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A Study in the Gated Blood Pool Imaging Determining Cardiac Function, the Predictable Cytokines Surveying in Serum of Cardiovascular Complication and the Genes Polymorphisms in the β1 Adrenergic Receptor of the Patients with Obstructive Sleep Apnea Hypo

Author: WangZuo
Tutor: LiuZhuoLa
School: Shanxi Medical
Course: Department of Respiratory Medicine
Keywords: Obstructive sleep apnea hypopnea syndrome (OSAHS) Cardiac gated blood pool imaging Dubotamin stress test Pro-inflammatory cytokines: interlukin-1β,18 Anti-inflammatory cytokine: interlukin-10 Soluble CD40 ligand(sCD40L) Insulin-like growth factor 2(IGF-2) β1-adrenorceptor Arg389Gly polymorphism
CLC: R56
Type: PhD thesis
Year: 2008
Downloads: 265
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Abstract


Background:Obstructive sleep apnea hypopnea syndrome(OSAHS) is a highly prevalent sleep disorder and its evidence is up to 3~4%in the population.Untreated OSAHS worsens the quality of life.The current knowledge on the OSAHS suggests that it is an independent risk factor for many kinds of diseases.The major health risk in OSAHS patients,however,is strongly associated with the cardiovascular events,and careful case-control studies have confirmed the blood pressure,coronary artery disease and myocardial infarction have increased notably. Considering the importance of earlier diagnose and prevention of the complication of the cardiovascular events in OSAHS,we have tried a series researches on the organic,molecular and genetical levels and hope to achieve a new method in diagnosing and treating the cardiovascular complication of patients with OSAHS.Aim:①Using the gated cardiac blood pool imaging to determine the possible risks of cardiovascular events so as to interpose earlier and decrease the fatal occurrences before the clinical appearance of the cardiovascular complication of patients with OSAHS.②After measuring the serum levels,we found the factors to diagnose the cardiovascular complication of patients with OSAHS early.We discussed the role of the inflammation reaction in the development of the cardiovascular complication of the patients with OSAHS and are trying to find an effective method to diagnose and treat the disease.③In view of the OSAHS has been shown to aggregate significantly within families,we analysed the impact of the genotype of theβ1-adrenoreceptor R389G polymorphism in order to better understanding theβ1 adrenergic receptor’s role in the stages of cardiovascular complication.Methods:Using the cast-control studies to do the following research.①To evaluate the heart function and the blood flow of myocardial by using the gate cardiac blood pool and dobutamine stress test myocardial perfusion imaging in 17 normal controls and 46 patients with OSAHS and without known heart disease.②The study population comprised OSAHS patients (n=56),the sonrings(n=10) and control subjects(n=15).We measured serum levels of pro-inflammation cytokins,including IL-β1,IL-18,anti-inflammation cytokine IL-10,soluble CD40 ligand(sCD40L) and insulin-like growth factor-2(IGF-2).All blood samples were determined by enzyme-linked immunosorbent assays(ELISA).③The present study in a cohort of 192 untreated OSAHS patients and 96 health control.We analysed the impact of the different genotypes of theβ1-adrenorceptor R389G polymorphism on the increase of cardiovascular complication morbidity and compared with the different genotypes carriers between groups.Results:①Except of the rEF2-4 the other indexs of the ventricular’s function chang in severe OSAHS were detected(P<0.05) at ECG-gated blood pool imaging.It points out that the heart function has been changed before the complication appeared.After dobutamin stress testing, every groups of the OSAHS patients have ventricular functional reduces,including reflecting the ventricular contracting functional LVEF,PER and reflecting relaxation functional PFR,1/3FF(P<0.0001).At same time,the rEF reflecting myocardial blood supply have obvious changed, coming down going to the tip of heart(rEF3) and the front wall(rEF4).That prompt the OSAHS patients whose the ventricular reserve function come down obviously before clinical cardiovascular complication appears.The part of the myocardial blood supply deficiency has appeared.②Increase in OSAHS patient serum pro-inflammation factor interleukin- 18(IL-18)’s levels than control group is obvious,difference has significant(P<0.05),and it is positively related with the apnea hypopnea index(AHI) and the longest apnea time(Tmax)(r=4.873,r = 1.863,P is equal<0.0001).But the serum levels of pro-inflammation factor interleukin-1βis not difference in every groups(P>0.05).It point out IL-1βhas not play obviously effect.③Anti-inflammation factor IL-10 serum levels in OSAHS patient obvious deceased and accompanied withthe patient’s condition.It has negatively linked to AHI and longest apnea time (Tmax)(r=-0.906,r=-0.608,P<0.0001).④The IGF-Ⅱlevel increases obviously in OSAHS patient serum,have notable difference comparing with control group(P<0.05),and discover IGF-Ⅱlevel has altitude to rectify correlativity with AHI(r=0.261,P=0.016) and negatively linked to SaO2min(r=-5.147,P<0.0001).⑤SCD40L level increases obviously in OSAHS patient serum comparing with control group (P<0.05).Correlativity analysis demonstrates positively relevance with AHI(r = 0.039,P =0.001).⑥The study ofβ1 adrenceptor polymorphism found that the SaO2min,Tmax and T<90%of CC genotype group have obvious difference comparing with the other genotypes.It reaches (21.77±8.98) occurrence rate higher than other two kinds genotypes occurrence rate(14.04±8.16,13.85±8.05,t=2.863 and t=4.361 respectively,P<0.05).At same time the CC is correlate to the drop of LVEF and PER(r=0254,t=0.218,P<0.05).After the dobutamine stress testing CC is correlated to the deceased of 1/3FF(r=0.294 P<0.01) and rEF3(r=0.744 P<0.01) and rEF4(r=0.500 P<0.01).Discovering prompts CC genotype having higher cardiovascular disease occurrence rate.Conclusion:①The parts of myocardial ischemia can be quantified and heart dysfunction be detected in the severe OSAHS patients without known heart disease using the gated blood pool SPECT and dobutamine stress test myocardial perfusion imaging.It indicates that the early damage of heart is appeared before clinical symptom.②The balance of pro-inflammatory and anti-inflammatory cytokines play a important role in prediction of risk of cardiovascular events.Plasma interlukin-18 levels,a pro-inflammatory cytokine,be closely related to body mass index and early damage of cardiovascular.It also promoted cardiovascular complications in OSAHS patients.The level of IL-10,a anti-inflammatory,is decreased and the protective effect against atherogenesis is reduced. Inflammatory markers such as IL-18 and IL-10 are taken into account in prospective risk,but a proper balance between pro- and anti-inflammatory cytokines may be a mechanism of cardiovascular outcomes in patients with OSAHS.③As a member of the tumor necrosis factor(TNF) the soluble CD40 ligand(sCD40L) plays an major role in the inflammatory response as promoter.Many studies support the nation that sCD40L takes a pivotal role in the various stages of atherosclerosis.Serum sCD40L levels in OSAHS patients were significantly higher.This result demonstrated that sCD40L has an independent prognostic value in cardiovascular disease.④Insulin-like growth factor-Ⅱ(IGF-Ⅱ) is closely related to hypertension.The level of IGF-Ⅱin OSAHS is increased.It may produce an effect on hypertension outcome of OSAHS.⑤Theβ1-adrenorceptor R389G polymorphism was associated with an increased risk of cardiovascular disease outcome with OSAHS.The R389 variant ofβ1-AR gene was a susceptible gene to heart problem.Subjects with allele CC ofβ1-adrenorceptor R389G showed higher incidence of heart function changes and myocardial ischemia compared with others allele.

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