Beyond the Lungs: A Narrative Review of Cardiopulmonary Risk Reduction and Management Perspectives in Thai COPD Patients

Introduction

Chronic obstructive pulmonary disease (COPD) has been considered a self-inflicted disease caused by tobacco smoking in genetically susceptible individuals, and it significantly impacts public health worldwide. Most patients with COPD have at least one additional, clinically relevant chronic disease, particularly cardiovascular diseases (CVD).¹ Respiratory failure is the cause of death among individuals with severe airflow obstruction, and CVD often causes death in patients with COPD.² The association between COPD and CVD could be explained by the presence of risk factors shared in both diseases, including smoking and aging, with potentially shared pathobiological mechanisms.^1,3 This increasing recognition leads to a paradigm shift from COPD being considered as a single disease to COPD with comorbidities. It highlights the need to recognize coexistence of CVD and to address CVD worsened by COPD exacerbation, and vice versa. The ultimate goal is to minimize exacerbation-associated cardiopulmonary events and reduce cardiopulmonary-related mortality. To do so, increasing awareness of the COPD-CVD link, optimizing preventive management for COPD exacerbations, and regularly monitoring CVD activity during the post-COPD exacerbation period are absolutely required. Strategies for post-COPD exacerbation management in developing countries have been developed but remain incompletely established, with challenges to their implementation.⁴ Between August and September 2025, a panel of nine experts, including six pulmonologists and three cardiologists from Thailand and Malaysia, collaborated through both in-person and virtual meetings to review and discuss cardiopulmonary risk and mortality reduction in COPD. The implementation under the cardiopulmonary risk concept has been initiated together with setting discharge protocols in Malaysia. These insights informed the development of tailored management approaches for COPD patients in Thailand, emphasizing the importance of structured care pathways to reduce recurrent COPD exacerbations and CV events during exacerbation-associated hospitalization and throughout post-COPD exacerbation periods.

This narrative review focuses on cardiopulmonary risks associated with COPD exacerbations, highlighting the heightened incidence of CV events after COPD exacerbations, post-COPD exacerbation management and effective treatment in reducing exacerbations, mortality and CV events. The review was developed through an evaluation of clinical studies, including randomized controlled trials, meta-analyses and real-world evidence, supplemented by guideline recommendations and relevant local data from Thailand. It further provides expert perspectives on integrated cardiopulmonary risk management within the context of COPD care in Thailand, emphasizing the need for coordinated multidisciplinary approaches.

COPD Exacerbation and Cardiopulmonary Risk

Burden of COPD and Health Care Impact

COPD is one of the major global health concerns, accounting for 5% of total deaths in 2021. In the same year, an estimated 16.90 million new COPD cases were reported globally, with 3.70 million deaths, ranking COPD the fourth leading cause of death.^5,6 However, the incidence rates declined by 2% from 1990 to 2021, which the pace and extent of this decline varied across age groups, sexes, and regions.^5,7 The burden of COPD is higher in low- and middle-income countries (LMICs), where nearly 90% of COPD-related deaths occur in individuals under 70 years of age.⁸ Additionally, the incidence of COPD in LMICs is increasing more rapidly than high-income countries, with projections estimating up to 426 million COPD cases worldwide by 2050.⁹

In Thailand, COPD prevalence has increased during the past two decades, rising from 2,268 cases per 100,000 people in 2000 to 7,035 cases per 100,000 people in 2010.¹⁰ However, data from the Global Burden of Disease, the Global Health Data Exchange database reported that the estimated COPD incident cases in Thailand were 131,403.5 cases in 2021, with an overall declining trend in incidence and mortality from 1990 to 2021.⁵ Furthermore, new COPD cases among individuals aged over 40 years decreased from 14,243 cases in 2019 to 11,349 cases in 2020, while COPD-related deaths declined from 18,925 cases to 18,169 cases during the same period.¹⁰

The main pathological features of COPD are obstructive bronchiolitis, emphysema, and, in many cases, mucus hypersecretion (chronic bronchitis); however, the relative contribution of each of these pathologies to COPD varies between patients.^11–14 Airflow obstruction and a significant loss (disappearance) of small airways occur even in early or mild COPD.¹⁵ In COPD, several processes narrow the small airways: inflammation thickens the bronchiolar periphery wall, fibrosis produces fixed narrowing, emphysema disrupts alveolar attachments, and mucus and inflammatory exudate cause luminal occlusion.¹³ Many patients with COPD experience an accelerated annual decline in lung function. As airway obstruction worsens, symptoms progress from reduced physical activity to shortness of breath on exertion, then to shortness of breath at rest, followed by respiratory failure including exacerbations.¹³ These symptoms also substantially impair patients’ quality of life.¹⁶ A mathematical modelling suggested that improvement of COPD management could reduce avoidable hospitalizations, improve survival and lead to cost reductions.¹⁷ The model evaluated interventions such as increased early follow-up after exacerbations and increased access to integrated disease management program. These findings indicate that preventing and promptly managing exacerbations is crucial to improving patient outcomes and reducing the healthcare burden of COPD.

Cardiopulmonary Linkage in COPD

There is a considerable correlation between COPD and CVD, with approximately 60% of individuals with COPD having coexisting CV conditions such as coronary heart disease, stroke, or heart failure (HF).¹⁸ Similarly, a retrospective cohort study in Thailand showed that 57.6% of COPD patients hospitalized with acute exacerbation had CVD comorbidities (11.6% atrial fibrillation, 13.4% congestive HF, 12.3% coronary artery disease, 8.5% cerebrovascular disease and 45.6% hypertension).¹⁹ Compared with individuals without COPD, COPD patients experience higher rates of major adverse cardiovascular events (MACE), including acute myocardial infarction, congestive HF, stroke, and CV death.^20,21 Moreover, CV-related deaths outnumber COPD-related deaths in individuals with severe or multiple exacerbations, underscoring the critical interplay between the heart and lungs.²² The co‑occurrence of COPD and CVD is now recognized as a syndemic, sharing risk factors such as smoking and aging, as well as common pathophysiological mechanisms between these disorders.^1,3,23,24 The spiral of lung morphological and functional decline that affects patients with stable COPD is underpinned by a substantial number of interconnected mechanisms including lung hyperinflation, systemic inflammation, and hypoxemia.^3,23 These pathophysiologic processes may intensify in response to triggers during an exacerbation episode, potentially causing CV events both during and after the exacerbation period. Briefly, long-term exposure to cigarette smoke and exogenous oxidants increases oxidative stress, which induces epithelial and endothelial damage and intensifies local inflammation.^3,23 Elevated inflammatory mediators in patients with COPD during stable and exacerbation phases can flood into systemic circulation and contribute to the onset and worsening of CVD.^23,25 Additionally, airflow obstruction and dynamic lung hyperinflation increase intrathoracic pressure and left ventricular (LV) wall stress with reduced LV filling and output, hence impairing cardiac performance.^3,23 In addition, ventilation/perfusion (V/Q) mismatch during exacerbation results in hypoxic enhancement of neutrophil-mediated endothelial injury that risks COPD exacerbators for CV events.²⁶

Heart failure and COPD have a pathophysiology that underscores the cardiopulmonary link. Chronic hypoxia-induced pulmonary vasoconstriction in COPD leads to pulmonary hypertension, which exerts strain on the right ventricle (RV) and results in right-sided HF. Elevated pressure in the RV inhibits filling of the left ventricle, impacting both ventricles.²⁷ Reduced LV end-diastolic volume, stroke volume, and cardiac output are associated with pulmonary emphysema in advanced COPD.²⁸ Dynamic hyperinflation during exertion further enhances positive intrathoracic pressures and diminishes venous return, and the flattened dome of the diaphragm also impacts both venous return and ventricular afterload during breathing cycles. Significant diaphragmatic atrophy noted in both COPD and HF also affects biventricular filling pressure patterns.²⁸ Conversely, elevated left atrial filling pressure during exercise in heart failure with preserved ejection fraction (HFpEF) leads to diminished airway cross-sectional area and heightened bronchial reactivity due to vascular engorgement in the bronchial mucosa.²⁸ While the volume shift from the vascular compartment to the interstitial space during exercise in patients with HF does not significantly alter diffusion, gas diffusion deteriorates as interstitial fluid traverses the alveolar-capillary membrane to clear the interstitial space. These alterations lead to V/Q mismatch and hypoxemia, thereby triggering pulmonary vasoconstriction and exacerbating dead space ventilation in patients with COPD.²⁸ Hyperventilation due to V/Q mismatch, sympathetic activation of chemoreceptors, and metaboreflex stimulation from skeletal and respiratory muscles in HF patients leads to exertional dyspnea in individuals with COPD.²⁸

Frequency and Severity of COPD Exacerbations Potentiate Immediate and Long-Term Risk of CV Events

Patients with COPD are two- to five-times more likely to be diagnosed with CVD compared to those without COPD, including ischemic heart disease, HF, stroke, and cardiac dysrhythmias.^20,29,30 Considering that COPD exacerbations significantly increase the likelihood of CV events and all-cause mortality, understanding the temporal relationship between these two conditions is crucial for the timely monitoring of CV risks that might be mitigated through effective preventive strategies.^31,32 A meta-analysis identified a vulnerable post-exacerbation period in which patients experience markedly increased risk of CV events within the first 30 days following an exacerbation: acute coronary syndrome (hazard ratio [HR], 3.74; 95% confidence interval [CI], 2.35–5.95), HF (HR, 6.81; 95% CI, 1.80–25.82), acute cerebrovascular events (HR, 2.46; 95% CI, 1.64–3.68) and arrhythmias (HR, 3.93; 95% CI, 1.94–7.95).³¹ Although heightened CV risk diminishes over time, it remains significant for up to one year following a COPD exacerbation related to acute coronary syndrome (HR, 1.43; 95% CI, 1.09–1.88) and all-cause mortality (HR, 1.11; 95% CI, 1.05–1.17).³¹ Nonetheless, some studies indicate that the long-term CV risk following a severe exacerbation may persist for over six years.³³ (Figure 1)

Figure 1 Cardiovascular outcomes following COPD exacerbation. All-cause mortality and CV events, including acute coronary syndrome (ACS), heart failure (HF) and arrhythmia, increase after exacerbation. The risk of CV events peak within the first 30 days after exacerbation. Abbreviations: ACS, acute coronary syndrome; COPD, chronic obstructive pulmonary disease; CV, cardiovascular; HF, heart failure.

The threshold for exacerbation-related CV event risk differs based on the severity of exacerbation and accompanying respiratory symptoms. CV events following moderate COPD exacerbations transpire somewhat later than those following severe exacerbations. The incidence rate of CV events was highest 14–30 days after moderate exacerbations, but peak CV events occurred 1–14 days after severe exacerbations, suggesting that the early period after an exacerbation offers a pivotal opportunity to perform clinical interventions and optimize therapy to avert future CV incidents.³² The incidence of CV events markedly escalates during a second exacerbation in comparison to the first episode, reaching a level comparable to that reported after a third exacerbation.³¹ The substantial and persistent rise in CV-related and all-cause mortality following exacerbation underscores the necessity for effective intervention, early prevention of recurrent exacerbations, and monitoring of cardiopulmonary risk to mitigate mortality in COPD patients during the post-exacerbation phase.

In Thailand, analogous findings have been noted, indicating elevated mortality rates among stable COPD patients with metabolic syndrome. This cohort exhibited a significantly increased annual exacerbation rate in COPD patients with metabolic comorbidities compared to patients devoid of metabolic syndromes, alongside an augmented likelihood of CVD, stroke, mortality, and exacerbation following a 5-year follow-up period.³⁴ Additionally, COPD exacerbators with coexisting atrial fibrillation and coronary artery disease had higher in hospital mortality compared to those without these comorbidities.¹⁹ A prospective study in Thailand reported annual exacerbation rates of 3 and 2 times per year in eosinophilic and non-eosinophilic COPD, respectively.³⁵ However, the availability of evidence in Thailand remains limited, with the existing data originating from individual hospitals in specific regions that may not represent the national population. Furthermore, national COPD data from Thailand reported exacerbation rates of 134 and 124.8 events per 100 patients per year in 2019 and 2020, respectively.¹⁰ These rates exceeded the target of lower than 110 events per 100 patients per year, highlighting the substantial burden of COPD exacerbations and the need to optimize preventive management to reduce exacerbation frequency, CV events and mortality in this population.

Cardiopulmonary Risk Management in COPD Patients

Cardiopulmonary risk in COPD is defined as the risk of serious respiratory and/or CV events in patients with COPD. These events include, but are not limited to, COPD exacerbations, myocardial infarction, stroke, HF decompensation, arrhythmia and death due to any of these events.³⁶ Understanding the association between COPD exacerbation and CV events, as well as the concept of cardiopulmonary linkage, promotes awareness and emphasizes the importance of cardiopulmonary risk management among healthcare professionals and COPD patients. Proactive strategies to manage cardiopulmonary risk are needed to guide clinician decision-making. This section discusses an effective and practical approach to managing cardiopulmonary risk, which has the potential to improve patient outcomes and reduce mortality, particularly during the vulnerable periods following COPD exacerbations. Furthermore, conceptual illustrations were developed for inpatient management strategies and discharge planning in post-COPD exacerbation, as shown in Figures 2 and 3, respectively. These diagrams were proposed based on available evidence and expert opinions, with the aim of providing structured strategies for clinical management and facilitating clinical decision-making. Notably, the approaches outlined in the diagrams should be selected and tailored to the specific clinical context.

Figure 2 Inpatient management strategies for post-COPD exacerbated patients with established or suspected CV diseases. A comprehensive evaluation of cardiopulmonary risk, pharmacological and non-pharmacological interventions should be performed to reduce risk and ensure optimal management. Abbreviations: CAC, coronary artery calcium; COPD, chronic obstructive pulmonary disease; CV, cardiovascular; CT, computed tomography; ECG, electrocardiogram; HbA1c, hemoglobin A1c; hs-cTn, high sensitivity cardiac troponin; ICS, inhaled corticosteroid; LABA, long-acting beta-2 agonist; LAMA, long-acting muscarinic antagonist; NT-proBNP, N-terminal pro-B-type natriuretic peptide.

Figure 3 Discharge planning for COPD patients following exacerbation. Key components of discharge planning can be divided into two phases (at discharge and post-discharge), aiming to reduce cardiopulmonary risk and prevent readmission.

Effective COPD Treatment That Comprehensively Reduces Exacerbations, All-Cause Mortality and CV Events

Pharmacological treatment for COPD patients depends on the level of symptoms and risk for exacerbations. The inhaled long-acting bronchodilator treatment—including a long-acting beta-2 agonist (LABA), a long-acting muscarinic antagonist (LAMA), a combination of LABA and LAMA (LABA+LAMA), or a triple inhaled therapy combination of LABA+LAMA and inhaled corticosteroid (ICS)—are recommended for frequent exacerbators by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2026 guidelines in the context of the initiate or follow-up treatment.³⁷ Furthermore, other second-line pharmacological treatments such as macrolides, mucolytics and biologic therapy (dupilumab and mepolizumab) can be used as add-on therapy after the unmet need of dual LAMA+LABA bronchodilators or triple therapy (ICS+LABA+LAMA) in reducing COPD exacerbations.³⁷

Because exacerbations are also associated with an increased risk of CV events, effective COPD treatment should not only aim to reduce exacerbation frequency but also lower mortality and CV events. Several studies have demonstrated the benefits of pharmacotherapy beyond COPD symptom control. Although clinical trials evaluating LABA+ICS and LAMA—such as those in the TORCH, SUMMIT, and UPLIFT studies—reported no significant effects on mortality or CV outcomes, the INSPIRE trial indicated lower mortality rate with LABA+ICS compared with LAMA.^38–41 However, this finding must be interpreted cautiously, as the trial was not powered to detect mortality differences.^42,43 Triple therapy significantly reduces exacerbations.^44–49 For mortality and CV benefits, the emerging triple therapy strategy is informed by two large randomized clinical trials: IMPACT and ETHOS (Table 1).^{46,48,50–52} In IMPACT study, the lower rate of moderate or severe exacerbations has been shown in the treatment with fixed-dose inhaled triple combination of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) compared to dual therapy with umeclidinium/vilanterol (rate ratio, 0.75; 95% CI, 0.70–0.81) or fluticasone furoate/vilanterol (rate ratio, 0.85; 95% CI, 0.80–0.90).⁴⁶ In ETHOS study, single-inhaler triple therapy (SITT) with budesonide/glycopyrrolate/formoterol (BGF) also significantly reduced annual exacerbation rate in a high-risk population of patients with moderate to very severe COPD exacerbations, severely impaired lung function (forced expiratory volume in one second [FEV₁] 25–65% of predicted normal), and multiple CV risk factors.⁴⁸ Compared with the dual therapy of glycopyrrolate/formoterol, the relative risks for moderate to severe exacerbations were 0.75 (95% CI, 0.69–0.83) for BGF containing 160-µg budesonide and 0.76 (95% CI, 0.69–0.83) for BGF containing 320-µg budesonide.⁴⁸ Post-hoc analyses of IMPACT and ETHOS showed that FF/UMEC/VI and BGF reduced all-cause mortality and significantly lower rates of CV deaths.^50–52 The ETHOS study showed that the BGF containing 320-μg budesonide was associated with a reduction in the time to first CV adverse event of special interest (HR, 0.63; 95% CI, 0.48–0.82), cardiac adverse event (HR, 0.60; 95% CI, 0.48–0.76) and severe cardiopulmonary events (HR, 0.80; 95% CI, 0.67–0.95) compared to glycopyrrolate/formoterol.⁵² Meta-analyses and real-world evidence also demonstrated improved patient outcomes after receiving the SITT, including reduced exacerbation rates, mortality and CV risks, as well as lower use of additional medication and care such as short-acting beta-2 agonists, oral corticosteroids, antibiotics, primary care visits, admissions to the emergency room and hospitalizations.^49,53–55

Table 1 Summary of Landmark Phase III Trials for Reducing Exacerbations, All-Cause Mortality and CV-Related Mortality in COPD Patients

The GOLD 2026 guidelines recommend that the initiation and escalation of triple therapy are beneficial for COPD exacerbators, and the use of SITT improves adherence over separate devices.^37,56 The triple therapy is considered as initial treatment in GOLD group E patient (≥1 moderate or severe exacerbations in the previous year) if eosinophil ≥300 cells/µL. For patients who continue to experience moderate or severe exacerbations despite receiving dual bronchodilator therapy (LABA+LAMA), escalation to triple therapy is suggested. Therapeutic response to the addition of ICS to dual LABA+LAMA bronchodilator may be observed at eosinophil counts ≥100 cells/µL, with greater efficacy at higher levels.³⁷ Blood eosinophil count serves as a predictive biomarker to predict the benefit of ICS-containing regimens in reducing exacerbation in COPD exacerbators by high blood eosinophils (≥2% or ≥300 cells/µL).^57–59

In non-pharmacological treatment, smoking cessation, pulmonary rehabilitation, long-term oxygen therapy and vaccination are recommended in local and GOLD 2026 guidelines for reducing exacerbation and mortality.^10,37 Smoking cessation is the key intervention to prevent disease progression and mortality.⁶⁰ All patients with COPD should receive vaccinations (influenza, pneumococcal, respiratory syncytial virus and SARS-CoV-2 vaccines) as per local guidelines in order to decrease the incidence of respiratory tract infections and reduce risk of acute exacerbation.^10,37,61 The influenza vaccination can reduce serious illness, with positive effect for exacerbation and mortality reduction.^62,63 Routine review of non-pharmacological treatment is advised to optimize intervention of exacerbation and related risk factors.

Considerations of CV Medications in Comorbid COPD and CVD

Comorbidities should be managed as per their specific guidelines regardless of the presence of COPD.³⁷ The effects of CV medications on COPD outcomes should be considered and evaluated to ensure safety and benefit.²⁴ Meta-analyses and observational studies suggest that beta-blockers used in patients with COPD have a positive effect for reducing exacerbations; but, clinical trial data are mixed and raised safety concerns in patients with high exacerbation risk.^64–69 However, beta-1 selective blockers improve survival in HF, and are considered safe and beneficial in COPD, as they reduce exacerbations and mortality without adverse pulmonary effects.^64–66,70 Therefore, beta-blockers should be used only for approved CV indications and not prescribed for preventing COPD exacerbations.³⁷

Other common CV medications are generally safe in COPD. Statins possess anti-inflammatory properties and may lower the risk of COPD exacerbations and hospitalizations.^24,71 Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are commonly used and well-tolerated in patients with COPD and/or CVD.^24,71 Overall, integrated management of both conditions following the local guidelines and experts, with careful consideration of drug effects on pulmonary and cardiac function, is essential to optimize outcomes.

Cardiovascular Risk Management in Patients with COPD Exacerbation

Timely identification of COPD patients at elevated risk for CV events is a crucial step in treatment and CV risk management. The GOLD 2026 and European Society of Cardiology (ESC) guidelines emphasize the importance of CV risk screening and recommend incorporating routine CV risk assessment into regular COPD management in all COPD patients.^37,72 The recommended assessment includes annual testing of physical examination, electrocardiogram (ECG) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), to facilitate early detection and treatment.³⁷ Therefore, patients with COPD, particularly those with recent exacerbations, should be screened for cardiopulmonary risk using a combination of clinical assessment tools, laboratory evaluations, and imaging or functional assessments (Figure 2). Annual screening of patient history, signs and symptoms, and CV risk is recommended, with additional CV diagnostic investigations performed as clinically indicated.^37,73 However, further CV risk evaluations should be tailored according to the results of initial clinical assessments or laboratory tests and would be performed as appropriate.

Clinical Assessment Tools

CV risk scores are used to estimate 10-year risk of CV events. The Atherosclerotic Cardiovascular Disease (ASCVD) Risk Score, Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) Score and QRISK4 are tools commonly used for CV risk estimation worldwide.^74,75 For Thailand, Thai CV risk score is a validated and widely used tool to estimate 10-year absolute CV risk.⁷⁶ The risk score includes variables such as age, sex, smoking status, diabetes, systolic blood pressure, levels of LDL-C and HDL-C, waist circumference and height. However, the use of established CV risk scores in the general population may underestimate risk of CVD in patients with COPD due to lack of COPD-specific adjustments.^73,77 Therefore, additional tests such as coronary artery calcium (CAC) scoring to the Thai CV risk score improve CV risk prediction.⁷⁸

Laboratory Evaluations

Fundamental baseline assessments should include measurement of blood pressure and routine laboratory test such as lipid profile, hemoglobin A1c (HbA1c), complete blood count, urea and electrolytes, and liver and renal function tests.⁷³ Additional laboratory tests related to CVD such as NT-proBNP and high sensitivity cardiac troponin (hs-cTn) are useful for the prediction of CV events, particularly in HF and myocardial injury, respectively.^79,80 The GOLD 2026 guidelines recommend annual NT-proBNP testing as a part of routine CV assessment in patients with COPD.³⁷ Furthermore, current other international recommendations are to measure NT-proBNP in patients with type 2 diabetes or suspected HF and may measure hs-cTn in individuals with intermediate 10-year CV risk.^81–83 A growing body of evidence also demonstrates a utility of hs-cTn and NT-proBNP for CV risk stratification during COPD exacerbation.^79,84,85

Imaging and Functional Assessments

The imaging and functional assessments such as ECG or chest radiography (CXR) support clinical evaluation and decision-making. ECG abnormalities can predict adverse outcomes, and the GOLD 2026 recommends annual assessment for CV comorbidity.^37,86 CAC scoring is an important tool for detecting coronary artery disease and stratifying CV risk.^73,87,88 It can be identified opportunistically on non-gated and low-dose CT scans, which are often performed for lung cancer screening in COPD patients.^89–92 Recognition of coronary calcification helps to identify a powerful prognostic factor that can provide a better risk stratification and influence therapeutic interventions.⁹⁰ Furthermore, transthoracic echocardiogram is useful for screening subclinical cardiac dysfunction in COPD patients, particularly suspected HF and pulmonary hypertension.^73,93,94

Overlapping symptoms between COPD and HF can obscure the underlying etiology, complicate clinical assessment and lead to suboptimal treatment decisions.²⁸ Diagnosing HFpEF can be difficult, especially in patients with COPD, because exertional dyspnea is a symptom of non-cardiovascular comorbid diseases.⁹⁵ It necessitates ruling out other conditions such as hypertrophic cardiomyopathy that resemble HF with intact ejection fraction. There are several indicators of HFpEF, including NT-proBNP levels and echocardiographic findings at rest and during exercise.⁹⁵ In conditions of euvolemic and normal cardiac filling pressure status, exercise hemodynamics may provide earlier and more accurate diagnosis.⁹⁶ Additionally, cardiopulmonary exercise testing (CPET) provides gas exchange analysis to identify pulmonary, cardiovascular and muscular limitations. It may also be considered to further assess the underlying cause if symptoms persist, as it helps differentiate cardiac, pulmonary, peripheral vascular disease and deconditioning contributors to persistent dyspnea.^97–99 However, the accessibility of CPET is limited and is predominantly available in major tertiary centers in Thailand. Importantly, clinicians should maintain a high index of suspicion for concomitant HF among COPD patients rather than relying solely on differential diagnosis. Additional diagnostic approaches as previously mentioned may be required to improve diagnostic accuracy and optimize management to maximize clinical benefits, as these conditions commonly coexist.

Other Assessments

Evidence suggests that body composition measures may offer further insights into CV risk among COPD patients. An elevated visceral fat-to-muscle mass ratio is associated with an increased risk of major adverse CV events.¹⁰⁰ Moreover, a higher body roundness index has been linked to increased all-cause and CV mortality in this population.¹⁰¹ These findings highlight the potential value of incorporating body composition metrics into comprehensive risk assessments for COPD patients.

Perspectives on Cardiopulmonary Risk Management in COPD Care in Thailand

Implementation of Cardiopulmonary Risk Management in Thai Healthcare Settings

As recommended by the GOLD 2026 guidelines, the primary treatment goals in patients with COPD following exacerbations are to minimize the negative impact of the current exacerbations and prevent the development of subsequent events.³⁷ In Thailand, the treatment goals also emphasized COPD symptoms reduction, lowering the risk of future exacerbations and managing cardiopulmonary risk, especially during post-exacerbation period. However, alignment of treatment goals across specialties, including pulmonologists and cardiologists, remains an area for improvement. Therefore, these goals should be addressed and implemented within a broader clinical context for increased awareness of cardiopulmonary risk and management during the vulnerable post-exacerbation period.

Multidisciplinary team (MDT) is ideal for providing holistic care to patients with COPD. The MDT should include pulmonologists, cardiologists, pharmacists, nurses, rehabilitation therapists, nutritionists and other relevant specialists to ensure quality outcomes.³⁷ In Thailand, combined MDT interventions at primary and tertiary care levels such as the Central Chest Institute of Thailand have demonstrated significant clinical and economic benefits, including reduced exacerbations, hospitalizations and improved quality of life.^102,103 However, due to the high patient volume, referral consultations may currently be a more practical approach than direct MDT management. The referral approach allows for targeted expertise while maintaining efficiency in COPD care, ensuring that patients receive appropriate evaluation and management to uncover and address cardiopulmonary risks. For example, pulmonologists could lead screening for coronary artery disease using chest CT scan results to assess coronary calcium and for HF using biomarkers such as NT-proBNP before referring to cardiologists.

Understanding the cardiopulmonary linkage and risk management in COPD patients following exacerbation is crucial for improving patient outcomes and reducing mortality. Without understanding the risk and management strategies, referral consultations often lead to frustration, with patients returning to their original clinical setting without further investigation or appropriate follow-up. An issue would occur in both directions between pulmonologists and cardiologists. This also highlights the need to raise awareness of the cardiopulmonary linkage among both pulmonologists and cardiologists to promote more collaborative and effective care during the post-exacerbation period. Implementation of cardiopulmonary risk management and interdisciplinary collaboration can be achieved through two different levels; 1) by raising awareness through professional education and continuing-development activities such as continuing medical education modules, case-based training and interactive workshops, and 2) by incorporating collaborative principles into national guidelines tailored to the Thai healthcare context to support effective nationwide implementation.

The post-exacerbation period is a critical window for symptom management and prevention of CV events and mortality, underscoring the importance of proactive evaluation and optimization of medications during this phase, particularly in hospitalized patients before discharge. Comprehensive discharge planning should include both pharmacological and non-pharmacological treatments such as medication review, inhaler technique training, comorbidity and CV risk screening, smoking cessation, vaccination, pulmonary rehabilitation and scheduled follow-up, promoting patient outcomes, and reducing readmissions and mortality (Figure 3).^4,37,104 A US study demonstrated that suboptimal management of COPD patients at the time of hospital discharge is strongly associated with an increased risk of readmission, including for cardiopulmonary events and mortality. Among patients discharged after hospitalization for a COPD exacerbation, the study found that 27% received no prescribed treatment, and only 18% were discharged on triple therapy.¹⁰⁵ These findings underscore the urgent need to optimize treatment in advance before discharge to ensure continuity of care and reduce preventable adverse outcomes. In Thailand, the discharge planning is currently implemented in some of secondary and tertiary hospitals but requires updating to incorporate more effective strategies regarding cardiopulmonary risk management.

Disease simulation models from high-income countries (England, Germany, Canada and Japan) demonstrated that improvement of COPD management—with early post-exacerbation follow-up and greater access to integrated disease management programs—reduces avoidable hospitalizations, improves survival rates, and lowers healthcare costs.¹⁷ In terms of LMICs, the COPD management gaps have been identified in Malaysia such as inconsistent care due to lack of continuity and limited specialized expertise, as well as absence of structured post-discharge programs. University Malaya Medical Centre developed a nurse-led discharge program (RED-COPD) and formal discharge protocol to standardize care, ensure proper medication review, and facilitate referrals, resulting in a 35% reduction in 30-day readmissions and increased pulmonary rehabilitation and vaccination uptake.¹⁰⁶ Broader initiatives of this program involve MDT and a national task force developing consensus on integrated cardiopulmonary risk management. This model could be applied to develop and promote cardiopulmonary risk management and COPD care in Thailand.

The exacerbation may be treated on an outpatient or inpatient setting depending on its severity and patient’s underlying diseases. While managing COPD patients with exacerbations and CV-related symptoms, such as chest pain, is relatively straightforward in the inpatient setting, but the key challenge is in the outpatient setting for stable COPD. In this case, early recognition and intervention are crucial to prevent disease progression, reduce hospital readmissions and improve long-term outcomes.

Other Considerations

Effective COPD treatment should be prescribed and optimized to improve clinical outcomes. When pulmonary symptoms are well-controlled, but patients continue to exhibit persistent clinical signs and symptoms, underlying cardiac disease should be suspected. Elevated NT-proBNP levels and/or abnormal ECG provide strong justification for referral to a cardiologist for further evaluation, as these markers are associated with increased risk of HF, pulmonary hypertension, and higher mortality in COPD patients.^79,107,108 Additionally, CAC scans or low-dose CT scans can help detect subclinical CV risks, especially when performed alongside lung cancer screening.

Inhalation therapies are key to COPD treatment. Available diverse options of inhaler devices require proper and accurate techniques for effective treatment. Incorrect inhaler technique is associated with poor symptom control and a higher risk of exacerbations.^109–111 Selecting an appropriate inhaler device and ensuring correct technique are important for optimal drug delivery and treatment outcomes. The choice of inhaler device depends on patient characteristics, including type of medication prescribed, lung function status, ability to use the device correctly, preferences, and cost considerations.^112,113 Similar efficacy and safety between SITT and multiple-inhaler triple therapy were reported in meta-analysis, with no significant differences in moderate to severe exacerbation rates or serious adverse events.¹¹⁴ Interestingly, SITT significantly improved lung function in COPD patients without compromising safety, likely due to treatment simplicity and fewer inhaler used.¹¹⁴ However, real-world evidence showed that patients using SITT significantly increased adherence, resulting in fewer exacerbations and hospitalizations compared to multiple-inhaler triple therapy.^56,115 In Thailand, patient access to SITT remains limited because these medications are not included in the National List of Essential Medicine (NLEM). This major barrier affects the availability and affordability of optimal treatment options, particularly in outpatient care where early intervention is critical. Addressing this gap is essential to ensure equitable access to effective therapies and improve long-term outcomes for patients with COPD.

Despite comprehensive literature reviews, there are knowledge gaps and limitations that should be addressed. Firstly, the direct effects of triple therapy in COPD patients with underlying HFpEF and ischemic heart diseases in preventing CV worsening/exacerbations and CV death remain unknown. Secondly, CV benefits of triple therapy are made by assumption as a result of the limited availability of randomized controlled studies and this requires more evidence to support. Thirdly, the synergistic effects between triple therapy and specific CV treatments remain inconclusive. Additionally, whether the anti-inflammatory effects of triple therapy are systemically mediated in reducing inflammation in atherosclerotic plaques remains elusive. Finally, validation of the proposed assessment tool for COPD patients with CV comorbidities (Figure 2) is certainly warranted.

Conclusions

Patients with stable COPD and with acute COPD exacerbations are associated with increased all-cause mortality, particularly higher rates of respiratory-related and CV events, especially within 30 days following exacerbation. Therefore, proactive cardiopulmonary risk management during the vulnerable period is important. Prior to discharge, patients should undergo comprehensive evaluation of cardiopulmonary risks. Regarding pharmacotherapy, clinicians should first assess inhaler adherence, then prioritize medications that support both COPD control and CV outcomes—such as triple inhaled therapy and other CV agents tailored to patient comorbidities. Non-pharmacological interventions, including smoking cessation and pulmonary rehabilitation, warrant consideration in COPD care plans.