| Background:The carotid artery is located between the aortic arch and the intracranial arterial circle of Willis.It is the only way to support intracranial blood supply,with respect to it,pathological changes at this position will directly or indirectly lead to the occurrence of a variety of cerebrovascular diseases.For example,the relationship between carotid artery stenosis(CAS)and ischemic stroke has been a hot research topic in recent years.Carotid artery morphological variations(CAMV)is another common imaging finding,which means that the artery is featured by its length is different from its normal path,with the emergence of various morphological changes,such as Tortuosity,Kinking or Coiling.Although CAMV had been confirmed in a number of studies that can cause various nervous system diseases,including ischemic stroke,carotid artery dissection and decline in cognitive function,and can significantly increase the risk of open-neck surgery and carotid artery intervention,the mechanism and risk factors of this kind of pathological change are still not clear even to nowadays.There has been a confrontation between two views of congenital variation and acquired changes.However,the vast majority of scholars agree that CAMV is a vascular degenerative change caused by the combined effects of various acquired factors on congenital susceptible individuals.Most noteworthy,there is still lacking of a large sample epidemiological survey on the characteristics and risk factors of CAMV in Han population at present,and the analysis of the occurrence and development of CAMV from the perspective of genetic polymorphism is also rarely reported.White matter lesion is also referred to as the Leukoaraiosis(LA),which is another common radiologic finding in the middle aged and elderly population.Although many individuals with LA can be asymptomatic for a long time,there is substantial evidence from prospective studies that LA may lead to an increased risk of stroke and recurrent stroke.Moreover,the occurrence and progression of LA is also significantly associated with clinical symptoms,such as cognitive impairments,gait disorders,urinary incontinence,and depression in some elderly patients.Up to now,cerebral chronic ischemia is one of the most possible pathogenesis for development of LA.Although most studies suggested that hemisphere hypoperfusion injury is caused by cerebral small-vessel pathologic changes in LA patients,some researchers continue to focus on the correlation between LA and extracranial large-vessel disease.For example,it has been recently reported that CAS may be a risk factor for LA.CAMV may also lead to chronic cerebral blood supply insufficiency by hemodynamic alteration.Hence,the relationship between CAMV and transient ischemic attack or stroke has been previously discussed.However,it is unclear whether CAMV could increase the risk of developing LA,and there are no relevant literature reports on relationship between CAMV and LA.Based on the above understanding,this study aimed to investigate the characteristics and risk factors of CAMV in the area of the Han population,especial for internal carotid artery kinking(ICK).Another target is to understand whether the polymorphism of COL3A1 gene was associated with the occurrence of ICK by using the polymerase chain reaction(PCR).In addition,a case-control method was also applied to analyze whether the internal carotid artery morphological changes may increase the risk of leukoaraiosis in the ipsilateral cerebral hemisphere.Section One Characteristics and risk factors of carotid artery kinkingBackground:CAMV,which means that the artery featured by its length is different from its normal path,with the emergence of various morphological changes,such as Tortuosity,Kinking or Coiling.Previous studies have indicated that CAMV may lead to various neurological disorders including ischemic stroke,so it is important to understand the characteristics and risk factors of CAMV in Chinese Han population.Methods:From November 1,2013,to January 30,2014,consecutive inpatients of our department who need to perform skull CTA for diagnosis were prospectively enrolled in this study,and patients with CAMV were further divided into three types according to the CTA imaging findings,including the Tortuosity(T),Kinking(K)and Coiling(C).The clinical information of patients was collected simultaneously.Furthermore,characteristics of various types of CAMV were statistically described,and the main demographic characteristics and vascular risk factors of the individuals without ICK(none-K group),with unilateral ICK(unilateral K group)and with bilateral ICK(bilateral K group)were compared and analyzed,the Logistic regression analysis was further conducted to confirm whether they could increase the risk of ICK.Results:1.Within the study period,902 consecutive patients who met the inclusion criteria were selected.The mean age of the study population was 60.2±13.3 years,and 53.7% were women.In the cohort,the prevalence rates of kinking were 9.0% in common carotid artery,21.0% in internal carotid artery and 31.6% in vertebral artery.The prevalence rates in three type arteries gradually increased for all age groups up to 70-79 years and decreased for patients aged 80 years and older.2.In the cohort,the prevalence rates of kinking for patients aged 60 years and older had significantly higher than patients aged under 60 years(P < 0.001),whether they are in common carotid artery,internal carotid artery,or vertebral artery.Also,the prevalence rates of kinking for female patients had significantly higher than male patients in the three type arteries(P < 0.001).3.In 902 cases,the prevalence rates of bilateral and unilateral ICK were 13.5% and 15.0% respectively,and there was no significant difference between the two groups(P > 0.05).Among the 135 patients who have unilateral ICK,the cases of left kinking were obviously higher than the cases of right kinking(P < 0.01).4.The univariate analysis in two groups for major demographic and clinical data indicated the 257 patients with ICK had significantly higher mean age and higher frequencies of females,body mass index,hypertension and diabetes mellitus than the 645 patients without ICK.However,patients without ICK had higher frequency in status of daily drinking.Furthermore,multivariate logistic regression analysis showed age(OR =1.05,95% CI: 1.03-1.06),gender(OR =1.40,95% CI: 1.27-1.58),body mass index(OR =1.08,95% CI: 1.03-1.13)and hypertension(OR =1.43,95% CI: 1.02-2.00)were significantly associated with an increased risk of ICK(P < 0.05).5.The comparison between bilateral ICK group and unilateral ICK group in major demographic and clinical data demonstrated the bilateral ICK group only had significantly higher frequency of females than the unilateral one(P < 0.01).No significant differences were observed between the two groups for the following parameters: mean age,body mass index,hypertension,diabetes mellitus,and hyperlipidemia frequencies,current smoking and daily drinking statuses,in univariate analysis(P > 0.05).In addition,using unilateral ICK as reference,multivariate logistic regression analysis indicated female gender(OR =1.34,95% CI: 1.18-1.65)was the only risk factor associated with the bilateral ICK.Conclusions:1.The prevalence rates of ICK gradually increased for all age groups up to 70-79 years and decreased for patients aged 80 years and older,and it is characterized by elderly group higher than younger group,female group higher than male group and left group higher than right group.However,there is no significant difference between the unilateral and bilateral group.2.The patients with ICK had significantly higher mean age and higher frequencies of females,body mass index,hypertension and diabetes mellitus than those without ICK.However,patients without ICK had higher frequency in status of daily drinking.Furthermore,multivariate logistic regression analysis indicated age,gender,body mass index and hypertension were significantly associated with an increased risk of ICK.3.Using unilateral ICK as reference,the patients with bilateral ICK only had significantly higher frequency of females than those with unilateral ICK.In addition,multivariate logistic regression analysis indicated female gender was the independent risk factor associated with bilateral ICK.Section Two Correlation between COL3A1 gene polymorphisms and ICKBackground:Type III collagen is encoded by the COL3A1 gene,and its quantity and quality are the biological basis for maintaining the elasticity of the artery wall and resisting the expansion.Previous studies have shown that COL3A1 gene mutation and polymorphism can lead to a variety of vascular diseases characterized by changes in arterial morphology,such as aneurysm and arterial dissection.Therefore,it is worthwhile to explore whether COL3A1 gene polymorphism is related to CAMV.Methods:The clinical information of inpatients from June 1,2012,to January 30,2013 who need to take the CTA for diagnosis and agree to donate the blood samples were analyzed retrospectively.The cohort was divided into patients with ICK(ICK group)and those without ICK(non-ICK group)according to the CTA image.The ligase detection reaction was performed to investigate genotype and allelic frequency of the COL3A1 gene.Compare to the frequency discrepancy of SNP between the ICK group and non-ICK group.Multivariate logistic regression analyses were performed to detect the association of ICK with COL3A1 gene SNPs.Results:1.In the study,a total of 597 subjects were enrolled.The mean age was 67.83 ± 9.4,53.7%were females.Among the participants,242 were selected for ICK group and 355 were included for non-ICK group.The ICK group had significantly higher mean age and higher frequencies of females,body mass index and hypertension than non-ICK group.2.More than 98.8% samples were genotyped successfully for each SNP.Every group conformed to the Hardy-Weinberg equilibrium(P > 0.05).3.As for rs2138533,the CC,CT and TT genotype frequency were 61.1%,35.2% and 3.7% in non-ICK group,whereas 50.4%,41.7% and 7.9% in ICK group respectively.The distribution of genotypes was significantly different between the two groups(χ2 = 9.238,P = 0.010).The C and T allele frequency were 78.7% and 21.3% in non-ICK group whereas 71.3% and 28.7% in ICK group,showing significant difference(χ2 = 12.562,P = 0.003).No statistical differences in genotype or allele frequency were observed in rs12693525,rs1800255,rs11887092,rs10497695,rs13028444 and rs2203601 between non-ICK group and ICK group.4.After adjustment for demographic and vascular risk factors,CT genotype(OR:1.47,95% CI:1.01-2.12)and TT genotype(OR:3.05,95% CI:1.37-6.82)were associated with higher risk of ICK independently.Moreover,In dominant model,CT/TT genotype was 1.61 times more likely to have ICK than CC genotype.Conclusions:1.In Chinese population,the rs2138533 in COL3A1 gene might be relate to ICK,and T allele was significantly associated with an increased risk of ICK.2.The present study failed to find out any association between ICK and other SNPs in COL3A1 gene including rs12693525,rs1800255,rs11887092,rs10497695,rs13028444 and rs2203601.Section Three Correlation between ICK and leukoaraiosisBackground:White matter lesion is also referred to as the Leukoaraiosis(LA).Although it is suggested the pathogenesis of LA is hemisphere hypoperfusion injury which caused by cerebral small-vessel pathologic changes in most articles,some studies continue to focus on the correlation between LA and extracranial large-vessel disease.ICK may also lead to chronic cerebral blood supply insufficiency by hemodynamic alteration.Hence,it is important to discuss whether ICK could increase the risk of developing LA in the ipsilateral hemisphere.Methods:From November 1,2013,to January 30,2014,consecutive inpatients aged 50 years and older of our department who need to perform skull CTA and MRI for diagnosis were prospectively enrolled in this study.CAMV were classified into tortuosity,kinking,and coiling by CTA while the presence and severity of LA were assessed by the age-related white matter changes rating scale for MRI.The prevalence rates of CAMV as well as the demographic and vascular risk factors were compared between the patients with LA(LA group)and those without LA(non-LA group).Logistic regression analyses were performed to examine the relationship between all types of CAMV and LA.Results:1.The mean age of the 702 subjects was 65.5±9.5 years,and 56.4% were women.A total prevalence rate of LA in 1404 hemispheres was 49.9%,and the rates of mild LA,moderate LA and severe LA were 34.1%,11.4%and 4.4% respectively.The prevalence rates of tortuosity,kinking and coiling were 43.9%,25.3% and 1.1% in 1404 carotid arteries.2.No matter it is left or right LA,The LA group had significantly higher mean age and higher frequencies of hypertension,diabetes mellitus,coronary artery disease,CAS(P < 0.05),and ipsilateral kinking than non-LA group(P < 0.001).However,no significant difference was observed between the 2 groups in gender,body mass index,hyperlipidemia,current smoking,daily drinking,ipsilateral tortuosity and coiling(P>0.05).3.After adjustment for demographic and vascular risk factors,multivariate logistic regression analysis indicated advanced age,hypertension and ipsilateral carotid kinking was associated with an increased risk of LA(P < 0.001).4.The prevalence of left carotid kinking in patients of non-LA,moderate LA and severe LA were 18.9%、30.8%、42.2% and 48.4%.The prevalence of right carotid kinking in patients of non-LA,moderate LA and severe LA were 14.6%、29.4%、39.0%and 43.3%.The prevalence of carotid kinking gradually increased with advancing grades of LA in both left and right hemisphere(P < 0.001).5.A multinomial logistic regression was performed with adjustments for age,gender,hypertension,diabetes mellitus,coronary artery disease and CAS.The results showed the ORs with left hemisphere LA were 1.93(95% CI: 1.29–2.90)for mild,3.68(95% CI: 2.05–6.63)for moderate and 5.34(95% CI: 2.28–12.52)for severe,whilst the ORs with right hemisphere LA were 2.22(95% CI: 1.45–3.40)for mild,3.39(95% CI: 1.83–6.28)for moderate and 5.52(95% CI: 2.22–13.73)for severe in ipsilateral ICK individuals.Conclusions:1.The prevalence of ICK in LA group was significantly higher than in non-LA group,but no differences were found between two groups in prevalence of carotid tortuosity and coiling.2.After adjustment for demographic and vascular risk factors,multivariate logistic regression analysis indicated advanced age,hypertension and ipsilateral ICK was significant associated with an increased risk of LA.The individuals with ICK were 2 to 3 times more likely to have LA than those without ICK.3.The prevalence of ICK gradually increased with advancing grades of LA in both left and right side.The multinomial logistic regression indicated the odds of LA in individuals with ICK increased with advancing grades of LA. |
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