Serum 25-hydroxyvitamin D, transitions between frailty states, and mortality in older adults: the Invecchiare in Chianti Study

Abstract

Objectives: To assess whether serum 25-hydroxyvitamin D (25(OH)D) concentrations relate to transitions between the states of robustness, prefrailty, and frailty and to mortality in older adults.

Design: The Invecchiare in Chianti (InCHIANTI) Study, a prospective cohort study.

Setting: Tuscany, Italy.

Participants: Adults aged 65 and older (N = 1,155).

Measurements: Serum 25(OH)D concentrations measured at baseline; frailty state (robust, prefrail, frail) assessed at baseline and 3 and 6 years after enrollment; and vital status determined 3 and 6 years after enrollment.

Results: The median (interquartile range) 25(OH)D concentration was 16.0 ng/mL (10.4-25.6 ng/mL; multiply by 2.496 to convert to nmol/L). Prefrail participants with 25(OH)D levels less than 20 ng/mL were 8.9% (95% confidence interval (CI) = 2.5-15.2%) more likely to die, 3.0% (95% CI = -5.6-14.6%) more likely to become frail, and 7.7% (95% CI = -3.5-18.7%) less likely to become robust than prefrail participants with 25(OH)D levels of 20 ng/mL or more. In prefrail participants, each 5-ng/mL decrement of continuous 25(OH)D was associated with 1.46 times higher odds of dying (95% CI = 1.18-2.07) and 1.13 higher odds of incident frailty (95% CI = 0.90-1.39) than with recovery of robustness. Transitions from robustness or frailty were not associated with 25(OH)D levels.

Conclusion: Results provide evidence that prefrailty is an "at risk" state from which older adults with high 25(OH)D levels are more likely to recover than to decline, but high 25(OH)D levels were not associated with recovery from frailty. Thus, 25(OH)D levels should be investigated as a potential therapy to treat prefrailty and prevent further decline.

Figure 1

Standardized Odds Ratios of Frailty Transitions, per 5 ng/mL Lower 25(OH)D Standardized odds ratios and 95% confidence intervals per 5 ng/mL lower 25(OH)D. Arrowheads indicate confidence intervals that extend beyond the figure limits. Standardized for age (years), sex, education (years), season of blood collection, smoking (pack-years), alcohol consumption (drinks/wk), body mass index (kg/m²), Mini-Mental State Examination, Center for Epidemiologic Studies – Depression Scale, comorbidities (congestive heart failure, peripheral arterial disease, hypertension, diabetes, osteoarthritis, renal disease, myocardial infarction, angina, chronic obstructive pulmonary disease), calcium intake (mg/day), and creatinine clearance (mL/min) Model 1: Relationship between 25(OH)D and frailty status without including parathyroid hormone (PTH) in the model as a potential mediator Model 2: Relationship between 25(OH)D and frailty status including parathyroid hormone in the model as a potential mediator; interpreted as the association between 25(OH)D and frailty status if PTH were set to low (<32.4 ng/L).

Figure 2

Standardized Odds Ratios of Transitions of Individual Frailty Criteria, per 5 ng/mL Lower 5(OH)D Standardized odds ratios and 95% confidence intervals per 5 ng/mL lower 25(OH)D. Arrowheads indicate confidence intervals that extend beyond the figure limits. Standardized for age (years), sex, education (years), season of blood collection, smoking (pack-years), alcohol consumption (drinks/wk), body mass index (kg/m²), Mini-Mental State Examination (range: 0–30), Center for Epidemiologic Studies – Depression Scale (range: 0–60), comorbidities (congestive heart failure, peripheral arterial disease, hypertension, diabetes, osteoarthritis, renal disease, myocardial infarction, angina, chronic obstructive pulmonary disease), calcium intake (mg/day), and creatinine clearance (mL/min) Model 1: Relationship between 25(OH)D and frailty status without including parathyroid hormone (PTH) in the model as a potential mediator Model 2: Relationship between 25(OH)D and frailty status including parathyroid hormone in the model as a potential mediator; interpreted as the association between 25(OH)D and frailty status if PTH were set to low (<32.4 ng/L).