Apolipoprotein ɛ4 Is Associated With Increased Risk of Fall- and Fracture-Related Hospitalization: The Perth Longitudinal Study of Ageing Women

Abstract

Apolipoprotein ɛ4 (APOE ɛ4) may be a genetic risk factor for reduced bone mineral density (BMD) and muscle function, which could have implications for fall and fracture risk. We examined the association between APOE ɛ4 status and long-term fall- and fracture-related hospitalization risk in older women. A total of 1 276 community-dwelling women from the Perth Longitudinal Study of Aging Women (mean age ± SD = 75.2 ± 2.7 years) were included. At baseline, women underwent APOE genotyping and detailed phenotyping for covariates including prevalent falls and fractures, as well as health and lifestyle factors. The association between APOE ɛ4 and fall-, any fracture-, and hip fracture-related hospitalizations, obtained over 14.5 years from linked health records, was examined using multivariable-adjusted Cox-proportional hazard models. Over 14.5 years, 507 (39.7%) women experienced a fall-related hospitalization and 360 (28.2%) women experienced a fracture-related hospitalization, including 143 (11.2%) attributed to a hip fracture. In multivariable-adjusted models, compared to noncarriers, APOE ɛ4 carriers (n = 297, 23.3%) had greater risk for a fall- (hazard ratio [HR] 1.48, 95% CI: 1.22-1.81), fracture- (HR 1.28, 95% CI: 1.01-1.63), or hip fracture-related hospitalization (HR 1.83, 95% CI: 1.29-2.61). The estimates remained similar when specific fall and fracture risk factors (fear of falling, plasma 25-hydroxyvitamin D, grip strength, timed up-and-go, hip BMD, vitamin K status, prevalent diabetes, HbA1c, cholesterol, and abbreviated mental test score) were added to the multivariable model. In conclusion, APOE ɛ4 is a potential risk factor for fall- and fracture-related hospitalization in community-dwelling older women. Screening for APOE ɛ4 could provide clinicians an opportunity to direct higher-risk individuals to appropriate intervention strategies.