Rationale and Objectives
The relationship between chronic obstructive pulmonary disease (COPD) and atherosclerosis has been suggested; this association may relate to systemic inflammation and endothelial dysfunction, which can lead to alteration of small pulmonary vessels. The relationship between atherosclerosis and small pulmonary vessel alteration, however, has not been assessed in COPD patients. We tested the hypothesis that the severity of thoracic aortic calcification measured by computed tomography (CT) would be associated with the total cross-sectional area of small pulmonary vessels (CSA) on CT images.
Materials and Methods
The study was approved by the institutional review board and was Health Insurance Portability and Accountability Act–compliant. Informed consent was waived. For 51 COPD patients enrolled in the National Heart, Lung, and Blood Institute Lung Tissue Research Consortium, we calculated the percentage of total CSAs of less than 5 mm 2 for the total lung area (%CSA<5). Thoracic aortic calcification, quantified by modified Agatston score, was measured. The correlations between thoracic aortic calcification score and %CSA<5, pulmonary function, and extent of emphysema were evaluated. Multiple linear regression analysis using aortic calcification score as the dependent outcome was also performed.
Results
The %CSA<5 had a significant negative correlation with the thoracic aortic calcification score ( r = −0.566, P < .0001). Multiple linear regression analysis showed significant correlation between the aortic calcification score and %CSA<5 ( P < .0001) independent of age, pack-years, extent of emphysema, and FEV1%.
Conclusions
Atherosclerosis, assessed by aortic calcification, is associated with the small pulmonary vascular alteration in COPD. Systemic inflammation and endothelial dysfunction may cause the close relationship between atherosclerosis and small pulmonary vessel alteration.
Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disorder in which inflammation may be associated to the development of cardiovascular diseases . Although the underlying mechanisms remain unknown, cardiovascular disease contributes significantly to morbidity and mortality in COPD . Atherosclerosis is the principal cause of cardiovascular diseases, including coronary heart disease, stroke, and peripheral vascular disease , and it is thought to be associated with systemic inflammation and endothelial dysfunction . Prior investigations suggested that systemic inflammation in COPD may promote atherosclerosis , and recent studies have reported relationships between atherosclerosis and COPD .
The development of arterial calcification is an active process seen at all stages of atherosclerotic plaque development, and is closely associated with vascular injury . Many researchers have reported the relationship between aortic calcification and an increased risk of cardiovascular events . Patients with calcification in the thoracic aorta have 3.8 times the relative risk for obstructive coronary artery disease independent of age . In addition, a recent study showed that the severity of thoracic aortic calcification measured by computed tomography (CT) strongly correlates with inflammatory markers such as interleukin-6 .
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Methods
Subjects
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Multislice CT Scanning
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CT Measurement of Small Pulmonary Vessels
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CT Measurement of the Thoracic Aortic Calcification
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Statistical Analysis
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Results
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Table 1
Demographics, Pulmonary Function, and CT Measurements ( n = 51)
Mean SD Range Age (y) 66 9 47–82 Gender, % female (%) 42.8 BMI 26.3 4.6 16.5–41.8 Pack-years 48.0 30.8 1–128 FEV1 (l) 1.42 0.77 0.5–3.9 FVC (l) 3.0 1.1 0.9–5.8 FEV1% predicted (%) 50.4 23.7 16.0–93.0 FEV1/FVC 0.46 0.15 0.23–0.69 DLco% predicted (%) 54.4 21.9 22.0–98.0 %CSA<5 (%) 0.63 0.15 0.38–1.02 %LAA-950 (%) 20.9 15.1 0.4–47.9
SD, standard deviation; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; DL CO , diffusing capacity of the lung for carbon monoxide; BMI, body mass index; %CSA<5, percentage of total lung area taken up by the cross-sectional area of pulmonary vessels <5 mm 2 ; %LAA-950, CT measurement of the percentage of low attenuation area less than −950 HU, defined as emphysema.
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Table 2
Correlations of Aortic Calcification Score with Continuous Variables (Spearman’s Rank Correlations) ( n = 51)
Aortic Calcification Score_r__P_ Age 0.508 .0001 BMI −0.001 .992 Pack-years 0.183 .197 FEV1% predicted 0.201 .156 DLco% predicted 0.014 .925 %CSA<5 −0.566 <.0001 %LAA-950 0.119 .405
SD, standard deviation; FEV1, forced expiratory volume in 1 second; DL CO , diffusing capacity of the lung for carbon monoxide; BMI, body mass index; %CSA<5, percentage of total lung area taken up by the cross-sectional area of pulmonary vessels <5 mm 2 ; %LAA-950, CT measurement of the percentage of low attenuation area less than −950 HU, defined as emphysema.
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Table 3
Multivariate Analysis of Aortic Calcification Score ( n = 51)
Partial Correlation Coefficient_P_ Value Age 0.351 .0049 Gender −0.053 .838 BMI −0.061 .672 Pack-years 0.007 .968 FEV1% predicted −0.044 .886 DLco% predicted 0.084 .601 %CSA<5 −0.564 <.0001 Total lung area −0.175 .223 %LAA-950 −0.223 .172
SD, standard deviation; FEV1, forced expiratory volume in 1 second; DL CO , diffusing capacity of the lung for carbon monoxide; BMI, body mass index; %CSA<5, percentage of total lung area taken up by the cross-sectional area of pulmonary vessels <5 mm 2 ; %LAA-950, CT measurement of the percentage of low attenuation area less than −950 HU, defined as emphysema.
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Discussion
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