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Natural-cause mortality and C-reactive protein levels in patients with schizophrenia spectrum disorders: A prospective total cohort study

F. Fathian,I. Divkovic,M. Fagerbakke Strømme,A. Mykletun,R. Kroken,C. Bartz-Johannessen,E. Johnsen

Published 2025 in Brain, behavior, & immunity - health

ABSTRACT

Background Schizophrenia spectrum disorders (SSD) are associated with an excess mortality risk compared with the general population. The involvement of low-grade inflammation and elevated C-reactive protein (CRP) levels is well established in SSD. However, associations between CRP and mortality risk in SSD are less investigated. Aim To investigate the association between the baseline CRP level and natural-cause mortality risk in SSD. Methods We included all patients with an SSD diagnosis and baseline CRP measurement from an open cohort study of consecutively admitted patients to a psychiatric acute unit at Haukeland University Hospital, Bergen, Norway, between May 1, 2005 and June 15, 2014. All patients were followed until the time of death or censoring/study end, up to 18.6 years, and only the assessments at admission were the focus of the present study. A competing risk model was used, adjusting for age and sex. Results Among 1315 individuals, 245 (19 %) died of natural causes; among these patients, 66 (27 %) deaths were related to cardiovascular disease (CVD). Elevated baseline CRP levels of 1.0 ≤ CRP <3.0 mg/L were significantly associated with increased natural-cause mortality risk (adjusted hazard ratio [AHR], 1.88; 95 % confidence interval [CI], 1.22–2.88; p-value, 0.004), with a stronger association for CRP ≥3.0 mg/L (AHR, 2.28; 95 % CI, 1.50–3.48; p-value, <0.001), compared with patients with CRP <1.0 mg/L. Moreover, baseline CRP ≥3.0 mg/L was associated with increased CVD-related mortality risk (AHR, 3.12; 95 % CI, 1.16–8.41; p-value, 0.024). Conclusions Elevated CRP levels were associated with increased natural-cause mortality and, specifically, with CVD-related mortality risk. The CRP level may thus be considered a predictive factor in mortality risk scoring algorithms in SSD.

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