Background: Among people with chronic obstructive pulmonary disease (COPD), time periods following an acute exacerbation of COPD (AECOPD) have been identified as periods of increased risk for severe cardiovascular (CV) events.
Objectives: To examine the risk of a severe CV event during time periods following an AECOPD compared to unexposed periods; to estimate this association for moderate and severe AECOPD separately; and to evaluate how the strength of the association may depend on the number of prior AECOPDs.
Methods: This retrospective cohort study used data from the PHARMO Data Network in the Netherlands. Persons aged ≥40 years with a new, confirmed diagnosis of COPD between 2014 and 2018 were included. Exposed time periods included 1-7, 8-14, 15-30, 31-180 and 181-365 days following an AECOPD. Moderate AECOPDs were defined by an outpatient visit with a dispensation of oral corticosteroids. Severe AECOPDs were those requiring a hospitalisation. The outcome was time to the first severe CV event of any type (acute coronary syndrome, heart failure decompensation, arrythmias, ischaemic stroke), or all-cause death. Adjusted time-dependent Cox proportional hazards models estimated hazard ratios (HR) for the association between each exposed period and the outcome.
Results: From 1,636,513 patients in the source population, 8,020 patients with newly diagnosed COPD were identified, of which 2,234 patients (28%) had ≥1 AECOPD during a median follow-up of 36 months. 631 patients (8%) had a non-fatal CV event and 461 patients (5%) died during follow-up. Compared to unexposed periods, periods following an AECOPD of any severity were associated with increased risk of severe CV events with a HR of 15.3 (95% confidence interval 11.8-20.0) in the first 1-7 days, HR 7.0 (4.9-10.0) in days 8-14, and HR 4.8 (3.5-6.5) in days 15-30. After a moderate AECOPD, the risk of a severe CV event was increased and roughly consistent in the first 180 days [HR 2.5 (1.3-4.8) in days 1-7 to HR 1.6 (1.3-2.1) in days 31-180]. After a severe AECOPD, the risk of a severe CV event increased substantially and remained noticeably higher than unexposed periods over the first 180 days [HR 48.6 (36.9-64.0) in days 1-7 to HR 2.8 (2.0-3.8) in days 31-180]. The HRs between exposed time periods and severe CV risk were similar following a first, second or third AECOPD of any severity.
Conclusions: In a newly diagnosed population of COPD patients, we observed a substantial increase in the risk of severe CV events after both a moderate or severe AECOPD. The increase in risk was strongest in the month after the occurrence of an AECOPD. These findings highlight the high cardiopulmonary risk in people living with COPD, and the importance of preventing AECOPD.
