Sleep Apnea and Asymptomatic Carotid Stenosis: A Complex Interaction

doi:10.1378/chest.14-1655

Chest

Volume 147, Issue 4, April 2015, Pages 1029-1036

https://doi.org/10.1378/chest.14-1655 Get rights and content

Abstract

BACKGROUND: Carotid arteriosclerosis and sleep apnea are considered as independent risk factors for stroke. Whether sleep apnea mediates severity of carotid stenosis remains unclear. Sleep apnea comprises two pathophysiologic conditions: OSA and central sleep apnea (CSA). Although OSA results from upper airway occlusion, CSA reflects enhanced ventilatory drive mainly due to carotid chemoreceptor dysfunction.

METHODS: Ninety-six patients with asymptomatic extracranial carotid stenosis of ≥ 50% underwent polysomnography to (1) determine prevalence and severity of sleep apnea for different degrees of carotid stenosis and (2) analyze associations between OSA and CSA, carotid stenosis severity, and other arteriosclerotic risk factors.

RESULTS: Sleep apnea was present in 68.8% of patients with carotid stenosis. Prevalence and severity of sleep apnea increased with degree of stenosis (P≤ .05) because of a rise in CSA (P≤ .01) but not in OSA. Sleep apnea (OR, 3.8;P≤ .03) and arterial hypertension (OR, 4.1;P≤ .05) were associated with stenosis severity, whereas diabetes, smoking, dyslipidemia, BMI, age, and sex were not. Stenosis severity was related to CSA (P≤ .06) but not to OSA. In addition, CSA but not OSA showed a strong association with arterial hypertension (OR, 12.5;P≤ .02) and diabetes (OR, 4.5;P≤ .04).

CONCLUSIONS: Sleep apnea is highly prevalent in asymptomatic carotid stenosis. Further, it is associated with arteriosclerotic disease severity as well as presence of hypertension and diabetes. This vascular risk constellation seems to be more strongly connected with CSA than with OSA, possibly attributable to carotid chemoreceptor dysfunction. Because sleep apnea is well treatable, screening should be embedded in stroke prevention strategies.

Section snippets

Materials and Methods

The study was approved by the Jena University Hospital Ethics Committee (N° 2020-05/07). Written informed consent was obtained from all study participants.

Patients

Ninety-six patients aged between 39 and 86 years (mean age, 65.9 ± 10.0 years) with asymptomatic extracranial stenosis were recruited for the study (64 men and 32 women). Of these, 21 patients had mild/moderate and 75 patients severe carotid stenosis. Patients with severe stenosis were older than those with mild/moderate stenosis (67.2 ± 9.0 years vs 61.4 ± 11.9 years,P≤ .05). Frequency of arterial hypertension (P≤ .01) and diabetes mellitus (P≤ .05) was higher in the severe stenosis group

Discussion

Sleep apnea is highly prevalent in patients with asymptomatic extracranial carotid stenosis and associated with arteriosclerotic carotid disease severity. Effects of sleep apnea on stenosis severity are primarily linked to CSA but not to OSA. Moreover, CSA but not OSA is associated with presence of arterial hypertension and diabetes mellitus in patients with asymptomatic carotid stenosis.

To our knowledge, this is the first prospective study examining the prevalence of sleep apnea and its

Conclusions

Sleep apnea is highly prevalent in asymptomatic extracranial carotid stenosis and associated with arteriosclerotic disease severity. Because it is well treatable, sleep apnea screening should be embedded in stroke prevention strategies.

Acknowledgments

Author contributions:S. R. is the guarantor of the content of the manuscript, including the integrity of the data and the accuracy of the data analysis. J. E. contributed to data analysis and interpretation of the results and prepared the manuscript; M. S., A. G., and O. W. contributed to critically revising the manuscript; S. F. and T. S. contributed to data acquisition; and S. R. contributed to study design, study conduction, data analysis, and interpretation of the results.

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We evaluated multiple cardiovascular measures to comprehensively evaluate carotid structure and function. Specifically, the measures used have been utilized in adult studies examining cardiovascular changes associated with OSA.32-36 Of note, there were not significant differences between the OSA and control groups with regard to cholesterol or triglycerides.
To evaluate structural and functional carotid changes and inflammatory profiles in children with obstructive sleep apnea (OSA) and healthy controls.
Patients with OSA and matched controls (ages 5-13 years) were recruited. Proinflammatory cytokines and acute phase reactants were measured at 6:00 p.m. Common carotid artery measures were determined using ultrasound. Confirmatory factor analysis was used to determine subgroups of cytokines and their effects on carotid measures.
Ninety-six patients participated (53 healthy controls, 43 patients with OSA). OSA was associated with increased proinflammatory cytokines (cluster of differentiation-40 ligand [CD40-L], interleukin [IL]-6, and IL-8) and high sensitivity C-reactive protein (P < .05 for all). One cytokine subgroup (IL-6 and IL-8) was negatively associated with markers of carotid function, indicating reduced arterial distensibility and increased stiffness (P < .05 for 3 ultrasound measures); and tumor necrosis factor-α had an opposing effect on carotid function compared with this cytokine subgroup (P < .05 for 2 ultrasound measures). Linear regression demonstrated significant associations between and tumor necrosis factor- α and 2 measures of carotid function (P < .05 for each). Children with OSA did not have functional or structural carotid changes compared with controls.
OSA was not directly associated with structural and functional carotid changes but was associated with upregulation of key proinflammatory cytokines (sCD40-L, IL-6, and IL-8). Together, IL-6 and IL-8 were associated with changes in carotid function. Longitudinal studies are needed to demonstrate that the inflammatory milieu observed in our population is a precursor of atherosclerosis in children.
Obstructive sleep apnea causes impairment of the carotid artery in patients with hypertrophic obstructive cardiomyopathy
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Direct effects are due to the repetitive cessation of breathing in OSA, resulting in intermittent hypoxia and sympathetic overactivity and, thus, eliciting direct effects. Indirectly, OSA promotes exacerbation of other risk factors such as hypertension, insulin resistance, diabetes, and dyslipidemia [7]. Furthermore, upregulation of pro-inflammatory mediators, such as CRP, molecules that mediate thrombosis, such as plasminogen activator I, lipid peroxidation as a result of oxidative stress.
Obstructive sleep apnea (OSA) prevalence is high among patients with hypertrophic cardiomyopathy (HCM). OSA can cause increase in carotid intima-media thickness (CIMT) in the general population. However, whether this phenomenon is applicable to patients with HCM is unclear.
A total of 130 consecutive patients with a confirmed diagnosis of hypertrophic obstructive cardiomyopathy (HOCM) at Fuwai Hospital between September 2017 and May 2018 were analyzed.
72 patients (55.4%) were diagnosed with OSA. Patients with OSA were older. Compared to those in patients without OSA, the left, right, and mean CIMTs were significantly increased in patients with OSA. In the multiple linear regression model, age (β = 0.341, p < 0.001), apnea-hypopnea index (AHI) (β = 0.421, p < 0.001), and fasting glucose level (β = 0.167, p < 0.03) were independently associated with mean CIMT increase (adjusted R² = 0.458, p < 0.001). In the receiver operating characteristic curve analysis, the area under the curve for CIMT was 0.813 (95% CI, 0.717–0.909, p < 0.001) with a sensitivity and specificity of 0.84 and 0.70 for unexplained syncope, respectively. In the multivariate logistic regression model, we found that the mean CIMT (OR = 10.4, 95% CI = 3.16–34.11, p < 0.001), left ventricular ejection fraction (LVEF) (OR = 0.90, 95% CI = 0.83–0.99, p = 0.03), and amaurosis (OR = 5.07, 95% CI = 1.47–17.49, p = 0.01) were independently associated with unexplained syncope occurrence.
In patients with HOCM, CIMT increased with OSA severity. Age, AHI, and fasting plasma glucose level were independently associated with mean CIMT increase. Moreover, amaurosis, LVEF, and higher mean CIMT were independently associated with unexplained syncope in patients with HOCM.
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: Funding/Support: The authors have reported toCHESTthat no funding was received for this study. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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Chest

Original Research: Sleep DisordersSleep Apnea and Asymptomatic Carotid Stenosis: A Complex Interaction

Abstract

Section snippets

Materials and Methods

Patients

Discussion

Conclusions

Acknowledgments

Respir Med

Can J Cardiol

Int J Cardiol

Med Hypotheses

Int J Cardiol

Prog Cardiovasc Dis

Am J Cardiol

Am J Med

Am J Surg

J Cardiol

Investigating the relationship between stroke and obstructive sleep apnea

Stroke

Diagnosis of and treatment for symptomatic carotid stenosis: an updated review

Acta Neurol Scand

Central sleep apnea is associated with increased risk of ischemic stroke in the elderly

Acta Neurol Scand

Sleep apnea is a stronger predictor for coronary heart disease than traditional risk factors

Sleep Breath

Independent association between obstructive sleep apnea and noncalcified coronary plaque demonstrated by noninvasive coronary computed tomography angiography

Clin Cardiol

Central sleep apnea indicates autonomic dysfunction in asymptomatic carotid stenosis: a potential marker of cerebrovascular and cardiovascular risk

Sleep

Prognostic implications of autonomic function assessed by analyses of catecholamines and heart rate variability in stable angina pectoris

Heart

Low heart rate variability in a 2-minute rhythm strip predicts risk of coronary heart disease and mortality from several causes: the ARIC Study. Atherosclerosis Risk In Communities

Circulation

Carotid artery stenosis: gray-scale and Doppler US diagnosis - Society of Radiologists in Ultrasound Consensus Conference

Radiology

American Academy of Sleep Medicine; Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine. Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events

J Clin Sleep Med

Atherosclerosis and obstructive sleep apnea in patients with ischemic stroke

Cerebrovasc Dis

Molecular mechanisms of cardiovascular disease in OSAHS: the oxidative stress link

Eur Respir J

Time course of sleep-related breathing disorders in first-ever stroke or transient ischemic attack

Am J Respir Crit Care Med

Original Research: Sleep Disorders
Sleep Apnea and Asymptomatic Carotid Stenosis: A Complex Interaction