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

Daniel G. Whitney* (Corresponding Author), Sanjana Kannikeswaran, Daniel Whibley

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Background
Non-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.

Methods
Data 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.

Results
Adults 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.

Conclusions
In 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.
Original languageEnglish
Article number106411
Number of pages8
JournalEpilepsy Research
Volume166
Early online date29 Jun 2020
DOIs
Publication statusPublished - Oct 2020

Bibliographical note

Acknowledgements
Funding: This work was supported by the University of Michigan Office of Health Equity and Inclusion Diversity Fund and the American Academy of Cerebral Palsy and Developmental Medicine (Dr. Whitney).

Role of funder: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Keywords

  • Epilepsy
  • Non-trauma fracture
  • Mortality
  • respiratory disease
  • Cardiovascular Disease
  • Clinical epidemiology
  • Respiratory disease
  • Cardiovascular disease
  • BONE-MINERAL DENSITY
  • DEATH
  • ELDERLY-PEOPLE
  • PREVALENCE
  • HIP FRACTURE
  • INTERNATIONAL LEAGUE
  • PREMATURE MORTALITY
  • TASK-FORCE
  • CLAIMS
  • INCOME COUNTRIES

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