The influence of comorbid disease on premature death due to natural and unnatural causes in persons with schizophrenia

Schizophr Res. 2023 Jul:257:27-33. doi: 10.1016/j.schres.2023.04.006. Epub 2023 May 25.

Abstract

Background: Comorbid disease may increase mortality in persons with schizophrenia, but how specific diseases are associated with natural and unnatural death in different age groups is unclear.

Aims: To investigate the association between eight major comorbid diseases and death from natural and unnatural causes in different age groups in persons with schizophrenia.

Method: Retrospective register-based cohort study in 77,794 persons with schizophrenia in Denmark, 1977-2015. Using Cox regression in matched cohorts, we estimated hazard ratios for natural and unnatural death in three age groups (<55 years, 55-64 years, ≥65 years).

Results: Hypertensive disease, atrial fibrillation, coronary heart disease, cerebrovascular disease, heart failure, type 2 diabetes, liver disease and chronic kidney disease were all strongly associated with natural death, with the strongest associations observed in persons <55 years (hazard ratio [HR] range 1.98-7.19). The strongest associations were observed for heart failure (HR 7.19, 95 % confidence interval [CI] 5.57-9.28; HR 4.56, CI 3.85-5.40; HR 2.83, CI 2.53-3.17), liver disease (HR 4.66, CI 3.59-6.05; HR 4.70, CI 3.55-6.22; HR 2.57, CI 1.98-3.34) and chronic kidney disease (HR 6.59, CI 1.66-26.1; HR 7.37, CI 3.03-17.9; HR 2.86, CI 1.84-4.46) for persons <55 years, 55-64 years and ≥65 years, respectively. Liver disease was strongly associated with unnatural death in persons <55 years (HR 5.42, CI 3.01-9.75); associations with the remaining comorbidities were weaker.

Conclusions: Comorbid disease was strongly associated with natural death, with the strength of the associations decreasing with age. Comorbid disease was also modestly associated with unnatural death, regardless of age.

Keywords: Comorbidity; Epidemiology; Mortality; Schizophrenia; Somatic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cause of Death
  • Cohort Studies
  • Comorbidity
  • Diabetes Mellitus, Type 2*
  • Heart Failure* / epidemiology
  • Humans
  • Middle Aged
  • Mortality, Premature
  • Renal Insufficiency, Chronic*
  • Retrospective Studies
  • Schizophrenia*