No association between exacerbation frequency and stroke in patients with COPD

Figures & data

Table 1 Baseline characteristics and univariable analysis of association with stroke

Characteristic	Cases (%), n=6,441	Controls (%), n=19,323	OR (95% CI)a
Male	3,473 (53.9)	10,419 (53.9)
Age, mean years ± SD	74.9 (9.2)	74.8 (9.1)
Frequent exacerbators	1,723 (26.8)	5,430 (28.1)	0.93 (0.87–0.99)
GOLD staging (n=22,272)
1	880 (13.7)	2,639 (13.7)	1
2	2,777 (43.1)	8,351 (43.2)	0.98 (0.90–1.08)
3	1,407 (21.8)	4,754 (24.6)	0.87 (0.79–0.97)
4	320 (5.0)	1,144 (5.9)	0.82 (0.70–0.96)
Smoking status (n=25,723)
Never smoked	627 (9.7)	2,062 (10.7)	1
Ex-smoker	2,776 (43.1)	8,806 (45.6)	1.04 (0.94–1.15)
Current smoker	3,028 (47)	8,424 (43.6)	1.20 (1.08–1.33)
Body mass index (n=24,999)
<20	917 (14.8)	2,516 (13.4)	1
20–25	1,999 (31.2)	5,964 (31.8)	0.92 (0.84–1.01)
25–30	1,948 (31.3)	6,078 (31.5)	0.87 (0.80–0.96)
>30	1,354 (21.8)	4,223 (22.5)	0.87 (0.79–0.96)
Stroke risk factors
Positive family history	1,615 (25.1)	4,688 (24.3)	1.05 (0.98–1.12)
Dyslipidemia	1,374 (21.3)	3,810 (19.7)	1.12 (1.04–1.20)
Hypertension	3,448 (53.5)	9,374 (48.5)	1.24 (1.17–1.31)
Diabetes	1,157 (18.0)	2,951 (15.27)	1.22 (1.13–1.32)
Cardiovascular disease
PCI	202 (3.1)	514 (2.7)	1.19 (1.01–1.40)
PAD	724 (11.2)	1,503 (7.8)	1.51 (1.37–1.66)
Acute coronary syndrome	50 (0.8)	113 (0.6)	1.33 (0.95–1.86)
MI	746 (11.6)	1,970 (10.2)	1.16 (1.06–1.26)
Heart failure	895 (13.9)	2,317 (12.0)	1.19 (1.09–1.30)
CABG	239 (3.7)	589 (3.1)	1.24 (1.06–1.44)
Angina	1,142 (17.8)	3,163 (16.4)	1.10 (1.02–1.19)
Atrial fibrillation	1,064 (16.5)	2,146 (11.1)	1.61 (1.48–1.75)
Cardiac medications
β-blocker	2,170 (33.7)	5,240 (27.1)	1.38 (1.30–1.47)
ACE inhibitor	3,017 (46.8)	8,051 (41.7)	1.24 (1.17–1.32)
Angiotensin II inhibitor	1,076 (16.7)	2,732 (14.1)	1.23 (1.14–1.33)
Nitrate	1,338 (20.7)	3,717 (19.2)	1.10 (1.03–1.18)
Calcium channel blocker	2,174 (33.8)	5,752 (29.8)	1.21 (1.14–1.29)
Lipid lowering medication	3,217 (50.0)	8,503 (44)	1.30 (1.22–1.37)
Antiplatelet	3,831 (59.5)	8,782 (45.5)	1.82 (1.71–1.93)
Anticoagulant	847 (13.2)	2,137 (11.1)	1.22 (1.12–1.32)

Note:

a Adjusted for age, sex, and GP.

Abbreviations: OR, odds ratio; CI, confidence interval; SD, standard deviation; GOLD, Global Initiative on Obstructive Lung Disease; PCI, percutaneous coronary intervention; PAD, peripheral arterial disease; MI, myocardial infarction; CABG, Coronary Artery Bypass Graft; ACE, angiotensin-converting enzyme; GP, general practice.

Table 2 Multivariable analysis of the odds of stroke and type of stroke, comparing COPD patients with frequent exacerbations to those with infrequent exacerbations

Stroke type	Exacerbation frequency	Cases (%)	Controls (%)	Crude ORa (95% CI)	Adjusted ORb (95% CI)
All stroke		n=6,431	n=19,292
	Infrequent	4,709 (73.2)	13,864 (71.9)	1	1
	Frequent	1,722 (26.8)	5,428 (28.1)	0.94 (0.88–1.00)	0.95 (0.89–1.01)
Ischemic		n=1,262	n=3,786
	Infrequent	944 (74.8)	2,769 (73.1)	1	1
	Frequent	318 (25.2)	1,017 (26.9)	0.93 (0.79–1.07)	0.93 (0.81–1.08)
Hemorrhagic		n=420	n=1,260
	Infrequent	331 (78.8)	900 (71.4)	1	1
	Frequent	89 (21.2)	360 (28.6)	0.68 (0.52–0.88)	0.67 (0.51–0.88)
TIA		n=2,457	n=7,371
	Infrequent	1,758 (71.6)	5,254 (71.3)	1	1
	Frequent	699 (28.5)	2,117 (28.7)	0.99 (0.89–1.09)	1.00 (0.90–1.11)

Notes:

a Adjusted for age, sex, GP, and smoking status,

b adjusted for age, sex, GP, smoking status, hypertension, diabetes, dyslipidemia, atrial fibrillation, heart failure, peripheral arterial disease, CABG, calcium channel blockers, β-blockers.

Abbreviations: COPD, chronic obstructive pulmonary disease; OR, odds ratio; CI, confidence interval; TIA, transient ischemic attack; GP, general practice; CABG, coronary artery bypass graft.

Figure 1 Association between number of COPD exacerbations per year and stroke.

Notes: *Adjusted for age, sex, GP, smoking, hypertension, diabetes, dyslipidemia, atrial fibrillation, CABG, PAD, heart failure, calcium channel blockers, β-blockers. P_trend =0.003.
Abbreviations: OR, odds ratio; CI, confidence interval; COPD, chronic obstructive pulmonary disease; GP, general practice; CABG, coronary artery bypass graft; PAD, peripheral artery disease.

Table S1 Comparison of characteristics, between individuals with missing data and individuals without missing data

Characteristic	Number of individuals with missing smoking status (%), (n=41)	Number of individuals without missing smoking status (%), (n=25,723)	Number of individuals with missing GOLD stage (%), (n=3,492)	Number of individuals without missing GOLD stage (%), (n=22,272)	Number of individuals with missing BMI (%), (n=765)	Number of individuals without missing BMI (%), (n=24,999)
Stroke
Yes	10 (24.4)	6,431 (25.0)	1,057 (30.3)	5,384 (24.2)	223 (29.2)	6,218 (24.9)
No	31 (75.6)	19,292 (75)	2,435 (69.7)	16,888 (75.8)	542 (75.0)	18,781 (75.1)
Exacerbations
Infrequent	38 (92.7)	18,573 (72.2)	2,736 (78.4)	15,875 (71.3)	593 (77.5)	18,018 (72.1)
Frequent	3 (7.3)	7,150 (27.8)	756 (21.7)	6,397 (28.7)	172 (22.5)	6,981 (27.9)
Age (years)
35–59	0 (0)	1,744 (6.8)	179 (5.1)	1,565 (7.0)	27 (3.5)	1,717 (6.9)
60–69	1 (2.4)	5,806 (22.6)	512 (14.7)	5,295 (23.8)	85 (11.1)	5,722 (22.9)
70–79	7 (17.1)	9,785 (38.0)	1,138 (32.6)	8,654 (38.9)	229 (29.9)	9,563 (38.3)
≥80	33 (80.5)	8,388 (32.6)	1,663 (47.6)	6,758 (30.3)	424 (55.4)	7,997 (40.0)
Sex
Male	26 (63.4)	13,866 (53.9)	1,611 (46.1)	12,281 (55.1)	376 (49.2)	13,516 (54.1)
Female	15 (36.6)	11,857 (46.1)	1,881 (53.9)	9,991 (44.9)	389 (50.9)	11,483 (45.9)

Abbreviations: GOLD, Global Initiative on Obstructive Lung Disease; BMI, body mass index.