Stroke risk in women with atrial fibrillation.

BACKGROUND AND AIMS: Female sex is associated with higher rates of stroke in atrial fibrillation (AF) after adjustment for other CHA2DS2-VASc factors. This study aimed to describe sex differences in age and cardiovascular care to examine their relationship with stroke hazard in AF. METHODS: Population-based cohort study using administrative datasets of people aged ≥66 years diagnosed with AF in Ontario between 2007 and 2019. Cause-specific hazard regression was used to estimate the adjusted hazard ratio (HR) for stroke associated with female sex over a 2-year follow-up. Model 1 included CHA2DS2-VASc factors, with age modelled as 66-74 vs. ≥ 75 years. Model 2 treated age as a continuous variable and included an age-sex interaction term. Model 3 further accounted for multimorbidity and markers of cardiovascular care. RESULTS: The cohort consisted of 354 254 individuals with AF (median age 78 years, 49.2% female). Females were more likely to be diagnosed in emergency departments and less likely to receive cardiologist assessments, statins, or LDL-C testing, with higher LDL-C levels among females than males. In Model 1, the adjusted HR for stroke associated with female sex was 1.27 (95% confidence interval 1.21-1.32). Model 2 revealed a significant age-sex interaction, such that female sex was only associated with increased stroke hazard at age >70 years. Adjusting for markers of cardiovascular care and multimorbidity further decreased the HR, so that female sex was not associated with increased stroke hazard at age ≤80 years. CONCLUSION: Older age and inequities in cardiovascular care may partly explain higher stroke rates in females with AF.

Donor Batf3 inhibits murine lung allograft rejection and airway fibrosis.

Chronic lung allograft dysfunction (CLAD) limits survival after lung transplantation. Noxious stimuli entering the airways foster CLAD development. Classical dendritic cells (cDCs) link innate and adaptive immunity and exhibit regional and functional specialization in the lung. The transcription factor basic leucine zipper ATF-like 3 (BATF3) is absolutely required for the development of type 1 cDCs (cDC1s), which reside in the airway epithelium and have variable responses depending on the context. We studied the role of BATF3 in a mouse minor alloantigen-mismatched orthotopic lung transplant model of CLAD with and without airway inflammation triggered by repeated administration of intratracheal lipopolysaccharide (LPS). We found that cDC1s accumulated in allografts compared with isografts and that donor cDC1s were gradually replaced by recipient cDC1s. LPS administration increased the number of cDC1s and enhanced their state of activation. We found that Batf3-/- recipient mice experienced reduced acute rejection in response to LPS; in contrast, Batf3-/- donor grafts underwent enhanced lung and skin allograft rejection and drove augmented recipient cluster of differentiation 8+ T-cell expansion in the absence of LPS. Our findings suggest that donor and recipient cDC1s have differing and context-dependent roles and may represent a therapeutic target in lung transplantation.