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Epidemiology of Obstructive Sleep Apnea: What is the Contribution of Hypertension and Arterial Stiffness?

The Journal of Clinical Hypertension

February 2022
24(6)

DOI:10.1111/jch.14426

License
CC BY-NC-ND 4.0

Authors:

Pasquale Mone

University of Molise

Urna Kansakar

Albert Einstein College of Medicine

Fahimeh Varzideh

Albert Einstein College of Medicine

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Obstructive sleep apnea (OSA) is defined as brief and repeated interruptions of breathing due to upper airway obstructive events during the sleep; these recurrent interruptions could be complete (apneas) and/or partial (hypopneas), resulting in intermittent hypoxemia, autonomic fluctuation, and sleep fragmentation. The apnea-hypopnea index (AHI) quantifies the episodes of apnea (cessation of airflow for at least 10 seconds) and hypopnea (reduction in airflow by at least 30% for at least 10 seconds with decrease in blood oxygen saturation). When defined as an AHI > 5 events per hour of sleep, the prevalence of OSA in the United States is ∼15-30% in males and 10–15% in females; instead, if defined as AHI ≥5 events per hour plus symptoms or AHI ≥15 events per hour), the prevalence is approximately 15% in males and 5% in females. OSA is typical in adults; males, older, and obese individuals are at a higher risk. The prevalence of OSA may also be influenced by race: indeed, it is common in African-Americans, independent of body weight

The complex relationship linking hypertension, arterial stiffness, and obstructive sleep apnea (OSA)

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Received: 17 December 2021 Accepted: 20 December 2021

DOI: 10.1111/jch.14426

COMMENTARY

Epidemiology of obstructive sleep apnea: What is the

contribution of hypertension and arterial stiffness?

Pasquale Mone MD1,2,3Urna Kansakar PhD1Fahimeh Varzideh PhD1

Eugenio Boccalone MD3Angela Lombardi PhD1Antonella Pansini MD3

Gaetano Santulli MD, PhD1

1Department of Medicine, Albert Einstein College of Medicine, New York, New York, USA

2Università degli Studi della Campania “Luigi Vanvitelli,”, Naples, Italy

3ASL Avellino, Italy

Correspondence

Gaetano Santulli, 1300 Morris Park Avenue,New York, NY,USA.

Email: gaetano.santulli@einsteinmed.edu

Funding information

National Institutes of Health, Grant/AwardNumbers: R01-HL146691, R01-HL159062, R01-DK123259, R01-DK033823, T32-HL144456; American Heart Association,

Grant/AwardNumber: AHA-22POST995561

1EPIDEMIOLOGY OF OBSTRUCTIVE SLEEP

APNEA

Obstructive sleep apnea (OSA) is defined as brief and repeated inter-

ruptions of breathing due to upper airway obstructive events during

the sleep1; these recurrent interruptions could be complete (apneas)

and/or partial (hypopneas), resulting in intermittent hypoxemia, auto-

nomic fluctuation, and sleep fragmentation.2The apnea-hypopnea

index (AHI) quantifies the episodes of apnea (cessation of airflow for

at least 10 seconds) and hypopnea (reduction in airflow by at least

30% for at least 10 seconds with decrease in blood oxygen saturation).

When defined as an AHI >5 events per hour of sleep, the prevalence of

OSA in the United States is ∼15-30% in males and 10–15% in females;

instead, if defined as AHI ≥5 events per hour plus symptoms or AHI

≥15 events per hour), the prevalence is approximately 15% in males

and 5% in females.3OSA is typical in adults; males, older, and obese

individuals are at a higher risk.4The prevalence of OSA may also be

influenced by race: indeed, it is common in African-Americans, inde-

pendent of body weight.5,6

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial- NoDerivs License, which permits use and distribution in any

medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

2OSA, HYPERTENSION, AND ARTERIAL

STIFFNESS: MÉNAGE À TROIS?

Patients with OSA have an increased incidence of hypertension, even

when asymptomatic.7–9

Arterial stiffness is common in hypertension and is a sign of struc-

tural and functional alterations of the vascular wall, associated with

organ damage.10,11 On the other side of the coin, patients with

resistant hypertension have a high prevalence of OSA.12,13 Hence,

hypertensive patients with arterial stiffness and OSA have many

complications and adverse outcomes.14 Nonetheless, the complex rela-

tionship linking hypertension, arterial stiffness, and OSA is not fully

clear (Figure 1). To elucidate this matter, Saeed and associates prospec-

tively investigated a large population of 6408 participants with sus-

pected OSA undergoing a standard respiratory polygraphy, and the

results have been published in this issue of the Journal of Clinical

Hypertension.15

The prevalence of hypertension was 70.8% in OSA patients

(defined as AHI ≥15/h) and 46.7% in non-OSA controls (P<.0001).

J Clin Hypertens. 2022;24:395–397. wileyonlinelibrary.com/journal/jch 395

396 MONE ET AL.

FIGURE 1 The complex relationship linking hypertension, arterial

stiffness, and obstructive sleep apnea (OSA)

Hypertension and obesity were the most common modifiable cardio-

vascular risk factors among OSA patients; approximately one-fourth

of OSA patients displayed an increased arterial stiffness, defined by a

brachial pulse pressure (PP) ≥60 mmHg. Albeit in an unadjusted logis-

tic regression model, OSA was associated with a 1.3-fold higher risk of

having increased PP, in a multivariable-adjusted model, OSA did not

retain its association with arterial stiffness, which was instead main-

tained by age, male sex, and history of hypertension. It is important to

note that the Authors only used PP to quantify arterial stiffness and

did not use PWV, generally considered the gold standard method; fur-

thermore, the duration of antihypertensive treatment in the popula-

tion was not known.

OSA is associated with a marked increase in sympathetic activity

during sleep, which influences heart rate and blood pressure.16

This augmented sympathetic activity in OSA patients is most

likely a result of intermittent hypoxemia, hypercapnia, and sleep

fragmentation.14,17,18 In a controlled trial, 318 patients with moderate-

to-severe OSA were randomized to either sleep education (control

arm) or continuous positive airway pressure (CPAP), or nocturnal sup-

plemental oxygen, for a period of 12 weeks; CPAP was associated with

a 2.8 mmHg greater reduction in mean arterial pressure compared

to controls, whereas supplemental oxygen alone did not significantly

reduce blood pressure.19

A recent large clinical trial conducted in 31 309 patients undergoing

overnight polysomnography revealed that patients with more severe

OSA as measured by the AHI are more likely to have incident venous

thromboembolism; however, adjusted analyses suggest that this asso-

ciation is explained due to confounding by obesity.20 Indeed, OSA

patients have been shown to have higher circulating levels of leptin

compared to controls, and these levels are positively correlated with

the AHI.21 Instead, the strong association between OSA and coronary

and cerebral vascular disease appears to be independent of shared risk

factors including adiposity.22

3OSA, HYPERTENSION, AND COGNITIVE

DYSFUNCTION

Hypertension is one of the main determinants of endothelial dysfunc-

tion, particularly in the aging population.23 Cognitive dysfunction is

a well-known complication of hypertension and other cardiovascular

diseases24,25 and several reports have highlighted the relationships

between arterial stiffness and cognition in hypertensive patients.26–28

Furthermore, OSA sleep-disordered breathing has been associated

with an increased risk of cognitive impairment.17,29 A recent study30

evidenced a significant correlation (r: 0.30; P: .002) between arte-

rial stiffness and executive function-processing speed performance in

patients with OSA and chronic obstructive pulmonary disease (COPD).

Therefore, it should be interesting to investigate the relationship

between arterial stiffness and cognitive dysfunction in hypertensive

patients with OSA.

4PERSPECTIVES: DIAGNOSING MORE,

TREATING BETTER

OSA remains too often underdiagnosed and undertreated in cardiovas-

cular practice, despite its high prevalence in patients with cardiovas-

cular disease and the vulnerability of cardiac patients to OSA-related

stressors. A recent scientific statement of the American Heart Asso-

ciation recommends screening for OSA in patients with resistant (or

poorly controlled) hypertension, pulmonary hypertension, and recur-

rent atrial fibrillation after either cardioversion or ablation.2

ACKNOWLEDGEMENTS

The Santulli’s Lab is supported in part by the National Institutes

of Health (NIH: R01-HL146691, R01-HL159062, R01-DK123259,

R01-DK033823, and T32-HL144456, to G.S.), by the Irma T. Hirschl

and Monique Weill-Caulier Trusts (to G.S.), and by the Diabetes

Action Research and Education Foundation (to G.S.); F.V. holds a

postdoctoral fellowship from the American Heart Association (AHA-

22POST995561).

CONFLICTS OF INTEREST

The authors have no competing interests.

ORCID

Gaetano Santulli MD, PhD https://orcid.org/0000-0001-7231-375X

REFERENCES

1. Dopp JM, Reichmuth KJ, Morgan BJ. Obstructive sleep apnea and

hypertension: mechanisms, evaluation, and management. Curr Hyper-

tens Rep. 2007;9(6):529-534. https://doi.org/10.1007/s11906-007-

0095-2

MONE ET AL.397

2. Yeghiazarians Y, Jneid H, Tietjens JR, et al. Obstructive Sleep Apnea

and Cardiovascular Disease: a Scientific Statement From the Amer-

ican Heart Association. Circulation. 2021;144(3):e56. https://doi.org/

10.1161/CIR.0000000000000988

3. McNicholas WT. COPD-OSA Overlap Syndrome: evolving Evidence

Regarding Epidemiology, Clinical Consequences, and Management.

Chest. 2017;152(6):1318-1326. https://doi.org/10.1016/j.chest.2017.

04.160

4. Carneiro G, Zanella MT. Obesity metabolic and hormonal disorders

associated with obstructive sleep apnea and their impact on the risk

of cardiovascular events. Metabolism. 2018;84:76–84. https://doi.org/

10.1016/j.metabol.2018.03.008

5. Redline S, Tishler PV, Hans MG, Tosteson TD, Strohl KP, Spry K. Racial

differences in sleep-disordered breathing in African-Americans and

Caucasians. Am J Respir Crit Care Med. 1997;155(1):186-192. https:

//doi.org/10.1164/ajrccm.155.1.9001310

6. Kapur VK, Auckley DH, Chowdhuri S, et al. Clinical Practice Guideline

for Diagnostic Testing for Adult Obstructive Sleep Apnea: an Ameri-

can Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep

Med. 2017;13(3):479-504. https://doi.org/10.5664/jcsm.6506

7. Tam W, Ng SS, To KW, Ko FW, Hui DS. The interaction between hyper-

tension and obstructive sleep apnea on subjective daytime sleepiness.

J Clin Hypertens (Greenwich). 2019;21(3):390-396. https://doi.org/10.

1111/jch.13485

8. Konecny T, Kara T, Somers VK. Obstructive sleep apnea and hyperten-

sion: an update. Hypertension. 2014;63(2):203-209. https://doi.org/10.

1161/HYPERTENSIONAHA.113.00613

9. Vgontzas AN, Li Y, He F, et al. Mild-to-moderate sleep apnea is associ-

ated with incident hypertension: age effect. Sleep. 2019;42(4):zsy265.

https://doi.org/10.1093/sleep/zsy265

10. Guo X, Li Y, Yang Y, et al. Noninvasive markers of arterial stiffness and

renal outcomes in patients with chronic kidney disease. J Clin Hypertens

(Greenwich). 2021;23(4):823-830. https://doi.org/10.1111/jch.14185

11. Wilson S, Mone P, Jankauskas SS, Gambardella J, Santulli G. Chronic

kidney disease: definition, updated epidemiology, staging, and mech-

anisms of increased cardiovascular risk. J Clin Hypertens (Greenwich).

2021;23(4):831-834. https://doi.org/10.1111/jch.14186

12. Sapina-Beltran E, Torres G, Benitez I, et al. Prevalence, Characteris-

tics, and Association of Obstructive Sleep Apnea with Blood Pres-

sure Control in Patients with Resistant Hypertension. Ann Am Tho-

rac Soc. 2019;16(11):1414-1421. https://doi.org/10.1513/AnnalsATS.

201901-053OC

13. Martinez-Garcia MA, Navarro-Soriano C, Torres G, et al. Beyond Resis-

tant Hypertension. Hypertension. 2018;72(3):618-624. https://doi.org/

10.1161/HYPERTENSIONAHA.118.11170

14. Mansukhani MP, Covassin N, Somers VK. Apneic Sleep, Insufficient

Sleep, and Hypertension. Hypertension. 2019;73(4):744-756. https://

doi.org/10.1161/HYPERTENSIONAHA.118.11780

15. Saeed S, Romarheim A, Mancia G, et al. Characteristics of hypertension

and arterial stiffness in obstructive sleep apnea: a Scandinavian experi-

ence from a prospective study of 6408 normotensive and hypertensive

patients. J Clin Hypertens (Greenwich). 2022;24(4):385-394.

16. Venkataraman S, Vungarala S, Covassin N, Somers VK. Sleep

Apnea, Hypertension and the Sympathetic Nervous System in

the Adult Population. J Clin Med. 2020;9(2):591. https://doi.org/

10.3390/jcm9020591

17. Prabhakar NR, Peng YJ, Nanduri J. Hypoxia-inducible factors and

obstructive sleep apnea. J Clin Invest. 2020;130(10):5042-5051.

https://doi.org/10.1172/JCI137560

18. Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural

mechanisms in obstructive sleep apnea. J Clin Invest. 1995;96(4):1897-

1904. https://doi.org/10.1172/JCI118235

19. Gottlieb DJ, Punjabi NM, Mehra R, et al. CPAP versus oxygen in

obstructive sleep apnea. NEnglJMed. 2014;370(24):2276-2285.

https://doi.org/10.1056/NEJMoa1306766

20. Genuardi MV, Rathore A, Ogilvie RP, et al. Incidence of venous

thromboembolism in patients with obstructive sleep apnea: a cohort

study. Chest. 2021. In press. https://doi.org/10.1016/j.chest.2021.

12.630

21. Li X, He J. The Association Between Serum/Plasma Leptin Levels

and Obstructive Sleep Apnea Syndrome: a Meta-Analysis and Meta-

Regression. Front Endocrinol (Lausanne). 2021;12:696418. https://doi.

org/10.3389/fendo.2021.696418

22. Gottlieb DJ. Sleep Apnea and Cardiovascular Disease. Curr Diab Rep.

2021;21(12):64. https://doi.org/10.1007/s11892-021-01426- z

23. Torngren K, Rylance R, Bjork J, et al. Association of coronary calcium

score with endothelial dysfunction and arterial stiffness. Atherosclero-

sis. 2020;313:70-75. https://doi.org/10.1016/j.atherosclerosis.2020.

09.022

24. Mone P, Gambardella J, Pansini A, et al. Cognitive Impairment in

Frail Hypertensive Elderly Patients: role of Hyperglycemia. Cells.

2021;10(8):2115. https://doi.org/10.3390/cells10082115

25. Mone P, Gambardella J, Pansini A, et al. Cognitive dysfunction corre-

lates with physical impairment in frail patients with acute myocardial

infarction. Aging Clin Exp Res. 2021. In press. https://doi.org/10.1007/

s40520-021- 01897-w

26. Hanon O, Haulon S, Lenoir H, et al. Relationship between arterial

stiffness and cognitive function in elderly subjects with complaints

of memory loss. Stroke. 2005;36(10):2193-2197. https://doi.org/10.

1161/01.STR.0000181771.82518.1c

27. Rensma SP, Stehouwer CDA, Van Boxtel MPJ, et al. Associ-

ations of Arterial Stiffness With Cognitive Performance, and

the Role of Microvascular Dysfunction: the Maastricht Study.

Hypertension. 2020;75(6):1607-1614. https://doi.org/10.1161/

HYPERTENSIONAHA.119.14307

28. Marfella R, Paolisso G. Increased Arterial Stiffness Trumps on Blood

Pressure in Predicting Cognitive Decline in Low-Risk Populations.

Hypertension. 2016;67(1):30-31.

29. Leng Y, McEvoy CT, Allen IE, Yaffe K. Association of Sleep-Disordered

Breathing With Cognitive Function and Risk of Cognitive Impair-

ment: a Systematic Review and Meta-analysis. JAMA Neurol.

2017;74(10):1237-1245. https://doi.org/10.1001/jamaneurol.2017.

2180

30. Luehrs RE, Moreau KL, Pierce GL, et al. Cognitive performance is

lower among individuals with overlap syndrome than in individuals

with COPD or obstructive sleep apnea alone: association with carotid

artery stiffness. J Appl Physiol (1985). 2021;131(1):131-141. https://

doi.org/10.1152/japplphysiol.00477.2020

How to cite this article: Mone P, Kansakar U, Varzideh F, et al.

Epidemiology of obstructive sleep apnea: what is the

contribution of hypertension and arterial stiffness? JClin

Hypertens. 2022;24:395–397.

https://doi.org/10.1111/jch.14426

Linear Relationship between Hepatic Steatosis Index and Major Adverse Cardiovascular Events in Hypertensive Patients with Obstructive Sleep Apnea: A Real-World Cohort Study from China

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We performed a wavelet analysis of oscillatory dynamics in brain activity of patients with obstructive sleep apnoea (OSA) (N=10, age

52.8\pm 13

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51. 5\pm 29.5

years, median 42 years; malefemale ratio: 87), based on the calculation of patterns from electroencephalographic (EEG) signals of ***nighttime polysomnography (PSG) recordings. It was shown that there were no statistical differences in the number and duration of nocturnal sleep stages in patients of the two groups. The distributions of the number N and duration T of oscillatory wavelet patterns of EEG signals in bands

\Delta f_i = [i; i+2]

, where i takes values from 2 to 38, have been estimated. Statistically significant differences in the characteristics of the distributions of the number and duration of patterns for the high-frequency bands

\Delta f_{17}

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\Delta f_{19}

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Background Obstructive sleep apnea (OSA) is an important but frequently overlooked risk factor for hypertension (HTN). The prevalence of hypertension is high in patients with OSA, but the differences in clinical symptoms and comorbidities between patients with OSA with hypertension and those with normal blood pressure have not been fully defined. Methods This study retrospectively analyzed OSA patients diagnosed for the first time in Lihuili Hospital Affiliated to Ningbo University from 2016 to 2020. Patients were divided into an OSA group with hypertension and an OSA group without hypertension. The sociodemographic information, clinical symptoms, comorbidities, and polysomnography results of the two groups were compared. The independent risk factors associated with hypertension in patients with OSA were explored. Results A total of 1108 patients with OSA initially diagnosed were included in the study, including 387 with hypertension and 721 without. Compared with OSA patients without hypertension, OSA patients with hypertension were older; had a higher body mass index (BMI) and Epworth sleepiness score (ESS); a higher incidence of nocturia; and a higher proportion of diabetes mellitus, coronary heart disease, and cerebrovascular disease. Multivariate analysis showed age (odds ratio [OR]:1.06, 95% confidence interval [CI]:1.04-1.08), BMI (OR:1.17, 95% CI:1.11-1.23), ESS score (OR:0.97, 95%CI: 0.94-1.00) and nocturia symptoms (OR:1.64, 95% CI:1.19-2.27) was independently associated with hypertension in OSA patients, and comorbid diabetes (OR: 3.86, 95% CI: 2.31-6.45), coronary heart disease (OR: 1.90, 95% CI:1.15-3.16), and ischemic stroke (OR: 3.69,95% CI:1.31-10.40) was independently associated with hypertension in OSA patients. Conclusion Compared to OSA patients with normal blood pressure, OSA patients with hypertension had more significant daytime sleepiness, more frequent nocturnal urination, and a higher risk of diabetes, coronary heart disease, and cerebrovascular disease.

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Dec 2023
HEMOGLOBIN

Previous studies have shown that patients with sickle cell disease (SCD) are at high risk for obstructive sleep apnea (OSA). In the current study, we aimed to systematically review the literature to address the prevalence of OSA and associated symptoms among patients with SCD. Electronic databases, including Web of Science, Scopus, PubMed, Google Scholar, and Embase were systematically searched to identify the relevant original articles on patients with SCD. Newcastle Ottawa scale was used for quality assessment. Data were pooled by using random effects models. Subgroup analyses were performed by age groups. Thirty-nine studies containing details of 299,358 patients with SCD were included. The pooled results showed that more than half of these patients had OSA with different severities. The prevalence rates of OSA among children with apnea hypopnea index (AHI) cutoffs of above 1, 1.5, and 5 were 51% (95% confidence interval (CI) 36–67%), 29% (95% CI 19–40%), and 18% (95% CI 14–23%), respectively. The prevalence of OSA among adults with AHI cutoff of 5 was 43% (95% CI 21–64%). The pooled rates of snoring, nocturnal enuresis, nocturnal desaturation, and daytime sleepiness were 55% (95% CI 42–69%), 37% (95% CI 33–41%), 49% (95% CI 26–72%), and 21% (95% CI 12–30%), respectively. Given the high prevalence of OSA in patients with SCD, probable greater burden of SCD complications, and irreversible consequences of OSA, screening for OSA symptoms and signs seems useful in these patients. By screening and identifying this heterogeneous disorder earlier, available treatment modalities can be individualized for each patient.

Arterial Stiffness, Body Mass Index and Cardiovascular Disease Risk in Chinese Females at Various Ages

Article

Full-text available

May 2023
REV CARDIOVASC MED

Background This study investigated the correlation in parameters of arterial stiffness and cardiovascular disease (CVD) risk on age and body mass index (BMI) in Chinese females. Methods This cross-sectional study enrolled 2220 females. Arterial stiffness was assessed by the measurement of arterial velocity pulse index (AVI) and arterial pressure volume index (API). Individual 10-year cardiovascular risk was calculated for each patient using the Framingham cardiovascular risk score (FCVRS). Results API and AVI had a significant J-shaped relationship with age. Beginning at the age of 30 years, the API started to increase, while after 49 years, the increase in API was even steeper. AVI increased from the age of 32 years, and increased more rapidly after 56 years. The linear association between API and BMI following adjustment for age was significant (β = 0.324, 95% CI 0.247–0.400, p < 0.001). In the total study cohort, FCVRS scores increased by 0.16 scores for every 1 kg/m² increase in BMI and by 0.11 scores for each 1 value increase in API in the age adjusted model. Conclusions API and BMI correlate with 10-year cardiovascular risk at various ages in females. Regardless of age, overweight females have a higher risk of increased API. Therefore API can be used for the early detection of CVD so that preventive therapy can be instituted in these high risk patients. Clinical Trial Registration Registered on the official website of the China Clinical Trial Registration Center (20/08/2020, ChiCTR2000035937).

Method for Carotid Artery 3-D Ultrasound Image Segmentation Based on CSWin Transformer

Article

Full-text available

Nov 2022
ULTRASOUND MED BIOL

Precise segmentation of carotid artery (CA) structure is an important prerequisite for the medical assessment and detection of carotid plaques. For automatic segmentation of the media–adventitia boundary (MAB) and lumen–intima boundary (LIB) in 3-D ultrasound images of the CA, a U-shaped CSWin transformer (U-CSWT) is proposed. Both the encoder and decoder of the U-CSWT are composed of hierarchical CSWT modules, which can capture rich global context information in the 3-D image. Experiments were performed on a 3-D ultrasound image data set of the CA, and the results indicate that the U-CSWT performs better than other convolutional neural network (CNN)-based and CNN–transformer hybrid methods. The model yields Dice coefficients of 94.6 ± 3.0% and 90.8 ± 5.1% for the MAB and LIB in the common carotid artery (CCA) and 92.9 ± 4.9% and 89.6 ± 6.2% for MAB and LIB in the bifurcation, respectively. Our U-CSWT is expected to become an effective method for automatic segmentation of 3-D ultrasound images of CA.

Characteristics of hypertension and arterial stiffness in obstructive sleep apnea: A Scandinavian experience from a prospective study of 6408 normotensive and hypertensive patients

Article

Full-text available

Feb 2022
J Clin Hypertens

The impact of obstructive sleep apnea (OSA) on arterial stiffness is less studied. We aimed to investigate the prevalence and covariates of increased pulse pressure (PP), a surrogate marker of arterial stiffness, in the entire study population as well as in separate analyses in normotensive and hypertensive patients. Further, we also explored the impact of smoking on brachial BP in hypertensive patients. Between 2012 and 2019, a total of 6408 participants with suspected OSA underwent a standard out-of-center respiratory polygraphy. OSA was defined by an apnea-hypopnea index (AHI) ≥15/h regardless of symptoms. PP ≥60 mmHg was used as a surrogate marker of increased arterial stiffness. Mean age was 49.3±13.7 years, 69.4% were male, and 34.5% had OSA. The prevalence of hypertension was 70.8% in OSA and 46.7% in No-OSA (AHI < 15/h) controls (P < .0001). Hypertension was controlled (clinic BP < 140/90 mmHg) in 45.5% and uncontrolled in 54.5% (P < .001). Mean PP was 50±12 mmHg in smokers and 52±12 mmHg in non-smokers (P = .001). Increased PP was found in 24.2% of the entire study population and was higher in patients with OSA compared to No-OSA group (27.5% vs 22.4%, P < .0001). In an unadjusted logistic regression model, OSA was associated with a 1.3-fold higher risk of having increased PP (95% CI 1.16-1.48, P < .001). In a multivariable-adjusted model, higher age, male sex, and history of hypertension, but not OSA (OR 0.89; 95% CI 0.77-1.02, P = .104) were associated with increased PP. In this large study of nearly 6500 participants who were referred with suspected OSA, one-third were diagnosed with OSA and a quarter had increased arterial stiffness by elevated brachial PP. Hypertension but not OSA per se was associated with increased arterial stiffness. Hypertension was highly prevalent and poorly controlled.

Sleep Apnea and Cardiovascular Disease

Article

Full-text available

Dec 2021
Curr Diabetes Rep

Daniel J. Gottlieb

Purpose of Review Obstructive sleep apnea (OSA) is associated with incident coronary and cerebral vascular disease. The mechanisms underlying this association are thought to include increased sympathetic nervous system activity, oxidative stress, and systemic inflammation, with these effects mediated in part by elevated blood pressure and impaired glucose metabolism. In observational studies, OSA treatment with positive airway pressure (PAP) is associated with a reduction in cardiovascular disease risk. The aim of this review is to evaluate evidence from recent clinical trials that tested the impact of OSA treatment on major cardiovascular disease outcomes. Recent Findings Multicenter randomized trials have demonstrated a significant, albeit modest, reduction in blood pressure with OSA treatment. Treatment of OSA has generally not demonstrated improvement in type 2 diabetes mellitus, although limited evidence suggests that treatment may be effective in the prediabetic period. However, recent randomized trials of PAP treatment for OSA failed to demonstrate a reduction in incident or recurrent cardiovascular disease events. This may reflect the enrollment of a mostly non-sleepy study sample, as recent evidence suggests that sleepiness is a predictor of adverse cardiovascular outcomes from OSA. Summary PAP treatment of OSA lowers blood pressure and may improve glucose metabolism; however, randomized clinical trials do not indicate a reduction in cardiovascular risk with treatment of minimally symptomatic OSA patients.

The Association Between Serum/Plasma Leptin Levels and Obstructive Sleep Apnea Syndrome: A Meta-Analysis and Meta-Regression

Article

Full-text available

Sep 2021

Background Obstructive sleep apnea syndrome (OSAS) is associated with various adipokines. Leptin, a common adipokine, has attracted considerable attention of many researchers in recent years. So far, there has been little agreement on whether blood leptin levels differ in patients with OSAS. Thus, this meta-analysis examined the relationship between serum/plasma leptin levels and the occurrence of OSAS. Method WanFang, Embase, CNKI, Medline, SinoMed, Web of Science, and PubMed were searched for articles before March 30, 2021, with no language limitations. STATA version 11.0 and R software version 3.6.1 were used to analyze the obtained data. The weighted mean difference and correlation coefficients were used as the main effect sizes with a random-effects model and a fixed-effects model, respectively. Trial sequential analysis was conducted using dedicated software. Result Screening of 34 publications identified 45 studies that met the inclusion criteria of this meta-analysis and meta-regression. Our results suggested that plasma/serum leptin levels were remarkably higher in individuals with OSAS than in healthy individuals. Subgroup analyses were performed based on OSAS severity, ethnicity, age, body mass index, assay type, and sample source. The serum and plasma leptin levels were increased in nearly all OSAS subgroups compared to those in the corresponding control groups. Meta-regression analysis indicated that age, BMI, severity, assay approaches, study design, PSG type and ethnicity did not have independent effect on leptin levels. Furthermore, a positive relationship between the serum/plasma leptin level and apnea-hypopnea index (AHI) was found in the meta-analysis. The results of the trial sequential analysis suggested that the enrolled studies surpassed the required information size, confirming that our study findings were reliable. Conclusion Our study results demonstrate that OSAS patients have higher leptin levels in serum/plasma compared to controls, and the serum/plasma leptin level is positively correlated with AHI, especially in adults.

Cognitive impairment in frail elderly with hypertension: role of hyperglycemia

Article

Full-text available

Aug 2021

Endothelial dysfunction is a key hallmark of hypertension, which is a leading risk factor for cognitive decline in older adults with or without frailty. Similarly, hyperglycemia is known to impair endothelial function and is a predictor of severe cardiovascular outcomes, independent of the presence of diabetes. On these grounds, we designed a study to assess the effects of high-glucose and metformin on brain microvascular endothelial cells (ECs) and on cognitive impairment in frail hypertensive patients. We tested the effects of metformin on high-glucose-induced cell death, cell permeability, and generation of reactive oxygen species in vitro, in human brain microvascular ECs. To investigate the consequences of hyperglycemia and metformin in the clinical scenario, we recruited frail hypertensive patients and we evaluated their Montreal Cognitive Assessment (MoCA) scores, comparing them according to the glycemic status (normoglycemic vs. hyperglycemic) and the use of metformin. We enrolled 376 patients, of which 209 successfully completed the study. We observed a significant correlation between MoCA score and glycemia. We found that hyperglycemic patients treated with metformin had a significantly better MoCA score than hyperglycemic patients treated with insulin (18.32 ± 3.9 vs. 14.94 ± 3.8; p < 0.001). Our in vitro assays confirmed the beneficial effects of metformin on human brain microvascular ECs. To our knowledge, this is the first study correlating MoCA score and glycemia in frail and hypertensive older adults, showing that hyperglycemia aggravates cognitive impairment.

Cognitive dysfunction correlates with physical impairment in frail patients with acute myocardial infarction

Article

Full-text available

Jan 2022
AGING CLIN EXP RES

Background – The association of physical impairment and cognitive decline has never been investigated in frail patients with acute myocardial infarction. Aim - The aim of our study is to assess the correlation between physical and cognitive decline in frail patients with ST-elevation myocardial infarction (STEMI). Methods - We examined consecutive frail patients with first STEMI treated with primary percutaneous coronary intervention (PPCI). All patients were evaluated with Mini Mental State Examination (MMSE) and 5-meter gait speed test after PPCI. Results - A total of 871 frail patients with suspected STEMI were admitted to the PCI center. We found that the gait speed significantly correlated with the MMSE score (r: 0.771; p: <0.001). The independent effects on MMSE score were confirmed in a linear multivariate analysis. Conclusions – Taken together, our findings indicate that an assessment of both cognitive and physical conditions should be included in the comprehensive geriatric evaluation of hospitalized older STEMI patients. Full text at: https://rdcu.be/cmbZv

Noninvasive markers of arterial stiffness and renal outcomes in patients with chronic kidney disease

Article

Full-text available

Feb 2021
J Clin Hypertens

Our study aimed to explore the intercorrelations of brachial-ankle pulse wave velocity (baPWV), ankle-brachial index (ABI), ambulatory arterial stiffness index (AASI), 24-hour mean pulse pressure (24-h PP), and augmentation index (AIx, AIx@75, the AIx standardized to a heart rate of 75) and compare the effectiveness of these markers for predicting renal outcomes. A total of 117 patients with chronic kidney disease (CKD) who received noninvasive arterial stiffness examinations were enrolled. We used correlation analysis and linear regression to explore the correlations between these five arterial stiffness markers and the Cox proportional hazards model and receiver operator characteristic (ROC) curve to assess the associations of markers with kidney disease outcomes. The median (interquartile range) of age and eGFR were 61 (49-65) years and 50.5 (35.5-84.1) ml/min/1.73 m2 , respectively. In Pearson correlation analysis, baPWV was significantly associated with 24-h PP (r = .531, p < .001), AIx@75 (r = .306, p < .001). Additionally, 24-h PP was associated with AASI (r = .507, p < .001) and AIx@75 (r = .217, p = .019). During follow-up for a median of 25 months, 26.5% (n = 31) of patients had a composite outcome; of these, 10 initiated dialysis, 17 had 40% eGFR loss, and 4 died. Increased AASI, 24-h PP, and baPWV were associated with poor renal outcomes in a univariate Cox analysis. After adjusting for age, sex, MAP, eGFR, and 24 hours proteinuria, 1-SD increase in AASI and 24-h PP was associated with renal outcomes. The ROC analysis yielded the largest area under the curve (AUC) of 0.727 (95% CI: 0.624 to 0.831; p < .001) for 24 -h PP. When the Youden's index was at its maximum, the 24-h PP value was 52 mmHg. In conclusion, 24-h PP, baPWV, and AIx@75 were linked well to one another. Arterial stiffness is a target for delaying the decline in kidney function. The use of 24-h PP as an arterial stiffness marker should be valued in CKD clinical practice.

Chronic Kidney Disease: Definition, Updated Epidemiology, Staging, and Mechanisms of Increased Cardiovascular Risk

Article

Full-text available

Jan 2021
J Clin Hypertens

According to the US Centers for Disease Control and Prevention (CDC) ~37 million people in the US — ~15% of adults — are estimated to have CKD. Of note, 90% of adults with CKD do not know they have it and 1 in 2 people with very low kidney function who are not on dialysis are not aware of the fact that they have CKD. Diabetes and hypertension are the major causes of CKD in adults: according to the CDC, 1 in 3 adults with diabetes and 1 in 5 adults with hypertension may have CKD.

Incidence of venous thromboembolism in patients with obstructive sleep apnea: a cohort study

Article

Dec 2021
CHEST

Background Previous studies suggesting that obstructive sleep apnea (OSA) may be an independent risk factor for venous thromboembolism (VTE) have been limited by reliance on administrative data and lack of adjustment for clinical variables, including obesity. Research Question Does OSA confer an independent risk of incident VTE among a large clinical cohort referred for sleep disordered breathing evaluation? Study Design and Methods We analyzed the clinical outcomes of 31,309 patients undergoing overnight polysomnography within a large hospital system. We evaluated the association of OSA severity with incident VTE using Cox proportional hazards modeling accounting for age, sex, body mass index (BMI), and common comorbid conditions. Results Patients were of mean age 50.4 years and 50.1% female. There were 1,791 VTE events identified over a mean follow-up of 5.3 years. In age and sex-adjusted analyses, each 10 event/hr increase in the apnea hypopnea index (AHI) was associated with a 4% increase in incident VTE risk (hazard ratio [HR] 1.04, 95% confidence interval [CI] 1.02-1.05). After adjusting for BMI, this association disappeared (HR 1.01, 95% CI 0.99–1.03). In contrast, nocturnal hypoxemia had an independent association with incident VTE. Patients with >50% sleep time spent with oxyhemoglobin saturation <90% are at 48% increased VTE risk compared to those without nocturnal hypoxemia (HR 1.48, 95% CI 1.16-1.69). Interpretation In this large cohort, we found that patients with more severe OSA as measured by the AHI are more likely to have incident VTE. Adjusted analyses suggest that this association is explained due to confounding by obesity. However, severe nocturnal hypoxemia may be a mechanism by which OSA heightens VTE risk.

Obstructive Sleep Apnea and Cardiovascular Disease: A Scientific Statement From the American Heart Association

Article

Jun 2021

Obstructive sleep apnea (OSA) is characterized by recurrent complete and partial upper airway obstructive events, resulting in intermittent hypoxemia, autonomic fluctuation, and sleep fragmentation. Approximately 34% and 17% of middle-aged men and women, respectively, meet the diagnostic criteria for OSA. Sleep disturbances are common and underdiagnosed among middle-aged and older adults, and the prevalence varies by race/ethnicity, sex, and obesity status. OSA prevalence is as high as 40% to 80% in patients with hypertension, heart failure, coronary artery disease, pulmonary hypertension, atrial fibrillation, and stroke. Despite its high prevalence in patients with heart disease and the vulnerability of cardiac patients to OSA-related stressors and adverse cardiovascular outcomes, OSA is often underrecognized and undertreated in cardiovascular practice. We recommend screening for OSA in patients with resistant/poorly controlled hypertension, pulmonary hypertension, and recurrent atrial fibrillation after either cardioversion or ablation. In patients with New York Heart Association class II to IV heart failure and suspicion of sleep-disordered breathing or excessive daytime sleepiness, a formal sleep assessment is reasonable. In patients with tachy-brady syndrome or ventricular tachycardia or survivors of sudden cardiac death in whom sleep apnea is suspected after a comprehensive sleep assessment, evaluation for sleep apnea should be considered. After stroke, clinical equipoise exists with respect to screening and treatment. Patients with nocturnally occurring angina, myocardial infarction, arrhythmias, or appropriate shocks from implanted cardioverter-defibrillators may be especially likely to have comorbid sleep apnea. All patients with OSA should be considered for treatment, including behavioral modifications and weight loss as indicated. Continuous positive airway pressure should be offered to patients with severe OSA, whereas oral appliances can be considered for those with mild to moderate OSA or for continuous positive airway pressure–intolerant patients. Follow-up sleep testing should be performed to assess the effectiveness of treatment.

Cognitive Performance is Lower Among Individuals with Overlap Syndrome than with COPD or Obstructive Sleep Apnea Alone: Role of Carotid Artery Stiffness

Article

May 2021

Background: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are both independently associated with increased cardiovascular disease (CVD) risk and impaired cognitive function. It is unknown if individuals with both COPD and OSA (i.e. overlap syndrome) have greater common carotid artery (CCA) stiffness, an independent predictor of CVD risk, and lower cognitive performance than either COPD or OSA alone. Elevated CCA stiffness is associated with cognitive impairment in former smokers with and without COPD in past studies. Methods: We compared CCA stiffness and cognitive performance between former smokers with overlap syndrome, COPD only, OSA only and former smoker controls using analysis of covariance (ANCOVA) tests to adjust for age, sex, body mass index (BMI), pack-years and post-bronchodilator FEV1/FVC. We also examined the association between carotid artery stiffness and cognitive performance among each group separately. Results: Individuals with overlap syndrome (n=12) had greater CCA β-stiffness index (p=0.015) and lower executive function-processing speed (p=0.019) than individuals with COPD alone (n=47), OSA alone (n=9) and former smoker controls (n=21), differences that remained significant after adjusting for age, BMI, sex, pack-years and FEV1/FVC. Higher CCA β-stiffness index was associated with lower executive function-processing speed in individuals with overlap syndrome (r=-0.58, p=0.047). Conclusion: These data suggest that CCA stiffness is greater and cognitive performance is lower among individuals with overlap syndrome compared with individuals with COPD or OSA alone and that CCA stiffening may be an underlying mechanism contributing to the lower cognitive performance observed in patients with overlap syndrome.