Low body mass is associated with reduced left ventricular mass in Chinese elderly with severe COPD

There is limited information on the association of body mass index (BMI) with left ventricular (LV) remodeling corresponding to severity of reduced lung function in patients with chronic obstructive pulmonary disease (COPD). Therefore, we investigated whether BMI is associated with cardiac atrial and ventricular dimensions according to severity of lung functional impairment in Chinese COPD elderly. A total of 563 hospitalized COPD patients with lung function impairment and 184 patients with non-COPD (aged 65–92 years) were collected retrospectively in a cross-sectional study in a university affiliated tertiary hospital in China. BMI and cardiac echocardiographic parameters were compared according to severity of lung functional impairment in COPD patients. BMI was 22.9 ± 3.9 kg/m2 in COPD patients, 24.0 ± 4.1 kg/m2 in non-COPD patients respectively. Reduced BMI, LV mass index, LV wall thickness and left atrial diameter, and dilated right ventricle (RV) existed in COPD patients with severe lung dysfunction as compared the COPD patients with mild to moderate lung functional reduction and non-COPD patients (P < 0.05), while there were no differences in BMI and echocardiographic parameters between the COPD patients with mild to moderate lung functional decline and non-COPD patients (P > 0.05). Logistic regression analysis showed that low BMI (BMI < 18.5 kg/m2) was correlated with reduced LV mass and wall thickness, dilated RV and reduced lung function in the COPD patients with severe lung dysfunction. In conclusion, this study demonstrates that lower BMI is associated not only with dilated RV and impaired pulmonary function, but also it is related to reduced LV mass in Asian COPD elderly with severe lung dysfunction.

www.nature.com/scientificreports/ Table 1); Plasma triglyceride, diastolic blood pressure, prevalence of hypertension, type 2 DM, coronary heart disease and stroke were lower in COPD patients with mild, moderate or severe lung functional reduction as compared with non-COPD patients (All P < 0.05, Table 1). www.nature.com/scientificreports/ Echocardiographic and clinical parameters among different BMI categories in patients with severe COPD. Comparison of echocardiographic, lung function and clinical parameters among different BMI categorized groups was performed in COPD patients with severe lung functional reduction (n = 280), as considering that the changes in echocardiographic parameters and reduced BMI existed in COPD patients with severe lung functional reduction. LA diameter, LV mass index and wall thickness, lung function, plasma total cholesterol, systolic blood pressure, prevalence of hypertension and type 2 DM were lower in underweight patients as compared with normal weight or overweight obesity patients in COPD with severe lung functional reduction (All P < 0.05, Table 2); While the RV and RA diameter, HDL-C and eGFR were higher in underweight patients as compared with normal weight or overweight obesity patients in COPD with severe lung functional reduction (All P < 0.05, Table 2).
Underweight, echocardiographic, lung functional and clinical parameters in patients with severe COPD. Correlation analysis for the underweight with echocardiographic parameters was underwent in COPD patients with severe lung functional reduction (n = 280), as considering that the changes in echocardiographic parameters and reduced BMI existed in COPD patients with severe lung functional reduction. Univariate correlation analysis showed that underweight was related to reduced LA diameter, LV mass index and wall thickness, impaired lung function, decreased plasma total cholesterol, systolic blood pressure, and prevalence of hypertension and type 2 DM in COPD patients with severe lung functional reduction; Meanwhile underweight was related to increased RV and RA diameter, HDL-C and eGFR in COPD patients with severe lung functional reduction (All P < 0.05, Table 2). Dichotomized variate regression analysis showed that underweight was independently associated with reduced LV mass and wall thickness, dilated RV and decreased lung function in COPD patients with severe lung functional reduction (All P < 0.05, Table 3).

Discussion
The present study shows that lowered BMI, LA diameter and LV mass index, and increased RV diameter existed in COPD patients with severe lung functional reduction. The results indicated that lower BMI was independently associated not only with increased RV diameter and impaired lung function, but also it is related to a decreased LV mass in elderly Asian population with severe COPD.
The present study confirmed that the elderly COPD patient population with its severe forms is more common among males than females. Chronic inflammation leads to fibrosis of lung parenchyma in the pathological process of COPD. The elasticity of respiratory bronchioles gradually decreases. The air in alveoli can not be completely discharged during the expiratory period. It gradually leads to the increase of residual air in the alveoli, formation of emphysema and dysfunction of airway ventilation. In the late stage of COPD, alveolar tissue fibrosis and capillary destruction in the lung further lead to declined pulmonary diffusional function. The destruction of pulmonary vascular bed gradually leads to increase of lung artery resistance, pulmonary hypertension and right-sided cardiac atrial and ventricular dilation and dysfunction, and exhibiting liver and gastrointestinal blood congestion, indigestion, absorption dysfunction, malnutrition and decreased BMI 22 . Our present results showed that underweight and the right-sided cardiac ventricular dilation were observed commonly in severe COPD. This finding is consistent with previous studies 4, 23,24 . However, our present study replenished that underweight was independently related to the right-sided cardiac ventricular dilation and impaired pulmonary function in this group of COPD patients with severe lung functional reduction.
With progression of COPD and pulmonary functional decline, the subsequent hypoxia activates sympathetic nervous and renin-angiotensin-aldosterone systems. The respiratory muscles are forced to do more work for maintaining adequate lung ventilation, which increases more energy consumption and produces more inflammatory molecules 25 . It raises the catabolism of glucose, fat and even protein, consequently leading to sarcopenia of skeletal muscles and increased systemic inflammation with resultant bodyweight loss, lower BMI 26,27 . It may also cause sarcopenia of cardiac muscles with decreased LV mass. At the same time, due to the destruction of pulmonary vessels, the blood volume from right-sided to left-sided heart (the left-sided cardiac preload) is reduced 11,12 . Then, the decreased left-sided cardiac ventricular mass and thickness would result, and the blood supply for peripheral tissues will further decline, which is another important reason for the decrease of BMI. On the basis of our knowledge, this is the first time that our present study confirmed that pulmonary functional impairment and reduced LV mass is associated with lower BMI in the elderly COPD with severe lung dysfunction. This study suggests that echocardiographic parameters can be considered to add into future revised COPD prognostic assessment scales 28,29 . Low BMI associated cardiac remodeling may provide a useful marker for prognosis of COPD patients. However, our results from Asian population are not consistent with a previous study, which reported that LV hypertrophy existed in COPD 30 . The previous study was consisted of relatively younger patients mainly with mild moderate COPD 30 . The underlying causes for these differences are still unclear. However, the discrepancies may come from the different studied populations and measurement methods for the LV mass. In our study, the decreased LV mass and thickness were found usually in the elderly COPD with severe lung dysfunction.
Although previous studies reported that low BMI can lead to lung dysfunction, and is closely related to the occurrence and development of COPD [31][32][33] , other investigations confirmed that low BMI is not a causal factor for the development of COPD 34,35 . In contrary, it suggested that lower BMI and its associated cardiac remodeling may be considered to result from the consequences of increased expenditure of energy, reduced nutritional intake and increased inflammation due to COPD and its complicated pulmonary heart disease 34,35 . Therefore, we advise that moderately active treatment of COPD may improve the patient's lung function and prognosis, and prevent progression of the disease into advanced stage with complicating lower BMI and cardiac adverse www.nature.com/scientificreports/ structural remodeling. Treatments including appropriate nutritional supplementation may help to improve the prognosis of COPD patients. On the other hand, it showed that COPD patients with higher BMI have better lung function and prognosis. It seems that overweight and obesity may partly even protect lung function and prevent the development of COPD, which is called "obesity paradox" 36,37 . Nevertheless, this inverse relationship between body mass and pulmonary poor prognosis in COPD could be explained by a speculation that a better lung function with its subsequent less energy exhaustion, anorexia and inflammation may contribute to  38,39 . Our present study also found that the COPD patients with relatively increased BMI have a better lung function, nevertheless, they are with more metabolic cardiovascular disorders and left-sided cardiac adverse hypertrophic remodeling. In addition, the prevalence of E/A reversal was not found to be significantly different among BMI categories in severe COPD patients. The E/A reversal assessment alone may not precisely reflect cardiac LV diastolic dysfunction. The present study has some limitations. It was a cross-sectional investigation. Data were collected retrospectively. The effects of unavoidable confounding factors need to be considered. In this study, the health assessment scale was not used to estimate the nutritional status in the subjects. It is still unclear whether malnutrition involves the association of low body weight with the cardiac remodeling in the COPD patients. Therefore, the observed findings in this study would be needed to reconfirm by future prospective studies. This study was conducted in elderly patients with COPD. The results should be carefully extrapolated to other populations.

Conclusion
The present study found that low BMI, decreased LV mass and LA diameter, and increased RV diameter existed more often in elderly COPD patients with severe lung dysfunction. Low BMI was not only independently related to RV dilation and lung functional impairment, but also it was associated with decreased LV mass in elderly Asian population with severe COPD.  Table 3. Regression analysis of parameters associated with underweight (BMI < 18.5 kg/m 2 ) in patients with severe COPD (n = 280). COPD, chronic obstructive pulmonary disease; BMI, body mass index; FEV1, forced expiratory volume in one second; FVC, forced vital capacity; RV, residual volume; TLC, total lung capacity; DLCO, diffusing capacity of carbon monoxide; RV, right ventricular; RA, right atrial; LA, left atrial; IV, interventricular; LV PWT, left ventricular posterior wall thickness; LV, left ventricular; HT, hypertension; SBP, systolic blood pressure; DM, diabetes mellitus; TC, total cholesterol; HDL-C, high density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate.