| Objective:Aortic dissection(AD)is a catastrophic vascular disease with complex clinical manifestations,high mortality and poor prognosis.With the continuous progress of AD-related research,a large variation in age distribution,in-hospital mortality,and disease prognosis between AD in China and western countries was observed.The most prominent manifestation is that Chinese patients are relatively young,which the average age of AD patients in China is nearly 10 years younger than patients in western countries.Among those young patients,the proportion of hypertension was higher but the proportion of Marfan syndrome and traumatic AD was relatively lower than that reported abroad.A large number of studies have shown that obstructive sleep apnoea(OSA)is one of the risk factors for type B aortic dissection(TBAD)in young patients with obesity.Therefore,it is necessary to explore the effect of OSA on aorta in patients with TBAD.An important issue facing the world in the diagnosis and treatment of TBAD at nowadays is the lack of a feasible screening method in disease prevention.If some biomarkers can be found to early screening in high-risk populations,it will have important clinical significance.In addition,according to the characteristics of AD in China,it is also necessary to screen patients’metabolites in blood and the microecosystem in gut based on systems biology.Methods:(1)A retrospective clinical study was conducted to confirm that the clinical characteristics of AD patients in China are significantly younger and with high complication rate of OSA.(2)A case control study was performed to clarify the effect of OSA on the vascular morphology changes in TBAD patients,which were divided into groups with and without OSA.(3)Based on proteomics technology,OSA populations was set as the high-risk group of TBAD,the differential proteins in serum were screened,and the biomarkers which can be used for high-risk group screening were identified.(4)Based on metabonomics technology and high-throughput sequencing of the 16S ribosomal RNA gene of intestinal flora,the serum differential metabolites and intestinal differential flora of TBAD patients were screened to clarify the issue in metabolic level and whether there is imbalance in intestinal flora structure,and further clarify the correlation between the two system differences.Results:(1)The results of retrospective clinical studies shows that the incidence of AD in China is mainly in the age group of middle-aged population,and the average age is lower than that reported abroad.The complication rate of hypertension in young and middle-aged AD patients is higher than that in foreign people which in the same age group.But the population with traumatic AD and congenital vascular disease is significantly lower than that in foreign countries.(2)TBAD patients had a high prevalence rate of OSA(64.3%),and the young and middle-aged TBAD patients were generally obesity(BMI=27.6±4.2 kg/m~2).Compared with the elderly TBAD patients,the prevalence rate of moderate and severe OSA was higher(31.5%vs 23.7%,P=0.037)in young age patients.(3)The image differences related to LAEs between TBAD patients with and without OSA included the maximum aortic diameter at onset(37.3±3.9 vs.40.3±4.5 mm,p<0.001),the FL diameter of the proximal descending thoracic aorta(16.0±6.8 vs.20.3±4.7 mm,p<0.001),and the proportion of the FL that was partially thrombosed(39.2 vs.64.1%,p=0.004).Additionally,in the multivariable analysis of patients with OSA,the risks of an aortic diameter≥40 mm,a proximal descending aorta FL≥22 mm and a partially thrombosed FL were 4.611(95%CI:1.796–11.838,p=0.001),2.544(95%CI:1.050–6.165,p=0.039),and 2.565(95%CI:1.167–5.637,p=0.019),respectively,after adjustment for confounding factors.Trend tests showed that the risks of an aortic diameter≥40 mm and a partially thrombosed FL increased with increasing OSA severity.(4)Proteomic results showed that 239 differential proteins were screened out from TBAD patients,including 208 up-regulated proteins and 31 down-regulated proteins.The differential proteins were mainly related to cytoskeleton and blood microparticles.Cluster analysis showed that the pathogenesis of TBAD was mainly related to immune pathway and endocrine metabolic pathway.(5)By further analyzing the proteomic results and comparing TBAD patients with OSA,filamin-a,transgelin-2,profilin-1,nidogen-1 and other biomarkers were selected as screening indicators for high-risk population of TBAD.The diagnostic efficacy of filamin-a and transgelin-2 in high-risk population(people with OSA)were 0.849(95%CI:0.706-0.992,P=0.001)and 0.831(95%CI:0.677-0.985,P=0.002),respectively.The diagnostic efficacy of nidogen-1 and transgelin-2 in TBAD patients was 0.967(95%CI:0.919-1.000,P<0.001)and 0.948(95%CI:0.882-1.000,P<0.001),respectively.(6)Based on metabonomics and 16S high-throughput sequencing of intestinal flora,the results showed that cyclic lysophosphatidic acid of lysophosphatides(LP)was highly expressed in serum in patients with TBAD(VIP=1.15,p=1.67E-05,FC=13.73).TBAD patients have imbalance of intestinal flora structure,mainly manifest as down-regulation of bacteroidetes and up-regulation of firmicutes.Correlation analysis showed that there was a strong correlation between LP metabolites and oscillobacter(Spearman coefficient=0.80,p<0.001),suggesting that the occurrence of TBAD is closely related to the imbalance of intestinal flora.Conclusion:Our study shows that the clinical characteristics of young and middle-aged TBAD patients in China are significantly different from those in foreign countries.TBAD patients with moderate to severe OSA have aortic dilatation in different parts of the aorta.OSA is an independent risk factor for multiple imaging signs related to lateaortic events,suggesting that OSA is an important factor affecting the prognosis ofTBAD patients.Filamin-A,transgelin-2,profilin-1,nidogen-1 can be used as screening for people with high risk of TBAD.The increase of serum cyclic hemolytic phosphate level in patients with TBAD related to the imbalance of intestinal flora structure... |
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