: 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.
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