The association between 10-year cardiovascular risk and fracture incidence in postmenopausal women: a prospective analysis from the Women's Health Initiative

Background: Cardiovascular disease (CVD) and fractures share pathophysiological mechanisms, yet the relationship between predicted CVD risk and fracture incidence remains unexplored. Using the PREventing cardiovascular disease eVENTs (PREVENT) score, this study aimed to determine the association between CVD risk and incident fractures in postmenopausal women. Methods: This study included 21,300 participants from the Women's Health Initiative (WHI) (1993-2024). PREVENT 10-year CVD risk was categorized as low (<5·0%), borderline (5·0%-7·4%), intermediate (7·5%-19·9%), or high (≥20·0%). Cox proportional hazards models estimated adjusted hazard ratios HR (95% CI) for incident fractures, including any clinical, major osteoporotic fracture (MOF), and hip fracture. Findings: In the sample mean (SD) age: 63·7 (7·3) years, 9224 (43·3%) experienced any clinical fracture, 4997 (23·5%) MOF, and 1717 (8·1%) hip fractures. Overall, 5370 (25·2%) had low, 4169 (19·6%) borderline, 10,661 (50·1%) intermediate, and 1100 (5·2%) high CVD risk. In fully adjusted models, compared with low-CVD risk, higher risk of MOF was observed in the intermediate- 1·14 (1·04-1·24) and high- 1·22 (1·07-1·40) CVD risk groups; and higher risk of hip fracture intermediate: 1·33 (1·14-1·56); high: 1·93 (1·55-2·42). Associations attenuated after accounting for the competing risk of mortality, but higher CVD risk remained associated with higher fracture risk. Interpretation: A higher 10-year predicted CVD risk was associated with higher MOF and hip fracture risk after adjustment for sociodemographic, lifestyle, and clinical factors. CVD risk may have implications for fracture risk assessment in postmenopausal women. Funding: WHI is funded by the US National Heart, Lung, and Blood Institute. No additional funding was received for this study.