Association between sepsis survivorship and long-term cardiovascular outcomes in adults: a systematic review and meta-analysis

Purpose We aimed to determine the association between sepsis and long-term cardiovascular events. Methods We conducted a systematic review of observational studies evaluating post-sepsis cardiovascular outcomes in adult sepsis survivors. MEDLINE, Embase, and the Cochrane Controlled Trials Register and Database of Systematic Reviews were searched from inception until April 21st, 2021. Two reviewers independently extracted individual study data and evaluated risk of bias. Random-effects models estimated the pooled crude cumulative incidence and adjusted hazard ratios (aHRs) of cardiovascular events compared to either non-septic hospital survivors or population controls. Primary outcomes included myocardial infarction, stroke, and congestive heart failure; outcomes were analysed at maximum reported follow-up (from 30 days to beyond 5 years post-discharge). Results Of 12,649 screened citations, 27 studies (25 cohort studies, 2 case-crossover studies) were included with a median of 4,289 (IQR 502-68,125) sepsis survivors and 18,399 (IQR 4,028-83,506) controls per study. The pooled cumulative incidence of myocardial infarction, stroke, and heart failure in sepsis survivors ranged from 3 to 9% at longest reported follow-up. Sepsis was associated with a higher long-term risk of myocardial infarction (aHR 1.77 [95% CI 1.26 to 2.48]; low certainty), stroke (aHR 1.67 [95% CI 1.37 to 2.05]; low certainty), and congestive heart failure (aHR 1.65 [95% CI 1.46 to 1.86]; very low certainty) compared to non-sepsis controls. Conclusions Surviving sepsis may be associated with a long-term, excess hazard of late cardiovascular events which may persist for at least 5 years following hospital discharge.