Risk of cardiovascular events in survivors of severe sepsis

Abstract

Rationale: The risk of cardiovascular events after severe sepsis is not known, and these events may explain increased long-term mortality in survivors of severe sepsis.

Objectives: To determine whether survivors of severe sepsis hospitalization have high long-term risk of cardiovascular events. We examined whether higher risk is due to severe sepsis hospitalization or poor prehospitalization health status, and if the higher risk is also observed in patients hospitalized for infectious and noninfectious reasons, and in other critically ill patients.

Methods: Unmatched and matched-cohort analyses of Medicare beneficiaries. For unmatched analysis, we compared patients with severe sepsis admitted to the intensive care unit (ICU) and survived hospitalization (n = 4,179) to unmatched population control subjects (n = 819,283). For matched analysis, we propensity-score-matched each patient with severe sepsis to four control subjects (population, hospitalized, non-severe sepsis ICU control subjects, and infection hospitalization). Primary outcome was 1-year incidence rate of hospitalization for cardiovascular events.

Measurements and main results: Cardiovascular events were common among patients discharged alive after severe sepsis hospitalization (29.5%; 498.2 events/1,000 person-years). Survivors of severe sepsis had a 13-fold higher risk of cardiovascular events compared with unmatched control subjects (498.2 vs. 36 events/1,000 person-years; P < 0.0001), and a 1.9-fold higher risk compared with matched-population control subjects (P < 0.0001). Survivors of severe sepsis had 1.1-fold higher risk compared with matched hospitalized patients and infection hospitalizations (P = 0.002 and 0.001) and similar risk compared with matched-ICU control subjects.

Conclusions: Survivors of severe sepsis have high risk of cardiovascular events. The higher risk is mainly due to poor prehospitalization health status, and is also seen in a broader population of acutely ill patients.

Figure 1.

Flowchart describing selection of subjects for unmatched and matched analyses. ICU = intensive care unit.

Figure 2.

Failure plots showing proportion of beneficiaries with at least one cardiovascular event after the index hospitalization. Data are shown by quarter in the calendar year, because exact hospitalization dates are not available. The first, second, third, and fourth quarter after the index hospitalizations are labeled as Q1, Q2, Q3, and Q4, respectively. ICU = intensive care unit.

Figure 3.

Incidence rates of cardiovascular events among patients with severe sepsis who required the intensive care unit (ICU) and survived hospitalization and matched and unmatched control subjects. Matched control subjects include ICU control subjects, infection hospitalizations, hospitalized patients, and general population.

Figure 4.

Incidence rates of cardiovascular events for matched analyses comparing patients with severe sepsis requiring intensive care unit (ICU) and surviving hospitalization, and control subjects. Each case was matched to four control subjects to form a pentad. Incidence rates are shown for those without preillness cardiovascular disease ([A] includes 1,840 pentads; n = 9,200), and those who did not incur a cardiovascular event during the index hospitalization ([B] includes 2,562 pentads; n = 12,810). CVD = cardiovascular disease.