Abstract P383: Possible Effect Modification of Beta-Blockers on the Association Between Heart Failure and Fracture Risk: A Cohort Study

Introduction: Heart failure (HF) is a chronic illness that occurs within a context of multiple comorbidities, including osteoporosis and fractures. While the causal pathway leading to elevated fracture risk in HF has yet to be determined, a potential mechanism may be increased sympathetic activation that inhibits bone formation and enhances resorption. By antagonizing sympathetic tone, β-blockers may protect against bone loss and, thereby, fractures. We assessed the association of HF with subsequent osteoporotic fractures by β-blocker use in a community setting. Methods: Olmsted County, Minnesota, residents meeting Framingham criteria for incident HF from 1990-2002 and community controls without HF, who were matched (1:1) to cases on age, sex, and index year, were studied using the resources of the Rochester Epidemiology Project. Major osteoporotic fracture (proximal femur, lumbar/thoracic vertebrae, distal forearm, or proximal humerus) risk in HF was compared directly with that in their matched controls utilizing a stratified Cox model with the case/control pairs forming the strata. Death as a competing risk was accounted for using the Fine & Gray model. Results: Among 1,050 participants (50% women; 525 with HF and 525 controls) 229 developed osteoporotic fractures during a mean follow-up of 6 years. The incidence rates of osteoporotic fracture per 1,000 person-years were 47.5 in HF cases and 30.4 in controls ( P =0.001). After adjustment for prior fracture and Charlson comorbidity score, the hazard ratio (HR) for fracture in HF cases vs. controls was 1.70 (95% CI: 1.17-2.47). β-blockers were prescribed in 45% of HF cases after diagnosis. The association between HF and fractures differed according to β-blocker usage. The HRs were 1.45 (95% CI: 0.86-2.47) and 2.16 (95% CI: 1.23-3.79) in HF cases prescribed and not prescribed β-blockers, respectively, when compared with their matched controls. Accounting for death as a competing risk, the HRs were 1.06 (95% CI: 0.64-1.76) and 1.63 (95% CI: 0.99-2.70) in HF cases on and off β-blockers, respectively. Conclusion: These findings suggest a modifying effect of β-blockers on the association between HF and osteoporotic fractures, which warrants a more thorough evaluation.