Abstract

Introduction: Sepsis results in dysregulated inflammation, coagulation, and metabolism, which may contribute to increased cardiovascular disease (CVD) risk. We conducted a systematic review and meta-analysis to determine the association between sepsis and subsequent long-term CVD events. Methods: MEDLINE, Embase, and the Cochrane Controlled Trials Register and Database of Systematic Reviews were searched from inception to May 2020 to identify observational studies of adult sepsis survivors (defined by diagnostic codes or consensus definitions) measuring long-term CV outcomes. The primary outcome was a composite of myocardial infarction, CV death, and stroke. Random-effects models estimated the pooled cumulative incidence and adjusted hazard ratios of CV events relative to hospital or population controls. Odds ratios were included as risk ratios assuming <10% incidence in non-septic controls, and risk ratios were taken as hazard ratios (HR) assuming no censoring. Outcomes were analyzed at maximum follow-up (primary analysis) and stratified by time (<1 year, 1-2 years, and >2 years) since sepsis. Results: Of 11,235 abstracts screened, 25 studies (22 cohort studies, 2 case-crossover studies, and 1 case-control) involving 1,949,793 sepsis survivors were included. The pooled cumulative incidence of CVD events was 9% (95% CI; 5-14%). Sepsis was associated with an increased risk (HR 1.59, 95% CI 1.37-1.86) of CVD events at maximum follow-up ( Figure ); between-study heterogeneity was substantial (I 2 =97.3%). There was no significant difference when comparing studies using population and hospital controls. Significantly elevated risk was observed up to 5 years following sepsis. Conclusions: Sepsis survivors experience an approximately 50% increased risk of CVD events, which may persist for years following the index episode. These results highlight a potential unmet need for early cardiac risk stratification and optimization in sepsis survivors.

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