European Journal of Cardiovascular Medicine

Chronic obstructive pulmonary disease (COPD) remains a major contributor to global morbidity and mortality. The World Health Organization (WHO) estimates that approximately 65 million individuals suffer from moderate to severe COPD, and over 3 million people succumbed to the disease in 2005, accounting for about 5% of global deaths. It is projected to become the third leading cause of death worldwide by 2030 (1). While much of the existing epidemiological data on COPD originates from high-income nations, an estimated 90% of COPD-related deaths now occur in low- and middle-income countries (2,3).

In India, the burden of COPD is considerable, yet accurate prevalence data are difficult to obtain due to the country's large and heterogeneous population. Current evidence suggests an estimated national prevalence of approximately 5% among adults, with significantly higher rates observed in men, smokers, rural populations, and those exposed to biomass fuel (4). Prevalence increases with age, from 2.6% in adults aged 18–34 years to 12.3% in those aged 75 years and above (5). Despite its high prevalence, many individuals with reduced pulmonary function remain undiagnosed, suggesting that the true burden may be underestimated (6).

Cardiovascular diseases, particularly heart failure (HF), are common comorbidities in COPD patients. Studies have reported that the prevalence of chronic heart failure in elderly individuals with COPD ranges between 10% and 46%, depending on the population studied and diagnostic methods used (7,8). Heart failure is especially prevalent among COPD patients presenting with dyspnoea, complicating the clinical diagnosis, as symptoms often overlap (9).

Distinguishing between COPD exacerbation and decompensated heart failure poses a diagnostic challenge for clinicians. While signs such as dyspnoea, cough, and fatigue are commonly attributed to COPD exacerbations, they may also signal underlying cardiac dysfunction (10,11). Consequently, biomarkers such as B-type natriuretic peptide (BNP) and its inactive cleavage product, N-terminal pro-BNP (NT-pro-BNP), have garnered attention for their utility in differentiating cardiac from pulmonary causes of dyspnoea.

This study aims to evaluate serum NT-pro-BNP concentrations in patients presenting with AECOPD, comparing levels in those with and without concurrent LVF, and to explore its potential role in assessing disease severity.

Study Design

This study was conducted as a hospital-based, prospective observational investigation to evaluate serum NT-pro-BNP levels in elderly patients presenting with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), with or without concurrent left ventricular failure (LVF).

Study Setting and Duration

The research was carried out in the internal medicine wards of SMS Hospital, Jaipur. Patient recruitment and data collection were conducted over a period of one year, with an additional two months allocated for data analysis.

Sample Size

The required sample size was calculated based on previous literature, aiming to detect a minimum difference in FEV₁/FVC values of 17.9 (24.4) with a standard deviation of 10.5 (15.5), assuming 80% statistical power and an alpha error of 0.05. Accordingly, 40 participants were enrolled in each group (cases and controls), totaling 80 patients.

Participant Selection

Patients aged 60 years and above who were admitted with AECOPD were screened for eligibility. Those meeting the inclusion criteria and providing informed consent were enrolled in the study. The presence or absence of LVF was determined by transthoracic echocardiography (2D Echo), and patients were categorized accordingly.

Inclusion Criteria

1. Age ≥ 60 years.
2. Confirmed diagnosis of COPD based on spirometry (post-bronchodilator FEV₁/FVC ratio < 70%).
3. Presence of LVF confirmed through echocardiographic evaluation.

Exclusion Criteria

• Age < 60 years.
• Renal impairment (serum creatinine > 2.8 mg/dL).
• Acute myocardial infarction.
• Cardiogenic shock or significant valvular heart disease.
• Sepsis (pyaemia) or severe hepatic/endocrine disorders.
• Radiological evidence of pneumothorax or pneumonia on chest X-ray.

Data Collection Procedure

After obtaining approval from the Institutional Ethics Committee and written informed consent from participants, clinical and laboratory evaluations were performed for each subject.

The following assessments were conducted:

• Clinical Evaluation: Comprehensive medical history and physical examination.
• Laboratory Tests: Hemoglobin, random blood sugar, renal and liver function tests, viral markers.
• Pulmonary Function Testing (PFT): For confirmation and classification of COPD.
• Serum NT-pro-BNP: Quantified from venous blood samples.
• Imaging and Cardiac Assessment:
• Chest radiography to rule out alternative diagnoses such as pneumonia or pneumothorax.
• 2D echocardiography to assess left ventricular function and confirm heart failure.

Statistical Analysis

All data were entered into Microsoft Excel and subsequently analyzed using appropriate statistical software. Descriptive statistics were used for both qualitative and quantitative variables. Categorical data were expressed as percentages and compared using the Chi-square test. Continuous variables were summarized using mean and standard deviation (SD), and analyzed with the student’s t-test for intergroup comparison. Pearson’s correlation coefficient was employed to evaluate the relationship between NT-pro-BNP levels and other continuous variables. A p-value of < 0.05 was considered statistically significant, while < 0.01 was considered highly significant.

Demographic Distribution (Table 1)

Interpretation:
Both groups had comparable age distributions, with the majority in the 61–65 age range. The mean ages were almost identical, and the difference was statistically non-significant (p = 0.9882), indicating age-matched groups. (Table 1)

NT-pro-BNP Levels (Table 2)

Interpretation:
A highly significant elevation in NT-pro-BNP levels was observed among cases compared to controls (p < 0.0001), indicating a strong association between elevated NT-pro-BNP and acute exacerbation of COPD (AECOPD) with possible cardiac involvement. (Table 2)

Pulmonary Function Test (PFT) Distribution (Table 3)

Interpretation:
A higher proportion of cases (57.5%) demonstrated severe pulmonary restriction compared to controls (37.5%). However, the difference in severity between groups was not statistically significant (p = 0.1458). (Table 3)

Association of NT-pro-BNP with COPD Severity (Table 9)

Interpretation:
Most patients in both NT-pro-BNP groups were in GOLD stage 2, indicating moderate COPD. A smaller proportion of patients with high NT-pro-BNP were in GOLD 3. No cases were observed in mild or very severe stages. This suggests that even in moderate COPD, NT-pro-BNP may be elevated due to underlying cardiac dysfunction. (Table 4)

This study aimed to evaluate the clinical utility of NT-pro-BNP levels in elderly patients presenting with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), particularly in those with concurrent left ventricular failure (LVF). The findings suggest that NT-pro-BNP is a valuable biomarker for differentiating cardiac involvement and stratifying disease severity among COPD patients.

In our study, the mean age of the case group was 66.1 years, with most participants between 61–65 years, and no significant age difference was observed between those with normal and elevated NT-pro-BNP levels. These findings are consistent with previous studies by Adrish et al. and Li et al., who also reported no significant association between age and NT-pro-BNP levels in patients with COPD and coexisting heart failure (1,2).

Gender distribution showed a male predominance in both groups. Notably, all patients with normal NT-pro-BNP were male, whereas 35% of those with elevated levels were female. Similar trends have been reported by Li et al. and Adrish et al., who found male predominance in both low and high NT-pro-BNP groups, albeit without statistical significance (1,2).

Biochemical analysis revealed significantly lower hemoglobin and albumin levels in patients with elevated NT-pro-BNP, consistent with findings from Adrish et al., who reported lower albumin and higher BUN levels among patients with elevated NT-pro-BNP (1). However, unlike Li et al., we did not observe a significant difference in serum creatinine levels between groups (2).

ECG and echocardiographic assessments further supported the presence of cardiac dysfunction in cases. Significant ST-segment and T-wave changes were noted among cases, along with reduced left ventricular ejection fraction (LVEF). Guo et al. also identified a substantial proportion of AECOPD patients with LVF confirmed by echocardiography, emphasizing the frequent coexistence of cardiac dysfunction in COPD (3). Similarly, Hawkins et al. demonstrated elevated NP levels among patients with left ventricular systolic dysfunction and cor pulmonale, suggesting overlap in cardiac and pulmonary pathophysiology (4).

Pulmonary function tests showed that 57.5% of cases had severe restriction, and the majority of patients with elevated NT-pro-BNP had corresponding severe impairments on spirometry. This pattern aligns with findings by Chi et al. and Watz et al., who found a positive correlation between NT-pro-BNP levels and COPD severity as defined by GOLD staging (5,6). However, Guo et al. noted that spirometric parameters did not differ significantly between AECOPD patients with or without LVF, indicating that NT-pro-BNP may reveal cardiac involvement undetectable by spirometry alone (3).

Regarding BMI, we observed no significant differences between groups. Adrish et al. similarly reported higher BMI in patients with normal NT-pro-BNP, but this was not statistically significant (1). Conversely, Li et al. found BMI to be significantly lower in patients with elevated BNP, suggesting a potential relationship between nutritional status and cardiac strain in COPD (2).

The strong association between elevated NT-pro-BNP levels and COPD exacerbation severity is highlighted by the fact that 87.88% of patients with GOLD stage 2 and 80% with stage 3 had elevated NT-pro-BNP. Similar findings were reported by Li et al., who found increased NT-pro-BNP levels in GOLD stage 2 and 3 COPD patients (2). In contrast, Adrish et al. and Watz et al. observed greater NT-pro-BNP elevation in GOLD stage 3 and 4 patients, reflecting the impact of advanced disease on cardiac function (1,6).

The significantly higher NT-pro-BNP levels observed in our case group compared to controls (13,373.8 ± 8,319.7 pg/mL vs. 1,135.15 ± 986.4 pg/mL, p < 0.0001) underscores the biomarker’s diagnostic value. These results echo those of AboEl-Magd et al., who found substantially higher NT-pro-BNP levels in stable COPD patients across all GOLD stages compared to healthy controls (7).

Our results further confirm that NT-pro-BNP is not solely elevated due to LVF. Factors such as pulmonary hypertension, right ventricular strain, hypoxia, and systemic inflammation in COPD may also contribute to increased NP levels (8–10). Moreover, some studies suggest that NT-pro-BNP levels may be elevated in COPD even in the absence of echocardiographic abnormalities, indicating subclinical cardiac dysfunction (11).

The prognostic value of NT-pro-BNP in COPD has also been explored. Rutten et al. and Steer et al. found that elevated NT-pro-BNP levels in COPD patients were independently associated with increased risk of mortality and hospital readmission, reinforcing its role in risk stratification (12,13). Furthermore, NT-pro-BNP levels correlate with the need for ICU admission and mechanical ventilation during exacerbations, as supported by Chang et al. and Kentsch et al. (14,15).

Given these findings, NT-pro-BNP appears to be a reliable marker for identifying cardiac dysfunction in AECOPD patients, facilitating timely intervention and optimizing patient outcomes.

Serum NT-pro-BNP levels are significantly elevated in elderly patients with acute exacerbation of COPD with left ventricular failure. This biomarker can aid in distinguishing cardiac involvement, assessing disease severity, and guiding timely clinical management. This study helps to determine prognosis of COPD patients. Patients with low NT Pro BNP value have better prognosis and fast recovery as compared to patients with high NT Pro BNP.

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