Abstract
AbstractBackgroundMany diseases are associated with chronic inflammation, resulting in widening indications for anti-inflammatory therapies. Whilst effective as disease modifying agents, these increase the risk of serious infection.ObjectiveTo determine if low-grade inflammation is associated with fatal infection, irrespective of associated comorbidity or anti-inflammatory therapy.DesignObservational cohort studySettingUK Biobank studyParticipants461,052 peopleInterventionsNoneMeasurementsIncidence rate ratio (IRR) of death from infection, cardiovascular disease, or other causes, adjusted for comorbidities and use of anti-inflammatory therapies, for serum C-reactive protein (CRP) at recruitment.ResultsLow grade inflammation was common in all morbidities considered and was more prevalent as multimorbidity accrued (CRP ≥2mg/L in 23.3% of people without disease and 58.7% with 3+ comorbidities; p<0.001). After adjusting for confounding factors, CRP ≥2mg/L was associated with a higher IRR of infection death (IRR 1.70; 95% confidence interval 1.51-1.92) than cardiovascular death (IRR 1.48; 1.40-1.57) or other causes of death (IRR 1.41; 1.37-1.45); CRP thresholds of ≥5 and ≥10 mg/L yielded similar findings. Absolute rates of infection, cardiovascular and other death were 0.43, 1.59 and 5.39 per 1000 participant-years, respectively, in people with CRP ≥2mg/L. Analyses stratified by disease type, or number of comorbidities, showed consistent associations between elevated CRP and infection death.LimitationsOur observational study design precludes assessment of causality. We lacked data on the use of anti-inflammatory therapies after study recruitment.ConclusionLow grade inflammation, irrespective of associated comorbidity, identifies people at particularly increased risk of infection death. Decisions to use anti-inflammatory therapies guided by low grade inflammation require careful consideration of the associated risks and benefits.
Publisher
Cold Spring Harbor Laboratory