the obstructive sleep apnea syndrome ( osas ) is a highly prevalent sleep disorder characterized by recurrent episodes of upper airway obstruction and subsequent recurrent arousal during sleep .
it is estimated that up to 5% of adults in western countries have osas . according to published data
emerging studies suggest that the repetitive episodes of hypoxia and reoxygenation , in a manner similar to that of the ischemia / reperfusion injury model , promote the activation of proinflammatory pathways and disrupt normal endothelial function .
brachial artery flow - mediated dilation ( fmd ) is a validated and widely used research tool for the quantification of endothelial function .
it is a sensitive marker of inflammation and an important marker of future cardiovascular risk .
elevated crp levels have been reported by several researchers in osas patients [ 1416 ] .
we hypothesized that the proper use of cpap should also help improve the levels of fmd and crp and thus reduce the risk for adverse cardiovascular events .
the aim of this study was to assess the effect of 3-month cpap therapy on fmd and plasma crp levels in patients with osas .
this study was conducted in the sleep laboratory of the department of clinical therapeutics at alexandra hospital ; athens medical school .
informed consent was obtained from each patient and approval was also obtained for the conduct of this study from the hospital ethics committee .
male patients with suspected osas , receiving no medication , and known not to suffer from diabetes mellitus , arterial hypertension , dyslipidemia , or inflammatory , cardiovascular , neuromuscular or pulmonary diseases were recruited into the study .
all patients underwent full overnight polysomnography . according to the standard criteria of the american academy of sleep medicine : 1 ) apnea was defined as a complete cessation of airflow for at least 10 seconds ; 2 ) hypopnea was defined as a reduction in airflow of at least 50% , a < 50% reduction associated with electroencephalographic arousals , or a > 3% decrease in oxygen saturation ; and 3 ) the apnea - hypopnea index ( ahi ) referred to the average number of apneas and hypopneas per hour of sleep .
subjects with an ahi 15 were assigned to receive cpap treatment and formed our study group .
subjects with an ahi<5 were defined as not having osas and were included in the control group .
patients with an ahi 515 were not eligible for cpap treatment and were excluded from the study analysis .
a high - resolution 12.0-mhz transducer ultrasound was used to measure brachial artery diameter at rest and during reactive hyperemia .
the assessment was carried out in a quiet room , with a stable temperature at 22 to 24c , by an experienced physician who was blinded to the patient s sleep recordings and blood analysis .
reactive hyperemia was induced by inflation of a blood pressure cuff placed on the lower part of the arm and inflated to 250 mm hg , followed by release after 5 minutes .
flow - mediated dilation ( fmd ) was calculated as the ratio of change in diameter ( maximum of 2 measurements  baseline ) over baseline value .
patients smoking status , body mass index ( bmi ) ( calculated as kilograms per meter squared ) , arterial blood pressure , and heart rate were recorded at baseline and 3 months after cpap treatment .
non - smokers were defined as those patients who had never smoked . furthermore blood analysis including : glucose , total cholesterol , low - density lipoprotein cholesterol ( ldl ) , high - density lipoprotein cholesterol ( hdl ) , triglycerides and crp ,
a standard statistical software package spss ( spss inc , chicago , il ) was used in the analysis .
difference regarding smoking status between osa and control subjects was assessed with the chi - square test .
the t test was used to detect differences in age , bmi , blood pressure , heart rate , lipidemic profile , sleep parameters , fmd and crp values between osa patients and control subjects .
the association between baseline crp and fmd values with age , bmi , and sleep parameters was assessed with the pearson correlation test .
paired - samples t test was used for comparison of the patients fmd and crp values at baseline and 3 months after cpap therapy .
ten patients had an ahi between 5 and 15 and were excluded from the study , 18 subjects were included in the control group ( ahi<5 ) , and 20 patients with ahi 15 formed the osas group in need of cpap treatment .
there were no significant differences between control subjects and osas patients with regard to the mean age , bmi , blood pressure , heart rate , lipid markers , glucose and smoking status .
compared to the controls , the osas group had significantly lower fmd values ( 6.720.86 vs. 9.591.15 ) and higher plasma crp levels ( 0.820.16 vs. 0.290.14 ) ( p=0.00 ) .
baseline fmd values were negatively correlated with age , bmi , ahi , dsi,% of time < 90% sa02 , and crp ( p<0.05 ) .
plasma crp values were positively correlated with bmi , ahi , dsi , and% of time < 90% sa02 ( p<0.05 ) ( table 2 ) .
after adjustment for age and bmi , fmd values retained their correlation with ahi ( b=0.08 , p=0.00 ) , dsi ( b=0.10 , p=0.00 ) and% of time < 90% sa02 ( b=0.28 , p=0.00 ) .
after adjustment for bmi , crp values also retained their correlation with% of time < 90% sao2 ( b=0.04 , p=0.00 ) , dsi ( b=0.01 , p=0.00 ) and ahi ( b=0.01 , p=0.00 ) .
out of 20 patients in the osas group , 6 failed to comply with the cpap treatment and returned the devise within 2 weeks . during the study period , patients bmi and smoking status did not change . in the group of patients who complied with the cpap treatment
, there was a significant increase in the fmd values ( 9.180.55 vs. 6.270.50 ) and a decrease in the levels of crp ( 0.670.15 vs. 0.840.18 ) ( p=0.00 ) .
no changes were detected in the group of patients who failed to comply with cpap ( figures 1 , 2 ) .
the measurement of endothelium - dependent dilation in response to reactive hyperemia is a non - invasive and validated method for the assessment of the endothelial function .
alterations in endothelium dependent dilatation have been documented in patients with coronary artery disease and diabetes and , recently , osas [ 1922 ] .
the regulation of vasomotor tone , as measured by the change in the forearm blood flow after transient ischemia , appears to be regulated by the availability of nitric oxide .
researchers have shown that in the osas the pathophysiologic stressors resulting from repetitive episodes of hypoxemia / reoxygenation downregulate the activity of the endothelial nitric oxide synthase and upregulate the expression of various vasoactive substances such as endothelin-1 and angiotensin ii [ 2325 ] . in this study
, fmd values appeared to be significantly higher in the control group compared to the osas patients , and were negatively correlated with the ahi , dsi and% of time < 90% sa02 . in accordance with our results ,
previous studies have also shown that endothelial dysfunction , as measured by fmd , was correlated with the severity of osas [ 911 ] .
furthermore , fmd values were negatively correlated with age . in a recent study by yim - yeh et al .
recently , data have emerged regarding the potential beneficial effects of cpap on endothelial function . a study by ip et al .
demonstrated that fmd was significantly improved after 4 weeks of cpap treatment , while bayram et al .
found that the improvement in the endothelial function was sustained after 6 months of treatment in complaint patients .
our results also confirm the beneficial role of cpap on fmd values after 3 months of treatment .
recently , a large amount of evidence has demonstrated the pivotal role of inflammation in cardiovascular disease . in view of this , c - reactive protein has gained increasing attention as an independent risk factor for coronary disease . in patients with osas ,
circulating levels of inflammatory markers appeared to be elevated , suggesting the presence of systemic inflammation . in agreement with previous reports , we showed that crp levels were positively correlated with the osas severity [ 1416 ] .
furthermore , crp was correlated with bmi , an observation consistent with the ability of adipose tissue to release certain cytokines , including interleukin-6 , and to stimulate crp synthesis .
although both fmd and crp are involved in the pathophysiology of cardiovascular complications , the association between these 2 parameters in osas remains elusive .
nevertheless , a study by nystrom et al in patients with coronary artery disease revealed a correlation between endothelial dysfunction ( measured with fmd ) and the levels of crp .
these discrepancies may be attributed to differences in methodology and inclusion criteria among published studies .
this study also demonstrated that appropriate use of cpap therapy can significantly decrease the levels of crp .
previous studies have also presented similar results , thus denoting the possible beneficial role of cpap in reducing systemic inflammation and cardiovascular risk in osas patients [ 3539 ] .
the study population consisted of patients with no prior history of cardiovascular or pulmonary disease , thus the study results should be interpreted with caution in patients beyond this particular group .
furthermore , female patients were excluded from the study analysis to avoid potential sex - based differences in hormone secretion that could affect both crp and endothelial function .
this single - center study demonstrated that male osas patients with no prior history of cardiovascular disease had significantly higher crp levels and lower fmd values compared to control subjects  a finding indicative of the possible presence of subclinical atherosclerosis and subsequent increased risk for developing cardiovascular disease .
appropriate cpap therapy improved both crp and fmd values , suggesting its potentially beneficial role in reducing cardiovascular morbidity and mortality in osas patients .
further well - designed prospective studies are needed to elucidate the effect of cpap on the reduction of cardiovascular risk .
 summarybackgroundcontinuous positive airway pressure ( cpap ) is the most effective method for treating obstructive sleep apnea syndrome ( osas ) and alleviating symptoms . 
 improved sleep quality with effective cpap therapy might also contribute to attenuated systemic inflammation and improved endothelial function , with subsequent reduction of cardiovascular risk.the aim of this study was to assess the effect of 3-month cpap therapy on brachial artery flow - mediated dilation ( fmd ) and plasma c - reactive protein ( crp ) levels in patients with osas.material/methodsour study group consisted of 38 male patients with no prior history of cardiovascular disease . 
 twenty patients with an apnea - hypopnea index ( ahi ) 15 were assigned to receive cpap treatment and 18 subjects with an ahi<5 were included in the control group . 
 six patients failed to comply with the cpap treatment . 
 measurement of fmd and blood analysis was performed at baseline and 3 months after cpap therapy.resultsbaseline fmd values were negatively correlated with age , bmi , ahi , dsi,% of time < 90% sa02 , and crp ( p<0.05 ) . 
 plasma crp values were positively correlated with bmi , ahi , dsi and% of time < 90% sa02 ( p<0.05 ) . in the group of patients who complied with the cpap treatment , there was a significant increase in the fmd values ( 9.180.55 vs. 6.270.50 ) and a decrease in the levels of crp ( 0.670.15 vs. 0.840.18 ) ( p<0.05).conclusionsappropriate cpap therapy improved both crp and fmd values , suggesting its potentially beneficial role in reducing cardiovascular risk in osas patients . 
Background
Material and Methods
Results
Discussion
Conclusions