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. 2024 Dec;166(6):1347-1359.
doi: 10.1016/j.chest.2024.07.150. Epub 2024 Jul 31.

Exacerbation History and Risk of Myocardial Infarction and Pulmonary Embolism in COPD

Oskar Wallström  1 , Caroline Stridsman  2 , Anne Lindberg  2 , Fredrik Nyberg  3 , Lowie E G W Vanfleteren  4
Affiliations

Exacerbation History and Risk of Myocardial Infarction and Pulmonary Embolism in COPD

Oskar Wallström et al. Chest. 2024 Dec.

Abstract

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.

Keywords: acute exacerbations of COPD; cardiovascular adverse events; comorbidity; myocardial infarction; pulmonary embolism; retrospective nationwide registry cohort.

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Conflict of interest statement

Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: L. E. G. W. V. reports relationships with GSK, AstraZeneca, Boehringer Ingelheim Pharmaceuticals Inc, Novartis, Chiesi, Resmed, and Pulmonx that includes speaking and lecture fees. C. S. reports relationships with AstraZeneca, Chiesi, Boehringer Ingelheim, and TEva that includes consulting or advisory and speaking and lecture fees. A. L. reports relationships with Boehringer Ingelheim, Novartis, GlaxoSmithKline, and AstraZeneca that includes consulting or advisory and speaking and lecture fees. F. N. was previously an employee of AstraZeneca until 2019 and owns stock in the company. None declared (O. W.).

Figures

Figure 1
Figure 1
Cohort design, covariate assessment, and follow-up period. CAT = COPD Assessment Test; mMRC = modified Medical Research Council Dyspnea Scale.
Figure 2
Figure 2
Flow diagram for distribution of exacerbation history groups. SNAR = Swedish National Airway Register.
Figure 3
Figure 3
Forest plot of adjusteda SHRs for myocardial infarction depending on baseline exacerbation history, from competing risk regression analysis for 66,422 Swedish patients diagnosed with COPD, registered in the Swedish National Airway Register, January 2014 to June 2022 and followed for up to 9 y. aAdjusted for sex, age, BMI, smoking status, FEV1 % predicted, presence of baseline cardiovascular comorbidity, cardioprotective medications, and socioeconomic factors. SHR = subdistribution hazard ratio.
Figure 4
Figure 4
Forest plot of adjusteda SHRs for pulmonary embolism depending on baseline exacerbation history, from competing risk regression analysis for 66,422 Swedish patients diagnosed with COPD, registered in the Swedish National Airway Register, January 2014 to June 2022 and followed for up to 9 years. aAdjusted for sex, age, BMI, smoking status, FEV1 % predicted, presence of baseline cardiovascular comorbidity, cardioprotective medications, and socioeconomic factors. SHR = subdistribution hazard ratio.
e-Figure 1
e-Figure 1
Cumulative incidence functions plot for the outcome of myocardial infarction with death from other causes as a competing risk, in 66422 Patients with COPD divided by baseline exacerbation history
e-Figure 2
e-Figure 2
Cumulative incidence functions plot for the outcome of pulmonary embolism with death from other causes as a competing risk, in 66422 Patients with COPD divided by baseline exacerbation history
See this image and copyright information in PMC

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