AUTHOR=Kang Wenhui , Zhong Jiyong , Wang Fei , Li Wulin , Dou Zhenfeng , Huang Shaoguan , Yin Shaohua , Yuan Lei , You Dali 

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

JOURNAL=Frontiers in Public Health

VOLUME=Volume 13 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2025.1666675

DOI=10.3389/fpubh.2025.1666675

ISSN=2296-2565

ABSTRACT=ObjectiveThis study aimed to examine the association between sepsis, including its subtypes, and all-cause and cause-specific premature mortality.MethodsThis 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.ResultsAmong 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).ConclusionSepsis, 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.