Chest ACCP Education Calendar
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (18)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Baguet, J.-P.
Right arrow Articles by Pépin, J.-L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Baguet, J.-P.
Right arrow Articles by Pépin, J.-L.
(Chest. 2005;128:3407-3412.)
© 2005 American College of Chest Physicians

The Severity of Oxygen Desaturation Is Predictive of Carotid Wall Thickening and Plaque Occurrence*

Jean-Philippe Baguet, MD, PhD; Laure Hammer, MD; Patrick Lévy, MD, PhD; Hélène Pierre, MSc; Sandrine Launois, MD, PhD; Jean-Michel Mallion, MD and Jean-Louis Pépin, MD, PhD

* From the Department of Cardiology and Hypertension (Drs. Baguet, Hammer, Pierre, and Mallion), University Hospital; and Sleep Laboratory (Drs. Lévy, Launois, and Pépin), EFCR University Hospital, Grenoble, France.

Correspondence to: Jean-Philippe Baguet, MD, PhD, Service de Cardiologie et Hypertension artérielle, CHU de Grenoble, BP 217 - 38043, Grenoble Cedex 09, France; e-mail: JPBaguet{at}chu-grenoble.fr


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Study objectives: To characterize carotid intima-media thickness (IMT) and plaque occurrence in patients with newly diagnosed obstructive sleep apnea (OSA) without known cardiovascular disease.

Design: Prospective study.

Setting: Sleep Laboratory and Department of Cardiology of Grenoble University Hospital.

Patients and intervention: OSA syndrome is associated with an increased cardiovascular risk. Carotid IMT is recognized as a marker of preclinic atheroma. A small number of studies have analyzed large-artery wall modifications in OSA syndrome. Eighty-three patients (74 men; mean age ± SD, 48 ± 11 years; mean body mass index, 27.4 ± 4.2 kg/m2) were included. Mean respiratory disturbance index was 40.7 ± 19.2/h, mean nocturnal arterial oxygen saturation (SaO2) was 93.1 ± 2.0%, and mean percentage of recording time spent at SaO2 < 90% was 8.6 ± 16.8%. Clinical BP was measured following European Society of Hypertension/European Society of Cardiology recommendations, and 24-h ambulatory BP monitoring was assessed. Ultrasonography was used to determine the carotid IMT and atheromatous plaque occurrence.

Measurements and results: Twenty-five of 83 patients (30%) had carotid wall hypertrophy (IMT > 0.8 mm). In a logistic regression model, mean nocturnal SaO2 < 92% (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.1 to 12.7) was associated with carotid wall hypertrophy. ORs were even higher after adjustment for BP status (OR, 10.6; 95% CI, 1.6 to 50.9 in normotensive patients) and glucose levels (OR, 4.5; 95% CI, 1.0 to 20.9). Mean nocturnal SaO2 < 92% and minimal nocturnal SaO2 < 80% (ORs, 3.1 and 3.1; 95% CIs, 1.0 to 9.4 and 1.0 to 8.5, respectively) were associated with the presence of carotid plaque formation independently of the BP status (hypertensive or normotensive).

Conclusions: The severity of oxygen desaturation appears to be one of the best predictors for carotid IMT and plaque occurrence in OSA patients without known cardiovascular disease. Thus, carotid IMT and plaque formation appeared as early cardiovascular consequences in OSA patients.

Key Words: atherosclerosis • carotid intima-media thickness • obstructive sleep apnea • oxygen desaturation


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Obstructive sleep apnea (OSA) syndrome is associated with increased cardiovascular risk. Indeed, it is well demonstrated that hypertension, stroke, coronary heart disease, arrhythmia, conduction disorders, and heart failure are more frequent in apneic patients.12

Carotid intima-media thickness (IMT), as evaluated by ultrasound, correlates well with anatomic measurements3 and is recognized as a marker of preclinic atheroma. An increased carotid IMT is accepted as a potent predictor of myocardial infarction and stroke, even after adjustment for other risk factors.456 Carotid IMT can be reassessed reliably over time and has been used as a primary end point in large clinical trials789101112 evaluating efficacy of treatments designed to reduce both carotid IMT and cardiovascular morbidity and mortality.

A small number of studies131415 have analyzed large-artery wall modifications in patients with OSA syndrome. The largest study13 showed a significant relationship between carotid IMT and oxygen desaturation severity. However, in this study,13 > 50% of the patients were hypertensive and treated with appropriate medications. Two other studies1415 reported a major association between carotid IMT/plaque formation and respiratory disturbance index (RDI). However, in the study by Kaynak et al,14 data were not provided regarding cardiovascular morbidity associated with OSA and medications received by the patients.14 Finally, Silvestrini et al15 reported on a small sample of 23 obese OSA patients (mean body mass index [BMI], 31.7 kg/m2), 65% of whom were treated with antihypertensive medications.

We hypothesized that the arterial wall should be modified structurally (ie, carotid wall thickening and/or plaque formation) even in early course of disease in patients with moderate-to-severe OSA never treated for both OSA and hypertension. The aims of our study were as follows: (1) to quantify carotid wall structural modifications in consecutive unselected patients with newly diagnosed OSA unknown by their general practitioner to have any cardiovascular disease, including hypertension; and (2) to analyze the relationship between carotid parameters and sleep respiratory disturbances.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusion
 References
 
Population
Eighty-three patients (74 men; mean age ± SD, 48 ± 11 years; age range, 23 to 74 years) referred to Grenoble University Hospital sleep laboratory for symptoms suggesting OSA were included consecutively between November 2001 and February 2004. They were recruited from the sleep laboratory, where they underwent full polysomnography, or from the ward sleep unit, where the diagnosis of OSA was confirmed by simplified polysomnography without EEG recordings. Three patients (4%) were treated for diabetes mellitus, and nine patients (11%) received statin treatment. None of the patients had known cardiovascular disease, and none received any vasoactive treatment. Exclusion criteria were as follows: disease potentially affecting BP regulation (Parkinson disease, renal or cardiac transplantation, cardiac heart failure), atrial fibrillation or frequent premature beats (≥ 10/min), previous treatment of OSA with continuous positive airway pressure (CPAP), oral appliances, or maxillofacial surgery. Ethical approval was obtained from the local ethics committee. All of the participants gave informed consent.

BP and Heart Rate Measurements
Clinical BP and heart rate (HR) were measured by mercury sphygmomanometry on three occasions according to European Society of Hypertension/European Society of Cardiology guidelines.16 The following parameters were assessed: systolic BP (SBP), diastolic BP (DBP), and HR. Pulse pressure (PP) was calculated using the following formula: PP = SBP – DBP. Clinical hypertension was defined as a clinical SBP ≥ 140 mm Hg and/or a clinical DBP ≥ 90 mm Hg.16 Ambulatory BP monitoring (ABPM) was also performed (Diasys Integra; Novacor SA; Rueil-Malmaison, France). Measurements were made every 15 min over 24 h as previously described.17 Daytime hypertension was defined as daytime SBP ≥ 135 mm Hg and/or daytime DBP ≥ 85 mm Hg, and nighttime hypertension was defined as nighttime SBP ≥ 120 mm Hg and/or nighttime DBP ≥ 70 mm Hg.18

Polysomnography
Full polysomnography was performed in 54 of 83 patients (65%). Continuous recordings were made with electrode positions C3/A2-C4/A1-Cz/01 of the International 10–20 Electrode Placement System, eye movements, chin electromyogram, and ECG with modified V2 lead. Sleep was scored manually according to standard criteria.19 Airflow was measured with nasal pressure associated with the sum of buccal and nasal thermistor signals. Respiratory efforts were monitored with abdominal and thoracic bands. An additional signal of respiratory effort (ie, pulse transit time) was recorded concurrently. Arterial oxygen saturation (SaO2) was measured using pulse oximetry (Biox-Ohmeda 3700; Ohmeda; Liberty Corner, NJ). The same variables were measured in the remaining 29 patients except for sleep variables, which were not recorded. Apnea was defined as a complete cessation of airflow for ≥ 10 s, and hypopnea was defined as a reduction ≥ 50% in the nasal pressure signal or a decrease between 30% and 50% associated with either oxygen desaturation ≥ 3% or an EEG arousal (defined according to the Chicago report),20 both lasting for ≥ 10 s. Apneas were classified as obstructive, central, or mixed according to the presence or absence of respiratory efforts. The classification of hypopneas as obstructive or central was based on the pulse transit time signal and the shape of the inspiratory part of nasal pressure (flow limited aspect or not). The RDI was calculated and defined as the number of apneas and hypopneas per hour of sleep (full polysomnography) or per hour of recording (polysomnography without EEG recording). Sleep apnea was defined as an RDI ≥ 15/h.

Carotid Ultrasonography
B-mode ultrasonography was performed (HP Sonos 2500; Hewlett-Packard; Santa Clara, CA) using a sectorial probe of 7.5 MHz with axial and lateral resolution of 0.15 mm. The methodology used to determine the mean common carotid IMT and luminal diameter has been previously described.17 Both common carotid arteries were studied consecutively in the long axis with a probe incidence allowing good-quality images. This image was defined by the presence of two hyperechogenic lines separated by a hypoechogenic zone from the posterior artery wall. The IMT was defined as the distance separating the most internal parts of these lines, and the luminal diameter was the distance between the blood/intima interfaces on the anterior and posterior walls. For all patients, a zoom was used to define a zone of interest of 20 mm in length (stretching from 10 to 30 mm above the carotid bifurcation). The images were recorded in end-diastole and then stored on an optical disk for subsequent analysis by a specific validated program (TIMC Laboratory, CHU; Grenoble, France). The measures of IMT and diameter were carried out on areas free of atheroma and then averaged. The values of IMT and luminal diameter for any subject were the mean values for the two common carotid arteries. Carotid wall hypertrophy was defined as a common carotid IMT > 0.8 mm.21 Plaque was defined as an echogenic structure encroaching into the vessel lumen with a distinct area and having an IMT > 50% greater than that of the neighboring sites. Carotid ultrasonography was performed by two sonographers who were blinded to the other study data. The analysis of the carotid parameters using the specific software was done by the same operator.

Biological Parameters
All of the patients underwent total plasma cholesterol (enzymatic colorimetry; normal range, 1.79 to 2.73 g/L), triglyceride (enzymatic colorimetry; normal range, 0.56 to 2.28 g/L), high-density lipoprotein cholesterol (enzymatic colorimetry; normal range, 0.39 to 0.63 g/L), low-density lipoprotein cholesterol (Friedwald formula; normal range, 1.01 to 1.81 g/L), glucose (enzymatic method; normal range, 3.8 to 5.5 mmol/L), and creatinine (enzymatic colorimetry; normal range, 65 to 115 µmol/L) measurements.

Statistical Analysis
Statistical analyses were performed using statistical software (SPSS version 6.1.3; SPSS; Chicago, IL). Normality of data distribution was assessed. Continuous data were expressed as mean ± SD. Relationships between the continuous variables normally distributed were evaluated by Pearson or Spearman correlation analysis when data were not normally distributed. Noncontinuous variables were compared using a {chi}2 test, and comparisons between hypertensive and normotensive patients for continuous variables were made with Student t test (or Mann-Whitney U test when groups without normally distributed data). Multivariate analysis was performed by a stepwise regression taking into account the variables correlated with the dependent variables. Values of p < 0.05 were considered significant. Odds ratios (ORs) were calculated to assess the significant association between a carotid wall hypertrophy or the presence of carotid plaque and different parameters of OSA severity or other cardiovascular risk factors. All ORs are presented with 95% confidence intervals (CIs).


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusion
 References
 
Table 1 shows anthropometric, biological, hemodynamic, and respiratory characteristics of the studied population. Patients were slightly obese (15 patients [18%] had BMI > 30 kg/m2) and exhibited moderate-to-severe OSA (35 patients [42%] had an RDI from 30 to 50/h [range, 15.9 to 103.5/h]). Half of the patients had symptoms of OSA for ≥ 5 years. Fifty-four of the 83 patients (65%) were hypertensive either in the clinic or during ABPM, although this was unknown before the study. Thirty-three patients of the whole population (40%) had clinical hypertension, 43 patients (52%) had daytime hypertension, and 37 patients (45%) had nighttime hypertension on ABPM. Hypertensive patients were older than normotensive patients (mean, 50.8 ± 10.3 years vs 45.8 ± 11.4 years, respectively; p = 0.045) but had a similar BMI, biological, and polysomnographic characteristics (Fig 1 ).


View this table:
[in this window]
[in a new window]

  		Table 1. Anthropometric, Biological, Hemodynamic, and Sleep Apnea Characteristics of the OSA Patients*

 


View larger version (10K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1. Distribution of BMI and corresponding apnea-hypopnea index (AHI).

 
In the whole population, mean carotid IMT was 0.67 ± 0.13 mm. Twenty-five of the 83 patients (30%) had carotid wall hypertrophy. Clinical hypertension patients had greater carotid IMT than normotensive patients (0.70 ± 0.13 mm and 0.65 ± 0.13 mm, respectively; p = 0.04). The proportion of patients with atheromatous carotid plaque (20 of 83 patients, 24%) was higher in hypertensive patients than in normotensive patients (13 of 33 patients [39%] and 7 of 50 patients [14%], respectively; p = 0.008).

Table 2 shows the results of the univariate analysis between carotid parameters and anthropometric variables, hemodynamic parameters, alcohol consumption, and biological and respiratory parameters. There was no relationship between any clinical PP/ABPM PP and carotid IMT.


View this table:
[in this window]
[in a new window]

  		Table 2. Univariate Analysis (Pearson or Spearman Test) Between Carotid IMT and Anthropometric Variables, Hemodynamic Parameters, Alcohol Consumption, Biological Factors, and Sleep Apnea Severity

 
In a logistic regression model (Table 3 ), a mean nocturnal SaO2 < 92% (OR, 3.9; 95% CI, 1.1 to 12.7) was associated with carotid wall hypertrophy. ORs were higher after adjustment for BP status (OR, 10.6; 95% CI, 1.6 to 50.9 in normotensive patients) and glucose levels (OR, 4.5; 95% CI, 1.0 to 20.9). Mean nocturnal SaO2 < 92% and minimal nocturnal SaO2 < 80% (ORs, 3.1 and 3.1; 95% CIs 1.0 to 9.4 and 1.0 to 8.5, respectively) were associated with the presence of carotid plaque independently of BP status (hypertensive or normotensive).


View this table:
[in this window]
[in a new window]

  		Table 3. Logistic Regression Analysis of Carotid Wall Hypertrophy and Plaque Occurrence on the Variables of Sleep Apnea Severity and BP Status*

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusion
 References
 
After studying a large group of patients with moderate-to-severe OSA without known cardiovascular disease, we found that the severity of oxygen desaturation and BP status were the best predictors for carotid wall hypertrophy. Plaque occurrence in this group of OSA patients was strictly related to the amount of oxygen desaturation independently of BP. Cautious clinical BP and 24-h ABPM allowed identifying 65% of patients with OSA having undiagnosed hypertension. These results suggest that atherosclerosis in OSA patients is largely determined by the severity of oxygen desaturation and can be exaggerated by the presence of frequently undiagnosed hypertension.

We reported on a large group of 83 cardiovascular disease-free apneic patients. Our subset of subjects was cautiously characterized in terms of vascular phenotype by clinical and 24-h ABPM, and carotid ultrasonography. As a whole group, our OSA patients were moderately obese and free of cardiovascular medications. In this context, the significant relationship found between carotid IMT/plaque formation and nocturnal oxygen desaturation is forceful. However, as there was a relatively narrow age range in the study population and they were almost exclusively male, the current results are not generalizable to an older population or to women.

How Does Oxygen Desaturation Severity Induce or Amplify Atherosclerotic Processes?
Atherosclerosis in OSA patients is probably mainly determined by the oxidative stress associated with the disease.22 The desaturation/reoxygenation sequence is a typical pattern coupled with the majority of respiratory events. This sequence leads to an oxidative/nitrosative stress with production of reactive oxygen species22 and reactive nitrogen species,23 which are the most important free radicals. A complex metabolic cascade potentially favoring atherosclerosis progression is then activated. The increased levels of reactive oxygen species contribute to produce systemic inflammation.24 Abnormalities in coagulation have also been recently described in OSA.2526 All these features are classical mechanisms associated with long-term appearance of atherosclerosis and cardiovascular diseases in other pathologic situations, and this probably also occurs in OSA syndrome. Also high sympathetic output, which is largely demonstrated in OSA, frequently leads to insulin resistance even in nonobese patients.2728 Insulin resistance per se increases oxidative stress and participates as a contributing factor to hypertension and vascular remodeling.

Taking into account all these pathophysiologic inputs, it is thus not surprising that the main determinant of oxidative stress (ie, the severity of cyclical oxygen desaturation) was significantly related to carotid IMT and plaque occurrence. In usual clinical OSA populations, obesity, current smoking, diabetes, and hyperlipidemia are frequent aggravating factors for atherosclerotic progression. As we studied OSA patients without a history of cardiovascular disease, these classical confounding factors were less represented and did not significantly correlate with IMT. The effects of oxygen desaturation are certainly cumulative over time and, interestingly enough, age was a factor related to carotid IMT.

Are There Other Pathophysiologic Modifications Associated With OSA That Can Run Atherosclerotic Processes?
In OSA syndrome, abnormal respiratory events do not lead exclusively to oxygen desaturation but are also associated with an increase in respiratory efforts and sleep fragmentation. Resistive breathing by inducing an oxidative stress increases proinflammatory cytokines production.29 In our study, as in others,131415 respiratory effort was only qualitatively monitored and the impact of inspiratory effort on vascular remodeling was impossible to assess. Sleep loss and sleep deprivation, in normal subjects, are known to result in elevated high-sensitivity C-reactive protein levels, an inflammatory marker of cardiovascular risk.30 In our study, microarousal index, a marker of sleep fragmentation, was not significantly related to carotid IMT. This could be different in mild OSA or upper airway resistance syndrome, in which nocturnal oxygen desaturation is very limited. Thus, even if nocturnal hypoxemia is probably the most important cause for oxidative stress, other contributors should be envisioned in studies addressing atheromatous modifications associated with OSA in various subgroups.

Underdiagnosed Hypertension: a Contributing Factor to Carotid IMT in OSA?
We have previously demonstrated that diastolic hypertension is a common underdiagnosed feature in OSA patients.31 In OSA patients, since hypertension is more prevalent than in the general population32 and frequently underdiagnosed, hypertension can be one of the major determinants for carotid IMT and secondary cardiovascular morbidity. Carotid IMT and plaque formation are related to different pathophysiologic mechanisms. IMT is classically more related to endoluminal increases of BP (hypertension), whereas plaque formation is related to atherosclerotic processes secondary to classical cardiovascular risk factors (hyperlipidemia, inflammation, etc). This explains why it was interesting to assess these two different parameters and why the explaining factors can be different. The current data are on line with these mechanisms. For IMT, BP status was one of the explaining factors. Moreover, hypoxemia was even more predictive of IMT in normotensive patients (OR, 10.6) as being then the only contributor to changes occurring in carotid walls. However, plaque formation is related to oxygen desaturation without influence of BP levels.

Effect of Nasal CPAP on the Arterial Wall
The mean value of 0.67 ± 0.13 mm that we found for common carotid IMT is low compared to previous studies131415 in OSA. This confirms that our patients were relatively free of confounding factors during the early course of the disease. Nasal CPAP is the first-line therapy in OSA syndrome. CPAP enables the reduction of cholesterol levels,26 systemic inflammation,33 and improves nitric oxide production.34 Conversely, coagulation factor abnormalities do not seem to change after 1 month of CPAP use.26 Taking into account these results, one can anticipate that nasal CPAP might reduce carotid IMT, but to our knowledge, no data are currently available in the literature regarding this issue.


   Conclusion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
References
 
The severity of oxygen desaturation is one of the main determinants of carotid IMT and plaque occurrence in apneic patients, and untreated hypertension also appears to be associated with carotid IMT. Further studies should evaluate whether nasal CPAP is able to reduce carotid IMT, particularly in the early course of the disease.


   Footnotes
 
Abbreviations: ABPM = ambulatory BP monitoring; BMI = body mass index; CI = confidence interval; CPAP = continuous positive airway pressure; DBP = diastolic BP; HR = heart rate; IMT = intima-media thickness; OR = odds ratio; OSA = obstructive sleep apnea; PP = pulse pressure; RDI = respiratory disturbance index; SaO2 = arterial oxygen saturation; SBP = systolic BP

Support was provided by grants from the French Society of Hypertension with the help of the Laboratoire Synthelabo (France); DRRC of Grenoble University Hospital (France); and Conseil Scientifique du Comité National contre les Maladies Respiratoires (France).

Received for publication February 18, 2005. Accepted for publication June 2, 2005.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 

  1. Lattimore, JD, Celermajer, DS, Wilcox, I (2003) Obstructive sleep apnea and cardiovascular disease. J Am Coll Cardiol 41,1429-1437[Abstract/Free Full Text]
  2. Parish, JM, Somers, VK Obstructive sleep apnea and cardiovascular disease. Mayo Clin Proc 2004;79,1036-1046[ISI][Medline]
  3. Pignoli, P, Tremoli, E, Poli, A, et al Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. Circulation 1986;74,1399-1406[Abstract/Free Full Text]
  4. Salonen, JT, Salonen, R Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb 1991;11,1245-1249[Abstract/Free Full Text]
  5. Fathi, R, Haluska, B, Isbel, N, et al The relative importance of vascular structure and function in predicting cardiovascular events. J Am Coll Cardiol 2004;43,616-623[Abstract/Free Full Text]
  6. for the Cardiovascular Health Study Collaborative Research Group. O’Leary, DH, Polak, JF, Kronmal, RA, et al Carotid artery intima-media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl J Med 1999;340,14-22[Abstract/Free Full Text]
  7. Zanchetti, A, Agabiti Rosei, E, Dal Palu, C, et al The Verapamil in Hypertension and Atherosclerosis Study (VHAS): results of long-term randomised treatment with either verapamil or chlorthalidone on carotid intima-media thickness. J Hypertens 1998;16,1667-1676[CrossRef][ISI][Medline]
  8. Lonn, EM, Yusuf, S, Dzavik, V, et al Effects of ramipril and vitamin E on atherosclerosis: the Study to Evaluate Carotid Ultrasound Changes in Patients Treated With Ramipril and Vitamin E (SECURE). Circulation 2001;103,919-925[Abstract/Free Full Text]
  9. Hedblad, B, Wikstrand, J, Janzon, L, et al Low-dose metoprolol CR/XL and fluvastatin slow progression of carotid intima-media thickness: main results from the Beta-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS). Circulation 2001;103,1721-1726[Abstract/Free Full Text]
  10. Simon, A, Gariepy, J, Moyse, D, et al Differential effects of nifedipine and co-amilozide on the progression of early carotid wall changes. Circulation 2001;103,2949-2954[Abstract/Free Full Text]
  11. Zanchetti, A, Bond, G, Hennig, M, et al Calcium antagonist lacidipine slows down progression of asymptomatic carotid atherosclerosis: principal results of the European Lacidipine Study on Atherosclerosis (ELSA), a randomized, double-blind, long-term trial. Circulation 2002;106,2422-2427[Abstract/Free Full Text]
  12. for the Diabetes and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Nathan, DM, Lachin, J, Cleary, P, et al Intensive diabetes therapy and carotid intima-media thickness in type 1 diabetes mellitus. N Engl J Med 2003;348,2294-2303[Abstract/Free Full Text]
  13. Suzuki, T, Nakano, H, Maekawa, J, et al Obstructive sleep apnea and carotid-artery intima-media thickness. Sleep 2004;27,129-133[ISI][Medline]
  14. Kaynak, D, Goksan, B, Kaynak, H, et al Is there a link between the severity of sleep-disordered breathing and atherosclerotic disease of the carotid arteries? Eur J Neurol 2003;10,487-493[CrossRef][ISI][Medline]
  15. Silvestrini, M, Rizzato, B, Placidi, F, et al Carotid artery wall thickness in patients with obstructive sleep apnea syndrome. Stroke 2002;33,1782-1785[Abstract/Free Full Text]
  16. 2003 European Society of Hypertension.. European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003;21,1011-1053[CrossRef][ISI][Medline]
  17. Baguet, JP, Mallion, JM, Moreau-Gaudry, A, et al Relationships between cardiovascular remodeling and the pulse pressure in never treated hypertension. J Hum Hypertens 2000;14,23-30[CrossRef][ISI][Medline]
  18. O’Brien, E, Asmar, R, Beilin, L, et al European Society of Hypertension recommendations for conventional, ambulatory and home blood pressure measurement. European Society of Hypertension Working Group on Blood Pressure Monitoring. J Hypertens 2003;21,821-848[CrossRef][ISI][Medline]
  19. Rechtschaffen, A, Kales, A A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. 1968 National Institutes of Health. Washington, DC:
  20. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research; the report of an American Academy of Sleep Medicine Task Force. Sleep 1999;22,667-689[ISI][Medline]
  21. Bonithon-Kopp, C, Ducimetiere, P, Touboul, PJ, et al Plasma angiotensin-converting enzyme activity and carotid wall thickening. Circulation 1994;89,952-954[Abstract/Free Full Text]
  22. Lavie, L Obstructive sleep apnoea syndrome: an oxidative disorder. Sleep Med Rev 2003;7,35-51[CrossRef][ISI][Medline]
  23. Svatikova, A, Wolk, R, Wang, HH, et al Circulating free nitrotyrosine in obstructive sleep apnea. Am J Physiol Regul Integr Comp Physiol 2004;287,R284-R287[Abstract/Free Full Text]
  24. Ciftci, TU, Kokturk, O, Bukan, N, et al The relationship between serum cytokine levels with obesity and obstructive sleep apnea syndrome. Cytokine 2004;28,87-91[CrossRef][ISI][Medline]
  25. Olson, LJ, Olson, EJ, Somers, VK Obstructive sleep apnea and platelet activation: another potential link between sleep-disordered breathing and cardiovascular disease. Chest 2004;126,339-341[Free Full Text]
  26. Robinson, GV, Pepperell, JC, Segal, HC, et al Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomised controlled trials. Thorax 2004;59,777-782[Abstract/Free Full Text]
  27. Punjabi, NM, Ahmed, MM, Polotsky, VY, et al Sleep-disordered breathing, glucose intolerance, and insulin resistance. Respir Physiol Neurobiol 2003;136,167-178[CrossRef][ISI][Medline]
  28. Coughlin, SR, Mawdsley, L, Mugarza, JA, et al Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome. Eur Heart J 2004;25,735-741[Abstract/Free Full Text]
  29. Vassilakopoulos, T, Katsaounou, P, Karatza, MH, et al Strenuous resistive breathing induces plasma cytokines: role of antioxidants and monocytes. Am J Respir Crit Care Med 2002;166,1572-1578[Abstract/Free Full Text]
  30. Meier-Ewert, HK, Ridker, PM, Rifai, N, et al Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol 2004;43,678-683[Abstract/Free Full Text]
  31. Baguet, JP, Hammer, L, Lévy, P, et al Nighttime and diastolic hypertension are common and underestimated conditions in newly diagnosed apnoeic patients. J Hypertens 2005;23,521-527[ISI][Medline]
  32. Peppard, PE, Young, T, Palta, M, et al Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000;342,1378-1384[Abstract/Free Full Text]
  33. Yokoe, T, Minoguchi, K, Matsuo, H, et al Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Circulation 2003;107,1129-1134[Abstract/Free Full Text]
  34. Schulz, R, Schmidt, D, Blum, A, et al Decreased plasma levels of nitric oxide derivatives in obstructive sleep apnoea: response to CPAP therapy. Thorax 2000;55,1046-1051[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 StrokeHome page
P. Lavie and L. Lavie
Is the Severity of Sleep Apnea Associated With Ischemic Stroke in the Elderly?
Stroke, February 1, 2007; 38(2): 249 - 249.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (18)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Baguet, J.-P.
Right arrow Articles by Pépin, J.-L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Baguet, J.-P.
Right arrow Articles by Pépin, J.-L.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS