Extracranial Large-artery Disease Research Articles

Non-coronary peripheral arterial complications in people with type 2 diabetes: a Swedish retrospective cohort study

BackgroundFew studies have explored long-term trends and risk factors for peripheral arterial complications in type 2 diabetes compared to the general population. Our research focuses on identifying optimal risk factors, their significance, multifactorial control risks, and trends for these complications in diabetic patients versus general controls. MethodsThis study included persons with type 2 diabetes mellitus entered into the Swedish National Diabetes Register 2001-2019 and controls matched for age-, sex- and county of residence. Outcomes comprised of extracranial large artery disease, aortic aneurysm, aortic dissection, lower extremity arterial disease and diabetes foot disease. Standardized incidence rates and Cox regression were used for analyses. FindingsThe study comprises 655,250 persons with type 2 diabetes mellitus; average age 64.2; 43.8% women. Among persons with type 2 diabetes mellitus, the incidence rates per 100,000 person years for each non-coronary peripheral arterial complication event changed between 2001 and 2019 as follows: extracranial large artery disease 170.0 to 84.9; aortic aneurysm 40.6 to 69.2; aortic dissection 9.3 to 5.6; lower extremity artery disease from 338.8 to 190.8; and diabetic foot disease from 309.8 to 226.8. Baseline hemoglobin A1c (HbA1c), systolic blood pressure (SBP), smoking status and lipid levels were independently associated with all outcomes in the type 2 diabetes mellitus cohort. Within the cohort with type 2 diabetes mellitus, the risk for extracranial large artery disease and lower extremity artery disease increased in a stepwise fashion for each risk factor not within target. Excess risk for non-coronary peripheral arterial complications in the entire cohort for persons with type 2 diabetes mellitus, compared to matched controls, were as follows: extracranial large artery disease adjusted hazard ratio (HR) 1.69 (95% confidence interval (CI), 1.65-1.73), aortic aneurysm HR 0.89 (95% CI, 0.87-0.92), aortic dissection HR 0.51 (95% CI, 0.46-0.57) and lower extremity artery disease HR 2.59 (95% CI, 2.55-2.64). InterpretationsThe incidence of non-coronary peripheral arterial complications has declined significantly among persons with type 2 diabetes mellitus, with the exception of aortic aneurysm. HbA1c, smoking and blood pressure demonstrated greatest relative contribution for outcomes and lower levels of cardiometabolic risk factors are associated with reduced relative risk of outcomes.Funding: Swedish governmental and the county support of research and education of doctors, the Swedish Heart and Lung Foundation and Åke-Wibergs grant.

Influential factors and clinical significance of fluid-attenuated inversion recovery vascular hyperintensities in transient ischemic attacks of carotid arterial system.

Fluid-attenuated inversion recovery vascular hyperintensity (FVH) is often observed in conjunction with acute ischemic stroke (AIS) of the carotid system. Despite its bearing on patient care outcomes, factors influencing FVH and its clinical significance in patients with transient ischemic attacks (TIAs) of the carotid arterial system have yet to be evaluated. Consecutive inpatients (N=154) diagnosed with TIAs of the carotid system in a 2-year period (2012-2014) were enrolled in our study. Each had undergone magnetic resonance imaging (MRI) within 72h of symptom onset, followed by intracranial and extracranial vascular imaging. We investigated the frequency and nature of factors associated with FVH, also examining its clinical significance in the 30-day prognosis of TIA. Of the 154 patients enrolled (male, 92; mean age 63.0±11.9), FVH was confirmed in 61 patients (39.6%). In logistic regression analysis, intracranial large-artery disease (LAD) (OR=2.39, 95% CI 1.16-4.92; p=0.018) and prior stroke (OR=3.33, 95% CI 1.48-7.51; p=0.004) emerged as factors independently associated with FVH positivity. Ultimately, 25 patients (16.2%) progressed to AIS within a 30-day follow-up period. Logistic regression analysis indicated that contralateral FVH positivity (OR=5.98, 95% CI 1.81-19.76; p=0.003), atrial fibrillation (OR=7.05, 95% CI 1.33-37.40; p=0.022), and extracranial LAD (OR=4.12, 95% CI 1.26-13.41; p=0.019) were independently associated with AIS during the 30-day follow-up of TIAs in these patients. Intracranial LAD and previous stroke are independently associated with FVH in patients experiencing carotid system TIAs. If present, FVH may predict an oncoming AIS in the 30days following a TIA.

Epidemiology of Intracranial and Extracranial Large Artery Stenosis in a Population-Based Study of Stroke in the Middle East

Background: Intracranial large-artery disease (LAD) is a predominant vascular lesion found in patients with stroke of Asian, African, and Hispanic origin, whereas extracranial LAD is more prevalent among Caucasians. These patterns are not well-established in the Middle East. We aimed to characterize the incidence, risk factors, and long-term outcome of LAD strokes in a Middle-Eastern population. Methods: The Mashhad Stroke Incidence Study is a community-based study that prospectively ascertained all cases of stroke among the 450,229 inhabitants of Mashhad, Iran between 2006 and 2007. Ischemic strokes were classified according to the TOAST criteria. Duplex-ultrasonography (98.6%), MR-angiography (8.3%), CT-angiography (11%), and digital-subtraction angiography (9.7%) were performed to identify involvements. Vessels were considered stenotic when the lumen was occluded by >50%. Results: We identified 72 cases (15.99 per 100,000) of incident LAD strokes (mean age 67.6 ± 11.7). Overall, 77% had extracranial LAD (58% male, mean age 69.8 ± 10.3; 50 [89%] carotid vs. 6 [11%] vertebral artery), and the remaining 23% (56% male, mean age 60.2 ± 13.4; 69% anterior-circulation stenosis) had intracranial LAD strokes. We were unable to detect differences in case-fatality between extracranial (1-year: 28.6%; 5-year: 59.8%) and intracranial diseases (1-year: 18.8%; 5-year: 36.8%; log-rank; p = 0.1). Conclusion: Extracranial carotid stenosis represents the majority of LAD strokes in this population. Thus, public health strategies may best be developed in such a way that they are targeted toward the risk factors that contribute to extracranial stenosis.

Association between hyperhomocysteinemia and stroke with atherosclerosis and small artery occlusion depends on homocysteine metabolism-related vitamin levels in Chinese patients with normal renal function.

This study was conducted to investigate the role of different homocysteine metabolism-related vitamin (HMRV) levels in the correlation between hyperhomocysteinemia (HHCY) and ischemic stroke (IS) subtypes. Three hundred and forty-eight IS patients manifesting different vascular subtypes were subclassified on the basis of HMRV deficiencies. Correlation between HHCY and IS subtypes was investigated in all the subgroups. In this study, HHCY was significantly correlated with the IS subtypes in large artery atherosclerosis (OR 1.126, 95%CI: 1.051~1.206, P=0.001) and small artery occlusion (OR 1.105, 95%CI: 1.023~1.193, P=0.012). Subgroup analysis revealed a correlation between HHCY and IS subgroup (OR 1.201, 1.178, 95%CI: 1.081~1.334, 1.058~1.313, P=0.001, P=0.003, respectively) in HMRV deficiency, but not significantly with the IS subgroup in normal HMRV levels. Serum vitamin B12 concentrations are inversely correlated with both IS subtypes in HMRV deficiency subgroups (OR 0.992, 0.995, 95%CI: 0.987~0.996, 0.991~0.999, P<0.001, P=0.007, respectively), which may contribute to HHCY incidence in these populations. The correlation between HHCY and IS subtypes is affected by HMRV levels in this case-control study. Our findings are helpful to understand the inconsistency in prior homocysteine studies. Serum vitamin B12 levels may play a critical role in HHCY incidence in this Chinese population.Cerebrovascular disease has emerged as the leading cause of disability and mortality in both urban and rural areas of China (Neurology branch of Chinese Medical Association 2015). Ischemic stroke (IS) constitutes 60% to 80% of all cerebrovascular disease (Neurology branch of Chinese Medical Association 2014). Among a variety of risk factors, hyperhomocysteinemia (HHCY) has been closely correlated with IS due to intracranial small-vessel disease and extracranial large-artery disease (Selhub et al. 1995; Eikelboom et al. 2000; Alvarez et al. 2012; Jeon et al. 2014). However, the failure to lower homocysteine (HCY) via homocysteine metabolism-related vitamin (HMRV, including folic acid and vitamin B12 but not vitamin B6 in this study) supplementation to reduce stroke morbidity questions the role of HCY as a risk factor for stroke (Lonn et al. 2006; Hankey et al. 2010). Theoretically, HMRV supplementation merely lowers the incidence of stroke induced by HHCY resulting from HMRV deficiency, whereas HHCY-induced stroke concomitant with normal HMRV levels may be refractory to treatment. The correlation between HCY varying with HMRV levels and IS subtypes is still unclear. In this study, we investigated the impact of variation in HMRV levels on the correlation between HHCY and IS subtypes in 348 acute IS patients with large and small vessel diseases. We sought to determine the factors underlying the conflicting results associated with lowering HCY by HMRV supplementation to reduce stroke incidence.

Arterial spin labeling magnetic resonance perfusion imaging in cerebral ischemia

Arterial spin labeling (ASL) is a noninvasive magnetic resonance perfusion imaging method for visualizing and quantifying whole-brain perfusion that does not require exogenous contrast agents. The goal of this review article is to explain the principles of ASL perfusion imaging and review the strengths and limitations of different ASL methods. There are several different approaches that vary mainly on the basis of the technique that is used to label the inflowing arterial blood. These methods can be used to assess perfusion at brain tissue level or the perfusion territories of the brain feeding arteries. In patients with acute ischemic stroke, ASL can be of clinical value by detecting brain regions with hypoperfusion and perfusion-diffusion mismatch. ASL has been used to detect decreased perfusion, delayed arrival of the arterial blood bolus and assessment of collateral blood flow in patients with extracranial large artery disease and moyamoya disease. Recent evidence indicates that perfusion and territorial perfusion imaging of the brain feeding arteries with ASL can help to assess the extent of hemodynamic compromise and to customize medicinal and surgical treatment, both in patients with acute and with chronic cerebrovascular disease.

Cognitive and functional impairments in ischemic stroke patients with concurrent small vessel and large artery disease

Background and purpose Concurrent small vessel, intracranial and extracranial large artery disease (SLAD) is common in Asian but its impact on cognitive and functional outcomes is unclear. We aimed to evaluate the clinical, cognitive and functional outcomes in ischemic stroke patients with SLAD. Methods Chinese ischemic stroke patients with diffuse white matter lesions (WMLs) were recruited as part of the VITATOPS Trial. They were studied with MRI and MRA of brain. Various neuropsychiatric batteries were used to assess the cognitive functions. Results Totally 97 patients with acute ischemic stroke and diffuse WMLs were included, of whom 44 (45%) had SLAD. Patients with SLAD had lower Mini Mental State Examination (MMSE) when compared with the patients without SLAD. They had more behavioral symptoms and caused more stress in caregivers as assessed by the Neuropsychiatric Inventory (NPI). Multivariate regression analysis showed SLAD contributed significantly to MMSE, NPI Patient (NPI P) and NPI Care Giver (NPI CG). Among 44 patients with SLAD, 30 (68%) had severe cognitive impairment. They were older and less educated. They had more diabetes and poorer performance in neuropsychiatric tests including Mattis Dementia Rating Scale Initiation/Perseveration subset (MDRS I/P) and Clinical Dementia Rating (CDR). They also had poorer functional outcomes as assessed by Barthel Index (BI) and Instrumental activities of daily living (IADL). Conclusions This was the first MRA-based study to take into consideration the clinical, cognitive and functional outcomes in ischemic stroke patients with SLAD. Patients with SLAD had poorer cognitive and functional outcomes when compared to patients without SLAD.

Poststroke depression in patients with small subcortical infarcts

Objectives Small subcortical infarcts (SSIs) can result from small vessel disease (SVD) and intracranial and extracranial large artery disease (LAD). No study has explored poststroke depression (PSD) in different etiological types of SSIs. Methods Patients with SSIs resulting from LAD and SVD were included in the study. Poststroke depression was evaluated with the 15-item version of the geriatric depression scale (GDS) 3 months after stroke. Results Of the 127 patients with SSIs, 44 had LAD and 83 had SVD. The LAD group had a significantly higher mean GDS score and higher frequency of PSD ( p < 0.05). The etiological type LAD was a significant independent risk factor for PSD. Conclusion PSD is more common in patients with SSIs resulting from LAD. This suggests that cerebral blood perfusion may play an important role in the development of PSD.

The Frequency of Symptoms in Transient Ischaemic Attack: Analysis of Nanjing Stroke Register Program Data

The clinical characteristics of 172 patients experiencing single or multiple (two or more) transient ischaemic attacks (TIAs) were investigated. Risk factors, clinical manifestations and vascular examinations were compared. Intracranial and extra-cranial large-artery disease (stenosis > or = 50%) occurred more frequently in multiple-TIA patients than in single-TIA patients, and weakness and atrial fibrillation were observed more frequently in single TIA than in multiple TIA patients. The type of aetiological examination performed in TIA patients should depend on the frequency of attacks.

Total Cerebral Blood Flow Estimated by Color Velocity Imaging Quantification Ultrasound: A Predictor for Recurrent Stroke?

Although the Virchow's triad on thrombosis includes reduced blood flow as a factor, there has been relatively little data on the importance of total cerebral blood flow on the risk of subsequent stroke. In the current study, we investigate whether total cerebral blood flow helps predict stroke recurrence. Extracranial arterial blood flow volume estimated by color velocity imaging quantification ultrasound (CVIQ) is an index of cerebral blood flow measurement. We performed a cohort study of 210 consecutive acute stroke patients. Patients were studied with transcranial Doppler and duplex ultrasound for intra- and extracranial large artery disease within 3 days of symptom onset. The association between the risk of recurrent stroke and CVIQ was analyzed with Cox proportional hazards model. Thirty-nine patients (17.7%) developed an ischemic stroke during a mean follow-up of 47.5 months. The mean extracranial blood flow volume was significantly lower for patients who had a recurrent stroke than those without (594.4+/-130.3 versus 683.8+/-176.9 mL/min; P=0.003). In a Cox proportional hazards model adjusting for potential confounding variables, extracranial blood flow volume (hazard ratio (HR) for lowest tertile, 4.1; 95% confidence interval (CI), 1.5 to 11.0) along with male sex (HR, 2.5; 95% CI, 1.3 to 5.1), diabetes (HR, 2.5; 95% CI, 1.2 to 5.0) and large artery stenosis (HR, 2.2; 95% CI, 1.1 to 4.4) were independent predictors for stroke recurrence. Our data indicated that patient with low amount of blood flow to the brain is at risk of recurrent stroke.

Stroke Risk of Asymptomatic Intra- and Extracranial Large-Artery Disease in Apparently Healthy Adults

Background: The predictive value of asymptomatic intracranial artery stenosis for future stroke remains uncertain. The aim of this study is to assess the stroke risk of asymptomatic intracranial artery stenosis and to compare it with that of extracranial artery disease. Methods: The study subjects were 2,924 participants (mean age 55 years) without any history of stroke. We examined the relation between intra- or extracranial large-artery disease and subsequent cerebrovascular events (mean follow-up 63 months). Results: The incidence rate of total cerebrovascular events in persons with intracranial artery stenosis was 1.3% per year. In the group without plaque in the extracranial carotid arteries, the annual rate of total cerebrovascular events was only 0.6%, but in the group with plaque, the rate was 3.6%. Kaplan-Meier analysis of total events showed a significant difference between the 2 groups (p = 0.002). Conclusions: The stroke risk in subjects with asymptomatic extracranial artery disease is markedly increased if intracranial artery stenosis is also present.

Spectrum of the Posterior Inferior Cerebellar Artery Territory Infarcts

Background and Purpose: The clinical, etiological and stroke mechanisms are defined well before but the detailed clinical and etiologic mechanisms regarding to all clinical spectrum of posterior inferior cerebellar artery (PICA) infarcts were not systematically studied by diffusion-weighted imaging (DWI). Methods: Seventy-four patients with PICA territory ischemic lesion proved by DWI with decreased apparent diffusion coefficient and FLAIR (fluid attenuation inversion recovery) included in our Registry, corresponding to 2% of 3,650 patients with ischemic stroke, were studied. The presence of steno-occlusive lesions in the posterior circulation were sought by magnetic resonance angiography, and reviewed with a three-dimensional rotating cineangiographic method. Results: We found six subgroups of PICA territory infarcts according clinico-topographical relationship: (1) 9 patients with lesion in the territory lateral branch of PICA; (2) 23 patients with an infarct in the territory of medial branch of PICA; (3) 9 patients with a lesion involving both medial and lateral branches of the PICA; (4) 9 patients with cortical infarcts at the boundary zones either between medial and lateral branches of the PICA or between PICA and m/l superior cerebellar artery (SCA); (5) 10 patients with a lesion at the deep boundary zones either between medial and lateral PICA, or between PICA and medial/lateral SCA; (6)14 patients with concomitant multiple lesions in the PICA and in other vertebrobasilar artery territories. The main cause of PICA infarcts was extracranial large-artery disease in 30 patients (41%) patients, cardioembolism and in situ branch disease in 15 patients (20%) each. Conclusions: Multiple PICA territory lesions on DWI were not uncommon and could be caused by multiple emboli originating from break-up of atherosclerotic plaque in the subclavian/innominate-vertebral arterial system. DWI findings of single or multiple small lesions could account for some cases with transient and subtle cerebellar symptoms which have been considered before as ‘vertebrobasilar insufficiency’ without morphologic lesion. Different clinical-DWI correlations allow us to determine better definition of the topographical and etiological spectrum of acute PICA territory lesions, which was previously defined by pathological and conventional MRI studies.

Cranial Computerized Tomography Stroke Patterns in Patients with Cardiac Sources of Embolism, Extracranial Large-Artery Disease or No Extracranial Source

The hypothesis of an association between stroke mechanisms (cardiac sources of embolism, extracranial large-artery disease, hypertension) and cranial computerized tomography stroke patterns was tested in a prospective study. 200 consecutive patients with focal brain ischemia were investigated by echocardiography (transthoracic and transesophageal approach), Doppler sonography, electrocardiography, and cranial computerized tomography (rated masked). Except for low-flow infarcts and carotid artery stenoses the association between stroke mechanisms and stroke patterns was weak. Lacunes were found with almost equal frequencies in patients with cardiac sources of embolism, extracranial large-artery disease or no extracranial source (with or without hypertension). The predictive value of cranial computerized tomography stroke patterns for the finding of possible stroke mechanisms is low. An embolic etiology of lacunes cannot be excluded.

Intracranial Large-Artery Disease and 'Lacunar' Infarction

Small ''lacunar'' infarcts in the territory of the deep perforators (ITDP) have usually been attributed to small-vessel disease associated with hypertension or diabetes, but recently also to embolism from extracranial large-artery atherosclerosis or heart disease. However, in several cases, the cause of ITDP remains undetermined. Of 1,800 patients with first-ever stroke from the Lausanne Stroke Registry, 320 had ITDP smaller than 1.5 cm on computed tomography or magnetic resonance imaging. In 26 (8%) of them, the etiology of ITDP remained undetermined, because they had no hypertension, diabetes, extracranial large-artery disease or a potential cardiac source of embolism. Angiography was performed prospectively in the last 16 patients with undetermined etiology for ITDP. In 10 of them, intracranial stenosis on the parent large artery (middle cerebral artery in 6, basilar artery in 4) was demonstrated at the presumed site of origin of the deep perforator. Local obstruction of the mouth of deep perforators by intracranial large-artery disease may not be an uncommon cause of ITPD and should be looked for in ITDP of ''undetermined'' origin.