A systematic review on the association of sleep-disordered breathing with cardiovascular pathology in adults.

Sleep-disordered breathing (SDB) is characterized by repeated breathing pauses during sleep. The prevalence of SDB varies widely between studies. Some longitudinal studies have found an association of SDB with incident or recurrent cardiovascular events. We sought to systematically describe the current data on the correlation between SDB and cardiovascular pathology. Studies were included if they were original observational population-based studies in adults with clearly diagnosed SDB. The primary outcomes include all types of cardiovascular pathology. We carried out pooled analyses using a random effects model. Our systematic review was performed according to the PRISMA and MOOSE guidelines for systematic reviews and was registered with PROSPERO. In total, 2652 articles were detected in the databases, of which 76 articles were chosen for full-text review. Fourteen studies were focused on samples of an unselected population, and 8 studies were focused on a group of persons at risk for SDB. In 5 studies, the incidence of cardiovascular pathology in the population with SDB was examined. In total, 49 studies described SDB in patients with cardiovascular pathology. We found an association between SDB and prevalent /incident cardiovascular disease (pooled OR 1.76; 95% CI 1.38-2.26), and pooled HR (95% CI 1.78; 95% CI 1.34-2.45). Notably, in patients with existing SDB, the risk of new adverse cardiovascular events was high. However, the relationship between cardiovascular disease and SDB is likely to be bidirectional. Thus, more large-scale studies are needed to better understand this association and to decide whether screening for possible SDB in cardiovascular patients is reasonable and clinically significant.

Introduction

Sleep-disordered breathing (SDB) is characterized by repeated breathing pauses during sleep[1]. According to the American Academy of Sleep Medicine (AASM), the main types of respiratory events are obstructive apnea or hypopnea, central apnea and mixed apnea[2]. A respiratory event is scored as an apneic episode if it meets the following criteria: a drop of the oronasal flow ≥90%, the duration of the event is over 10 s, and it is associated with continued inspiratory effort[2]. In obstructive hypopnea, the duration of the ≥30% drop in oronasal flow lasts ≥10 s and is associated with ≥3% oxygen desaturation from a pre-event baseline or with an arousal[2]. The event is defined as central if it meets apnea criteria and is associated with a lack of inspiratory effort[2]. If the event meets the apnea criteria and is associated with a lack of inspiratory effort at the beginning of the event, followed by resumption of inspiratory effort in the second portion of the event, it is classified as mixed apnea[2]. In the AASM guidelines, there are three additional types of respiratory events that are less prevalent: respiratory effort-related arousals (RERA), hypoventilation and periodic breathing. SDB is labeled as mild, moderate or severe based on the number of apnea and/or hypopnea episodes per hour of sleep, known as the apnea-hypopnea index (AHI)[3]. The prevalence of SDB varies widely because of the heterogeneity of the study methodology, different diagnostic standards (full polysomnography or portable sleep monitoring) and different AHI cut-offs. The prevalence of SDB has been reported to range between 17 and 49% for AHI ≥ 5[4,5] and between 4.6 and 43.7% for AHI ≥ 15[6,7].

Some longitudinal studies have found an association of SDB with incident or recurrent cardiovascular events: heart failure, myocardial infarction, stroke/transient ischemic attack[8-12]. Previous studies[7,13,14] have shown that there is a dose-response relationship between the severity of SDB and the risk of various clinical manifestations of cardiovascular disease (CVD). These studies were conducted predominantly in cardiology patients or patients with an established diagnosis of SDB. Only a few studies focusing on this association in an unselected population have been published[14-16].

SDB influences CVD through numerous pathophysiological mechanisms. The most likely causal pathway through which SDB causes CVD is thought to be intermittent hypoxia, endothelial dysfunction and inflammation, repetitive arousal from sleep, large intrathoracic pressure variations and increased sleeping blood pressure[17-19]. While the acute, unfavorable effects of sleep disorders on cardiovascular physiology have been well characterized, less research is available on how strong the effect of SDB is on symptomatic CVD. Previous systematic reviews were mostly based on a particular type of cardiovascular pathology or cardiovascular outcome[20-22].

The main objective of this systematic review is to systemize the current data on the association between SDB and cardiovascular pathology.

Methods

Search question and search strategy

Our systematic review was performed according to the PRISMA and MOOSE guidelines for systematic reviews[23,24]. A systematic literature review was added to the PROSPERO register (registration number is CRD42018082314).

A ‘PACO’ (Patient-Type of Association-Comparison-Outcome) analogous to the ‘PICO’ (Patient-Intervention-Comparison-Outcome) for systematic reviews of interventional studies, was created to guide our systematic review of observational studies.

Our basic aim was to review the association between SBD and prevalent and/or incident CVD. Our research question was further operationalised as: (P) Patients with a documented SBD (A): cross-sectional or longitudinal associations (C) Persons without SBD, (O) Prevalent/incident CVD.

Since we aimed to investigating the association between SBD and CVD in a bidirectional way, we decided to search for complementary studies that investigated the prevalence and/or incidence of SBD in patients with an established CVD.

The search was made in PubMed, Ovid and EMBASE databases in February 2022 without limitations on language, publication year or country. The search strategy included only terms relating to or describing the association of SDB and cardiovascular pathology. The search terms were adapted for use with bibliographic databases separately and in combination with database-specific filters.

The search terms were obstructive sleep apnea syndrome, obstructive sleep apnea, sleep apnea, obstructive sleep apnea hypopnea syndrome, sleep-disordered breathing, heart failure, cardiac insufficiency, heart insufficiency, atrial fibrillation, cerebral vascular accident, stroke and myocardial infarction.

The identified articles were screened by title and abstract and selected for full text review if they met the following inclusion criteria developed according to the objectives of the review.

Original observational (including cross-sectional, cohort and case–control studies) that were population-based and concerned the adult population.

Studies in hospital cardiovascular departments, in sleep centers and studies of unselected populations.

The diagnosis of SDB was based on the apnea-hypopnea index or respiratory disturbance index (RDI), which were obtained by the gold standard for diagnosing full polysomnography or portable home sleep apnea testing[2].

The primary outcome concerned the following types of cardiovascular pathology: heart failure, cardiovascular disease, coronary heart disease, atrial fibrillation, stroke, myocardial infarction.

A diagnosis of cardiovascular pathology was based on the clinical evidence, laboratory data and/or functional methods of examination.

Exclusion criteria.

Studies on children and pregnant women.

The diagnosis of SDB was based on a questionnaire or ICD-9 diagnosis code.

If only risk factors for CVD were studied as an outcome.

Data extraction

Titles and/or abstracts of studies retrieved by the search strategy were screened independently by two reviewers (AH and EA) to identify studies that potentially met the inclusion criteria. The full text versions of these potentially eligible studies were retrieved and independently assessed for eligibility by two review team members. Any disagreement between them over the eligibility of studies was resolved through discussion with a third reviewer (JD). A standardized form was used to extract data from the included studies for assessment of study quality and evidence synthesis. Extracted information included study setting; study population and participant demographics and baseline characteristics; study design and methodology; type of SDB and cardiovascular pathology; observation time, if possible; and results (prevalence in percentage, odds ratios and hazard ratios, if possible). Two reviewers extracted data independently; discrepancies were identified and resolved through discussion (with a third author when necessary). Missing data were requested from study authors.

Quality assessment

Two reviewers (AH and EA) independently assessed the methodological quality of the selected studies with the Quality Assessment Tool for Case-Control, Cohort and Cross-sectional Studies, depending on the study design (https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools).

Statistical analysis

We looked at data from cross-sectional studies and cohort studies separately to estimate the effect of SDB on the risk of cardiovascular pathology. We collected multivariable-adjusted (if possible) hazard ratios (HR) or odds ratios (OR) from the original studies. When a study did not report the OR of the outcomes of interest, we calculated an unadjusted OR based on the original data of events. We performed random effects analysis to quantify the dispersion of effect sizes in a meta-analysis. We pooled the HR and OR separately with a 95% confidence interval (CI) for adverse cardiovascular outcomes within a random effects model (DerSimonian-Laird) that incorporates between-study heterogeneity. The Cochran Q test (at a significance level of p < 0.10) and the I2 statistic were used to examine statistical heterogeneity across studies. We planned to assess publication bias using visual evaluation of the funnel plots. All analyses were performed with Cochrane Review Manager software (version 5.3).

Table 1

Association of sleep-disordered breathing and cardiovascular disease in an unselected population: study characteristics, outcomes and results.

First author	Year	Country	Study Design	Sample Size	Age	Diagnostic Standard	Outcome	Follow-up Period	AHI cut-off		Overall prevalence	Odds ratio (95% CI)	Hazard ratio (95% CI)	Adjusted for
Roca G.Q. et al.	2015	USA	cohort	1645	62.5 ± 5.5	PSG	All-cause mortality, incident CHD and HF	13.6 ± 3.2 years	15		Men 23%	–	–	Age, BMI, prevalent hypertension and diabetes, systolic BP, smoking status, and use of medications.
											Women 10.4%	OR: 1.25 (1.02–1.52)	HR: 1.33 (1.03–1.74)
Javaheri S. et al.	2015	USA	cohort	2865	76.3 ± 5.5	PSG	Incident HF	7.3 years	AHI > 15		43.7%	OR: 1.9 (1.4–2.6)	–	Clinic, age, race, BMI, history CAD, HF, stroke, diabetes, hypertension, smoking, alcohol use, and physical activity.
									CAI > 5		7.3%	OR: 2.16 (1.4–3.4)	HR: 1.79 (1.16–2.77)
Redline S. et al.	2010	USA	cohort	5422	median 72	PSG	Incident stroke (nonfatal or fatal)	8.7 years	15		20.2%	OR: 2.26 (1.45–3.52)	HR: 2.64 (1.01–6.88)	Age, BMI, smoking status, systolic BP, use of medications, diabetes status, and race.
Gottlieb D.J. et al.	2010	USA	cohort	4422	64 (57, 72) men	PSG	CHD, HF	Median of 8.7 years	15		24% men	–	CHD HR: 1.10 (1.00–1.21) HF HR: 1.13 (1.02–1.26)	Age, race, BMI, smoking, total and HDL cholesterol, lipid- lowering meds, diabetes mellitus, systolic BP, diastolic BP, and anti- hypertensive medications.
					66 (58, 74) women						11% women
Munoz R. et al.	2007	Spain	cohort	394	median 77, 28 years	PSG	Ischemic stroke	6 years	30		24.1%	–	HR: 2.52 (1.04–6.01), P 0.04	Sex
Marshall N.S. et al.	2014	Australia	cohort	400	55.1 ± 8.2	PSM	All-cause mortality (CVD, CHD, Stroke)	20 years	5		20.6%	–	HR: 0.5 (0.27–0.99)	Age, sex, BMI, smoking status, total cholesterol, HDL cholesterol, mean arterial pressure, diabetes, angina, and history of CVD.
									15		4.6%		HR: 4.2 (1.9–9.2)
Stone K.L. et al.	2015	USA	cohort	2872	76.3 ± 5.5	PSG	Incident stroke	7.3 years	5		–	–	HR: 1.83 (1.12–2.98)	Age, clinic, race, BMI, and smoking
Munoz R. et al.	2012	Spain	cohort	394	median 77.3	PSG	Ischemic stroke	4.5 years	CAI > 1		–	–	HR: 2.65 (1.08–6.49)	AF
									CAI > 3				HR: 3.08)1.26–7.52)	AF and sex.
Hla Khin Mae et al.	2015	USA	cohort	1280	47 ± 8	PSG	CHD, HF	24 years	5–15		14%	_	HR: 1.9 (1.05–3.5)	Age, sex, BMI, and smoking.
									15–30		5%		HR: 1.8 (0.85–4.0)
									>30		4%		HR: 2.6 (1.1–6.1)
May A. M. et al.	2016	USA	cohort	843	75 ± 5	PSG	Incident AF	65 ± 0.7 years	CSA > 5		6%	OR: 9.97 (2.72–36.50)	_	Age, clinic, race, BMI, history of CVD, hypertension, diabetes, stroke, COPD, pacemaker placement, total cholesterol, use of medications, and alcohol use.
									AHI > 15		41,7%	OR: 2.64 (1.16–6.00)
Tung P. et al.	2017	USA	cohort	2912	62.8 ± 11.2	PSG	Incident AF	5.3 years	AHI	5	49%	–	_	Age, clinic, race, BMI, history of CVD, hypertension, diabetes mellitus, stroke, COPD, pacemaker placement, total cholesterol, use of cardiovascular medications, and alcohol.
										15	19%	–
										30	7%	–
									CAI > 5		2.5%	OR: 3.00 (1.40–6.44)
Kwon Y. et al.	2015	USA	cross-sectional	2048	68.4 ± 9.2	PSG	AF	–	15		33.74%	OR: 1.23 (1.01–1.50)	_	Age, field center, race/ethnicity, sex, BMI, height, smoking status, diabetes, systolic BP, and medications.
Arzt M. et al.	2005	USA	cross-sectional	1475	47 ± 8	PSG	Stroke	–	5		17%		–
									20		7%	OR: 3.83 (1.17–12.56)		Age, sex, BMI, alcohol, smoking, diabetes, and hypertension.
Cho E.R. et al.	2013	Korea	cross-sectional	746	59.3 ± 7.2	PSG	Cerebral infarction	–	15		12.06%	SCI OR: 2.44 (1.03–5.80)	–	Age, hypertension and diabetes mellitus.
												Lacunar infarction OR: 3.48 (1.31–9.23)

AF atrial fibrillation, AHI apnea-hypopnea index, BMI body mass index, BP blood pressure, CAD coronary artery disease, CAI central apnea index, CHD coronary heart disease, COPD chronic obstructive pulmonary disease, CVD cardiovascular disease, HDL high density lipoprotein, HF heart failure, HR hazard ratio, OR odds ratio, PSM portable sleep monitor, PSG polysomnography, SCI silent cerebral infarction.

Table 2

Association of sleep-disordered breathing and cardiovascular disease in a population at risk of SDB: study characteristics, outcomes and results.

Author	Year	Country	Study Design	Sample Size	Age	Outcome	Follow-up period	AHI cut-off	Prevalence	OR (95% CI)	HR (95% CI)	Adjusted for
Cadby G. et al.	2015	Australia	cohort	6841	48.3 ± 12.5	AF	11.9 years	5	63.6%	OR: 2.8 (2.2–3.6)	HR: 1.55 (1.21–2.00)	Age, sex, height, BMI, hypertension, valvular disease, stroke/TIA, coronary or peripheral artery disease, COPD, chronic renal disease, HF, and diabetes.
Gami A.S. et al.	2013	USA	cohort	10,701	53 ± 14	Sudden cardiac death	5.3 years	5	78%	–	–
								20	–		HR 1.05 (1.00–1.09)	Univariate analyses
Shah N.A. et al.	2010	USA	cohort	1436	60	CVD	2.8 years	5	71%	–	HR: 2.06 (1.10–3.86)	Age, race, sex, smoking, alcohol use, BMI, AF, hypertension, hyperlipidemia, and diabetes.
Yaggi H. K. et al.	2005	USA	cohort	1022	60,9	Incident stroke/TIA or all-cause death	3.4 years	5	68%	–	HR: 1.97 (1.12–3.48)	Age, sex, race, smoking, alcohol use, BMI, presence of diabetes mellitus, hyperlipidemia, AF, and hypertension.
Gami A.S. et al.	2007	USA	cohort	3542	49 ± 14	Incident AF	4.7 years	5	74%	–	HR: 2.18 (1.34–3.54)	Univariate analyses
Kendzerska T. et al.	2014	Canada	cohort	10,149	49,9 ± 14,1	MI, stroke, CHF, revascularization procedure, all-cause death	68 months	5	79.2%	–	HR: 1.12 (1.05–1.2)	BMI, age, sex, smoking, hypertension, diabetes, MI, stroke, and HF.
Selim B.J. et al.	2016	USA	cross-sectional	697	58.7 ± 12.1	Nocturnal cardiac arrhythmias	–	5	77%	–	–
								15	56%	OR: 2.24 (1.48–3.39)		Age, BMI, sex, and CVD.
Roche F. et al.	2002	Switzerland	cross-sectional	147	54.5 ± 10.7	Nocturnal paroxysmal asystole	0	10	44.9%	OR: 9.5 (1.14–79.2)	–	Not adjusted

AF atrial fibrillation, AHI apnea-hypopnea index, BMI body mass index, COPD chronic obstructive pulmonary disease, CVD cardiovascular disease, HF heart failure, HR hazard ratio, MI myocardial infarction, OR odds ratio, PSM portable sleep monitor, PSG polysomnography, TIA transient ischemic attack.

Table 3

Association of sleep-disordered breathing and cardiovascular disease in patients with an established cardiovascular pathology.

First Author	Year	Country	Sample Size	Age	Diagnostic standard	Type of CVD	Outcome	Follow-up period	AHI cut-off	Prevalence		Odds ratio (95% CI)	Hazard ratio (95% CI)	Adjusted for
Sano K. et al.	2013	Japan	178	71.4 ± 1.3	PSG	CHF	Death from CV causes (worsening HF, ventricular tachyarrhythmia systemic embolism, stroke, acute MI, or aortic dissection)	22 months	CAI >7.5	38.7%		AF OR: 1.03 (1.02–2.51)	HR: 1.29 (1.16–2.32)	For OR: age, sex, BMI, NYHA class, LVEF, brain natriuretic peptide, CAI, minimum SpO2, duration of SpO2 <90%, C-reactive protein, and the use of a beta-blocker. For HR: age, NYHA class, LVEF, C-reactive protein, brain natriuretic peptide, and minimum SpO2.
												Sinus pause OR: 1.12 (1.08–1.35)
												Nonsustained ventricular tachycardia daytime OR: 1.22 (1.00–6.92), nighttime OR: 3.57 (1.06–13.1)
Mooe T. et al.	2001	Sweden	408	< 70 years	PSG	CAD	Composite of death, CV events, and MI	5.1 years	≥10	34%		composite end point OR: 1.62 (1.09–2.41)	HR: 2.98 (1.43–6.20)	Age, sex, BMI, and hypertension.
												CV events OR: 3.41 (1.73–6.71)
Silvia L. et al.	2016	Portugal	73	63.5 ± 10.3	PSM	Acute Coronary Syndrome	All-cause mortality, MI, and myocardial revascularization	75 months	>5	63%		–	–	Sex
									≥15	–			HR: 3.58 (1.09 −17.73)
Shah R.V. et al.	2014	USA	403	median 57	PSG	AF	All-cause mortality/HF hospitalization	3.3 ± 0.5 years	>5	19%		–	HR: 2.14 (1.16–3.98)	Age, male sex, BMI, history of HF, hyperlipidemia, hypertension, diabetes, left ventricle mass-to-volume ratio, left ventricular end-systolic volume index, left ventricular myocardial infarction, and right ventricular ejection fraction.
Ponsaing L.B. et al.	2017	Denmark	63	median 67.5	PSG	Stroke/ TIA	Mortality	19–37 months	>24	–		–	stroke severity HR: 10.95 (1.25–95.14	Age, disability measured with the modified Barthel index, and atrial fibrillation were nonsignificant.
													disability HR: 11.08 (1.23–99.52)
Emdin M. et al.	2017	Italy	525	66 ± 12	PSM	Systolic HF	Cardiac mortality	median 34 month	>5	CSA 38.2%	nighttime 49.9%	–	HR: 1.02 (1.01–1.04)	Age, N-terminal pro–B-type natriuretic peptide, estimated glomerular filtration rate, and LVEF.
											daytime 28.4%		HR: 1.03 (1.01–1.06)
										OSA 4.5%	nighttime 9%		HR: 1.02 (1.01–1.04)
											daytime 1.5%
Lee Chi-Hang et al.	2011	Singapore	120	52.7 ± 9.8	PSM	Acute MI	Death, reinfarction, stroke, unplanned target vessel revascularization, and HF requiring hospitalization.	18 months	<30	58%		–	–	Age, and BMI.
									≥30	42%			HR: 5.36 (1.01–28.53)
Javaheri S. et al.	2010	USA	30,719	67.1 ± 12.1	PSG	Chronic HF	Incidence, treatment, outcomes, and economic cost of sleep apnea in new-onset HF.	2-year survival rate	>5	97%		–	HF HR: 0.33 (0.21–0.51)	Age, sex, and Comorbidities.
Khayat R. et al.	2014	USA	1117	CSA 60.3 ± 14.7 OSA 60.3 ± 13.0	PSM	Acute HF	Mortality	3 years	>15	CSA − 31%		–	HR: 1.61 (1.1–2.4)	LVEF, age, BMI, sex, race, creatinine, diabetes, type of cardiomyopathy, CAD, chronic kidney disease, discharge systolic BP < 110, hypertension, discharge medications, initial length of stay, admission sodium, hemoglobin, and blood urea nitrogen.
										OSA − 47%			HR: 1.53 (1.1–2.2)
O. Parra A. et al.	2004	Spain	161	72 ± 9	PSM	Stroke/ TIA	Death and time of survival since the neurological event.	22.8 months	>10	72%		–	HR: 1.05 (1.01–0.08)	Age, middle cerebral artery involvement, and coronary disease.
									>20	47.2%
									>30	28%
									>40	11.2%
									>50	5%
Hang L.C. et al.	2016	Singapore, China, Brazil, India, Myanmar	1311	58.2 ± 10.3	PSM	Percutaneous coronary intervention	MACCEs, secondary end points: all-cause mortality, target vessel revascula-rization, stent thrombosis, and hospitalization for HF.	1.9 years	≥15	45.3%		–	HR: 1.57 (1.10–2.24)	Age, sex, ethnicity, BMI, diabetes mellitus, and hypertension.
Bolotova M.N. et al.	2008	Russia	120	57.5 ± 1.2	PSG	HPT	Death stroke, MI, HF, and AF.	4.1 years	>15	53%		Stroke OR: 1 (0.32–11)	–	Not adjusted
												MI OR: 0.56 (0.17–1.42)
												HF OR: 1.44 (0.36–1.33)
												AF OR: 1.54 (0.63–3.79)
Uchoa C. et al.	2015	Brazil	67	58 ± 8	PSG	CAD	MACCEs, Secondary end points (individual MACCEs, typical angina, and arrhythmias).	4.5 years	>15	56%		MASSE OR: 4.10 (1.94–385.24)	–	Age, Male sex, waist circumference, statins, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, and LVEF.
												New vascularization OR: 2.02 (1.21–64.22)
												Typical angina OR: 10.05 (1.12–62.25)
												Atrial fibrillation OR: 12.56 (1.44–159.21)
Szymanski F.M. et al.	2015	Poland	251	57.6 ± 10	PSM	AF	Reoccurrence of the AF	30 months	>5	45.4%		OR: 2.58 (1.52–4.38)	–	Multivariate logistic regression analysis.
Zhao Liang-Ping et al.	2015	Singapore	41	52.2 ± 9.6	PSM	Acute MI	Cardiac death, nonfatal MI, hospitalization for angina and/or congestive HF.	5 years	>5	34.1%	15-30 22.0%	OR: 1.044 (1.003–1.086)	–	–
											>30 34.1%
Fan Jingyoa et al.	2019	China	804	57 ± 10.2	PSM	Acute CoronarySyndrome	MACCE	1 Year	>15	50.1%			HR: 1.55 [0.94–2.57] after 1 Year HR: 3.87 [1.20–12.46]	Age, sex, BMI, HT, diabetes, PCI procedure and minimum oxygen saturation.
Yuhui Huang et al.	2020	China	382	No Osa: 51 ± 16 Osa: 57±	PSM	Decompensated HF	Death, heart transplantation or implantation of LVAD. Unplanned hospitalization for worsening HF, ACS, significant arrhythmias, Stroke	19.7 months	>15	49.5%			HR: 1.14 [0.859–1.532]	No

AF atrial fibrillation, AHI apnea-hypopnea index, BMI body mass index, BP blood pressure, CAD coronary artery disease, CAI central apnea index, CHF congestive heart failure, CV cardiovascular, CSA central sleep apnea, HF heart failure, HPT hypertension, HR hazard ratio, LVEF left ventricle ejection fraction, MACCEs major adverse cardiac and cerebrovascular events, MI myocardial infarction, OSA obstructive sleep apnea, OR odds ratio, PSM portable sleep monitor, PSG polysomnography.

Cohort studies: characteristics, outcomes and results.

Table 4

Association of sleep-disordered breathing and cardiovascular disease in patients with established cardiovascular pathology.

Author	Year	Country	Sample Size	Age	Diagnostic standard	Type of CVD	AHI cut-off	Prevalence		OR (95% CI)	Adjusted for
Vazir A. et al.	2006	UK	55	61 ± 12	PSG	CHF	5	80%		–	–
							15	53%
							30	22%
Otero L. et al.	2016	Colombia	834	40–80	PSG	CAD. AF	5	overall 91%		OR: 5.52 (2.9–10.7) for OSA	Not adjusted
										OR: 2.44 (1.2–5.2) for CSA
Strotmann J. et al.	2018	Germany	211	68.7 ± 8.6	PSM	AF	5	93.4%		–	–
							15	59.7%
Losurdo A. et al.	2018	Italy	140	66.9 ± 11.9	PSM	Ischemic stroke	10	51.40%		–	–
Zhao L.P. et al.	2014	Singapore	162	58.6 ± 0.8	PSM	CAD	15	37.9%	35.0% men	–	–
									40.3% women
Logan A.G. et al.	2001	Canada	41	57.2 ± 1.6	PSG	RHTN	10	82.9%	95.8% men	–	–
									64.7% women
Gessner V. et al.	2017	Germany	223	63.2 ± 11.2	PSM	Acute MI	5	85.6%	40.8% OSA	–	–
									7% CSA
									3.1% mixed
Prinz C. et al.	2011	Germany	63	59.5 ± 13.0	PSM	Hypertrophic Cardiomyopathy	5	82.5%	61.9% OSA	–	–
									20.6% CSA
Lee C.H. et al.	2009	Singapore	105	53 ± 10	PSM	Acute MI	15	65.70%		–	–
Bazan V. et al.	2013	Spain	56	66 ± 11	PSG	AF	5	82%		–	–
							30	45%
Glantz H. et al.	2013	Sweden	662	64.1 ± 8.7	PSM	CAD	15	63.7%		–	–
							30	24.6%
Strotmann J. et al.	2017	Germany	211	68.7 ± 8.5	PSM	AF	15	57.9%	55.9% OSA	–	–
									36.5% CSA
Muxfeldt E. et al.	2014	Brazil	422	62.4 ± 9.9	PSG	RHTN	5	82.2%		–	–
							15	55.5%
Paulino A. et al.	2008	France	316	59 ± 3	PSM	CHD	10	81%	56% OSA	–	–
									25% CSA
NorAdina A.T. et al.	2006	Malaysia	28	60.3 ± 8.9	PSM	Ischemic stroke	5	92.8%		–	–
							10	78.5%
							15	44.8%
							20	37.7%
Redeker N.S. et al.	2010	USA	170	60.3 ± 16.8	PSG	CHD	5	84.1%		–	–
Albuquerque F.N. et al.	2011	USA	151	69.1 ± 11.7	PSG	AF	5	78.1%		–	–
							15	52.3%
							30	29.1%
Brooks D. et al.	2010	USA	45	67 ± 12	PSG	Stroke	10	91%		–	–
Lutohin G.M.	2016	Russia	54	66 (57; 72)	PSM	Ischemic stroke	5	92%	81.5% OSA	–	–
									11.1% CSA
Abumuamar A.M. et al.	2018	Canada	100	63.6 ± 13.3	PSG	AF	5	85%		–	–
Boulos M.I. et al.	2016	Canada	102	68.7 ± 13.7	PSM	Stroke/TIA	5	63.40%		–	–
Hoyer F.F. et al.	2010	Germany	46	65 ± 7	PSM	AF	5	67%		–	–
Cai A. et al.	2018	China	1157	56.6 ± 11.7	PSG	RHTN	5	33.1%		OR: 1.049 (1.021–1.079)	Age, male sex, neck girth, BMI, mean SaO2 level, serum uric acid level, presence of diabetes mellitus and CHD.
Koo B. B. et al.	2016	USA	164	62 ± 11.3	PSG	Ischemic stroke	5	80.20%		men OR: 1.04 (1.00–1.09)	Age, diabetes, AF, and PHQ-8 score.
										women OR: 0.88 (0.78–0.99)
Shah N. et al.	2013	USA	136	Median 57.2	PSM	Acute MI	5	77%		–	Age, sex, race, smoking, hyperlipidemia, hypertension, CVD history, diabetes mellitus, and baseline creatinine.
							30	10%		OR: 0.038 (0.002–0.610)
Pedrosa R. et al.	2010	Brazil	80	47	PSM	AF	15	40%		OR: 1.07 (1.01–1.13)	Multivariate analysis
							30	21%
Geovanini G. et al.	2016	Brazil	80	62 ± 10	PSG	Refractory angina	5	75%		–	Not adjusted
							51	25%		OR: 4.00 (1.17–13.73)
Kohno T. et al.	2018	Japan	197	60 ± 9	PSM	AF	10	68.5%	60.9%-OSA	Hyp OR: 2.6 (1.3–5.1)	Not adjusted
									7.6%-CSA
Sin D.D. et al.	2002	Canada	301	CSA 67.2 ± 0.9. OSA 59.4 ± 1.1	PSG	HF	10	40%		OR: 2.89 (1.25–6.73)	BMI, age, sex, mean and minimum SaO2, and LVEF.
Grimm W. et al.	2014	Germany	267	60 ± 14	PSG	Systolic HF	15	43%		–	Age, male sex, arterial hypertension, chronic kidney disease, brain natriuretic peptide, left atrial diameter, NYHA heart failure class, the use of digitalis, the lack of angiotensin-converting enzyme, inhibitors or angiotensin II receptor blockers
							30	25%		AF OR: 5.21 (1.67–16.27)
Kumar R. et al.	2017	India	50	54.6 ± 12.49	PSG	Stroke	5	78%		OR: 1.14 (1.03–1.25)	Age, sex, BMI, and stroke severity.
							15	46%
							30	18%
Macdonald M. et al.	2007	USA	108	57 ± 11	PSM	CHF	15	61%	30% OSA	AF: OR: 11.56 (1.43–93.02) worse functional class of HF: OR: 2.77 (1.14–6.73)	Male sex, age >60 years, BMI, and LVEF.
									31% CSA
Cadilhac D. A. et al.	2005	Australia	78	63.5 ± 14.7	PSG	Stroke	5	81%		–	Age, neck circumference and stroke severity.
							15	64.4%		OR: 4.15 (1.05–16.38)
Braga B. et al.	2007	Brazil	84	60.5 ± 9.5	PSG	AF	10	81.60%		OR: 2.87 (1.07–7.70)	Not adjusted
Bekfani T. et al.	2020	Germany	111	67.6 ± 10.2	PSG	HF	5	66.7% (OSA 42.3%,CSA 21.6%, Mixed 2.7%)

AF atrial fibrillation, AHI apnea-hypopnea index, BMI body mass index, CAD coronary artery disease, CAI central apnea index, CHD coronary heart disease, CHF congestive heart failure, CSA central sleep apnea, CVD cardiovascular disease, HF heart failure, HR hazard ratio, LVEF left ventricle ejection fraction, MACCEs major adverse cardiac and cerebrovascular events, MI myocardial infarction, OSA obstructive sleep apnea, OR odds ratio, PHQ-8 eight-item Patient Health Questionnaire depression scale, PSM portable sleep monitor, PSG polysomnography, RHTN resistant hypertension, TIA transient ischemic attack.

Cross-sectional studies: characteristics, outcomes and results.

Table 5

Association of sleep-disordered breathing and cardiovascular disease in patients with established SDB.

Author	Year	Country	Study Design	Sample Size	Diagnostic Standard	Outcome	Results
Gunbatar H. et al.	2016	Turkey	cross-sectional	56	PSG	Silent prestroke damage	OR: 3.7 (1.2–11.9)
Davies C.WH et al.	2000	UK	case-control	90	PSM	Arterial hypertension	High SBP OR: 9.2 (2.3–16.1) High DBP OR: 7.2 (3.7−10.6)
Chang Chih-Cheng et al.	2014	Taiwan	case-control	149805	PSG	New diagnosis of stroke, and death.	HR: 1.19 (1.09–1.30)
Mansukhani M.P. et al.	2013	USA	case-control	108	PSG	Ischemic stroke	OR: 5.34 (1.79–17.29)
Won C.H. et al.	2012	USA	cohort	281	PSG	All-cause mortality	HR: 1.72 (1.01–2.91)

Study characteristics, outcomes and results.

DBP diastolic blood pressure, HR hazard ratio, OR odds ratio, PSM portable sleep monitor, PSG polysomnography, SBP systolic blood pressure.