MR Imaging Characteristics And Associated Risk Factors Of Bilateral Carotid High-risk Plaques And Their Relationships With Clinical Symptoms

Stroke is one of the major causes of death worldwide due to its high morbidity,disability rate and mortality.Previous studies have demonstrated that high-risk atherosclerotic plaque(HRP)of carotid artery is one of the major etiology for ischemic stroke.Histologically,the main features of HRP include intraplaque hemorrhage(IPH),large lipid-rich necrotic core(>40% of wall area)(LRNC)and fibrous cap rupture(FCR).Atherosclerosis is a systemic disease,which often involves multiple vascular beds.Patients with multivascular atherosclerotic plaques have a higher risk of cardiocerebrovascular events compared to those with single vascular plaque.Studies have shown that a substantial number of patients have bilateral carotid HRPs.It has been established that age,gender,hypertension,hyperlipidemia,diabetes and smoking are important risk factors for HRP formation in carotid artery.However,there lacks evidence for the risk factors of bilateral carotid HRPs.A number of prospective studies have proved that HRPs were strongly associated with increased risk of cerebrovascular events.However,not all HRPs led to ischemic cerebrovascular events.Previous studies using magnetic resonance imaging(MRI)reported that the prevalence of T1-highsignal intensity which represents IPH was 8.1% in asymptomatic carotid atherosclerotic patients,and this prevalence would be higher in the elderly patients(17.9%)or those with moderate stenosis(47%).It has been shown that carotid HRP can effectively predict the risk of ischemic stroke.Nevertheless,the relationship between bilateral carotid HRPs and cerebrovascular symptoms is unclear.Based on above background,in this thesis,we conducted the following three studies:In the first part of the thesis,we compared clinical risk factors among patients with bilateral carotid HRPs,unilateral carotid HRP,and patients without carotid HRP.This study will provide a clue to the risk factors of bilateral carotid HRPs and the potential targets for clinical treatment.In the second part of the thesis,we compared the plaque characteristics between symptomatic and asymptomatic sides in patients with bilateral carotid HRPs using MR vessel wall imaging.This study will provide a basis for the prediction of cerebrovascular symptoms in bilateral carotid HRPs patients.In the third part of the thesis,we compared the plaque characteristics of patients with bilateral carotid HRPs between patients with recurrent stroke and those without recurrent stroke using MR vessel wall imaging.We will also determine the association between HRP plaque features and recurrent stroke in patients with bilateral carotid HRPs.This study will provide the evidence for predictive value of HRP characteristics for the risk of recurrent stroke in bilateral carotid HRPs patients.Part 1: Risk Factors for Bilateral Carotid High-Risk Plaques Determined by MR Vessel Wall ImagingPurpose: This study compared clinical risk factors in patients with bilateral carotid HRPs,unilateral carotid HRP,and patients without carotid HRP.Methods: A total of 585 patients(mean age,61.8±10.0 years;430 males)were recruited from a cross-sectional,multicenter study of CARE-II(Chinese Atherosclerosis Risk Evaluation)and underwent carotid multi-contrast MR vessel wall imaging.Clinical characteristics including age,gender,body mass index(BMI),smoking,blood pressure,hypertension,hyperlipidemia,levels of TC,HDL,LDL,and TG,diabetes,family history of cardiovascular disease,history of coronary heart disease,antihypertensive or statin therapy were collected.Clinical characteristics were compared using One-Way ANOVA and Kruskal-Wallis test for continuous variables and Chi-square analysis or Fisher’s exact test for categorical variables among carotid HRPs,unilateral carotid HRP,and non-carotid HRP groups.Logistic regression was conducted to determine the association between grouping variable and clinical characteristics.Results: Of the 585 included patients,80 had bilateral carotid HRPs,95 had unilateral carotid HRPs,and 410 had no HRPs,respectively.Bilateral HRPs patients were more likely older(P <0.001),male(P <0.001)and showed greater BMI(P = 0.045),lower diastolic blood pressure(P = 0.018),TC(P <0.001),LDL(P <0.001),HDL(P = 0.031)and more antihypertensive therapy(P = 0.006),statin therapy(P <0.001)than patients without HRP.The level of TC(P <0.001)and LDL(P <0.001)of bilateral HRPs patients were significantly lower than that of unilateral HRPs patients.Multivariate logistic regression showed that the differences in age(OR: 1.09,95% CI: 1.05-1.12,P <0.001),male(OR: 11.12,95% CI: 3.85-32.16,P <0.001),antihypertensive(OR: 2.26,95% CI: 1.14-4.48,P = 0.020),statin therapy(OR: 2.96,95% CI: 1.67-5.25,P <0.001),diastolic blood pressure(OR: 0.97,95% CI: 0.95-1.00,P = 0.021)、TC(OR: 0.62,95% CI: 0.47-0.81,P = 0.001)and LDL(OR: 0.56,95% CI: 0.41-0.77,P <0.001)between bilateral HRPs and without HRP groups,and age(OR: 1.04,95% CI: 1.00-1.09,P = 0.041),TC(OR: 0.49,95% CI: 0.34-0.69,P <0.001),LDL(OR: 0.50,95% CI: 0.34-0.74,P = 0.001),and diabetes mellitus(OR: 0.47,95% CI: 0.24-0.93,P = 0.030)between bilateral and unilateral HRP groups remained statistically significant.Conclusion: The present study found that age,gender,diastolic blood pressure and lipid level might be risk factors for bilateral carotid HRPs.Part 2: Comparing the MR Imaging Characteristics of Symptomatic and Asymptomatic Carotid High-risk PlaquesPurpose: To compare the plaque characteristics between symptomatic and asymptomatic sides in patients with bilateral carotid HRPs using MR vessel wall imaging.Methods: A total of 67 patients(mean age: 65.8±7.7 years,61 males)with recent stroke or TIA(within 2 weeks after onsets of symptoms)and bilateral carotid HRPs were included and underwent carotid MR vessel wall imaging.The plaque burden including lumen area(LA),wall area(WA),total vessel area(TVA),maximum wall thickness(WT),normalized wall index(NWI)and luminal stenosis was evaluated.Presence and the size of lipid-rich necrotic core(LRNC),intraplaque hemorrhage(IPH),juxta luminal IPH and/or thrombus,calcification,juxta luminal calcification,and fibrous cap rupture(FCR)were assessed and compared.Paired t-test,Signed-rank Wilcoxon test or Mc Nemar’s test were used to compare the MR imaging characteristics of HRP between symptomatic side and asymptomatic side.Multiple Logistic regression was used to further analyze the difference of MR imaging characteristics of HRP between symptomatic and asymptomatic HRP after adjusting plaque burden.Results: Compared with asymptomatic sides,symptomatic HRPs showed smaller mean LA(P <0.001),greater mean WA(P =0.028),greater maximum WT(P =0.006),larger mean NWI(P <0.001),and greater stenosis(P =0.002).Symptomatic HRPs showed greater LRNC volume(P = 0.003),IPH volume(P = 0.030),Max%LRNC(P = 0.002),Max%IPH(P = 0.022),cumulative slices of LRNC(P = 0.005),and more juxta luminal IPH and/or thrombus(P =0.007)than asymptomatic ones.After adjusted for the NWI and stenosis,the differences in juxta luminal IPH and/or thrombus(P = 0.007)and FCR(P = 0.022)between symptomatic HRPs and asymptomatic HRPs remained statistically significant.Conclusion: For bilateral carotid HRPs patients,symptomatic HRPs are more likely to have larger plaque burden,more juxta luminal IPH and/or thrombus,and FCR compared to asymptomatic ones.Our findings suggest that in patients with bilateral carotid HRPs,plaques with larger plaque burden and more high-risk features may be at higher risk of cerebrovascular symptoms.Part 3: The Relationship between MR Imaging Characteristics of Bilateral Carotid High-risk Plaques and Recurrence of StrokePurpose: To compare the plaque characteristics between patients with and without recurrent stroke in patients with bilateral carotid HRPs using MR vessel wall imaging.The relationship between HRPs characteristics and recurrent stroke was also determined.Methods: A total of 71 subjects(mean age: 66.4±7.3 years,66 males)with recent stroke or TIA(within 2 weeks after onsets of symptoms)and bilateral carotid HRPs were included and underwent carotid MR vessel wall imaging.The plaque burden including LA,WA,TVA,maximum WT,NWI and luminal stenosis was evaluated.Presence and the size of lipid-rich necrotic core(LRNC),intraplaque hemorrhage(IPH),juxta luminal IPH and/or thrombus,calcification,juxta luminal calcification,and fibrous cap rupture(FCR)were assessed and compared.Independent sample t test,Mann-Whitney U test or Chi-square test were used to compare the differences of MR image characteristics of HRPs between recurrent group and non-recurrent group.Multivariate Logistic regression was used to analyze the relationship between MR imaging characteristics of HRP and recurrent stroke after adjusting confounding factors.Results: Compared the HRPs in non-recurrent stroke group,HRPs in recurrent stroke group showed greater WT(P = 0.010),NWI(P = 0.003)and stenosis(P = 0.001).HRPs in recurrent stroke group had significantly higher prevalence of juxta luminal IPH and/or thrombus(52.6% vs.19.2%;P = 0.006)and juxta luminal calcification(42.1% vs.9.6%;P = 0.004).After adjusted for age,gender and BMI.mean NWI(OR: 1.12,95% CI: 1.03-1.21,P = 0.008),luminal stenosis(OR: 1.04,95% CI: 1.02-1.07,P = 0.001),juxta luminal IPH and/or thrombus(OR: 5.15,95% CI: 1.59-16.63,P = 0.006),and juxta luminal calcification(OR: 9.35,95% CI: 2.24-38.94,P = 0.002)were found to be associated with recurrent stroke.After further adjusted for NWI and luminal stenosis,juxta luminal IPH and/or thrombus(OR: 5.33,95%CI: 1.30-21.83,P = 0.020)and juxta luminal calcification(OR: 7.70,95%CI: 1.37-43.22,P = 0.020)showed significant association with recurrent stroke.Conclusions: For patients with bilateral carotid HRPs,those with larger plaque burden,more juxta luminal IPH and/or thrombus,and juxta luminal calcification in HRPs were more likely to have recurrent stroke.