Low grade systemic inflammation is a risk factor for infection death: an observational cohort study

medRxiv

Abstract

Abstract Background Many 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. Objective To determine if low-grade inflammation is associated with fatal infection, irrespective of associated comorbidity or anti-inflammatory therapy. Design Observational cohort study Setting UK Biobank study Participants 461,052 people Interventions None Measurements Incidence 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. Results Low 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. Limitations Our observational study design precludes assessment of causality. We lacked data on the use of anti-inflammatory therapies after study recruitment. Conclusion Low 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.

Authors 7

1. Michael Drozd

   University of Leeds

   Affiliation as printed

   Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, United Kingdom

2. Mar Pujades‐Rodríguez

   University of Leeds

   Affiliation as printed

   Leeds Institute of Health Sciences, School of Medicine, The University of Leeds, Leeds, United Kingdom

3. Ann Wendy Morgan

   University of Leeds · Leeds Teaching Hospitals NHS Trust · NIHR Leeds In Vitro Diagnostics Co-operative

   Affiliation as printed

   Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, United Kingdom

   NIHR Leeds Biomedical Research Centre and NIHR Leeds Medtech and In vitro Diagnostics Co-operative, Leeds Teaching Hospitals NHS Trust, United Kingdom

4. Patrick J. Lillie

   Castle Hill Hospital

   Affiliation as printed

   Department of Infection, Castle Hill Hospital, Hull University Hospitals NHS Trust, Kingston Upon Hull, United Kingdom

5. Klaus Karl Witte Aachen Medical Clinic 1

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Medical Clinic 1, University Hospital Aachen, RWTH, Aachen, Germany

6. Mark T. Kearney

   University of Leeds

   Affiliation as printed

   Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, United Kingdom

7. Richard M. Cubbon corresponding

   University of Leeds

   Affiliation as printed

   Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, United Kingdom