Study Supports Recognition of Sepsis as Cardiovascular Risk Factor

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Using data from more than 2 million US adults with nonsurgical hospitalizations, a new study from the Mayo Clinic is sounding the alarm on the increased cardiovascular risk associated with developing sepsis.

Developing sepsis during a non-surgical hospitalization is linked to a significant increase in cardiovascular and mortality risk, according to a new study from the Mayo Clinic.1

An analysis of data from more than 2 million US adults who survived a nonsurgical hospitalization of 2 nights, results of the study indicate sepsis was associated with a 27% greater risk of death, 38% greater risk of rehospitalization, 43% greater risk of rehospitalization for cardiovascular causes, and 51% greater risk of developing heart failure following discharge compared to people without sepsis.

“We know that infection may be a potential trigger for myocardial infarction or heart attack, and infection may also predispose a patient to other cardiovascular events, either directly during infection or later when the infection and related effects on the body promote progressive cardiovascular disease,” said lead investigator Jacob C. Jentzer, MD, assistant professor of medicine in the department of cardiovascular medicine at the Mayo Clinic in Rochester, Minnesota.2 “We sought to describe the association between sepsis during hospitalization and subsequent death and rehospitalization among a large group of adults.”

With US Centers for Disease Control and Prevention statistics indicating upwards of 1.7 million adults in the US develop sepsis each and at least 350,000 will die during hospitalization or be discharged to hospice3, Jentzer and a team of colleagues from the Mayo Clinic sought to explore associations between sepsis and elevated cardiovascular risk using contemporary data from US patients. To do so, investigators designed their study as an analysis of adult patients with a nonsurgical hospitalization lasting at least 2 nights with data recorded within the OptumLabs Data Warehouse from 2009-2019. Using this data, investigators planned to estimate associations between sepsis during hospitalization with subsequent death and rehospitalization using Kaplan-Meier survival analysis and multivariable Cox proportional-hazards models.

Of note, diagnoses of sepsis were identified within the OptumLabs Data Warehouse using ICD‐9/ICD‐10 diagnostic codes at discharge.

Overall, investigators identified 2,258,464 adult survivors of nonsurgical hospitalization with a total follow-up of 5,3956,051 patients-years. This cohort had a mean age of 64.4 (SD, 14.6) years, 54.4% were women, 62.5% were White, and 53.6% were enrolled in a Medicare Advantage plan. Among the 2.258 million patient cohort, 808,673 (35.8%) had a sepsis hospitalization, including implicit sepsis only in 448,644, explicit sepsis only in 124,841, and both in 235,188 individuals. Initial analyses indicated those with sepsis hospitalizations were more likely to be older, a Medicare Advantage enrollee, experience more infection and organ failure, have more comorbidities and cardiovascular risk factors, have preexisting and inpatient CVD diagnoses, have greater use of critical care therapies, and have a longer hospital length of stay.

Upon analysis, results indicated patients hospitalized with sepsis had a greater risk of all-cause mortality (adjusted hazard ratio [aHR], 1.27 [95% CI, 1.25-1.28]; P <.001), all‐cause rehospitalization (aHR, 1.38 [95% CI, 1.37-1.39]; P <.001), cardiovascular hospitalization (aHR, 1.43 [95% CI, 1.41-1.44]; P <.001), and hospitalization for heart failure (aHR, 1.51 [95% CI, 1.49-1.53]; P <.001). Investigators pointed out the risk for postdischarge events was elevated for across the implicit sepsis, explicit sepsis, and both subgroups relative to their counterparts without sepsis, but a greater risk of the aforementioned adverse outcomes was observed for those with implicit sepsis compared to their counterparts with explicit sepsis.

“Our findings indicate that after hospitalization with sepsis, close follow-up care is important, and it may be valuable to implement cardiovascular prevention therapies with close supervision,” Jentzer added.2 “Professionals need to be aware that people who have previously had sepsis are at very high risk for cardiovascular events, and that it may be necessary to advise them to increase the intensity of their cardiovascular prevention.”

In a linked editorial, Gabriel Wardi, MD, MPH, Alex Pearce, MD, Anthony DeMaria, MD, and Atul Malhotra, MD, all of whom are affiliated with University of California of San Diego, applaud the investigators for what they purport is the largest study to date evaluating sepsis and postdischarge events. In their editorial, the group also calls for other clinicians, cardiologists and noncardiologists alike, to recognize sepsis as a risk factor for cardiovascular disease.4

“How should clinicians use these new findings to improve patient care? To begin, as Jentzer et al suggest, sepsis may be a nontraditional risk factor for cardiovascular disease. Next, the association between sepsis and cardiovascular complications in this study was present both in early (within 6–12 months of admission) and long‐term time periods (years after discharge), each of which may serve as targets for intervention,” wrote the UCSD-affiliated group.4


  1. Jentzer JC. Cardiovascular Events Among Survivors of Sepsis Hospitalization: A Retrospective Cohort Analysis. Journal of the American Heart Association. February 2023. doi:10.1161/JAHA.122.027813
  2. Sepsis increased risk of heart failure and rehospitalization after hospital discharge. American Heart Association Newsroom. February 2023. Accessed February 1, 2023.
  3. What is sepsis? Centers for Disease Control and Prevention. Published August 9, 2022. Accessed February 1, 2023.
  4. Wardi G. Describing Sepsis as a Risk Factor for Cardiovascular Disease. Journal of the American Heart Association. February 2023.