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. 2023 Mar 1;8(3):268-272.
doi: 10.1001/jamacardio.2022.5124.

Association of Plasma High-Density Lipoprotein Cholesterol Level With Risk of Fractures in Healthy Older Adults

Sultana Monira Hussain  1   2 , Peter R Ebeling  3 , Anna L Barker  1   4 , Lawrence J Beilin  5 , Andrew M Tonkin  1 , John J McNeil  1
Affiliations

Association of Plasma High-Density Lipoprotein Cholesterol Level With Risk of Fractures in Healthy Older Adults

Sultana Monira Hussain et al. JAMA Cardiol. .

Abstract

Importance: Increased 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 osteoblast number and function. However, the clinical significance of these findings is unclear.

Objective: To determine whether higher HDL-C levels are predictive of an increased fracture risk in healthy older adults.

Design, setting, 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 primary prevention trial of aspirin that recruited participants between 2010 and 2014. These comprised community-based older adults (16 703 Australians aged ≥70 years, 2411 US participants ≥65 years) without evident cardiovascular disease, dementia, physical disability, and life-limiting chronic illness. The ASPREE-Fracture substudy collected data on fractures reported postrandomization from Australian participants. Cox regression was used to calculate hazard ratio (HR) and 95% CI. Data analysis for this study was performed from April to August 2022.

Exposure: Plasma HDL-C.

Main outcomes and measures: Fractures included were confirmed by medical imaging and included both 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 participants [55%] and 7319 male [45%]), 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 increment in HDL-C level was associated with a 14% higher risk of fractures (HR, 1.14; 95% CI, 1.08-1.20). The results remained similar when these analyses were stratified by sex. Sensitivity and stratified analyses demonstrated that these associations persisted when the analyses were repeated to include only (1) minimal trauma fractures, (2) participants not taking osteoporosis medications, (3) participants who were never smokers and reported that they did not drink alcohol, and (4) participants who walked outside for less than 30 minutes per day and reported no participation in moderate/vigorous physical activity and to examine only (5) statin use. No association was observed between non-HDL-C levels and fractures.

Conclusions and relevance: This study suggests that higher levels of HDL-C are associated with an increased fracture risk. This association was independent of common risk factors for fractures.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Hussain reported receiving a National Health and Medical Research Council (NHMRC) Early Career Fellowship (APP1142198). Dr Ebeling reported grants from Amgen, Alexion, and Sanofi and honoraria from Amgen outside the submitted work. Dr Barker reported grants from the NHMRC related to this and other projects. Dr Tonkin reported grants from the National Institute of Aging and NHMRC during the conduct of the study and advisory board, data monitoring committee, and lecture fees from Amgen, The Medicines Company, Pfizer, Boehringer Ingelheim, and Merck outside the submitted work. Dr McNeil reported support from an NHMRC Leadership Fellowship (IG1173690). No other disclosures were reported.

Figures

Figure.
Figure.. Association Between Levels of High-Density Lipoprotein (HDL) Cholesterol and Fractures
The dotted blue line indicates the reference value of 58 mg/dL. To convert HDL cholesterol to millimoles per liter, multiply by 0.0259.
See this image and copyright information in PMC

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