European Journal of Cardiovascular Medicine

Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disorder with a high morbidity and mortality rate, characterized by not fully reversible airflow restriction.^1,2 COPD is not a disorder limited to the lungs and it proceeds with extrapulmonary comorbidities due to systemic inflammation. Among these, cardiovascular diseases (CVDs) are the most frequently encountered disorders, also contributing to mortality rates in COPD.³ The publications related to the association of these two disorders are limited, and the information available is not clear. The leading cause of cardiac comorbidity frequently observed in COPD may be shared risk factors such as smoking, advanced age, and sedentary lifestyle. Another mechanism is the development of systemic inflammatory response due to the release of acute phase reactants such as C-reactive protein (CRP), fibrinogen, serum amyloid A, surfactant protein D, and leucocytes following local inflammation in the airway and vascular lumen.^3,4 Cor pulmonale, coronary artery disease, and heart failure, which are the frequently seen comorbidities, are considered as components of a systemic inflammatory syndrome, affecting the morbidity and mortality.^5,6 Some of the proinflammatory cytokines reported to be playing a key role in systemic inflammation in both diseases are interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), chemokines, IL-8, Clara cell protein (CCL-16), and leukotriene B4 (LTB4).^3,4 Especially CRP is an important acute phase reactant in COPD exacerbations and also associated with mortality due to CVDs and cancer comorbidities in COPD.^7,8 IL-8 (CXCL8) is a chemokine effective in the accumulation of neutrophils and monocytes in COPD patients.³ CCL-16 is known to be related to inflammation rather than the pathogenesis of COPD; however, the relationships of IL-8 and CCL-16 with COPD and CVD have not been clearly identified.⁹

Brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are the natriuretic hormones formed by fragmentation of 108-amino acid prohormone proBNP into two pieces, released from cardiac myocytes, and used in diagnosing acute decompensated cardiac failure, risk stratification, and management.

The plasma half-life of NT-proBNP, the inactive form, is longer than BNP; therefore, its quantification in blood is easier. Natriuretic peptides increase in COPD patients with cardiac failure. These peptides are known to be released from the right heart particularly in pulmonary hypertension and cor pulmonale, due to hypoxemia and chronic inflammation.^7,10 However, knowledge related to the BNP levels in COPD patients without any known heart failure is limited.

Fetuin-A is a human plasma protein, which is released from the liver, has a weight of 60 kDa, and is known as an inhibitor of systemic inflammation. Fetuin-A increases the cellular uptake of cationic inhibitors of proinflammatory cytokine synthesis and inhibits the insulin receptor auto phosphorylation and tyrosine kinase activity. The associations of low fetuin-A levels with COPD and atherosclerosis have been recently investigated. In various studies, it has been shown that low fetuin-A levels were associated with the presence of coronary artery disease and was an independent predictor of the mortality following myocardial infarct.^11,12

The aim of the present study was to determine the frequency of left ventricular dysfunction in patient with chronic obstructive pulmonary disease.

A prospective observational study was conducted in which all eligible indoor and outdoor male and female patients above 40 years of age participated after meeting the inclusion and exclusion criteria from 1st May 2023 to 30 Nov 2024. A total of 151 individuals diagnosed with COPD were enrolled as cases in this hospital-based study. These patients reported to the Department of General Medicine and Respiratory Medicine at the National Institute of Medical Sciences & Research & Hospital, Jaipur, Rajasthan. Written consent was obtained from all participants prior to their inclusion in the study. The severity of COPD was assessed at the time of admission using the GOLD criteria.

Study population: All diagnosed cases of COPD, above the age of 35 years including males and females in the stipulated time period considering the inclusion and exclusion criteria.

INCLUSION CRITERIA

1. Age Above 35 years.
2. Patients diagnosed with symptoms and confirmed by radiographic and pulmonary function test
3. Willing to participate in the study

EXCLUSION CRITERIA

Patient with: -

1. Hypertension, coronary artery disease, Arrythmias, valvular or congenital heart disease.
2. Chronic lung disease like asthma, Interstitial lung disease and pulmonary tuberculosis.
3. Chronic kidney disease.
4. Diabetes, Hypothyroidism.
5. History of malignancy.

The following data were recorded for each COPD patient:

• 2D echocardiogram results
• Pulmonary function test findings
• Chest X-ray findings
• Demographic and clinical information, including age, sex, history of diabetes, hypertension, and smoking
• Biochemical profile, including complete blood counts, blood sugar levels (random), liver function tests, renal function tests, and serum electrolytes

All information was documented on a pre-designed proforma. After data collection, statistical analysis was performed using the licensed version of Statistical Package for Social Science (SPSS-25) or Microsoft Excel.

Table 1: Baseline demographic characteristics of Study participants

The distribution of sex was nearly equal, with 49.7% males and 50.3% females. Most participants were Hindu (57.0%), followed by Muslims (31.1%) and Sikhs (11.9%). Regarding occupation, teachers formed the largest group (25.2%), followed by unemployed individuals (21.9%) and shopkeepers (21.2%). A larger proportion of the study population resided in urban areas (57.0%) compared to rural regions (43.0%). BMI categorization revealed that 45.0% of participants were of normal weight, while a considerable proportion were overweight (21.2%) or obese (20.5%). Underweight individuals constituted 13.2% of the population. Smoking was reported in 52.3% of participants, whereas 47.7% were ex-smokers. Clinically, shortness of breath was the most common presenting complaint (52.3%), followed closely by cough (47.7%). In terms of family history, 35.8% reported a history of COPD, 30.5% reported a family history of heart disease, and 33.8% had no relevant family history. According to GOLD staging, 37.7% had moderate COPD, while 32.5% had severe and 29.8% had mild COPD, reflecting an even distribution across severity grades.

Table 2: Association of Clinical and Radiological Variables with COPD Severity (GOLD Stage)

No statistically significant differences were observed in pulse rate (p=0.266), respiratory rate (p=0.913), systolic BP (p=0.286), diastolic BP (p=0.342), or pulse oximetry (p=0.276) across COPD stages. The values for these parameters remained consistent across all three groups, suggesting similar hemodynamic and respiratory baseline characteristics despite differing spirometric severity. CNS, CVS, and GIT examination findings were reported as normal in all patients, with no abnormalities noted in any group, and hence were not subjected to statistical testing. In contrast, a significant association was observed in respiratory system examination (p=0.021). Ronchi was more frequently detected in mild and moderate COPD (66.7% each), while wheezing was predominant in severe COPD cases (57.1%). Additionally, chest radiograph (CXR) findings showed a statistically significant variation (p=0.027). Hyperinflated lungs were more commonly noted in moderate COPD (59.6%), whereas consolidation was observed predominantly in mild (62.2%) and severe COPD (63.3%) groups. These radiological changes may reflect underlying pathophysiological differences in disease presentation across the GOLD stages.

Table 3: Comparison of Laboratory Parameters across GOLD Stages of COPD

Hemoglobin levels showed a statistically significant decline with increasing COPD severity (p<0.001), with the highest mean observed in mild COPD (13.22 ± 0.48 g/dL) and the lowest in severe COPD (9.88 ± 0.62 g/dL). Total leukocyte count (TLC) progressively increased from mild to severe stages (8043.25 to 9736.12 cells/mm³, p<0.001), indicating escalating inflammatory activity. Liver enzymes SGOT and SGPT were also significantly elevated in severe COPD (44.09 ± 8.97 U/L and 49.83 ± 11.10 U/L, respectively), compared to mild cases (21.76 ± 7.23 U/L and 22.74 ± 9.08 U/L), with both showing p-values <0.001. Similarly, serum bilirubin, blood urea, and creatinine levels were significantly higher in the severe group, with creatinine rising from 0.83 ± 0.19 mg/dL in mild to 1.43 ± 0.27 mg/dL in severe COPD (p<0.001), reflecting worsening systemic involvement. In contrast, random blood sugar levels did not differ significantly across the groups (p=0.374). A significant association was observed in the distribution of DLC categories (p=0.001). Elevated neutrophils were most common in moderate COPD (33.3%), while high neutrophil counts and low lymphocyte levels were more frequently observed in severe COPD (20.4% and 26.5%, respectively). Normal DLC patterns were most prominent in mild COPD (31.1%), while slightly high lymphocytes appeared more frequently in mild and moderate stages. These findings suggest a progressive shift in inflammatory cell profiles with advancing disease.

Table 4: Pulmonary Function Test Parameters across GOLD Stages of COPD

All three key spirometric indicators—FEV1 (%), FVC (%), and FEV1/FVC ratio—showed highly significant differences across disease severity (p<0.001 for all). FEV1% demonstrated a marked decline from mild (89.25 ± 5.74) to moderate (64.61 ± 8.43) and further to severe COPD (40.13 ± 5.57), reflecting progressive airflow limitation. Similarly, FVC% decreased from 90.53 ± 5.55 in mild cases to 60.61 ± 5.19 in severe cases. The FEV1/FVC ratio, a hallmark marker for obstructive pathology, also declined consistently with severity, dropping from 0.75 ± 0.03 in mild COPD to 0.54 ± 0.02 in severe COPD. These findings align with GOLD classification criteria and confirm the worsening pulmonary function with advancing COPD stages. The results establish a strong spirometric gradient that corresponds with the clinical categorization of COPD severity.

Table 5: Comparison of 2D-ECHO Parameters across GOLD Stages of COPD

A statistically significant difference was observed in both ejection fraction and E/A ratio across the severity groups. The mean ejection fraction increased progressively from 49.55 ± 12.17% in mild COPD to 52.48 ± 11.15% in severe COPD (p = 0.041), suggesting a subtle compensatory enhancement or relative preservation of systolic function in more advanced stages. Similarly, the E/A ratio, a surrogate marker of diastolic function, demonstrated a modest yet statistically significant variation across the groups (p = 0.049). Although the mean values were closely spaced—1.30 ± 0.64 in mild, 1.32 ± 0.68 in moderate, and 1.28 ± 0.72 in severe COPD—the significance implies early stage-dependent diastolic alterations. These findings highlight that even conventional 2D-ECHO parameters, such as ejection fraction and E/A ratio, can exhibit measurable differences with advancing COPD severity, thereby reinforcing the importance of routine cardiac assessment in these patients.

Table 6: Association of Left Ventricular Systolic and Diastolic Dysfunction with GOLD Stages of COPD

A statistically significant difference was observed across the GOLD stages (p = 0.021), indicating that the prevalence of LV dysfunction varied meaningfully with COPD severity. LV dysfunction was present in more than half of the patients overall (54.3%), with the highest proportions observed in mild (60.0%) and severe (59.2%) COPD groups, and a comparatively lower frequency in the moderate group (45.6%). Conversely, the absence of LV dysfunction was most common in moderate COPD (54.4%). These findings suggest that LV dysfunction is not uniformly progressive across GOLD stages but does exhibit significant distributional differences. This underscores the need to consider both systolic and diastolic function during the routine evaluation of COPD patients, as cardiac impairment may evolve independently or disproportionately relative to spirometric classification.

Chronic Obstructive Pulmonary Disease, a very common disease, and it is the 4th leading cause of death in worldwide. In India, it is the 2nd most common lung disorder after pulmonary tuberculosis. It is one of the preventable and treatable disease. Smoking and air pollution are the main risk factors.¹³ COPD is a systemic disease, because inflammation is not only involved in lung airways, but also seen in systemically. So, COPD is associated with variety of extra pulmonary manifestations.¹⁴ Among COPD patients, cardiovascular disease is responsible for 50% of hospitalization and 20% of deaths. Inflammation is one of the systemic manifestations of COPD and provides a hypothesis to explain the relationship between cardiovascular risk and airflow limitation.¹⁵

Pulmonary function parameters, including FEV1, FVC, and FEV1/FVC ratio, declined significantly with increasing COPD severity (p < 0.001). These spirometric trends are consistent with the GOLD classification criteria and findings by Gupta et al., who noted that FEV1 and FEV1/FVC ratios are crucial for evaluating disease progression in COPD patients and strongly correlate with clinical severity.¹⁶ Significantly elevated leukocyte counts and altered differential leukocyte patterns (notably increased neutrophils and reduced lymphocytes) were noted in moderate and severe COPD, reflecting heightened systemic inflammation. This trend mirrors previous reports suggesting that inflammation extends beyond the lungs and plays a role in the progression of extrapulmonary comorbidities in COPD.¹⁵

Biochemical markers such as bilirubin, SGOT, SGPT, blood urea, and creatinine were significantly deranged in patients with higher GOLD stage COPD. These abnormalities may be attributed to chronic hypoxemia, systemic oxidative stress, and reduced perfusion, which compromise organ function. Kraiczi et al. similarly reported associations between oxygen desaturation and impaired vascular/end-organ function in chronic respiratory disease.¹⁷ Radiological findings also demonstrated significant variation with disease severity. Hyperinflated lungs were most frequently observed in moderate COPD, while consolidation was more common in mild and severe groups. Caram et al. previously reported that radiological patterns may reflect underlying mechanical or infectious complications that influence cardiac load and diastolic function.¹⁸

Importantly, the present study demonstrated a statistically significant association between GOLD stages and echocardiographic parameters, specifically the presence of LV systolic and diastolic dysfunction (p = 0.021). These findings align with those reported by Mohammed RA et al¹⁷ and Kannan and Ahmed²⁰, who found a progressive increase in diastolic dysfunction with advancing COPD stages. The findings emphasize the need for early cardiovascular evaluation in COPD patients, especially those in moderate to severe GOLD stages. Incorporating echocardiographic screening into routine COPD assessments could help identify cardiac dysfunction early and potentially improve long-term outcomes.

Limitations and Strengths

This study offers valuable insights into the cardiopulmonary interplay in COPD by comprehensively evaluating clinical, radiological, biochemical, pulmonary, and echocardiographic parameters across disease severities. One of its major strengths lies in the inclusion of both continuous and categorical cardiac measures, such as ejection fraction, E/A ratio, and LV dysfunction status, which allows for a nuanced understanding of cardiac involvement in COPD. The use of objective diagnostic tools like spirometry and 2D-ECHO enhances the clinical validity of the findings. Additionally, the balanced representation of patients across GOLD stages ensures appropriate subgroup comparisons.

However, the study also has several limitations. As a cross-sectional analysis conducted at a single center, causal inferences regarding the progression of cardiac dysfunction with COPD severity cannot be established. The exclusion of patients with known cardiovascular diseases may have underestimated the true burden of LV dysfunction in real-world COPD populations. Furthermore, the study relied solely on standard 2D-ECHO without advanced modalities such as tissue Doppler imaging or cardiac MRI, which may have detected more subtle functional abnormalities. Despite these limitations, the findings contribute meaningfully to the growing evidence of cardiovascular alterations in COPD and underscore the importance of integrated cardiopulmonary assessment in clinical practice

This study highlighted the intricate relationship between chronic obstructive pulmonary disease (COPD) severity and cardiac function. Through a comprehensive assessment of clinical, biochemical, radiological, pulmonary, and echocardiographic parameters across GOLD- defined COPD stages, it was observed that systemic and cardiac involvement becomes more pronounced with advancing disease. Key laboratory markers, including hemoglobin, TLC, liver and renal function tests, and differential leukocyte count, demonstrated significant deterioration in higher COPD stages, reflecting systemic inflammation and hypoxic burden.

Pulmonary function tests showed a clear and expected decline in FEV1, FVC, and FEV1/FVC ratio with increasing severity, validating spirometry as a robust tool for COPD classification. Importantly, echocardiographic evaluation revealed significant associations between disease severity and both systolic and diastolic function, as evidenced by variations in ejection fraction, E/A ratio, and prevalence of left ventricular dysfunction. These findings support the growing recognition of cardiovascular comorbidity in COPD, even in the absence of overt heart disease.

The study underscores the importance of integrating routine cardiac screening—particularly echocardiography—into the clinical management of COPD patients. Early identification of subclinical cardiac dysfunction may enable timely intervention and improve patient outcomes in this high-risk population.

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