Risk for respiratory and cardiovascular disease and mortality after non-trauma fracture and the mediating effects of respiratory and cardiovascular disease on mortality risk among adults with epilepsy

Abstract

BackgroundNon-trauma fracture (NTFx), an indicator of skeletal fragility, is a risk factor for mortality among adults with epilepsy. NTFx may elicit its effect on mortality through development of respiratory disease (RD) and cardiovascular disease (CVD). Therefore, the objective was to determine if NTFx increases risk for RD and CVD, and if incident RD and CVD mediates the association between NTFx and mortality for adults with epilepsy. MethodsData were gathered from Optum Clinformatics® Data Mart years 2011–2016 for this retrospective cohort study. Diagnosis codes identified adults (≥18 years) with epilepsy, NTFx, RD (pneumonia, chronic obstructive pulmonary disease, interstitial/pleura disease), CVD (ischemic heart disease, heart failure, cerebrovascular disease), and baseline comorbidities. Crude incidence rate (IR) and crude IR ratio (IRR and 95 % confidence intervals [CI]) was estimated for mortality and incidence of RD and CVD for up to 2 years of follow up. Cox regression estimated hazard ratios (HR and 95 % CI) for each outcome, comparing adults with vs. without NTFx after adjusting for sociodemographics and baseline comorbidities. Separate mediation analyses estimated the extent that incident RD and CVD mediated the association between NTFx and mortality. ResultsAdults with epilepsy with vs. without NTFx had a higher crude incidence of mortality (IRR = 2.42; 95 %CI = 2.24–2.60) and each RD and CVD measure (IRR = 1.60–2.02). After adjustments, the HR remained elevated for mortality (HR = 1.66; 95 %CI = 1.54–1.79) and each RD and CVD measure (HR = 1.18–1.61). Incident pneumonia and interstitial/pleura disease mediated 9.82 % and 7.51 %, respectively, of the association between NTFx and mortality. ConclusionsIn a relatively short follow up of 2 years, NTFx was a robust risk factor for mortality, RD, and CVD among adults with epilepsy, and post-NTFx incidence of RD mediated a portion of the association between NTFx and mortality.