Major cardiovascular events in patients with severe COPD with and without asthma: a nationwide cohort study

Abstract

Background: Chronic low-grade inflammation as in asthma may lead to a higher risk of cardiovascular events. We evaluated whether patients with COPD and asthma have a higher risk of acute cardiovascular events than patients with COPD without asthma.

Methods: Nationwide multicentre retrospective cohort study of Danish outpatients with a specialist diagnosis of COPD with or without asthma. Patients with both COPD and asthma were propensity-score matched 1:2 to patients with COPD without asthma. The primary end-point was severe major adverse cardiac events (MACE), defined as mortal cardiovascular events and events requiring revascularisation or hospitalisation.

Results: A total of 52 386 Danish patients with COPD were included; 34.7% had pre-existing cardiovascular disease, and 20.1% had asthma in addition to their COPD. Patients with pre-existing cardiovascular disease were then propensity-score matched: 3690 patients with COPD and asthma versus 7236 patients with COPD without asthma, and similarly, for patients without pre-existing cardiovascular disease (6775 matched with 13 205). The risk of MACE was higher among patients with asthma and COPD versus COPD without asthma: hazard ratio (HR) 1.25 (95% CI 1.13-1.39, p<0.0001) for patients with pre-existing cardiovascular disease and HR 1.22 (95% CI 1.06-1.41, p=0.005) for patients without pre-existing cardiovascular disease.

Conclusion: Among patients with COPD, asthma as a comorbid condition is associated with substantially increased risk of cardiovascular events. The signal was an increased risk of 20-25%. Based on our study and other smaller studies, asthma can be considered a risk factor for cardiovascular events among COPD patients.

FIGURE 1

Flowchart of included patients, cohorts with and without prior cardiovascular disease, and propensity-score match. DrCOPD: Danish Register of Chronic Obstructive Pulmonary Disease.

FIGURE 2

Cumulated incidence plots of severe and any major adverse cardiac events (MACE) occurring in the propensity-matched cohorts stratified by pre-existing cardiovascular disease with other-cause mortality as a competing risk. Patients with COPD and asthma and with COPD without asthma were propensity matched 1:2 by age, gender, tobacco exposure, Medical Research Council dyspnoea score, body mass index and forced expiratory volume in 1 s stratified into populations based on pre-existing cardiovascular disease. “Severe MACE” was defined as lethal cardiovascular events, and cardiovascular events requiring revascularisation or hospitalisation; “any MACE” was defined as severe MACE or an event requiring a prescription of ADP receptor inhibitors or nitrates. a) Severe MACE in the propensity score matched cohort of patients with pre-existing cardiovascular disease (n=10 926); b) any MACE in the propensity score matched cohort of patients with pre-existing cardiovascular disease (n=10 926); c) severe MACE in the propensity score matched cohort of patients without pre-existing cardiovascular disease (n=19 980); d) any MACE in the propensity score matched cohort of patients without pre-existing cardiovascular disease (n=19 980).

FIGURE 3

Forest plots showing hazard ratios for severe major adverse cardiac events (MACE) in cohorts of all included patients with COPD and asthma compared to patients with COPD without asthma stratified by pre-existing cardiovascular disease. Hazard ratios were calculated by adjusted Cox analysis. a) Patients with pre-existing cardiovascular disease (n=18 176). b) Patients without pre-existing cardiovascular disease (n=34 210). Age, body mass index (BMI) and forced expiratory volume in 1 s (FEV₁) were analysed as continuous variables; gender, asthma, tobacco exposure and Medical Research Council (MRC) dyspnoea score as binary variables. For tobacco exposure, current and previous smokers were compared to never-smokers, passive smokers and patients with unknown smoking status (the latter comprising 9.1% of patients with prior cardiovascular disease and 8.5% in patients without prior cardiovascular disease). Patients with MRC ≥3 were compared to patients with MRC ≤2.