Objective Sepsis is the syndrome of life-threatening organ dysfunction resulting from dysregulated host response to infection. Aspirin, an anti-inflammatory agent, may play a role in attenuating the inflammatory response during infection. We evaluated the association between aspirin use and long-term rates of sepsis as well as sepsis outcomes. Methods We analyzed data from 30,239 adults 45 years old in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The primary exposure was aspirin use, identified via patient interview. The primary outcome was sepsis hospitalization, defined as admission for infection with two or more systemic inflammatory response syndrome criteria. We fit Cox proportional hazards models assessing the association between aspirin use and rates of sepsis, adjusted for participant demographics, health behaviors, chronic medical conditions, medication adherence, and biomarkers. We used a propensity-matched analysis and a series of sensitivity analyses to assess the robustness of our results. We also examined risk of organ dysfunction and hospital mortality during hospitalization for sepsis. Results Among 29,690 REGARDS participants with follow-up data available, 43% reported aspirin use (n = 12,869). Aspirin users had higher sepsis rates (hazard ratio 1.35; 95% CI: 1.22–1.49) but this association was attenuated following adjustment for potential confounders (adjusted HR 0.99; 95% CI: 0.88–1.12). We obtained similar results in propensity-matched and sensitivity analyses. Among sepsis hospitalizations, aspirin use was not associated with organ dysfunction or hospital death. Conclusions In the REGARDS cohort, baseline aspirin use was not associated with long-term rates of sepsis.
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