The application and development of imaging play a crucial role in the study of the mechanism of ischemic stroke in CAD patients. The stenosis or occlusion of the lumen caused by the arterial dissection could result in hemodynamic disturbance and the hypoperfusion in the corresponding blood supply area would lead to cerebral ischemia in the end. However, the fact that the formation of thrombus secondary to the damaged artery endothelium caused thromboembolism by the detachment of thrombus fragments is the major mechanism of cerebral infarction [7-8]. Oliveira et al [9] demonstrated that high intensity transient signals (HITS) known as microembolic signals, were frequently seen downstream of dissected arteries in patients with CAD by transcranial Doppler sonography (TCD) monitoring, supporting that artery to artery embolism was an important mechanism of ischemic stroke in CAD patients. In a small sample study [10], HITS were found not only in the middle but also in the posterior cerebral artery. In addition, the type of cerebral infarction shown by neuroimaging of CAD patients also supported microembolism as the main mechanism of stroke. The CT or T2-weighted imaging examination of extracranial internal carotid artery dissection patients with ischemic stroke found that the majority of them were cortical infarctions, large subcortical infarctions, or mixed cortical-subcortical infarctions, and the prevalence of infarctions in the border zone, which is closely related to hemodynamic disorders, was only 3% to 16%. Audrey Morel et al [11] conducted a retrospective study to identify the most likely mechanism of stroke combining the cerebrovascular ultrasound, stroke brain MRI, and cervical MRA. Of 172 consecutive cervical artery dissection patients, 100 patients had acute ischemic stroke on DWI, which was attributed to a thromboembolic mechanism in 85 patients, a hemodynamic mechanism in 12 patients and a mixed mechanism in the remaining patients. And there were no differences between anterior and posterior circulation stroke in the proportion of embolic and hemodynamic stroke.
Cervicocerebral artery dissection mainly cause ischemic events. In the present study, 80.8% (42/52) of artery dissection in the anterior circulation and 62.8% (49/78) of artery dissection in the posterior circulation presented with ischemic events, and there was a significant difference in dissection site, in contrast with the previous studies [12-13], in which they speculated that artery dissections in the posterior circulation could more frequently be subintimal, expanding toward the arterial lumen, thus resulting in a higher prevalence of ischemic stroke, while artery dissections in the anterior circulation could more frequently be subadventitial, expanding externally, leading to aneurysmal dilatations, which were more likely to rupture followed by subarachnoid hemorrhage (SAH). Consistent with our study, the prior report from Taiwan found that ischemia was the predominant presentation of anterior circulation artery dissection [14]. One could hypothesize that it could be ascribed to ethnic difference so that Chinese patients with CAD carry unique clinical characteristics different from western counterparts. Hence CAD patients located in the anterior circulation may be at increased risk for ischemic events and should be paid more attention on in order to prevent the poor outcome. Furthermore, our findings still should be reconfirmed through a national, multicenter, consecutive, prospective cohort study from China in the near future [1].
High-density lipoprotein is recognized as the "scavengers" of blood vessels. The most important function is to reversely transport cholesterol from the peripheral tissues and cells to the liver and then convert it into bile acids or remove it directly from the intestines through bile. Rohatgi et al [15] demonstrated a negative correlation between the inverse cholesterol transport function of HDL and the risk of atherosclerotic cardiovascular disease through a population-based cohort study. Patients with severe stenosis or complete occlusion of the internal carotid dissection artery are more likely to have cerebral ischemic symptoms [16], whereas patients with mild stenosis or non-stenosis have more local signs and symptoms. The results of this study showed that high-density lipoprotein level in CAD patients were inversely related to the occurrence of ischemic event. We hypothesized that HDL reduced the degree of stenosis in the lumen of dissected artery by exerting its function of anti-atherosclerosis, thereby alleviating hypoperfusion in the blood supply area of the brain. In addition, HDL had a protective effect on vascular endothelial cells [17-19], and serum HDL level was negatively correlated with platelet activity in the human body [20], and HDL had anticoagulant function as well. Therefore, HDL could reduce the formation of local thrombus in the dissected artery through the above-mentioned complex mechanisms, thus preventing the occurrence of ischemic stroke due to artery to artery embolism.
An observational study [16] suggested that hypercholesterolemia occurred more often in internal carotid artery dissection with than without ischemic events, which may result in endothelial dysfunction and then enhance thrombus formation. Although hypertension is an independent risk factor for stroke, it is undefined whether CAD patients with hypertension have a high risk for stroke. A case-control study from Italy discovered that hypertension had a more pronounced effect on cervical artery dissection patients with cerebral infarction as opposed to others without [21]. But in the present study, we observed no significant association between ischemic events and hypercholesterolemia or hypertension. In consequence, further prospective population-based studies are necessary to explore the predictors of ischemic events in CAD patients.
This study had several limitations as follows. The number of our cases was limited. There would be recall bias in history of recent infection in the previous week. All patients were enrolled from the first affiliated hospital of zhengzhou university, a tertiary teaching hospital, with an underlying referral bias. Moreover, CAD patients with mild local symptoms may not seek medical attention, which was likely to increase the proportion of CAD patients with ischemic events.