Keywords

Beta blockers, bronchodilators, chronic obstructive pulmonary disease, heart failure, systemic inflammation

Abbreviations

AFib: atrial fibrillation

COPD: chronic obstructive pulmonary disease

CVD: cardiovascular disease

HF: heart failure

PH: pulmonary hypertension

Take-home messages

1. COPD and cardiovascular disease frequently coexist, with shared risk factors and pathophysiological mechanisms including systemic inflammation, oxidative stress, and vascular dysfunction.
2. COPD independently increases the risk of multiple cardiovascular conditions, including coronary artery disease, heart failure, pulmonary hypertension, atrial fibrillation, and aortic aneurysms.
3. Beta blockers, particularly cardioselective agents, provide significant benefits in COPD-CVD patients and should not be withheld when appropriately indicated.
4. An integrated approach to COPD-CVD management, addressing both pulmonary and cardiovascular aspects of disease, is essential for optimising outcomes in this complex patient population.

Patient-oriented message

Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) are leading causes of reduced quality of life and increased risk of death, sharing some modifiable risk factors, the most relevant of these being smoking. In people with COPD, conditions such as heart failure (HF), arrhythmias, and coronary artery disease are common and often play a key role in worsening symptoms, triggering flare-ups, and leading to emergency visits, hospital admissions, or even mortality. For this reason, identifying cardiovascular risk factors and diagnosing heart-related conditions is crucial in the management of COPD. At every medical appointment, healthcare providers should assess for signs and symptoms of heart disease and ensure that both respiratory and cardiovascular treatments are optimised.

Epidemiology and global burden

COPD affects around 300 million people worldwide, although estimations vary widely depending on the definition used. It is directly linked to tobacco smoking, especially in developed countries, ranking as the fourth leading cause of mortality worldwide in 2021 [1].  CVD represents the most common comorbidity in COPD patients [2]. It is projected that both these conditions will keep increasing over the coming years.

The relationship between COPD and CVD extends beyond coincidental occurrence. Epidemiological studies consistently demonstrate that COPD, independent of cigarette smoking and ageing, doubles the risk of CVD hospitalisation, in-hospital mortality, 30-day readmission, and death [2].

Pathophysiological links between COPD and CVD

While smoking, ageing, and inactivity are important shared risk factors for both diseases, it is believed that these are not the only reasons for this association. COPD and CVD may have common interconnected pathophysiological mechanisms.

COPD is now recognised not merely as a pulmonary disease but as the manifestation of a systemic inflammatory condition. This may be important, for example, to atherosclerotic plaque formation and progression. Acute exacerbations play a prominent role and are linked to the highest level of risk of cardiovascular events. Furthermore, both COPD and CVD share increased oxidative stress as a common pathophysiological feature, which further promotes systemic inflammation, contributing to its persistence [3].

Both these mechanisms of COPD and CDV lead to vascular dysfunction, reflecting heightened atherosclerotic burden and contributing to cardiovascular events. They also result in accelerated ageing, contributing to a low-grade inflammation and pronounced degradation of lung, skin, and arterial elastin [3].

Finally, chronic hypoxemia in COPD can lead to pulmonary vascular remodelling, including intimal hyperplasia and smooth muscle hypertrophy and hyperplasia [4]. This vascular strain can lead to increased pressure in pulmonary circulation, ultimately placing a burden on the right ventricle and impairing its function [3]. Hypoxia has also been identified as a key trigger for atrial remodelling and arrhythmogenesis, particularly atrial fibrillation [5].

Table 1. Pathophysiological links between chronic obstructive pulmonary disease and cardiovascular disease.

COPD: chronic obstructive pulmonary disease; CRP: C-reactive protein; ROS: reactive oxygen species; HF: heart failure

COPD and specific cardiovascular conditions

Many patients with COPD also present with at least one other clinically relevant comorbidity, with CVD being among the most common. Studies suggest that up to 60% of individuals with COPD have coexisting cardiovascular conditions, such as arterial hypertension, ischemic heart disease, heart failure, or arrhythmia [2]. This high rate of coexistence highlights the importance of integrated management, as these conditions can exacerbate each other through the shared pathophysiological mechanisms discussed previously.

For instance, heart failure and arrhythmias can lead to fluid retention and impaired gas exchange, exacerbating respiratory symptoms. Conversely, COPD exacerbations —often characterised by increased inflammation, hypoxia, and elevated sympathetic tone —can precipitate malignant cardiovascular events such as myocardial infarction, stroke, acute heart failure, or increased risk of cardiovascular death [6]. This bidirectional relationship is well documented in the literature. Managing cardiovascular comorbidities is essential to improve outcomes in COPD patients [7].

Figure 1. Schematic representation of the relationship between chronic obstructive pulmonary disease pathophysiology and heart failure.

HF: heart failure

Arterial hypertension

Systemic arterial hypertension is one of the most frequently observed comorbidities in individuals with COPD, with prevalence estimates ranging from 30% to over 50% depending on the population and diagnostic criteria used [7].

In clinical practice, the management of hypertension in patients with COPD can be challenging. Beta blockers have been shown to be safe in most COPD patients and are underused despite evidence of their benefits to cardiovascular comorbidities [8]. Other antihypertensive agents, including ACE inhibitors, Angiotensin receptor blockers (ARBs), calcium channel blockers, and thiazide diuretics can be used safely, although individualisation is essential to account for potential interactions with COPD medications or side effects such as volume depletion or electrolyte imbalances.

Coronary artery disease

COPD is an independent predictor of atherosclerosis development and progression [9]. It shares with CVD an important pathophysiological mechanism – inflammation – that plays a pivotal role in plaque development and rupture. Patients with COPD display increased intensity and severity of atherosclerotic disease, with more critical coronary lesions and enhanced calcification compared to non-COPD patients [9]. During COPD exacerbations, and for as much as one year after, the risk of acute coronary events increases significantly due to plaque destabilization and rupture triggered by the heightened inflammatory state [6]. Within five days after a COPD exacerbation, the risk of myocardial infarction is increased twofold [6].

Heart failure

HF is a complex clinical syndrome characterised by structural or functional cardiac dysfunction. Diagnosis typically relies on a combination of clinical features, imaging, and biomarker assessment. However, the clinical presentation of HF may overlap significantly with COPD, complicating accurate diagnosis. Common symptoms such as exertional dyspnoea, paroxysmal nocturnal dyspnoea, and signs of right-sided heart failure can be shared by both conditions, making differentiation difficult in clinical practice [10].

This diagnostic overlap often leads to under-recognition of coexisting disease. Clinicians may make one diagnosis — such as COPD — and fail to investigate concurrent HF, leading to undertreatment. Complicating matters further, transthoracic echocardiography in COPD patients can be technically challenging due to hyperinflated lungs creating poor acoustic windows, particularly in those with severe airflow obstruction [10].

Natriuretic peptides can aid in differentiating cardiac from pulmonary causes of dyspnoea. While very high or low values of natriuretic peptides are strongly predictive for or against HF, respectively, intermediate levels often fall into a diagnostic “grey zone” in these patients [10]. The prevalence of COPD among patients with chronic heart failure is reported to range between 23% and 33% [11]. In a large cohort study, HF with preserved ejection fraction was more common (70%) than HF with reduced ejection fraction (20%) in patients with COPD [12].

Pulmonary hypertension

Mild-to-moderate pulmonary hypertension (PH) is a common and clinically significant complication of COPD, associated with an increased risk of exacerbations and reduced survival [13]. This form of PH typically arises from pulmonary vascular remodelling and increase in pulmonary vasculature resistance, which is driven by a combination of chronic hypoxia, systemic and local inflammation, and the loss of pulmonary capillaries [13]. Over time, the progression of PH can lead to right ventricular hypertrophy and dilation, ultimately resulting in right-sided heart failure, known as cor pulmonale.

Recognising and appropriately managing PH in COPD is crucial, as its presence significantly impacts clinical outcomes, including increased morbidity and mortality. Given the poor prognosis associated with severe PH in COPD and the complexity of management, patients suspected of having out-of-proportion PH or those with unclear diagnoses should be referred to specialised PH centres.

Arrythmia

COPD is strongly associated with an increased risk of various types of cardiac arrhythmia, including atrial fibrillation (AFib), ventricular arrhythmias, and sudden cardiac death [14]. Notably, COPD has been linked to a 28% increased risk of developing AFib, with frequent exacerbations further doubling this risk [5]. Pulmonary function parameters such as forced expiratory volume in one second and forced vital capacity are inversely associated with the incidence of AFib, highlighting the correlation between impaired lung function and arrhythmogenesis [5].

In addition, commonly used COPD medications — including β₂ agonists, anticholinergics, methylxanthines, and systemic glucocorticoids — may independently promote arrhythmogenesis through sympathetic stimulation, altered electrolyte balance, or direct myocardial effects [3, 5].

It is important to note, however, that uncontrolled COPD itself is a significant risk factor for arrhythmia. Therefore, appropriate pharmacological control of COPD symptoms may reduce the overall arrhythmic burden despite concerns regarding medication-induced side effects. Evidence suggests that long-acting bronchodilators are associated with a lower arrhythmogenic potential compared to short-acting agents, making them the preferred option for maintenance therapy [5].

Pharmacologic strategies

Bronchodilators — particularly long-acting beta-agonists and long-acting muscarinic antagonists — are crucial to the pharmacological management of COPD. These agents improve airflow, reduce symptoms, and decrease the frequency of exacerbations. Although the evidence is somewhat mixed, some studies have raised concerns about their cardiovascular safety, especially in patients with pre-existing CVD [3].

Cardiovascular risks associated with β-adrenergic receptor agonists

Some observational studies and meta-analyses have suggested a potential association between the use of long acting βagonists and an increased risk of cardiovascular events in patients with COPD. These events include AFib, ventricular arrhythmias, and exacerbations of heart failure. The proposed mechanism behind this association is the stimulation of cardiac beta-1 adrenergic receptors, which can increase heart rate, myocardial contractility, and oxygen demand [15].

However, it is important to recognise that these findings are not universally consistent across the literature. While some observational data raise concerns, randomised controlled trials have not consistently demonstrated a significant increase in cardiovascular risk.

In fact, when used appropriately, long-acting beta agonists may offer indirect cardiovascular benefits by improving oxygenation, reducing lung hyperinflation, and decreasing the frequency of exacerbations — all of which may help reduce cardiovascular stress [15].

Therefore, while caution is warranted — particularly in high-risk patients or those with known cardiovascular disease — the totality of evidence suggests that these can be used safely in most COPD patients when prescribed judiciously.

Beta blockers in COPD - risks and benefits

Despite historical concerns about bronchospasm, current evidence strongly supports beta blocker use in COPD patients with concurrent CVD. Patients with COPD usually receive less secondary prevention for myocardial infarction and heart failure, and this may be more evident in beta blocker usage due to fear of precipitating bronchospasm [11].

Beta blocker use is associated with reduced risk of COPD exacerbations, all-cause mortality, and in-hospital mortality among COPD-CVD patients [11].

The benefits appear to be specific to cardioselective agents. The evidence suggests beta blockers should not be withheld from COPD patients with appropriate cardiovascular indications, with preference given to cardioselective agents.

Regarding other drugs, the cardiovascular benefits of statins and blockers of the renin-angiotensin axis in different cardiovascular diseases and risk factors are well established, underscoring their pivotal role in the management of CVD. This method of application, however, is independent of their effects on COPD outcomes or outcomes in COPD populations, which appear beneficial in observational data but are insufficient to make strong recommendations [16, 17].

The role of (cardiac) rehabilitation

Cardiac rehabilitation (CR) represents one of the cornerstone interventions for patients with cardiac disease. It offers multidimensional benefits that transcend improvements in exercise tolerance alone. The intersection of COPD with many cardiac diseases (as seen previously) is clinically challenging, particularly regarding overlapping symptoms such as exertional dyspnoea and fatigue.

Despite these complexities, evidence demonstrates that structured CR (or pulmonary rehabilitation) programs, which combine aerobic and resistance training with education and psychosocial support, are both feasible and effective in this population [18]. Nevertheless, it is important to recognise that COPD patients tend to be less enrolled in CR programs compared with patients without COPD. Those who do participate, however, complete programs at comparable rates, suggesting that tailored interventions addressing breathlessness and functional limitations can overcome initial barriers to engagement [19]. Functional gains, as measured by the six-minute walk test and peak oxygen uptake, are consistently observed [20].

Beyond physical performance, CR is associated with significant reductions in dyspnoea, anxiety, and depression, as well as marked enhancements in disease-specific quality-of-life indices, benefits that are sustained when maintenance strategies are employed [21].

Conclusion

The current underdiagnosis and undertreatment of CVD in patients with COPD can be attributed to several factors. One key issue is the lack of comprehensive and integrated clinical guidelines specifically addressing the management of cardiovascular comorbidities within the context of COPD. Most COPD guidelines acknowledge the relationship between these two entities but focus primarily on pulmonary symptoms, often giving limited attention to concurrent cardiac conditions.

Additionally, the overlapping symptomatology between COPD and CVD — particularly with heart failure — complicates diagnosis. This clinical overlap can obscure the presence of underlying heart disease and hinder timely intervention.

Furthermore, there may be hesitancy among clinicians to pursue aggressive cardiovascular management in COPD patients due to concerns about polypharmacy, drug interactions, or potential adverse effects on respiratory function. Together, these factors contribute to the systemic under-recognition and suboptimal treatment of CVD in the COPD population, despite the significant impact such comorbidities have on morbidity and mortality.