The Study On Risk Factors Between Patterns Of Symptomatic Intracranial And Extracranial Artery Atherostenosis

Background and PurposeLarge artery atherosclerosis (LAA) is the most important cause of ischemic stroke (IS). According to the location of cervicocerebral atherosclerosis, the stenotic lesions were divided into three patterns, namely isolated intracranial (IC) atherosclerosis, isolated extracranial (EC) atherosclerosis, and combined IC and EC atherosclerosis. Treatment modality and prognosis may differ among patients with different patterns of atherosclerosis. Moreover, stroke recurrence and long-term prognosis may be not the same between patients with single vessel lesions and multivessel lesions even though both the two lesions belong to the intracranial lesions, because the latter has a worse outcome. Therefore, if screening the risk factors and serum markers of predictors for the locations and the extent of the LAA, and actively intervening them, it will provided an important basis for stratified prevention and treatment in patients with LAA-related stroke.Some studies have confirmed that the distribution of LAA differs by race and ethnicity. EC atherosclerosis is common in Whites whereas IC atherosclerosis is frequent in Asians. Chinese studies have showed the prevalence of IC stenosis in33%-50%of patients with ischemic stroke or transient ischemic attack (TIA). The reason and mechanisms of racial differences is unclear. Some studies have tried to attribute ethnic differences in the distribution of cerebral atherosclerosis to differences in the prevalence of the classic risk factor profiles or lifestyle among different ethnic groups. However, these studies have not achieved consistence about any risk factor.Recent studies have shown that symptomatic IC atherosclerosis in Asians are related with Metabolic Syndrome (MetS), but the mechanism of impact of MetS on IC atherosclerosis remains unclear. Adiponectin (ADIPOQ) is an adipocyte-specific protein secreted by fat cells, which mediates a range of anti-inflammatory, anti-atherosclerosis and insulin sensitivity. Therefore, some researchers think that one of the mechanisms of MetS attributed to IC atherosclerosis may be mediated by ADIPOQ. However, it is unclear whether the MetS and ADIPOQ can predict the location and extent of IC/EC atherosclerosis. Moreover, these studies have focus on Korea and Europe groups, but there are no published data on Chinese Han population-study.Based on Nanjing stroke registry system, the study was aimed to analyze distribution characteristics of symptomatic IC or EC or both IC and EC atherosclerosis patterns in patients with IS or TIA; to explore the independent risk factors of the three patterns respectively, including traditional risk factors, MetS, and serum ADIPOQ levels; and to further find the predictors for the location of cerebral atherosclerosis and the extent of IC atherosclerosis.MethodsWe retrospectively analyzed the data in Nanjing Stroke Registry system of consecutive hospitalized patients with acute IS or TIA between April2009to October2010. All enrolled patients underwent complete imaging work-up, including DWI sequences, MRA and CTA, or DSA. According to clinical characteristics and angiogram outcomes, all patients with IS or TIA were divided into four groups, including non-stenosis group (small artery occlusion and undetermined etiology), IC, EC, and combined IC and EC stenosis group. IC/EC stenosis is defined as the vessel lumen diameter loss more than50%or occlusion. This study focuses on the following four aspects: ①The533patients from the Nanjing Stroke Registry system were categorized as the aid of a modification of the Trial of Org10172in Acute Stroke Treatment (TOAST) classification. We analyzed the epidemiology of stroke subtypes and especially explored location and distribution of LAA in301patients, including261patients with IS and40patients with TIA.②The489patients with IS and TIA met the inclusion criteria were classified into four groups, namely IC stenosis (n=140), EC stenosis (n=66), combined IC and EC stenosis (n=95), and no stenosis group (n=188). Served no-stenosis group as reference group, independent associations of conventional risk factors with each subtype group of LAA were evaluated. In a direct comparison between the EC, IC, and both IC and EC stenosis groups, predictors for location of cerebral artery were also explored.③Using the same analytic method above-mentioned, the frequency of MetS and its components were compared among subtypes. The478patients were enrolled into this analysis, after11patients were excluded due to lack of diagnosis in one or several components of MetS. To define the MetS, we used revised version of the National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP III) in2005. According to the median numbers of stenoses, the139patients with IC stenosis were divided into single-vessel disease group and multivessel disease group (≥2stenoses). Predictors of multivessel disease were evaluated.④Using clinical, imaging, and laboratory data,343consecutive patients with IS were categorized as five groups:small artery occlusion (n=97), cardioembolism (n=26), IC stenosis (n=90), EC stenosis (n=50), and combined IC and EC stenosis (n=80). Independent associations of serum ADIPOQ levels with the location of cerebral stenosis were evaluated, and the relationship of ADIPOQ levels with the extent of IC stenosis was also analyzed especially.Results①LAA was the most common subtype (49.0%) according TOAST system. Of all261patients with LAA-related stroke, IC stenosis was the most frequent (22.9%), followed by combined IC and EC stenosis (15.4%), and EC stenosis at least (10.7%). Multivessel lesions (≥2stenoses) in IC stenosis group were found in183patients (60.8%) and single vessel lesions in118patients (39.2%).②When compared with non-stenosis group, the EC stenosis group was independently associated with older age, hyperglycemia and low HDL cholesterol, and IC stenosis group was associated with hypertension, diabetes and hyperglycemia, whereas older age and hypertension were the independent risk factors for combined IC and EC stenosis group. Furthermore, in a direct comparison between isolated EC and isolated IC and combined IC and EC stenosis group, male sex was an independent marker for EC stenosis group. The age of IC stenosis group was the youngest among the three groups and diabetes had more predictive value in IC group than in EC group. Additionally, hypertension and high LDL cholesterol levels were the independent predictors for combined IC and EC stenosis group.③In all patients with symptomatic cerebral large artery atherosclerosis or no stenosis, the total prevalence of MetS was57.5%; IC stenosis group had a highest prevalence of MetS (70.5%), followed by combined IC and EC group (67.4%), EC stenosis group (51.5%), and non-stenosis group (45.1%)(P<0.001). After adjusting for age, male sex, hypertension, diabetes, hypercholesterolemia, smoking, history of previous stroke or TIA and history of coronary disease, MetS was independent risk factor for IC stenosis group. Among the MetS components, high blood sugar was associated with IC stenosis group, and low HDL levels was an independent risk factor for isolated EC group and combined EC and IC stenosis group. However, in multivariate logistic regression analysis among the three subtypes of LAA, we did not observe that MetS and its components were determinants of location for atherosclerosis in IC or EC or combined IC and EC arteries. On the contrary, the present of MetS and the more number of MetS complements (more than2components) were an independent predictor of a greater extent of IC stenosis.④Median S-adiponectin levels differed by acute stroke subtypes:highest in the cardioembosim group (6.19,5.03-7.04ug/mL), lowest in the small artery occlusion group (5.43,4.78-5.96ug/mL), and intermediate in LAA group (P<0.001). The serum levels of adiponectin were different depending on the LAA subtypes:median adiponectin of EC stenosis group was6.02(5.30-7.00ug/mL), which was significant higher than that of combined IC and EC stenosis group (5.68,4.65-6.51ug/mL; P=0.027). Those in IC stenosis group were intermediate (5.80,5.11-6.67ug/mL) After adjusting for age, male sex, hypertension, diabetes, hypercholesterolemia, smoking, history of previous stroke or TLA, history of coronary disease and MetS, we observed that low serum adiponectin levels was not a determinant of location for atherosclerosis in IC or EC or combined IC and EC arteries in multivariate logistic regression analysis.Ninety patients with144IC stenoses were documented. Thirty-nine (43.3%) patients had two or more stenoses (greater-extent group). Patients in the highest adiponectin quartile had a lower risk of a greater extent than those in the lowest quartile (OR0.242,95%CI0.062-0.967). A negative correlation was found between adiponectin concentration and the number of stenoses (r=-0.248, P=0.018). Moreover, adiponectin level decreased gradually with the number of stenoses (P=0.02). A multiple logistic regression model identified low adiponectin (adjusted OR=3.207,95%CI=1.103-9.324, P=0.032) and MetS (adjusted OR=21.513,95%CI=3.821-121.120, P=0.001) as independent markers of a greater extent of IC stenoses. Interestingly, the highest number of IC stenoses was observed in MetS patients with a low adiponectin (P＜0.001).ConclusionThe results indicate that in consecutive patients with acute ischemic stroke from the Nanjing Stroke Registry system, LAA is the most common subtype, accounting for about50%; in the LAA subtypes, IC-LAA is the most frequent subtype, followed by CC-LAA and EC-LAA. This study confirms that some of the classic atherosclerotic risk factors can predict the distribution and location of IC or EC or combined IC and EC. When compared with non-stenosis group, MetS was not an independent risk factor for EC or combined IC and EC stenosis but for IC stenosis group. Furthermore, MetS and low serum adiponectin levels were also not determinants of location for atherosclerosis in IC or EC or combined IC and EC arteries but the predictive markers for a greater extent of IC stenosis. According to our results, if screening the risk factors and the special serum marker above-mentioned predicting the locations and the extent of the LAA, and actively intervening them, it will provided an important basis for stratified prevention and treatment in patients with LAA-related stroke.