Abstract
Objectives: We aimed to compare right and left ventricular functions by echocardiography (ECHO) according to chronic obstructive pulmonary disease (COPD) groups, and to determine their associations with functional parameters.
Methods: Data of patients with COPD who underwent ECHO between 2015 and 2018 were analyzed retrospectively. The results of pulmonary function tests, 6-minute-walking test (6MWT), Modified Medical Research Council (mMRC), COPD assessment test (CAT), and BODE scores were recorded together with ECHO results showing right and left ventricular functions.
Results: 126 COPD patients were evaluated. Of these, 37.3% was in group A, 28.6% in group B, 12.7% in group C, and 21.4% in group D. Most common comorbidities were cardiovascular diseases (CVD) and pulmonary hypertension (PH); these were most frequently seen in groups D and B. Regarding ECHO parameters, differences were present among groups in systolic pulmonary arterial pressure (sPAP) and left ventricle end-systolic diameter (LVEF) (p < 0.001 and 0.004, respectively). sPAP was highest in groups D and B whereas LVEF was lowest in group D.
Conclusion: Our results suggest that patients’ symptoms in symptomatic COPD groups B and D might be related to increased PAP and concomitant cardiovascular comorbidities. Therefore, a detailed cardiovascular investigation should be performed from early stages in COPD.
Introduction
Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disorder characterized by permanent airflow restriction [Citation1,Citation2]. Currently, it is considered that COPD is an umbrella term, and the disorder has numerous clinical, physiopathological, and radiological phenotypes [Citation3]. In these phenotypes, clinical features such as symptoms, exacerbations, response to treatment, disease progression rate, or mortality can show different patterns. According to the 2017 GOLD report, COPD patients are divided into four groups regarding symptoms and exacerbation risk [Citation1,Citation4]. Patients having fewer symptoms are included in groups A and C, and those with a high exacerbation risk are included in groups C and D [Citation1,Citation5].
Numerous comorbidities might be observed due to systemic inflammation or similar risk factors in COPD. These comorbidities may develop at any stage of the disease and affect the prognosis negatively by increasing the severity of the disease [Citation6,Citation7]. Among comorbidities accompanying COPD, the most common and significant ones are coronary artery disease (CAD) and cardiovascular disorders (CVDs) [Citation8], including heart failure (HF) [Citation9–11]. Cardiovascular comorbidities affect the quality of life and survival in patients with COPD [Citation12,Citation13]. Therefore, all COPD patients should be evaluated regarding cardiac functions [Citation14]. Transthoracic echocardiography (ECHO) is a rapid and noninvasive method for evaluating the functions of the right and left heart [Citation15,Citation16].
Numerous studies investigating the right and left cardiac functions are present in the literature [Citation6]; however, the number of studies in which cardiac function was compared according to COPD groups is small. In this study, we aimed to compare cardiac functions according to COPD groups and to determine the relationships of these with clinical and functional respiratory parameters.
Methods
The study protocol
After obtaining the approval of the Local Ethics Committee (approval number: 2018/1525), the data of patients who had been diagnosed with COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria [Citation17] at the Pulmonary Diseases Outpatient Clinic between January 2015 and January 2018 were retrospectively investigated in the electronic environment. Demographic data including age, sex, body mass index (BMI), smoking history, and comorbidities were recorded. Body mass index (BMI) was calculated as follows: weight/(height)2 (kg/m2). Smoking history was recorded as cigarette pack-years.
All patients with COPD were clinically evaluated using the modified Medical Research Council (mMRC) and COPD assessment (CAT) tests. mMRC is a scale that measures the extent of activity limitation due to dyspnea and is graded from 0 to 4 [Citation18]. CAT is used to assess the health status of COPD patients and includes eight statements related to symptoms, sleep, confidence and exercise limitation, each of which is scored by the patient on a scale of 0 to 5, with the total score ranging from 0 to 40 [Citation19]. The mMRC and CAT scores were used to classify patients into those with fewer symptoms (mMRC grade, 0–1; CAT score, < 10) and those with more symptoms (mMRC ≥ grade 2; CAT score, ≥10) [Citation20]. The risk of exacerbations was evaluated based on the history of exacerbations in the year prior to the study, and patients who had less than two exacerbations in the previous year or were not hospitalized due to exacerbation were classified as low-risk patients. The patients were classified as four groups (A, B, C, and D) according to the frequency of symptoms and exacerbations. Group A was described as low risk and low symptoms, group B was described as low risk and more symptoms, group C was described as high risk and fewer symptoms, and group D was described as high risk and high symptoms. All subjects underwent spirometry and the 6-minute walk test (6MWT). Spirometry was performed at the pulmonary function test laboratory of the Adnan Menderes University Hospital, Turkey, using a Jaeger Master Scope spirometer with the subject in a seated position, in accordance with the American Thoracic Society/European Respiratory Society criteria [Citation21]. A single technician with a pulmonary function testing certification performed all the tests.
The bronchodilation test was conducted 15 min after salbutamol inhalation (4 puffs, 400 μg). The test was performed by measuring FEV1 (%), FVC (%) and FEV1/FVC. The 6MWT was used to determine the functional capacity of the patient and performed by letting the patient walk for 6 minutes on a flat surface with his/her own maximum speed. The patient’s oxygen saturation was measured both before and after the 6MWT test by pulse oximetry, and dyspnea and fatigue were also recorded. All subjects underwent the 6MWT, and their data were recorded [Citation22]. The data were used to calculate the BODE index score that is used to determine COPD-related mortality risk, wherein an increased BODE index score is associated with an increased risk of mortality. BMI, airway obstruction based on FEV1, dyspnea based on the mMRC dyspnea score, and exercise capacity based on the 6MWT are evaluated to determine the BODE index score [Citation23].
The transthoracic ECHO reports of all cases were evaluated, and left ventricle ejection fraction (LVEF), systolic pulmonary arterial pressure (sPAP), left ventricle end-diastolic diameter (LVEdiast), left ventricle end-systolic diameter (LVEsyst), and right ventricle end-diastolic diameter (RVEdiast) were recorded. sPAP values above 35 mmHg were considered as pulmonary hypertension (PH) [Citation24]. Patients whose pulmonary function test results, respiratory functional parameters, and ECHO reports were absent in the system were excluded from the study.
Statistical analysis
Kolmogorov–Smirnov test was used to determine whether quantitative variables were normally distributed in COPD groups. ANOVA was used for the comparisons between the COPD groups for the variables with normal distribution, while the Kruskal–Wallis H test for the variables not normally distributed. For the variables that are statistically significant, multiple comparison tests (Tukey HSD, Tamhane's T2 or Dunn’s multiple comparison test) were used to determine which groups were different. The relationship between quantitative variables was examined by Pearson or Spearman correlation analysis. The dependence between qualitative variables was determined by chi-square analysis. Descriptive statistics for quantitative variables were given as mean ± standard deviation for normally distributed variables and as median (25th–75th percentiles) for non-normally distributed variables. Descriptive statistics for qualitative variables were given as frequency (%). p < .05 was considered statistically significant.
Results
One hundred six COPD patients, with an average age of 66.73 ± 9.76 years and 119 of whom were male, were included in the study. 47 (37.3%) of the cases were in group A, 36 (28.6%) were in group B, 16 (12.7%) were in group C, and 27 (21.4%) in group D. No significant differences were found among groups regarding age, sex, BMI, and smoking status (p = .075, p = .240, p = .056, and p = .524, respectively). The most common comorbidities were CVD and PH. Of all COPD cases, 35% had CVD (CAD 17.5% and HF 17.5%), and 26.2% had PH. Regarding groups, CVD was most commonly seen in group D, followed by groups B, C, and A, respectively. PH was most common in group D, and this was followed by groups B, A, and C, respectively. The demographic data of the cases were shown in . Regarding the functional assessment of the cases, FVC (%), FEV1 (%), FEV1/FVC, 6MWT, CAT, mMRC, and BODE index scores were different among the groups (). When ECHO parameters were compared, there were significant differences among the groups regarding sPAP and LVEF (p < .001, .004, respectively). However, no significant differences were found to be present among the groups regarding LVEdiast, LVEsyst, and RVEdiast (p = .097, p = .067, and p = .936, respectively). According to this, sPAP was highest in group D, followed by groups B, A, and C, respectively. LVEF was lowest in group D, followed by groups C, B, and A, respectively (). When a correlation analysis was performed between respiratory functional parameters and ECHO data, negative correlations were determined between sPAP FVC (%), FEV1 (%) and 6MWT, and positive correlations were determined between CAT, mMRC, and BODE scores. Also, positive correlations were found to be present between LVEF, FVC (%), FEV1 (%), and 6MWT, and negative correlations between CAT, mMRC, and BODE scores ().
Table 1. The demographic characteristics in COPD groups.
Table 2. The functional parameters in the COPD groups.
Table 3. The ECHO parameters in the COPD groups.
Table 4. The correlation analysis of ECHO data with functional parameters.
Discussion
In our study, the most common comorbidities were found as CVD and PH in COPD; these were most frequently observed in groups D and B. Regarding ECHO parameters, sPAP was highest in groups D and B, and LVEF was lowest in group D.
The incidence of cardiovascular comorbidities has increased in COPD patients, and approximately 25% of patients die because of CVD [Citation11,Citation25]. In the literature, the frequency of cardiovascular morbidities in patients with COPD is within the range of 28–70% [Citation26–28]. Kulej-LykO et al. reported that since concomitant diseases such as COPD may increase the risk of depression, prevention is very important [Citation8]. Treatment of atherosclerosis and arterial hypertension, ceasing smoking are only examples of methods how to reduce the risk of developing disorders mentioned above [Citation29]. In this sense, health expense may increase due to increase prevalence of COPD. The results of the Ture et al. [Citation7] showed that the costs of COPD are an important factor affecting health expenditures in COPD subjects. In COPD disease management, it will be a cost-effective approach for family physicians, pulmonary specialists, and other physicians.
In our study, CVDs were found to be present in 35% of the COPD patients. Even though CVDs are frequently present in COPD, few studies have evaluated their distributions according to the COPD subgroups. In a study conducted by Lange et al., CAD was reported to be most common in COPD patients in groups B and D [Citation30]. In the study by Figueira et al. Also, CVDs were reported to be more common in groups B and D compared to groups A and C [Citation31]. In our study, CVDs were determined to be most common in group D; 66.6% of the COPD patients in group D had concomitant CVD. Although statistically insignificant, the frequency of CVD was higher in group B compared to group C (41.6 and 37.4%, respectively).
According to Francesco and Michelle, cardiovascular problems are attributable to risk factors such as smoking, saturated fat diet, physical inactivity, excessive alcohol consumption, psychosocial problems, and others [Citation32]. These risk factors are mostly behavioral risks, which account for more than 60% of CVD deaths globally [Citation14]. Even though right heart catheterization is the gold standard method for diagnosing PH, since its procedure is noninvasive and less complicated, using transthoracic ECHO is more appropriate for initial evaluation. The exact sPAP limit values for PH in transthoracic ECHO are yet unknown; however, the sPAP value being above 35 mmHg might be considered as PH [Citation24]. In our study, the pulmonary arterial pressure was measured as sPAP, using ECHO. The prevalence of PH in COPD patients is not fully known; however, conducted studies have shown that the prevalence varies from 18 to 91% [Citation33,Citation34]. In our study, when the threshold sPAP value for PH was considered as 35 mmHg, PH was determined to be present in 26.2% of all COPD cases. According to its distribution among COPD groups, it was most frequently seen in group D, followed by groups B, A, and C, respectively (p < .001). The pulmonary arterial pressure (PAP) increases because of developing hypoxic pulmonary vasoconstriction, inflammation, and remodeling in COPD patients [Citation35]. Such increases in PAP lead to deteriorations in clinical and functional parameters of the patients. Even though the presence of PAP elevation in COPD is a well-known entity, differences among groups have not been sufficiently identified. In our study, sPAP was determined to have higher values in groups D and B compared to groups A and C (p < .001). The common characteristics of the patients in groups B and D are being symptomatic. For this reason, we consider that the symptoms of the patients in groups B and D might be due to the PAP elevation or concomitant CVDs. One of the significant factors in determining mortality in COPD patients is the PAP level [Citation36,Citation37]. In our study, a positive correlation was identified between sPAP and BODE index, used in mortality prediction. Conducted studies on COPD patients have shown that PAP was positively correlated with mMRC score, which shows the severity of patients’ symptoms, and negatively correlated with functional parameters such as 6MWT and FEV1 [Citation38–40]. In our study also, PAP was positively correlated with mMRC and CAT scores, and negatively correlated with 6MWT, FVC (%), and FEV (%).
LVEF is a parameter showing the systolic function of the left ventricle. In our study, the lowest LVEF value was determined in group D (p = .0004); however, the only statistically significant difference was found to be present with group A. Group D consists of symptomatic COPD patients at advanced stage, who have high exacerbation risk. We suggest that low LVEF might be among the factors which increase the severity of symptoms and the frequency of exacerbations in this group of patients. In our study, LVEF was found to be negatively correlated with mMRC and CAT scores, and positively correlated with 6MWT, FVC (%), and FEV1 (%). These results show that symptoms are more severe, and functional parameters are worse in patients with low ejection fraction. Conducted studies have shown that low ejection fraction was an independent risk factor for mortality in COPD [Citation41–43]. In our study, a negative correlation was determined to be present between ejection fraction and the BODE index.
Conclusions
Our results suggest that symptoms might be manifested due to PAP elevation and concomitant cardiovascular comorbidities in COPD patients classified in groups B and D, which are the symptomatic groups. Therefore, the evaluation of patients with COPD should not only be performed for the primary disorder but also considering the cardiovascular aspect from the early stages.
Disclosure statement
No potential conflict of interest was reported by the authors.
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