Mechanisms of Ischemic Stroke Secondary to Large Artery Atherosclerotic Disease - ScienceDirect

Neuroimaging Clinics of North America

Volume 17, Issue 3, August 2007, Pages 303-311

Neuroimaging Clinics of North America

https://doi.org/10.1016/j.nic.2007.03.001 Get rights and content

Atherosclerotic occlusive disease of the cervical and intracranial arteries leads to ischemic stroke through two separate, but interrelated, mechanisms: local thrombosis or embolism from atherosclerotic plaque, and hemodynamic failure (low flow). In this article, the author discusses the evidence linking these two mechanisms with cerebral ischemia, and the evidence for the synergistic effects of thromboembolism and impaired hemodynamics. An understanding of these two mechanisms is important because these mechanisms provide the rationale for revascularization for patients who have atherosclerotic stenosis or occlusion. In addition, the biologic imaging of atherosclerotic plaques and hemodynamic assessment eventually will play an important role in stratifying patient risk and guiding physiologically based patient selection for intervention.

Section snippets

Cerebral ischemia

Brain tissue requires the continuous delivery of oxygen and glucose to maintain normal neuronal function. When an artery becomes occluded, the brain supplied by that artery may become ischemic, depending on the adequacy of flow through collateral channels. The cortical surface of the brain often, but not always, has an abundant network of pial collaterals connecting arterial branches. Penetrating arteries into the white matter do not have the benefit of such a network [8]. The survival of brain

Compensatory mechanisms to low flow

Patients who have symptomatic atherosclerotic occlusive disease may have reduced flow to the distal territory, owing to poor sources of collateral flow. Conversely, many patients who have occlusive disease, even complete occlusion, have normal flow, owing to good collateral sources [14]. When perfusion pressure (the difference between mean arterial pressure and the venous backpressure) falls in any arterial territory, the brain and brain vasculature may compensate through two mechanisms (Fig. 1

Thromboembolic mechanisms

Thromboembolism from atherosclerotic plaque is the primary mechanism of stroke in most patients who have LAA. The current concept of the vulnerable plaque is accepted widely and is discussed fully elsewhere in this issue. Plaque rupture may lead to platelet aggregation, local thrombosis, or thromboembolism. Plaque material, itself, may embolize [26].

Most of the current knowledge regarding the biology of atherosclerotic plaque and the cascade of events that lead to plaque rupture and platelet

Primary low-flow mechanisms

Low-flow states are common in patients who have symptomatic LAA [34], [35]. When compared with asymptomatic patients who have similar degrees of stenosis, symptomatic patients, as a group, show evidence of hemodynamics impairment (discussed later) [36]. Approximately one half of patients who have complete carotid artery occlusion and prior ischemic symptoms have compensatory mechanisms to low flow in the distal circulation [34]. The presence of hemodynamic impairment in these patients is

Association of low flow and stroke risk

Although hemodynamic or low-flow stroke is unlikely to be a primary cause of stroke in patients who have atherosclerotic disease, strong empiric evidence suggests that hemodynamic impairment is a powerful predictor of stroke risk. Several well-designed prospective studies of hemodynamic status and stroke risk in patients who have LAA have been performed and many have shown a strong association between pre-existing hemodynamic impairment and stroke risk [14]. The strongest associations have been

Synergistic effects of embolic and hemodynamic factors

Although low flow is infrequent as a primary cause of stroke in patients who have LAA, it is associated strongly with stroke risk. Several lines of evidence support a synergistic effect of embolic and hemodynamic factors. As mentioned earlier, patients who have symptomatic carotid stenosis, as a group, are much more likely to have impaired vasodilatory responses than asymptomatic patients who have similar degrees of atherosclerotic carotid stenosis. Low flow increases infarct volume in animal

Future research directions

The development of molecular imaging methods and tools of hemodynamic assessment have great potential to advance our knowledge of stroke risk in patients who have atherosclerotic occlusive disease. In addition, the ability to identify subgroups of patients with higher or lower natural history risks may allow us to address more specific therapies and improve patient outcome. At present, the primary criteria for determining eligibility for intervention are primitive (ie, the degree of stenosis

Summary

In conclusion, the mechanism of stroke in patients who have atherosclerotic occlusive disease of the carotid artery and its intracranial branches includes both thromboembolic and hemodynamic mechanisms. Either may occur in isolation, but most strokes likely represent a synergistic effect of both mechanisms. In the future, identification of hemodynamic and thromboembolic risk factors will play an important role in selecting patients for medical or endovascular intervention, based on differential

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Arterial stiffness is a risk factor for stroke [36]. Stiffening of the arteries may result in the development of atherosclerotic carotid plaques [37] and increased risk of large artery stroke [38]. Impaired fasting glucose status is also associated with arterial endothelial dysfunction and intima-media thickening [39], which is related to stroke risk [40,41].
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Eighteen cohort studies involving 2,555,666 participants were included. The pooled relative risk for the high-versus-low categories was 1.79 (95% CI: 1.68–1.91) in all people, and 1.16 (95% CI: 1.11–1.21) in non-diabetic people. In addition, there was a non-linear relationship between fasting blood glucose and stroke risk. The incidence of stroke was reduced to its lowest point when fasting blood glucose level was 70–100 mg/dL.
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Background and Purpose: Perioperative stroke remains a devastating complication after cardiac surgery and is associated with significant morbidity and mortality. Despite the significant contribution of stroke to perioperative mortality, risk factors for perioperative stroke-related mortality have not been well characterized. Our aim was to identify independent predictors of perioperative stroke-related mortality after cardiac surgery, using the Pennsylvania Health Care Cost Containment Council (PHC4) database which provides information on cause of death. Methods: We retrospectively examined patient medical records from 2012 to 2014 of 3345 patients (ages 18-99) who underwent a cardiac surgical procedure and suffered perioperative (30-day) mortality. Perioperative stroke-related mortality was identified by International Classification of Diseases, Tenth Revision, Clinical Modification cause of death codes. We performed Fisher's exact test and multivariate analysis to identify comorbidities that independently predict perioperative stroke-related mortality. Results: After controlling for all variables with multivariate analysis, we found that patients with carotid stenosis were 4.9 (adjusted odds ratio [aOR], 95% confidence interval [CI] 1.8-12.8) times more likely to die from a stroke than from other causes, when compared to patients without carotid stenosis. Other independent predictors of perioperative stroke-related mortality included in-hospital stroke (aOR 108.8, 95%CI 48.2-245.9), history of stroke (aOR 17.1, 95%CI 3.3-88.4), and age ≥ 80 (aOR 4.9, 95%CI 2.1-11.2). Conclusions: This is the first study to establish carotid stenosis, among other comorbidities, as an independent predictor of perioperative stroke-related mortality after cardiac surgery. Understanding risk factors for mortality from stroke will help enhance the efficacy of preoperative screening, intraoperative neurophysiological monitoring, and potential treatments for stroke. Interventions to manage carotid stenosis and other identified risk factors prior to, during, or immediately after surgery may have the potential to reduce perioperative stroke-related mortality after cardiac surgery.
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Natural history data suggest that the risk of recurrent ischemia in patients with atherosclerotic VA stenosis is highest during the first days and few weeks [21]. The pathophysiological mechanisms underpinning recurrence, including artery-to-artery embolism and distal hypo-perfusion, attenuate over time due to stabilization of vulnerable plaque and improvement of collateral blood flow [22–24]. Accordingly, any intervention of secondary prevention is likely to have greater effect if undertaken early after the presenting event.
The study aim was to evaluate the safety and efficacy of endovascular treatment (EVT) versus medical treatment (MT) in patients with symptomatic vertebral artery (VA) stenosis.
Randomized controlled trials with active and control groups receiving EVT plus MT and MT alone in patients with vertebro-basilar transient ischemic attack (TIA) or stroke and VA stenosis were identified. Primary endpoints included the occurrence of any stroke, any vertebro-basilar stroke, vertebro-basilar ischemic stroke, and vertebro-basilar TIA. Secondary endpoints were myocardial infarction, vascular death, and composite vascular outcome. All endpoints were assessed at short and long-term. Risk ratios (RRs) with 95% confidence intervals (CIs) have been estimated.
Four trials were included involving 370 participants, 194 and 176 for EVT and MT arms, respectively. There was no overall effect of EVT on the occurrence of any stroke [short-term: RR 3.05 (95% CI 0.33-28.49); long-term: RR 0.75 (95% CI 0.40-1.40)], any vertebro-basilar stroke [short-term RR 3.05 (95% CI 0.33-28.49); long-term RR 0.91 (95% CI 0.42-1.99)], vertebro-basilar ischemic stroke [short-term: RR 1.02 (95% CI 0.07-15.88); long-term RR 1.27 (95% CI 0.36-4.50)], vertebro-basilar TIA [short-term: RR 5.00 (95% CI 0.28-90.18); long-term: RR 0.85 (95% CI 0.39-1.81)]. There were no differences across the treatments in any secondary outcome.
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: This article was supported by the National Institute of Neurological Disorders and Stroke, the granting agency, KO8 NS02029 and R01 NS051631.

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