European Journal of Cardiovascular Medicine

Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating respiratory condition characterized by persistent airflow limitation and chronic inflammatory responses in the airways and lungs. It is a major global health concern, contributing significantly to morbidity, mortality, and healthcare costs. According to the Global Burden of Disease Study, COPD is the third leading cause of death worldwide, with its prevalence and impact expected to increase in the coming decades due to aging populations, persistent smoking habits, and environmental pollution.^[1,2]

Pulmonary hypertension (PH) is a well-documented and severe complication of COPD that adversely affects the prognosis and quality of life of patients. PH in COPD arises primarily due to chronic hypoxia and associated vascular remodeling, leading to increased pulmonary arterial pressures. The presence of PH in COPD patients is associated with worsened exercise capacity, increased risk of hospitalization, and higher mortality rates. Despite its clinical significance, PH often remains underdiagnosed and underappreciated in COPD patients, as its symptoms, such as dyspnea and fatigue, overlap significantly with those of COPD itself.^[3,4]

The pathophysiology of PH in COPD involves a complex interplay of mechanisms, including hypoxic pulmonary vasoconstriction, endothelial dysfunction, vascular remodeling, and the presence of systemic inflammation. Chronic alveolar hypoxia, a hallmark of advanced COPD, induces sustained vasoconstriction and vascular remodeling, leading to increased pulmonary vascular resistance. Over time, these changes culminate in right ventricular strain and eventual heart failure, significantly compounding the morbidity associated with COPD. ^[5,6]

Studies have reported varying prevalence rates of PH in COPD patients, ranging from 20% to 70%, depending on the diagnostic criteria, population characteristics, and severity of the disease. These variations highlight the need for standardized and robust methodologies to assess the burden of PH in COPD. Echocardiography, particularly the measurement of right ventricular systolic pressure (RVSP), remains a widely used non-invasive tool for screening PH, although right heart catheterization is the gold standard for definitive diagnosis. ^[7,8,9]

Understanding the prevalence and risk factors for PH in COPD is vital for several reasons. Firstly, identifying high-risk patients enables early diagnosis and targeted therapeutic interventions, potentially mitigating disease progression and improving outcomes. Secondly, recognizing modifiable risk factors, such as smoking and hypoxemia, can inform preventative strategies and public health policies. Lastly, comprehensive data on the burden of PH in COPD can guide resource allocation and healthcare planning, particularly in resource-limited settings.

The primary objective of this study is to estimate the prevalence of PH among patients with COPD in a defined population. Additionally, the study aims to identify significant risk factors contributing to the development of PH, including demographic, clinical, and physiological parameters. By addressing these objectives, the study seeks to bridge existing knowledge gaps and provide actionable insights into the management of PH in COPD patients.

Significance of the Study This study holds significant clinical and public health relevance. Early identification and management of PH in COPD patients can reduce morbidity, prevent complications, and improve quality of life. Moreover, understanding the interplay between COPD and PH can pave the way for novel therapeutic strategies and multidisciplinary approaches to care. The findings of this study are expected to contribute to the existing body of evidence and inform clinical guidelines and practice.

This cross-sectional observational study was conducted to assess the prevalence and risk factors for pulmonary hypertension (PH) in patients diagnosed with chronic obstructive pulmonary disease (COPD). The study was carried out at tertiary care institute over a period of 2 years. A total of 200 patients diagnosed with COPD, based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, were enrolled in the study. Participants were recruited consecutively from the outpatient and inpatient departments of pulmonary Medicine.

Inclusion Criteria

• Adults aged 40 years and above.
• Clinically and spirometrically confirmed diagnosis of COPD (post-bronchodilator FEV1/FVC ratio < 0.70).
• Stable COPD patients without acute exacerbations in the preceding four weeks.

Exclusion Criteria

• Patients with other known causes of pulmonary hypertension, such as left heart disease, congenital heart disease, or chronic thromboembolic pulmonary hypertension.
• Significant comorbidities affecting survival, such as malignancies or advanced renal failure.
• Patients who declined consent or were unable to undergo echocardiographic assessment.

Data Collection

Demographic, clinical, and physiological data were collected using a structured proforma. Information gathered included: Demographics: Age, sex, smoking history (pack-years), body mass index (BMI). Clinical Parameters: Duration of COPD, history of exacerbations, and presence of comorbidities (e.g., sleep apnea, diabetes, hypertension).Pulmonary Function Tests: Spirometry was performed to measure FEV1, FVC, and FEV1/FVC ratio, with severity graded according to GOLD guidelines. Echocardiography: All participants underwent transthoracic echocardiography to estimate right ventricular systolic pressure (RVSP). PH was defined as an RVSP > 25 mmHg. Oxygen Saturation: Measured using pulse oximetry to assess resting SpO2 levels.

Ethical Considerations- The study was approved by the Institutional Ethics Committee of the institution. Written informed consent was obtained from all participants before enrollment. Confidentiality and privacy of the participants were maintained throughout the study.

Outcome Measures

The primary outcome was the prevalence of PH among COPD patients. Secondary outcomes included the identification of significant risk factors contributing to PH development, such as severity of COPD, smoking history, BMI, and oxygen saturation levels.

Statistical Analysis

Data were analyzed using SPSS version 26.0. Mean, standard deviation, median, and interquartile ranges were used to summarize continuous variables. Categorical variables were expressed as frequencies and percentages. The proportion of COPD patients with PH was calculated. Chi-square test or Fisher’s exact test was used to assess associations between categorical variables and PH. To identify independent risk factors for PH, variables with a p-value < 0.05 in univariate analysis were included in the model. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were reported.

Table 1: Baseline Characteristics of the Study Population

As per table 1 the mean age of the study population was 61.4 ± 9.8 years, indicating that COPD and associated complications like pulmonary hypertension (PH) are predominantly observed in older adults. There was a male predominance (70%), which aligns with the higher prevalence of smoking and occupational exposure to pollutants among males in many populations. A significant proportion of the patients (85%) had a history of smoking, highlighting its crucial role as a primary risk factor for developing COPD and potentially PH. The average duration of COPD was 10.2 ± 3.6 years, reflecting the chronic progression of the disease and its long-term impact on pulmonary and cardiovascular health. The mean BMI was 24.1 ± 4.3 kg/m², suggesting that most patients were in the normal to slightly overweight category. This is relevant since both underweight and obesity can influence the severity and outcomes of COPD. These baseline characteristics emphasize the need for targeted interventions focusing on smoking cessation, regular monitoring of COPD progression, and lifestyle management to mitigate the risks associated with PH development.

Table 2: Prevalence of Pulmonary Hypertension (PH)

 As per table 2 Pulmonary Hypertension (PH) was prevalent in 38% of the COPD patients, indicating that PH is a common complication in individuals with COPD. Among the 76 patients with PH: Mild PH was the most frequent category, observed in 17% of the total study population. Moderate PH was noted in 14%. Severe PH accounted for 7%, representing the smallest but clinically significant subset. The higher proportion of mild and moderate cases suggests that PH is often detected at earlier stages in COPD patients, possibly due to routine echocardiographic evaluations. Severe PH, though less common, represents a critical subset requiring aggressive management due to its association with poorer outcomes. The prevalence of PH highlights the importance of regular screening for early detection, particularly in COPD patients with advanced disease or frequent exacerbations. Early identification and management of mild to moderate PH could potentially slow the progression to severe PH and improve the quality of life and prognosis for COPD patients.

Table 3: Risk Factors Associated with Pulmonary Hypertension

As per table 3 Severe airflow limitation was prevalent in 62% of the PH group, with a statistically significant association (p < 0.001) and an odds ratio of 3.2. This indicates that patients with severe airflow limitation are over three times more likely to develop PH, underscoring its critical role as a major contributing factor. Chronic hypoxemia was the most prevalent risk factor, present in 74% of the PH group, with a highly significant association (p < 0.001) and an odds ratio of 4.5. Patients with chronic hypoxemia are nearly 4.5 times more likely to develop PH, emphasizing the need for early detection and oxygen therapy to mitigate this risk. A smoking history exceeding 20 pack-years was noted in 88% of the PH group, showing a strong association (p < 0.01) with an odds ratio of 2.1. This highlights smoking as a crucial modifiable risk factor, further supporting the importance of smoking cessation programs for COPD patients. Frequent exacerbations were observed in 58% of the PH group, with a significant association (p < 0.01) and an odds ratio of 1.8. This suggests that recurrent exacerbations may exacerbate pulmonary vascular changes, increasing the risk of PH. Advanced age was seen in 40% of the PH group, with a significant but relatively weaker association (p = 0.03) and an odds ratio of 1.5. Older age likely contributes to PH development through cumulative lung damage and comorbidities. The strong association of chronic hypoxemia and severe airflow limitation with PH highlights the need for aggressive management of these conditions in COPD patients. Smoking cessation, managing exacerbations, and proactive care for older patients are essential to reduce the risk of PH and its progression.

Table 4: Echocardiographic Parameters in COPD Patients

As per table 4 The mean PASP was significantly higher in the PH group (46.8 ± 10.5 mmHg) compared to the non-PH group (24.1 ± 6.8 mmHg) with a p-value < 0.001. This confirms that elevated PASP is a hallmark of pulmonary hypertension in COPD patients, aiding in the diagnosis and severity assessment. The RV diameter was significantly increased in the PH group (36.2 ± 4.1 mm) compared to the non-PH group (29.8 ± 3.7 mm) with a p-value < 0.001. This suggests that right ventricular remodeling and hypertrophy are common in COPD patients with PH due to increased pulmonary vascular resistance. The mean TRV was notably higher in the PH group (3.4 ± 0.5 m/s) than in the non-PH group (2.6 ± 0.3 m/s) with a p-value < 0.001. Elevated TRV reflects increased right heart pressures and serves as a non-invasive marker for diagnosing PH. All three echocardiographic parameters (PASP, RV diameter, and TRV) showed statistically significant differences, reinforcing their utility in distinguishing between COPD patients with and without PH. Regular echocardiographic evaluation is critical for early detection of PH in COPD patients. Identifying elevated PASP, increased RV diameter, and higher TRV can guide timely intervention to prevent disease progression and associated complications. The findings underscore the impact of chronic hypoxia and increased vascular resistance in causing right ventricular remodeling and elevated pulmonary pressures in COPD-associated PH.

This study comprehensively analyzed the prevalence, risk factors, and echocardiographic findings of pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) patients. The findings provide valuable insights into the interplay between COPD and PH, emphasizing the clinical burden and management implications of this comorbidity.

Our study found a 38% prevalence of PH among COPD patients. This is within the range reported in prior research. For instance, Chaouat et al. (2005) observed PH prevalence between 30–50% in patients with moderate-to-severe COPD.^[1] Similarly, Zielinski (1995) highlighted that PH is common even in mild COPD due to the interplay of chronic hypoxia and vascular remodeling. ^[2]

The distribution of PH severity in our study showed a higher proportion of mild to moderate cases (31% combined) compared to severe PH (7%). This aligns with findings from Sørensen et al. (2010), who noted that severe PH is less frequent but associated with worse clinical outcomes. The relatively higher prevalence of mild PH may also reflect increased diagnostic sensitivity due to routine echocardiographic screening in COPD patients.^[13]

This distribution underscores the importance of early detection and intervention, as PH often progresses insidiously, contributing to increased mortality. Chaouat et al. (2005) emphasized that even mild elevations in pulmonary pressures can predict poor outcomes, reinforcing the need for vigilance in COPD management. ^[1]

In our study, 62% of PH cases had severe airflow limitation, with an odds ratio (OR) of 3.2. This finding aligns with Thabut et al. (2005), who demonstrated that advanced airflow obstruction is a major contributor to PH development. Severe airflow limitation leads to persistent alveolar hypoxia, triggering pulmonary vasoconstriction, vascular remodeling, and increased vascular resistance.^[3] The GOLD Initiative (2021) also emphasizes that worsening airflow limitation correlates with increased pulmonary vascular pressures, independent of hypoxia. This suggests that addressing airflow obstruction with optimized pharmacotherapy and rehabilitation is crucial in PH prevention.

Chronic hypoxemia was the strongest predictor of PH in our study, present in 74% of cases (OR 4.5). Hypoxemia induces pulmonary vasoconstriction and structural changes in the pulmonary vasculature, a mechanism well-documented in studies like Oswald-Mammosser et al. (1995)^[4] and Peinado et al. (2008) ^[5] The latter study showed that sustained hypoxia causes endothelial dysfunction, promoting smooth muscle proliferation and intimal fibrosis, which contribute to PH.

Long-term oxygen therapy (LTOT) has been shown to mitigate these effects. The Nocturnal Oxygen Therapy Trial (1980) [6] and The Medical Research Council Trial (1981)^[7] demonstrated that LTOT reduces mortality and slows PH progression in COPD patients. A smoking history exceeding 20 pack-years was observed in 88% of PH cases (OR 2.1). Smoking contributes to endothelial damage, oxidative stress, and inflammation, which are critical in COPD and PH pathogenesis. Morbini et al. (2006)^[8] highlighted that smoking-induced endothelial injury leads to structural and functional pulmonary vascular changes, even in the absence of hypoxemia. Smoking cessation is paramount, as demonstrated in studies like Tashkin et al. (1996), which showed significant improvements in lung function and reduced vascular inflammation among ex-smokers.^[9]

 Frequent exacerbations were reported in 58% of PH cases (OR 1.8). Exacerbations accelerate hypoxemia, systemic inflammation, and vascular injury, creating a feedback loop that worsens PH. Cabrera López et al. (2016) emphasized that patients with frequent exacerbations have a higher risk of PH and worse survival outcomes. Preventive strategies, including influenza and pneumococcal vaccination and timely use of maintenance therapy, can reduce exacerbation rates and PH progression. ^[10]

 Advanced age was seen in 40% of PH cases (OR 1.5). Aging contributes to reduced pulmonary vascular compliance, increased stiffness, and higher vascular resistance. Studies like Hurd et al. (2000)^[11] and Naeije et al. (2017) underscore that older COPD patients are more vulnerable to developing PH due to cumulative lung damage and comorbidities.^[12]

The mean PASP in the PH group (46.8 ± 10.5 mmHg) was significantly higher than in the non-PH group (24.1 ± 6.8 mmHg, p < 0.001). This finding is consistent with Sørensen et al. (2010), who demonstrated that elevated PASP is a reliable marker for PH diagnosis. Elevated PASP reflects increased vascular resistance due to chronic hypoxia, and its measurement through echocardiography provides a non-invasive diagnostic tool. [13] D’Alonzo et al. (1991) showed that PASP > 40 mmHg is associated with increased mortality in PH patients, emphasizing the prognostic significance of this parameter. ^[14]

The RV diameter was significantly larger in the PH group (36.2 ± 4.1 mm) than in the non-PH group (29.8 ± 3.7 mm, p < 0.001). This finding reflects right ventricular hypertrophy and dilation, common in chronic PH due to sustained pressure overload. McGoon et al. (2009) reported similar findings, linking RV remodeling to adverse outcomes in PH patients. Early detection of RV changes through echocardiography is crucial for initiating timely interventions. ^[15]

Elevated TRV in the PH group (3.4 ± 0.5 m/s) compared to the non-PH group (2.6 ± 0.3 m/s, p < 0.001) underscores its diagnostic importance. Chemla et al. (2004) demonstrated that TRV correlates strongly with PASP and serves as a surrogate marker for PH severity.^[16] Regular echocardiographic screening, particularly for high-risk COPD patients, can facilitate early PH detection. Timely identification of elevated PASP, RV dilation, and TRV abnormalities can prompt early interventions, reducing morbidity and mortality.

Addressing chronic hypoxemia with LTOT, optimizing airflow limitation with bronchodilators, and implementing smoking cessation programs are critical strategies. As noted by Celli et al. (2004) ^[17], reducing exacerbation frequency and improving lung function can significantly delay PH progression. Further studies exploring biomarkers such as NT-proBNP and advanced imaging techniques like cardiac MRI could improve diagnostic accuracy and risk stratification in COPD-associated PH. Genetic predisposition studies, such as those by Gao et al. (2012), may also provide insights into individualized treatment approaches.^[18]

The high prevalence of PH in COPD underscores its clinical significance. Risk factors such as chronic hypoxemia, severe airflow limitation, and smoking highlight the need for proactive management. Echocardiographic parameters (PASP, RV diameter, and TRV) are indispensable in diagnosis and monitoring. Early interventions targeting modifiable risk factors can improve outcomes and reduce the burden of PH in COPD patients.

1. Chaouat A, Naeije R, Weitzenblum E. Pulmonary hypertension in COPD. Eur Respir J. 2005;21(5):892–905.
2. Zielinski J. Effects of hypoxia and other respiratory disturbances on pulmonary hypertension. Int J Tuberc Lung Dis. 1995;76(2):101–5.
3. Thabut G, Dauriat G, Stern JB, Logeart D, Levy A, Marrash-Chahla R, et al. Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation. 2005;127(5):1531–6.
4. Oswald-Mammosser M, Weitzenblum E, Quoix E, Moser G, Hirth C, Kessler R. Pulmonary hemodynamics in chronic obstructive pulmonary disease. Eur Respir J. 1995;8(3):339–45.
5. Peinado VI, Gómez FP, Barberà JA. Pulmonary vascular involvement in COPD. 2008;134(4):808–14.
6. The Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: A clinical trial. Ann Intern Med. 1980;93(3):391–8.
7. Medical Research Council Working Party. Long-term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. 1981;1(8222):681–6.
8. Morbini P, Inghilleri S, Bertolini V, Pigini P, Zorzetto M, Luisetti M, et al. The role of oxidative stress in pulmonary hypertension of smokers and COPD patients. Respir Res. 2006;7(1):1–7.
9. Tashkin DP, Simmons MS, Chang P. Effects of smoking cessation on lung function in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1996;153(3):893–901.
10. Cabrera López C, Casanova Macario C, Marín Trigo JM, Miravitlles M, de Torres JP, Cosio BG. Determinants of severe exacerbations in patients with chronic obstructive pulmonary disease. PLOS One. 2016;11(6):e0157374.
11. Hurd SS. The impact of COPD on lung health worldwide: Epidemiology and incidence. 2000;117(2 Suppl):1S–4S.
12. Naeije R, Vanderpool R, Dhakal BP, Saggar R, Saggar R, Vachiéry JL, et al. Aging and the pulmonary circulation: Physiology and pathophysiology. J Am Coll Cardiol. 2017;70(6):756–67.
13. Sørensen TJ, Hilde JM, Svendsen O, Steine K, Holm AM. Prevalence and prognosis of pulmonary hypertension in patients with COPD. Respir Med. 2010;104(7):1024–31.
14. D’Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, et al. Survival in patients with primary pulmonary hypertension: Results from a national prospective registry. Ann Intern Med. 1991;115(5):343–9.
15. McGoon MD, Krichman A, Farber HW, Barst RJ, Raskob GE, Liou TG, et al. Design of the REVEAL registry for US patients with pulmonary arterial hypertension. Mayo Clin Proc. 2009;84(11):923–31.
16. Chemla D, Humbert M, Sitbon O, Montani D, Hervé P, Simonneau G. Systolic pulmonary artery pressure measured at echocardiography as a prognostic factor in pulmonary arterial hypertension. 2004;126(4):1295–301.
17. Celli BR, MacNee W, Agusti A, Anzueto A, Berg B, Buist AS, et al. Standards for the diagnosis and treatment of patients with COPD: A summary of the ATS/ERS position paper. Eur Respir J. 2004;23(6):932–46.
18. Gao L, Holden V, DiSilvestre D, Tiziani S, Surapaneni S, Halperin J, et al. Genetic predisposition to pulmonary vascular remodeling in COPD. Am J Respir Crit Care Med. 2012;186(8):784–90.