Association between sepsis and all-cause and cause-specific premature mortality: a prospective cohort study

Wenhui Kang¹Jiyong Zhong¹Fei Wang¹Wulin Li¹Zhenfeng Dou¹Shaoguan Huang¹Shaohua Yin²Lei Yuan³Dali You^4*

• ¹Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
• ²Peking University Third Hospital, Beijing, China
• ³Naval Medical University, Shanghai, China
• ⁴Jiading District Central Hospital, Shanghai, China

Objective: This study aimed to examine the association between sepsis, including its subtypes, and all-cause and cause-specific premature mortality. Methods: This population-based prospective cohort study included 371 558 participants from the UK Biobank recruited between 2006 and 2010. Sepsis was identified from hospital records using ICD-10 codes. Cox proportional-hazards models estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for premature mortality. Results: Among 371 558 participants, 47 149 (12.7%) were diagnosed with sepsis, including 21 148 with implicit sepsis, 620 with explicit sepsis, and 25 381 with both. Sepsis was associated with a higher risk of all-cause premature mortality (aHR 2.36, 95% CI 2.26–2.46). Cause-specific analyses showed elevated risks for cardiovascular (aHR 2.35, 95% CI 2.18– 2.54), respiratory (aHR 7.30, 95% CI 6.23–8.55), cancer-related (aHR 1.76, 95% CI 1.66– 1.87), and infection-related premature mortality (aHR 9.75, 95% CI 6.97–13.62). Participants with explicit sepsis alone had elevated risk of all-cause mortality (aHR 1.72, 95% CI 1.21– 2.45), which was lower than implicit sepsis alone (aHR 2.05, 95% CI 1.94–2.17) and highest for those with both implicit and explicit sepsis (aHR 2.60, 95% CI 2.48–2.73). Risks were more pronounced in participants with older age, multiple comorbidities, and unhealthy lifestyle (Pinteraction <0.001). Conclusion: Sepsis, especially implicit and combined implicit-explicit sepsis, was associated with increased risks of all-cause and cause-specific premature mortality. These associations were stronger in older participants, those with comorbidities, and unhealthy lifestyles.