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Original Research: COPD |

Percent Emphysema and Right Ventricular Structure and FunctionEmphysema and Right Ventricular Function: The Multi-Ethnic Study of Atherosclerosis-Lung and Multi-Ethnic Study of Atherosclerosis-Right Ventricle Studies FREE TO VIEW

Maria Grau, MD, PhD, MPH; R. Graham Barr, MD, DrPH; Joao A. Lima, MD; Eric A. Hoffman, PhD; David A. Bluemke, MD, PhD; J. Jeffrey Carr, MD; Harjit Chahal, MD, PhD; Paul L Enright, MD; Aditya Jain, MD; Martin R. Prince, MD, PhD; Steven M. Kawut, MD, FCCP*
Author and Funding Information

From the Department of Medicine (Drs Grau and Barr), the Department of Epidemiology (Dr Barr), and the Department of Radiology (Dr Prince), Columbia University Medical Center, New York, NY; the Department of Medicine (Drs Lima, Chahal, and Jain), Johns Hopkins University, Baltimore, MD; National Institutes of Health Clinical Center (Dr Bluemke), Bethesda, MD; University of Iowa (Dr Hoffman), Iowa City, IA; Wake Forest University (Dr Carr), Winston-Salem, NC; University of Arizona (Dr Enright), Tucson, AZ; Penn Cardiovascular Institute, Department of Medicine and Center for Clinical Epidemiology and Biostatistics (Dr Kawut), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and the Cardiovascular Epidemiology and Genetics Group (Dr Grau), Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.

Correspondence to R. Graham Barr, MD, DrPH, Department of Medicine, Columbia University Medical Center, 630 W 168th St, PH 9 E-Room 105, New York, NY 10032; e-mail: rgb9@columbia.edu


*

A full list of investigators and institutions participating in the Multi-Ethnic Study of Atherosclerosis (MESA) can be found at www.mesa-nhlbi.org.

Funding/Support: The MESA, MESA-Lung, and MESA-Right Ventricle Studies are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) [Contracts N01-HC-95159-N01-HC-95169 and Grants R01 HL077612, R01 HL086719, R01 HL075476, and RC1 HL100543] in collaboration with the MESA, MESA-Lung, and MESA-Right Ventricle investigators. Dr Kawut was supported by the NHLBI [K24 HL103844]. Dr Grau was funded by grants from Health Institute Carlos III-FEDER, Spain [Red HERACLES RD06/0009, CM08/00141, and CP12/03287].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(1):136-144. doi:10.1378/chest.12-1779
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Background:  Severe COPD can lead to cor pulmonale and emphysema and is associated with impaired left ventricular (LV) filling. We evaluated whether emphysema and airflow obstruction would be associated with changes in right ventricular (RV) structure and function and whether these associations would differ by smoking status.

Methods:  The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRI on 5,098 participants without clinical cardiovascular disease aged 45 to 84 years. RV and emphysema measures were available for 4,188 participants. Percent emphysema was defined as the percentage of voxels below −910 Hounsfield units in the lung windows on cardiac CT scans. Generalized additive models were used to control for confounders and adjust for respective LV parameters.

Results:  Participants consisted of 13% current smokers, 36% former smokers, and 52% never smokers. Percent emphysema was inversely associated with RV end-diastolic volume, stroke volume, cardiac output, and mass prior to adjustment for LV measures. After adjustment for LV end-diastolic volume, greater percent emphysema was associated with greater RV end-diastolic volume (+1.5 mL, P = .03) among current smokers, smaller RV end-diastolic volume (−0.8 mL, P = .02) among former smokers, and similar changes among never smokers.

Conclusions:  Percent emphysema was associated with smaller RV volumes and lower mass. The relationship of emphysema to cardiac function is complex but likely involves increased pulmonary vascular resistance, predominantly with reduced cardiac output, pulmonary hyperinflation, and accelerated cardiopulmonary aging.

Figures in this Article

Chronic lower respiratory disease, which encompasses emphysema and COPD, is the third-leading cause of death in the United States.1 Emphysema is characterized by the destruction of alveolar walls and the permanent enlargement of air spaces distal to the terminal bronchioles.2 COPD is defined by a reduction in the FEV1/FVC ratio that is incompletely reversible to bronchodilators.3

COPD is characterized by increased pulmonary artery pressure either at rest or with exercise.4,5 A subset of patients with COPD have increased pulmonary arteriovenous pressure gradient, right ventricular (RV) enlargement (termed cor pulmonale), and RV failure, classically in association with gas trapping and bronchitis.5,6 Other (and currently most) patients with very severe COPD do not develop cor pulmonale or RV failure but still have reduced cardiac output. This latter group classically has emphysema.7

Although the RV changes in response to severe lung disease are reasonably well described, the impact of milder and subclinical emphysema and airflow obstruction on the right ventricle is less clear. We observed previously that emphysema on CT scan and airflow obstruction on spirometry were associated with significant decrements in left ventricular (LV) filling, stroke volume, and cardiac output, particularly in cigarette smokers, in a large, population-based study.8 Whether these changes are accompanied by an increase in pulmonary arteriovenous pressure gradient with increased RV volumes and mass or, alternatively, reduced cardiac output with reduced RV dimensions is unknown.

We, therefore, examined the relationships between the percent emphysema on CT scan and airflow obstruction on spirometry and RV structure and function on MRI in a large population-based cohort. We first examined associations of lung measures with the right ventricle unadjusted for LV measures. We then evaluated associations of lung measures and the right ventricle adjusted for LV measures because an increased pulmonary arteriovenous pressure gradient should exert a differential effect on the right ventricle and the left ventricle. We used two-tailed P values to provide a valid statistical test of either possibility. Given prior findings of effect modification of emphysema-LV associations by smoking status,8 we tested for similar effect modification for the right ventricle.

Study Participants

The Multi-Ethnic Study of Atherosclerosis (MESA) is a multicenter, prospective cohort study of the prevalence, correlates, and progression of subclinical cardiovascular diseases in whites, blacks, Hispanics, and Asians.9 Between 2000 and 2002, MESA recruited 6,814 participants who were 45 to 84 years of age, did not report clinical cardiovascular disease, weighed < 136 kg (300 lb), and had no impediment to long-term participation. Written informed consent was obtained from all participants. The protocols of MESA were approved by the institutional review boards of all collaborating institutions and by the National Heart, Lung, and Blood Institute (e-Appendix 1).

Measurements of RV Structure and Function

The MESA-Right Ventricle Study measured RV morphology in 4,204 MESA participants with interpretable cardiac MRIs at the baseline examination (Fig 1). The protocol, its reliability, and the characteristics of MESA participants with MRI measurements have been described previously (e-Appendix 2).10

Figure Jump LinkFigure 1. Flow diagram of participant selection in the MESA study. LV = left ventricular; MESA = Multi-Ethnic Study of Atherosclerosis; RV = right ventricular.Grahic Jump Location
Assessment of Emphysema

The MESA-Lung Study quantitatively assessed the extent of emphysema on the lung fields of all baseline MESA cardiac CT scans, which included approximately 70% of the lung volume from the carina to the lung bases. Cardiac CT scans were obtained at full inspiration on multidetector and electron-beam CT scanners according to a standardized protocol.11 Two scans were obtained for each participant, and the scan with the greater volume of lung air was used for analyses, except in cases of discordant scan quality, when the higher-quality scan was analyzed (e-Appendix 2).12

Spirometry

The MESA Lung Study performed spirometry between 2004 and 2006 in a subset of MESA participants. Spirometry was performed in accordance with the American Thoracic Society-European Respiratory Society recommended guidelines13 (e-Appendix 2).

Smoking Status and Other Covariates

Age, sex, race or ethnic group, educational level, cigarettes smoked per day, number of pack-years of smoking, and medical history were self-reported. Height, weight, resting BP, serum glucose level, C-reactive protein level, and fibrinogen level were measured using standard techniques.14 A history of hypertension or diabetes and the use of insulin or hypoglycemic or antihypertensive agents were determined. Study participants who reported having smoked at least one cigarette in the 30 days before the CT scan examination or who had a urinary cotinine level > 100 ng/mL on the day of the CT scan examination were classified as current smokers.

Statistical Analysis

The data are presented as the mean ± SD for continuous variables and as percentages for discrete variables for all participants and are stratified by smoking status. Effect modification of the relationship of pulmonary measures with RV measures by smoking status was anticipated a priori8 and was tested with the −2 log-likelihood test of nested models with and without interaction terms.

We used generalized additive models to regress RV end-diastolic volume, stroke volume, ejection fraction, and mass on percent emphysema stratified by smoking status and on the FEV1/FVC ratio. The first model was adjusted for age, race or ethnicity, sex, height and weight, cigarettes smoked per day, number of pack-years of smoking, serum glucose, diabetes, systolic and diastolic BP, hypertension, educational attainment, serum glucose level, C-reactive protein level, and fibrinogen level. Analysis of percent emphysema was further adjusted for CT scanner type and tube current in milliamperes, which affect attenuation. Corresponding LV parameters were then added (except for stroke volume because of the interrelatedness of the variables).

Sensitivity analyses were conducted using percent emphysema in lung cores, peels, and upper-lobe regions as independent variables, stratifying by pack-years of smoking instead of smoking status and in the subsample of individuals with no restrictive ventilatory defect on spirometry. The test of the primary hypothesis, 95% CIs, and P values were estimated from generalized additive models. A two-tailed P value < .05 was considered to indicate statistical significance. Analyses were performed using R statistical software, version 2.13.0 (R Foundation for Statistical Computing).

Of the 6,814 MESA participants, 5,098 underwent cardiac MRI examination, of whom 5,004 had interpretable LV measures; 4,634 were selected for RV interpretation, and 4,204 were completed (Fig 1). Three were missing CT scans, and 13 were missing information on covariates, resulting in a sample size of 4,188 with percent emphysema measures. Spirometric measures were available for 2,741.

The mean age of the study sample was 61 years, and 47% were men (Table 1, e-Table 1). One-half were never smokers, 36% had smoked in the past, and 13% were current smokers. Mean spirometric measurements and RV parameters are shown in Table 2 and e-Table 2. The median value for percent emphysema was 18.4%.

Table Graphic Jump Location
Table 1 —Characteristics of Participants With Right Ventricular Measures in the Multi-Ethnic Study of Atherosclerosis Study Stratified by Smoking Status

Data are presented as No. (%), median (IQR), or mean ± SD. IQR = interquartile range.

a 

In ever smokers.

Table Graphic Jump Location
Table 2 —Percent Emphysema on CT Scan, Lung Function, and RV Structure and Function on MRI Stratified by Smoking Status

Data are presented as mean ± SD unless indicated otherwise. RV = right ventricular. See Table 1 legend for expansion of other abbreviations.

a 

n = 313, 951, and 1,485 for current, former, and never smokers, respectively.

Emphysema and RV Function

Percent emphysema was inversely associated with RV end-diastolic volume, stroke volume, cardiac output, and mass in the main multivariable models (all P < .001). However, there were significant interactions between RV end-diastolic volume and smoking status and percent emphysema (P = .012 for interaction); hence, analyses for percent emphysema were stratified by smoking status.

Greater percent emphysema was associated with smaller RV end-diastolic volume after adjustment for covariates in current, former, and never smokers (Table 3). The magnitude of this association was greater among current and former smokers compared with never smokers. Generalized additive models did not reveal a nonlinear component of the relationships (Fig 2).

Table Graphic Jump Location
Table 3 —Mean Differences in RV Parameters per 10 Percentage-Point Change in Percent Emphysema According to Smoking Status in Multivariable Models

Adjusted for age, weight, height, sex, race/ethnicity, cigarettes per day (current smokers only), pack-y of smoking (current and former smokers only), glucose, diabetes (physician diagnosis or treatment), systolic and diastolic BP, hypertension (physician diagnosis or treatment), educational attainment, fibrinogen, and C-reactive protein, and CT scanner type and tube current in milliamperes. See Table 2 legend for expansion of abbreviations.

Figure Jump LinkFigure 2. Relationship between RV end-diastolic volume and % emphysema across smoking categories. Models were adjusted for age, weight, height, sex, race/ethnicity, CT scanner type and tube current in milliamperes, cigarettes per day (only current smokers), pack-y of smoking (only current and former smokers), glucose, diabetes (physician diagnosis or treatment), systolic and diastolic BP, hypertension (physician diagnosis or treatment), educational attainment, fibrinogen, and C-reactive protein. See Figure 1 legend for expansion of abbreviations.Grahic Jump Location

Greater percent emphysema was also associated with smaller RV stroke volume, irrespective of smoking status, and lower RV mass in adjusted models (Table 3). These findings were statistically significant, except for RV mass among current smokers. Percent emphysema was inversely associated with cardiac output among never smokers, but there was no evidence of an association with RV ejection fraction or cardiac output in current smokers.

After additional adjustment for respective LV measures, greater percent emphysema was associated with larger RV end-diastolic volume and greater RV cardiac output among current smokers ( Fig 3, Table 4). Among former smokers, percent emphysema was associated with smaller RV end-diastolic volume and greater RV cardiac output after adjustment for LV measures. Among never smokers, there was no evidence of an association between percent emphysema and RV end-diastolic volume or RV cardiac output after adjustment for LV measures. Greater percent emphysema was also weakly associated with RV ejection fraction in former smokers and with lower RV mass among former and never smokers after adjustment for respective LV measures (Table 4).

Table Graphic Jump Location
Table 4 —Mean Differences in RV Parameters per 10 Percentage-Point Change in Percent Emphysema According to Smoking Status in Multivariable Models After Adjustment for Respective LV Parameters

Adjusted for age, weight, height, sex, race/ethnicity, cigarettes per day (current smokers only), pack-y of smoking (current and former smokers only), glucose, diabetes (physician diagnosis or treatment), systolic and diastolic BP, hypertension (physician diagnosis or treatment), educational attainment, fibrinogen, and C-reactive protein, and CT scanner type and tube current in milliamperes, and respective LV parameters. LV = left ventricular. See Table 2 legend for expansion of other abbreviations.

Figure Jump LinkFigure 3. Relationship between RV end-diastolic volume and % emphysema across smoking categories after adjustment for respective left ventricular parameters. Models were adjusted for age, weight, height, sex, race/ethnicity, CT scanner type and tube current in milliamperes, left ventricular end-diastolic volume, cigarettes per day (only current smokers), pack-y of smoking (only current and former smokers), glucose, diabetes (physician diagnosis or treatment), systolic and diastolic BP, hypertension (physician diagnosis or treatment), educational attainment, fibrinogen, and C-reactive protein. See Figure 1 legend for expansion of abbreviations.Grahic Jump Location
Airflow Obstruction and RV Function

There was no evidence of interactions between RV parameters and spirometry by smoking status; therefore, these analyses were not stratified by smoking status (Table 5). Lower FEV1/FVC ratio was associated with lower RV mass after adjustment for LV mass. There were no other associations between FEV1/FVC ratio and RV parameters (Table 5, e-Table 3).

Table Graphic Jump Location
Table 5 —Mean Differences in RV Parameters per 1 Percentage-Point Change in the FEV1/FVC Ratio (n = 2,741)

See Table 2 and 4 legends for expansion of abbreviations.

a 

Model 1 adjusted for age, weight, height, sex, race/ethnicity, cigarettes per day (current smokers only), pack-y of smoking (current and former smokers only), glucose, diabetes (physician diagnosis or treatment), systolic and diastolic BP, hypertension (physician diagnosis or treatment), educational attainment, fibrinogen, and C-reactive protein, and CT scanner type and tube current in milliamperes.

b 

Model 2: Model 1 + LV measures.

Additional Analyses

There was no evidence of effect modification by sex, race or ethnic group, or obesity (all P > .23 for interaction). Associations between percent emphysema and RV measures were similar when percent emphysema in lung core, peel, and upper-lobe regions were used as independent variables (e-Tables 4-6). Effect modification by smoking history was also present (eg, P = .021 for RV end-diastolic volume), and results stratified by pack-years of smoking yielded results similar to those stratified by smoking status (e-Fig 1, e-Table 7). Results were similar when a −950 threshold was used to define percent emphysema (e-Table 8) and when we considered individuals with no restrictive ventilatory defect on spirometry (e-Table 9).

Percent emphysema was inversely associated with RV end-diastolic volume, stroke volume, and mass, independent of major confounders in this large, population-based cohort free of clinical cardiovascular disease. Associations varied according to smoking status and were of greater magnitude among ever smokers compared with never smokers. Relative to previously observed decrements in LV volumes and mass, percent emphysema was associated with higher RV end-diastolic volume and RV cardiac output in current smokers, lower RV end-diastolic volume in former smokers, and similar decrements in RV and LV end-diastolic volumes in never smokers.

These findings, along with the previously reported large decrement in LV end-diastolic volume with emphysema,8 suggest that greater percent emphysema may lead to reduced filling of the right ventricle and reduced cardiac output (with reduced pulmonary blood flow). In fact, there was indirect evidence of increased RV afterload only among current smokers (ie, large RV end-diastolic volume and greater RV cardiac output relative to LV parameters, the latter presumably due to regurgitant flow into the low-pressure vena cava), which was mild (ie, no accompanying increase in RV mass). The underlying mechanisms of these findings may include destruction of the pulmonary vascular bed in emphysema related to apoptosis of the pulmonary endothelium,15,16 endothelial dysfunction17 or hypercoagulability,18 a reduction in pulmonary blood flow and LV cardiac output, and an increase in pulmonary vascular resistance.

In addition, there may be a direct effect of hyperinflation and unloading of both ventricles, particularly among never and former smokers.19,20 Hyperinflation of the lungs has two principal causes: hyperexpansion of the chest due to emphysema-related loss of elastic recoil and increased intrathoracic pressure (ie, intrinsic positive end-expiratory pressure) due to gas trapping and airflow obstruction. Hyperexpansion due to loss of elastic recoil may reduce venous return to the right ventricle and left ventricle because of cardiac rotation and distortions in the systemic and pulmonary vascular structure, respectively. Hyperinflation and gas trapping due to intrinsic positive end-expiratory pressure may impair cardiac filling by reduced venous return to the thorax19 and by direct compression of the heart and pulmonary vessels,21 increasing end-diastolic stiffness of the right ventricle and increasing pulmonary arteriovenous pressure gradients, as has been suggested previously in moderate-severe COPD.19,20 Although intrathoracic pressure was not measured (and was infeasible) in this large epidemiologic study, the former mechanism (hyperinflation and gas trapping) appears a more likely explanation for our findings in most of the sample, given that associations were predominantly observed with percent emphysema rather than airflow obstruction.22

Reduced LV preload due to chronic thromboembolic pulmonary hypertension causes a reduction in LV mass and ventricular atrophy.23 Our observations could also be consistent with a similar off-loading of the right ventricle from reduced systemic venous return from emphysema-related hyperinflation.

Among current smokers, percent emphysema was positively associated with greater RV end-diastolic volume and less of a reduction in RV cardiac output after adjustment for LV end-diastolic volume. This finding suggests that increased RV afterload in early, mostly subclinical, emphysema occurs predominantly in current smokers.

Alternatively, biologic aging contributes to lung function decline (approximately 20-25 mL/y in nonsmokers) and to alterations in LV and RV structure and function.24,25 It is well known that emphysema occurs with age, in addition to occurring with smoking. In addition, percent emphysema was associated with decreasing LV volumes in never smokers.8 Therefore, the links between radiologic emphysema and RV morphology may also reflect biologic aging.

Study Limitations

This study has several potential limitations. Smoking may be an important confounder, and former smokers had higher percent emphysema than did current smokers. Previous studies have shown similar results,8,22,2627 likely because inflammatory cell infiltration and mucus from current smoking make the lung appear denser (ie, lower percent emphysema). To address this limitation, we adjusted all analyses for cigarettes smoked per day. In addition, we performed sensitivity analyses controlling for cotinine level (in the large subset with cotinine measures) and excluding current smokers, which yielded similar results.

Given the limited number of current smokers and the relatively modest smoking exposure among former smokers, we were unable to differentiate effect modification from smoking status from that due to cumulative smoking history. Current smoking was precisely assessed by cotinine levels; the multivariate results changed little with adjustment for multiple measures of smoking (data not shown), and percent emphysema was associated with RV parameters even among never smokers.

Percent emphysema was measured only on partial-lung rather than full-lung CT scans; however, MESA cardiac scans image approximately 70% of the lung volume in the field of view, and percent emphysema measures from these scans correlate with full-lung measures (r = 0.93).12 The upper lobes are classically involved in smoking-related centrilobular emphysema, and a recent study showed that upper-lobe-predominant emphysema was significantly associated with greater lung function decline in former and current heavy smokers.28 However, cardiac scans assess lower and central regions of the lung, which receive the greatest amount of pulmonary blood flow in the upright position.29,30 Finally, the sensitivity analysis considering the emphysema in the region of the upper lobes included yielded similar results.

Lung function was measured in a subsample approximately 4 years after the other measures. The reduced sample size limited power in this analysis. In addition, we did not measure diffusing capacity for carbon monoxide, which has been associated with more CT scan-quantified emphysema and could refine the COPD phenotype·31,32

Selection bias may affect any cross-sectional study, but is likely to be modest in magnitude in this study because it was population based and participants were not selected on the basis of the presence or absence of lung disease or symptoms. In addition, this design cannot establish temporality. Measurement of right and left atrial volumes, and hypoxemia and pulmonary artery pressures were not available.

In conclusion, percent emphysema was inversely associated with RV end-diastolic volume, stroke volume, and mass, independent of major confounders in this large, population-based cohort. Associations differed from those observed for the left ventricle and varied according to smoking status and severity, which suggests that several potential mechanisms underlie cardiopulmonary interactions in a community-based population.

Author contributions: Dr Barr is the guarantor of the study.

Dr Grau: contributed to the study concept and design, data analysis and interpretation, writing of the article, critical revision of the manuscript for intellectual content, and final approval of the submitted manuscript.

Dr Barr: contributed to the study concept and design; data acquisition, analysis, and interpretation; critical revision of the manuscript for intellectual content; and final approval of the submitted manuscript.

Dr Lima: contributed to the study concept and design, data acquisition, critical revision of the manuscript for intellectual content, and final approval of the submitted manuscript.

Dr Hoffman: contributed to the study concept and design, data acquisition, critical revision of the manuscript for intellectual content, and final approval of the submitted manuscript.

Dr Bluemke: contributed to the study concept and design, data acquisition, critical revision of the manuscript for intellectual content, and final approval of the submitted manuscript.

Dr Carr: contributed to the data acquisition, critical revision of the manuscript for intellectual content, and final approval of the submitted manuscript.

Dr Chahal: contributed to the data acquisition, critical revision of the manuscript for intellectual content, and final approval of the submitted manuscript.

Dr Enright: contributed to the data acquisition, critical revision of the manuscript for intellectual content, and final approval of the submitted manuscript.

Dr Jain: contributed to the data acquisition, critical revision of the manuscript for intellectual content, and final approval of the submitted manuscript.

Dr Prince: contributed to the data acquisition, critical revision of the manuscript for intellectual content, and final approval of the submitted manuscript.

Dr Kawut: contributed to the study concept and design; data acquisition, analysis, and interpretation; critical revision of the manuscript for intellectual content; and final approval of the submitted manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Barr is a principal investigator or coinvestigator on grants from National Institutes of Health (NIH), US-EPA, the Alpha-1 Foundation, and Columbia University; was reimbursed by Boehringer-Ingelheim GmbH for travel to the TransAtlantic Airways Conference; and received an in-kind donation of a nutritional supplement from Cenestra Health for an NIH-sponsored clinical trial. Dr Hoffman is a founder and shareholder of VIDA Diagnostics. Dr Prince has patent agreements with General Electric Company; Philips; Siemens; Hitachi, Ltd; Toshiba Corporation; Mallinckrodt Group; Nemoto & Co Ltd; Medrad Inc; Bayer; Bracco Imaging; Topspins Inc; and Lantheus Medical Imaging, who sell MRI-related products. Drs Grau, Lima, Bluemke, Carr, Chahal, Enright, Jain, and Kawut have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.

Other contributions: This manuscript has been reviewed by the MESA Investigators for scientific content and consistency of data interpretation with previous MESA publications and significant comments have been incorporated prior to submission for publication. The authors thank the other investigators, staff, and participants of the MESA, MESA-Lung, and MESA Right Ventricle studies for their valuable contributions.

Additional information: The e-Appendix and e-Tables can be found in the “Supplemental Materials” area of the online article.

LV

left ventricular

MESA

Multi-Ethnic Study of Atherosclerosis

RV

right ventricular

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Hardziyenka M, Campian ME, Reesink HJ, et al. Right ventricular failure following chronic pressure overload is associated with reduction in left ventricular mass evidence for atrophic remodeling. J Am Coll Cardiol. 2011;57(8):921-928. [CrossRef] [PubMed]
 
Kawut SM, Lima JA, Barr RG, et al. Sex and race differences in right ventricular structure and function: the Multi-Ethnic Study of Atherosclerosis-Right Ventricle Study. Circulation. 2011;123(22):2542-2551. [CrossRef] [PubMed]
 
Cheng S, Fernandes VR, Bluemke DA, McClelland RL, Kronmal RA, Lima JA. Age-related left ventricular remodeling and associated risk for cardiovascular outcomes: the Multi-Ethnic Study of Atherosclerosis. Circ Cardiovasc Imaging. 2009;2(3):191-198. [CrossRef] [PubMed]
 
Camiciottoli G, Cavigli E, Grassi L, et al. Prevalence and correlates of pulmonary emphysema in smokers and former smokers. A densitometric study of participants in the ITALUNG trial. Eur Radiol. 2009;19(1):58-66. [CrossRef] [PubMed]
 
Grydeland TB, Dirksen A, Coxson HO, et al. Quantitative computed tomography: emphysema and airway wall thickness by sex, age and smoking. Eur Respir J. 2009;34(4):858-865. [CrossRef] [PubMed]
 
Mohamed Hoesein FA, van Rikxoort E, van Ginneken B, et al. Computed tomography-quantified emphysema distribution is associated with lung function decline. Eur Respir J. 2012;40(4):844-850. [CrossRef] [PubMed]
 
Hakim TS, Lisbona R, Dean GW. Gravity-independent inequality in pulmonary blood flow in humans. J Appl Physiol. 1987;63(3):1114-1121. [PubMed]
 
Glenny RW, Lamm WJ, Albert RK, Robertson HT. Gravity is a minor determinant of pulmonary blood flow distribution. J Appl Physiol. 1991;71(2):620-629. [PubMed]
 
Mohamed Hoesein FA, Zanen P, van Ginneken B, van Klaveren RJ, Lammers JW. Association of the transfer coefficient of the lung for carbon monoxide with emphysema progression in male smokers. Eur Respir J. 2011;38(5):1012-1018. [CrossRef] [PubMed]
 
Bafadhel M, Umar I, Gupta S, et al. The role of CT scanning in multidimensional phenotyping of COPD. Chest. 2011;140(3):634-642. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Flow diagram of participant selection in the MESA study. LV = left ventricular; MESA = Multi-Ethnic Study of Atherosclerosis; RV = right ventricular.Grahic Jump Location
Figure Jump LinkFigure 2. Relationship between RV end-diastolic volume and % emphysema across smoking categories. Models were adjusted for age, weight, height, sex, race/ethnicity, CT scanner type and tube current in milliamperes, cigarettes per day (only current smokers), pack-y of smoking (only current and former smokers), glucose, diabetes (physician diagnosis or treatment), systolic and diastolic BP, hypertension (physician diagnosis or treatment), educational attainment, fibrinogen, and C-reactive protein. See Figure 1 legend for expansion of abbreviations.Grahic Jump Location
Figure Jump LinkFigure 3. Relationship between RV end-diastolic volume and % emphysema across smoking categories after adjustment for respective left ventricular parameters. Models were adjusted for age, weight, height, sex, race/ethnicity, CT scanner type and tube current in milliamperes, left ventricular end-diastolic volume, cigarettes per day (only current smokers), pack-y of smoking (only current and former smokers), glucose, diabetes (physician diagnosis or treatment), systolic and diastolic BP, hypertension (physician diagnosis or treatment), educational attainment, fibrinogen, and C-reactive protein. See Figure 1 legend for expansion of abbreviations.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Characteristics of Participants With Right Ventricular Measures in the Multi-Ethnic Study of Atherosclerosis Study Stratified by Smoking Status

Data are presented as No. (%), median (IQR), or mean ± SD. IQR = interquartile range.

a 

In ever smokers.

Table Graphic Jump Location
Table 2 —Percent Emphysema on CT Scan, Lung Function, and RV Structure and Function on MRI Stratified by Smoking Status

Data are presented as mean ± SD unless indicated otherwise. RV = right ventricular. See Table 1 legend for expansion of other abbreviations.

a 

n = 313, 951, and 1,485 for current, former, and never smokers, respectively.

Table Graphic Jump Location
Table 3 —Mean Differences in RV Parameters per 10 Percentage-Point Change in Percent Emphysema According to Smoking Status in Multivariable Models

Adjusted for age, weight, height, sex, race/ethnicity, cigarettes per day (current smokers only), pack-y of smoking (current and former smokers only), glucose, diabetes (physician diagnosis or treatment), systolic and diastolic BP, hypertension (physician diagnosis or treatment), educational attainment, fibrinogen, and C-reactive protein, and CT scanner type and tube current in milliamperes. See Table 2 legend for expansion of abbreviations.

Table Graphic Jump Location
Table 4 —Mean Differences in RV Parameters per 10 Percentage-Point Change in Percent Emphysema According to Smoking Status in Multivariable Models After Adjustment for Respective LV Parameters

Adjusted for age, weight, height, sex, race/ethnicity, cigarettes per day (current smokers only), pack-y of smoking (current and former smokers only), glucose, diabetes (physician diagnosis or treatment), systolic and diastolic BP, hypertension (physician diagnosis or treatment), educational attainment, fibrinogen, and C-reactive protein, and CT scanner type and tube current in milliamperes, and respective LV parameters. LV = left ventricular. See Table 2 legend for expansion of other abbreviations.

Table Graphic Jump Location
Table 5 —Mean Differences in RV Parameters per 1 Percentage-Point Change in the FEV1/FVC Ratio (n = 2,741)

See Table 2 and 4 legends for expansion of abbreviations.

a 

Model 1 adjusted for age, weight, height, sex, race/ethnicity, cigarettes per day (current smokers only), pack-y of smoking (current and former smokers only), glucose, diabetes (physician diagnosis or treatment), systolic and diastolic BP, hypertension (physician diagnosis or treatment), educational attainment, fibrinogen, and C-reactive protein, and CT scanner type and tube current in milliamperes.

b 

Model 2: Model 1 + LV measures.

References

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Mohamed Hoesein FA, de Hoop B, Zanen P, et al. CT-quantified emphysema in male heavy smokers: association with lung function decline. Thorax. 2011;66(9):782-787. [CrossRef] [PubMed]
 
Hardziyenka M, Campian ME, Reesink HJ, et al. Right ventricular failure following chronic pressure overload is associated with reduction in left ventricular mass evidence for atrophic remodeling. J Am Coll Cardiol. 2011;57(8):921-928. [CrossRef] [PubMed]
 
Kawut SM, Lima JA, Barr RG, et al. Sex and race differences in right ventricular structure and function: the Multi-Ethnic Study of Atherosclerosis-Right Ventricle Study. Circulation. 2011;123(22):2542-2551. [CrossRef] [PubMed]
 
Cheng S, Fernandes VR, Bluemke DA, McClelland RL, Kronmal RA, Lima JA. Age-related left ventricular remodeling and associated risk for cardiovascular outcomes: the Multi-Ethnic Study of Atherosclerosis. Circ Cardiovasc Imaging. 2009;2(3):191-198. [CrossRef] [PubMed]
 
Camiciottoli G, Cavigli E, Grassi L, et al. Prevalence and correlates of pulmonary emphysema in smokers and former smokers. A densitometric study of participants in the ITALUNG trial. Eur Radiol. 2009;19(1):58-66. [CrossRef] [PubMed]
 
Grydeland TB, Dirksen A, Coxson HO, et al. Quantitative computed tomography: emphysema and airway wall thickness by sex, age and smoking. Eur Respir J. 2009;34(4):858-865. [CrossRef] [PubMed]
 
Mohamed Hoesein FA, van Rikxoort E, van Ginneken B, et al. Computed tomography-quantified emphysema distribution is associated with lung function decline. Eur Respir J. 2012;40(4):844-850. [CrossRef] [PubMed]
 
Hakim TS, Lisbona R, Dean GW. Gravity-independent inequality in pulmonary blood flow in humans. J Appl Physiol. 1987;63(3):1114-1121. [PubMed]
 
Glenny RW, Lamm WJ, Albert RK, Robertson HT. Gravity is a minor determinant of pulmonary blood flow distribution. J Appl Physiol. 1991;71(2):620-629. [PubMed]
 
Mohamed Hoesein FA, Zanen P, van Ginneken B, van Klaveren RJ, Lammers JW. Association of the transfer coefficient of the lung for carbon monoxide with emphysema progression in male smokers. Eur Respir J. 2011;38(5):1012-1018. [CrossRef] [PubMed]
 
Bafadhel M, Umar I, Gupta S, et al. The role of CT scanning in multidimensional phenotyping of COPD. Chest. 2011;140(3):634-642. [CrossRef] [PubMed]
 
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