Chronic Obstructive Pulmonary Disease (COPD) remains one of the leading causes of morbidity and mortality worldwide, with a substantial and growing burden in low- and middle-income countries [9,16]. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) defines COPD as a heterogeneous lung condition characterized by chronic respiratory symptoms due to abnormalities of the airways and/or alveoli that cause persistent, often progressive, airflow obstruction [16]. Beyond its pulmonary manifestations, COPD is increasingly recognized as a multisystem disorder with significant extrapulmonary effects, among which cardiovascular disease (CVD) is the most clinically consequential [9,16].

The association between COPD and cardiovascular morbidity is well established [16,18]. Patients with COPD have between two and five times the risk of ischemic heart disease compared to individuals without COPD, even after adjusting for shared confounding factors such as smoking and age [9,16]. The prevalence of cardiovascular disease in COPD patients has been estimated to range from 25% to 70%, which is two to five times higher than in the general population [17,16]. This elevated risk persists across all severity levels of COPD and is particularly pronounced during and following acute exacerbations [20].

Left ventricular (LV) dysfunction represents a particularly important but often under-recognized cardiovascular comorbidity in COPD [6,8]. The spectrum of LV dysfunction encompasses both systolic dysfunction, defined as a reduction in left ventricular ejection fraction (LVEF < 50%), and diastolic dysfunction, characterized by impaired ventricular relaxation and filling despite preserved ejection fraction [2,5,7]. While the pathophysiological mechanisms linking COPD to LV dysfunction are complex and multifactorial, they include systemic inflammation, oxidative stress, hypoxemia, hypercapnia, pulmonary hypertension, and ventricular interdependence [11,16].

The true prevalence of LV dysfunction in COPD patients has been the subject of considerable investigation, with conflicting results reported across different studies [8]. A systematic review and meta-analysis reported a prevalence of undiagnosed left ventricular systolic dysfunction (LVSD) of 15.8% (95% CI: 11.1–21.1%) when defined as LVEF < 50% [8]. More recent echocardiographic studies have found diastolic dysfunction in 67.5% of COPD patients, with a significant increase from 41.2% in GOLD stage II to 92.2% in GOLD stage IV [2,5]. Similarly, a study from Pakistan reported LV systolic dysfunction in 14.1% and diastolic dysfunction in 38.8% of stable COPD patients [12].

Hypertension is a well-established risk factor for LV dysfunction and is commonly present as a comorbidity in COPD patients [16,9]. However, the prevalence and characteristics of LV dysfunction in the subset of COPD patients who are non-hypertensive have received comparatively less attention [6]. A large cohort study found that among 948 COPD patients without isolated hypertension, 38.2% had LVEF < 50% and 53.4% had LVEDD > 56 mm, highlighting that a substantial proportion of non-hypertensive COPD patients have undiagnosed cardiac abnormalities [6]. This observation raises important clinical questions: Is hypertension necessary for the development of LV dysfunction in COPD, or does COPD itself confer independent risk for cardiac impairment even in normotensive individuals?

The clinical significance of this question is substantial. If LV dysfunction occurs independently of hypertension in COPD patients, then reliance on blood pressure measurements alone as a marker of cardiovascular risk would be inadequate. Conversely, if LV dysfunction in COPD is primarily driven by coexisting hypertension, then aggressive blood pressure control might be the primary intervention needed. Understanding the true prevalence and determinants of LV dysfunction in non-hypertensive COPD patients is therefore essential for developing appropriate screening and management strategies.

In Pakistan, where COPD prevalence is high due to substantial tobacco use, biomass fuel exposure, and occupational hazards, the cardiovascular consequences of COPD represent a major public health concern [4,12]. However, data on LV dysfunction in Pakistani COPD patients, particularly in the non-hypertensive subset, remain limited [4,12]. A study from Sargodha, Pakistan, reported that heart failure prevalence increased progressively with COPD severity from 5.9% in GOLD I to 70.0% in GOLD IV, but this study did not specifically focus on non-hypertensive patients or characterize the patterns of LV dysfunction [4].

Against this background, the present study was designed to address the following research questions: (1) What is the prevalence of LV systolic and diastolic dysfunction in non-hypertensive patients with COPD? (2) Does the prevalence of LV dysfunction increase with COPD severity as measured by GOLD stage? (3) What are the independent predictors of LV dysfunction in this population? By focusing specifically on non-hypertensive patients, this study aims to isolate the independent contribution of COPD to LV dysfunction and provide evidence to guide clinical practice in the management of this high-risk population.

Study Design and Setting This was a cross-sectional analytical study conducted at the Department of Pulmonology and the Department of Cardiology, Shaikh Zayed Medical Complex and District Headquarters (DHQ) Hospital, Rahim Yar Khan, Pakistan. The study was carried out over a period of seven months, from November 2025 to May 2026. Study Population The study population comprised patients with confirmed COPD attending the pulmonology outpatient department and inpatient wards of Shaikh Zayed Medical Complex and DHQ Hospital, Rahim Yar Khan. Patients were eligible for inclusion if they met the following criteria: (1) age 40 to 75 years; (2) spirometrically confirmed diagnosis of COPD with a post-bronchodilator FEV1/FVC ratio < 0.70; (3) GOLD stage II, III, or IV; (4) absence of hypertension defined as systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg on at least two separate occasions and no history of antihypertensive medication use; and (5) clinically stable for at least four weeks prior to enrollment (no acute exacerbations, no change in medication). Patients were excluded if they had: (1) known cardiovascular disease including ischemic heart disease, heart failure, or valvular heart disease; (2) diabetes mellitus; (3) chronic kidney disease (serum creatinine > 2.0 mg/dL); (4) thyroid disorders; (5) pregnancy; (6) malignancy; (7) inability to undergo echocardiography; or (8) refusal to provide informed consent. Sample Size Calculation Sample size was calculated using the formula for estimating a single proportion. Based on previous studies reporting a prevalence of LV dysfunction in COPD patients of approximately 17%, with a desired precision of 5% and a 95% confidence level, the minimum required sample size was calculated as 217. Accounting for a 10% non-response or incomplete data rate, a total of 240 patients were approached, of whom 220 provided complete data and were included in the final analysis. Data Collection Demographic and Clinical Data: A structured proforma was used to collect demographic information including age, gender, occupation, and residence. Clinical data included smoking history (pack-years), duration of COPD, history of exacerbations in the preceding year, medication use, and symptoms using the modified Medical Research Council (mMRC) dyspnea scale. Anthropometric Measurements: Height and weight were measured using standard techniques, and body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared. Spirometry: Spirometry was performed using a portable spirometer (Cosmed Quark PFT, Italy) according to American Thoracic Society/European Respiratory Society guidelines. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio were recorded. Post-bronchodilator values were used for classification. COPD severity was classified according to GOLD criteria: GOLD II (50% ≤ FEV1 < 80% predicted), GOLD III (30% ≤ FEV1 < 50% predicted), and GOLD IV (FEV1 < 30% predicted). Echocardiography: All patients underwent comprehensive transthoracic echocardiography using a Philips EPIQ 7 ultrasound system (Philips Healthcare, Andover, MA, USA) with a 2.5–3.5 MHz phased-array transducer. Echocardiographic assessments were performed by a single experienced cardiologist who was blinded to the patients' clinical and spirometric data. Left ventricular ejection fraction (LVEF) was measured using the biplane Simpson's method. Systolic dysfunction was defined as LVEF < 50%. Left ventricular diastolic function was assessed according to the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines, evaluating the following parameters: peak early (E) and late (A) diastolic mitral inflow velocities, E/A ratio, deceleration time (DT), septal and lateral tissue Doppler velocities (e'), and E/e' ratio. Diastolic dysfunction was graded as: Grade I (impaired relaxation, E/A < 0.8), Grade II (pseudonormal, E/A 0.8–1.5 with elevated E/e' > 14), and Grade III (restrictive filling, E/A > 2 with short DT < 160 ms). Left ventricular end-diastolic diameter (LVEDD) and left atrial volume index (LAVI) were also recorded. Statistical Analysis Data were entered and analyzed using IBM SPSS Statistics version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation, and categorical variables as frequencies and percentages. The Shapiro-Wilk test was used to assess normality of continuous variables. Differences between groups were compared using independent t-tests or Mann-Whitney U tests for continuous variables and chi-square tests for categorical variables. One-way analysis of variance (ANOVA) was used to compare continuous variables across GOLD stages. Multivariate logistic regression analysis was performed to identify independent predictors of LV dysfunction (systolic and/or diastolic). Variables with p < 0.10 in univariate analysis were entered into the final model. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. A p-value < 0.05 was considered statistically significant. Ethical Considerations The study protocol was reviewed and approved by the Institutional Review Board and Ethics Committee of Shaikh Zayed Medical Complex, Rahim Yar Khan. All participants provided written informed consent after receiving detailed information about the study purpose, procedures, potential risks, and benefits. Confidentiality of patient data was maintained throughout the study. Participation was voluntary, and patients were free to withdraw at any time without affecting their medical care.

A total of 220 non-hypertensive COPD patients were enrolled in the study and completed all assessments. The demographic and clinical characteristics of the study population are presented in Table 1.

Table 1: Baseline Demographic and Clinical Characteristics of the Study Population

*Statistical significance at p < 0.05 (one-way ANOVA for continuous variables, chi-square for categorical variables).

Explanation of Table 1: The baseline characteristics of the 220 non-hypertensive COPD patients are presented stratified by GOLD stage. The mean age of the study population was 59.3 ± 8.7 years, with a significant increase in age across GOLD stages (p < 0.001), reflecting the progressive nature of the disease with advancing age. Males constituted the majority (67.3%), consistent with the higher prevalence of smoking and occupational exposures in males in this region. The mean BMI was 24.6 ± 4.2 kg/m², indicating a predominantly normal to overweight population, with no significant variation across GOLD stages. Smoking history was reported by 70.9% of patients, with a mean pack-year exposure of 28.6 ± 14.2 years; notably, pack-years increased significantly with GOLD stage (p = 0.023), suggesting a dose-response relationship between cumulative smoking exposure and disease severity. The duration of COPD also increased significantly with GOLD stage (p = 0.004), from 6.2 years in GOLD II to 9.3 years in GOLD IV, consistent with the progressive nature of the disease. Dyspnea, as measured by mMRC score ≥ 2, was present in 58.2% of patients and increased markedly with GOLD stage (p < 0.001), confirming that symptom burden escalates with disease severity. As expected, all spirometric parameters (FEV1, FVC, and FEV1/FVC ratio) showed significant progressive decline across GOLD stages (p < 0.001 for all). These baseline findings confirm that the study population represents a typical COPD cohort with progressive disease severity and highlight the importance of controlling for these factors in subsequent analyses of LV dysfunction.

Table 2: Echocardiographic Parameters and Prevalence of Left Ventricular Dysfunction

*Statistical significance at p < 0.05 (one-way ANOVA for continuous variables, chi-square for categorical variables).

Explanation of Table 2: This table presents the echocardiographic findings and the prevalence of LV dysfunction in the study population. Left ventricular systolic dysfunction, defined as LVEF < 50%, was observed in 15.9% of patients overall, with a progressive increase from 8.6% in GOLD II to 25.5% in GOLD IV (p = 0.024). The mean LVEF showed a significant decline across GOLD stages, from 60.2% in GOLD II to 53.1% in GOLD IV (p < 0.001). Structural remodeling was evident, with LVEDD increasing significantly with GOLD stage (p = 0.008), and the proportion of patients with LVEDD > 56 mm more than doubling from GOLD II (14.3%) to GOLD IV (32.7%, p = 0.038).

Diastolic dysfunction was considerably more prevalent than systolic dysfunction, affecting 64.5% of the study population. The prevalence increased dramatically across GOLD stages from 41.4% in GOLD II to 89.1% in GOLD IV (p < 0.001). The predominant pattern was Grade I diastolic dysfunction (impaired relaxation), present in 44.5% of patients, with Grade II (pseudonormal pattern) affecting 16.8% and Grade III (restrictive filling) affecting 3.2%. The E/A ratio declined significantly (p < 0.001), and the E/e' ratio increased significantly (p < 0.001) with advancing GOLD stage, indicating progressive impairment of diastolic filling and elevated left ventricular filling pressures. Left atrial volume index also increased significantly with GOLD stage (p < 0.001), reflecting chronic elevation of left ventricular filling pressures. These findings demonstrate that diastolic dysfunction is the predominant pattern of LV dysfunction in non-hypertensive COPD patients and that its prevalence and severity are strongly associated with the degree of airflow obstruction.

Table 3: Prevalence of Left Ventricular Dysfunction by GOLD Stage

Explanation of Table 3: This table summarizes the prevalence of systolic dysfunction, diastolic dysfunction, and combined LV dysfunction (systolic and/or diastolic) stratified by GOLD stage. The overall prevalence of any LV dysfunction (systolic or diastolic) was 66.8%, indicating that nearly two-thirds of non-hypertensive COPD patients have echocardiographic evidence of LV impairment. The prevalence increased markedly with GOLD stage, from 44.3% in GOLD II to 90.9% in GOLD IV. Systolic dysfunction alone affected 15.9% overall, but the pattern of LV dysfunction was predominantly diastolic, with diastolic dysfunction alone accounting for the majority of cases in each GOLD stage. The proportion of patients with diastolic dysfunction increased from 41.4% in GOLD II to 89.1% in GOLD IV, representing a more than two-fold increase. This striking gradient across GOLD stages suggests a strong dose-response relationship between COPD severity and LV dysfunction, independent of hypertension. These findings underscore the importance of routine echocardiographic evaluation, particularly in patients with advanced COPD (GOLD III–IV), where the prevalence of LV dysfunction exceeds 70–90%.

Figure 1: Prevalence of Left Ventricular Dysfunction by GOLD Stage

(Bar chart illustrating the progressive increase in systolic and diastolic dysfunction across GOLD stages II, III, and IV)

Explanation of Figure 1: This bar chart visually demonstrates the progressive increase in both systolic and diastolic dysfunctions with advancing COPD severity. Diastolic dysfunction (shown in blue bars) is consistently more prevalent than systolic dysfunction (shown in orange bars) across all GOLD stages. The gap between diastolic and systolic dysfunction prevalence widens with increasing GOLD stage, from a difference of 32.8 percentage points in GOLD II to 63.6 percentage points in GOLD IV. This observation highlights that diastolic dysfunction is not only the dominant pattern of LV impairment in non-hypertensive COPD patients but also that its prevalence escalates more rapidly with disease progression than systolic dysfunction. The near-universal prevalence of diastolic dysfunction (89.1%) in GOLD IV patients is particularly noteworthy and suggests that advanced COPD is almost invariably associated with some degree of diastolic impairment.

Figure 2: Distribution of Diastolic Dysfunction Grades by GOLD Stage

(Stacked bar chart showing the distribution of diastolic dysfunction grades across GOLD stages)

Explanation of Figure 2: This stacked bar chart illustrates the distribution of diastolic dysfunction grades across GOLD stages. In GOLD II, the majority of patients (58.6%) had no diastolic dysfunction, while among those with diastolic dysfunction, Grade I (impaired relaxation) was the predominant pattern (34.3%), with only 7.1% having Grade II and none having Grade III. In GOLD III, the proportion without diastolic dysfunction decreased to 32.6%, while Grade I increased to 46.3%, Grade II to 17.9%, and Grade III appeared at 3.2%. In GOLD IV, only 10.9% of patients had normal diastolic function, while the majority had Grade I (54.5%) or Grade II (27.3%) dysfunction, with 7.3% having the most severe Grade III restrictive pattern. This progression from predominantly Grade I dysfunction in milder disease to a higher proportion of Grades II and III in severe disease indicates that not only does the prevalence of diastolic dysfunction increase with COPD severity, but the severity of diastolic impairment also worsens progressively.

Table 4: Multivariate Logistic Regression Analysis of Predictors of Left Ventricular Dysfunction

Explanation of Table 4: This table presents the results of multivariate logistic regression analysis to identify independent predictors of LV dysfunction (systolic and/or diastolic) in non-hypertensive COPD patients. In univariate analysis, several factors were significantly associated with LV dysfunction: age ≥ 60 years (OR: 2.56, p = 0.001), smoking history (OR: 2.18, p = 0.007), pack-years > 30 (OR: 2.87, p < 0.001), COPD duration > 5 years (OR: 1.95, p = 0.019), GOLD III (OR: 2.86, p = 0.001), GOLD IV (OR: 6.29, p < 0.001), mMRC score ≥ 2 (OR: 3.12, p < 0.001), and frequent exacerbations (OR: 2.74, p = 0.001). After adjustment for potential confounders in the multivariate model, GOLD stage IV remained the strongest independent predictor (adjusted OR: 4.82, 95% CI: 2.31–10.05, p < 0.001), followed by GOLD III (adjusted OR: 2.54, 95% CI: 1.31–4.92, p = 0.006). Age ≥ 60 years (adjusted OR: 2.14, p = 0.012), smoking history (adjusted OR: 1.89, p = 0.036), pack-years > 30 (adjusted OR: 2.23, p = 0.012), mMRC score ≥ 2 (adjusted OR: 1.96, p = 0.029), and frequent exacerbations (adjusted OR: 2.06, p = 0.024) also remained significant independent predictors. COPD duration > 5 years lost statistical significance in the adjusted model (p = 0.132), suggesting that its effect is mediated through GOLD stage. Male gender and low BMI were not significant predictors. These findings indicate that COPD severity, as measured by GOLD stage, is the most important independent determinant of LV dysfunction in non-hypertensive patients, with age, smoking burden, dyspnea severity, and exacerbation frequency also contributing independently.

This study provides, to our knowledge, one of the first comprehensive assessments of left ventricular dysfunction in non-hypertensive COPD patients from Pakistan [4,12]. The key findings are that (1) LV dysfunction is highly prevalent, affecting 66.8% of the study population; (2) diastolic dysfunction (64.5%) is considerably more common than systolic dysfunction (15.9%); (3) the prevalence of both systolic and diastolic dysfunction increases progressively with GOLD stage; and (4) GOLD stage IV is the strongest independent predictor of LV dysfunction, followed by age, smoking burden, dyspnea severity, and exacerbation frequency. The prevalence of systolic dysfunction (15.9%) observed in our study is remarkably consistent with the findings of a recent systematic review and meta-analysis that reported a prevalence of undiagnosed LVSD of 15.8% (95% CI: 11.1–21.1%) [8]. This consistency across different geographic regions and study populations strengthens the generalizability of our findings and confirms that LV systolic dysfunction is a significant and under-recognized comorbidity in COPD patients [8]. However, it is notable that some studies have reported lower prevalence rates, with five studies comprising 283 COPD patients finding LVSD prevalence ranging from 3.8% to 16%, while others have reported higher rates up to 26.7% [3,6,7]. These variations may reflect differences in patient selection, LVEF thresholds used, or the inclusion of patients with hypertension and other cardiovascular risk factors [8]. The prevalence of diastolic dysfunction (64.5%) in our study is consistent with the growing body of evidence highlighting diastolic impairment as the dominant cardiac manifestation in COPD [2,5,15]. A recent study found diastolic dysfunction in 67.5% of COPD patients, with Grade I affecting 53.5%, Grade II 13.2%, and Grade III 0.9% [2]. Another study reported LVDD in 60% of COPD patients compared to only 12.2% in healthy controls [13]. Our findings, with Grade I in 44.5%, Grade II in 16.8%, and Grade III in 3.2%, are broadly consistent with these reports [2,13]. The high prevalence of diastolic dysfunction, particularly in patients with advanced COPD, underscores the importance of including diastolic assessment in routine echocardiographic evaluation of COPD patients [2,5,15]. Several pathophysiological mechanisms may explain the high prevalence of LV dysfunction, particularly diastolic dysfunction, in non-hypertensive COPD patients. First, systemic inflammation plays a central role [16,11]. COPD is characterized by chronic low-grade systemic inflammation, with elevated circulating levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) [16]. These inflammatory mediators can directly impair myocardial function by inducing oxidative stress, promoting fibrosis, and altering calcium handling in cardiomyocytes [11,16]. The inflammatory burden increases with disease severity, which may explain the progressive increase in LV dysfunction across GOLD stages observed in our study [16]. Second, hypoxemia is a well-established contributor to cardiac dysfunction in COPD [11]. Chronic hypoxemia leads to pulmonary vasoconstriction, pulmonary hypertension, and right ventricular pressure overload [11,16]. Through ventricular interdependence, right ventricular pressure and volume overload can impair left ventricular filling by septal bowing and pericardial constraint [11,16]. The finding that hypoxemia (oxygen saturation below 88%) was significantly associated with LV dysfunction in other studies supports this mechanism [11]. In our study, although we did not specifically measure arterial blood gases, the strong association between GOLD stage (a marker of disease severity and, by extension, hypoxemia) and LV dysfunction is consistent with this pathophysiological pathway [11,16]. Third, increased arterial stiffness and endothelial dysfunction are common in COPD patients [9,16]. The systemic inflammatory state promotes endothelial dysfunction and accelerates atherosclerosis, leading to increased arterial stiffness [9,16]. Increased arterial stiffness raises left ventricular afterload, contributing to concentric LV remodeling, impaired relaxation, and diastolic dysfunction [9,16]. This mechanism may be particularly relevant in non-hypertensive patients, where hypertension is absent but arterial stiffness remains elevated due to COPD-related inflammation [6,9]. Fourth, shared risk factors, particularly smoking, contribute to both COPD and cardiovascular disease [16,9]. Smoking induces oxidative stress, endothelial dysfunction, and inflammation in both the airways and the vasculature [16]. In our study, smoking history and cumulative smoking burden (pack-years > 30) were independent predictors of LV dysfunction, even after adjusting for GOLD stage. This suggests that smoking contributes to cardiac dysfunction through pathways that are at least partially independent of its effects on airflow obstruction [16,9]. The strong independent association between GOLD stage and LV dysfunction observed in our study (adjusted OR for GOLD IV: 4.82) is consistent with findings from a Pakistani study that reported a progressive increase in heart failure prevalence from 5.9% in GOLD I to 70.0% in GOLD IV [4]. Similarly, another study found that diastolic dysfunction prevalence increased from 41.2% in GOLD II to 92.2% in GOLD IV [5]. The dose-response relationship between COPD severity and LV dysfunction supports the concept that COPD itself, independent of hypertension, contributes to cardiac impairment through the mechanisms discussed above [4,5]. The finding that age ≥ 60 years was an independent predictor of LV dysfunction (adjusted OR: 2.14) is not surprising, given that advancing age is associated with both increased cardiovascular risk and progressive decline in myocardial function [16,9]. However, the fact that age remained a significant predictor even after adjusting for GOLD stage suggests that age-related cardiac changes and COPD-related cardiac changes may have additive or synergistic effects [16]. This is clinically important because it identifies older COPD patients as a particularly high-risk group for LV dysfunction, regardless of their blood pressure status [6,16]. The independent association between dyspnea severity (mMRC score ≥ 2) and LV dysfunction (adjusted OR: 1.96) is noteworthy. Dyspnea is a cardinal symptom of both COPD and heart failure, and distinguishing between pulmonary and cardiac causes of dyspnea is a common clinical challenge [1,19]. Our finding that higher mMRC scores are independently associated with LV dysfunction suggests that echocardiographic evaluation may be particularly valuable in COPD patients with significant dyspnea, as a proportion of their symptoms may be attributable to undiagnosed cardiac dysfunction [1]. This is consistent with the COSYCONET cohort findings, which revealed an independent link between left ventricular size and exertional symptoms [1]. The independent association between frequent exacerbations (≥ 2 per year) and LV dysfunction (adjusted OR: 2.06) has important clinical implications [20]. Acute exacerbations of COPD are associated with increased systemic inflammation, hypoxemia, and hemodynamic stress, which may precipitate or worsen cardiac dysfunction [20]. Conversely, pre-existing LV dysfunction may increase the risk of exacerbations by impairing gas exchange and reducing exercise capacity [19,20]. This bidirectional relationship suggests that patients with frequent exacerbations should be considered for cardiovascular screening, and conversely, that patients with known LV dysfunction should receive optimized COPD management to reduce exacerbation risk [19,20]. The predominantly diastolic nature of LV dysfunction in our study has important therapeutic implications [2,5,16]. Unlike systolic dysfunction, for which there are multiple evidence-based therapies (ACE inhibitors, beta-blockers, mineralocorticoid receptor antagonists), diastolic dysfunction has fewer proven pharmacological interventions [16]. However, certain strategies may be beneficial, including control of heart rate, optimization of volume status, and treatment of underlying conditions such as hypoxemia and inflammation [11,16]. The high prevalence of diastolic dysfunction in non-hypertensive COPD patients suggests that these patients may benefit from therapies that reduce left ventricular filling pressures, such as diuretics (in volume-overloaded patients) and beta-blockers (which improve diastolic relaxation through heart rate reduction) [16]. The clinical significance of our findings extends to screening and diagnostic practices [8,16]. Current guidelines for COPD management emphasize the importance of identifying and treating cardiovascular comorbidities, but there is no universal recommendation for routine echocardiographic screening in all COPD patients [8,16]. Our finding that 66.8% of non-hypertensive COPD patients have echocardiographic evidence of LV dysfunction, with the prevalence exceeding 90% in GOLD IV patients, suggests that the threshold for echocardiographic evaluation should be low, particularly in patients with advanced disease, significant dyspnea, or frequent exacerbations [2,4,8]. As noted in a systematic review, “undiagnosed left ventricular systolic dysfunction is found to be present in 10–20% of patients with COPD, highlighting the enormous burden of unrecognised, and therefore untreated, heart disease in the global COPD population” [8]. The strengths of this study include its focused examination of non-hypertensive COPD patients, which allows isolation of the independent contribution of COPD to LV dysfunction; the use of comprehensive echocardiographic assessment according to standardized guidelines; the inclusion of patients across a range of GOLD stages, allowing assessment of dose-response relationships; and the use of multivariate analysis to identify independent predictors [2,6,8]. However, several limitations should be acknowledged. First, the cross-sectional design precludes assessment of causality or temporal relationships. While our findings demonstrate strong associations between COPD severity and LV dysfunction, we cannot determine whether COPD causes LV dysfunction, whether LV dysfunction exacerbates COPD, or whether both are consequences of shared underlying processes. Longitudinal studies are needed to establish temporal relationships. Second, the study was conducted at a single tertiary care center in Pakistan, which may limit the generalizability of the findings to other settings or populations [4]. However, the consistency of our findings with international studies suggests that the prevalence and patterns of LV dysfunction in non-hypertensive COPD patients are broadly similar across different geographic regions [8]. Third, we excluded patients with diabetes mellitus, which is a common comorbidity in COPD and an important risk factor for LV dysfunction [16,9]. While this exclusion was necessary to isolate the effect of COPD on LV dysfunction, it limits the applicability of our findings to the broader COPD population, many of whom have diabetes [16]. Future studies should include diabetic patients and assess the interaction between diabetes and COPD in the development of LV dysfunction [16,19]. Fourth, we did not measure inflammatory biomarkers (such as CRP, IL-6, or TNF-α) or arterial blood gases, which would have allowed us to explore the mechanistic pathways linking COPD to LV dysfunction more directly [11,16]. Future studies should incorporate biomarker assessments to elucidate the pathophysiological mechanisms [11,16]. Fifth, we used LVEF < 50% as the threshold for systolic dysfunction, which is the conventional definition [8]. However, some studies have used LVEF < 40% or < 45% as thresholds, and the prevalence of systolic dysfunction would be lower with a more stringent definition [6,8]. The use of a consistent definition facilitates comparison with other studies but should be considered when interpreting the results [8]. Sixth, we did not perform right heart catheterization to confirm pulmonary hypertension, which is an important intermediary in the pathway from COPD to LV dysfunction [6,11]. However, echocardiographic assessment of right ventricular function and pulmonary artery pressure was beyond the scope of this study [6,11]. Finally, the study did not include a control group of non-COPD patients without hypertension, which would have allowed estimation of the excess risk of LV dysfunction attributable to COPD [6]. However, the high prevalence of LV dysfunction in our study population, combined with the progressive increase across GOLD stages, strongly suggests that COPD itself is a significant contributor to LV dysfunction [4,5,6].

This study demonstrates that left ventricular dysfunction is highly prevalent among non-hypertensive patients with COPD, affecting nearly two-thirds of the study population. Diastolic dysfunction is the predominant pattern, affecting 64.5% of patients, while systolic dysfunction affects 15.9%. The prevalence of both systolic and diastolic dysfunction increases progressively with GOLD stage, from 44.3% in GOLD II to 90.9% in GOLD IV. GOLD stage IV is the strongest independent predictor of LV dysfunction, followed by age ≥ 60 years, smoking history, pack-years > 30, dyspnea severity, and frequent exacerbations.

These findings have important clinical implications. First, hypertension should not be considered a prerequisite for LV dysfunction in COPD patients. The absence of hypertension does not rule out significant cardiac impairment. Second, the high and progressive prevalence of LV dysfunction across GOLD stages supports routine echocardiographic screening, particularly in patients with advanced COPD (GOLD III–IV), significant dyspnea, or frequent exacerbations. Third, the predominantly diastolic nature of LV dysfunction in this population suggests that diastolic function should be specifically assessed in echocardiographic evaluations, as isolated assessment of LVEF would miss the majority of cases.

Given the substantial burden of COPD and cardiovascular disease in Pakistan and other low- and middle-income countries, these findings underscore the need for integrated approaches to COPD management that incorporate cardiovascular risk assessment and screening. Early detection of LV dysfunction in COPD patients offers the opportunity for timely intervention, which may improve symptoms, reduce exacerbations, and ultimately improve prognosis. Future research should focus on longitudinal studies to establish causality, mechanistic studies to elucidate the pathways linking COPD to LV dysfunction, and interventional studies to determine whether treatment of LV dysfunction improves outcomes in COPD patients.