Sex-Related Differences in the Risk of Hospital-Acquired Sepsis and Pneumonia Post Acute Ischemic Stroke

Abstract

Background and Goal Infectious complications after ischemic stroke are frequent and lead to neurologic deterioration, poor functional outcomes, and higher mortality. Local and systemic inflammatory responses to brain ischemia differ between males and females, but little is known about differences in post-stroke susceptibility to infection by sex. The purpose of this study was to compare sex-related differences in the risk of hospital-acquired sepsis and pneumonia after acute ischemic stroke (AIS). Materials and Methods This was a retrospective, secondary analysis of the 2010–2011 California State Inpatient Database. Previously validated ICD-9 codes were used to identify adult hospitalizations for AIS. The primary outcome was hospital-acquired sepsis or pneumonia, also identified using ICD-9 codes. Associations between sex and hospital-acquired sepsis or pneumonia were adjusted for baseline characteristics and comorbidities using multivariable logistic regression. Findings There were 91,643 visits for AIS included in this analysis, of which 1,027 had hospital-acquired sepsis and 1,225 had hospital-acquired pneumonia. The in-hospital mortality without infection was 4.6%; the presence of hospital-acquired infections was associated with higher mortality for sepsis (32.7%) and pneumonia (21.9%). Female (vs. male) sex was associated with a lower adjusted odds of hospital-acquired sepsis (OR 0.74, 95%CI 0.65–0.84) and pneumonia (OR 0.69, 95%CI 0.62–0.78). This difference was similar across age strata. Among visits with either hospital-acquired sepsis or pneumonia, sex did not influence mortality. Conclusions Female sex was associated with a lower risk of hospital-acquired sepsis and pneumonia after AIS. Further investigation is needed to determine the mechanisms underlying this clinical observation.

High-throughput profiling of the circulating proteome suggests sexually dimorphic corticosteroid signaling following ischemic stroke

“…Consistent with the known role of cortisol as an immunosuppressant, cortisol is believed to be a key mediator of this phenomenon, as cortisol levels are strongly negatively correlated with poststroke lymphocyte counts (45) and are predictive of poststroke immune complications (20). An attenuated cortisol response to stroke in women, such as that suggested by our results, would act to limit the degree of poststroke adaptive immune suppression; this would be highly consistent with a recent study of over 90,000 stroke cases that revealed that women exhibit lower rates of poststroke infection than men (12). Furthermore, such an effect could also explain preclinical and clinical studies that suggest that females may exhibit stronger autoantigen responses following stroke relative to male counterparts (30,44).…”

Association Between Splenic Contraction and the Systemic Inflammatory Response After Acute Ischemic Stroke Varies with Age and Race

“…The data suggest that SIRS is more likely to be associated with SC in African American patients but race was not an independent predictor for the development of SIRS as seen in other studies. Patients of African American race have been found to have higher rates of non-infectious SIRS after stroke [15,26] and there is data demonstrating higher rates of infection and sepsis in African American patients [27][28][29]. African American race has also been included in a non-infectious SIRS prediction model [26].…”

Admission Glucose Levels May Increase the Risk for Early Neurological Deterioration in Females With Acute Ischemic Stroke

“…Sex-related differences in antioxidant enzyme activity are associated with differences in circulating sex hormone levels (27). Stroke-induced immunodepression has been identified in clinical and experimental studies and considered to be associated with lymphopenia and T cell dysfunction (28,29), leading to increased risk for infection after stroke and worsening neurological deterioration (30). Estrogen may directly regulate the post-stroke immune response through sex steroid receptors in the cells (including microglia, astrocytes, and various circulating immune cells) in the brain (31).…”