Despite improvements in recognizing and managing patients with sepsis, short‐term mortality among this population continues to be high, and survivors of hospitalization remain at elevated risk for death and other adverse clinical events. Sepsis survivors may suffer from neurocognitive impairment, physical weakness, and other functional limitations, but cardiovascular disease (CVD) is increasingly being acknowledged as an important risk factor for sepsis.

“Although some prior studies have suggested that sepsis survivors may be at higher risk for post-discharge cardiovascular events for years after they’re hospitalized, those analyses have relevant limitations,” explains Jacob C. Jentzer, MD, FACC, FAHA. “It’s important to increase our understanding of cardiovascular risks among sepsis survivors. Links between infection and CVD have been proposed for many years in clinical research, but sepsis has not been well recognized as a cardiovascular risk factor in and of itself.”

A More Robust Approach for Higher-Quality Evidence

For a study published in the Journal of the American Heart Association, Dr. Jentzer and colleagues described associations between sepsis during hospitalization and subsequent death and rehospitalization among survivors while accounting for preexisting CVD and acute organ failure during hospitalization. “We wanted to confirm and expand on prior literature to better understand the association between sepsis and specific cardiovascular outcomes, including individual types of cardiovascular events,” Dr. Jentzer says. “We used what we believe are more robust methods to minimize limitations and provide higher-quality evidence.”

The study included data on patients who survived a medical or nonsurgical hospitalization for sepsis lasting at least 2 nights from 2009 to 2019. The study population included more than 2 million survivors of nonsurgical hospitalization. Nearly one-third (35.8%) of patients had a sepsis hospitalization, including implicit sepsis in 448,644 cases, explicit sepsis in 124,841 cases, and both implicit and explicit sepsis in 235,188 cases.

Sepsis Raises Risks of Severe Outcomes for Cardiovascular Events

When compared with hospitalized patients who did not have a sepsis diagnosis, those hospitalized with sepsis had higher risks of all post-discharge adverse events examined in the study. “Patients with, or at risk for CVD who survived sepsis were at substantially elevated risk for death from cardiovascular events after hospital discharge,” says Dr. Jentzer (Figure). “These patients were also at considerably higher risk of all-cause rehospitalization and rehospitalization for cardiovascular events after hospital discharge. This elevated risk was additive to preexisting CVD and other known risk factors.”

Patients with sepsis during hospitalization differed substantially from those without sepsis in the study. Patients hospitalized with sepsis were at increased risk for all types of CVD events, including atherosclerotic and nonatherosclerotic events. Those hospitalized with sepsis also had a higher overall risk profile, including a greater degree of critical illness and more acute and chronic CVD. Even after adjusting or stratifying for these factors, patients with sepsis remained at higher risk of subsequent adverse outcomes.

Sepsis Survivors Might Be Candidates for Intensifying Cardiovascular Prevention

According to the study team, clinicians caring for survivors of sepsis should be aware of their high risk of atherosclerotic and nonatherosclerotic CVD events. “Our results suggest that patients who survive sepsis are important candidates for optimization or intensification of cardiovascular prevention efforts, such as managing known CVD and preexisting CVD risk factors,” Dr. Jentzer says. “It’s well known that ‘deprescription’—a temporary or permanent discontinuation of prior preventive cardiovascular medications—is not infrequent in hospitalized patients, even in those with sepsis. It’s critically important to avoid deprescription or to reinstitute prescriptions after discharge as soon as feasible.”

The increased risk for CVD after sepsis hospitalization warrants careful follow‐up and optimization of guideline‐directed medical therapies in patients with pre-existing CVD. “In future research, it’s important to determine whether adding, changing, or uptitrating new or existing cardiovascular preventive medications around the time of discharge can reduce risks for future cardiovascular events among sepsis survivors,” says Dr. Jentzer.