The Association Of Metabolic Disorders In Obstructive Sleep Apnea Hypopnea Syndrome With Cardiovascular Disease And The Cardiac Autonomic Function

Part 1:Relationships between metabolic disorders and obstructive sleep apnea-hypopnea syndrome: Implications for cardiovascular disease risk Background: Previous studies have reported the effects of obstructive sleep apnea-hypopnea syndrome(OSAHS)and cardiometabolic disorders on cardiovascular disease(CVD),but associations between cardiometabolic biomarkers and two cardinal features of OSAHS(chronic intermittent hypoxia and sleep fragmentation)and their interactions on CVD in OSAHS populations remain unclear.Methods:We consecutively recruited 2022 patients from July 2013 to January2017 who were suspected to have OSAHSin the sleep center.A total of 1727 subjects were finally included in this observational study.Data on overnight polysomnography parameters,biochemical biomarkers,and anthropometric measurements were collected.The independent association between the metabolic biomarkers such as blood pressure,waist circumference(WC),fasting glucose,triglycerides(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C),and two cardinal features of OSAHS(AHI、MAI)were evaluated via the multivariate linear regression.Multiplicative and additive interaction effects were evaluated using binary logistic regression and Excel sheet procedure.Results: WC,mean arterial pressure,TG,fasting glucose and LDL-C were independently associated with apnea-hypopnea index(AHI)after adjustment for confounding factors(β=0.578,P < 0.001;β=0.157,P=0.001;β=1.003,P=0.019;β=0.648,P=0.012,and β=4.067,P=0.005,respectively).Furthermore,the interaction analysis revealed joint effects between hypertension,abdominal obesity,hyperglycemia,and LDL-C dyslipidemia and AHI on CVD.The relative excess risks of CVD due to the interactions with OSAHS were 2.06,1.02,0.48,and 1.42,respectively(all P<0.05).In contrast,LDL-C level and some MS components(WC,TG)were associated with MAI(β=0.324,P=0.001;β=0.991,P<0.001;β=4.444,P<0.001).However,there was positive interaction between LDL-C level and MAI on CVD(RERI=0.64,P=0.024).Conclusion: Our findings indicate that OSAHS and cardimetabolic disorders may potentiate their unfavorable effects on CVD.Thus,cardiometabolic disorders and OSAHS synergistically influence cardiometabolic risk patterns.Part 2: Glycolipid metabolism involved in the stage-special variation in cardiac autonomic function in obstructive sleep apneaBackground: Cardiac autonomic neuropathy(CAN)is common and causes significant cardiovascular disease(CVD)and mortality.Metabolic disorders(diabetes,dyslipidemia and obesity)are important pathogenic factors that cause CAN and cardiac dysfunction.These metabolic disorders,as obstructive sleep apnea-hypopnea syndrome(OSAHS)the common complications,whether involved in the cardiac autonomic nerves system(ANS)in OSAHS remained unclear.Methods: A total of 4152 subjects with suspected OSAHS were consecutively recruited in the sleep center from July 2010 to September 2017 and 3400 subjects were finally included.OSAHS was examined and quantified using the polysomnography(PSG).Biochemical and anthropometric variables were also collected.Heart rate variability(HRV)of electrocardiographic signal was used to evaluate cardiac ANS activity and oscillations.Abnormal heart rate alteration(MEANHR)or sympathovagal imbalance(LF/HF)or reduced HRV(standard deviation of all normal RR intervals)(SDNN)as the common CAN features.An initial analysis was conducted using the propensity score matching(PSM)to explore that whether metabolic factors involved on the HRV in OSAHS.Furthermore,ordinal logistic regression was used to examine the relationship between HRV and the metabolic factors.The dose-response relationships between CAN and OSAHS severity were evaluated via the nonlinear model of restricted cubic spline(RCS)analysis and the independent relationships between HRV indices and risk factors were evaluated by segmented multivariate linear regression(MLR).Results: The PSM analysis showed both metabolic disorders and OSAHS had significant relationship with HRV indices.The ordinal logistic regression suggested that the relationship may be nonlinear.OSAHS severity often was quantified by apnea hypopnea index(AHI),oxygen desaturation index(ODI),or the microarousal index(MAI).RCS analysis showed the CAN risk had nonlinear dose response with the fluctuation stage to rapidly change stage in OSAHS.After integrating the clinical definition and RCS selected knots,we obtained the new four OSAHS stages(10、30、55)(Stage I: AHI<10,Stage II: 10≤AHI<30,Stage III:30≤AH<55,Stage Ⅳ: AHI≥55).The associations of AHI with MEANHR(β=0.125,P<0.001),with LF/HF(β=0.049,P<0.001)remained significant(AHI≥55).The MAI had a positive association with SDNN in the last two stage(β=0.285,P<0.001;β=0.286,P <0.001).The segmented MLR showed that the metabolic biomarkers and the covariates were differentially associated with special HRV indices(MEANHR,SDNN,LF/HF)across different OSAHS stages.Insulin level was significantly associated with MEANHR in all stages,and fasting lipid such as total cholesterol(TC)was associated with MEANHR in the first stage(β=0.804,P<0.001).Metabolic biomarkers were negatively associated with SDNN(AHI<10 or AHI≥50,insulin:β=-0.691,P<0.05;β=-0.312,P<0.05;AHI≥30,TG:β=-2.218,P<0.01).Conclusions: Our study indicated that not only OSAHS(chronic intermittent hypoxia and sleep fragmentation),but also metabolic disorders play an important role in the CAN.This stage-special association demonstrated there was obviously complex feature of ANS in OSAHS,which may contribute to reveal the different risk factors in the different stages for individualized treatment.The treatment for metabolic disorders may be an indispensable component for prevention and treatment of CAN in OSAHS.