Project description:There are approximately 800,000 strokes in the United States (U.S.) annually. This number has remained the same for decades despite efforts at prevention. The Center for Disease Control (CDC) estimates that 80% of strokes could be prevented. A prime reason for failure of prevention is that the three immediate modifiable causes of strokes, carotid artery disease (CAD), atrial fibrillation (AFib), and hypertension (HTN) are asymptomatic in 80% of cases prior to the stroke. Strokes occur predominantly in seniors and the only possible means of reducing strokes on a large scale is to screen seniors for the asymptomatic disease so that it can be preemptively managed. We present a quick, accurate and cost-effective method of screening the senior population for asymptomatic carotid disease. The technique is a quick carotid scan (QCS). The QCS is a 1-minute long, image only, rapid, color flow ultrasound scan of the cervical carotid arteries that had a sensitivity of 97% when evaluated at New York University (NYU). Once identified by the QCS the approximately 8% of those screened found to have a positive QCS can then be referred for a full carotid duplex ultrasound (DUS). Those patients with a positive DUS can then be referred for further evaluation and appropriate stroke prevention management. The use of a full carotid DUS for screening widely for carotid disease is too time consuming and too costly. Approximately 160,000 or nearly 20% of the 800,000 strokes that occur annually in the U.S. are due to CAD that could in large part be prevented by screening the senior population with the QCS, finding those with CAD, evaluating them, and preemptively managing them prior to the occurrence of the stroke.
Project description:BackgroundCarotid-artery stenting and carotid endarterectomy are both options for treating carotid-artery stenosis, an important cause of stroke.MethodsWe randomly assigned patients with symptomatic or asymptomatic carotid stenosis to undergo carotid-artery stenting or carotid endarterectomy. The primary composite end point was stroke, myocardial infarction, or death from any cause during the periprocedural period or any ipsilateral stroke within 4 years after randomization.ResultsFor 2502 patients over a median follow-up period of 2.5 years, there was no significant difference in the estimated 4-year rates of the primary end point between the stenting group and the endarterectomy group (7.2% and 6.8%, respectively; hazard ratio with stenting, 1.11; 95% confidence interval, 0.81 to 1.51; P=0.51). There was no differential treatment effect with regard to the primary end point according to symptomatic status (P=0.84) or sex (P=0.34). The 4-year rate of stroke or death was 6.4% with stenting and 4.7% with endarterectomy (hazard ratio, 1.50; P=0.03); the rates among symptomatic patients were 8.0% and 6.4% (hazard ratio, 1.37; P=0.14), and the rates among asymptomatic patients were 4.5% and 2.7% (hazard ratio, 1.86; P=0.07), respectively. Periprocedural rates of individual components of the end points differed between the stenting group and the endarterectomy group: for death (0.7% vs. 0.3%, P=0.18), for stroke (4.1% vs. 2.3%, P=0.01), and for myocardial infarction (1.1% vs. 2.3%, P=0.03). After this period, the incidences of ipsilateral stroke with stenting and with endarterectomy were similarly low (2.0% and 2.4%, respectively; P=0.85).ConclusionsAmong patients with symptomatic or asymptomatic carotid stenosis, the risk of the composite primary outcome of stroke, myocardial infarction, or death did not differ significantly in the group undergoing carotid-artery stenting and the group undergoing carotid endarterectomy. During the periprocedural period, there was a higher risk of stroke with stenting and a higher risk of myocardial infarction with endarterectomy. (ClinicalTrials.gov number, NCT00004732.)
Project description:ObjectiveWe have shown that almost 50% of patients with asymptomatic carotid stenosis (ACS) will demonstrate cognitive impairment. Recent evidence has suggested that cerebral hypoperfusion is an important cause of cognitive impairment. Carotid stenosis can restrict blood flow to the brain, with consequent cerebral hypoperfusion. In contrast, cross-hemispheric collateral compensation through the Circle of Willis, and cerebrovascular vasodilation can also mitigate the effects of flow restriction. It is, therefore, critical to develop a clinically relevant measure of net brain perfusion in patients with ACS that could help in risk stratification and in determining the appropriate treatment. To determine whether ACS results in cerebral hypoperfusion, we developed a novel approach to quantify interhemispheric cerebral perfusion differences, measured as the time to peak (TTP) and mean transit time (MTT) delays using perfusion-weighted magnetic resonance imaging (PWI) of the whole brain. To evaluate the utility of using clinical duplex ultrasonography (DUS) to infer brain perfusion, we also assessed the relationship between the PWI findings and ultrasound-based peak systolic velocity (PSV).MethodsStructural and PWI of the brain and magnetic resonance angiography of the carotid arteries were performed in 20 patients with ≥70% ACS. DUS provided the PSV, and magnetic resonance angiography provided plaque geometric measures at the stenosis. Volumetric perfusion maps of the entire brain from PWI were analyzed to obtain the mean interhemispheric differences for the TTP and MTT delays. In addition, the proportion of brain volume that demonstrated a delay in TTP and MTT was also measured. These proportions were measured for increasing severity of perfusion delays (0.5, 1.0, and 2.0 seconds). Finally, perfusion asymmetries on PWI were correlated with the PSV and stenosis features on DUS using Pearson's correlation coefficients.ResultsOf the 20 patients, 18 had unilateral stenosis (8 right and 10 left) and 2 had bilateral stenoses. The interhemispheric (left-right) TTP delays measured for the whole brain volume identified impaired perfusion in the hemisphere ipsilateral to the stenosis in 16 of the 18 patients. More than 45% of the patients had had ischemia in at least one half of their brain volume, with a TTP delay >0.5 second. The TTP and MTT delays showed strong correlations with PSV. In contrast, the correlations with the percentage of stenosis were weaker. The correlations for the PSV were strongest with the perfusion deficits (TTP and MTT delays) measured for the whole brain using our proposed algorithm (r = 0.80 and r = 0.74, respectively) rather than when measured on a single magnetic resonance angiography slice as performed in current clinical protocols (r = 0.31 and r = 0.58, respectively).ConclusionsInterhemispheric TTP and MTT delay measured for the whole brain using PWI has provided a new tool for assessing cerebral perfusion deficits in patients with ACS. Carotid stenosis was associated with a detectable reduction in ipsilateral brain perfusion compared with the opposite hemisphere in >80% of patients. The PSV measured at the carotid stenosis using ultrasonography correlated with TTP and MTT delays and might serve as a clinically useful surrogate to brain hypoperfusion in these patients.
Project description:With the aging of the general population and the availability of noninvasive imaging studies, carotid artery stenosis is a disease commonly seen in general medical practice. Differentiation between symptomatic and asymptomatic disease is critical to the treatment course because the natural history differs markedly between them. Antiplatelet therapy and aggressive treatment of vascular risk factors are the mainstays of medical therapy. Class I evidence shows that carotid endarterectomy (CEA) is effective in preventing ipsilateral ischemic events in patients with symptomatic moderate- and high-grade stenosis. The procedure is also effective in selected patients with asymptomatic stenosis, but the benefit is marginal. In the past decade, carotid angioplasty and stenting has been proposed as a valid alternative to CEA. Currently, it is unclear whether carotid angioplasty and stenting is as safe as CEA in patients with carotid artery stenosis who need invasive treatment. Large clinical trials are under way to answer this question.
Project description:Various surgical treatments are available for occlusive subclavian and common carotid artery diseases. Nevertheless, to date, when cerebral endovascular treatment is utilized, revascularization via direct surgery may be required. This study reported five symptomatic cases of revascularization for CCA and SCA occlusive and stenotic lesions that were expected to be challenging to treat with endovascular treatment. We performed subclavian artery-common carotid artery or internal carotid artery bypass using artificial blood vessels or saphenous vein grafts in five patients with subclavian steal syndrome, symptomatic common carotid artery occlusion, and severe proximal common carotid artery stenosis. In this study, good bypass patency was achieved in all five cases. Although there were no intraoperative complications, one patient had a postoperative lymphatic leak. Moreover, there was no recurrence of stroke during postoperative follow-up for an average of 2 years. Conclusively, subclavian artery-common carotid artery bypass can be an effective surgical treatment for common carotid artery occlusion, proximal common carotid artery stenosis, and subclavian artery occlusion.
Project description:This study was conducted in order to assess the effects of the compound Mycophenolate mofetil (MMF), an inhibitor of the enzyme inosine monophosphate dehydroxygenase (IMPDH) with a strong cytostatic effect on T-cells, on the phenotype of human carotid artery stenosis in humans in vivo. This was done at the transcriptome level by comparing the gene expression profiles of carotid endarterectomy samples from patients with carotid artery stenosis (>70% diameter stenosis on angiography) that were randomly assigned to treatment with MMF 1000 mg (N=9) or Placebo (N=11), respectively. MMF or placebo was given for at least 2 weeks prior to undergoing carotid endarterectomy (CEA).
Project description:The present study analyzed gene expression arrays to identify differentially-expressed genes (DEGs) between mycophenolate mofetil (MMF)‑treated and placebo‑treated patients with symptomatic carotid artery stenosis (SCAS). In addition, the key genes involved in the pharmacology of MMF treatment in patients with SCAS were identified. The gene expression dataset was obtained from a Gene Expression Omnibus database, which included 9 MMF‑treated and 11 placebo‑treated samples. The DEGs were identified between MMF and placebo groups using R software. Furthermore, a protein‑protein interaction (PPI) network of the identified DEGS was constructed. The Database for Annotation, Visualization and Integrated Discovery was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the 19 most significant DEGs. A total of 210 DEGs between the MMF and placebo groups were screened and their PPI was constructed. GO function analysis revealed that the 19 DEGs were predominantly involved in the tyrosine phosphorylation of signal transducer and activator of transcription‑5 protein, which is closely associated with the activation of T cells. The KEGG pathway analysis suggested that the main metabolic pathways of the 19 DEGs were associated with the pharmacological functioning of MMF in activated T cells. In conclusion, the present study identified numerous key DEGs associated with SCAS, and the results suggested that v‑kit Hardy‑Zuckerman 4 feline sarcoma viral oncogene homolog and apelin may serve important roles in the MMF treatment of SCAS.