Role of sleep disorders in patients with cardiovascular disease: A systematic review

Abstract

In compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we conducted this systemic review on the prevalence, mechanism, and therapy of sleep disorder in patients with cardiovascular disease (CVD). After searching PubMed and Embase, 78 articles were selected for this review. This review discusses the bidirectional relationship between CVD and sleep disorders. Sleep impairment is highly prevalent in patients with CVD and mainly involves insomnia and sleep-breathing disorders. Several valuable biomarkers could be implicated in predicting sleep disorders in CVD patients, such as placental growth factor, vascular endothelial growth factor family, high sensitivity C-reactive protein, endoglin, fms-like tyrosine kinase-1, plasminogen activator inhibitor-1, erythropoietin. Moreover, non-drug therapies, namely physical exercise, cognitive behavioral therapy for insomnia (CBT-I), and continuous positive airway pressure benefit the prognosis of patients with CVD. In conclusion, this study highlights the importance of sleep quality, which is responsible for long- and short-term cardiac outcomes in patients with CVD.

Graphical abstract

The outline of this systematic review. CVD, cardiovascular disease; CAD, coronary artery disease; SBD, sleep breathing disorders; CBT, cognitive behavioral therapy; CPAP, continuous positive airway pressure; IMT, inspiratory muscle training; OSA, obstructive sleep apnea; HF, heart failure; HTN, hypertension.

1. Introduction

Sleep accounts for one-third of our lives and plays a crucial role in maintaining public health. However, many individuals experience sleep disorders throughout their lifetime. According to the International Classification of Sleep Disorders-3 (ICSD-3) diagnostic criteria, sleep disorders are classified into seven major categories: insomnia disorders, sleep-related breathing disorders (SBD), central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, sleep-related movement disorders, parasomnias, and other sleep disorders [1]. Approximately 10–30% of the general population is affected by insomnia [2]. Moreover, approximately one billion adults (aged 30–69 years) are affected by obstructive sleep apnea (OSA), and half of these have moderate to severe OSA [3]. One-third of the patients with OSA also have insomnia [4].

There is a bidirectional correlation between sleep disorders and cardiovascular disease (CVD) [5,6]. Accumulating evidence has shown a high prevalence of sleep disorders among patients with CVD [7]. Pengo et al. [8] have highlighted this global problem and urged cardiologists to focus on sleep health. As cardiologists, we must recognize sleep impairments in patients in clinical practice. In cardiology departments, many patients report sleep disorders. A high prevalence (40–80%) of OSA is observed in patients with CVD, including those with coronary artery disease (CAD), atrial fibrillation (AF), heart failure (HF), and hypertension, leading to adverse cardiac outcomes [9]. Moreover, the combination of insomnia and OSA was associated with a higher CVD risk after adjustment for confounding factors. The sleep-breathing impairment index (SBII) is considered a new metric for evaluating the severity of OSA. Cao et al. showed that a higher SBII score was strongly associated with a higher 10-year Framingham CVD risk score [10]. Poor sleep increases risk and mortality of CVD (hazard ratio (HR):1.67, 95% confidence interval (CI): 1.27–2.19) [-[11], [12]]. Similarly, Yan et al. [13] also identified that poor objective sleep efficiency could significantly predict CVD mortality (HR: 1.887, 95% CI: 1.224–2.909, P < 0.05). Sleep quality can be evaluated not only by subjective feelings but also by polysomnography.

The potential mechanisms underlying sleep disorders and CVD include parasympathetic and sympathetic nerve imbalance, immune inflammation, genetics, interactions in the microbiome-gut-brain axis, blood lipid abnormalities, and altered hematopoiesis. Sleep deficiency increases the expression of interleukin −6 (IL-6) and tumor necrosis factor-alpha (TNF-α) via the nuclear factor-kappa B (NF-κB) signaling pathway [14]. Moreover, the inflammation affects small peripheral arteries and sympathetic and sensory-motor nerves, leading to blood elevation, which exacerbates the CVD prognosis. Inflammation is closely associated with blood lipid abnormalities. Insomnia disturbs the blood lipid metabolism, The elevated LDL cholesterol is a risk factor for carotid artery intima-media thickness (CIMT) and plaque incidence, indicating the relationship between insomnia, higher CIMT values, plaque incidence, and CVD [15].

Improving sleep disorders benefits cardiovascular recovery and vice versa. Despite the sedative-hypnotics for treating sleep disorders, we recommend some non-drug therapies. Exercise, cognitive behavioral therapy for insomnia (CBT-I), and continuous positive airway pressure (CPAP) are the most commonly used non-drug treatments. Exercise is an easy and convenient method for most patients. Both the American College of Cardiology and the American Heart Association recommend exercise and physical activity to prevent CVD primarily [16]. Furthermore, traditional Chinese exercises such as Tai Chi help improve sleep quality by reducing waking time [17]. Exercise can also benefit patients with OSA and CVD by reducing inflammation and sympathetic activation [18]. Strong evidence has shown that CBT is an effective method for treating CVD and insomnia. Conventionally, CBT is conducted face-to-face by physicians, although internet technology has also been implicated in CBT. Internet-based CBT (ICBT) helps alleviate depressive symptoms in patients with CVD; hence, ICBT is beneficial for CVD treatment [19]. CPAP can improve physical activity, relieve depressive mood, and reduce adverse cardiac events in patients with co-occurring CVD and OSA [20]. CPAP is a valuable therapy for reducing the risk of CVD by controlling risk factors, such as lowering blood pressure or blood glucose [21].

Therefore, to improve sleep health and reduce cardiac events in patients with CVD, the interrelationship between sleep disorders and CVD should be explored further. In this systematic review, we illustrate the epidemiology, mechanisms, drug therapy, and non-drug therapy of sleep disorders in patients with CVD.

2. Method

2.1. Design

This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The protocol was registered in PROSPSPERO (CRD42023451234).

2.2. Search strategy

We searched the related literature with the Pubmed and Embase databases using the key words:((sleep) OR (insomnia)) AND (((((((((coronary artery disease) OR (cardiac arrhythmia)) OR (hypertension)) OR (valvular heart disease)) OR (dilated cardiomyopathy)) OR (hypertrophic cardiomyopathy)) OR (myocarditis)) OR (heart failure)) OR (cardiovascular disease)).

2.3. Inclusion and exclusion criteria

Inclusion criteria: 1) patients with cardiovascular disease and sleep disorders; 2) age ≥18 years; 3) both women and men; 4) clinical research.

Exclusion criteria: 1) pregnancy; 2) no full text; 3) text not in English.

2.4. Study screening and data extraction

Two authors independently reviewed the papers by extracting the following data: author, publication date, study type, sleep disorders, methods of sleep assessment, type of CVD, and the main outcomes. If there were different opinions, a third author was consulted to reach an agreement.

2.5. Outcomes

This review highlights the prevalence, mechanisms, and therapies of sleep disorders in patients with CVD.

2.6. Study quality and risk of bias assessment

The Cochrane Risk of Bias (CoB) tool was used to assess the risk of bias/quality of randomized controlled trials (RCT) [22], the Newcastle-Ottawa (cohort) scale (NOS) was used for cohort studies [23], Combie was used for cross-sectional studies [24], and methodological index for non-randomized studies (MINORS) was used for non-randomized studies.

3. Results

3.1. Search results

A total of 66795 references were identified in the two databases. After careful reading, 78 articles were included in this systemic review [[25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81], [82], [83], [84], [85], [86], [87], [88], [89], [90], [91], [92], [93], [94], [95], [96], [97], [98], [99], [100], [101], [102]]. The selection flowchart was shown in Fig. 1.

Fig. 1.

Flow chart of article selection.

3.2. Characteristics of the studies

Table 1 summarized the basic characteristics of the included studies. There were 22 articles on sleep disorders in patients with CAD [[25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46]], 19 on hypertension [[47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65]], 16 on HF [[66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81]], 10 on cardiac arrhythmia [[82], [83], [84], [85], [86], [87], [88], [89], [90], [91]], 11 on other CVD [[92], [93], [94], [95], [96], [97], [98], [99], [100], [101], [102]]. Except for one study including 36 countries [29], the other studies covered 19 countries, comprising China (n = 12) [33,41,44,50,57,59,63,64,86,89,94,101], USA (n = 14) [56,61,62,68,[72], [73], [74],77,81,83,87,88,90,102], Lithuania (n = 3) [25,32,37], Brazil (n = 4) [26,30,31,54], Israel (n = 1) [27], Iran (n = 2) [35,100], Spain (n = 3) [39,58,65], Germany (n = 11) [28,38,49,67,69,75,78,84,[97], [98], [99]], Sweden (n = 5) [36,40,46,55,95], Egypt (n = 1) [79], Turkey (n = 2) [70,85], Japan (n = 3) [42,92,96], France (n = 3) [45,76,93], Nigeria (n = 2) [53,66], India (n = 2) [51,71], Malaysia (n = 1) [52], Canada (n = 4) [43,48,82,91], Pakistan (n = 1) [34], Poland (n = 1) [60], Romania (n = 1) [80], and Italy (n = 1) [47]. These articles included several types of study designs: cross-sectional studies (n = 33), prospective cohort studies (n = 26), RCT (n = 7), retrospective cohort studies (n = 7), case-control studies (n = 3), pilot study (n = 1), longitudinal study (n = 1). These studies investigated the sleep conditions of patients with CVD, including SDB, insomnia disorders, and sleep quality. Polysomnography and the Berlin Questionnaire were used to assess SBD, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality.

Table 1.

The study characteristics of sleep disorders in patients with CVD.

No.	First author Publication year	Country	Study design	CVD	Sleep disorders	Sample /Age (years)	Sleep measurement	Main findings	Study quality assessment
Coronary artery disease
1	Alonderis2020 [25]	Lithuania	Cross-sectional study	CAD with LVEF≥ 50%	SA	N = 450	Polysomnography	Up to 35% of coronary artery disease patients were likely to have undiagnosed sleep apnoea.	Combie high quality
						AMI+SA+
						N = 156/59.4 ± 9.2yrs
						AMI+SA-
						N = 294/56.1 ± 9.1yrs
2	Andrechuk2015 [26]	Brazil	Cross-sectional study	AMI	OSA	N = 113/59.7 ± 12.3 yrs	Berlin Questionnaire	The high prevalence of obstructive sleep apnoea was 60.2%	Combie high quality
3	Araújo2009 [31]	Brazil	Cross-sectional study	CAD	OSA	N = 53	Polysomnography	OSA was not related to myocardial ischemia, heart rate variability or arrhythmias in patients with SCAD.	Combie high quality
						Control
						n = 23/57.47 ± 10.59yrs
						Apnea
						n = 30/59.00 ± 10.42yrs
4	Aronson2014 [27]	Israel	Prospective cohort study	AMI	SDB	N = 180	Watch-PAT 100	A high prevalence of previously undiagnosed SDB among patients with AMI. SDB in the setting of AMI is associated with higher pulmonary artery systolic pressure. SDB was not associated with adverse clinical outcomes.	NOS high quality
						AMI + SDB
						N = 116/59±9yrs
						AMI non-SDB
						N = 64/56 ± 11yrs
5	Assari2013 [35]	Iran	Cross-sectional study	CAD	Sleep quality	N = 717/57.7 ± 11.7yrs	PSQI	Among female patients with CAD, low education and income were associated with poor sleep quality.	Combie high quality
6	Barcelo2016 [39]	Spain	RCT	ACS	OSA	N = 312/61.2 ± 10.3yrs	Polygraph	In patients with ACS, elevated plasma levels of PlGF are associated with the presence of OSA and with adverse outcomes during short-term follow up.	CoB
						Controls
						N = 226/56.5 ± 11.5yrs
						OSA
						N = 312/61.2 ± 10.3yrs
7	Barger2017 [29]	36 countries	Prospective cohort study	ACS	Short sleep duration OSA	N = 12924/64years	Berlin questionnaire a sleep survey	Short sleep duration, and OSA, are under-recognized as predictors of adverse outcomes after acute coronary syndrome.	NOS high quality
						No OSA
						N = 8084/65 (60,71)
						OSA
						N = 4840/63 (57, 69)
8	Buchner2015 [28]	Germany	Prospective cohort study	AMI	SDB	N = 54	Polysomnography	SDB may contribute to enlargement of the right heart after AMI.	NOS high quality
						AMI + SDB+
						N = 29/55 ± 10yrs
						AMI + SDB-
						N = 25/53 ± 10yrs
9	Cai 2022 [33]	China	Cross-sectional study	CAD	Sleep quality	N = 84	PSQI	MDD may be responsible for poor sleep quality, in patients with CHD, treatment for depressive symptoms may also improve CHD prognosis.	Combie high quality
						CHD MDD (+)
						58.46 ± 6.12yrs
						CHD MDD (−)
						57.68 ± 5.50yrs
10	Clark2014 [36]	Sweden	Prospective cohort study	AMI	Sleep impairment	N = 1588/60±7yrs	Karolina Sleep Questionnaire	In women, disturbed sleep showed a consistently higher risk of long-term cardiovascular events; In men, a strong effect on case fatality was observed in regard to impaired awakening	NOS high quality
						Women
						No disturbed sleep
						N = 418/62±7yrs
						Disturbed sleep
						N = 78/61±7yrs
						Men
						No disturbed sleep
						N = 1008/59±7yrs
						Disturbed sleep
						N = 77/59±7yrs
11	Correia2012 [30]	Brazil	Prospective cohort study	UA NSTEMI	OSA	N = 168/70 ± 12yrs	Berlin Questionnaire	During a median hospitalization of 8 days, the incidence of cardiovascular events was 13%. Incidence of the primary endpoint was 18% in individuals with high probability of OSA.	NOS high quality
						Low OSA probability
						N = 45/69 ± 14yrs
						High OSA probability
						N = 123/71 ± 12yrs
12	Feng2022 [43]	Canada	Prospective cohort study	CAD	Sleep quality	N = 113/63.7 ± 6.4yrs	PSQI	A marker of late-stage lipid peroxidation is elevated in CAD patients with poor sleep and associated with daily disturbances, but not with other factors or with sleep quality and its factors after exercise intervention.	NOS high quality
						Normal sleep quality
						N = 54/64.8 ± 6.6yrs
						Poor sleep quality
						N = 59/62.6 ± 6.1yrs
13	Huang2020 [41]	China	Cross-sectional study	CAD	OSA	N = 1243	Overnight portable respiratory monitoring	Elevated levels of MHR were independently associated with a higher likelihood of OSA in patients with CAD.	Combie high quality
						MHR Quartile 1
						N = 311/63.3 ± 9.1yrs
						MHR Quartile 2
						N = 311/62.6 ± 9.5yrs
						MHR Quartile 3
						N = 311/62.6 ± 13.0yrs
						MHR Quartile 4
						N = 310/60.2 ± 10.8yrs
14	Juskiene2018 [32]	Lithuania	Cross-sectional study	CAD	Sleep quality OSA	N = 879/58 ± 9 yrs	Polysomnography PSQI	In CAD patients, type D personality and NA are associated with worse subjective sleep quality and this association is mediated by depression and anxiety symptoms irrespective of OSA presence.	Combie high quality
						Men
						No OSA
						N = 374/55.0 ± 9.2yrs
						OSA
						N = 286/59.0 ± 8.8yrs
						Women
						No OSA
						N = 156/60.5 ± 7.9yrs
						OSA
						N = 63/63 ± 6.9yrs
15	Katsumata2020 [42]	Japan	Cross-sectional study	CAD	OSA	N = 178	Polysomnography	Elevated SNX16-Ab level associated with the history of CAD.	Combie high quality
						Healthy adults
						N = 64/42.5yrs
						OSA N = 82/59yrs
						ACS N = 96/67yrs
16	Kazukauskiene2022 [37]	Lithuania	Cross-sectional study	CAD	OSA	N = 328/57 ± 10yrs	Polysomnography	CAD males with OSA and clinically elevated NT-proBNP levels experienced inferior psychomotor performance	Combie high quality
						OSA
						N = 75/59.7 ± 8.1yrs
						No OSA
						N = 253/56.1 ± 10.1yrs
17	Khan2014 [34]	Pakistan	Cross-sectional study	CAD	OSA	N = 400	Berlin questionnaire	A significant proportion of CAD patients are at high risk of OSA in Pakistan. Moreover, OSA is also associated with greater levels of anxiety in CAD patients	Combie high quality
						CAD
						N = 200/55.07 ± 6.88yrs
						Healthy
						N = 200/55.19 ± 6.69yrs
18	Labeix2022 [46]	Sweden	RCT	CAD	OSA	N = 45	PSQI	A specific IMT during cardiac rehabilitation contributes to reduce significantly AHI in CAD patients with moderate OSA.	CoB
						Control
						N = 23/59.3 ± 10.3yrs
						IMT
						N = 22/61.0 ± 8.4yrs
19	Li2020 [44]	China	Cross-sectional study	CAD	OSA	N = 154/54.9 ± 9.4yrs	Portable cardiorespiratory monitoring device	Plasma CTRP9 levels were independently related to the prevalence of moderate/severe OSA in patients with CAD.	Combie high quality
						Moderate/severe OSA
						N = 89/54.4 ± 8.8yrs
						No/mild OSA
						N = 65/55.1 ± 10.3yrs
20	Milleron2004 [45]	France	Long-term prospective cohort study	CAD	OSA	N = 54/57.3 ± 10.1yrs	Polysomnography	The treatment of OSA in CAD patients is associated with a decrease in the occurrence of new cardiovascular events, and an increase in the time to such events.	NOS high quality
						OSA-treated
						N = 25/57.7 ± 10.1yrs
						OSA-untreated
						N = 29/57.0 ± 10.2yrs
21	Strehmel2016 [38]	Germany	Cross-sectional study	CAD	OSA	N = 41	Polysomnography	CPAP has the potential to normalize elevated NT-proBNP serum levels in patients with severe OSA and coexisting CAD. Levels of NT-proBNP and hs-TropT correlated with AHI and oxygen desaturation	Combie high quality
						OSA + CAD
						N = 21/61 ± 11yrs
						OSA
						N = 20/54 ± 12yrs
22	Thunström2015 [40]	Sweden	Cross-sectional study	CAD	OSA	N = 439	Cardiorespiratory Polygraphy	Obstructive sleep apnea with oxygen desaturation index ≥5 was independently associated with increased inflammatory activity in this nonobese coronary artery disease cohort.	Combie high quality
						CAD + nonobese + OSA
						N = 234/65.3 ± 7.1yrs
						CAD + nonobese + nonOSA
						N = 95/61.4 ± 9.5yrs
						CAD + obese + OSA
						N = 110/62.9 ± 8.6yrs
Hypertension
1	Akintunde2014 [53]	Nigeria	Cross-sectional study	HTN	OSA	N = 104	Berlin questionnaire	OSA is associated with significant additional left ventricular changes in hypertensive subjects.	Combie high quality
						Low risk of OSA
						N = 49/58.8 ± 12.6
						High risk of OSA
						N = 55/58.6 ± 11.2
2	Ayanaw2022 [47]	Italy	Cross-sectional study	HTN	Sleep quality	N = 563/65yrs	PSQI	More than one-third of the study participants had poor sleep quality.	Combie high quality
3	Bacci2017 [54]	Brazil	Cross-sectional study	HTN	OSA Sleep quality	N = 43/52.9 ± 14.5yrs	PSQI ESS BQ	Patients at high risk for OSAHS had poor sleep quality and high levels of DBP.	Combie high quality
4	Bengtsson Boström2010 [55]	Sweden	Cross-sectional study	HTN	OSA	N = 170	Polysomnography	Hypertensive men carrying the Arg389Arg genotype had higher crude and age-adjusted AHI than carriers of the Arg389Gly/Gly389Gly genotypes	Combie mid quality
						Normotension
						N = 96/60 ± 6.3yrs
						HTN
						N = 74/62 ± 6.2yrs
5	Cai2017 [50]	China	Cross-sectional study	HTN	OSA	N = 971	Polysomnography	In a Chinese hypertensive population, OSA prevalence is strikingly high. Hypertensive subjects with the most severe OSA are at greater cardiovascular risk.	Combie high quality
						Without OSA
						N = 286/56.5 ± 13.3yrs
						With OSA
						N = 685/59.3 ± 11.7yrs
6	Cai2022 [57]	China	Single-center, observational, Retrospective cohort study	HTN	OSA	N = 2067/49.51 ± 10.73 yrs	Polysomnography	There was a positive association between CMI levels and the risk of new-onset CVD in patients with hypertension and OSA.	NOS high quality
						CMI˂0.73
						52.13 ± 11.41yrs
						0.73–1.21
						49.05 ± 10.87yrs
						≥1.21
						47.52 ± 9.43yrs
7	Chang2013 [59]	China	Retrospective cohort study	HTN	Insomnia	N = 4063	ICD-9-CM	The use of bisoprolol and atenolol was associated with the lowest risk of insomnia in elderly patients, as compared to propranolol. β-blockers with high selectivity in β1-receptors and/or low lipophilicity were associated with a lower risk of insomnia	NOS high quality
						Propranolol user
						N = 760/73.3 ± 6.3yrs
						Non-propranolol user
						N = 3303/72.3 ± 6.1yrs
8	Chaudhary2023 [51]	India	Cross-sectional study	HTN	OSA	N = 179/52.07 ± 11.40yrs	Polysomnography	More than half (53.1%) of the patients enrolled in the study had OSA. More than half of our hypertensive patients had OSA. These two conditions often co-exist and are known as a dangerous pair.	Combie high quality
9	Chen2020 [64]	China	RCT	HTN	OSA	N = 60/18–75yrs	Polysomnography	The CPAP treatment did not show significant ambulatory BP lowering effect in patients with moderate-severe OSAS and nocturnal hypertension. However, it may be effective in lowering daytime BP in patients with a faster pulse rate.	CoB
10	Ching2023 [52]	Malaysia	Cross-sectional study	HTN	OSA	N = 410/56.4 ± 11.3yrs	Polysomnography	The prevalence of probable OSA among patients with hypertension was 54.4%.	Combie high quality
						Probable OSA
						N = 223/58.3 ± 10.6yrs
						Non-probable OSA
						N = 187/54.2 ± 11.7yrs
11	Friedman2010 [48]	Canada	Case-control study	Drug-resistant hypertension	Sleep quality	N = 156	Polysomnography	Compared to subjects with CH or normotension, those with RH have shorter total and REM sleep times and lower sleep efficiency independently of OSA. These data suggest that reduced sleep time may contribute to the severity of hypertension	NOS high quality
						Normotension
						N = 40/52.2 ± 9.9yrs
						Control HTN
						N = 54/58.5 ± 11.3yrs
						Resistant HTN
						N = 62/58.9 ± 10.8yrs
12	Gaddam2010 [62]	USA	Prospective cohort study	Resistant hypertension	OSA	N = 12/56.5 ± 6.5yrs	Polysomnography	This study provides preliminary evidence that treatment with a mineralocorticoid receptor antagonist substantially reduces the severity of OSA.	NOS mid quality
13	Gonzaga2010 [61]	USA	Retrospective study	HTN	OSA	N = 109/55.9 ± 9.1yrs	Polysomnography	Severity of OSA was greater in those patients with hyperaldosteronism and related to the degree of aldosterone excess.	NOS mid quality
						High aldosterone level
						N = 31/56.4 ± 7.8
						Normal aldosterone level
						N = 78/55.7 ± 9.7
14	Jafari2013 [56]	USA	Cross-sectional study	HTN	OSA	N = 95	Polysomnography	These data show that patients with OSA and hypertension have marked impairment of FMD, independent of hypoxia exposure, which is associated with increased sEng.	Combie mid quality
						Non-OSA
						Normotension
						N = 19/47.5 ± 2.1yrs
						HTN
						N = 13/45.7 ± 2.3yrs
						OSA
						Normotension
						N = 27/47.9 ± 2.2yrs
						HTN
						N = 36/56.1 ± 1.4yrs
15	Li2021 [49]	Germany	Prospective cohort study	HTN	Sleep quality	N = 1959/25–65 yrs	A three-point Likert response scale	Our findings add a new piece of evidence that work stress together with impaired sleep increase risk of coronary and cardiovascular mortality in hypertensive workers.	NOS high quality
16	Lui2021 [63]	China	RCT	HTN	OSA	N = 92/53.2 ± 8.7yrs	Polysomnography	In a cohort with OSA and multiple cardiovascular risk factors including difficult-to-control hypertension, short-term CPAP treatment improved ambulatory BP, and alleviated subclinical myocardial injury and strain.	CoB
						CPAP
						N = 46/52.5 ± 9.0yrs
						Control
						N = 46/53.9 ± 8.4yrs
17	Martínez-García 2013 [65]	Spain	RCT	Resistant hypertension	OSA	N = 194/56.0 ± 9.5yrs	Respiratory polygraphy	Among patients with OSA and resistant hypertension, CPAP treatment for 12 weeks compared with control resulted in a decrease in 24-h mean and diastolic blood pressure and an improvement in the nocturnal blood pressure pattern.	CoB
						Control
						N = 96/58.2 ± 9.6yrs
						CPAP
						N = 98/57.8 ± 9.5yrs
18	Wolf2016 [60]	Poland	Cross-sectional study	HTN	OSA	N = 88	Polysomnography	Beta-blockers do not potentiate apnea-induced HR decelerations, attenuate apnea-induced increases in heart rate and do not influence incidence of ectopies and conduction abnormalities in patients with hypertension and moderate-to-severe, untreated OSA	Combie high quality
						BB−
						N = 32/55 (46–63)yrs
						BB+
						N = 56/57.5 (54–62)yrs
19	Zamarrón2008 [58]	Spain	Cross-sectional study	HTN	OSA	N = 96/53.3 ± 8.2yrs	Polysomnography	OSAS patients presented higher circulating levels of PAI than the control group, which was even greater when patients had associated hypertension.	Combie high quality
						Control
						N = 32/48.2(43.6, 52.9)yrs
						OSAS
						N = 32/52.7(49.9,55.4)yrs
						OSAS + HT
						N = 32/54.1 (50.6, 57.6)yrs
Heart failure
1	Abdelbasset2020 [79]	Egypt	Pilot study	HF	Sleep disturbance	N = 8/69.4 ± 4.2 yrs	PSQI	Low-intensity exercise program five sessions weekly for four weeks. low-intensity aerobic exercise may improve the quality of sleep and ventilator efficiency in elderly HF patients.	MINORS mid quality
2	Alosco2013 [68]	USA	Cross-sectional study	HF	Sleep quality	N = 53/69.81 ± 8.79yrs	PSQI	75.5% of HF patients reported impaired sleep. Decreased cerebral perfusion and greater WMH may contribute to sleep difficulties in HF.	Combie high quality
3	Arzt2017 [69]	Germany	Cross-sectional study	HFrEF	SDB	N = 1557	Polysomnography	Prevalence of SDB in HFpEF, HFmrEF and HFrEF (36%, 41% and 48%, respectively). The prevalence of coexisting OSA-CSA, OSA and CSA were 40%, 29% and 31% in patients with HFrEF respectively.	Combie high quality
						OSA
						N = 452/66 ± 11yrs
						OSA-CSA
						N = 624/69 ± 10yrs
						CSA
						N = 481/69 ± 10yrs
4	Avci2021 [70]	Turkey	Cross-sectional study	HF	Sleep quality	N = 95/75.44 ± 6.36yrs	PSQI	Elderly patients with HF experienced significant sleep problems and that their sleep quality decreased as the depression symptom levels increased.	Combie high quality
5	Awotidebe2017 [66]	Nigeria	Case-control study	CHF	Sleep quality	N = 100	Pittsburgh Sleep	Patients with heart failure demonstrated lower functional capacity and poorer sleep quality.	NOS high quality
						Patient
						N = 50/57.8 ± 8.9yrs
						Control
						N = 50/54.9 ± 7.9yrs
6	Beres2022 [80]	Romania	Prospective, mono-center, cohort study	HF	CSA	N = 36/65.7 ± 10.8yrs	Polysomnography	The association of PAP therapy with drug therapy in patients with HFrEF and CSAS improves hemodynamic parameters and quality of life.	NOS mid quality
7	Bhalla2020 [71]	India	Prospective cohort study	CHF	OSA	N = 77/30–80 yrs	Polysomnography	The prevalence of OSA in CHF was 50.6%. Predictors of OSA in CHF were left ventricular ejection fraction (LVEF) 20%–30% and NYHA class 2.	NOS high quality
8	Bitter2011 [67]	Germany	Prospective cohort study	CHF	OSA	N = 255	Cardiorespiratory polygraphy	In patients with CHF, CSA and OSA are independently associated with an increased risk for ventricular arrhythmias and appropriate cardioverter-defibrillator therapies.	NOS high quality
						AHI≥5h-1
						OSA
						N = 82/67.9 (63.9,73.7)yrs
						CSA
						N = 87/68.4 (62.1,72.4)yrs
						noSDB
						N = 86/65.7 (56.5,71.6)yrs
9	Bughin2021 [76]	France	A longitudinal study	HF	Sleep patterns	N = 119/69yrs	PSQI ESS ISI BQ	CNS drugs intake and decreased total sleep time were independently associated with an increased risk of MACE in patients with HF.	MINORS high quality
10	Calvin2014 [72]	USA	Prospective cohort study	HF LVEF≤35%	CSA	N = 46	Polysomnography	Increased LAVI is associated with heightened CO2 chemosensitivity and greater frequency of CSA.	NOS mid quality
						HF without CSA
						N = 21/59.3 ± 9.9yrs
						HF with CSA
						N = 25/68.5 ± 8.1yrs
11	Calvin2010 [73]	USA	Prospective cohort study	HF	CSA	N = 51	Polysomnography	In non-anaemic HF patients, advanced HF and hypoxaemia due to CSA may each be independently associated with increased serum EPO concentration.	NOS mid quality
						Healthy controls
						N = 18/54.7 ± 16.8yrs
						HF without CSA
						N = 15/59.9 ± 12.0yrs
						HF with CSA
						N = 14/65.7 ± 10.7yrs
12	Calvin2011 [74]	USA	Prospective cohort study	HF	CSA	N = 33	Polysomnography	ANP and BNP concentrations performed similarly for detection of CSA; low concentrations appear associated with low risk for CSA in men.	NOS mid quality
						HF without CSA
						N = 9/61.1 ± 12.4yrs
						HF with CSA
						N = 24/66.7 ± 9.9yrs
13	Cundrle2018 [77]	USA	Cross-sectional study	HF	CSA	N = 56/65 ± 10yrs	Polysomnography	Low leptin concentration may have utility for the screening of heart failure patients for central sleep apnea.	Combie mid quality
						CSA
						N = 18/67 ± 10yrs
						Mixed apnea
						N = 15/64 ± 10yrs
						No apnea
						N = 11/59 ± 10yrs
						OSA
						N = 12/68±8yrs
14	Ferreira2020 [75]	Germany	RCT	HF	OSA	N = 749/69 ± 10 yrs	Not mentioned	Three biomarkers added significant prognostic information on top of the best clinical model: soluble suppression of tumorigenicity 2 (primary outcome), Notch-3 (CV and all-cause death), and GDF-15 (all-cause death).	CoB
						Control
						N = 368/69.1 ± 10.2yrs
						ASV
						N = 381/69.3 ± 9.4yrs
15	Gerçek2022 [78]	Germany	Retrospective study	HF	SDB	N = 146	Polysomnography	SDB treatment in HF patients with ICD leads to significant improvements in VT burden, ATP and shock therapy, and may even affect survival.	NOS high quality
						Control
						N = 73/67.67 ± 10.78 yrs
						SDB-treated
						N = 73/67.2 ± 10.10 yrs
16	Redeker2022 [81]	USA	RCT	HF	Insomnia	N = 175/63 ± 12.9 yrs	PSQI	CBT-I produced sustained improvements in insomnia, fatigue, daytime sleepiness, and objectively measured physical function among adults with chronic HF, compared with a robust HF self-management program that included sleep hygiene education.	CoB
						Healthy sleep
						N = 91/62.0 ± 13.1yrs
						Healthy heart
						N = 84/64.1 ± 12.6yrs
Cardiac arrhythmia
1	Abumuamar2018 [82]	Canada	Prospective cohort study	AF	OSA	N = 123/63.6 ± 13.3yrs	Polysomnography	OSA was detected in 85% of these patients.	NOS high quality
2	Abumuamar2019 [91]	Canada	Prospective cohort study	AF	OSA	N = 100/63 ± 13yrs	Polysomnography	There is a significant decrease in atrial and ventricular ectopy count/24 h in patients with AF and OSA at 3 and 6 months of CPAP treatment compared to baseline.	NOS high quality
						OSA
						N = 85/65 ± 13yrs
						Non-OSA
						N = 15/55 ± 14yrs
3	Albuquerque2012 [83]	USA	Prospective cohort study	AF	SDB	N = 151/69.1 ± 11.7yrs	Polysomnography	The prevalence of SDB in this population was 81.4%.	NOS mid quality
						No EDS
						N = 98/70.1 ± 1.2yrs
						EDS
						N = 53/67.1 ± 1.6yrs
4	Anter2017 [87]	USA	Cross-sectional study	PAF	OSA	N = 184	polysomnography or a home sleep apnea testing device	In patients with paroxysmal AF, OSA is associated with structural and functional atrial remodeling and increased incidence of extra-PV triggers.	Combie mid quality
						(+)OSA(+)PVI(+) Triggers
						N = 43/49 ± 12yrs
						(−)OSA(+)PVI(+) Triggers
						N = 43/54 ± 14yrs
						(−)OSA(+)PVI(−) Triggers
						N = 48/59 ± 12yrs
						(+)OSA(+)PVI(−) Triggers
						N = 50/51 ± 15yrs
5	Bitter2009 [84]	Germany	Cross-sectional study	AF	SDB	N = 150/66.1 ± 1.7yrs	Cardiorespiratory polygraphy	Patients with AFib were found to have not only a high prevalence of obstructive sleep apnea, as has been described previously, but also a high prevalence of CSA/CSR.	Combie mid quality
						CSA/CSR
						N = 47/64.1 ± 5.0yrs
						OSA
						N = 64/67.4 ± 2.1yrs
						No SDB
						N = 39/65.4 ± 4.8yrs
6	Brgdar2021 [90]	USA	Retrospective study	AF	OSA	N = 156,521	ICD-10	Although OSA is highly prevalent in AF patients, inpatient mortality and cardiovascular outcomes such as cardiac arrest, stroke, or major bleeding were similar in AF patients with or without concomitant OSA with no significant differences in length of stay.	NOS high quality
						Pre-match
						OSA
						N = 23,678/65.18 ± 10yrs
						Non-OSA
						N = 132,843/71.4 ± 13yrs
						Post-match
						OSA
						N = 23,678/65.18 ± 12.7yrs
						Non-OSA
						N = 23,678/65.09 ± 12.7yrs
7	Cang2023 [86]	China	Retrospective cohort study	AF	Sleep quality	N = 416	Questionnaire Self-reported sleep pattern	Sleep disorders such as inadequate sleep time (time <7 h or >8 h), insomnia and excessive sleepiness during daytime were associated with a higher risk of recurrence.	NOS high quality
						Healthy sleep score 0-1
						N = 20/63.50 ± 7.99yrs
						Healthy sleep score 2-3
						N = 188/63.65 ± 9.55yrs
						Healthy sleep score 4-5
						N = 208/63.15 ± 9.72yrs
8	Dalgaard2020 [88]	USA	Retrospective cohort study	AF	OSA	N = 22,760/73.0 (65.0–80.0)yrs	A medical history and prior diagnosis.	Among patients with AF, OSA is an independent risk factor for MACNE and, more specifically, stroke/SE.	NOS high quality
						OSA
						N = 4045/68.0 (61.0–75.0)yrs
						No OSA
						N = 18,715/74.0 (66.0–81.0)yrs
9	Kayrak2013 [85]	Turkey	Case-control study	AF	Sleep quality	N = 303	PSQI	Patients with AF have shorter sleep duration and poor SQ. Maintenance of sinus rhythm after DCC may have a favorable effect on the SQ of patients with AF. Nevertheless, AF is an independent predictor of poor SQ.	NOS high quality
						AF
						N = 153/63 ± 12yrs
						Control
						N = 150/61 ± 14yrs
10	Tang2009 [89]	China	Prospective cohort study	paroxysmal AF	OSA	N = 178	Berlin questionnaire	The recurrence rate and incidence of complications did not differ in patients with different risk profiles for OSA.	NOS high quality
						Low risk of OSA
						N = 74/56 ± 12yrs
						High risk of OSA
						N = 104 58 ± 11yrs
Other CVD
1	Abe2009 [96]	Japan	Cross-sectional study	HF with MV and/or AV Valve repair surgery	SAS (OSA, CSA)	N = 150	Polysomnography	The treatment led to a significant improvement in PCWP and mean PAP, and CSA-AI, improvement of cardiac function with valvular surgery reduces the severity of CSA in HF patients with valvular heart diseases.	Combie high quality
						mild-to-no SA
						N = 47/66.0 ± 11.4yrs
						SAS
						N = 103/69.5 ± 8.8yrs
2	Amofah2016 [95]	Sweden	Prospective cohort study	SAVR or TAVI surgery	Sleep quality	N = 143/83 ± 2.7yrs	Self-reports actigraphy MISS	In patients undergoing SAVR or TAVI, sleep evolves differently during the in-hospital postoperative phase.	NOS high quality
						SAVR
						N = 78/82 ± 2.0yrs
						TAVI
						N = 65/85 ± 2.8yrs
3	Banno2004 [92]	Japan	Cross-sectional study	Idiopathic cardiomyopathy (DCM, HCM)	SDB	N = 35	PSG	Of these 35, 16 (80%) of the DCM patients and 7 (47%) of the HCM patients had sleep-disordered breathing.	Combie mid quality
						DCM
						CSAHS
						N = 10/48.4 ± 14.2yrs
						OSAHS
						N = 6/43.3 ± 9.5yrs
						non-SAHS
						N = 4/47.0 ± 14.0yrs
						HCM
						OSAHS
						N = 7/48.4 ± 8.3yrs
						non-SAHS
						N = 8/47.8 ± 15.7yrs
4	Biener2023 [97]	Germany	Prospective cohort study	Mitral regurgitation Mitral valve repair surgery	SDB	N = 53/76.0 ± 8.5yrs	polygraphy	TMVR may be a suitable therapy not only for MR but also for the accompanying CSA. LAVI may be a useful indicator for CSA in patients with MR.	NOS high quality
						SDB
						N = 36/75.8 ± 8.1yrs
						No SDB
						N = 17/76.5 ± 9.6yrs
5	Bodez2016 [93]	France	Cross-sectional study	Cardiac Amyloidosis	SDB	N = 70/71 ± 12 yrs	nocturnal polygraphy	In CA population, prevalence of SDB is high (90%) and dominated by the obstructive pattern.	Combie high quality
						AL
						N = 31/65 ± 12yrs
						m-TTR
						N = 22/71 ± 12yrs
						WT-TTR
						N = 17/81±7yrs
6	Roggenbach2014 [98]	Germany	Prospective cohort study	Elective cardiac surgery	SDB	N = 92/67.5 ± 8.9yrs	Polygraphic recordings	Preoperative SDB were strongly associated with postoperative delirium, and may be a risk factor for postoperative delirium.	NOS mid quality
						No postoperative delirium
						N = 48/64.5±9yrs
						Postoperative delirium
						N = 44/70.8 ± 7.8yrs
7	Javaherforooshzadeh 2022 [100]	Iran	Prospective cohort study	cardiac surgery	OSA	N = 306	STOP-Bang questionnaire	OSA is common in patients undergoing cardiac surgery. Our findings indicate that these patients manifest a higher incidence of postoperative complications compared to those with a lower risk of OSA.	NOS high quality
						Low risk
						N = 33/54.5 ± 12.9yrs
						Intermediate risk
						N = 100/59.1 ± 10.2yrs
						High risk
						N = 173/60.1 ± 8.6yrs
8	Tafelmeier2019 [99]	Germany	Prospective cohort study	cardiac surgery	SDB	N = 141/68±9yrs	Polysomnography	Among the established risk factors for delirium, central sleep apnoea was independently associated with delirium. Our findings contribute to identifying patients at high risk of developing post-operative delirium who may benefit from intensified delirium prevention strategies.	NOS high quality
9	Xu2021 [94]	China	Cross-sectional study	hypertrophic cardiomyopathy	OSA	N = 589/50.5 ± 12.8yrs	Polysomnography	Data from clinical characteristics and polysomnography studies were recorded. OSA was present in 346 patients (58.7%). Patients who had OSA were older, more likely to be male and had more clinical comorbidities such as hypertension, atrial fibrillation and cardiac remodeling	Combie high quality
						No OSA
						N = 243/45.7 ± 13.7yrs
						OSA
						N = 346/53.8 ± 11.1yrs
10	Foldvary-Schaefer 2015 [102]	USA	Prospective cohort study	Cardiovascular Surgery	OSA	N = 107/67.3 ± 13.3yrs	Polysomnography	OSA is highly prevalent in patients undergoing cardiovascular surgery. It could not be shown that OSA was significantly associated with adverse postoperative outcomes, but this may have been due to an insufficient number of subjects.	NOS mid quality
						AHI˂15
						N = 56/65.1 ± 13.8yrs
						AHI≥15
						N = 51/69.7 ± 12.5yrs
11	Ding2016 [101]	China	A Prospective Single-Center Study	Cardiac Valve Replacement Surgery	OSA	N = 290/51.4 ± 10.4yrs	polysomnography	RVHD patients with OSA have an increased incidence of perioperative adverse events. OSA was independently associated with overall postoperative recovery, respiratory insufficiency, and higher rate of postoperative pacemaker use, while CSA was not associated with postoperative events.	NOS mid quality
						No SDB
						N = 175/49.13 ± 10.51yrs
						OSA
						N = 54/54.43 ± 9.49yrs
						CSA
						N = 61/55.20 ± 9.05yrs

ACS: acute coronary syndrome; AF: atrial fibrillation; AL: light-chain amyloidosis; AMI: acute myocardial infarction; AV: aortic valvular; ASV: adaptive servo-ventilation.

BQ: Berlin Questionnaire.

CHF: chronic heart failure; CoB: Cochrane Risk of Bias; CRT-D:cardioverter-defibrillator; CSA:central sleep apnea.

DCC: direct current cardioversion; DCM: dilated cardiomyopathy; ESS: Epworth Sleepiness Scale; EDS: excessive daytime sleepiness.

HCM: hypertrophic cardiomyopathy; HFrEF: HF with reduced ejection fraction; HTN: hypertension; HTN: hypertension; IMT: inspiratory muscle training; ISI: Insomnia Severity Scale.

LAVI: left atrial volume index; LVEF: left ventricular ejection fraction.

MDD: major depressive disorder; MISS: Minimal Insomnia Symptom Scale; MHR: monocyte to high-density lipoprotein ratio; MV: mitral valvular.

MINORS: methodological index for non-randomized studies; m-TTR: hereditary transthyretin amyloidosis.

NOS: Newcastle-Ottawa (cohort) scale; NSTEMI: non-ST elevation acute myocardial infarction.

OSA: obstructive sleep apnea.

PAF: paroxysmal AF; PAP: Positive respiratory pressure therapy.

PSQI: Pittsburgh Sleep Quality Index.

RCT: randomized controlled trial; RVHD: rheumatic valvular heart disease.

SAVR: surgical aortic valve replacement; SAS: sleep apnea syndrome; SA: sleep apnea; SR: sinus rhythm; SSD: Short sleep duration.

TAVI: transcatheter aortic valve implantation; TMVR: transcatheter mitral valve repair.

UA: unstable angina; WT-TTR: wild-type transthyretin amyloidosis.

3.3. Sleep disorders in patients with CAD

In this review, 22 studies [[25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46]] focused on sleep disorders in patients with CAD. Three studies [[25], [26], [27]] reported a high prevalence of sleep disorders in patients with CAD. Patients with acute myocardial infarction (AMI) had a higher prevalence of OSA than those with stable CAD (64% vs. 35%). Four studies [[28], [29], [30], [31]] elucidated the adverse effects of sleep disorders on cardiac function and reported increased adverse cardiac outcomes in patients with CAD and OSA. Seven studies [[32], [33], [34], [35], [36], [37], [38]] uncovered an association between psychological conditions and sleep disorders in patients with CAD. The personality disorders included type D personality, depression, anxiety, and cognition. Six studies [[39], [40], [41], [42], [43], [44]] reported several biomarkers that were implicated in predicting sleep disorders in patients with CAD, such as placental growth factor (PIGF), vascular endothelial growth factor family (VEGF), high sensitivity C-reactive protein (hs-CRP) et al. Three studies [38,45,46] reported that patients with CAD benefited from sleep disorder therapies, namely CPAP and inspiratory muscle training (IMT).

3.4. Sleep disorders in patients with hypertension

In this review, 19 studies [[47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65]] focused on sleep disorders in patients with hypertension. Eight studies [[47], [48], [49], [50], [51], [52], [53], [54]] reported the prevalence (>30%) and adverse cardiac outcomes of sleep disorders in hypertensive patients. Four studies [[55], [56], [57], [58]] uncovered the potential mechanisms of hypertension combined with OSA and listed several biomarkers implicated in predicting sleep disorders in hypertensive patients, such as endoglin (sEng), fms-like tyrosine kinase-1 (sFlt-1), and plasminogen activator inhibitor-1 (PAI-1). Four studies [[59], [60], [61], [62]] illustrated the effects of antihypertensive drugs on poor sleep. Three studies [[63], [64], [65]] highlighted the beneficial effects of CPAP in the treatment of hypertensive patients with OSA.

3.5. Sleep disorders in patients with HF

In this review, 16 studies [[66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81]] focused on sleep disorders in patients with HF were included. Four studies [[66], [67], [68], [69]] showed that sleep disorders were highly prevalent (31–75.5%) in patients with HF. One study [70] revealed an association between depression and sleep quality in patients with HF. Five [[71], [72], [73], [74], [75]] studies explored several potential predictors of sleep disorders in patients with HF, including left ventricular ejection fraction (LVEF), left atrial volume index (LAVI), and erythropoietin (EPO). Two studies [76,77] showed that sedative-hypnotics for treating sleep disorders presented inconsistent effects in patients with HF, either positive or negative. Four studies [[78], [79], [80], [81]] reported several non-drug therapies, including CPAP and CBT-I, for treating sleep disorders in patients with HF.

3.6. Sleep disorders in patients with cardiac arrhythmia

In this review, ten studies [[82], [83], [84], [85], [86], [87], [88], [89], [90], [91]] focused on sleep disorders in patients with cardiac arrhythmias. Nine studies [[82], [83], [84], [85], [86], [87], [88], [89], [90]] reported the prevalence and cardiac outcomes of sleep disorders in patients with arrhythmias. One study [91] demonstrated the important role of CPAP in treating patients with AF and OSA.

3.7. Sleep disorders in patients with other CVD

In this review, 11 studies [[92], [93], [94], [95], [96], [97], [98], [99], [100], [101], [102]] focused on sleep disorders in patients with other CVDs such as cardiomyopathy, mitral regurgitation, and cardiac surgery. Three studies [[92], [93], [94]] reported the prevalence of sleep disorders in patients with cardiomyopathy. Other studies [[95], [96], [97], [98], [99], [100], [101], [102]] have elucidated the prevalence and adverse effects of sleep disorders on cardiac function after cardiac surgery.

3.8. Study quality assessment

Seven studies were evaluated by CoB, and the risk of bias was shown in Fig. 2, Fig. 3. Thirty-six studies were assessed by NOS, including 26 studies of high quality and 10 studies of mid quality. Thirty-three studies were assessed by Combie, including 28 studies of high quality and 5 studies of mid quality. Two studies were evaluated by MINORS, including 1 study of high quality and 1 study of mid quality (Table 1).

Fig. 2.

Risk of bias graph.

Fig. 3.

Risk of bias summary.

4. Discussion

This review comprised data on the prevalence, mechanisms, and therapies for sleep disorders in patients with CVD, including CAD, hypertension, HF, cardiac arrhythmia, and other CVD.

4.1. Sleep disorders in patients with CAD

Sleep disorders are considered risk factors for worsening cardiac function and increasing cardiac events in patients with CAD. Buchner et al. [28] found that patients with AMI and OSA had larger right atria and ventricles than those without OSA, implying that OSA may damage right heart function. A multinational, double-blind, placebo-controlled trial including data from 36 countries revealed that short sleep duration and OSA could predict adverse outcomes (major cardiac events and major adverse cardiac events) in patients with ACS after a median follow-up of 2.5 years [29]. In patients with unstable angina (UA) or non-ST-elevation acute myocardial infarction (NSTEMI), there is a high prevalence of cardiovascular events in the hospital, and this was a primary endpoint in those with a high probability of OSA [30]. In contrast, Araújo et al. [31] reported that OSA had no significant effect on myocardial ischemia or cardiac arrhythmia in patients with stable CAD. However, the conclusion may be biased due to the small sample size (CAD + OSA n = 30) and short study period. In a prospective Israeli study with a follow-up period of 68 months, Aronson et al. [27] showed that SDB did not affect clinical outcomes (involving HF, MI, UA, and death); however, they found a relationship between SDB and pulmonary artery systolic pressure.

Personality and psychosocial state may influence sleep quality in patients with CAD. Regardless of OSA, patients with CAD with type D personality and negative affectivity have worse sleep quality, which may be related to depression and anxiety [32]. Patients with CAD and major depressive disorder (MDD) have higher PSQI scores than those without [33]. An investigation in Pakistan showed a high prevalence of anxiety in patients with CAD and OSA, indicating a close relationship between anxiety and sleep disorders, especially in patients with CAD [34]. Sex differences in social status were associated with poor sleep quality and poor sleep quality-related adverse outcomes. Low education and income are related to poor sleep quality in women with CAD, but not in men [35]. Therefore, this highlights the health benefits of improving the social status of women. Another study [36] focused on sex specificity and cardiac prognosis in patients with AMI and poor sleep quality and showed that women with sleep disturbances had a higher risk of long-term cardiac events, while men with impaired awakening had short-term case fatality (death within 28 days of initial AMI). Sleep disorders also affect cognitive function in patients with CAD. Kazukauskiene et al. [37] evaluated the inflammatory factors and NT-proBNP levels in men with CAD and OSA. They found that OSA and NT-proBNP levels were associated with cognitive dysfunction. Patients with CAD, OSA, and higher NT-proBNP levels had lower digit span and digit symbol test scores, which were used to measure cognition [38].

Certain biomarkers may be effective for evaluating sleep disorders in patients with CAD. PlGF is an angiogenic protein that belongs to the VEGF family. PlGF plays a vital role in pathological angiogenesis, especially in cardiac tissues. According to a multicenter randomized controlled trial, higher PIGF levels can predict OSA and cardiovascular complications in patients with acute coronary syndrome (ACS) [39]. Inflammation and lipid metabolism are associated with CAD and OSA prognoses. Patients with CAD and OSA have higher high-sensitivity C-reactive protein (hs-CRP) and IL-6 levels [40]. The monocyte-to-high-density lipoprotein ratio (MHR), which reflects the inflammatory response during CVD, is considered a new predictor of CVD. Huang et al. [41] conducted a study on patients with CAD, uncovering the association between an elevated MHR and a high risk of OSA. Sorting nexins, which act on sorting membrane proteins, have been implicated in arteriosclerosis. SNX16-Ab levels are elevated in patients with CAD and OSA. Thus, SNX16-Ab may serve as a potential biomarker for predicting CAD in patients with OSA [42]. There is a high level of late-stage (8-isoprostane, 8-ISO) lipid peroxidation products in patients with CAD and poor sleep quality [43]. C1q tumor necrosis factor-related protein 9 (CTRP9) protects cardiac function. Lower CTRP9 levels increase the risk of OSA and cardiac dysfunction in patients with CAD [44].

Accumulating evidence has shown that the treatment of OSA benefits cardiac function and reduces adverse cardiac outcomes [45]. CPAP is regarded as the first-line treatment for OSA. CPAP therapy reduced the NT-proBNP concentration in patients with OSA [38]. A resistive loading device was used to perform IMT, which helps improve the function of specific upper airway dilator muscles. After receiving 6-week IMT, patients with CAD and moderate OSA showed improved inspiratory pressure (MIP) and reduced AHI [46].

4.2. Sleep disorders in patients with hypertension

A history of hypertension predicts future insomnia in older but not middle-aged adults [103]. More than one-third of hypertensive patients report poor sleep quality [47]. In particular, those with resistant hypertension have reduced sleep time and poor sleep quality [48]. The MONICA/KORA study, which included 1959 hypertensive workers, indicated that work stress, impaired sleep, and work stress combined with impaired sleep increased the risk of CVD mortality in hypertensive workers compared with that of those with low work stress and non-impaired sleep [49]. Patients with hypertension have a high prevalence of OSA [50]. Chaudhary et al. [51] reported that more than half of hypertensive patients suffer from OSA. This prevalence was similar to that reported in Ching's study [52]. OSA may influence the prognosis of hypertensive patients, by increasing the left ventricular mass, posterior wall, and interventricular septum [53]. Moreover, hypertensive patients with OSA have poorer sleep quality and higher diastolic blood pressure [54].

Based on potential pathophysiological mechanisms, there are some special markers that assist in the evaluation of OSA in hypertensive patients. β1-adrenergic receptor gene polymorphisms are correlated with OSA severity. Bengtsson et al. [55] found that the Arg389Arg genotype is associated with the apnea-hypopnea index (AHI) in men with hypertension, but not in women. Compared with those carrying the Arg389Gly/Gly389Gly genotypes, the AHI was higher in hypertensive men with the Arg389Arg genotype. Moreover, the inflammatory response and hypercoagulability can impair the endothelial function of blood vessels. Endothelial dysfunction is associated with hypertension and OSA [56]. Certain angiogenesis inhibitors, including sEng and fms-like tyrosine kinase-1 (sFlt-1), could reflect the inflammatory response. Patients with OSA have higher serum sEng and sFlt-1 levels, indicating impaired flow-mediated vasodilation (FMD). In addition, the cardiometabolic index (CMI) plays an important role in evaluating metabolic prognosis. This index is calculated using the waist-to-height ratio and triglyceride/high-density lipoprotein cholesterol ratio. Thus, the CMI could be used as an indicator to assess CVD risk in hypertensive patients [57]. Moreover, the coagulation system was activated by OSA. Furthermore, the levels of plasminogen activator inhibitor-1 (PAI-1), which is a procoagulant molecule that inhibits fibrinolysis, are much higher in patients with hypertension and OSA [58].

Nondrug therapy is vital for treating OSA in hypertensive patients. CPAP also reduces serum troponin I and brain natriuretic peptide levels in patients with OSA and hypertension [63]. Moreover, CPAP effectively lowered daytime blood pressure in patients with nocturnal hypertension and OSA [64]. Similarly, in a randomized clinical trial that included patients with resistant hypertension and OSA, Martínez-García et al. [65] showed that a 12-week CPAP treatment reduced the 24-h mean and diastolic blood pressure and improved the nocturnal blood pressure pattern. In addition, regular physical exercise is an excellent way to lower blood pressure in patients with hypertension or pre-hypertension [104].

4.3. Sleep disorders in patients with HF

Patients with HF frequently experience sleep problems [66], which may be due to insufficient cerebral perfusion. Sleep disorders increase the risk of ventricular arrhythmias and require appropriate cardioverter-defibrillator (CRT-D) implantation in patients with HF [67]. Alosco et al. [68] reported that 75.5% of patients with HF exhibit impaired sleep. The incidence of SDB was 36%, 41%, and 48% in patients with HF and preserved ejection fraction (HFpEF), HF and mid-range ejection fraction (HFmrEF), and HF and reduced ejection fraction (HFrEF), respectively. Meanwhile, there were differences in the SDB subtypes. Among patients with HFrEF, the incidence of central sleep apnea (CSA), OSA, and OSA-CSA was 31%, 29%, and 40%, respectively [69]. Poor sleep quality is also associated with depression, and sleep quality worsens as depressive symptoms become more severe [70].

Owing to the important role of SDB in cardiac function, suitable predictors of SDB in patients with HF are necessary. Indicators of heart function, such as LVEF and LAVI, are potential predictors. Bhalla et al. [71] found that LVEF (20–30%) and NYHA class 2 were predictors of OSA in patients with HF. Calvin et al. [72] showed that an increase in LAVI was associated with an increase in CSA incidence. Therefore, LAVI was used as an indicator of CSA in patients with HF. Serum biomarkers can also be used as predictors. EPO is a glycoprotein hormone involved in the pathogenesis of CVD and OSA. Elevated serum EPO levels are linked to the development of CSA-induced HF in patients with non-anemic HF [73]. Furthermore, among the many circulating protein biomarkers involved in the cardiovascular pathways, there are representative biomarkers of HF and sleep disorders. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are important cardiac markers for heart function. ANP and BNP concentrations are related to the risk of CSA. Thus, lower ANP and BNP levels present a lower risk of CSA [74]. In a randomized clinical study involving patients with HFrEF and CSA, soluble suppression of tumorigenicity 2, neurogenic locus notch homolog protein 3 (Notch-3), and growth differentiation factor 15 (GDF-15) were suitable for predicting prognostic outcomes [75].

Nondrug therapy for sleep disorders is common in patients with HF. Gerçek et al. [78] conducted a retrospective study investigating the effect of SDB treatment on ventricular tachycardia (VT) burden in patients with HF and an implantable cardioverter-defibrillator (ICD). The study included several types of SDB treatments such as CPAP, Assisted Spontaneous Breathing, phrenic nerve stimulation, and Bilevel Positive Airway Pressure. They demonstrated that SDB treatment significantly reduced the VT burden, lowered the rate of anti-tachycardia pacing, and decreased the number of shocks, thereby improving the quality of life for these patients. Abdelbasset [79] reported that 4-week low-intensity exercise program was beneficial for improving sleep quality and increasing maximum oxygen uptake (VO_2peak) in older adult patients with HF. In addition, a prospective cohort study showed that positive respiratory pressure therapy at home for 3 months increased LVEF and decreased AHI in patients with HFrEF and CSA [80]. Furthermore, CBT-Is are commonly used to treat insomnia. CBT-I improves sleep quality in patients with HF and insomnia by relieving insomnia severity, fatigue, excessive daytime sleepiness, and ameliorating the 6-min walk distance [81].

4.4. Sleep disorders in patients with cardiac arrhythmia

Patients with cardiac arrhythmias have a high prevalence of sleep disorders. In a prospective cohort study including 100 consecutive patients with AF from two major arrhythmia clinics in Canada, the prevalence of OSA was 85%. This study also found that during rapid eye movement sleep, 27% of patients had a higher AHI, even though they had a normal AHI overall during sleep [82]. In another prospective study, 81.4% of patients with AF also had SDB [83]. Patients with AF also have a high prevalence of CSA [84]. In a controlled clinical trial including 150 patients with nonvalvular AF and 150 age-matched individuals with sinus rhythm, stepwise multivariate logistic regression was used to analyze the association between AF and sleep disorders. After controlling for confounders, including age, sex, body mass index, SBP, and heart rate, patients with nonvalvular atrial fibrillation exhibited shorter sleep duration and poorer sleep quality than those with a normal rhythm [85]. OSA affects the structure and remodeling of the atrium. The association between OSA and arrhythmia recurrence in patients with AF remains controversial. Sleep disorders increase the risk of AF recurrence after catheter ablation [86]. Anter et al. [87] reported a higher incidence of extraPV triggers and arrhythmia recurrence in patients with paroxysmal AF and OSA. Moreover, OSA was associated with an elevated risk of major adverse cardiac and neurologic events in patients with AF (HR: 1.16, 95% CI: 1.03–1.31, P = 0.011) [88]. Conversely, Tang et al. showed that OSA might not affect the recurrence of paroxysmal AF after catheter ablation [89]. Similarly, Brgdar et al. [90] showed no differences in inpatient cardiac outcomes between patients with AF with or without OSA.

Non-drug therapy plays an important role in the treatment of patients with cardiac arrhythmia and OAS. For patients with both AF and OSA, the combined treatment exerts a better effect than treatment for AF alone [105]. A meta-analysis of 17 studies and 6523 patients, showed that CPAP treatment could reduce the risk of AF (OR: 0.51, 95% CI: 0.27–0.97, P = 0.04) [106]. In a prospective non-randomized interventional study, CPAP was beneficial in reducing atrial and ventricular ectopy count/24 h in patients with AF and OSA. After 3 months of CPAP treatment, the atrial premature beat count/24 h reduced significantly in patients with paroxysmal AF, whereas the ventricular premature beat count/24 h reduced significantly in patients with permanent AF [91].

4.5. Sleep disorders in patients with other CVD

Sleep disorders are highly prevalent among patients with cardiomyopathy. In a cross-sectional study, Banno et al. [92] investigated 35 patients with idiopathic cardiomyopathy and found that the incidence of SDB was 80% among 20 patients with dilated cardiomyopathy, and 47% among 15 patients with hypertrophic cardiomyopathy (HCM). The prevalence of SDB was 90% in patients with cardiac amyloidosis [93]. Xu et al. [94] reported that the incidence of OSA was 58.7% (346/589) in patients with HCM, particularly in those who were older or had other complications (hypertension, AF, etc.). Patients with HCM and OSA exhibit specific characteristics, including a higher body mass index (BMI), higher prevalence of AF, and larger waist and neck circumference [107]. In addition, Konecny et al. [108] identified that exercise tolerance was impaired and the prevalence of SDB was 32% among patients with HCM.

Cardiac surgery is stressful to trigger sleep disorders in CVD patients. In hospitals, patients undergoing surgical aortic valve replacement or transcatheter aortic valve implantation reported insomnia and disturbed sleep-wake patterns during the postsurgical phase [95]. However, the improvement of heart function would benefit sleep health. Abe et al. [96] showed that OSA symptoms were relieved in patients who underwent valve repair surgery because of improved cardiac function. Biener et al. [97] reported that transcatheter mitral valve repair surgery improved heart function and reduced the AHI and central events in patients with mitral regurgitation and CSA with 3.9 ± 4.4 months follow-up. The different results of these studies may be explained by their specific follow-up periods. Moreover, cardiac surgery and sleep disorders are associated with postoperative cognitive dysfunction in patients with CVD post-surgery. OSA increases the risk of post-surgery delirium in patients undergoing cardiac surgery (OR: 6.4, 95% CI: 2.6–15.4, P < 0.001). Therefore, OSA could be regarded as a risk factor for post cardiac surgery delirium [98]. Patients taking zolpidem are more likely to develop delirium after cardiac surgery [109]. Tafelmeier et al. [99] demonstrate that central sleep apnea is associated with the risk of post-surgery delirium in patients undergoing cardiac surgery (OR 4.99, 95% CI 1.41–17.69; p = 0.013). Javaherforooshzadeh et al. [100] reported that patients with a higher risk of OSA had a higher prevalence of postcardiac surgery complications. OSA increases the risk of perioperative adverse events in patients with rheumatic valvular heart disease undergoing cardiac valve replacement surgery [101]. In contrast, although there is a high incidence of OSA after cardiac surgery, Foldvary-Schaefer et al. [102] identified no association between OAS and adverse cardiac outcomes.

Certain indicators may be useful for predicting CAS in patients with mitral regurgitation (MR). LAVI was used to evaluate the structure of left atrial and cardiac diastolic functions. Biener et al. [97] found that LAVI is a valuable indicator of CSA in patients with MR.

5. Limitation

First, this review focused on patients with CVD only, excluding those without, which hindered further examinations of the interrelationship between sleep disorders and CVD. Therefore, the study lacks evidence to prove that sleep disorders would lead to CVD. Second, we did not include animal studies, which could help elucidate the biological mechanisms of sleep disorders in patients with CVD. Therefore, this review is limited in that it only illustrates the underlying pathophysiological mechanisms.

6. Conclusion

This systematic review highlighted the significant prevalence and adverse cardiac outcomes of sleep disorders which hinder treatment among patients with CVD. In conclusion, clinical physicians should carefully consider the sleep quality of patients with CVD to improve their prognosis.

Ethics approval and consent to participate

Not applicable.

Consent for publication

All the authors agree to publish this manuscript.

Availability of data and materials

Not applicable.

Funding

It is supported by China Women's Development Foundation (No.2021573), National Academy of Innovation Strategy (Grant No. 2022-pgs-11), China International Medical Foundation (z-20114-03-2205).

CRediT authorship contribution statement

Lijun Zhang: Data curation, Methodology, Software, Writing – original draft. Guo Li: Data curation, Methodology. Yanping Bao: Writing – review & editing. Meiyan Liu: Conceptualization, Funding acquisition, Project administration, Supervision, Validation, Visualization, Writing – review & editing.

Declaration of competing interest

All the authors declared no competing interests of this manuscript.

Handling editor: D Levy

Abbreviations

ACh

acetylcholine

ACS

acute coronary syndrome

AF

atrial fibrillation

AHI

apnea-hypopnea index

AMI

acute myocardial infarction

ANP

Atrial natriuretic peptide

BDZs

benzodiazepines

BMI

body mass index

BNP

brain natriuretic peptide

CAD

coronary artery disease

CBT-I

cognitive behavioral therapy for insomnia

CIMT

carotid artery intima-media thickness

CMI

cardiometabolic index

CNS

central nervous system

CoB

Cochrane Risk of Bias

CPAP

continuous positive airway pressure

CRT-D

cardioverter-defibrillator

CSA

central sleep apnoea

CTRP9

C1q tumor necrosis factor related protein 9

CVD

cardiovascular disease

PO

erythropoietin

FMD

flow mediated vasodilation

GDF-15

growth differentiation factor 15

HCM

hypertrophic cardiomyopathy

HF

heart failure

HFmrEF

heart failure with mid-range ejection fraction

HFpEF

heart failure and preserved ejection fraction

HFrEF

heart failure and reduced ejection fraction

HR

hazard ratio

hs-CRP

high sensitivity C-reactive protein

ICBT

Internet-based CBT

ICD

implantable cardioverter-defibrillator

ICSD-3

International Classification of Sleep Disorders-3

IL-6

interleukin (IL)-6

IMT

inspiratory muscle training

LAVI

left atrial volume index

LVEF

left ventricular ejection fraction

MACEs

major adverse cardiovascular events

MDD

major depressive disorder

MIP

inspiratory pressure

MR

mitral regurgitation

NF-κB

nuclear factor-kappa B

NOS

Newcastle-Ottawa (cohort) scale

Notch-3

neurogenic locus notch homolog protein 3

NREM

nonrapid eye movements

NSTEMI

non-ST elevation acute myocardial infarction

OSA

obstructive sleep apnea

PAI-1

plasminogen activator inhibitor-1

PIGF

placental growth factor

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-Anlyses

PSQI

Pittsburgh Sleep Quality Index

RCTs

randomized controlled trials

sEng

endoglin

sFlt-1

fms-like tyrosine kinase-1

SNXs

Sorting nexins

TAVI

transcatheter aortic valve implantation

TMVR

transcatheter mitral valve repair

TNF-α

tumor necrosis factor-alpha

UA

unstable angina

VEGF

vascular endothelial growth factor family

VO2peak

maximum oxygen uptake

VT

ventricular tachycardia