Risk Factors for Major Cardiovascular Events in Adult Sepsis Survivors: A Population-Based Cohort Study*

Abstract

OBJECTIVES: To describe risk factors for major cardiovascular events in adults following hospital discharge after sepsis. DESIGN: Population-based cohort study. SETTING: Ontario, Canada (2008–2017). PATIENTS: Adult patients (age 18 yr or older) who survived a first sepsis hospitalization without preexisting cardiovascular disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary composite outcome was myocardial infarction, stroke, or cardiovascular death up to 5 years following hospital discharge. We used cause-specific Cox proportional hazards models that accounted for the competing risk of noncardiovascular death to describe factors associated with major cardiovascular events. We identified 268,259 adult patients without cardiovascular disease (median age, 72 yr), of whom 10.4% experienced a major cardiovascular event during a median follow-up of 3 years. After multivariable adjustment, age (hazard ratio [HR], 1.53 for every 10 yr; 95% CI, 1.51–1.54), male sex (HR, 1.23; 95% CI, 1.20–1.26), diabetes mellitus (HR, 1.24; 95% CI, 1.21–1.27), hypertension (HR, 1.34; 95% CI, 1.30–1.38), prevalent atrial fibrillation (HR, 1.46; 95% CI, 1.40–1.52), and chronic kidney disease (HR, 1.11; 95% CI, 1.06–1.16) were associated with major cardiovascular events during long-term follow-up. Sepsis characteristics such as site of infection (pneumonia vs other: HR, 1.09; 95% CI, 1.05–1.12), septic shock (HR, 1.08; 95% CI, 1.05–1.11), and renal replacement therapy (HR, 1.51; 95% CI, 1.38–1.64) were also associated with subsequent cardiovascular events. In an analysis restricting to patients with troponin values measured during the hospitalization (26,400 patients), an elevated troponin was also associated with subsequent cardiovascular events (HR, 1.23; 95% CI, 1.13–1.33). CONCLUSIONS: Classic cardiovascular risk factors, comorbid conditions, and characteristics of the sepsis episode were associated with a higher hazard of major cardiovascular events in adult sepsis survivors. These findings may inform enrichment strategies for future studies.