Asymptomatic carotid stenosis: Medicine alone or combined with carotid revascularization.
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ABSTRACT:
SUBMITTER: Heck DV
PROVIDER: S-EPMC5440242 | biostudies-literature | 2017 May
REPOSITORIES: biostudies-literature
Publications
Asymptomatic carotid stenosis: Medicine alone or combined with carotid revascularization.
Heck Donald V DV Roubin Gary S GS Rosenfield Kenneth G KG Gray William A WA White Christopher J CJ Jovin Tudor G TG Matsumura Jon S JS Lal Brajesh K BK Katzen Barry T BT Dabus Guilherme G Jankowitz Brian T BT Brott Thomas G TG
Neurology 20170426 21
Two positive randomized trials established carotid endarterectomy (CEA) as a superior treatment to medical management alone for the treatment of asymptomatic carotid artery stenosis. However, advances in medical therapy have led to an active and spirited debate about the best treatment for asymptomatic carotid stenosis. The Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis (CREST 2) trial aims to better define the best treatment for the average patient with sever ...[more]
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Project description:Internal carotid artery stenosis is a risk factor for ischemic stroke. Even in the absence of visible structural brain changes, patients with asymptomatic stenosis are prone to cognitive impairment. On a neuronal level, it was suggested that stenosis may lead to disturbed functional brain connectivity. If so, carotid revascularization should have an effect on hypothesized brain network disturbances. We studied functional connectivity in a motor network by resting-state electroencephalography in 12 patients with high grade asymptomatic carotid stenosis before and after interventional or surgical revascularization as compared to 23 controls. In patients with stenosis, functional connectivity of neural oscillations was significantly decreased prior and improved returning to normal connectivity after revascularization. In a subgroup of patients, also studied by contrast perfusion magnetic resonance imaging, reduced connectivity was associated with decreased regional brain perfusion reflected by increased mean transit time in the middle cerebral artery borderzone. Cognitive testing revealed only minor differences between patients and controls. In summary, we identified oscillatory connectivity changes in patients with asymptomatic carotid stenosis correlating with regional hypoperfusion, which both normalized after revascularization. Hence, electrophysiological changes might be a reversible precursor preceding macroscopic structural brain damage and behavioral impairment in patients with asymptomatic carotid stenosis.
| S-EPMC7446560 | biostudies-literature
Project description:RationaleFor patients with asymptomatic high-grade carotid stenosis, clinical investigations have focused on preventing cerebral infarction, yet stenosis that reduces cerebral blood flow may independently impair cognition. Whether revascularization of a hemodynamically significant carotid stenosis can alter the course of cognitive decline has never been investigated in the context of a randomized clinical trial.HypothesisAmong patients randomized in the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis (CREST-2) trials, the magnitude of treatment differences (revascularization versus medical management alone) with regard to cognition will differ between those with flow impairment compared to those without flow impairment.Sample sizeWe will enroll approximately 500 patients from CREST-2, of which we anticipate 100 will have hemodynamic impairment. We estimate 93% power to detect a clinically meaningful treatment difference of 0.5 SD.Methods and designWe will use perfusion-weighted magnetic resonance imaging to stratify by hemodynamic status. Linear regression will compare treatment differences, controlling for baseline cognitive status, age, depression, prior cerebral infarcts, silent infarction, white matter hyperintensity volume, and cerebral microbleeds.Study outcomesThe primary outcome is change in cognition at one year. Secondary outcomes include silent infarction, change in white matter hyperintensity volume, number of cerebral microbleeds, and cortical thickness over one year.DiscussionIf cognitive impairment can be shown to be reversible by revascularization, then we can redefine "symptomatic carotid stenosis" to include cognitive impairment and identify a new population of patients likely to benefit from revascularization.Trial registrationUS National Institutes of Health (NIH) clinicaltrials.gov NCT03121209.
| S-EPMC6384010 | biostudies-literature
Project description:Rationale Trials conducted decades ago demonstrated that carotid endarterectomy by skilled surgeons reduced stroke risk in asymptomatic patients. Developments in carotid stenting and improvements in medical prevention of stroke caused by atherothrombotic disease challenge understanding of the benefits of revascularization. Aim Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) will test whether carotid endarterectomy or carotid stenting plus contemporary intensive medical therapy is superior to intensive medical therapy alone in the primary prevention of stroke in patients with high-grade asymptomatic carotid stenosis. Methods and design CREST-2 is two multicenter randomized trials of revascularization plus intensive medical therapy versus intensive medical therapy alone. One trial randomizes patients to carotid endarterectomy plus intensive medical therapy versus intensive medical therapy alone; the other, to carotid stenting plus intensive medical therapy versus intensive medical therapy alone. The risk factor targets of centrally directed intensive medical therapy are LDL cholesterol <70 mg/dl and systolic blood pressure <140 mmHg. Study outcomes The primary outcome is the composite of stroke and death within 44 days following randomization and stroke ipsilateral to the target vessel thereafter, up to four years. Change in cognition and differences in major and minor stroke are secondary outcomes. Sample size Enrollment of 1240 patients in each trial provides 85% power to detect a treatment difference if the event rate in the intensive medical therapy alone arm is 4.8% higher or 2.8% lower than an anticipated 3.6% rate in the revascularization arm. Discussion Management of asymptomatic carotid stenosis requires contemporary randomized trials to address whether carotid endarterectomy or carotid stenting plus intensive medical therapy is superior in preventing stroke beyond intensive medical therapy alone. Whether carotid endarterectomy or carotid stenting has favorable effects on cognition will also be tested. Trial registration United States National Institutes of Health Clinicaltrials.gov NCT02089217.
| S-EPMC5987521 | biostudies-literature
Project description:Patients with asymptomatic carotid stenosis (ACS) are at very high risk of coronary events, so they should all receive intensive medical therapy. What is often accepted as "best medical therapy" is usually suboptimal. Truly intensive medical therapy includes lifestyle modification, particularly smoking cessation and a Mediterranean diet. All patients with ACS should receive intensive lipid-lowering therapy, should have their blood pressure well controlled, and should receive B vitamins for lowering of plasma total homocysteine (tHcy) if levels are high; a commonly missed cause of elevated tHcy is metabolic B12 deficiency, which should be diagnosed and treated. Most patients with ACS would be better treated with intensive medical therapy than with either carotid endarterectomy (CEA) or stenting (CAS). A process called "treating arteries instead of treating risk factors" markedly reduced the risk of ACS in an observational study; a randomized trial vs. usual care should be carried out. The few patients with ACS who could benefit (~15%, or perhaps more if recent evidence regarding the risk of intraplaque hemorrhage is borne out) can be identified by a number of features. These include microemboli on transcranial Doppler, intraplaque hemorrhage, reduced cerebrovascular reserve, and echolucency of plaques, particularly "juxtaluminal black plaque". No patient should be subjected to CAS or CEA without evidence of high-risk features, because in most cases the 1-year risk of stroke or death with intervention is higher with either CEA (~2%) or CAS (~4%) than with intensive medical therapy (~0.5%). Most patients, particularly the elderly, would be better treated with CEA than CAS. Most strokes can be prevented in patients with ACS, but truly intensive medical therapy is required.
| S-EPMC7607083 | biostudies-literature
Project description:IntroductionRevascularization procedures in carotid artery stenosis have shown a positive effect in the restoration of cerebral oxygen metabolism as assessed by T2' (T2 prime) imaging as well as capillary homeostasis by measurement of capillary transit time heterogeneity (CTH); however, data in patients with asymptomatic carotid stenosis without manifest brain lesions are scarce.Patients and methodsThe effect of revascularization on the hemodynamic profile and capillary homeostasis was evaluated in 13 patients with asymptomatic high-grade carotid stenosis without ischemic brain lesions using dynamic susceptibility contrast perfusion imaging and oxygenation-sensitive T2' mapping before and 6-8 weeks after revascularization by endarterectomy or stenting. The cognitive performance at both timepoints was further assessed.ResultsPerfusion impairment at baseline was accompanied by an increased CTH (p = 0.008) in areas with a time to peak delay ≥ 2 s in the affected hemisphere compared to contralateral regions. Carotid intervention improved the overall moderate hemodynamic impairment at baseline by leading to an increase in normalized cerebral blood flow (p = 0.017) and a decrease in mean transit time (p = 0.027), oxygen extraction capacity (OEC) (p = 0.033) and CTH (p = 0.048). The T2' values remained unchanged.ConclusionThis study presents novel evidence of a state of altered microvascular function in patients with high-grade carotid artery stenosis in the absence of ischemic brain lesions, which shows sustained normalization after revascularization procedures.
| S-EPMC8894147 | biostudies-literature
Project description:Even clinically "asymptomatic" carotid stenosis is associated with multidomain cognitive impairment, gray matter (GM) atrophy, and silent lesion. However, the links between them remain unclear. Using structural MRI data, we examined GM asymmetry index (AI) and white matter hyperintensity (WMH) in 24 patients with severe asymptomatic carotid stenosis (SACS), 24 comorbidity-matched controls, and independent samples of 84 elderly controls and 22 young adults. As compared to controls, SACS patients showed worse verbal memories, higher WMH burden, and right-lateralized GM in posterior middle temporal and mouth-somatomotor regions. These clusters extended to pars triangularis, lateral temporal, and cerebellar regions, when compared with young adults. Further, a full-path of WMH burden (X), GM volume (atrophy, M1), AI (asymmetry, M2), and neuropsychological variables (Y) through a serial mediation model was analyzed. This analysis identified that left-dominated GM atrophy and right-lateralized asymmetry in the posterior middle temporal cortex mediated the relationship between WMH burden and recall memory in SACS patients. These results suggest that the unbalanced hemispheric atrophy in the posterior middle temporal cortex is crucial to mediating relationship between WMH burden and verbal recall memories, which may underlie accelerated aging and cognitive deterioration in patients with SACS and other vascular cognitive impairment.
| S-EPMC8559457 | biostudies-literature
Project description:Background: Specific microRNAs (miRs) have been implicated in the pathophysiology of atherosclerosis and may represent interesting diagnostic and therapeutic targets in carotid stenosis. We hypothesized that the levels of specific circulating miRs are altered in patients with symptomatic carotid stenosis (sCS) in comparison to those in patients with asymptomatic carotid stenosis (aCS) planned to undergo carotid endarterectomy (CEA). We also studied whether miR levels are associated with plaque vulnerability and stability over time after CEA. Methods: Circulating levels of vascular-enriched miR-92a, miR-126, miR-143, miR-145, miR-155, miR-210, miR-221, miR-222, and miR-342-3p were determined in 21 patients with sCS and 23 patients with aCS before CEA and at a 90-day follow-up. Transcranial Doppler ultrasound for detection of microembolic signals (MES) in the ipsilateral middle cerebral artery was performed prior to CEA. Carotid plaques were histologically analyzed. Results: Mean levels of miRs were not considerably different between groups and were only marginally higher in sCS than aCS concerning miR-92a, miR-210, miR-145, and miR-143 with the best evidence concerning miR-92a. After adjustment for vascular risk factors and statin pre-treatment, the effect sizes remained essentially unchanged. At follow-up, however, these modest differences remained uncorroborated. There were no relevant associations between miR-levels and MES or histological plaque vulnerability features. Conclusions: This study does not provide evidence for strong associations between specific circulating miRs and symptomatic state in a collective of comprehensively characterized patients with carotid stenosis. Further work is needed to elucidate the role of circulating miRs as targets in advanced carotid atherosclerosis.
| S-EPMC8651616 | biostudies-literature
Project description:Background and purposeHigh-grade carotid artery stenosis may alter hemodynamics in the ipsilateral hemisphere, but consequences of this effect are poorly understood. Cortical thinning is associated with cognitive impairment in dementia, head trauma, demyelination, and stroke. We hypothesized that hemodynamic impairment, as represented by a relative time-to-peak (TTP) delay on MRI in the hemisphere ipsilateral to the stenosis, would be associated with relative cortical thinning in that hemisphere.MethodsWe used baseline MRI data from the NINDS-funded Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis-Hemodynamics (CREST-H) study. Dynamic contrast susceptibility MR perfusion-weighted images were post-processed with quantitative perfusion maps using deconvolution of tissue and arterial signals. The protocol derived a hemispheric TTP delay, calculated by subtraction of voxel values in the hemisphere ipsilateral minus those contralateral to the stenosis.ResultsAmong 110 consecutive patients enrolled in CREST-H to date, 45 (41%) had TTP delay of at least 0.5 seconds and 9 (8.3%) subjects had TTP delay of at least 2.0 seconds, the maximum delay measured. For every 0.25-second increase in TTP delay above 0.5 seconds, there was a 0.006-mm (6 micron) increase in cortical thickness asymmetry. Across the range of hemodynamic impairment, TTP delay independently predicted relative cortical thinning on the side of stenosis, adjusting for age, sex, hypertension, hemisphere, smoking history, low-density lipoprotein cholesterol, and preexisting infarction (P=0.032).ConclusionsOur findings suggest that hemodynamic impairment from high-grade asymptomatic carotid stenosis may structurally alter the cortex supplied by the stenotic carotid artery.
| S-EPMC9911846 | biostudies-literature
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.
| S-EPMC8209736 | biostudies-literature
Project description:BackgroundIntraplaque neovascularization (IPN) is a biomarker for vulnerable atherosclerotic plaques and can be effectively visualized via contrast-enhanced ultrasound (CEUS). Plaque elasticity is influenced by elements such as lipid core and fibrosis and can be quantitatively assessed on shear wave elastography (SWE). Studies combining the use of CEUS and SWE for the assessment of stroke risk are currently lacking. Our study thus aimed to determine the predictive value of IPN combined with plaque elasticity among patients with asymptomatic carotid plaque.MethodsConsecutive patients with mild carotid stenosis who underwent CEUS and SWE were retrospectively analyzed. IPN was graded according to the presence and location of microbubbles within the plaque, while plaque elasticity was measured in terms of mean shear wave velocity (SWV). All patients were followed up for 6 months to monitor the development of ischemic stroke. The predictive values of IPN and SWV, individually and in combination, were assessed.ResultsA total of 121 patients were included, of whom 95 (78.5%) were male. The mean age was 63.1±10.7 years. Both grade 2 IPN [hazard ratio (HR) =2.37, 95% confidence interval (CI): 1.58-9.65; P=0.039] and SWV (HR =0.43, 95% CI: 0.20-0.95; P=0.038) were independently associated with future ischemic stroke events. The combined model demonstrated a significantly better predictive performance (HR =3.243, 95% CI: 1.87-6.17; P=0.027).ConclusionsThe combination of IPN and SWV demonstrated significantly better predictive value for the risk of stroke. Our combined model thereby has the potential to guide the clinical stratification and management of patients with asymptomatic mild carotid stenosis.
| S-EPMC11250308 | biostudies-literature