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Background: Acute exacerbations (AEs) of COPD are increasingly recognized as episodes of heightened risk of cardiovascular events. It is not known whether exacerbation history is differentially associated with future myocardial infarction (MI) or pulmonary embolism (PE).

Research Question: Is the number and severity of AEs of COPD associated with increased risk of MI or PE in a real-life cohort of patients with COPD?

Study Design and Methods: We identified a cohort of 66,422 patients (≥ 30 years of age) with a primary diagnosis of COPD in the Swedish National Airway Register from January 2014 to June 2022, with complete data on lung function. Patients were classified by moderate (prescription of oral corticosteroids) and severe (hospitalization) exacerbations the year before index date and were followed until December 2022 for hospitalization or death from MI or PE, corresponding to > 265,000 patient-years, with a maximum follow-up time of 9 years. Competing risk regression, according to the Fine-Gray model, was used to calculate subdistribution hazard ratios with 95% CIs.

Results: Compared with no AEs of COPD in the baseline period, AE of COPD number and severity were associated with increased long-term risk of both MI and PE in a gradual fashion, ranging from a subdistribution hazard ratio of 1.10 (95% CI, 0.97-1.24) and 1.33 (95% CI, 1.11-1.60), respectively, for one moderate exacerbation, to 1.82 (95% CI, 1.36-2.44) and 2.62 (95% CI, 1.77-3.89), respectively, for two or more severe exacerbations. In a time-restricted follow-up sensitivity analysis, the associations were stronger during the first year of follow-up and diminished over time.

Interpretation: The risk of MI and PE increased with the frequency and severity of AEs of COPD in this large, real-life cohort of patients with COPD.