COPD exacerbations not only contribute to the progression of lung disease, but can also increase the risk of cardiovascular disease (CVD). An American research group investigated the relationship between COPD exacerbations and subsequent cardiovascular events in a group of patients with varying degrees of lung damage.
COPD patients have an increased risk of cardiovascular disease compared to people without the disease, regardless of smoking status or GOLD spirometry grade. In addition, previous studies suggest that patients with chronic obstructive pulmonary disease not only have an increased risk of CVD, but also of cardiovascular risk factors such as diabetes and hypertension. Exacerbations also contribute significantly to the burden of COPD, with moderate to severe exacerbations being associated with a deterioration in lung function and significant healthcare costs. Therefore, clarifying the relationship between COPD exacerbations and the risk of subsequent CVD events is important to better manage these patients, explain Dr. Han-Mo Yang of the Channing Division of Network Medicine at Brigham and Women’s Hospital in Boston, USA, and colleagues [1].
The researchers conducted an analysis to determine whether COPD exacerbations increase the risk of subsequent CVD events, using prospective longitudinal data from the COPDGene study over a period of up to 15 years. The COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) Study is a prospective, multicenter, longitudinal cohort study investigating the epidemiology, genetics, and natural history of COPD at 21 centers in the United States [2]. Subjects aged 45 to 80 years who had smoked for at least 10 years participated in the study. Cox proportional hazards models and Kaplan-Meier survival curves were used to assess the risk of a composite endpoint of CVD based on COPD exacerbation rate.
Dr. Yang and colleagues used the data to determine the temporal relationship between COPD exacerbations and cardiovascular events by closely tracking the time from patient admission to the first cardiovascular event and assessing the frequency of COPD exacerbations.
Of the 10,652 eligible patients in phase 1 of COPD-Gene, participants who had undergone lung transplantation or lung volume reduction surgery, for whom no longitudinal follow-up data were available or who had normal spirometry values were excluded. The remaining group of subjects (n=5083) was divided into subgroups based on spirometric values. Each subgroup was further divided into groups with or without CVD at baseline.
COPD exacerbations associated with increased risk of subsequent CVD
Frequent exacerbators had a higher cumulative incidence of composite cardiovascular endpoints than infrequent exacerbators, regardless of the presence of cardiovascular disease at baseline. After adjustment for covariates, frequent exacerbators still had higher hazard ratios (HR) than the infrequent exacerbator group (without CVD: HR 1.81; 95% CI 1.47-2.22; with CVD: HR 1.92; 95% CI 1.51-2.44). This observation remained consistently significant in people with moderate to severe COPD and in the population with preserved impaired spirometry. In the population with mild COPD, frequent exacerbations showed a trend towards more frequent CVD events.
Previous studies that have shown an association between COPD exacerbations and cardiovascular events have included limited subgroups and examined specific cardiovascular endpoints, depending on the purpose of the study. According to the authors, their work included not only subjects with varying degrees of COPD severity – from mild to very severe – but also PRISm patients, examining a wide range of cardiovascular outcomes. (The term PRISm refers to individuals who have a reduced one-second capacity (FEV1) while maintaining a normal Tiffeneau index (FEV1/FVC >70%)).
Higher CVD risk in PRISm population vs. people with normal lung function
The physiological abnormality in PRISm individuals, who have a preserved FEV1/FVC ratio but whose FEV1% predicted is reduced, has several potential causes, including restrictive lung diseases (e.g. interstitial lung disease, neuromuscular weakness, chest wall abnormalities and obesity) or airway obstruction (such as COPD). The association between the PRISm population and CVD is not yet clear, but some studies suggest that individuals with PRISm have a higher risk of CVD compared to those with normal lung function. This increased risk may be due to shared risk factors for COPD and CVD, such as smoking, ageing and inflammation. The presence of respiratory symptoms and impaired lung function in the PRISm population may also contribute to the development of CVD by increasing cardiac stress or systemic inflammation.
Analysis of the PRISm population showed that frequent exacerbators had a higher incidence of composite CVD events than infrequent exacerbators (without CVD: HR 1.81; 95% CI 1.06-3.09; with CVD: HR 2.03; 95% CI 1.19-3.47) (Fig. 1). After adjustment for covariates, the multivariable HRs for the PRISm population were higher than the univariable HRs.
According to Dr. Yang and his colleagues, their study is the first to demonstrate an association between COPD exacerbations and subsequent cardiovascular events in the PRISm population. The results of this study could therefore be used to identify effective strategies to detect and manage CVD risk in these individuals. Furthermore, once effective therapies are available, the identification and treatment of PRISm could help to prevent or delay the progression of COPD and CVD, ultimately improving health outcomes for these patients.
CVD often underdiagnosed in COPD patients – and vice versa
COPD and CVD have many common risk factors, such as smoking and advanced age, which contribute to endothelial dysfunction. Endothelial dysfunction is a major contributor to the development of atherosclerosis, which eventually leads to ischemic heart disease. The mechanism by which COPD increases CVD risk is not clear, but patients with COPD often have abnormally high levels of circulating systemic inflammatory biomarkers such as CRP (C-reactive protein), IL-6 (interleukin-6) and fibrinogen, which may contribute to the development and progression of atherosclerosis. During a COPD exacerbation, the release of the aforementioned proinflammatory cytokines and other mediators in the lungs can spill over into the bloodstream, leading to a temporary deterioration in endothelial function and an increased inflammatory status throughout the body. This could contribute to an increased risk of macrovascular complications such as myocardial infarction and stroke. In addition, hypoxemia due to COPD exacerbation can stress the heart, increase blood pressure and promote blood clot formation, all of which increase the risk of cardiovascular events. The drugs used to treat COPD (e.g. macrolide antibiotics) can also have cardiac side effects. All of these factors may cause COPD exacerbations to increase the risk of acute cardiovascular complications. According to the authors, further research is needed to determine which mechanisms are most important in specific groups of COPD patients.
Despite the known close link between COPD and cardiovascular disease, there are still numerous cases where CVD is underdiagnosed and undertreated in COPD patients and vice versa, the authors emphasize. For example, one study showed that many patients who underwent coronary intervention were not simultaneously diagnosed with COPD. Furthermore, in 70% of patients with acute COPD exacerbations, electrocardiographic indicators of a previous myocardial infarction remain unrecognized. This challenge mainly concerns early or moderate stages of COPD, where improved preventive and therapeutic measures are still possible.
Existing guidelines largely focus on individual cardiac or respiratory diseases. However, according to the US researchers, an integrated approach is needed, especially given the limited long-term data on patients with COPD and CVD. By considering the link between COPD and CVD, appropriate patient management could help minimize adverse events associated with both conditions. In addition, the results of their study also provided evidence of the association between COPD exacerbations and subsequent cardiovascular events in people with varying degrees of lung injury, Dr. Yang and colleagues said. This emphasizes the importance of optimal treatment of COPD exacerbations to reduce the risk of cardiovascular events in this patient group.
Literature:
- Yang HM, et al.: Chronic Obstructive Pulmonary Disease Exacerbations Increase the Risk of Subsequent Cardiovascular Events: A Longitudinal Analysis of the COPDGene Study. Journal of the American Heart Association 2024; doi: 10.1161/JAHA.123.033882.
- Regan EA, et al.: Genetic epidemiology of COPD (COPDGene) study design. COPD 2010; 7(1): 32–43; doi: 10.3109/15412550903499522.
InFo PNEUMOLOGIE ALLERGOLOGIE 2024; 6(3): 34–35
