The Association of Vitamin D Deficiency and Incident Frailty in Older Women: The Role of Cardiometabolic Diseases

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 (seven visits from 1994–2008).

SETTING

Baltimore, Maryland.

PARTICIPANTS

Three hundred sixty-nine women from 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 ≥30ng/mL. Frailty incidence was determined based on presence of three or more criteria: weight loss, low physical activity, exhaustion, weakness, 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<10ng/mL, compared to 12.9 per 1000 person-years in those with 25(OH)D ≥30ng/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=0.057). In regression models adjusted for demographics, smoking, and season, 25(OH)D<10ng/mL (vs ≥30ng/mL) was associated with nearly three-times greater frailty incidence (hazard ratio (HR)=2.77, 95%CI=1.14,6.71, p=0.02). After adjusting for BMI, the relationship of 25(OH)D <10ng/mL (vs ≥30ng/mL) with incident frailty persisted, but was attenuated after further accounting for cardiometabolic diseases (HR=2.29, 95%CI=0.92,5.69, p=0.07).

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.