The Comparation Between HRMRI And Carotid Ultrasound Based On The Carotid Atherosclerosis And Its Relationship With APOE Gene Polymorphism

BackgroundStroke is the second most common cause of death and the third most common cause of disability in the world.And carotid atherosclerosis(CAS)was determined as one of the main sources of ischemic stroke,early detection of carotid lesions is beneficial for early intervention.In the process of development and progression of CAS,the intima-media membrane of the artery is the earliest involved site,and the growing of the intima-media thickness(IMT)is a marker of the development of atherosclerosis.Carotid ultrasound can evaluate the IMT precisely and provide hint of the extent of carotid stenosis,besides evaluating the stability of plaques based on the its echo and homogeneity.Therefore,in clinic,it is the first-line examination for screening the presence and nature of carotid plaques.High-resolution magnetic resonance imaging(HRMRI)is an emerging imaging technique that can more accurately identify the components and stability of plaque.Studies have shown that HRMRI has higher sensitivity and accuracy than carotid ultrasound in detecting ? 50% carotid stenosis.Most of the HRMRI studies were aimed at relatively advanced CAS which cause greater than 50% carotid stenosis and have a thickness of several millimeters.The comparative studies of small carotid plaque detection ability of the two examination are rare.Apolipoprotein E(Apo E)has three alleles: ?2,?3 and ?4.?3 is the wild type,?2 and ?4 are variant types,thus there are three protein isotypes: Apo E2,Apo E3 and Apo E4.Apo E is an important component in lipoproteins and functional lipoprotein in human body,which plays an important role in lipid metabolism.Previous studies have revealed that the three protein isotypes have different effects on lipid metabolism due to different structures.Approximately 7% of the variation in total lipids is due to APOE gene polymorphism.Because hypercholesterolemia is an independent risk factor for atherosclerosis(AS),the Apo E gene polymorphism is also likely to affect the development of AS through lipid metabolism.In fact,a number of domestic and foreign studies have focused on the relationship between APOE gene polymorphism and AS,but the results of these studies are not consistent.Besides,the pathway of APOE gene polymorphism to affect the development and progression of AS is still elusive.Many studies have demonstrated that APOE gene polymorphism may affect AS through lipid metabolism,but non-lipid pathways may also exist.AS is a disease caused by multiple genes and environmental factors,it is critical to explore the interaction effect of genetic and environmental factors on AS.Previous studies have revealed that the interaction effect of APOE gene polymorphism with gender and smoking may be related to AS progression.However,previous studies mainly targeted on foreign populations and the number of these studies is limited.In summary,our study is divided into two parts.Study one uses the results of carotid artery carotid ultrasound as control group,to explore the detection performance of HRMRI on carotid plaque(not limited to luminal stenosis?50%),in the purpose of providing a basis for the selection of clinical testing of CAS.Study two analyses the association between APOE gene polymorphism and the presence of CAS,and the possible interaction effect between APOE gene polymorphism and environmental factors on CAS,hoping it can provide new directions and individualized treatment options for the treatment of AS.Study OneExplore the carotid plaque detection ability of HRMRI compared to carotid ultrasoundObjectivesCarotid ultrasound was used as a control to evaluate the ability of HRMRI to detect plaque,which may provide a basis for selection of clinical methods for CAS detection.MethodsDuring the same hospitalization period,the carotid arteries which have both examined by carotid ultrasound and HRMRI were enrolled.Those with poor image quality of HRMRI were excluded.A total of 47 carotid arteries were enrolled in the end.If plaque was detected at the bifurcation of the common carotid artery,it was marked as positive,otherwise negative.If positive,the echogenic nature of the plaque and plaque thickness were recorded at the same time.The paired chi-square test was used to compare the difference between the results of the two tests,and then the t-test was used to compare the difference between plaque thickness of the HRMRI+ and HRMRIgroup,which were all positive on the ultrasound.ResultsThere was a significant difference in the results of plaque detection between HRMRI and ultrasound(P=0.001).The difference in plaque thickness between HRMRI+ and HRMRI-group showed that the plaque thickness of HRMRI-group was significantly smaller than that of HRMRI+ group(t=-3.213,P=0.003).The number of plaques which are positive for HRMRI and negative on ultrasound was 2,one of which was an isointensity plaque on fat-suppressed T1 WI,with a thickness of 2.9 mm,and the other one was a hypointensity plaque on fat-suppressed T1 WI with a thickness of 2.0 mm.ConclusionFor early CAS lesions,the sensitivity of HRMRI is weaker than carotid ultrasound,and the consistency of the two tests for advanced CAS lesions is higher.The two tests can be combined clinically to detect carotid plaque to improve the detection sensitivity and accuracy of component analysis.Study TwoThe effect of APOE gene polymorphism and its interaction with environmental factors on CASObjectiveClarify the association between APOE gene polymorphism and the presence of CAS,and the possible interaction effect of APOE gene polymorphism and environmental factors on CAS,hoping it can provide new directions and individualized treatment options for the treatment of AS.MethodsPatients with APOE genotype and carotid ultrasonography results during the same hospitalization period were enrolled,and excluded those with diseases affecting plasma lipid levels such as liver and kidney dysfunction,thyroid disease,tumor,chronic obstructive pulmonary disease,familial hyperlipidemia and long-term lipid-lowering drug users.A total of 337 people were enrolled.Then,the ?3 is the wild type,and the ?2 and ?4 are variant types,the ?2/4 type is not classified into any group because it carries the two variant types,thus it is excluded.322 people were enrolled in the end.The clinical data of patients enrolled includes: gender,age,blood lipids level,uric acid,history of diabetes,history of hypertension and history of smoking.The Hardy-Weinberg equilibrium test was performed to determine the genetic polymorphism balance of subjects.The differences in age,plasma lipid levels,uric acid,gender,hypertension,diabetes,and smoker distribution between different genotypes and CAS groups were analyzed.Binary logistic regression analysis was performed to correct other confounding factors and to determine whether APOE gene polymorphism and its interaction effect with environmental factors were independent risk factors for CAS presence.ResultsThe APOE genotype of 332 patients was tested by Hardy-Weinberg priciple,with a result of?2=3.125,P=0.537>0.05,which means the population enrolled were representative.In this study,the proportions of the five genotypes(?2/2,?2/3,?3/3,?3/4,?4/4)were: 0.3%,7.8%,77.7%,13.3% and 0.9%,respectively.The proportions of the three alleles(?2,?3 and ?4)were: 4.22%,88.25%and 7.53%,respectively.There was no significant difference in the distribution of APOE gene phenotypes and gene alleles between different CAS groups(gene phenotypes: ?2=3.832,P=0.429;alleles: ?2=0.806,P=0.688).Compared with the plaque positive group,the plaque negative group had lower age,and lower hypertensive and male patients proportion(P<0.05).There was no significant difference in the distribution of E2(?2+:?2/2,?2/3),E3(?3/3),E4(?4+:?3/4,?4/4)between the two groups(?2=2.077,P=0.354).The Apo B of ?2+(E2)was lower than ?2-(E3 and E4)(P<0.05),and the LDL level of ?2+ was lower than ?2-(P=0.056),but it had not reached statistical significance.In the total population,before and after adjusting the blood lipid levels(excluding TC after collinearity diagnosis),binary logistic regression analysis showed that age-growing,male,and hypertension history were independent risk factors for the presence of CAS(P<0.05).After stratification according to gender and smoking history,the female smokers(n=6)were excluded,and before and after blood lipids were adjusted(excluding TC),in male smokers(n=135)and female non-smokers(n=125),age-growing was a consistent risk factor for the presence of CAS(P<0.05),and APOE gene polymorphism showed no significant effect on the presence of CAS.In male non-smokers(n=71),age-growing was also an independent risk factor for CAS before adjusting the blood lipids and the genetic polymorphism of APOE had a significant influence on the presence of CAS,with the risk of CAS for E2 was significantly lower than that of E3 group(OR: 0.055(0.007,0.458)),E4 and E3 groups showed no significant difference.After adjusting for blood lipid levels(excluding TC),high LDL level was a protective factor for the development of CAS.Apo E gene polymorphism still had a significant impact on the presence of CAS.The risk of CAS for E2 is significantly lower than that of E3 group(OR: 0.011(0.000,0.227)),and the influence strengthened compared with before the adjustment of blood lipids,E4 and E3 groups still had no significant difference on the risk of CAS.ConclusionAge-growing,hypertension history and male are independent risk factors for CAS development,but APOE gene polymorphism has no significant correlation with the presence of CAS.The stratification analysis based on gender and smoking history suggests that among non-smokers,compared to ?3,?2 has a protective effect on men but no protection upon women.In males,?2 has a protective effect against non-smokers but that protection is not significant for smokers compared to ?3.After adjusting for blood lipids,the protection effect is enhanced,indicating that the effect of APOE gene polymorphism on the presence of CAS does not completely rely on the lipid metabolism pathway.Whether there is an interaction effect between APOE gene polymorphism and gender in smokers,and whether APOE gene polymorphism interacts with smoking in women still need further exploration in the future.