Increased brachial intima-media thickness is associated with circulating levels of asymmetric dimethylarginine in patients with COPD

Figures & data

Table 1 Subject characteristics

Subject characteristics	COPD	Smokers	Never-smokers	P-value
Clinical characteristics
Age, years	64±7.8	60±9.2	64±11.0	0.068A, 0.881B, 0.191C
Male sex, %	53	40	30	0.339A, 0.083B, 0.520C
Body mass index, kg/m^2	24±3.6	26±3.4	25±3.1	0.074A, 0.406B, 0.379C
Systolic blood pressure, mmHg	125±13	121±12	126±9.8	0.220A, 0.649B, 0.119C
Diastolic blood pressure, mmHg	76±6.6	73±8.5	75±5.5	0.223A, 0.536B, 0.598C
Heart rate, beats per minute	88±18	73±16	73±13	0.02A, <0.001B, 0.938C
Smoking history, pack-years	65±37	39±23	0±0	0.04A, <0.001B, <0.001C
Acute exacerbation rate, n/year	1.0 (0–1.6)
Lung function testing
FVC, % predicted	78±17	104±13	103±16	<0.001A, <0.001B, 0.880C
FEV1, % predicted	41±18	99±12	101±16	<0.001A, <0.001B, 0.655C
FEV1/FVC ratio	43±15	82±8.2	84±10	<0.001A, <0.001B, 0.503C
Laboratory parameters
LDL/HDL ratio	1.6±0.80	1.7±0.72	1.4±0.69	0.543A, 0.584B, 0.269C
HbA1c, %	5.4±0.35	5.3±0.16	5.5±0.37	0.054A, 0.946B, 0.058C
Creatinine, mg/dL	0.8±0.19	0.82±0.20	0.81±0.18	0.415A, 0.469B, 0.923C
Neutrophils, ×10^3/mL	4.7±1.6	4.3±1.2	4.3±1.4	0.302A, 0.208B, 0.844C
Interleukin-6, pg/mL	2.7 (1.6–5.3)	2.2 (1.5–3.4)	0.97 (0.74–1.8)	0.051A, <0.001B, 0.123C
Cardiovascular parameters
B-IMT, mm	0.37±0.08	0.32±0.06	0.33±0.06	0.007A, 0.033B, 0.559C
B-IMA, mm^2	4.7±1.4	3.9±1.2	3.9±1.3	0.027A, 0.022B, 0.910C
Pro-BNP, pg/mL	82 (47–161)	74 (45–166)	76 (36–177)	0.975A, 0.771B, 0.814C
ADMA, μmol/L	0.47 (0.42–0.54)	0.55 (0.52–0.62)	0.54 (0.43–0.59)	0.131A, 0.817B, 0.135C

Notes: P-values are not significant unless presented.

A COPD versus smokers;

B COPD versus nonsmokers;

C nonsmokers versus smokers.

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; HDL, high-density lipoprotein; LDL, low-density lipoprotein; HbA1c, glycated hemoglobin; B-IMT, brachial intima-media thickness; B-IMA, brachial intima-media area; Pro-BNP, pro b-type natriuretic peptide; ADMA, asymmetric dimethylarginine.

Table 2 Univariate associations (Pearson’s correlation coefficient) between brachial intima-media thickness and characteristics of patients with COPD and the complete sample

Subject characteristics	COPD		Smokers		Never-smokers
	r-value	P-value	r-value	P-value	r-value	P-value
Age, years	0.421	<0.001	0.408	0.074	0.468	0.037
Body mass index, m/kg^Citation2	0.131	0.321	−0.235	0.319	0.108	0.650
Smoking history, pack-years	0.046	0.732	0.331	0.154
Systolic blood pressure, mmHg	0.314	0.016	−0.101	0.672	0.224	0.357
Acute exacerbation rate, n/year	0.251	0.014
FEV1, % predicted	−0.185	0.160	0.303	0.194	0.181	0.445
FVC, % predicted	0.034	0.799	0.355	0.125	0.094	0.693
FEV1/FVC ratio	−0.286	0.028	0.115	0.631	−0.280	0.231
HbA1c, %	0.180	0.188	0.058	0.808	0.329	0.156
HDL/LDL ratio	0.047	0.69	0.376	0.151	0.440	0.115
Neutrophil count, ×10^3/mL	−0.056	0.681	0.018	0.943	0.278	0.235
Ln interleukin-6, pg/mL	0.365	0.006	0.229	0.346	−0.229	0.331
Ln pro-BNP, pg/mL	0.225	0.101	0.185	0.477	0.338	0.169
Ln ADMA, μmol/L	0.331	0.013	0.048	0.840	−0.283	0.226

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; HbA1c, glycated hemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein; Ln, natural logarithm; Pro-BNP, pro b-type natriuretic peptide; ADMA, asymmetric dimethylarginine.

Figure 1 B-IMT in patients with stable COPD (n=60) versus smoking (n=20) and nonsmoking controls (n=20).

Abbreviations: COPD, chronic obstructive pulmonary disease; B-IMT, brachial intima-media thickness.

Figure 2 10-year risk for cardiovascular events expressed as Framingham risk score in COPD patients above (n=39) and below (n=21) the suggested reference value for B-IMT (0.345 mm).

Abbreviations: COPD, chronic obstructive pulmonary disease; B-IMT, brachial intima-media thickness.

Figure 3 Linear regression analysis between B-IMT and interleukin-6 in patients with COPD (n=60).

Abbreviations: COPD, chronic obstructive pulmonary disease; B-IMT, brachial intima-media thickness; Ln, natural logarithm.

Table 3 Independent predictors of brachial intima-media thickness in patients with COPD

Subject characteristics	β	Standardized β	P-value
Male sex	0.075	0.487	<0.001
Ln ADMA	0.084	0.311	0.011

Notes: Forward selection multiple linear regression including the following covariates: age, male sex, ln IL-6, ln ADMA, systolic blood pressure, FEV₁/FVC ratio, exacerbation rate, and ln pro-BNP. R²=0.402.

Abbreviations: COPD, chronic obstructive pulmonary disease; Ln, natural logarithm; IL-6, interleukin-6; ADMA, asymmetric dimethylarginine; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; Pro-BNP, pro b-type natriuretic peptide.

Figure 4 Linear regression analysis between ADMA and B-IMT in patients with COPD (n=60).

Abbreviations: COPD, chronic obstructive pulmonary disease; B-IMT, brachial intima-media thickness; Ln, natural logarithm; ADMA, asymmetric dimethylarginine.

ManninoDMDohertyDESonia BuistAGlobal Initiative on Obstructive Lung Disease (GOLD) classification of lung disease and mortality: findings from the Atherosclerosis Risk in Communities (ARIC) studyRespir Med2006100111512215893923

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