Eosinophilic vs Non-Eosinophilic Acute Exacerbations of COPD and Subsequent Cardiovascular Event

Background: Acute exacerbation of COPD (AE-COPD) is associated with increased cardiovascular risk, but whether this risk differs between eosinophilic and non-eosinophilic AE-COPD remains unclear. Research Question: Is eosinophilic AE-COPD associated with a lower risk of major adverse cardiovascular events (MACEs)? Study Design and Methods: This retrospective cohort study was conducted by using the TriNetX Analytics Network. Patients aged ≥ 40 years with AE-COPD between January 1, 2022, and December 31, 2024, were included. Eosinophilic AE-COPD was defined as a blood eosinophil count ≥ 300/μL within the window of 3 days before to 1 day following the event. The primary outcome was the 1-year risk of MACEs (heart failure, reduced left ventricular ejection fraction, acute myocardial infarction, cerebral infarction, cardiac arrest, and arrhythmia). Propensity score matching (1:1) was performed, and Cox proportional hazards models and Kaplan-Meier analyses were used. Sensitivity analyses included negative/positive control outcomes, alternative eosinophil cutoff definitions, and landmark analyses. Results: A total of 143,517 patients were included (33,761 eosinophilic and 109,756 non-eosinophilic AE-COPD). After matching, 33,756 patients were retained in each group. During the 1-year follow-up, non-eosinophilic AE-COPD was associated with a higher risk of MACEs compared with eosinophilic AE-COPD (5,967 vs 5,160 events; hazard ratio, 1.22; 95% CI, 1.17-1.26; P < .001). Kaplan-Meier analysis confirmed higher MACE-free survival in patients with eosinophilic AE-COPD (log-rank test, P < .001). Eosinophilic AE-COPD was also associated with reduced risks of heart failure, acute myocardial infarction, stroke, arrhythmia, and all-cause mortality. Findings were consistent across sensitivity analyses, including alternative eosinophil thresholds and landmark time windows. Interpretation: Our results show eosinophilic AE-COPD was associated with a significantly lower risk of MACE compared with non-eosinophilic AE-COPD. Blood eosinophil count at the time of exacerbation may serve as a valuable biomarker for stratifying not only pulmonary outcomes but also long-term cardiovascular risk in COPD.