Key points Is high-density lipoprotein cholesterol (HDL-C) level associated with increased risk of fractures in healthy older adults? Findings In this cohort study of 16,262 healthy community-dwelling participants aged 70 years or older, 1,659 participants experienced at least 1 fracture during a median follow-up of 4 years. In the fully adjusted model, each 1 SD increase in HDL-C level was associated with a 14% increased risk of fractures , and when HDL-C level was analyzed in categories, people in the highest quintile they had a 33% higher risk of fractures than those in the lowest quintile. Meaning The findings of this study indicate that higher levels of HDL-C may be associated with an increased risk of fractures. |
Summary
Importance
Elevated levels of high-density lipoprotein cholesterol (HDL-C) have been associated with osteoporosis. Preclinical studies have reported that HDL-C reduces bone mineral density by reducing the number and function of osteoblasts. However, the clinical significance of these findings is unclear.
Aim
To determine whether higher HDL-C levels are predictive of increased fracture risk in healthy older adults.
Design, environment and participants
This cohort study is a post hoc analysis of data from the Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial and the ASPREE-Fracture substudy . ASPREE was a double-blind, randomized, placebo-controlled aspirin primary prevention trial that recruited participants between 2010 and 2014. These included community-dwelling older adults (16,703 Australian participants aged ≥70 years, 2,411 American participants aged ≥65 years) without obvious history of cardiovascular disease, dementia, physical disability, and chronic life-limiting illnesses.
The ASPREE-Fracture substudy collected data on fractures reported after randomization from Australian participants. Cox regression was used to calculate the hazard ratio (HR) and 95% CI. Data analysis for this study was conducted from April to August 2022.
Exposure
Plasma HDL-C.
Main results and measures
Included fractures were confirmed by medical imaging and included traumatic and minimal trauma fractures. Fractures were adjudicated by an expert review panel.
Results
Of the 16,262 participants who had a plasma HDL-C measurement at baseline (8945 female [55%] and 7319 male [45%] participants), 1659 experienced at least 1 fracture over a median (IQR) of 4.0 years (0.02 -7.0 years).
In a fully adjusted model, each 1 SD increase in HDL-C level was associated with a 14% increased risk of fractures (HR, 1.14; 95% CI, 1.08-1.20). Results remained similar when these analyzes were stratified by sex.
Sensitivity and stratified analyzes demonstrated that these associations persisted when analyzes were repeated to include only (1) minimal trauma fractures, (2) participants not taking osteoporosis medications, (3) participants who never smoked and reported no drank alcohol, and (4) participants who walked outdoors for less than 30 minutes per day and did not report engaging in moderate/vigorous physical activity and only examined (5) statin use.
No association was observed between non-HDL-C levels and fractures.
Conclusions and relevance
This study suggests that higher HDL-C levels are associated with a higher risk of fracture . This association was independent of common risk factors for fractures.
