0
Original Research: SLEEP MEDICINE |

Effects of Continuous Positive Airway Pressure on Cardiovascular Risk Profile in Patients With Severe Obstructive Sleep Apnea and Metabolic Syndrome FREE TO VIEW

Zuzana Dorkova, MD; Darina Petrasova, PhD; Angela Molcanyiova, MD; Marcela Popovnakova, MD; Ruzena Tkacova, MD, PhD
Author and Funding Information

*From the Department of Respiratory Medicine (Drs. Dorkova and Tkacova), Faculty of Medicine, P.J. Safarik University and L. Pasteur Teaching Hospital; Institute of Experimental Medicine (Dr. Petrasova), Faculty of Medicine; and Department of Biochemistry (Drs. Molcanyiova and Popovnakova), LABMED, Kosice, Slovakia.

Correspondence to: Ruzena Tkacova, MD, PhD, Department of Respiratory Medicine, Faculty of Medicine and L. Pasteur Teaching Hospital, Rastislavova 43, Kosice 041 90, Slovakia; e-mail: rtkacova@medic.upjs.sk


For editorial comment see page 675

This work was supported by the Slovak Research and Development Agency under the contract No. APVV-0122-06, and Ministry of Health under the contract No. 2005/5-FNLPKE-01, Slovakia.

This work was performed at the Department of Respiratory Medicine, Faculty of Medicine and L. Pasteur Teaching Hospital, Kosice.

The authors have no conflicts of interest to disclose.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).


Chest. 2008;134(4):686-692. doi:10.1378/chest.08-0556
Text Size: A A A
Published online

Background:  The increased risk of atherosclerotic morbidity and mortality in patients with obstructive sleep apnea (OSA) has been linked to arterial hypertension, insulin resistance, systemic inflammation, and oxidative stress. We aimed to determine the effects of 8 weeks of therapy with continuous positive airway pressure (CPAP) on glucose and lipid profile, systemic inflammation, oxidative stress, and global cardiovascular disease (CVD) risk in patients with severe OSA and metabolic syndrome.

Methods:  In 32 patients, serum cholesterol, triglycerides, high-density lipoprotein cholesterol, fibrinogen, apolipoprotein A-I, apolipoprotein B (ApoB), high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor (TNF)-α, leptin, malondialdehyde (MDA), and erythrocytic glutathione peroxidase (GPx) activity were measured at baseline and after 8 weeks of CPAP. The insulin resistance index (homeostasis model assessment [HOMA-IR]) was based on the homeostasis model assessment method, the CVD risk was calculated using the multivariable risk factor algorithm.

Results:  In patients who used CPAP for ≥ 4 h/night (n = 16), CPAP therapy reduced systolic BP and diastolic BP (p = 0.001 and p = 0.006, respectively), total cholesterol (p = 0.002), ApoB (p = 0.009), HOMA-IR (p = 0.031), MDA (p = 0.004), and TNF-α (p = 0.037), and increased erythrocytic GPx activity (p = 0.015), in association with reductions in the global CVD risk (from 18.8 ± 9.8 to 13.9 ± 9.7%, p = 0.001). No significant changes were seen in patients who used CPAP for < 4 h/night. Mask leak was the strongest predictor of compliance with CPAP therapy.

Conclusions:  In patients with severe OSA and metabolic syndrome, good compliance to CPAP may improve insulin sensitivity, reduce systemic inflammation and oxidative stress, and reduce the global CVD risk.

Trial registration:  Clinicaltrials.gov Identifier: NCT00635674.

Figures in this Article

Patients with obstructive sleep apnea (OSA) are at increased risk for atherosclerotic morbidity and mortality.1,2 OSA is associated with high risk of arterial hypertension, a traditional risk factor of atherosclerosis.3 Moreover, OSA has been linked to novel factors related to atherogenesis-metabolic syndrome,4,5 systemic inflammation,6 and oxidative stress7,8; and early signs of atherosclerosis have been observed in patients with OSA free of overt cardiovascular diseases.9

Numerous studies have selectively examined the effects of continuous positive airway pressure (CPAP) ventilation, the primary treatment for OSA, on the traditional and novel risk factors of atherosclerosis. A recent metaanalysis10 of 16 randomized trials indicated that CPAP decreases BP in patients with OSA. Furthermore, reductions in serum total cholesterol, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and markers of oxidative stress were demonstrated after effective CPAP therapy.68,11 Improvements in insulin sensitivity have been reported in some1215 but not in all studies.4,16,17 Importantly, substantial evidence links the effects of CPAP to compliance with this treatment.7,11,18

Most observational studies examined the effects of CPAP across a broad-range of OSA severity and have included patients with and without the metabolic syndrome. Up to now, no study has analyzed the effects of CPAP on glucose and lipid metabolism, systemic inflammation, oxidative stress, and the global cardiovascular disease (CVD) risk within the same cohort of subjects with severe OSA and concurrent metabolic syndrome. Importantly, the metabolic syndrome exacerbates CVD risk over and above that attributable to OSA alone.19 Therefore, reduction of CVD risk in patients with OSA and concurrent metabolic syndrome is of paramount importance. The primary purpose of the present study was to determine, in patients with severe OSA and metabolic syndrome compliant to CPAP, the effects of 8 weeks of therapy on the glucose and lipid profile, systemic inflammation, oxidative stress, and global CVD risk.

Subjects

Clinically stable subjects with severe OSA (≥ 30 obstructive apneas or hypopneas per hour of sleep and excessive daytime sleepiness) and metabolic syndrome20 were prospectively recruited in the sleep unit at the tertiary referral teaching hospital. Exclusion criteria were as follows: (1) endocrine or metabolic disorders other than metabolic syndrome; (2) history of myocardial infarction, angina, or stroke; (3) inflammatory or other chronic disease; (4) respiratory disorder other than OSA; (5) neurologic lesions; and (6) regular use of sedative medication or alcohol. The study had local ethics committee approval, and all subjects gave written consent to the study.

Sleep Assessment and CPAP Titration

Subjects underwent an attended diagnostic overnight polysomnography using standard techniques and scoring criteria (Alice 4 System; Respironics; Murrysville, PA). Polysomnography consisted of continuous recording of EEG, electrooculography, electromyography, ECG, thoracic and abdominal impedance belts for respiratory effort, thermistors for nasal and oral airflow, pulse oximetry, and tracheal microphone for snoring. Polysomnograms were scored manually according to established criteria.21 Apnea was identified by a complete cessation of airflow for > 10 s; hypopnea was defined as a discernible reduction in tidal volume and airflow accompanied by a decrease in oxyhemoglobin saturation > 3% or by an EEG-recorded arousal, persisting for > 10 s. The apnea-hypopnea index (AHI) was defined as the number of apneas and hypopneas per hour of sleep. Sleepiness was evaluated using the Epworth sleepiness scale (ESS).

CPAP titration was performed during subsequent overnight polysomnography using the Autoset self-adjusting CPAP device (REMstar-auto; Respironics). Since the pattern of adherence to CPAP is established within the first days of treatment,22 we have invited all initially nonadherent patients and those with the mask leak > 0.4 L/s for additional 2 nights within the first week of CPAP use to maximize adherence and to adjust the mask. In patients for whom significant leak persisted, and who expressed their nonadherence to the given pressure, the pressure was manually decreased in 1 cm H2O increments while maintaining the AHI at < 10/h. The effective pressure was defined as the lowest pressure at which the patient had an AHI < 10/h,23 and which has been embraced by the patient in the laboratory. All patients were advised to use CPAP with heated humidification (REMstar Plus; Respironics) every night at the effective fixed-pressure mode and to adhere to physical exercise and diet. After 8 weeks, all patients returned for a follow-up sleep study, clinical assessment, and biochemical analysis. Compliance was measured electronically using a SmartCard embedded in the CPAP machine (EncorePro; Respironics).

Biochemical Analysis

Peripheral venous blood samples were collected from 6:00 to 7:00 am following an overnight 12-h fast and polysomnography. Blood sample was taken from the antecubital vein; after immediate centrifugation, aliquots of plasma and serum were stored at − 70°C until analysis. Serum insulin was determined with electrochemiluminiscence immunoassay kits on Roche Elecsys 1010/2010 and modular analytics E170 immunoassay analyzers (Roche Diagnostics GmbH; Mannheim, Germany); plasma glucose was measured by the glucose oxidase method on a Beckman autoanalyzer. Fasting cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, fibrinogen, apolipoprotein A-I (ApoA-I), and apolipoprotein B (ApoB) were measured by routine enzymatic methods. Low-density lipoprotein (LDL) cholesterol was derived using the Friedewald equation. High-sensitivity CRP levels were assessed by chemiluminiscent immunoassay method; TNF-α, IL-6, and leptin concentrations were measured by commercially available enzyme-linked immunosorbent assay kits. Serum malondialdehyde (MDA) concentrations were assessed using spectrophotometry.24 Glutathione peroxidase (GPx) activity in erythrocytes was determined in washed RBCs obtained immediately after sampling from the whole blood anticoagulated with ethylenediamine tetraacetic acid.

Metabolic Syndrome and CVD Risk

Metabolic syndrome was diagnosed according to the International Diabetes Federation definition.20 Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR) using the following formula: fasting serum insulin (mU/L) ×fasting plasma glucose (mmol/L)/22.5.25 Waking BP was measured in the supine position and was recorded as the mean of three measurements taken at 1-min intervals according to the British Hypertension Society guidelines. Pulmonary function tests were evaluated with the use of body plethysmography (Jaeger; Wurzberg, Germany).

The assessment of CVD risk was based on the recently published sex-specific multivariable risk factor algorithm.26 The scores consider sex, age, total cholesterol, HDL cholesterol, systolic BP, smoking, and diabetes, and are used to predict the 10-year risk of CVD events (coronary, cerebrovascular, peripheral artery disease, and heart failure).26

Data Analysis

Acceptable compliance was considered if the patient used CPAP for ≥ 4 h/night. Based on the adherence to therapy, patients were classified into two categories: good (≥ 4 h/night) and poor (< 4 h/night) compliance. Analysis of variance was used to determine the intergroup differences at baseline and the intragroup differences over 8 weeks. The prevalences of various variables were compared using the χ2 test. Least-squares linear regression analysis (Spearman test) was used to assess the unadjusted relationships. In the multivariate analysis, multiple linear regression was used with CPAP compliance as the dependent variable, and age, gender, body mass index (BMI), and mask leak as independent variables. Analyses were conducted using statistical software (SPSS for Windows, version 14.0; SPSS; Chicago, IL). Results are presented as mean ± SD; p < 0.05 was considered statistically significant.

Characteristics of the Subjects

Thirty-two of 66 subjects referred to our sleep unit between January 2007 and October 2007 met the inclusion criteria. Of the remaining patients, 9 had OSA but no metabolic syndrome, 3 had mild-to-moderate OSA, 6 had central sleep apnea, and 16 subjects did not have sleep-disordered breathing (Fig 1). No patient in the study cohort underwent surgery of the upper airway, changed hypolipidemic and/or antihypertensive medications, or changed weight (> 5%) during the follow-up. Baseline characteristics of the entire cohort and of the two groups according to CPAP compliance are displayed in Table 1. Compared to patients who used CPAP for ≥ 4 h/night, noncompliant patients had higher BMI (p = 0.037) and higher mask leak (p = 0.003). No differences were observed in the medication use (Table 1), AHI during the CPAP titration night (4.3 ± 4.0/h 6.5 ± 4.8/h, p = 0.167), or weight change during the study period between the two groups (0.03 ± 1.03 kg vs 0.28 ± 0.89 kg, p = 0.473).

Figure Jump LinkFigure 1 Flowchart diagram of patients examined in the sleep unit between January and October 2007Grahic Jump Location
Table Graphic Jump Location
Table 1 Baseline Characteristics and Polysomnographic Findings in the Entire Cohort of Patients With Severe OSA and Metabolic Syndrome, and in the Two Groups According to CPAP Compliance*

*Values are given as No. of patients or mean ± SD. Spo2 = oxygen saturation by pulse oximetry.

Cardiovascular Disease Risk

In patients who used CPAP for ≥ 4 h/night, CPAP therapy over 8 weeks significantly reduced morning systolic and diastolic BP (p = 0.001 and p = 0.006, respectively), total serum cholesterol (p = 0.002), ApoB (p = 0.009), and HOMA-IR (p = 0.031) [Table 2]. In contrast, no significant changes were observed in the noncompliant group. The global CVD risk was reduced in patients who used CPAP for ≥ 4 h/night (18.8 ± 9.8% vs 13.9 ± 9.7%, p = 0.001), whereas it remained unchanged in the noncompliant group (18.6 ± 8.4% vs 18.2 ± 8.8%, p = 0.589) [Fig 2.

Table Graphic Jump Location
Table 2 Changes in Components of the Metabolic Syndrome and CVD Risk in the Two Groups According to CPAP Compliance*

*Values are given as mean ± SD.

†Comparison between baseline and follow-up measurements.

‡Comparison between changes in the outcome variables over 8 weeks between the compliant and noncompliant groups.

Figure Jump LinkFigure 2 CVD risk at baseline and after 8 weeks of CPAP treatment for OSA in the two groups according to compliance with CPAP therapy. *p = 0.001Grahic Jump Location
Oxidative Stress and Systemic Inflammation

In patients who used CPAP for ≥ 4 h/night, significant increases in erythrocytic GPx activity (p = 0.015), reductions in serum MDA (p = 0.004), and reductions in TNF-α (p = 0.037) were observed, whereas concentrations of IL-6, high-sensitivity CRP, and leptin did not change (Table 3). No significant changes in oxidative stress or systemic inflammation markers were seen in the group noncompliant with CPAP therapy. Table 4 indicates linear relationships between compliance with CPAP and changes in the outcome variables over 8 weeks in the entire cohort.

Table Graphic Jump Location
Table 3 Changes in Systemic Inflammation and Markers of Oxidative Stress in the Two Groups According to CPAP Compliance*

*Values are given as the mean ± SD. ox-LDL = oxidized LDL cholesterol; hsCRP = high-sensitivity CRP.

†Comparison between baseline and follow-up measurements.

‡Comparison between changes in the outcome variables over 8 weeks between the compliant and noncompliant groups.

Table Graphic Jump Location
Table 4 Linear Relationships Between Compliance With CPAP Therapy and Changes in Absolute Values in Morning BP, Components of the Metabolic Syndrome, CVD Risk, and Markers of Systemic Inflammation and Oxidative Stress Over 8 Weeks in the Entire Cohort
Factors Related to Compliance With CPAP

No relationships were observed between CPAP compliance and age or AHI (r = − 0.130, p = 0.478, and r = − 0.154, p = 0.400, respectively). In contrast, CPAP compliance was significantly inversely related to BMI (r = − 0.370, p = 0.037) and mask leak (r = − 0.518, r = 0.002). A close direct relationship between BMI and mask leak was also observed (r = 0.686, p < 0.001). In multiple linear regression analysis with CPAP compliance as an independent variable, and age, gender, BMI, and mask leak as dependent variables, only mask leak was an independent predictor of CPAP compliance (R2 = 0.297, p = 0.031).

This observational study demonstrated that 8 week of CPAP therapy reduced the global CVD risk in patients with severe OSA and concurrent metabolic syndrome. Reductions in CVD risk were linked to reductions in BP and total cholesterol levels. In addition, patients effectively treated with CPAP had reductions in insulin resistance, TNF-α, and oxidative stress markers. Nevertheless, these beneficial effects of therapy were confined to the group of patients who used CPAP for ≥ 4 h/night. Previously, beneficial effects of CPAP on insulin sensitivity,1215 total and HDL cholesterol,11,27,28 oxidative stress,7,8 and systemic inflammation6,29 were selectively documented in some but not all reports.16,17,30 Most studies examined patients with a broad range of OSA severity, and included patients with and without the metabolic syndrome. Some of them did7,11,12 whereas others did not8,13 relate the outcomes to compliance with CPAP. To our knowledge, our data are the first to examine all variables within the same subjects and to demonstrate reductions in the global CVD risk, in association with improvements in novel risk factors related to atherogenesis, in patients with severe OSA and metabolic syndrome and compliant with CPAP therapy.

Strategies to decrease the high prevalence and associated morbidity of OSA are critically needed.31 In the present study, calculation of the CVD risk was based on the recently published sex-specific multivariable risk factor algorithm.26 This algorithm estimates the general CVD risk and risk of individual CVD events (coronary, cerebrovascular, peripheral arterial disease, and heart failure). For predicting CVD risk, this general CVD risk prediction function performs better than the traditionally used Framingham risk function.26 Importantly, our data on the CVD risk observed at the time of CPAP initiation parallel the event rates in patients with severe OSA reported previously,2 thus reinforcing the value of our further observations on the reduction of CVD risk with CPAP therapy.

The present observations on the reductions of insulin resistance (mean reduction in HOMA-IR of 38%) agree with previous findings that reported a 24% increase in insulin sensitivity after 3 months of CPAP therapy in patients with BMI > 30 kg/m2.12 Importantly, despite significant reductions in HOMA- IR its average values after 8 weeks of CPAP (2.93) remained higher than the population-based cutoff for insulin resistance (2.29 for the central European population).32 Therefore, although CPAP might improve insulin sensitivity in subjects with OSA and concurrent metabolic syndrome, these patients remain insulin resistant and need to be managed further following the appropriate guidelines.33

Similarly to previous reports,68 our data demonstrate reductions in serum TNF-α and amelioration of oxidative stress (reductions in serum MDA and increases in erythrocytic GPx activity) by effective CPAP therapy. Inhibition of nuclear factor-κB– dependent inflammatory pathways by abolishing intermittent hypoxia represents a possible underlying mechanism of TNF-α reductions.6 In contrast, we failed to observe any change in either serum CRP, IL-6, or leptin concentrations with CPAP. These findings correspond with previous reports suggesting that obesity rather than OSA drive raised CRP, IL-6, or leptin levels in patients with OSA.6,7,34

Studying a well-defined cohort of patients represents one of the strengths of the present report. Previously, most studies included patients with and without metabolic syndrome within the same group. In the study of Coughlin et al,4 30% of patients with OSA did not suffer from the concurrent metabolic syndrome. Therefore, lower baseline insulin resistance, fasting glucose, total cholesterol, and triglycerides levels were reported in this compared to our study.4 Importantly, Borgel et al27 observed that the magnitude of cholesterol change with CPAP was most evident in patients with abnormal initial values, thus suggesting that the beneficial effects of CPAP likely occur in metabolically more severe patients, such as those in our study. The second strength of the present study was the careful assessment of compliance with CPAP followed by vigorous effort to minimize mask leak, and to enhance the embracement of this treatment. Indeed, compliance with therapy likely represents the key factor affecting CPAP effects on cardiovascular risk factors. Recently, Coughlin et al4 found no change in baroreflex sensitivity after 6 weeks of CPAP; however, in the subset of patients with good compliance, significant improvements were achieved. Compliance with CPAP also determines the effects of therapy on systemic BP35 and on serum cardiovascular risk factors.11 In the present study, we have achieved adequate titration (AHI < 10/h) in all patients during the CPAP titration night. Nevertheless, this was associated with mask leak of 0.4 to 0.8 L/s in eight grossly overweight patients. Despite 2 more nights in the laboratory, adjustments to the mask, and emotional support, the leak remained > 0.4 L/s, and none of these patients became compliant with CPAP use later. Nevertheless, in the view of the frequent (46 to 83%) nonadherence to CPAP in patients with OSA,18 poor compliance with CPAP in 50% of our patients with concurrent metabolic syndrome is not unexpected.

There are some limitations in the current study. CVD risk rather than hard cardiovascular end points was used as an outcome. Ideally, randomized trials should be employed to address the effects of CPAP on cardiovascular morbidity. Furthermore, insulin sensitivity was approximated by using HOMA-IR instead of the euglycemic insulin clamp. Nevertheless, insulin sensitivity indexes derived from the homeostatic model are strongly related to values obtained by the clamp method.36

In conclusion, our study demonstrated a significant reduction in the global CVD risk in patients with severe OSA and concurrent metabolic syndrome by effective CPAP therapy, in association with improvements in insulin sensitivity, and reductions in systemic inflammation and oxidative stress. Our findings highlight the need to study these effects of CPAP in patients adherent to CPAP therapy in randomized trials.

AHI

apnea-hypopnea index

ApoA-I

apolipoprotein A-I

ApoB

apolipoprotein B

BMI

body mass index

CPAP

continuous positive airway pressure

CRP

C-reactive protein

CVD

cardiovascular disease

ESS

Epworth sleepiness scale

GPx

glutathione peroxidase

HDL

high-density lipoprotein

HOMA-IR

homeostasis model assessment

IL

interleukin

LDL

low-density lipoprotein

MDA

malondialdehyde

OSA

obstructive sleep apnea

TNF

tumor necrosis factor

The authors wish to express their gratitude to Mrs. Katarina Pollakova, the head nurse, and Mrs. Anna Schejbalova and Slavka Zemanova, the technicians in the sleep laboratory, Department of Respiratory Medicine, Faculty of Medicine and L. Pasteur Teaching Hospital, Kosice, Slovakia.

Mooe T, Franklin KA, Holmstrom K, et al. Sleep-disordered breathing and coronary artery disease: long-term prognosis. Am J Respir Crit Care Med. 2001;164:1910-1913. [PubMed]
 
Marin JM, Carrizo SJ, Vicente E, et al. Long-term cardiovascular outcomes in men with obstructive sleep apnea-hypopnea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005;365:1046-1053. [PubMed]
 
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. [PubMed] [CrossRef]
 
Coughlin SR, Mawdsley L, Mugarza JA, et al. Cardiovascular and metabolic effects of CPAP in obese males with OSA. Eur Respir J. 2007;29:720-727. [PubMed]
 
Vgontzas AN, Bixler EO, Chroussos GP. Sleep apnea is a manifestation of the metabolic syndrome. Sleep Med Rev. 2005;9:211-224. [PubMed]
 
Ryan S, Taylor CT, McNicholas WT. Predictors of elevated nuclear factor-κB-dependent genes in obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 2006;174:824-830. [PubMed]
 
Barcelo A, Barbe F, Llompart E, et al. Effects of obesity on C-reactive protein level and metabolic disturbances in male patients with obstructive sleep apnea. Am J Med. 2004;117:118-121. [PubMed]
 
Minoguchi K, Yokoe T, Tanaka A, et al. Association between lipid peroxidation and inflammation in obstructive sleep apnoea. Eur Respir J. 2006;28:378-385. [PubMed]
 
Drager LF, Bortolotto LA, Lorenzi MC, et al. Early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med. 2005;172:613-618. [PubMed]
 
Bazzano LA, Khan Z, Reynolds K, et al. Effect of nocturnal nasal continuous positive airway pressure on blood pressure in obstructive sleep apnea. Hypertension. 2007;50:417-423. [PubMed]
 
Steiropoulos P, Tsara V, Nena E, et al. Effect of continuous positive airway pressure treatment on serum cardiovascular risk factors in patients with obstructive sleep apnea-hypopnea syndrome. Chest. 2007;132:843-851. [PubMed]
 
Harsch IA, Schahin SP, Radespiel-Troger M, et al. Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 2004;169:156-162. [PubMed]
 
Harsch IA, Schahin SP, Bruckner K, et al. The effect of continuous positive airway pressure treatment on insulin sensitivity in patients with obstructive sleep apnoea syndrome and type 2 diabetes. Respiration. 2004;71:252-259. [PubMed]
 
Babu AR, Herdegen J, Fogelfeld L, et al. Type 2 diabetes, glycemic control, and continuous positive airway pressure in obstructive sleep apnea. Arch Intern Med. 2005;165:447-452. [PubMed]
 
Lindberg E, Berne C, Elmasry A, et al. CPAP treatment of a population-based sample: what are the benefits and the treatment compliance? Sleep Med. 2006;7:553-560. [PubMed]
 
Smurra M, Philip P, Taillard J, et al. CPAP treatment does not affect glucose-insulin metabolism in sleep apneic patients. Sleep Med. 2001;2:207-213. [PubMed]
 
West SD, Nicoll DJ, Wallace TM, et al. The effect of CPAP on insulin resistance and hbA1c in men with obstructive sleep apnoea and type 2 diabetes. Thorax. 2007;62:969-974. [PubMed]
 
Weaver TE, Grunstein RR. Adherence to continuous positive airway pressure therapy: the challenge to effective therapy. Proc Am Thorac Soc. 2008;5:173-178. [PubMed]
 
Shiina K, Tomyiama H, Takata Y, et al. Concurrent presence of metabolic syndrome in obstructive sleep apnea syndrome exacerbates the cardiovascular risk: a sleep clinic cohort study. Hypertens Res. 2006;29:433-441. [PubMed]
 
International Diabetes Federation The IDF consensus worldwide definition of the metabolic syndrome. 2005; Brussels, Belgium International Diabetes Federation
 
Rechtschaffen A, Kales A. A manual of standardized terminology, techniques and scoring systems for sleep stages of human subjects. 1968; Los Angeles, CA UCLA Brain Information Service/Brain Research Institute
 
Weaver TE, Kribbs NB, Pack AI, et al. Night-to-night variability in CPAP use over the first three months of treatment. Sleep. 1997;20:278-283. [PubMed]
 
Oliver Z, Hoffstein V. Predicting effective continuous positive airway pressure. Chest. 2000;117:1061-1064. [PubMed]
 
Yagi K. A simple fluorometric assay for lipoperoxide in blood plasma. Biochem Med. 1976;15:212-216. [PubMed]
 
Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412-419. [PubMed]
 
D'Agostino RB, Vasan RS, Pencina MJ, et al. General cardiovascular risk profile for use in primary care: the Framingham heart study. Circulation. 2008;117:743-753. [PubMed]
 
Borgel J, Sanner BM, Bittlinsky A, et al. Obstructive sleep apnoea and its therapy influence high-density lipoprotein cholesterol serum levels. Eur Respir J. 2006;27:121-127. [PubMed]
 
Robinson GV, Pepperell JC, Segal HC, et al. Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomized controlled trials. Thorax. 2004;59:777-782. [PubMed]
 
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. [PubMed]
 
Svatikova A, Wolk R, Lerman LO, et al. Oxidative stress in obstructive sleep apnoea. Eur Heart J. 2005;26:2435-2439. [PubMed]
 
Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med. 2002;165:1217-1239. [PubMed]
 
Radikova Z, Koska J, Huckova M, et al. Insulin sensitivity indices: a proposal of cut-off points for simple identification of insulin-resistant subjects. Exp Clin Endocrinol Diabetes. 2006;114:249-256. [PubMed]
 
Nathan DM, Davidson MB, DeFronzo RA, et al. Impaired fasting glucose and impaired glucose tolerance. Diabetes Care. 2007;30:753-759. [PubMed]
 
Harsch IA, Konturek PC, Koebnick C, et al. Leptin and ghrelin levels in patients with obstructive sleep apnoea: effect of CPAP treatment. Eur Respir J. 2003;22:251-257. [PubMed]
 
Martinez-Garcia MA, Gomez-Aldaravi R, Soler-Cataluna JJ, et al. Positive effect of CPAP treatment on the control of difficult-to-treat hypertension. Eur Respir J. 2007;29:951-957. [PubMed]
 
Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004;27:1498-1495
 

Figures

Figure Jump LinkFigure 1 Flowchart diagram of patients examined in the sleep unit between January and October 2007Grahic Jump Location
Figure Jump LinkFigure 2 CVD risk at baseline and after 8 weeks of CPAP treatment for OSA in the two groups according to compliance with CPAP therapy. *p = 0.001Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 Baseline Characteristics and Polysomnographic Findings in the Entire Cohort of Patients With Severe OSA and Metabolic Syndrome, and in the Two Groups According to CPAP Compliance*

*Values are given as No. of patients or mean ± SD. Spo2 = oxygen saturation by pulse oximetry.

Table Graphic Jump Location
Table 2 Changes in Components of the Metabolic Syndrome and CVD Risk in the Two Groups According to CPAP Compliance*

*Values are given as mean ± SD.

†Comparison between baseline and follow-up measurements.

‡Comparison between changes in the outcome variables over 8 weeks between the compliant and noncompliant groups.

Table Graphic Jump Location
Table 3 Changes in Systemic Inflammation and Markers of Oxidative Stress in the Two Groups According to CPAP Compliance*

*Values are given as the mean ± SD. ox-LDL = oxidized LDL cholesterol; hsCRP = high-sensitivity CRP.

†Comparison between baseline and follow-up measurements.

‡Comparison between changes in the outcome variables over 8 weeks between the compliant and noncompliant groups.

Table Graphic Jump Location
Table 4 Linear Relationships Between Compliance With CPAP Therapy and Changes in Absolute Values in Morning BP, Components of the Metabolic Syndrome, CVD Risk, and Markers of Systemic Inflammation and Oxidative Stress Over 8 Weeks in the Entire Cohort

References

Mooe T, Franklin KA, Holmstrom K, et al. Sleep-disordered breathing and coronary artery disease: long-term prognosis. Am J Respir Crit Care Med. 2001;164:1910-1913. [PubMed]
 
Marin JM, Carrizo SJ, Vicente E, et al. Long-term cardiovascular outcomes in men with obstructive sleep apnea-hypopnea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005;365:1046-1053. [PubMed]
 
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. [PubMed] [CrossRef]
 
Coughlin SR, Mawdsley L, Mugarza JA, et al. Cardiovascular and metabolic effects of CPAP in obese males with OSA. Eur Respir J. 2007;29:720-727. [PubMed]
 
Vgontzas AN, Bixler EO, Chroussos GP. Sleep apnea is a manifestation of the metabolic syndrome. Sleep Med Rev. 2005;9:211-224. [PubMed]
 
Ryan S, Taylor CT, McNicholas WT. Predictors of elevated nuclear factor-κB-dependent genes in obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 2006;174:824-830. [PubMed]
 
Barcelo A, Barbe F, Llompart E, et al. Effects of obesity on C-reactive protein level and metabolic disturbances in male patients with obstructive sleep apnea. Am J Med. 2004;117:118-121. [PubMed]
 
Minoguchi K, Yokoe T, Tanaka A, et al. Association between lipid peroxidation and inflammation in obstructive sleep apnoea. Eur Respir J. 2006;28:378-385. [PubMed]
 
Drager LF, Bortolotto LA, Lorenzi MC, et al. Early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med. 2005;172:613-618. [PubMed]
 
Bazzano LA, Khan Z, Reynolds K, et al. Effect of nocturnal nasal continuous positive airway pressure on blood pressure in obstructive sleep apnea. Hypertension. 2007;50:417-423. [PubMed]
 
Steiropoulos P, Tsara V, Nena E, et al. Effect of continuous positive airway pressure treatment on serum cardiovascular risk factors in patients with obstructive sleep apnea-hypopnea syndrome. Chest. 2007;132:843-851. [PubMed]
 
Harsch IA, Schahin SP, Radespiel-Troger M, et al. Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 2004;169:156-162. [PubMed]
 
Harsch IA, Schahin SP, Bruckner K, et al. The effect of continuous positive airway pressure treatment on insulin sensitivity in patients with obstructive sleep apnoea syndrome and type 2 diabetes. Respiration. 2004;71:252-259. [PubMed]
 
Babu AR, Herdegen J, Fogelfeld L, et al. Type 2 diabetes, glycemic control, and continuous positive airway pressure in obstructive sleep apnea. Arch Intern Med. 2005;165:447-452. [PubMed]
 
Lindberg E, Berne C, Elmasry A, et al. CPAP treatment of a population-based sample: what are the benefits and the treatment compliance? Sleep Med. 2006;7:553-560. [PubMed]
 
Smurra M, Philip P, Taillard J, et al. CPAP treatment does not affect glucose-insulin metabolism in sleep apneic patients. Sleep Med. 2001;2:207-213. [PubMed]
 
West SD, Nicoll DJ, Wallace TM, et al. The effect of CPAP on insulin resistance and hbA1c in men with obstructive sleep apnoea and type 2 diabetes. Thorax. 2007;62:969-974. [PubMed]
 
Weaver TE, Grunstein RR. Adherence to continuous positive airway pressure therapy: the challenge to effective therapy. Proc Am Thorac Soc. 2008;5:173-178. [PubMed]
 
Shiina K, Tomyiama H, Takata Y, et al. Concurrent presence of metabolic syndrome in obstructive sleep apnea syndrome exacerbates the cardiovascular risk: a sleep clinic cohort study. Hypertens Res. 2006;29:433-441. [PubMed]
 
International Diabetes Federation The IDF consensus worldwide definition of the metabolic syndrome. 2005; Brussels, Belgium International Diabetes Federation
 
Rechtschaffen A, Kales A. A manual of standardized terminology, techniques and scoring systems for sleep stages of human subjects. 1968; Los Angeles, CA UCLA Brain Information Service/Brain Research Institute
 
Weaver TE, Kribbs NB, Pack AI, et al. Night-to-night variability in CPAP use over the first three months of treatment. Sleep. 1997;20:278-283. [PubMed]
 
Oliver Z, Hoffstein V. Predicting effective continuous positive airway pressure. Chest. 2000;117:1061-1064. [PubMed]
 
Yagi K. A simple fluorometric assay for lipoperoxide in blood plasma. Biochem Med. 1976;15:212-216. [PubMed]
 
Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412-419. [PubMed]
 
D'Agostino RB, Vasan RS, Pencina MJ, et al. General cardiovascular risk profile for use in primary care: the Framingham heart study. Circulation. 2008;117:743-753. [PubMed]
 
Borgel J, Sanner BM, Bittlinsky A, et al. Obstructive sleep apnoea and its therapy influence high-density lipoprotein cholesterol serum levels. Eur Respir J. 2006;27:121-127. [PubMed]
 
Robinson GV, Pepperell JC, Segal HC, et al. Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomized controlled trials. Thorax. 2004;59:777-782. [PubMed]
 
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. [PubMed]
 
Svatikova A, Wolk R, Lerman LO, et al. Oxidative stress in obstructive sleep apnoea. Eur Heart J. 2005;26:2435-2439. [PubMed]
 
Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med. 2002;165:1217-1239. [PubMed]
 
Radikova Z, Koska J, Huckova M, et al. Insulin sensitivity indices: a proposal of cut-off points for simple identification of insulin-resistant subjects. Exp Clin Endocrinol Diabetes. 2006;114:249-256. [PubMed]
 
Nathan DM, Davidson MB, DeFronzo RA, et al. Impaired fasting glucose and impaired glucose tolerance. Diabetes Care. 2007;30:753-759. [PubMed]
 
Harsch IA, Konturek PC, Koebnick C, et al. Leptin and ghrelin levels in patients with obstructive sleep apnoea: effect of CPAP treatment. Eur Respir J. 2003;22:251-257. [PubMed]
 
Martinez-Garcia MA, Gomez-Aldaravi R, Soler-Cataluna JJ, et al. Positive effect of CPAP treatment on the control of difficult-to-treat hypertension. Eur Respir J. 2007;29:951-957. [PubMed]
 
Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004;27:1498-1495
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

CHEST Journal Articles
CHEST Collections
PubMed Articles
Guidelines
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543