Sepsis associated with higher cardiovascular risk after hospitalization

A retrospective cohort analysis of 2.25 million U.S. patients found that those with sepsis were at higher risk for all-cause mortality and rehospitalization for each major type of cardiovascular disease event, particularly heart failure, than those without.

Sepsis may be associated with an elevated risk of late cardiovascular events among hospital survivors, according to a recent study. The excess risk developed early after hospitalization (within the first six to 12 months) and accumulated over time out to 12 years of follow-up.

To evaluate the association between sepsis and subsequent death and rehospitalization, including for cardiovascular disease (CVD) events, researchers analyzed 2009-2019 administrative claims data from U.S. patients who survived a nonsurgical hospitalization that lasted at least two nights. Patients were classified as having sepsis or not; within the sepsis group, explicit sepsis was defined as having diagnosis codes for sepsis or septic shock in the medical record, while implicit sepsis was defined as having at least one diagnosis of infection plus at least one diagnosis of acute organ dysfunction during the index hospitalization. Follow-up lasted from index hospital discharge until the end of the study period (Dec. 31, 2020), the end of insurance enrollment, or death, whichever happened first. The study results were published Feb. 1 by the Journal of the American Heart Association.

Overall, 2,258,464 patients who had survived a nonsurgical hospitalization were included in the study, with 5,396,051 total patient-years of follow-up. Mean age was 64.4 years, 54.4% were women, 62.5% were White, and 53.6% were enrolled in Medicare Advantage. A total of 808,673 patients (35.8%) had sepsis while hospitalized (implicit sepsis in 448,644, explicit sepsis in 124,841, and both in 235,188). Those who had sepsis were at higher risk for all-cause mortality (adjusted hazard ratio [HR], 1.27 [95% CI, 1.25 to 1.28]; P<0.001), all-cause rehospitalization (adjusted HR, 1.38 [95% CI, 1.37 to 1.39]; P<0.001), and rehospitalization for each major type of CVD event, particularly heart failure (adjusted HR, 1.51 [95% CI, 1.49 to 1.53]). Risk for all outcomes was higher in patients with implicit versus explicit sepsis. The researchers conducted a sensitivity analysis and a propensity-weighted analysis of the first hospitalization and found concordant results for the outcome of cardiovascular hospitalization (adjusted HRs, 1.78 [95% CI, 1.76 to 1.78] and 1.52 [95% CI, 1.50 to 1.54], respectively; P<0.001 for both).

This retrospective observational study took place before the COVID-19 pandemic and may have been affected by residual confounding, among other limitations, the authors noted. They concluded that patients who have sepsis during hospitalization may be at higher risk for subsequent death, rehospitalization, and CVD events. “The increased risk for CVD after sepsis hospitalization necessitates diligent follow-up and optimization of guideline-directed medical therapies in patients with preexisting CVD,” they wrote. “It is imperative to determine the mechanisms underlying this association and whether standard medical therapies for cardiovascular prevention are efficacious for reducing the risk of CVD events associated with sepsis survivorship in the absence of preexisting CVD.”

An accompanying editorial also pointed out the limitations of the study but agreed with the researchers that sepsis could be considered a nontraditional risk factor for short- and long-term CVD. “Although many questions remain, the findings of this article should alert providers to the importance of an episode of sepsis as a major event in their patient's medical history,” the editorialists wrote. “Prompt attention and recognition of the postdischarge burden of sepsis coupled with meticulous postdischarge care and cardiovascular risk stratification may potentially improve patient-centered outcomes.”