COPD: Journal of Chronic Obstructive Pulmonary Disease

ISSN: 1541-2555 (Print) 1541-2563 (Online) Journal homepage: https://www.tandfonline.com/loi/icop20

Obstructive Sleep Apnea Increases the Prevalence

of Hypertension in Patients with Chronic
Obstructive Disease

Weihua Hu, Zhiling Zhao, Bin Wu, Zhihong Shi, Minglin Dong, Mengqing
Xiong, Yan Jiang, Dan Liu, Huimin Li & Ke Hu

To cite this article: Weihua Hu, Zhiling Zhao, Bin Wu, Zhihong Shi, Minglin Dong, Mengqing
Xiong, Yan Jiang, Dan Liu, Huimin Li & Ke Hu (2020) Obstructive Sleep Apnea Increases the
Prevalence of Hypertension in Patients with Chronic Obstructive Disease, COPD: Journal of
Chronic Obstructive Pulmonary Disease, 17:5, 523-532, DOI: 10.1080/15412555.2020.1815688

To link to this article: https://doi.org/10.1080/15412555.2020.1815688

Published online: 09 Sep 2020.

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COPD: JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE
2020, VOL. 17, NO. 5, 523–532
https://doi.org/10.1080/15412555.2020.1815688

Obstructive Sleep Apnea Increases the Prevalence of Hypertension in Patients

with Chronic Obstructive Disease
Weihua Hua, Zhiling Zhaob, Bin Wuc, Zhihong Shid, Minglin Donga, Mengqing Xionga, Yan Jiange, Dan Liue,
Huimin Lie, and Ke Hua
a
Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China; bDepartment of Respiratory
and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China;
c
Institute of Respiratory Diseases, Department of Respiratory, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China;
d
Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Xian Jiaotong University, Xian, Shanxi, China; eDivision of Respiratory
Disease, the Fifth Hospital of Wuhan City, Wuhan, China

ABSTRACT ARTICLE HISTORY

Whether there are increased rates of chronic diseases associated with the combination of chronic Received 12 May 2020
obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) overlap syndrome (OVS) Accepted 21 August 2020
has not been determined. The purpose of this study was to assess the prevalence of five comorbid-
KEYWORDS
ities in COPD and OVS patients. A total of 968 patients with confirmed COPD were included in this
Chronic obstructive
study. Participants were requested to fill out a questionnaire involving their basic information and pulmonary disease;
medical history. All subjects underwent one overnight polysomnography and were then divided obstructive sleep apnea;
into an OVS group or a COPD only group according to their apnea–hypopnea index. The preva- overlap syndrome;
lence of hypertension, diabetes, cardiovascular disease, arrhythmia and cerebrovascular disease comorbidity; hyperten-
were compared and risk factors for comorbidities in COPD patients were identified. Compared with sion; arrhythmia
the COPD only group, the prevalence of hypertension was significantly higher in the OVS group,
however, the prevalence rates of the other four kinds of diseases were not statistically different
between the two groups. In COPD patients, the prevalence of hypertension increased with the
severity of OSA and the prevalence of arrhythmia increased with airflow limitation severity. Risk fac-
tors for OSA in patients with COPD included BMI, FEV1%, Epworth Sleepiness Scale score and the
Sleep Apnea Clinical Score. OSA was an independent risk factor for hypertension. The other risk fac-
tors for hypertension in COPD patients included age, BMI, CAT score and alcohol consumption.
Age, lower FEV1% may be risk factors for arrhythmia. OVS patients were associated with a high
prevalence rate of hypertension, while OSA was an independent risk factor for hypertension.

Introduction desaturation and have more total time with profound hyp-
oxemia during sleep [16,17], since patients with COPD do
Chronic obstructive pulmonary disease (COPD) is a highly
not typically return to normal baseline oxygen saturation
prevalent condition, which has an estimated prevalence in
levels [18]. Additionally, OVS patients are more likely to
adults in the USA of 13.9% [1,2] and in adults in China
have a worse prognosis [19].
aged 40 years or older of 13.7% [3]. COPD often coexists
Since the association between the comorbidities of OSA or
with other diseases that may have a significant impact on
COPD is well known, the exact relationship of COPD overlap-
disease course [4–9], especially cardiovascular diseases [10].
ping OSA associated comorbidities should be further elucidated.
Furthermore, comorbidities are common with any severity
However, whether the positive effect on comorbidities is more
of COPD [11]. On the other hand, due to the sleep disor-
pronounced in OVS patients than in patients with COPD only
dered-breathing and the repeated episodes of upper airway
is unclear because there have been few studies on this issue.
closing, obstructive sleep apnea (OSA) not only affects
The purpose of this study was to assess the prevalence of five
9–26% of adults in the USA [12], but its effect on adverse
separate comorbidities in COPD only and OVS patients.
cardiovascular consequences is increasingly being recognized
[13] as well. OSA seems to be more common in patients
with COPD and it has bidirectional interactions with COPD Subjects and study protocol
[14]. The term “overlap syndrome” (OVS) has been used to
Design
describe both conditions in a single patient [15]. Compared
with either COPD only or with OSA, patients with OVS Since January 2016, we have been participating in a project
may suffer more frequent episodes of nocturnal oxygen entitled “Study on the diagnosis and treatment of

CONTACT Ke Hu huke-rmhospital@163.com Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Zhangzhidong
Road No. 99, Wuhan 430060, China
ß 2020 Taylor & Francis Group, LLC
524 W. HU ET AL.
complications and comorbidities in patients with chronic
obstructive pulmonary diseases” supported by the National
Key Research and Development Program of China (project
number: 2016YFC1304403). As part of one of its five sub-
projects, this observational study analyzed baseline data for
eligible consecutive participants in order to examine differ-
ences in the prevalence rates of hypertension, diabetes, car-
diovascular disease, arrhythmia and cerebrovascular diseases
between patients with OVS and those with COPD only.
Subjects
From January 2016 to December 2018, 968 patients with
confirmed COPD were consecutively recruited for overnight
polysomnography (PSG) examination in a sleep laboratory
from the Outpatient Department of Respiratory and Critical
Care Medicine, Renmin Hospital of Wuhan University.
Inclusion criteria for the study were as follows [20]: (1) age
between 40 to 80 years; (2) having typical symptoms of
COPD (chronic cough, breathlessness or sputum produc-
tion) and/or a history of exposure to risk factors such as
tobacco use; (3) the presence of a post-bronchodilator ratio
of forced expiratory volume in one second (FEV1)/forced
vital capacity (FVC) <0.70, and the FEV1/FVC being less
than the lower limit of normal (LLN). Exclusion criteria
included: (1) patients who had been hospitalized for cardiac
failure or respiratory exacerbations within the previous
6 weeks and those who could not undergo PSG for various
reasons; (2) needing oxygen supplementation or having
other major causes of airway limitation such as tuberculosis
or other lung diseases; (3) those with renal insufficiency
(blood creatinine level
1.5 mg/dL); (4) regular use of seda-
tive drugs such as benzodiazepines, opiates, antipsychotics,
etc.; (5) having evidence of narcolepsy, insomnia or any
other comorbid sleep disorder and (6) those who were
unwilling to participate in the study.
This study procedure was approved by the Scientific
Research and Technology Ethics Committee of Renmin Hospital
of Wuhan University and is registered in ClinicalTrials.gov
(Clinical Trials ID: NCT 03182309). All participants recruited in
this study provided their written consent.
Study protocol
Patients were initially eligible to take part in the study if
they had suspected COPD.
Patients were asked whether they had been previously
diagnosed with hypertension, diabetes mellitus, heart attack,
angina pectoris, stroke or other comorbidities. We ascer-
tained their history of using tobacco (current or past use of
any type of tobacco product) and/or alcohol (>2 drinks per
day), pharmacologic therapies of COPD. The Epworth
Sleepiness Scale (ESS), the Sleep Apnea Clinical Score
(SACS), the Modified British Medical Research Council
(mMRC) and the COPD Assessment Test (CATTM) were
used to evaluate daytime sleepiness, sleep complaints and
COPD symptoms, respectively. A nurse and/or doctor
revised the questionnaire during the consultation to make
sure the answers were reliable. Changes were made
if necessary.
After the first interview, each patient was scheduled to
undergo PSG. Blood glucose measurement and blood pres-
sure (BP) screening were taken before and after the PSG.
According to the apnea–hypopnea index (AHI), each patient
was categorized into a COPD only group (AHI < 5 events/
hour) or an OVS group (COPD patients had an AHI of
5
events/hour).
Figure 1 shows a flowchart of the study design and pro-
cess; 1105 patients with suspected COPD received a spirom-
etry test and were the study candidates. Based on the
principles mentioned above, 137 subjects were excluded, 43
of them due to an FEV1/FVC
0.70 and 94 because of
their unwillingness to undergo a PSG (n ¼ 36) or the lack of
an adequate PSG record for severe breathlessness (n ¼ 58).
In total, 968 patients were recruited for the study.
Spirometry
The FVC and the FEV1 post-bronchodilator were measured
using a body plethysmograph (MasterScreen Body, Jaeger,
Germany) and the FEV1/FVC ratio was calculated. The clas-
sification of severity of airflow limitation was based on post-
bronchodilator FEV1%.
PSG monitoring
All patients underwent an overnight PSG (SOMNOscreen
Plus Tele PSG, SOMNOmedics GmbH, Randersacker,
Germany). Sleep recordings included EEG, EOG and chin
EMG. Respiratory parameters were recorded with a nasal
cannula, thoracic and abdominal strains and pulse oxyhemo-
globin saturation (SpO2). All tracings were scored manually
by trained personnel according to the AASM guidelines
[21]. The following sleep variables were calculated: total
sleep time, average pulse oxygen saturation (mean SpO2),
lowest pulse oxygen saturation (Min SpO2), oxygen desatur-
ation index (ODI), percentage of sleep time with SpO2
<90% (T90) and AHI. A cutoff point of AHI
5 events/
hour was used to classify patients with or without OSA.
BP measurements and judgment
The BP of each patient was measured using a pneumoelec-
tric microprocessor - controlled instrument with appropri-
ate-sized cuffs (YE 660D, Yuyue Ltd, Nanjing, China) at
three time points: at the first interview, in the evening about
half an hour before the PSG and in the next morning after
the PSG but while still in bed. The recorded BP was calcu-
lated as the average of three awake consecutive measure-
ments during a 5-minute period after resting for
10 min.
Hypertension was defined as a systolic BP (SBP)
140 mm
Hg or a diastolic BP (DBP)
90 mmHg [22]; or the noctur-
nal mean systolic pressure
120 mmHg and/or nocturnal
mean diastolic BP
70 mmHg [23]. In this study, four con-
ditions were judged as hypertension: (1) having a diagnosis
of hypertension by a physician as per clinical history; (2)

Figure 1. Flowchart of study design and process.
having orally taken anti-hypertensive medications; (3) SBP

140 mmHg and/or DBP
90 mmHg at either the evening
or morning measurement and (4) PSG diagnosed nocturnal
hypertension, which was measured by the Somnotouch-
NIBP noninvasive continuous BP monitor. Beat-to-beat BP
was monitored continuously during PSG examination via
the pulse transit time (PTT)-based method [24,25].
Calibration of PTT was implemented when measurement by
cuff realized three consecutive stable results after a supine
resting period of 10 min. All systolic and diastolic BP values,
as well as pulse oximetry values were synchronized with
PSG and analyzed by “DOMINO” software (version 2.7.0,
GmbH, Randersacker, Germany).
Evaluation for diabetes mellitus and cardio-
cerebrovascular comorbidities
Diabetes mellitus was diagnosed according to a previous
diagnosis or from examination for fasting blood glucose

7.0 mmol/l or random blood glucose
11.1 mmol/l or 2 h
value in the 75 g oral glucose tolerance test
11.1 mmol/l
[26] tested by a portable blood glucose meter (Type GA-3,
SANNUO, Shuangxu Electronics Ltd, Shanghai, China) dur-
ing the first interview or before and after PSG.
The judgment for cardio-cerebrovascular diseases was
based on each patient’s previous diagnosis of cardiovascular
disease, myocardial infarction, a history of angina or cardiac
dysfunction caused by cardiovascular disease or a history of
COPD: JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE 525
cerebral infarction or cerebral hemorrhage. Twelve-lead elec-
trocardiograph (ECG) was conducted for all participants.
Holter ECG was performed on whom the ECG had an inde-
terminate diagnosis or had a history of arrhythmia.
Arrhythmia was diagnosed according to the comprehensive
results of ECG traces, Holter ECG, ECG on PSG or past
medical history.
Other key measurements
ESS was used to evaluate daytime sleepiness and SACS was
used as a screening tool for OSA. In non-COPD populations,
a cutoff point of ESS
10 was defined as subjective excessive
daytime sleepiness [27] and those with SACS scores
15
points are considered as having a high likelihood of OSA [28].
Main outcome measures
The primary end point in this study was to examine differ-
ences in the prevalence rate of specific types of comorbid-
ities between patients with COPD only and those with OVS.
The secondary end point was to analyze major risk factors
for comorbidities.
Statistical analysis
Continuous variables are expressed as means ± standard
deviation and categorical variables are expressed as absolute
526 W. HU ET AL.

Table 1. Patients’ baseline characteristics, sleep data, scores and comorbidities of the COPD only group and the OVS group.
Parameters COPD only group OVS group p value
Number of patients, n (%) 308 (31.82) 660 (68.18) –
Sex [male/female, male (%)] 256/52 (83.12) 560/100 (84.85) 0.490
Age (years) 65.45 ± 9.24 65.79 ± 9.69 0.601
BMI (kg/m2) 22.41 ± 4.04 23.68 ± 4.40 <0.0001
Neck circumference (cm) 37.93 ± 3.18 38.40 ± 3.56 0.047
Tobacco use, n (%) 247 (80.19) 523 (79.24) 0.732
Alcohol use, n (%) 115 (37.34) 275 (41.67) 0.201
AHI (events/hour) 2.20 ± 1.50 19.01 ± 15.63 <0.0001
ODI [n, x ± s (events/hour)] 267 (5.19 ± 13.76) 637 (16.04 ± 16.88) <0.0001
Mean SpO2 (%) 93.68 ± 3.33 92.15 ± 3.85 <0.0001
Min SpO2 (%) 85.21 ± 7.63 78.54 ± 1.25 <0.0001
T90 (%) 8.13 ± 20.39 16.42 ± 25.18 <0.0001
FVC (L) 2.58 ± 0.91 3.13 ± 7.34 0.191
FVC% 77.29 ± 26.80 84.92 ± 25.23 <0.0001
FEV1 (L) 1.58 ± 3.32 1.97 ± 7.04 0.355
FEV1% 49.68 ± 22.02 57.70 ± 27.23 <0.0001
FEV1/FVC (%) 47.63 ± 14.69 51.08 ± 14.39 0.001
LLN (%) 71.18 ± 1.69 71.30 ± 1.79 0.324
mMRC score 1.71 ± 0.94 1.73 ± 0.74 0.743
CAT score 16.21 ± 8.33 15.30 ± 7.04 0.077
ESS score 4.74 ± 3.94 6.52 ± 4.50 <0.0001
SACS score 6.00 ± 6.92 9.00 ± 10.97 <0.0001
CCI (n, x ± s) 302 (3.36 ± 1.70) 658 (3.54 ± 1.71) 0.150
Hypertension, n (%) 98 (31.81) 270 (40.91) 0.007
Diabetes, n (%) 29 (9.42) 74 (11.21) 0.399
Cardiovascular diseases, n (%) 66 (21.43) 161 (24.39) 0.310
Cerebrovascular diseases, n (%) 28 (9.09) 63 (9.55) 0.821
Arrhythmia, n (%) 122 (39.61) 222 (33.64) 0.070
Atrial fibrillation, n (%) 7 (2.27) 17 (2.58) 0.778
Premature atrial contraction, n (%) 15 (4.87) 24 (3.64) 0.363
Ventricular premature contraction, n (%) 12 (3.40) 19 (2.88) 0.402
Intraventricular block, n (%) 17 (5.52) 54 (8.19) 0.823
Nodal tachycardia, n (%) 15 (4.87) 30 (4.55) 0.139
Sinus bradycardia, n (%) 7 (2.27) 17 (2.58) 0.778
LAMA, n (%) 85 (27.60) 219 (33.18) 0.081
LABA þ ICS, n (%) 51 (16.57) 112 (16.97) 0.873
LAMA þ LABA þ ICS, n (%) 21 (6.82) 42 (6.64) 0.789
AHI: apnea–hypopnea index; BMI: body mass index; CAT: COPD assessment test; CCI: Charlson comorbidity index; ESS: Epworth
sleepiness scale; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; ICS: inhaled corticosteroids; LABA: long-acting
beta 2-agonist; LAMA: long-acting anticholinergics; LLN: lower limits of normal; mMRC: modified British medical research council
questionnaire; ODI: oxygen desaturation index; OVS: overlap syndrome; SACS: sleep apnea clinical score; SpO2: oxyhemoglobin
saturation; T90: percentage of sleep time with SpO2 <90%.

numbers and percentages. The normality of the distribution
of variables was tested using the Kolmogorov–Smirnov test
and the COPD only group was statistically compared with
the OVS group using a t-test. The v2 test was used to com-
pare dichotomous variables. Interrelations among variables
were examined using Pearson’s correlation coefficient.
Binary logistic regression was used to assess the effects of
OSA severity and the severity of airflow limitation on the
co-existence of morbidities, and was also used to explore the
risk factors for comorbidity. Independent variables without
multicollinearity were included in univariate regression ana-
lysis. Further multivariate analysis involved regression of
variables that were showed a univariate p value <0.05. A p
value <0.05 was considered significant. All statistical analy-
ses were performed using SAS 9.4 software (SAS Institute
Inc, Cary, NC).
Results
Coexisting rate of OSA in COPD patients and
characteristics
The participants had a ratio of FEV1/FVC < 0.70 and their
FEV1/FVC were less than LLN. Furthermore, all the patients
aged 75–80 years had FEV1/FVC < 65% and the mean
FEV1/FVC in patients >70 years was 48.0 ± 13.9%. Among
the 968 patients with confirmed COPD, 660 (68.18%) of
those patients coexisted with OSA (AHI
5) and 308
(31.82%) patients had COPD only. 30.48% of the COPD
population had a AHI of at least
15 events/hour.
Compared with the COPD only group, the OVS group
(AHI
5) had a significantly higher BMI, AHI and a larger
neck circumference, however, there were no significant dif-
ferences in sex, age and tobacco and/or alcohol use between
the two groups (Table 1).
All patients in this study were surveyed with question-
naires and were monitored by overnight PSG. The ODI,
mean SpO2, Min SpO2, T90, FVC%, FEV1%, FEV1/FVC,
ESS score and SACS score in the OVS group were signifi-
cantly different from those in the COPD only group.
Nevertheless, there were no statistical differences in mMRC,
CAT and CCI scores between the two groups (Table 1).
Prevalence of comorbidities
In terms of comorbidities, we found that the prevalence of five
comorbidities in the 968 COPD patients were hypertension
 COPD: JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE 527

Table 2. Prevalence rates of five comorbidities in COPD patients according to AHI (events/hour).
Parameters No OSA (COPD-only) (0–4.9) Mild OSA (5–14.9) Moderate OSA (15–29.9) Severe OSA (>30.0) p value
Number, n 308 365 176 119
Hypertension, n (%) 98 (31.82) 128 (35.07) 83 (47.16) 59 (49.58) <0.0001
Diabetes, n (%) 29 (9.42) 36 (9.86) 23 (13.07) 15 (12.61) 0.541
Cardiovascular diseases, n (%) 66 (21.43) 86 (23.56) 47 (26.7) 28 (23.53) 0.628
Arrhythmia, n (%) 122 (39.61) 122 (33.42) 61 (34.70) 39 (32.77) 0.334
Cerebrovascular diseases, n (%) 28 (9.09) 27 (7.40) 23 (13.07) 13 (10.92) 0.182

Figure 2. The prevalence of hypertension increased with the increasing severity of OSA. A Chi-square test indicated that the prevalence of hypertension increased
with the OSA severity (v2 ¼ 19.364, p < 0.0001). There were no significant relationships between OSA severity and diabetes (v2 ¼ 2.292, p ¼ 0.541), coronary heart
disease (v2 ¼ 1.743, p ¼ 0.628), arrhythmia (v2 ¼ 3.398, p ¼ 0.334) or cerebrovascular disease (v2 ¼ 4.895, p ¼ 0.182).

Table 3. Prevalence rates of five comorbidities in COPD patients according to the severity of airflow limitation.
Grade 1 Grade 2 Grade 3 Grade 4 p value
Number of patients, n 168 348 315 137 –
OSA, n (%) 132 (78.57) 247 (70.98) 201 (63.81) 80 (58.39) <0.0001
Hypertension, n (%) 68 (40.48) 144 (41.3) 113 (35.87) 43 (31.39) 0.153
Diabetes, n (%) 21 (12.5) 42 (12.07) 29 (9.21) 11 (8.03) 0.388
Cardiovascular diseases, n (%) 46 (27.38) 78 (22.41) 64 (20.32) 39 (28.47) 0.151
Cerebrovascular diseases, n (%) 13 (7.74) 37 (10.63) 29 (9.21) 12 (8.76) 0.742
Arrhythmia, n (%) 35 (20.83) 112 (32.18) 134 (42.54) 63 (45.99) <0.0001
Atrial fibrillation, n (%) 6 (3.57) 12 (3.45) 4 (1.27) 2 (1.46) 0.197
Premature atrial contraction, n (%) 5 (2.98) 12 (3.45) 15 (4.6) 7 (5.11) 0.651
Ventricular premature contraction, n (%) 3 (1.79) 12 (3.45) 12 (3.81) 7 (5.11) 0.458
Intraventricular block, n (%) 7 (4.17) 22 (6.32) 29 (9.21) 13 (9.49) 0.135
Nodal tachycardia, n (%) 2 (1.19) 7 (2.01) 27 (8.57) 9 (6.57) <0.0001
Sinus bradycardia, n (%) 6 (3.57) 11 (3.16) 5 (1.59) 2 (1.46) 0.373

(38.02%), diabetes (10.64%), cardiovascular disease (23.45%),
arrhythmia (35.54%) and cerebrovascular disease (9.40%). The
prevalence of hypertension in the OVS group was significantly
higher than in the COPD only group (40.91% vs. 31.81%,
p ¼ 0.007). However, we did not find that there were signifi-
cant statistical differences in the prevalence of diabetes, cardio-
vascular disease, arrhythmia or cerebrovascular disease between
the two groups, neither in several types of arrhythmia includ-
ing atrial fibrillation, premature atrial contraction, ventricular
premature contraction, intraventricular block, nodal
tachycardia and sinus bradycardia (Table 1). In terms of
pharmacologic therapies of COPD, there was no significant dif-
ference between patients with COPD only and OVS groups
(Table 1).
According to their AHI, patients with COPD were classi-
fied into four groups: non-OSA (AHI 0–4.9), mild OSA
(AHI 5–14.9), moderate OSA (AHI 15–29.9) and severe
OSA (AHI
30). Statistical analysis showed that the preva-
lence of hypertension had obvious differences among those
four groups (Table 2), which increased with the increasing
528 W. HU ET AL.

Figure 3. The prevalence of arrhythmia increased with the increasing severity of airflow limitation. A v2 test indicated that the prevalence of arrhythmia increased
with the airway limitation severity (v2 ¼ 30.835, p < 0.0001). There were no significant relationships between the varying degrees of airway limitation and hyperten-
sion (v2 ¼ 5.271, p ¼ 0.153), diabetes (v2 ¼ 3.022, p ¼ 0.388), coronary heart disease (v2 ¼ 5.297, p ¼ 0.151) or cerebrovascular disease (v2 ¼ 1.245, p ¼ 0.182).

Table 4. Results of logistic regression in analyzing the effect of OSA severity on comorbidities (Crude OR, 95% CI).
Cardiovascular diseases Cerebrovascular diseases
OSA (AHI, Hypertension (crude OR, Diabetes (crude OR, (crude OR, 95% CI, Arrhythmia (crude OR, (crude OR, 95% CI,
events/hour) 95% CI, p value) 95% CI, p value) p value) 95% CI, p value) p value)
No OSA (0–4.9) 1 1 1 1 1
Mild (5–14.9) 1.150 (0.839–1.597), 0.374 1. 053 (0.629–1.761), 0.845 1.130 (0.785–1.270), 0.510 0.765 (0.558–1.049), 0.097 0.799 (0.460–1.387), 0.425
Moderate (15–29.9) 1.912 (1.307–2.799), 0.001 1.446 (0.808–2.587), 0.214 1.336 (0.868–2.055), 0.188 0.809 (0.550–1.189), 0.280 1.503 (0.837–2.700), 0.173
Severe (
30) 2.070 (1.368–3.246), 0.001 1.388 (0.715–0.692), 0.333 1.128 (0.682–1.867), 0.639 0.743 (0.476–1.161), 0.192 1.226 (0.612–1.457), 0.565

Table 5. Results of logistic regression in analyzing the effect of the severity of airflow limitation on comorbidities.
Cardiovascular diseases Cerebrovascular diseases
Hypertension (crude OR, Diabetes (crude OR, (crude OR, 95% CI, Arrhythmia (crude OR, (crude OR, 95% CI,
Gold 95% CI, p value) 95% CI, p value) p value) 95% CI, p value) p value)
Gold 1 1 1 1 1 1
Gold 2 1.038 (0.714–1.510), 0.845 0.961 (0.549–1.681), 0.889 0.766 (0.502–1.169), 0.217 1.803 (1.167–2.786), 0.008 1.419 (0.733–2.746), 0.300
Gold 3 0.823 (0.560–1.209), 0.320 0.710 (0.391–1.288), 0.259 0.676 (0.437–1.046), 0.079 2.813 (1.822–4.343), <0.0001 1.209 (0.611–2.393), 0.586
Gold 4 0.673 (0.419–1.081), 0.101 0.611 (0.284–1.316), 0.208 1.055 (0.638–1.745), 0.833 3.235 (1.959–5.342), <0.0001 1.145 (0.505–2.597), 0.747

Table 6. Results of logistic regression used to explore risk factors for OSA in Table 7. Results of logistic regression used to explore risk factors for
COPD patients. hypertension.
Multiple regression Univariate regression analysis Multiple regression analysis
Univariate regression analysis analysis
Parameters OR a
95% CIa
p value a
ORb 95% CIb p valueb
Parameters OR a
95% CI p value OR
a a b
95% CIb
p value b
Sex 0.911 0.636–1.306 0.612 – – –
Sex 1.137 0.789–1.641 0.491 – – – Age (years) 1.038 1.023–1.052 <0.0001 1.058 1.041–1.075 <0.0001
Age (years) 1.004 0.990–1.018 0.601 – – – BMI (kg/m2) 1.114 1.079–1.151 <0.0001 1.105 1.056–1.156 <0.0001
2
BMI (kg/m ) 1.073 1.038–1.109 <0.0001 1.057 1.012-1.104 0.013 Neck 1.115 1.072–1.160 <0.0001 1.022 0.970–1.076 0.423
Neck 1.041 1.001–1.084 0.047 0.950 0.892-1.012 0.113 circumference (cm)
circumference (cm) AHI (events/hour) 1.017 1.008–1.026 <0.0001 1.009 1.001–1.019 0.047
FEV1% 1.015 1.009–1.021 <0.0001 1.011 1.005-1.018 0.001 T90 (%) 1.009 1.004–1.015 <0.0001 0.974 0.954–1.005 0.514
mMRC score 1.020 0.904–1.152 0.743 – – – FEV1% 1.004 0.999–1.009 0.151 1.000 0.994–1.005 0.890
CAT score 0.984 0.966–1.002 0.984 – – – mMRC score 1.004 0.895–1.126 0.947 – – –
ESS score 1.109 1.071–1.149 <0.0001 1.089 1.050-1.130 <0.0001 CAT score 0.977 0.960–0.995 0.010 0.974 0.954–0.995 0.014
SACS score 1.043 1.023–1.064 <0.0001 1.035 1.008-1.062 0.010 ESS score 1.042 1.012–1.073 0.006 1.017 0.984–1.052 0.319
Alcohol use 1.199 0.908–1.583 0.201 – – – Alcohol use 1.510 1.160–1.966 0.002 1.539 1.157–2.047 0.003
Tobacco use 0.943 0.673–1.321 0.732 – – – Tobacco use 1.093 0.790–1.511 0.591 – – –
a a
Results of univariate regression analysis when OSA was considered as the Results of univariate regression analysis when hypertension was considered
dependent variable and sex, age, BMI, neck circumference, FEV1%, mMRC as the dependent variable and sex, age, BMI, neck circumference, AHI, T90
score, CAT score, ESS score, alcohol and tobacco use as independ- (%TIB), FEV1%, mMRC score, CAT score, ESS score, alcohol and tobacco use
ent variables. as independent variables.
b b
Results of multiple logistic regression when OSA was considered as Results of multiple logistic regression when hypertension was considered as
the dependent variable and BMI, neck circumference, FEV1%, ESS score the dependent variable and age, BMI, neck circumference, AHI, T90 (%),
and SACS score as the independent variables. Variables (p < 0.05) in FEV1%, CAT score, ESS score and alcohol use as the independent variables.
univariate regression analysis were included in multiple regres- Variables (p < 0.05) in univariate regression analysis were included in mul-
sion analysis. tiple regression analysis.
 COPD: JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE 529

severity of OSA (Figure 2). However, the prevalence rates of Table 8. Results of logistic regression used to explore risk factors
for arrhythmia.
the other four complications in COPD patients were not sig-
Multiple regression
nificantly different. Univariate regression analysis analysis
COPD patients were stratified into four groups based on
Parameters ORa 95% CIa p valuea ORb 95% CIb p valueb
the GOLD classification of the severity of airflow limitation.
Sex 1.954 1.310–2.914 0.001 1.492 0.899–2.476 0.122
The prevalence of the five comorbidities in COPD patients is Age (years) 1.058 1.042–1.075 <0.0001 1.051 1.035–1.069 <0.0001
shown in Table 3. We found that the prevalence of arrhyth- BMI (kg/m2) 0.958 0.928–0.988 0.007 0.998 0.963–1.033 0.897
mia significantly increased with the increasing severity of air- Neck 1.005 0.967–1.044 0.815 – – –
circumference (cm)
flow limitation (Figure 3). There was statistical significant AHI (events/hour) 0.994 0.986–1.003 0.224 – – –
differences among the four groups in nodal tachycardia T90 (%) 1.006 1.001–1.011 0.020 1.005 1.000–1.011 0.060
(p < 0.0001); no statistical difference in atrial fibrillation, pre- FEV1% 0.983 0.977–0.989 <0.0001 0.990 0.983–0.997 0.004
mMRC score 1.442 1.258–1.653 <0.0001 1.153 1.000–1.329 0.051
mature atrial contraction, ventricular premature contraction, CAT score 1.053 1.034–1.072 <0.0001 1.017 0.994–1.039 0.145
intraventricular block and sinus bradycardia (Table 3). ESS score 1.029 0.999–1.060 0.062 – – –
SACS score 1.012 0.899–1.026 0.080 – – –
Alcohol use 1.046 0.800–1.368 0.742 – – –
Tobacco use 1.828 1.286–2.600 0.001 1.257 0.804–1.996 0.316
Risk factors for comorbidities a
Results of univariate regression analysis when arrhythmia was considered as
When hypertension, diabetes, cardiovascular diseases, the dependent variable and sex, age, BMI, neck circumference, AHI, T90
(%TIB), FEV1%, mMRC score, CAT score, ESS score, SACS score, alcohol and
arrhythmia and cerebrovascular diseases were recognized as tobacco use as independent variables.
the dependent variables, OSA severity was recognized as the b
Results of multiple logistic regression when arrhythmia was considered as the
independent variable [0 ¼ AHI (0–4.9), 1 ¼ AHI (5–14.9), dependent variable and sex, age, BMI, T90(%), FEV1%, mMRC score, CAT
score, tobacco use as the independent variables. Variable (p < 0.05) in uni-
2 ¼ AHI (15–29.9), 3 ¼ AHI (
30)], binary logistic regres- variate regression analysis were included in multiple regression analysis.
sion analysis showed that the prevalence of hypertension
increased with OSA severity (non-OSA OR ¼ 1, mild OSA
demonstrated that age, BMI, neck circumference, AHI, T90,
OR ¼ 1.15, 95% CI 0.839–1.597; moderate OSA OR ¼ 1.912,
FEV1%, CAT score, ESS score and alcohol consumption had
95% CI 1.307–2.799; severe OSA OR ¼ 2.07, 95% CI
correlation with the prevalence rate of hypertension.
1.368–3.246). After adjusting for sex, age, BMI and neck cir-
Independent variables related to hypertension were included
cumference, the prevalence of hypertension was still posi-
in the multivariate logistic regression analysis, which
tively correlated with the severity of OSA (mild OSA OR ¼
revealed that age, AHI, BMI and alcohol consumption were
1.112, 95% CI 0.794–1.557; moderate OSA OR ¼ 1.531, 95%
positive correlated with the prevalence of hypertension, CAT
CI 1.025–2.287; severe OSA OR ¼ 1.621,95% CI
score was negative correlated with the prevalence of hyper-
1.018–2.581), which implied that OSA was an independent
risk factor for hypertension. However, logistic regression tension (Table 7). The same approach was used to explore
analysis did not show a significant relationship between the risk factors for arrhythmias in COPD patients. Univariate
other four comorbidities and OSA severity (Table 4). logistic regression analysis indicated that sex, age, BMI, T90,
When the five comorbidities were recognized as the FEV1%, mMRC score, CAT score and using tobacco were
dependent variables and the severity of airflow limitation significantly associated with prevalence rate of arrhythmia,
(GOLD grade) was the independent variable, logistic regres- multivariate logistic regression analysis showed that age was
sion analysis found that the prevalence of arrhythmia positive correlated with the prevalence of arrhythmia,
increased with the severity of airflow limitation (GOLD 1 OR FEV1% was negative correlated with the prevalence of
¼ 1, GOLD 2 OR ¼ 1.803, 95% CI 1.167–2.786; GOLD 3 arrhythmia (Table 8).
OR ¼ 2.813, 95% CI 1.822–4.343; GOLD 4 OR ¼ 3.235, 95%
CI 1.959–5.342). After adjusting for confounding factors, the Discussion
prevalence of arrhythmia was still positively correlated with
the severity of airflow limitation (GOLD 2 OR ¼ 1.531, 95% In present study, we found that the OVS patients were asso-
CI 0.976  2.400; GOLD 3 OR ¼ 2.166, 95% CI 1.375–3.412; ciated with a high prevalence rate of hypertension, OSA was
GOLD 4 OR ¼ 2.733, 95% CI 1.606–4.649) (Table 5). an independent risk factor for hypertension. These results
Logistic regression was used to explore the risk factors for indicated that COPD patients with hypertension should be
OSA in COPD patients. Univariate regression analysis showed screened for OSA, and OVS patients should also be screened
that the BMI, neck circumference, FEV1%, ESS score, SACS for hypertension.
score were positively correlated with the prevalence of OSA An important factor involving in the prognosis and
in COPD patients; multivariate logistic regression showed health-related outcomes of COPD patients is the comorbid-
that the BMI, FEV1%, ESS score and SACS score were posi- ity [4]. Both COPD and OSA are highly prevalent and have
tively correlated with OSA prevalence (Table 6). similar physiological consequences, which may contribute to
Multicollinearity diagnosis was performed on all inde- cardiovascular and other comorbidities [29,30]. However,
pendent variables except SACS score and CCI, for which the prevalence of comorbidities in patients with OVS has
were directly related to the prevalence of hypertension. The been less investigated. Papachatzakis et al. [31] found that
results showed that there was no collinearity among the comorbidities in patients with OVS were at least as preva-
respective variables. Univariate logistic regression analysis lent as those in OSA only, however, their study was
530 W. HU ET AL.
Adjusted OR, 95% CI, Adjusted OR, 95% CI,
OSA (AHI, events/h) p value p value
No OSA (0–4.9) 1 1
Mild (5–14.9) 1.112 (0.794–1.557), 0.536 1.006 (0.591–1.713), 0.981 1.100 (0.753–1.607), 0.621 0.759 (0.574–1.054), 0.100 0.759 (0.432–1.333), 0.337
Moderate (15–29.9) 1.531 (1.025–2.287), 0.038 1.059 (0.576–1.949), 0.853 1.060 (0.673–1.670), 0.802 0.739 (0.493–1.109), 0.144 1.190 (0.647–2.190), 0.576
Severe (
30) 1.621 (1.018–2.581), 0.042 0.811 (0.393–1.675), 0.571 0.919 (0.536–1.567), 0.759 0.799 (0.496–1.788), 0.357 1.067 (0.513–2.219), 0.863
Gold Adjusted OR, 95% CI, p value Adjusted OR, 95% CI, p value Adjusted OR, 95% CI, p value Adjusted OR, 95% CI, p value Adjusted OR, 95% CI, p value
Gold 1 1 1 1
Gold 2 0.983 (0.661–1.462), 0.983 0.915 (0.510–1.641), 0.915
Gold 3 0.831 (0.548–1.260), 0.831 0.745 (0.398–1.396), 0.745
Gold 4 0.884 (0.528–1.478), 0.884 0.859 (0.383–1.929), 0.859
conducted on a small group of 38 patients with coexisting
COPD and OSA.
In this hospital population-based study, we selected five
main harmful chronic complications that are closely related
to both COPD and OSA [32] as the primary factors. We
found that COPD patients had a high prevalence of hyper-
tension, diabetes, cardiovascular disease, arrhythmia and
cerebrovascular disease, which was similar to the results
published by Mannino et al. [6]. The OVS group had a
higher prevalence of hypertension than the COPD only
group, but did not have significant differences in the preva-
lence of the other four chronic diseases. An observational
study in a Swiss cohort of COPD patients also showed that
the cardiovascular disease was not more frequent in the
patients with OVS compared with patients with COPD alone
[33], although 61% (20/33) of arterial hypertension in OVA
patients were found in their study, however, which was a
small sample, unattended sleep studying at home, and with
a different cutoff value (AHI >10) for OSA. The results in a
retrospective study [34] showed that the prevalence of arter-
ial hypertension was as high as 82% in OVS patients. In
which, however, all the patients were referred to the sleep
center for sleep diagnostic testing, with the BMI of
33.32 ± 7.23 kg/m2 and an AHI of 42.69 ± 23.74 events/hour.
Du et al. [35] investigated the role of OSA on all-cause mor-
tality in patients with COPD, they found that there was no
significant difference in overall mortality between OVS
patients and patients with COPD alone, which implied that
OSA did not significantly increase the risk of death in
patients with COPD.
Our data also showed that COPD patients had a high
prevalence of OSA. Compared with patients with COPD
only, the OVS patients had significantly higher BMI, neck
circumference, AHI, ODI, T90, ESS and SACS scores, lower
mean SpO2 and Min SpO2 and longer SpO2 <90% during
sleep, which were also consistent with the results of other
previous studies [36,37]. Although male and older age are
generally considered as risk factors for OSA [38], we did not
find that the COPD only group and the OVS group had
obvious differences in sex and age, perhaps the older, male-
dominated Chinese COPD patients in our study may con-
tribute to this lack of difference. In the present study, the
COPD patients had an average age of (65.68 ± 9.546) years
and males accounted for 84.3% of the patients, other studies
had the same results [3,39]. Tobacco [37] and alcohol use
[40] were also suggested as risk factors for OSA, but the
Adjusted OR, 95% CI, Adjusted OR, 95% CI, Adjusted OR, 95% CI,
p value p value p value
1 1 1
1 1
0.647 (0.413–1.012), 0.056 1.531 (0.976–2.400), 0.064 1.230 (0.624–2.423), 0.550
0.574 (0.319–0.917), 0.020 2.166 (1.375–3.412), 0.001 1.061 (0.522–2.154), 0.870
1.213 (0.710–2.908), 0.490 2.733 (1.606–4.649), <0.0001 1.296 (0.550–3.057), 0.553
results are conflicting [41]. We did not find significant dif-
ferences in tobacco or alcohol use between patients with
OVS or with COPD only.
We also found that the prevalence of arrhythmia
increased with the severity of airflow limitation. Increased
arrhythmogenicity in COPD patients has been recognized
for decades [41], especially during acute exacerbation [42].
The oxidative stress, low oxygenation, pulmonary hyperten-
sion and the use of b-agonistic bronchodilators are specu-
lated to be liable causative factors [43].
The interaction between COPD and OSA has been
studied for a long time and the results are controversial.
Earlier studies showed higher prevalence of OVS in patients
with more severe grade of COPD, however, recent studies
demonstrated that there was no or an inverse correlation
between the AHI and the severity of emphysema [44,45].
The investigators proposed that lung volume is an important
“protective” determinant for upper airway stability. Potential
mechanisms are (1) mediastinal caudal traction generated by
the diaphragm; and (2) an increase in the transmural dis-
tending pressure in the upper airway induced by thoracic
expansion during inspiration [45].
Multivariate logistic regression analysis showed that the
prevalence rate of hypertension in COPD patients had posi-
tive correlation with age, BMI and alcohol consumption,
which had already been believed as the risk factors for
hypertension by other researchers [46]. Logistic regression
analysis also found that the risk factors for arrhythmia
included older age and lower FEV1%. The high prevalence
of arrhythmia in COPD patients was speculated to be ultim-
ately caused by hypoxia, hypercapnia, pulmonary arterial
hypertension [47].
It was reported that LLN of FEV1/FVC was superior to
FEV1/FVC < 0.7 in the diagnosis of COPD [48], for fixed
ratio defined airflow limitation may lead to over-diagnosis
in the elderly. However, the results from Bhatt et al. [49]
showed that the diagnostic value of LLN was equivalent to a
fixed value of 0.7. We used the reference equations provided
by the Global Lung Initiative for North East Asia to calcu-
lated LLN [48], and the results showed that all participants
had FEV1/FVC < LLN, which indicated no over-diagnosis of
COPD in this cohort.
The major strength of our study was that all diagnoses of
OSA in COPD patients were established by overnight PSG,
which is the gold standard for diagnosing OSA. Questionnaires

are of great value for screening simple OSA, however, there is
controversy about their significance in screening OVS [50].
We also acknowledge several limitations of this study.
First, although this study had a large sample size, only base-
line results have been evaluated so far and follow-up studies
are being conducted. Second, the enrolled patients were
from hospitals rather than the community population and
therefore, there is likely a population selective bias in this
study. Third, we did not rule out the effect of the “first
night” of PSG on results. Forth, for baseline data evaluation,
only five major comorbidity diseases were selected for obser-
vation, and other comorbidities that required special exam-
ination or subjective diseases were not included. Last, this
study did not observe comorbidities in the OSA only group
at the same time.
Conclusions
Our study revealed that: (a) OSA was associated with
68.18% of patients with confirmed COPD; and (b) in
patients with coexisting OSA, the frequency of hypertension
was high and increased with the severity of OSA. OSA was
an independent risk factor for hypertension; (c) the preva-
lence of arrhythmia increased with the severity of COPD.
Funding
This work was supported by the National Key Research and
Development Program of China (project number:
2016YFC1304403).
Disclosure statement
No potential conflict of interest was reported by the author(s).
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