Aspirin use and long-term rates of sepsis: A population-based cohort study

Abstract

ObjectiveSepsis 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.MethodsWe 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.ResultsAmong 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.ConclusionsIn the REGARDS cohort, baseline aspirin use was not associated with long-term rates of sepsis.

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“…Activation of relevant inflammatory cells leads to production and release of a large number of endogenous inflammatory substances, including cytokines, lysosomal enzymes, vasoactive substances, plateletactivating factors, bradykinin, and alexin; these inflammatory factors interact to create a cytokine storm that causes systemic organ and tissue damage. 3,4 Increased levels of inflammatory mediators, such as tumor necrosis factor a (TNF-a) and interleukins (e.g., IL-6, IL-1, and IL-10), are closely related to the development of sepsis; higher serum concentrations of IL-6 and IL-10 have been associated with a more serious state of sepsis. [5][6][7] Patients with sepsis often exhibit an oxidative stress state that triggers the release of excess free radicals, thereby causing oxidative damage and aggravating the inflammatory response.…”

Influence of Acetylsalicylic Acid Use on Risk and Outcome of Community-Acquired Staphylococcus aureus Bacteremia: A Population-Based Study

“…However, a Canadian population-based case-control study of 449 patients and 4 156 controls receiving hemodialysis reported no association between ASA use and risk of vascular access-related infections and sepsis (OR, 1.03; 95% CI, 0.82–1.28), which remained unchanged with increasing ASA dose [21]. Also in support of our findings, a recent US historical cohort study of 30 239 patients reported an aHRR of 0.99 (95% CI, 0.88–1.12) for hospitalization with sepsis associated with ASA use [22].…”

“…The majority of previous studies did not access microbiological data to identify infections, including sepsis [21–23]. Thus, misclassification cannot be entirely ruled out, and some lacked complete follow-up [22, 25]. Moreover, information on ASA exposure use was in some cases collected exclusively from medical charts that may be incomplete [10, 25], and variations in the duration of ASA use were not taken into account [10, 21, 24, 25].…”

Aspirin and Infection: A Narrative Review

“…Forty-three percent of individuals reported ASA use and the median follow-up was 6.2 years. No associations between long-term exposure to ASA and onset of sepsis and sepsis-related death were found [ 57 ]. In 2020, the ANTISEPSIS trial was published: 16,703 participants aged 70 years and older without major illnesses were enrolled and followed up for a median of 4.6 years.…”