Biomarkers And Endothelial Function Of Obstructive Sleep Apnea With Different Clinical Phenotypes

PART 1:Study on biomarkers,vascular endothelial function and arterial Stiffness of OSAObjective:Obstructive sleep apnea(OSA)is a heterogeneous disorder,and it is difficult to assess OSA with polysomnography alone comprehensively.The purpose of this study was to evaluate OSA with biomarkers,vascular endothelial function and arterial stiffness in young and middle-aged men without severe complications,and to determine the value of these markers.Methods:We recruited consecutively 75 young and middle-aged male subjects without serious complications including uncontrol led hypertension,coronary vascular diseases and diabetes in the sleep clinic of Peking union medical college hospital.All participants finished clinical evaluation,biomarkers tests,reactive hyperemia index(RHI)and arterial stiffness marker augmentation index(AIx)measured by peripheral arterial tonometry(PAT).Using apnea hyponea index(AHI)?5 times/h and AHI?15 times/h as cut-offs respectively for grouping OSA,and analyze the clinical characteristics of each marker and OSA and the correlations between different groups.Results:A total of 75 subjects were included,including 42 patients with moderate and severe OSA.Moderate and severe OSA patients had higher ALT,glucose,HbA1C,TG,hsCRP,tumor necrosis factor alpha(TNF-?)and vascular endothelial growth factor(VEGF)levels,lower HDL levels and higher AIx75 compared with the control group,while there was no statistical difference in RHI between the two groups.After controlling for age,13MI,hypertension,smoking,rhinitis,blood lipid,blood glucose,uric acid,and renal function,TNF-? was negatively correlated with the average SpO2(r=-0.258,P=0.043),RHI was related to the proportion of REM stage(r=0.306,P=0.016),but had no correlation with clinical characteristics,OSA severity and hypoxia(P>0.05).Arterial stiffness AIx75 was positively correlated with arousal index(AI)(r=0.289,P=0.023),but the correlation between AIx75 and AHI did not reach statistical significance(r=0.248,P=0.052).Mul tiple stepwise regression analysis showed that TNF-?was positively correlated with N1%(B=0.166,P=0.025),and negatively correlated with average SpO2,HDL,and TG(B=-0.398,P=0.034;B=-5.263,P=0.002;B=-0.657,P=0.013).RHI was positively correlated with hypertension and REM%(B=0.275,P=0.013;B=0.026,P=0.003);AIx75 was positively correlated with age,AI and TC(B=1.201,P<0.001;B=0.547,P=0.001;B=6.036,P=0.004).Conclusion:There are some systematic inflammatory biomarkers with mild abnormalities in young and middle-aged patients with moderate and severe OSA without severe complications.TNF-? and arterial stiffness marker AIx is independently associated with OSA.The relationship between RHI and OSA remains to be determined.In the future,we can integrated these markers together to guide OSA precise therapyPART 2:Biomarkers and vascular endothelial function of OSA with different clinical phenotypesObjective:OSA has dif ferent clinical phenotypes,and the comprehensive evaluation of OSA combined with clinical phenotypes is crucial to develop precise medicine of OSA.It is not clear whether different clinical phenotypes of OSA have different biomarkers,vascular endothelial function and arterial stiffness.Methods:On the basis of previous studies,the middle-aged and young male patients with AHI?5 times/h without significant complications were analyzed.According to the ESS scores,subjects were divided into the OSA without sleepiness group and OSA with sleepiness group.Biomarkers,endothelial function and arteries stiffness were compared.After developing clinical phenotype by hierarchical cluster analysis,we compared the biomarkers,vascular endothelial function and arterial stiffness of different OSA subtypes.Results:Among 57 males without serious complications,the average SpO2,and LSpO2 of the sleepiness group were lower than those of the control group,and ET-1 was higher than that of the control group.There was no significant difference in AHIbetween the two groups.Multivariate regression analysis showed that sleepiness was associated with LSpO2 and VEGF(OR=0.894,95%CI 0.814-0.981,P=0.018;OR=0.980,95%CI 0.962-0.999,P=0.040),but not related to ET-1,RHI and AIx75.According sympto ms,subjects can be divided into the medium symptom group(40 cases,70.2%),daytime sleepiness group(9 cases,15.8%),mild group(14.0%).There were significant difference between three groups in ALT,TG(P=0.041,P=0.002,respectively).ALT is 22.75(12.13,48.53)U/L,56(35.5,66.00)U/L,28(19.25,40.50)U/L in three groups,respectively.TG is 1.31(0.97,2.08)mmol/L,2.78(1.63,5.61)mmol/L,2(1.49,3.99)mmol/L in three groups,respectively.There were no significant differences between three groups in AHI,glucose metabolism,inflammatory markers,endothelial function and arterial stiffness.Conclusion:Different level of sleepiness in OSA subjects had different hypoxia burden although there was no difference in AHI,vascular endothelial function and arterial stiffness.Different clinical phenotypes of OSA have different liver function and triglyceride levels despite no differences in AHI,vascular markers.In the future,we need to further expand the sample size to search for effective biomarkers of OSA in different clinical phenotypes to promote precise medicine in clinical practice.