Table 2.

Study design, diseases addressed, major findings, and the quality appraisal of the articles.

Author [Ref]	Country of Study	Study Design	Sample Size	Cardiovascular and Other Comorbidities Addressed	Major Findings	Quality Appraisal (0 to 4)
Almeneessier et al., 2020 [20]	Saudi Arabia	Cross-sectional study	32; mean age of 50.2 ± 12 years	Hypertension	Mean Apnea-Hypoxia Index (AHI) was 40.1 ± 27.6 events/h. AHIs were 38.3 ± 30.6 and 51.9 ± 28.3 events/h for non-rapid eye movement (NREM) and rapid-eye movement (REM) sleep, respectively. No differences were detected in obstructive respiratory event duration or degree of desaturation between REM and NREM sleep. Oxygen desaturation index was a predictor of increased systolic blood pressure during obstructive events and post-obstructive event period.	Score = 2; moderate; study design = 1 robust analyses = 1; others = 0.
Alvarez-Sabín et al., 2017 [21]	Spain	Matched cross-sectional study	183	Hypertension with or without silent cerebral infarct; obesity	The frequency of severe OSA syndrome (AHI > 30) was 44.3% in patients with silent cerebral infarct (SCI) and 38.5% in the control group. Severe OSA syndrome is highly prevalent among hypertensive subjects and is independently associated with lacunar silent cerebral infarct.	Score = 2; moderate; study design = 1 robust analyses = 1; others = 0.
Barreto et al., 2020 [22]	Brazil	Prospective cohort study	102 (male = 64%)	Ischemic stroke; hypertension; diabetes; heart disease; physical inactivity	Wake-up stroke occurred in 1 of 3 of cases. Irrespective of stroke, half of the patients had moderate to severe sleep apnea. Type 2 diabetes mellitus was independently associated with stroke (OR = 2.76; CI: 1.10–6.05; p = 0.03).	Score = 2; moderate; study design = 1 robust analyses = 1; others = 0.
Borsini et al., 2018 [23]	Argentina	Prospective follow-up study for one year	168	Hypertension; obesity with a mean BMI of 34.7 ± 6.79; and diabetes mellitus	Of the individuals with hypertension, 44% had an AHI of >15 events/h, and CPAP was recommended in 69 (41%) patients. Based on the American College of Cardiology/American Heart Association (ACC/AHA) Risk Calculator, there was a gradual increase in the risk of cardiovascular events (coronary event or stroke) proportional to the increase in AHI severity categories: 8.7% for patients with normal AHI; and 19.7%, 27.8%, and 30.3% for patients with OSA of 5.1–14.9, 15–29.9, and ≥30, respectively.	Score = 2; moderate; study design = 1 robust analyses = 1; others = 0.
Choudhury et al., 2019 [24]	India	Community based cross-sectional study	200	Hypertension, obesity	Patients with high risk of OSA, snoring was reported by 70%, excessive daytime sleepiness by 50%, 28% were smokers and 48% reported alcohol use. The associated risk factors were age > 35 years (OR = 4.5, 95% CI, 1.4 to 13.8), BMI ≥ 25 kg/m2 (aOR = 3.5, 95% CI, 1.2 to 10.5), alcoholism (aOR = 4.5, 95% CI, 1.8 to 11.1), and hypertension (aOR = 11.5, 95% CI, 4.7 to 28.0).	Score = 3; moderate; study design = 1, sample selection = 1, robust analyses = 1; sample size = 0.
Cohen et al., 2018 [25]	United States	Prospective follow-up study	3101	Narcolepsy, hypertension, thyroid disease, obesity, hyperlipidemia, anxiety, peripheral neuropathy, diabetes mellitus	There was an increased association of narcolepsy with anxiety, thyroid disease, hypertension, and hyperlipidemia. At the end of 9.9 years (SD 7.27 years), there was increased association of narcolepsy with peripheral neuropathy, glucose intolerance, and automobile-related trauma. OSA symptoms were significantly increased in the narcolepsy group as compared to controls (at diagnosis: OR = 69.25, 95% CI = 9.26 to 517.99, p < 0.0001; at end (after about 10 years) OR = 13.55, 95% CI = 5.08 to 36.14, p < 0.0001).	Score = 4; high; study design, sample size, sample selection and data analyses, each scored 1.
Coussa-Koniski et al., 2020 [26]	Lebanon	Prospective longitudinal study	663	Hypertension; coronary artery disease; myocardial infarction; stroke; arrhythmias; chronic heart failure; asthma; COPD; diabetes mellitus; kidney disease; depression; overweight/obesity.	Comorbidities were reported by 90% of the patients with 60% reporting 2–4 comorbidities. The severity of OSA was higher in men compared with women; however, comorbidities were higher in women. In multiple regression, increasing age (OR = 1.91, 95% CI, 1.22–3.0), male gender (OR = 3.16, 95% CI, 1.86–5.39), and obesity (OR = 2.39, 95% CI, 1.53–3.73) associated with hypertension and diabetes, symptoms of snoring, excessive daytime somnolence, and witnessed apneas were significantly associated with severe sleep apnea. Significant declines in systolic and diastolic blood pressure, intima-media thickness, and renal resistance index and increase in the left ventricular ejection fraction were observed after a 6-month therapy with CPAP.	Score = 3; moderate; study design = 1, sample size = 1, robust analyses = 1; sample selection = 0.
Frigy et al., 2019 [27]	Romania	Cross-sectional study (hospital based)	51 consecutive cases (13 women and 38 men) (mean age 60.8 years).	Acute heart failure; diabetes mellitus; obesity; renal dysfunction.	Patients underwent 24-h combined monitoring of ECG and blood pressure and sleep apnea testing before discharge. The presence of significant sleep apnea was found to influence blood pressure and nocturnal ventricular ectopy in patients with stabilized acute heart failure.	Score = 2; moderate; study design = 1, sample selection = 1; others = 0.
Ghesquière et al. [28]	United States	Prospective longitudinal study	67 pregnant women	Obesity (mean BMI of 42.4 ± 6.2 kg/m2); hypertension.	29 pregnant women (43%) had OSA (95% CI, 31.4 to 55.2%); mild or moderate OSA was in 25 (37%) women and severe OSA in 4 (6%). Women in the OSA group were older, had chronic hypertension more frequently, and had a higher mean BMI.	Score = 2; moderate; study design = 1, robust analyses = 1; others = 0.
Gürün et al., 2020 [29]	Turkey	Cross-sectional study	266; normal blood pressure (n = 125) and high blood pressure (n = 141).	Hypertension	Hypertension is associated OSA. The risk factors included: older age (OR: 1.095, 95% CI 1.05 to 1.14), higher Epworth sleepiness scale (ESS) (OR: 1.19, 95% CI 1.07 to 1.31), mean apnea duration (OR: 1.07, 95% CI 1.03 to 1.11), oxygen desaturation index (ODI) (OR: 1.06, 95% CI 1.03 to 1.10), and nocturnal oxygen desaturation (NOD) (OR: 2.44, 95% CI 1.17 to 5.09).	Score = 2; moderate; study design = 1, robust analyses = 1; others = 0.
Haarmann et al., 2019 [30]	Germany	Prospective longitudinal study (10 years)	378	Hypertension, diabetes mellitus, atherosclerotic disease, and chronic heart failure; 206 (60%) had OSA.	OSA was classified as none (AHI < 5/h), mild (AHI 5–14/h), moderate (AHI 15–29/h), or severe (AHI ≥ 30/h). Overall mortality was higher in the OSA group (14.9% vs. 5.9%; p = 0.007); however, the mortality difference disappeared after adjustment for age and sex. The study did not find evidence of an adverse effect of OSA on cardiovascular morbidity and mortality.	Score = 4; high; study design, sample size, sample selection and data analyses, each scored 1.
Hein et al., 2019 [31]	Belgium	Hospital-based cross-sectional study	703	Major depression; hypertension	Multivariate logistic regression analysis revealed that severe objective insomnia, low complaints of repeated nighttime awakenings or early morning awakening, and intermediate or low self-reported insomnia complaints were significant risk factors of high blood pressure in major depression.	Score = 4; high; study design, sample size, sample selection and data analyses, each scored 1.
Hein et al., 2019 [32]	Belgium	Cross-sectional study	1272	Hypertension	The prevalence of high blood pressure with insomnia was 30.03%. Short sleep duration (<5 h), severely reduced sleep efficiency (<65%), high sleep fragmentation (sleep fragmentation index ≥ 18/h), and long-term use of short or intermediate half-life benzodiazepine receptor agonists were significant risk factors for hypertension in individuals with insomnia.	Score = 3; moderate; study design = 1, sample size = 1, robust analyses = 1; sample selection = 0.
Hobzova et al., 2018 [33]	Czech Republic	Cohort study; multicenter sample selection	188	Hypertension; obesity	AHI was classified as mild for AHI = 5–14.9, moderate for AHI = 15–29.9 and severe for AHI ≥ 30. Undiagnosed sleep apnea (SA) was found in 72.9% patients (29.3% mild, 26.6% moderate, 17.0% severe) patients with blood pressure. Moderate/severe SA (AHI ≥ 15) was associated with BMI ≥ 30 kg/m2 (OR = 6.22, 95% CI, 3.10–12.49), and central obesity (OR = 3.73, 95% CI, 1.57–8.83), but not with ambulatory blood pressure.	Score = 3; moderate; study design = 1 sample selection = 1; robust analyses = 1; others = 0.
Hsu H.-C. et al., 2018 [34]	Taiwan	Cross-sectional study (hospital based)	215	Hypertension	Nearly 82% of the hypertensive participants were found having undiagnosed OSA, 80% of which were of mild to moderate severity. Severe OSA was significantly associated with excessive daytime sleepiness (OR, 20.27; 95% CI, 1.58 to 26.97) and oxygen desaturation index (OR, 4.05; 95% CI, 1.86 to 8.81).	Score = 2; moderate; study design = 1 robust analyses = 1; others = 0.
Johnson et al., 2019 [12]	United States	Cross-sectional study	913 African Americans (mean age of 64.0 ± 10.6 years).	Hypertension; obesity (58.6%); diabetes mellitus (28.2%).	Overall, 48% of participants had uncontrolled hypertension and 14% had resistant hypertension. Untreated African American patients with moderate or severe sleep apnea had an increased risk of resistant hypertension. Severe OSA (AHI ≥ 30) compared with no OSA (AHI < 5) was associated with a 3.5 times higher odds of resistant hypertension (95% CI, 1.54 to 7.91). After adjustment for confounders, individuals with moderate or severe sleep apnea had a 2.0 times higher odds of resistant hypertension (95% CI, 1.14 to 3.67).	Score = 4; high; study design, sample size, sample selection and data analyses, each scored 1.
Karhu et al., 2021 [35]	Finland	Prospective longitudinal study	2535 Sleep Heart Health Study participants	Hypertension (n = 1164), diabetes (n = 170) and cardiovascular diseases (n = 265)	The increase in oxygen desaturation index (β = 2.73, 95% CI: 1.15 to 4.32, p = 0.001) and desaturation duration (β = 1.85, 95% CI: 0.62 to 3.08, p = 0.003) were higher among participants with cardiovascular diseases. These results suggest that patients with pre-existing diabetes or cardiovascular diseases are at increased risk for an expedited worsening of intermittent hypoxemia.	Score = 4; high; study design, sample size, sample selection and data analyses, each scored 1.
Kim et al., 2018 [36]	Korea	Prospective cohort study	1825	Hypertension	The prevalence of hypertension was higher among subjects with OSA and with high homocysteine (Hcy) levels. After adjusting for confounding factors, subjects with OSA and high Hcy levels had a 1.86-fold risk of developing hypertension compared to those without OSA and high Hcy levels.	Score = 4; high; study design, sample size, sample selection and data analyses, each scored 1.
Kolluri et al., 2020 [37]	United States	Retrospective study	264	Chronic venous disease (CVD), diabetes mellitus, pulmonary embolism, renal insufficiency	22.7% of the patients had elevated central venous pressure (CVP) and 26.9% had OSA. There was no significant difference in the prevalence of OSA. The predictors of elevated CVP were age > 64.6 years (OR, 1.03; 95% CI, 1.003 to 1.05; p = 0.026), diabetes mellitus (OR, 2.19; 95% CI, 1.05–4.5; p = 0.035), and right lower extremity Venous Clinical Severity Score of ≥8.5 (OR, 1.098; 95% CI, 1.011–1.193; p = 0.026).	Score = 3; moderate; study design = 1, sample size = 1, robust analyses = 1; sample selection = 0.
Lai et al., 2019 [38]	Italy	Prospective longitudinal study	24	Resistant hypertension; overweight	Elderly patients (mean age of 60.3 ± 9.9 years, mean BMI of 28.7 ± 3.3 kg/m2) with resistant hypertension and OSA were controlled through 6-month long treatment with continuous positive airway pressure (CPAP). The treatment was considered effective if the patient was compliant, and the AHI was reduced by ≥50% from baseline or below 10 events per hour.	Score = 2; moderate; study design = 1 robust analyses = 1; others = 0.
Li et al., 2018 [39]	China	Cross-sectional study	144	Hypertension	There were no significant differences between subjects with and without morning hypertension in sleep disturbances and sleep respiratory parameters.	Score = 2; moderate; study design = 1 robust analyses = 1; others = 0.
Louis et al., 2018 [40]	United States	Cross-sectional study	3264 women in early pregnancy and 2512 women in late pregnancy	Hypertension, obesity (n = 380, 11.8%), morbid obesity (n = 349, 10.8%) hypothyroidism (n = 172, 5.5%)	The prevalence of sleep-disordered breathing (SDB) was 3.6% and 8.3% in early pregnancy and late pregnancy, respectively. Logistic regression models showed age, BMI, and frequent snoring as predictors of SDB.	Score = 4; high; study design, sample size, sample selection and data analyses, each scored 1.
Manov et al., 2018 [41]	Bulgaria	Cross-sectional study	279; 162 (58%) men; mean age 42.8 ± 12.4 years	Pericardial effusion in patients without PH; obesity (mean BMI of 37.3 ± 7.8 kg/m2).	Severity of OSA was graded as follows: mild (AHI 5–15), moderate (AHI 15–30), and severe (AHI > 30). Pericardial effusion was found in 102 (36.56%)—all of them with moderate to severe OSA syndrome. A significant positive correlation was found between the presence of pericardial effusion and AHI (r = 0.374, p < 0.001), BMI (r = 0.473, p < 0.001), and desaturation time during sleep (r = 0.289, p < 0.001).	Score = 4; high; study design, sample size, sample selection and data analyses, each scored 1.
Morinaga et al., 2018 [42]	Japan	Cross-sectional study	2208 men (mean age, 44.4 ± 0.2 years)	Hypertension	The prevalence of mild-to-moderate (AHI of 5–29) and severe (AHI ≥ 30) OSA in the studied subjects were 7.1%, and 6.1%, respectively. Associations between hypertension and OSA were observed after adjustments for age, body mass index (BMI), estimated glomerular filtration rate, current alcohol intake, current smoking habits, and OSA treatment.	Score = 4; high; study design, sample size, sample selection and data analyses, each scored 1.
Nozato et al., 2019 [43]	Japan	Cross-sectional study	29 patients (aged 65 years or older)	Hypertension; obesity.	The patients were categorized into two groups: no-to-mild OSA and moderate-to-severe OSA, by using the respiratory disturbance index (RDI) and 3% oxygen desaturation index (ODI). BMI was correlated with RDI and 3% ODI (r  =  0.56 and 0.43, respectively). Sleep apnea severity was associated with pulse rate variability but not with blood pressure variability.	Score = 2; moderate; study design = 1 robust analyses = 1; others = 0.
Paine et al., 2019 [44]	New Zealand	Cross-sectional study	12,500 adults	Hypertension, obesity, diabetes mellitus, heart disease	The prevalence of each sleep complaint measure was highest for the indigenous Māori population. Reporting any sleep complaint was associated with higher odds of poorer mental health, diagnosed high blood pressure, diagnosed diabetes, diagnosed heart disease, poor/fair self-rated health, obesity, current smoking, and hazardous drinking.	Score = 3; moderate; study design = 1, sample size = 1, robust analyses = 1; sample selection = 0.
Poka-Mayap et al., 2020 [45]	Cameroon	Cross-sectional hospital based study	359 (56% women)	Hypertension, diabetes mellitus, acute heart failure, stroke, HIV infection, and epilepsy.	The prevalence of high risk of OSA and hypopnea syndrome (OSAHS), as assessed from the STOP-BANG questionnaire, was 64.1% (95% CI, 59.1 to 69.1%) in the whole population, 78.3% (95% CI, 71.9 to 81.7%) in men and 53% (95% CI, 46.1 to 59.9%) in women (p < 0.001). Moderate to severe sleep apnea was associated with hypertension (OR, 3.24; 95% CI, 1.08 to 9.72; p = 0.036.	Score = 4; high; study design, sample size, sample selection and data analyses, each scored 1.
Saraei et al., 2020 [46]	Iran	Cross-sectional study	281 locomotive drivers (mean age of 43 ± 10 years)	Hypertension, obesity	Mean BMI was 26.9 ± 3.9 kg/m2; 166 (59.9%) drivers had two or more of the following risk factors: blood pressure ≥ 140/90 mmHg, history of drug use, BMI > 35 kg/m2, age > 50 years, and neck circumference > 40 cm.	Score = 1; low; study design = 1; others = 0.
Schiavone et al., 2019 [47]	Argentina	Cross-sectional clinic-based study	382 patients; 234 men (61.3%) and 148 women; Mean age: 54.5 ± 13.7 years.	Hypertension; obesity (BMI, 33.1 ± 7.8 kg/m2)	Adult patients were recruited from a hypertension center. Among the patients analyzed, 57.2% had moderate to severe OSA, while 42.8% had mild OSA. The high-risk Berlin questionnaire was the most sensitive tool to identify AHI > 5 eV/hour, while STOP-BANG questionnaire (SBQ) > 5 performed better at identifying patients with >15 eV/hour with a high discrimination power.	Score = 4; high; study design, sample size, sample selection and data analyses, each scored 1.
Seguro et al., 2018 [48]	France	Retrospective case–control study	200; normal blood pressure (n = 100), high blood pressure (n = 100).	Hypertension; obesity (n = 126, 63%); asthma (n = 5, 3%), and COPD (n = 8, 4%).	Cases were hypertensive patients and controls were age- and gender-matched normotensive patients. Severe OSA was defined as an AHI ≥ 30. OSA was considered symptomatic when ESS > 10. Associations were found between resistant hypertension and untreated obstructed sleep apnea. However, individuals with hypertension were less symptomatic with episodes of sleep apnea with a lower rate of the ESS (10.0 vs. 11.9, p  <  0.01).	Score = 2; moderate; study design = 1 robust analyses = 1; others = 0.
Sun et al., 2019 [49]	China	Cross-sectional study	106	COPD; pulmonary hypertension (PH) mean age 69.5 years, 91.5% men	56 (52.8%) patients with COPD were diagnosed with OSA, and 24 (22.6%) patients with COPD had PH. Multiple regression analysis showed a significant and independent effect of both FEV1% predicted and AHI on PH, indicating declining lung function and increased severity of OSA in patients with COPD.	Score = 2; moderate; study design = 1 robust analyses = 1; others = 0.
Sunwoo et al., 2018 [50]	Korea	Cross-sectional study	2740	Hypertension, diabetes, hyperlipidemia, myocardial infarction, angina pectoris, other heart diseases, stroke and psychiatric comorbidities.	The prevalence of a “high risk” for OSA was 15.8% (95% CI, 14.5 to 17.2%). Multiple logistic regression analysis showed that BMI ≥ 25 kg/m2 (OR 10.75, 95% CI, 8.21–14.06), hypertension (OR = 5.83, 95% CI, 3.91–8.69), diabetes (OR = 2.54, 95% CI, 1.46–4.42), hyperlipidemia (OR = 2.85, 95% CI, 1.36–5.95), and anxiety (OR = 1.63, 95% CI, 1.03–2.59) were significantly related with a “high risk” for OSA, whereas physical activity ≥ 3 times/week (OR = 0.85, 95% CI, 0.66–1.09) had a protective effect.	Score = 4; high; study design, sample size, sample selection and data analyses, each scored 1.
Wächter et al., 2020 [51]	11 Sleep centers in 8 European countries	Multicenter retrospective cohort study	1877 (OSA patients and healthy controls)	Hypertension; obesity	Effects of OSA severity and potential confounders on sleep architecture were small, but transition patterns still linked sleep fragmentation directly to OSA-related clinical outcomes such as arterial hypertension and daytime sleepiness.	Score = 4; high; study design, sample size, sample selection and data analyses, each scored 1.
Wilson et al., 2018 [52]	Australia	Cross-sectional study	80 women (40 cases and 40 controls)	Gestational hypertension, pre-eclampsia	The frequency of sleep-disordered breathing was 1.4 times higher in the cases than controls (52.5% vs. 37.5%, respectively; p = 0.18). Severity of sleep-disordered breathing was more than twice as common in women with gestational hypertension or pre-eclampsia compared to controls (35% vs. 15%, p = 0.039).	Score = 2; moderate; study design = 1 robust analyses = 1; others = 0.