Subclinical carotid atherosclerosis in patients with chronic obstructive pulmonary disease: a meta-analysis of literature studies

Figures & data

Table 1. Demographic and clinical data of patients with chronic obstructive pulmonary disease (COPD) and controls in included studies.

Study	Pop (n)	Males (%)	Age (years)	Diabetes (%)	BMI (kg/m^2)	HT (%)	Smokers (%)	Ex-smokers (%)	Pack-years (n)	HL (%)	TC (mmol/l)	LDLc (mmol/l)	HDLc (mmol/l)	TGs (mmol/l)	CRP (mg/l)
Albu 2011
COPD	38	63.1	65.8	18.4	26.5	38	23.6	44.7	30	39	5.46	–	1.00	1.41	–
Controls	36	61.1	65.2	25	26.9	36	14	16.6	14	36	5.54	–	1.01	1.45	–
Arsovski 2013^a
COPD	55	55.4	–	–	–	–	–	–	–	–	–	–	–	–	–
Controls	20	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Beşir 2012
COPD	46	36.9	66.3	–	28		27	–	–	–	4.46	2.57	1.19	1.55	–
Controls	47	72.3	62.8	–	26.8		0	–	–	–	4.77	2.72	1.25	1.71	–
Chindhi 2015^a
COPD	142	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Controls	124	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Ekin 2016
COPD	91	56	61.3	–	–	–	73.6	–	–	–	–	–	–	–	–
Controls	15	40	56.2	–	–	–	53.3	–	–	–	–	–	–	–	–
Fisk 2015^a
COPD	432	61	67	–	–	–	–	–	–	–	–	–	–	–	–
Controls	324	61	67	–	–	–	–	–	–	–	–	–	–	–	–
Flu 2009
COPD	126	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Controls	382	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Frantz 2012
COPD	130	–	–	–	–	–	56.9	37.7	–	–	–	–	–	–	–
Controls	318	–	–	–	–	–	45.9	28.3	–	–	–	–	–	–	–
Golpe 2016
COPD	67	77.6	59.4	–	27.7	71.6	50.7	–	52.7	–	5.16	–	1.41	1.46	5.50
Controls	67	77.6	58.2	–	29.4	62.7	70.1	–	43.7	–	5.39	–	1.24	1.79	–
Iwamoto 2009
COPD	61	100	55.2	0	22.5	16.4	74	26	41	16.4	–	3.14	1.38	1.72	1.02
Controls	244	100	55.3	0	23.4	21.3	40	9.8	19.5	13.9	–	3.09	1.44	1.55	–
Joshi 2016
COPD	50	90	–	0	–	0	74	–	–	0	–	–	–	–	–
Controls	50	90	–	0	–	0	–	–	–	0	–	–	–	–	–
Karakas 2013
COPD	30	–	59.2	0	–	0	–	–	–	0	–	–	–	–	–
Controls	30	–	59.2	0	–	0	–	–	–	0	–	–	–	–	–
Kim 2011
COPD	42	90.5	60.1	0	23.5	0	38.1	38.1	23.9	0	5.01	3.17	1.10	1.59	1.16
Controls	84	90.5	59.6	0	23.9	0	38.1	38.1	22.7	0	5.08	3.26	1.19	1.49	–
Köseoğlu 2016
COPD	108	75	66.4	44	27.5	–	Any smoking history: 82.4%		–	–	5.02	3.01	–	–	–
Controls	78	78.2	65.6	38	26.3	–	Any smoking history: 74.3%		–	–	4.91	3.03	–	–	–
Lahousse 2013
COPD	253	56.1	79	15.8	25.9	53.8	17.4	62.8	27.5	–	5.20	–	1.40	–	–
Controls	920	39.8	78	13.3	27	50.9	6	56.5	14.4	–	5.30	–	1.40	–	–
Moro 2008
COPD	44	61.4	76.7	22.7	27.2	72.7	29.5	40.9	24.7	–	4.90	3.10	1.30	1.52	–
Controls	48	27.1	73.4	14.6	29	81.2	14.6	31.2	15.2	–	5.10	2.30	1.30	1.60	–
Ozgen Alpaydin 2013^b
COPD	50	90	61.3	0	27.2	44	66	–	–	–	–	–	1.10	1.02	2.22
Controls	40	85	58.4	0	27.6	38	52	–	–	–	–	–	1.05	1.32	–
Pan 2015
COPD	158	78.5	65	11.4	22.8	43	36.1	25.9	–	–	5.69	3.26	1.60	1.60	3.13
Controls	1467	47.5	58.7	9.3	23.9	33.2	15.2	12.4	–	–	5.87	3.39	1.57	1.87	–
Sadek 2015^c
COPD	62	90.3	61.6	–	24.9	0	45.8	32.3	–	0	4.44	2.54	1.26	1.29	13.1
Controls	62	83.9	62.7	–	23.8	0	45.8	29	–	0	2.46	2.04	1.29	0.66	–
Van Gestel 2010
COPD	97	–	–	–	–	–	–	–	–	–	–	–	–	–	–
Controls	488	–	–	–	–	–	–	–	–	–	–	–	–	–	–

COPD: chronic obstructive pulmonary disease; Pop: population; DM: diabetes mellitus; BMI: body mass index; HT: hypertension; HL: hyperlipidaemia; TC: total cholesterol; LDLc: LDL-cholesterol; HDLc: HDL-cholesterol; TGs: triglycerides. Age, BMI, TC, LDLc, HDLc, and TGs are expressed as mean values, unless otherwise indicated.

^a Only abstract available.

^b TG levels and CRP levels are expressed as median value.

^c CRP is expressed as IU/l.

Table 2. Measures of disease severity in patients with chronic obstructive pulmonary disease (COPD) in included studies.

Author	Pts (n)	FEV1 (% predicted)	FEV1/FVC	GOLD I (%)	GOLD II (%)	GOLD III (%)	GOLD IV (%)
Albu 2011	38	47.3	–	18.4	42.1	29	10.5
Arsovski 2013^a	55	–	–	–	–	–	–
Beşir 2012	46	67	59.2	–	–	–	–
Chindhi 2015^a	142	–	–	–	–	–	–
Ekin 2016	91	55.6	–	–	–	–	–
Fisk 2015^a	432	–	–	–	–	–	–
Flu 2009	126	–	–	–	–	–	–
Frantz 2012	130	–	–	66.9	GOLD II–IV → 33.1
Golpe 2016	67	58.4	51.3	16.4	44.8	32.8	6
Iwamoto 2009	61	83.3	64.7	–	–	–	–
Joshi 2016	50	–	–	0	14	60	26
Karakas 2013	30	–	–	–	–	–	–
Kim 2011	42	90.5	61.6	–	–	–	–
Köseoğlu 2016	108	66	–	GOLD I–II → 66.7		GOLD III–IV → 33.3
Lahousse 2013	253	80.5	65.6	51	41.1	GOLD III–IV → 7.9
Moro 2008	44	–	–	–	–	–
Ozgen Alpaydin 2013^b	50	46.3	53	–	–	–
Pan 2015	158	–	–	–	–	–	–
Sadek 2015^c	62	–	–	0	22.5	45.2	32.3
Van Gestel 2010	97	–	–	44.3	GOLD II–IV → 55.7

Pts: patients with chronic obstructive pulmonary disease; FEV₁: forced expiratory volume in 1 second; FVC: forced vital capacity; GOLD: Global Initiative for Chronic Obstructive Lung Disease class.

^a Only abstract available.

^b CRP is expressed as median value.

^c CRP is expressed as IU/l.

Figure 1. Common carotid artery intima-media thickness (CCA-IMT) in chronic obstructive pulmonary disease (COPD) patients and controls. 95%CI: 95% confidence interval; COPD: chronic obstructive pulmonary disease; CCA: common carotid artery.

Figure 2. Prevalence of carotid plaques in chronic obstructive pulmonary disease (COPD) patients and controls. 95%CI: 95% confidence interval; COPD: chronic obstructive pulmonary disease.

Table 3. Sensitivity analyses. Panel a: “high quality” studies (i.e. Newcastle–Ottawa Scale ≥5); Panel B: exclusion of studies potentially reporting on the same population as other included studies; Panel C: exclusion of studies providing a composite IMT; panel D: prospective studies; panel E: exclusion of studies with only abstract available.

	No. of studies	No. of patients	Effect size MD or OR [95%CI]
Panel A
CCA-IMT	9 (10 data-sets)	499 patients 506 controls	MD: 0.254 mm [0.147, 0.362]; p < .0001 I^2 = 98.5%; p < .0001
Carotid plaques	7	620 patients 1901 controls	OR: 2.703 [1.772, 4.123]; p < .0001 I^2 = 53.6%; p = .044
Panel B
CCA-IMT	11 (12 data-sets)	1150 patients 2282 controls	MD: 0.206 mm [0.139, 0.273]; p < .0001 I^2 = 98.4%; p < .0001
Carotid plaques	11	1105 patients 3840 controls	OR: 2.671 [2.111, 3.381]; p < .0001 I^2 = 38.3%; p = .094
Panel C
CCA-IMT	10 (11 data-sets)	1068 patients 2200 controls	MD: 0.105 mm [0.065, 0.145]; p < .0001 I^2 = 90.9%; p < .0001
Carotid plaques	11	1169 patients 4160 controls	OR: 2.457 [3.072, 7.882]; p < .0001 I^2 = 43.3%; p = .061
Panel D
CCA-IMT	10 (11 data-sets)	1068 patients 2200 controls	MD: 0.105 mm [0.065, 0.145]; p < .0001 I^2 = 90.9%; p < .0001
Carotid plaques	11	1169 patients 4160 controls	OR: 2.457 [3.072, 7.882]; p < .0001 I^2 = 43.3%; p = .061
Panel E
CCA-IMT	11 (12 data-sets)	748 patients 1988 controls	MD: 0.212 mm [0.117, 0.306]; p < .0001 I^2 = 98.4%; p < .0001
Carotid plaques	10	1034 patients 4078 controls	OR: 2.380 [1.832, 3.093]; p < .0001 I^2 = 51.7%; p = .028

MD: mean difference; OR: odds ratio; 95%CI: 95% confidence intervals; CCA-IMT: common carotid artery intima-media thickness.

Table 4. Subgroup analysis. Panel A: studies on mild/moderate COPD (i.e. GOLD class I and II); Panel B: studies on severe/very severe COPD (GOLD class III and IV).

Panel A
CCA-IMT	NE	NE	NE
Carotid plaques	3 (three data-sets)	225 patients 1470 controls	OR: 1.789 [1.272, 2.515]; p = .001 I^2 = 0%; p = .830
Panel B
CCA-IMT	NE	NE	NE
Carotid plaques	3 (three data-sets)	225 patients 1470 controls	OR: 3.237 [1.403, 7.472]; p = .006 I^2 = 69.3%; p = .038

COPD: chronic obstructive pulmonary disease; GOLD: Global Initiative for Chronic Obstructive Lung Disease; NE: not evaluable.

Figure 3. Meta-regression analyses. Impact of male gender (Panel A) and hypertension (Panel B) on common carotid artery intima-media thickness (CCA-IMT) in chronic obstructive pulmonary disease patients (COPD) patients and controls.

Figure 4. Meta-regression analyses. Impact of GOLD class III (Panel A) and IV (Panel B) on the prevalence of carotid plaques in chronic obstructive pulmonary disease patients (COPD) patients and controls. GOLD: Global Initiative for Chronic Obstructive Lung Disease.