Prevalent diabetes and long-term cardiovascular outcomes in adult sepsis survivors: a population-based cohort study

Background — Sepsis survivors are at elevated risk for cardiovascular disease during long-term follow-up. Whether diabetes influences cardiovascular risk after sepsis survival remains unknown. We sought to describe the association of diabetes with long-term cardiovascular outcomes in adult sepsis survivors.

Methods — Population-based cohort study in the province of Ontario, Canada (2008–2017). Adult survivors of a first sepsis-associated hospitalization, without pre-existing cardiovascular disease, were included. Main exposure was pre-existing diabetes (any type). The primary outcome was the composite of myocardial infarction, stroke, and cardiovascular death. Patients were followed up to 5 years from discharge date until outcome occurrence or end of study period (March 2018). We used propensity score matching (i.e., 1:1 to patients with sepsis but no pre-existing diabetes) to adjust for measured confounding at baseline. Cause-specific Cox proportional hazards models with robust standard errors were used to estimate hazard ratios (HR) alongside 95% confidence intervals (CI). A main secondary analysis evaluated the modification of the association between sepsis and cardiovascular disease by pre-existing diabetes.

Results — 78,638 patients with pre-existing diabetes who had a sepsis-associated hospitalization were matched to patients hospitalized for sepsis but without diabetes. Mean age of patients was 71 years, and 55% were female. Median duration from diabetes diagnosis was 9.8 years; mean HbA1c was 7.1%. Adult sepsis survivors with pre-existing diabetes experienced a higher hazard of major cardiovascular disease (HR 1.25; 95% CI 1.22–1.29)—including myocardial infarction (HR 1.40; 95% CI 1.34–1.47) and stroke (HR 1.24; 95% CI 1.18–1.29)—during long-term follow-up compared to sepsis survivors without diabetes. Pre-existing diabetes modified the association between sepsis and cardiovascular disease (risk difference: 2.3%; 95% CI 2.0–2.6 and risk difference: 1.8%; 95% CI 1.6–2.0 for the effect of sepsis—compared to no sepsis—among patients with and without diabetes, respectively).

Conclusions — Sepsis survivors with pre-existing diabetes experience a higher long-term hazard of major cardiovascular events when compared to sepsis survivors without diabetes. Compared to patients without sepsis, the absolute risk increase of cardiovascular events after sepsis is higher in patients with diabetes (i.e., diabetes intensified the higher cardiovascular risk induced by sepsis).