Systemic inflammation is associated with future risk of fatal infection: an observational cohort study

Background

Many diseases are associated with chronic inflammation, resulting in widening application of anti-inflammatory therapies. Whilst effective as disease modifying agents, these increase the risk of serious infection; however, it remains unknown if chronic systemic inflammation per se is also associated with fatal infection.

Methods

Using serum C-reactive protein (CRP) data from 461,052 UK Biobank participants, we defined incidence rate ratios (IRR) for death from infection, cardiovascular disease, or other causes, adjusted for comorbidities and the use of anti-inflammatory therapies.

Results

Systemic inflammation, defined as CRP ≥2 mg/L, was common in all comorbidities considered. After adjusting for confounding factors, systemic inflammation was associated with a higher IRR point estimate for infection death (1.70; 95% confidence interval 1.51-1.92) than cardiovascular (1.48; 1.40-1.57) or other death (1.41; 1.37-1.45), although confidence intervals overlapped. CRP thresholds of ≥5 and ≥10 mg/L yielded similar findings, as did analyses in people with ≥2, but not <2, comorbidities.

Conclusions

Systemic inflammation per se identifies people at increased risk of infection death, potentially contributing to the observed risks of anti-inflammatory therapies in clinical trials. Future clinical trials of anti-inflammatory therapies should carefully consider risks and benefits in target populations, guided by research into mechanisms of infection risk.