Risk for Adverse CVD Events Elevated Following Sepsis Survival

The residual risk of death and potential for both all-cause and major cardiovascular disease (CVD) event–related hospitalization were higher among a very large cohort of patients who had sepsis during a hospitalization—whether they were hospitalized because of it or developed sepsis during their stay—according to the findings of a new retrospective analysis. In particular, heart failure was the most common reported CVD event and the CVD event with the highest risk associated with hospitalization-related sepsis.

Findings were published online today with Journal of the American Heart Association.

“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,” said lead study author Jacob C. Jentzer, MD, FAHA, Mayo Clinic in Rochester, Minnesota, in a statement. “We sought to describe the association between sepsis during hospitalization and subsequent death and rehospitalization among a large group of adults.”

For their analysis, they examined data from the OptumLabs Data Warehouse on 2,258,464 patients hospitalized for a nonsurgical reason between January 1, 2009, and December 31, 2019; this data source is a repository for claims and enrollment records for both commercial and Medicare Advantage enrollees. These patients totaled 5 million–plus patient-years of follow-up. Each hospitalization had to be for at least 2 nights, and International Classification of Diseases, Ninth Revision/Tenth Revision explicit and implicit diagnosis codes were used to classify hospital charge. The study period ended December 31, 2020.

Of the entire study population, 35.8% (n = 808,673) had a sepsis-related hospitalization. Breaking this total down, 55.5% (n = 448,644) had implicit sepsis only, 15.4% (n = 124,841) had explicit sepsis only, and 29.1% (n = 235,188) had both.

The investigators’ analyses also determined that all-cause mortality was increased by 27% (HR, 1.27; 95% CI, 1.25-1.28; P < .001), all-cause rehospitalization by 38% (HR, 1.38; 95% CI, 1.37-1.39; P < .001), and CVD-related hospitalization by 43% (HR, 1.43; 95% CI, 1.41-1.44; P < .001) among patients with a documented sepsis case during hospitalization. Among the CVD-related hospitalizations, heart failure had the highest elevated sepsis-associated risk, at 51% (HR, 1.51; 95% CI, 1.49-1.53).

Patients in this study were a mean (SD) 64.4 (14.6) years, made up of a majority of female patients (54.4%), lived in the South region of the United States (45.8%), and had Medicare Advantage coverage (53.6%).

Between the patients with sepsis and those who did not have sepsis, respectively, the following characteristics differed significantly:

• Patient of an older age (55-64, 65-74, and 75 years and older): 84.6% vs 69.0%
• Medicare Advantage enrollees: 68.1% vs 45.6%
• History of prior CVD: 61.4% vs 44.3%
• CVD during index hospitalization: 56.1% vs 44.9%
• Sepsis/bacteremia during index hospitalization: 20.8% vs 0.2%
• Pulmonary infection during index hospitalization: 34.3% vs 4.7%
• Organ failure during index hospitalization: 84.9% vs 23.3%
• Mean length of hospital stay: 6.7 (7.5) vs 4.2 (4.2) days

Within the group of patients with sepsis, more patients with implicit sepsis alone were older (> 75 years), at 44.5% vs 29.0% of patients with explicit sepsis alone and 40.5% of patients with both types. In addition, the patients with implicit sepsis only had higher rate of all the prior CVDs evaluated, among then coronary artery disease, heart failure, atrial fibrillation, stroke, and implanted device (all P < .001).

Sensitivity analyses findings continued the trend of elevated risk among those with sepsis, with risks for all-cause mortality, all-cause rehospitalization, and CVD hospitalization all increased among this group (all P < .001):

• All-cause mortality: 33% (HR, 1.33; 95% CI, 1.32-1.35)
• All-cause rehospitalization: 47% (HR, 1.47; 95% CI, 1.46-1.48)
• CVD hospitalization: 52% (HR, 1.52; 95% CI, 1.50-1.54)

The study investigators noted that the elevated risk was not transient. It both developed early, within 6 to 12 months of hospitalization, and persisted over the 12 years of study follow-up. They also underscored that their findings mirror much of the existing literature of higher short- and long-term risks among patients who survived a sepsis infection.

In addition, they noted that the strength of their findings include the inclusion of higher-risk patients “to ensure we did not use low-risk patients as a comparator group” and their robust methodology in a broader study population.

Moving forward, they urge health care providers to remain vigilant of patients’ changing risk status following a sepsis infection, particularly among those who present for a hospitalization with an initial low-risk status, in light of evidence that demonstrates downstream risks sepsis survivors face after hospital discharge.

An accompanying editorial stresses the importance of the study’s findings, noting the investigation is the largest to date of associations between sepsis and postdischarge adverse events.

“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 editorial’s authors 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.”

Reference

Jentzer JC, Lawler PR, Van Houten HK, Yao X, Kashani KB, Dunlay SM. Cardiovascular events among survivors of sepsis hospitalization: a retrospective cohort analysis. J Am Heart Assoc. Published online February 1, 2023. doi:10.1161/JAHA.122.027813