Sex Differences in Risk Factors for Incident Sepsis Hospitalizations: A Prospective Cohort Study Using the UK Biobank.

Summary

In 490,783 UK Biobank participants, 21,468 had incident sepsis hospitalizations; men had higher age-standardized risk than women. COPD was the strongest risk factor with excess risk in women, and dyslipidemia, myocardial infarction, and smoking likewise conferred greater excess risk in women; dementia doubled risk among men.

Key Findings

• Among 490,783 participants, 21,468 experienced incident sepsis hospitalization.
• Men had higher age-standardized risk than women (40.2 vs 31.2 per 10,000 person-years; HR 1.26, 95% CI 1.23–1.29).
• COPD was the strongest risk factor with excess risk in women (RHR 1.23, 95% CI 1.10–1.38).
• Dyslipidemia (RHR 1.08, 95% CI 1.02–1.16), myocardial infarction (1.22, 1.05–1.41), and smoking (1.19, 1.09–1.29) conferred greater excess risk in women.
• Dementia was associated with more than twice the risk of sepsis hospitalization in men (HR 2.21, 95% CI 1.37–3.55).

Clinical Implications

Clinicians should incorporate sex-stratified risk profiles into sepsis risk assessment: prioritize COPD, dyslipidemia, prior MI, and smoking in women, and recognize heightened risk with dementia in men to guide targeted prevention and vigilance.

Limitations

• Observational design limits causal inference and may retain residual confounding.
• Sepsis identified by hospitalization records may miss milder cases and be subject to misclassification.

Future Directions

External validation across diverse populations and age ranges; develop and test sex-specific sepsis risk scores; interventional studies targeting modifiable risks (e.g., smoking cessation, COPD optimization) with sepsis outcomes.