Research On The Clinical Features Of Acute Aortic Dissection And Its Correlation With Snps Of FBN1 Gene In China

Aortic dissection(AD) presents a sudden onset and high mortality based on population study. Over the ensuing two centuries from AD first described, the understanding of its classfication, pathophysiology, presentation, diagnosis and treatment has matured. With the improvement of diagnostic technology, the incidence of AD seems to be incressing. Because of the high morbidity, mortality and relative low incidence of acute aortic dissection(AAD), it’s necessary to collect data on larger number of patients over a short period of time to effectively describe the clinical manifestation, diagnosis, management, and outcomes of this aggressive disease. Therefore, the International Registry of Acute Aortic Dissection(IRAD) was established in 1996. IRAD is a multi-national registry designed to provide an unbiased representative population of patients with AAD. The data from IRAD were helpful in improving the diagnosis and management of AAD. However, most patients included in IRAD are from developed countries with advanced medical care. Its data can’t reflect the current reality of AAD patients in China. In order to analyze the clinical characteristics, diagnosis, management and outcomes of AAD in China, the first Registry of Aortic Dissection in China(Sino-RAD) including 15 large cardiovascular centers all over China was sponsored by Xijing Hospital. Sino-RAD can provide potentially useful insights into further understanding of the disease for cardiovascular disease. On the other hand, in recent years, the role of genetic factors on the pathogenesis of AD has drawn more and more attention. With the completion of human genome project as well as the development of molecular biology, especially molecular genetic technology, a large amount of variation related to complex diseases have been found through genome-wide association studies(GWAS). Therefore, the study of genetic susceptility on AD is helpful to determine the molecular mechanism of AD.Part one: Research on clinical fentures of AAD in ChinaObjective:The research was designed to analyse the clinical features included the subtype of AAD in China in order to better understand the risk factors, manifestation, diagnosis and treatment. Meanwhile, the data were compared with those from IRAD to find if there was difference in the two populations.Methods:The data of AAD were extracted from the database of Sino-RAD. The patients were enrolled in hospital from January 1, 2012 to December 31, 2013. Statistical analysis was used to analyse the epidemiological characteristics of demographic characteristics, clinical manifestation, diagnosis, treatment and the death rate. The published data from IRAD were used to compare the differences between the two groups.Results:Research one: A total of 1003 patients with AAD were enrolled in Sino-RAD from January 1, 2012 to December 31, 2013. The average age was 51.8 years with a male/female ratio 3.5:1. Compared to IRAD, AAD patients in Sino-RAD is significantly younger(51.8±11.4 vs 63.1±14.0, P<0.01). The male was more predominant(77.8% vs 65.3%, P<0.01). Moreover, patients with hypertension(58.7% vs 72.1%, P<0.01), arteriosclerosis(15.0% vs 31.0%, P<0.01), diabetes(1.5% vs 5.1%, P<0.01) and Marfan syndrome(2.5% vs 4.9%, P<0.01) in Sino-RAD were less. The incidence of pain was less(89.6% vs 95.5%, P<0.01). Fewer patients chose conservative treatment(27.4% vs 47.6%, P<0.01) and surgical treatment(25.0% vs 52.3%, P<0.01). The in-hospital mortality was lower(10.3% vs 27.4%, P<0.01). The mortality of surgical treatment was also lower(5.6% vs 26.7%, P<0.01), however, there was no statistical difference between the mortality of conservative treatment(28.0% vs 28.1%, P=0.99).Research two: A total of 430 patients with type A AAD were enrolled in Sino-RAD from January 1, 2012 to December 31, 2013. The average age was 50.5 years with a male/female ratio 3.2:1. Compared to IRAD, type A AAD patients in Sino-RAD is significantly younger(50.5±11.2 vs 61.1±14.1, P < 0.01). The male was more predominant(77.8% vs 65.3%, P<0.01). Patients with hypertension were less(51.4% vs 67.0%, P<0.01). There was no significance between patients with arteriosclerosis(30.7% vs 27.7%, P=0.24), diabetes(1.9% vs 4.0%, P=0.06), BAV(0.9% vs 4.2%, P=0.1) and Marfan syndrome(5.1% vs 6.2%, P=0.48). More patients in Sino-RAD chose conservative treatment(35.6% vs 17.8%, P<0.01) and less chose surgical treatment(52.6% vs 82.2%, P<0.01). The in-hospital mortality of type A AAD was lower(18.1% vs 30.6%, P<0.01). The mortality of conservative treatment(42.5% vs 58.2%, P<0.01) and surgical treatment(5.3% vs 24.7%, P<0.01) was lower.Research three: A total of 573 patients with type B AAD were enrolled in Sino-RAD from January 1, 2012 to December 31, 2013. The average age was 52.7 years with a male/female ratio 3.8:1. Compared to IRAD, type B AAD patients in Sino-RAD is significantly younger(52.7±11.1 vs 64.2±13.5, P < 0.01). The male was more predominant(78.9% vs 68.9%, P<0.01). Patients with hypertension(64.3% vs 77.9%, P<0.01), arteriosclerosis(3.1% vs 35.8%, P<0.01), diabetes(1.2% vs 6.4%, P<0.01) and Marfan syndrome(0.5% vs 2.7%, P<0.01) in Sino-RAD were less. Fewer patients in Sino-RAD chose conservative treatment(21.3% vs 71.1%, P < 0.01) and surgical treatment(4.4% vs 15.7%, P<0.01), more patients in Sino-RAD chose endovascular treatment(69.6% vs 13.3%, P<0.01). The in-hospital mortality(4.5% vs 12.3%, P<0.01), the mortality of surgical treatment(8.0% vs 30.8%, P<0.05) and endovascular treatment(2.5% vs 9.1%, P<0.05) was lower. There was no statistical difference between the mortality of conservative treatment(9.8% vs 8.8%, P=0.16).Research four: 430 patients with type A AAD(42.9%) and 573 patients with type B AAD(57.1%) were enrolled in Sino-RAD from January 1, 2012 to December 31, 2013. Compared to type B AAD patients, type A AAD was significantly younger(50.5±11.2 vs 52.7±11.1, P<0.01). More patients with type A AAD had a history of drinking(23.2% vs 14.6%, P<0.01) and/or smoking(43.1% vs 29.3%, P<0.01). Fewer patients with type A AAD had hypertension(51.4% vs 64.3%, P<0.01). More patients with type A AAD suffered from arteriosclerosis(30.7% vs 3.1%, P<0.01), Marfan syndrome(5.1% vs 0.5%, P<0.01) and BAV(0.9% vs 0.2%, P<0.01). More type A AAD suffered from back pain(71.9%) while more type B AAD suffered from back pain(80.8%). Of all type A AAD patients, 52.6% chose surgical treatment and the mortality of surgical treatment was 5.3%. 35.6% of patients chose conservative treatment and the mortality was 42.5%. Of all type B AAD patients, 69.6% chose endovascular treatment and the mortality was 2.5%. 21.3% of patients chose conservative treatment and the mortality was 9.8%.Part two: Research on correlation between SNPs of FBN1 gene and acute aortic dissection in ChinaObjective:Based on studies of the association between AAD and FBN1 SNPs in China, the research was designed to find the possible gene associated with the onset of AAD in China and detect whether there is a difference in FBN1 genetic susceptibility between Chinese and west AAD patients.Methods:The case group included patients with sporadic AAD(AAD with a family genetic history, caused by trauma or belong to part of a syndrome were excluded) from January 1, 2012 to January 1, 2014. The control group was from the health people. Genomic DNA was extracted from the anticoagulant blood. Eleven SNPs of FBN1 were chosen. The genotypes of the SNPs were analyzed by Mass ARRAY. The dominant model, recessive model and additive model were used to find the association between AAD and SNPs of FBN1.Results:In tota, 746 samples were included. The case group included 299 samples(male to female was 229 to 70). The control group included 447 samples(male to female was 296 to 151). According to the genotype study of 11 SNPs associated with FBN1, there was no significant difference between the case group and the control group. There was no finding in the dominant model, recessive model or additive model. Linkage disequilibrium analysis found that there was disequilibrium between rs1036477 and rs140598, rs4774517 and rs755251. MDR analysis found that there was strong interaction between rs1036477 and rs1042078, rs1036477 and rs4774517.Conclusions1. The average age of AAD patients in Sino-RAD were 51.8 years old with type A 50.5 years old and type B 52.7 years old. Compared with IRAD, AAD patients in Sino-RAD were significantly younger. Patients under 40 years old in Sino-RAD were more than those in IRAD which make it meaningful to prevent AAD patients in much younger age in China.2. The ratio of male patients in Sino-RAD(77.8%) was significantly greater than that in IRAD.3. The ratio of AAD patients in Sino-RAD with hypertension(58.7%), arteriosclerosis(15.0%), diabetes(1.5%) and Marfan syndrome(2.5%) was lower than that in IRAD, however, we also need positive prevention and treatment of hypertension, atherosclerosis and other risk factors of AAD.4. Chest pain(89.6%) is one of the main manifestations in AAD patients in Sino-RAD.5. Compared with IRAD, more type A AAD patients in Sino-RAD chose conservative treatment(35.6% vs 17.8%, P<0.01) and less chose surgical treatment(52.6% vs 82.2%, P<0.01). The mortality of conservative treatment(42.5%) was higher than surgical treatment(5.3%) which shows that actively surgical treatment could improve treatment effect.6. More patients in Sino-RAD chose endovascular treatment(69.6%). The mortality of endovascular treatment was lower than that in IRAD(2.5% vs 9.1%, P<0.05).7. MDR analysis of 11 SNPs associated with FBN1 found that there was strong interaction between rs1036477 and rs1042078, rs1036477 and rs4774517. People with rs1036477 and rs1042078 or rs1036477 and rs4774517 may predispose AAD. However, no exact association between the above SNPs of FBN1 gene and sporadic AAD was found in Chinese population which needs further research.