Association of covert brain infarcts and white matter hyperintensities with risk of hip fracture in older adults: the Cardiovascular Health Study

Summary: Covert brain infarcts and white matter hyperintensities (WMHs), incidental markers of brain microvascular disease commonly seen on brain MRIs in older adults, have been associated with falls and lower bone mineral density. We found covert infarcts and WMHs may also be associated with an increased risk of future hip fracture. Introduction: To determine whether covert infarcts and white matter hyperintensities (WMHs) are associated with increased risk of incident hip fracture. Methods: A prospective cohort of 3373 community-dwelling adults aged ≥ 65 years enrolled in the Cardiovascular Health Study with a brain MRI (1992–1993) was analyzed. Covert infarcts were categorized by number of infarcts and largest infarct size. WMH burden was assessed by radiologists and graded qualitatively from 0 (no WMHs) to 9 (extensive). Results: Participants had 465 incident hip fractures during a mean follow-up of 12.8 years. The demographic-adjusted hazard of incident hip fracture was 32% higher among participants with ≥ 1 covert infarct compared to those without infarcts (hazard ratio (HR) 1.32; 95% CI, 1.08–1.62). The hazard of incident hip fracture was similar after further adjustment for medications and medical history (HR = 1.34; 95% CI, 1.08–1.65), but attenuated following additional adjustment for functional status, frailty, and falls (HR = 1.25; 95% CI, 0.99–1.57). Fully adjusted hazard of incident hip fracture per increase in infarct number was 1.10 (95% CI, 0.98–1.23); risk in individuals whose largest infarct was ≥ 20 mm versus 3 to < 20 mm was similar. Compared with WMH grades 0–1, the demographic-adjusted hazard of hip fracture was 1.34 (95% CI, 1.09–1.66) and 1.83 (95% CI, 1.37–2.46), respectively, for WMH grades 2–3 and 4–9. The hazard was similar following adjustment for medications and medical history (grades 2–3: HR = 1.32; 95% CI, 1.05–1.64; grades 4–9: HR = 1.69; 95% CI, 1.23–2.30), but attenuated following additional adjustment for functional status, frailty, and falls (grades 2–3: HR = 1.24; 95% CI, 0.98–1.56; grades 4–9: HR = 1.34; 95% CI, 0.95–1.90). Conclusion: Older, community-dwelling adults with covert infarcts or WMHs may be at increased risk of hip fracture.