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Following moderate exacerbations of chronic obstructive pulmonary disease (COPD), cardiovascular events occur slightly later than after severe exacerbations, with increased relative rates after 1 year regardless of severity, suggest the findings of a recent study published in the American Journal of Respiratory and Critical Care Medicine.¹

鈥淲e had shown a few years ago that people with COPD are at increased risk of having a stroke or heart attack in the period shortly after an exacerbation compared with a baseline period,鈥� the study鈥檚 corresponding author, Jennifer K. Quint, FRCP, School of Public Health and National Heart and Lung Institute, Imperial College London, U.K., told 澳门老奇人论坛. 鈥淲hat was less clear, though, is how much the severity of your exacerbation mattered with respect to the increased risk鈥攄epending on whether you had one managed in the community or were hospitalized, or whether there was an increased risk with other cardiovascular outcomes, such as heart failure or arrhythmias.鈥�

Study design and patient population

This open cohort study tapped information from a U.K. primary care database and included 213,466 people with a new or long-standing COPD diagnosis recorded from 2014 to 2020.¹ At the beginning of the follow-up period, the investigators discovered, roughly 1 in 3 patients (31.4%) had no exacerbations. Of the remaining two-thirds with any type of exacerbation, 119,124 (55.8%) had moderate exacerbations managed by a general practitioner and 27,324 (12.8%) had severe exacerbations requiring hospitalization.

At study entry, the average participant age was 68.8 years. More than half (52.2%) were men, 55.3% were ex-smokers, and 75.6% were White. Prior prevalent cardiovascular disease was reported in 18.3% of participants.

Cardiovascular events and exacerbations

Over a median of 2.4 years of follow-up, there were 40,773 cardiovascular events recorded. Of these, 49.3% were classified as arrhythmias, 31.1% as heart failure, 10.1% as acute coronary syndrome, 5.9% as ischemic stroke, and 3.7% as pulmonary hypertension. For every 100 exacerbations that required hospitalization, about 28 people experienced 1 or more cardiovascular event. For every 100 people managed in a primary care setting for an exacerbation, approximately 22 people experienced a cardiovascular event.

For the whole cohort, the crude incidence rate for any cardiovascular event was 7.01 per 100 person-years. However, among those with any exacerbation, there was a higher crude rate, of 8.79 per 100 person-years. By contrast, participants with no exacerbations had a much lower crude incidence rate of any cardiovascular event, of 3.66 per 100 person-years. There was a difference in crude rates by exacerbation severity: 7.79 per 100 person-years among patients with moderate exacerbations, and 15.70 per 100 person-years among those with severe exacerbations.

Participants with exacerbations had a higher risk of composite future cardiovascular events compared with those who did not have exacerbations. The highest relative rate for cardiovascular events was observed in the 2 weeks following any type of exacerbation (adjusted hazard ratio [aHR] 3.19, 95% confidence interval [CI] 2.71 to 3.76), a rate that declined afterward; however, an elevated hazard ratio persisted after 1 year (aHR 1.84, 95% CI 1.78 to 1.91). (Note: P values for each range cited in this article are <.0001 and are statistically significant.)

Participants with severe exacerbations had the highest rate of cardiovascular events in the 2 weeks following an exacerbation (aHR 14.5, 95% CI 12.2 to 17.3), a rate that remained elevated after 1 year (aHR 2.71, 95% CI 2.59 to 2.86). Participants with moderate exacerbations had the highest rate of cardiovascular events between 14 and 30 days following an exacerbation (aHR 1.94, 95% CI 1.63 to 2.31), which persisted after 1 year (aHR 1.74, 95% CI 1.67 to 1.80).

Higher rates for all types of cardiovascular outcomes

鈥淚 anticipated we would see an increase in the cardiovascular outcomes following exacerbation,鈥� Prof. Quint explains. 鈥淲hat surprised me was the difference in magnitude of risk between a hospitalized and moderate exacerbation event.鈥�

An increased relative rate for all individual cardiovascular outcomes except ischemic stroke was observed for participants with any exacerbations, compared with those without exacerbations. The highest hazard ratios were seen for pulmonary hypertension (aHR 3.15, 95% CI 2.81 to 3.52) and heart failure (aHR 2.33, 95% CI 2.24 to 2.42). The greatest magnitudes of effects were seen in the 2 weeks following an exacerbation for arrhythmias, heart failure, and pulmonary hypertension.

Limitations and conclusions

鈥淲hat this work clearly shows is that there is a period of increased risk of a cardiovascular event following a COPD exacerbation,鈥� Prof. Quint says. 鈥淲hat we need to know now is can we intervene and do something differently in the way we manage a COPD exacerbation or take that point of opportunity to optimize cardiovascular risk factors to help to reduce the cardiovascular risk.鈥�

Limitations of this study include the possibility for residual confounding, misdiagnosis or misclassification of COPD exacerbations with cardiovascular events, and the data in the electronic health record, which, the authors noted, 鈥渁re ultimately limited by the clinical accuracy and the ultimate diagnosis made by the physician seeing the patient.鈥�¹

The bottom line is that patients should be treated 鈥渉olistically,鈥� Prof. Quint concluded. 鈥淭ake the opportunity to optimize other conditions and risk factors when patients are admitted with a COPD exacerbation, and don鈥檛 just focus on the COPD exacerbation itself.鈥�

Published: May 28, 2024