Lung health for all: Focus more on the cardiopulmonary risk in patients with COPD

Chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, led to approximately 3.23 million deaths in 2019 and imposed significant economic and health burdens. However, cardiovascular mortality accounts for approximately one-third of deaths in patients with COPD,[1] particularly in those with mild or moderate disease severity.[2] Studies have also identified a substantial increase in the risk of cardiovascular events in patients with COPD.[3,4] Given the notable risk of cardiopulmonary (pulmonary and cardiovascular) events in COPD, the management of COPD should incorporate strategies aiming at reducing the risk of cardiopulmonary events. Optimized treatment of patients with COPD may reduce their risk of cardiopulmonary events and potentially enhance survival benefit. Fully understanding the risk of cardiovascular events in patients with COPD is crucial for comprehensive management of disease. Thus, this article aims to offer an update on the risk of cardiovascular events in COPD and emphasize the importance of cooperation between pulmonologists and cardiologists. Increased Risk of Cardiovascular Events in COPD Patients with COPD exhibit a notably elevated susceptibility to cardiovascular events, with higher incidence and prevalence than individuals without COPD, even after adjustment for age and gender. A comprehensive systematic review revealed that compared with the non-COPD population, patients with COPD exhibit a higher incidence of cardiovascular disease (CVD) diagnosis as indicated by a pooled odds ratio (OR) of 2.46 (95% CI, 2.02–3.00; P <0.0001). Specifically, there is two to five times higher risk of various CVDs including ischemic heart disease (pooled OR, 2.28; 95% CI, 1.76–2.96; P <0.0001), cardiac dysrhythmia (pooled OR, 1.94; 95% CI, 1.55–2.43; P <0.0001), heart failure (HF) (pooled OR, 2.57; 95% CI, 1.90–3.47; P <0.0001), diseases of the pulmonary circulation (pooled OR, 5.14; 95% CI, 4.07–6.50; P <0.0001), and arterial diseases (pooled OR, 1.35; 95% CI, 1.48–3.74; P <0.0001).[3] A large primary care population study in patients with COPD and no history of CVD reported a 25% increase in the adjusted risk of major adverse cardiovascular events (MACEs), including acute myocardial infarction (MI), stroke, or cardiovascular death.[4] In addition, cardiovascular event is a common cause of mortality in patients with COPD. Five prospective large-scale studies with follow-up periods of 3 to 14 years reported that the rate of mortality attributable to cardiovascular events ranged from 16% to 39% among patients with COPD.[5] These findings emphasize the importance of raising awareness about the risk of cardiovascular events in patients with COPD. While the mechanism underlying the associations between COPD and cardiovascular events has not yet been fully elucidated, several potential contributing factors have been identified, including systemic inflammation, lung hyperinflation, hypoxemia, oxidative stress, and exacerbations. Exacerbation of COPD Further Increases the Risk of Cardiovascular Events Recent studies suggest that the significantly increased risk of cardiovascular events in COPD might also be related to the acute exacerbation of COPD.[6–8] Exacerbation is an important event in the natural course of COPD, and approximately 30–50% of patients with COPD have at least one exacerbation annually. Furthermore, up to 77% of patients with COPD experience at least one moderate or severe acute exacerbation within three years.[9] The impact of COPD exacerbation extends beyond the lungs, and a single moderate exacerbation can increase the risk of cardiovascular events. A self-controlled case series study investigated the magnitude and timing of the risk of MI and stroke after COPD exacerbation, and showed a 2.27-fold increased risk of MI within one to five days after a moderate exacerbation, along with 40% increase in the risk of stroke in the subsequent six to ten days.[6]. EXACOS-CV study in Canada has found that compared to time prior to exacerbation, the risk of primary outcome (the composite of all-cause death or a first hospitalisation for acute coronary syndrome, HF, arrhythmia or cerebral ischaemia) was significantly increased in the 1–7 days post-exacerbation (adjusted HR 15.86, 95% CI 15.17 to 16.58) and remained increased for up to one year in patients with COPD.[7] Exacerbations also increase the risk of death, including CVD-related death. A retrospective observational study investigated the associations of baseline exacerbations with the subsequent risk of mortality in a COPD cohort. The authors discovered that the rate of all-cause mortality has a positive correlation with the frequency and severity of exacerbations at baseline. In the group of patients with one moderate exacerbation, the rates of COPD-related mortality and CVD-related mortality increased by 17% and 23%, respectively. The mortality due to CVD in patients with moderate exacerbation is higher than the mortality related to COPD.[8] These findings underscore the crucial necessity for both clinicians and patients to sustain vigilance to early cardiovascular events following a COPD exacerbation. Influence of Comorbid COPD and Cardiovascular Disease CVD is one of the most frequent comorbidities in patients with COPD, with a prevalence reaching 50%.[10] The prevalence of COPD in individuals with CVD is also considerable, ranging from 7% to 16% among patients with acute myocardial infarction (MI) and 11% to 52% among individuals with heart failure (HF) in the USA.[11] The co-existence of COPD and CVD is associated with worse outcomes than either condition alone, including higher medical research council dyspnea score, poorer quality of life, and increased risk of rehospitalization and long-term mortality.[12] In addition, the presence of CVD increases the risk of frequent exacerbations and mortality in patients with COPD. A retrospective cohort study investigated the association between chronic (co)morbidities and exacerbations in primary care patients with COPD. The authors found that HF (OR, 1.72; 95% CI, 1.38–2.17) exhibits statistically significant association with frequent exacerbations (i.e., ≥2 moderate exacerbations/year).[13] Two additional prospective observational studies further suggested that HF (HR, 1.9; 95% CI, 1.3–2.9), ischemic heart disease (HR, 1.5; 95% CI, 1.1–2.0),[12] and atrial fibrillation (HR, 1.56; 95% CI, 1.25–1.96)[4] significantly increase the risk of mortality in COPD. On the other hand, COPD and reduced pulmonary function are independent risk factors for CVD after adjustment for traditional CVD risk factors.[14] A retrospective study revealed that, in comparison to patients without COPD undergoing percutaneous coronary intervention (PCI), those with COPD exhibited elevated rates of mortality and repeated revascularization within one year post-PCI.[15] Therefore, it is imperative to advocate for appropriate and aggressive treatments of patients with comorbid COPD and CVD to improve the quality of life and reduce mortality. More Attention Should be Directed Towards Optimizing the Diagnosis and Management of COPD in CVD, and vice versa Insufficient diagnosis and treatment are very common in patients with comorbid COPD and CVD. A cross-sectional, observational study in Europe performed spirometry among outpatients with ischemic heart disease. The study detected airflow limitation in 30.5% of patients, of whom most patients (70.6%) had no prior history of spirometry testing or diagnosis of pulmonary disease.[16] There is currently no data available for this field in China. Therefore, further study is needed to ascertain the prevalence and diagnosis rate of COPD among patients with CVD in China. In terms of treatment, patients with MI and COPD are less likely to receive guideline-recommended reperfusion therapy, as well as medications known to reduce mortality such as selective β-blockers, statins, or antiplatelet therapy upon discharge from the hospital. The study by Andell et al[17] showed that the HR for mortality in patients with COPD decreased from 1.32 (95% CI, 1.24–1.40) to 1.14 (95% CI, 1.07–1.21) following adjustment for in-hospital and discharge treatment. These findings suggest that adhering to current guidelines for cardiac treatment in MI patients with COPD could potentially lead to improved survival. On the other hand, the actual survival benefit of inhalation treatment for patients with both CVD and COPD has yet to be fully clarified. Further research is still necessary. Advocating for Multidisciplinary Collaboration Currently, there is lack of clinical guidelines and consensus regarding the co-management of COPD and CVD. To reduce cardiopulmonary risks in patients with COPD, it is necessary and urgent for pulmonologists and cardiologists to engage in multidisciplinary collaboration, which is of vital importance for standardizing the diagnosis and treatment for comorbid COPD and CVD. In conclusion, the lungs and the heart are inherently linked and interact with each other. Patients with COPD are particularly vulnerable to cardiovascular events, and COPD exacerbation significantly increases the risk of cardiovascular events and cardiovascular-related mortality. Clinicians and patients alike should maintain heightened vigilance for early cardiovascular events following a COPD exacerbation. To reduce the risk of cardiopulmonary events of patients with COPD, it is crucial to establish multidisciplinary collaboration between pulmonologists and cardiologists to develop an effective management plan. Conflicts of interest None.

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