Large Artery Disease Research Articles

Ischaemic posterior circulation stroke in State of Qatar

Ischaemic stroke features may show regional differences. Posterior circulation stroke (PCS) is of special interest, as symptomatology, course and outcome are usually different and complex. No significant studies or registries have reported on the characteristics and outcomes of PCS in our region. We prospectively collected data of 116 patients with PCS admitted from 2005 through 2008 in the only stroke admitting hospital in Qatar. Demographics, risk factors, clinical signs/symptoms, pattern of presentation, aetiology, imaging features, complications and outcome at discharge and follow-up were recorded. Mean age was 53 years with 25% aged < or = 45, 85% were males. Demographically 47% were Arabs and 51% of South-Asian origin. Mean duration from onset to presentation was 29 h. Major risk factors were obesity (66%) and hypertension (61%). Minimal or fluctuating symptoms were present in 64%, while 9% had maximal deficit at onset. Thirty nine per cent had lesions in proximal territory and 23% in multiple territories. Around 41% had no occlusion, 16% had vertebro-basilar, 16% vertebral, 8% basilar occlusion. Etiologically 53% patients had large artery disease, 16% small vessel disease, and 17% cardioembolism. Seventy per cent of patients were discharged home, while 10% expired. Modified Rankin score (mRS) at discharge was < or = 2 in 53% and > or = 4 in 13% patients. At 30-day follow-up, 68% had mRS of < or = 2. Ninety-day survival status showed 89% alive with mRS < or = 2 in 73%. The aetiology and lesion topography of PCS in this heterogeneous population differs from the pattern observed in other populations.

Implicaciones diagnósticas del perfil de recurrencia tras un ataque isquémico transitorio

Background and objective Early stroke recurrence risk alter a transient ischemic attack (TIA) is high. We studied the diagnostic implications of the recurrence pattern after TIA. Methods 210 consecutive TIA patients were studied. Ultrasonographic (US), neuroimaging and cardiologic data were collected. Results At 90 day follow-up, 14 patients (6.7%; 95% CI: 3.3–10.1) among 209 suffered an ischemic infarction (II), 9 (4.3%; 1.5–7.1) a TIA and 6 (2.9%; 0.6–5.1) a cardiac ischemic event. Moreover, 13 patients (6.2%; 2.8–9.6) among 210 with a seven-day follow-up had an II. Multivariate analyses only identified the presence of intracranial stenoses (HR, 23.29; 95% CI, 3.49 to 23.57; p<0.018) as independent predictors of stroke within the first 7 days, and large-artery occlusive disease (HR, 9.07; CI, 3.49 to 23.57; p<0.001) as a predictor of stroke recurrence at 90 day follow-up. A new diagnosis of atrial fibrillation was observed in 21 subjects (10.0%), and it was documented in the baseline ECG in 62% cases. Acute diffusion abnormalities were identified in 81 (44,5%) of 182 patients, and chronic ischemic lesions were observed in 110 (60.4%) on MRI vs 56 (26.7%) among 210 on CT scan. Conclusion Due to very early recurrence, the routine use of ultrasonography within the first hours after an index TIA will be useful to identify those patients at high risk. The prognostic usefulness of diffusion-weighted studies will be only achieved if it is performed early. Routine noninvasive cardiac rhythm monitoring has a low detection rate.

Arterial stiffness is associated with intracranial large artery disease among ethnic Chinese and South Asian ischemic stroke patients

Intracranial large artery disease (ICLAD) is a common stroke subtype that carries a poor prognosis. We studied the association of arterial stiffness, a recognized risk factor for atherosclerosis and ICLAD among ethnic Chinese and South Asian ischemic stroke patients. In this prospective study, we recruited consecutive ischemic stroke patients of Chinese and South Asian ethnicity. ICLAD was assessed by transcranial color-coded Doppler or magnetic resonance angiographic studies. Arterial stiffness was measured by carotid-femoral pulse wave velocity (cPWV). Among the 268 patients studied, the prevalence of ICLAD was 54% and median cPWV was 11.4 m/s (interquartile range 9.0-13.6 m/s). Patients with ICLAD had higher cPWV compared with those without (median 11.7 vs. 11.0 m/s, P = 0.015). In multivariate analysis, patients with ICLAD were significantly more likely to have cPWV measurements in the highest quintile (>14.1 m/s) compared with patients without ICLAD independently of other covariates [odds ratio 2.21, P = 0.038]. This study revealed a novel association between arterial stiffness and ICLAD among ischemic stroke patients. The findings suggest that arterial stiffness may be involved in the pathophysiology of ICLAD. Future studies should investigate the effects of reducing arterial stiffness among stroke patients with ICLAD.

Simultaneous Occurrence and Interaction of Hypoperfusion and Embolism in a Patient With Severe Middle Cerebral Artery Stenosis

The coincidence of hemodynamic and embolic findings in patients with stroke from large artery stenosis has suggested an interaction of both pathologies. This has emerged into the hypothesis of an impaired washout of emboli in the presence of hypoperfusion. We propose an additional link between both pathologies. A 48-year-old woman presented with a recurrent symptomatic severe left middle cerebral artery stenosis. MRI depicted left hemispheric ischemic infarcts in the deep and subcortical white matter and in the cortical border zone. One-hour transcranial Doppler monitoring detected 64 microembolic signals distal to the arterial stenosis. Monitoring also revealed recurrent thrombus formation at the stenotic plaque with decline of poststenotic flow velocity followed by embolism with abrupt excessive flow velocity increase and subsequent normalization at the initial baseline level. Cerebrovascular reserve in the distribution territory of the stenosed artery as assessed by transcranial Doppler after carbon dioxide stimulation revealed a normal reserve capacity in periods with baseline poststenotic flow velocity and an exhausted reserve capacity when flow velocity was decreased due to stenotic thrombus formation. In our patient, adherent thrombus formation resulted in an increasing severity of the stenosis with subsequent vasodilatation and diminution of flow resistance in the depending vascular distribution territory. MRI suggested that adherent thrombi were predominantly washed into terminal supply and border zone brain regions, ie, into regions with supposed maximum vasodilatation and least flow resistance immediately before thrombus avulsion. Preferred wash-in of emboli into regions with low blood flow resistance might be an additional mechanism besides impaired washout in patients with severe large artery disease.

Intracranial large artery disease in Alzheimer’s disease and vascular dementia among ethnic Asians

An underlying vascular etiology underpins vascular dementia (VaD) and possibly Alzheimer's disease (AD). Intracranial large artery disease (ICLAD) is a common site of disease among ethnic Asians, and carries a poor prognosis. We studied the prevalence of ICLAD among ethnic Asian patients with AD and VaD. We recruited patients with AD and VaD from a retrospective review of consecutive ethnic Asian patients presenting to our dementia clinic. ICLAD was evaluated by visual inspection of brain magnetic resonance angiography by two observers in consensus, and defined as >50% luminal narrowing. There were 56 patients with probable AD and 47 with probable VaD. ICLAD was prevalent among 53% of VaD patients and 18% of AD patients. There is a relatively high burden of ICLAD among AD and VaD patients of Asian ethnicity. We suggest that ethnic Asian dementia patients are a potential group to investigate if ICLAD is associated with clinical symptoms or prognosis and if treatment strategies targeted at ICLAD retard the progression of cognitive impairment.

Sensorimotor stroke; clinical features, MRI findings, and cardiac and vascular concomitants in 32 patients.

Sensorimotor stroke (SMS) is often included among the lacunar syndromes, although the underlying cause of this stroke-subtype is less well documented. To this end we analysed 32 patients presenting with a sensorimotor syndrome. The study protocol included vascular risk factors, echocardiography, Doppler sonography of carotid arteries, CT scan and MRI of the brain. There were 23 men and 9 women, mean age 65.7 years. Hypertension was present in 28% and diabetes in 19%. In all, 63% had sensorimotor deficit of faciobrachiocrural areas and 37% had faciobrachial or brachiocrural deficits. MRI disclosed a presumably relevant infarct in 26 patients (81%); 20 patients (62%) localized to the territory of small perforating arteries, 3 patients (9.5%) in the internal borderzone, and 3 patients (9.5%) in cortical territories. Eight of 20 deep infarcts were larger than 15 mm. No hemorrhage or non-vascular lesion was found. A potential cardioembolic source was present in 5 patients (16%), whereas 2 patients (6%) had an ipsilateral carotid stenosis >50%. Small vessel disease was the most likely cause in 69% of our patients with SMS, whereas 31% had a potential cardioembolic source, large artery disease or infarcts not compatible with perforating artery disease.

Folgoration as an Example of Pathergy in a Patient Affected by Pyoderma Gangrenosum and Takayasu's Arteritis

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown aetiology. Clinical manifestations of PG are characterized by destructive, necrotizing, and noninfective ulceration of the skin. 20–30% of cases are initiated and aggravated by minor trauma or surgery, a phenomenon named pathergy. PG is related to several autoimmune diseases including ulcerative colitis, Crohn's disease, rheumatoid arthritis, and monoclonal gammopathy. The association with Takayasu's arteritis (TA), a chronic inflammatory and stenotic disease of large and medium-sized arteries, is instead less common. We report a case of PG associated with TA that was induced by an accident with folgoration of the skin; in this case the folgoration can be considered as an exemple of Pathergy, that is, a characteristic feature of PG.

Advances in Coronary Microvascular Dysfunction

Considerable focus has been directed towards coronary arterial disease in the management of coronary heart disease, however the coronary microcirculation plays a major role in the regulation of coronary blood flow. Thus while we have multiple medical and revascularisation therapies to treat large vessel coronary artery disease, therapies directed towards the microcirculation are very limited. This review paper summarises important aspects of coronary microvascular dysfunction including (a) methods of assessment, (b) clinical classification of associated disorders, (c) possible pathophysiological mechanisms, and (d) potential therapies. Hence this will provide important background to advancing our understanding and management of coronary heart disease by targeting the coronary microcirculation.

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 Role of High-Sensitivity C-Reactive Protein in Asymptomatic Intra- and Extracranial Large Artery Diseases

Background: It remains unclear whether high-sensitivity CRP (hs-CRP) is predictive of atherosclerosis in the intracranial artery. The aim of this study is to assess the role of hs-CRP in asymptomatic intracranial artery occlusive diseases. Methods: Of the 3,366 apparently healthy subjects who received a brain checkup, 138 with ≧25% intracranial artery stenosis on magnetic resonance angiography, 267 with ≧25% extracranial carotid artery stenosis on B-mode ultrasonography and 435 without intracranial artery or extracranial carotid artery stenosis (age-matched controls) were selected for this study. Results: The mean CRP concentration in the subjects with intracranial artery stenosis was not significantly different from that in the control subjects, and the differences of mean CRP concentrations among the subgroups with 25–49, 50–74 and 75% or greater stenosis in the intracranial artery were not significant. The odds ratios of hs-CRP for extracranial carotid artery stenosis tended to increase with increasing CRP concentrations, but those of hs-CRP for intracranial artery stenosis showed no significant difference. Conclusion: The degree of atherogenic inflammation in asymptomatic intracranial artery stenosis may be less than that in extracranial carotid artery stenosis.

TRANSLATIONAL IMPACT

Atherosclerosis is a progressive, chronic inflammatory disease of large arteries in which lesions preferentially occur at vessel sites exposed to rapid changes in blood flow. Low density lipoprotein (LDL) deposition and leukocyte infiltration leads to plaque formation and narrowing of the artery (stenosis), which restricts blood flow and causes angina. Atherosclerosis can also induce thrombus formation if lipids from plaques come into contact with blood, and plaque associated weakening of artery walls can lead to eventual rupture (aneurysm).PECAM-1 is a membrane protein expressed on the surface of many cells in the blood, as well as the endothelial cells lining blood vessels. PECAM-1 participates in the adhesion cascade necessary for leukocyte extravasation and serves as a sensor responding to changes in mechanical shear force that result from changes in blood flow.In this report, the authors determine that PECAM-1 induces susceptibility to atherosclerosis. Using mice deficient in the cell adhesion molecule PECAM-1 (PECAM-1−/−), researchers found a 50–60% reduction of atherosclerotic lesions in the aortae of mice with a genetic susceptibility to atherosclerosis (ApoE−/−). Since some athlerosclerotic lesions are found in PECAM-1−/− animals, it is likely that the absence of PECAM-1 is not completely preventative, but delays the onset of pathology.PECAM-1 functions in processes of inflammation and in the sensing of shear stress related to blood flow. It is possible that one or both of these processes contribute to the development and progression of atherosclerosis, suggesting that PECAM-1 is a potential candidate for drug targeting to limit the disease process.

PECAM-1 is a critical mediator of atherosclerosis

Atherosclerosis is a chronic inflammatory disease of large arteries in which lesion development preferentially occurs at vessel sites exposed to rapid changes in flow. We have previously shown that platelet endothelial cell adhesion molecule (PECAM-1), a surface receptor of the immunoglobulin superfamily, is involved in mechanosensing of rapid changes in flow. We wondered whether apolipoprotein E deficient (ApoE(-/-)) mice, predisposed to development of atheromas, would be protected from atherosclerosis by deficiency in PECAM-1. Using double knockout (DKO) mice for both PECAM-1 and ApoE (ApoE(-/-)/PECAM-1(-/-)) we found a significant reduction of sudanophilic lesions in their aortae compared to single knockout (SKO) (ApoE(-/-)/PECAM-1(+/+)) mice maintained on a high-fat Western diet. Immunostaining of aortic sinus cross sections demonstrated significantly lower ICAM-1 expression in DKO lesions compared with SKO lesions, and en face preparations of vessel regions subjected to disturbed and laminar flow showed less disruption of junctional connexin 43 in DKO than in SKO mice. Thus, PECAM-1 deficiency reduced the extent of lesions at the aortic arch and the aortic sinus, and lowered atherogenic indices. These results suggest that PECAM-1 is an important factor in the atherogenic changes seen in the ApoE-deficient mouse model and thus should be considered as a potential target for protection against atherosclerosis.

The leukoaraiosis is more prevalent in the large artery atherosclerosis stroke subtype among Korean patients with ischemic stroke

BackgroundSeveral studies have suggested that the specific stroke subtype may influence the presence of leukoaraiosis in patients with ischemic stroke. We investigated the association between stroke subtype and leukoaraiosis in Korean patients with ischemic stroke by MRI.MethodsThere were 594 patients included in this study that were classified as large artery disease, lacune and cardioembolic stroke. For large-artery disease, the analysis focused on the intracranial or extracranial location of the stenosis, and the multiplicity of the stenotic lesions. Leukoaraiosis grading was performed according to the Atherosclerosis Risk in Communities Study.ResultsThere was a significant association between leukoaraiosis and the stroke subtypes; the large-artery-disease group had a higher prevalence of leukoaraiosis than did the other groups (55.4% in the large-artery-disease group, 30.3% in the lacunar group and 14.3% in the cardioembolic group, P = 0.016 by chi-square test). On the multivariate linear regression analysis, age, the presence of hypertension, previous stroke and stroke subtype were independently associated with the presence of leukoaraiosis. In the sub analysis of the large-artery-disease group, the leukoaraiosis had a tendency to be more prevalent in the mixed and intracranial stenosis group than did the extracranial stenosis group (45.5% in the mixed group, 40.3% in the intracranial group and 26.9% in the extracranial group, P = 0.08 by chi-square test).ConclusionThe association of leukoaraiosis with large-artery disease in this study might be due to the relatively high prevalence of intracranial occlusive lesions in Korean stroke patients compared to other ethnic groups.

Age-dependent differences in demographics, risk factors, co-morbidity, etiology, management, and clinical outcome of acute ischemic stroke

Comparisons between younger and older stroke patients including comorbidities are limited. Prospective data of consecutive patients with first ever acute ischemic stroke were compared between younger (< or = 45 years) and older patients (> 45 years). Among 1004 patients, 137 (14 %) were < or = 45 years. Younger patients were more commonly female (57 % versus 34 %; p < 0.0001), had a lower frequency of diabetes (1 % versus 15 %; p < 0.0001), hypercholesterolemia (26 % versus 56 %; p < 0.0001), hypertension (19 % versus 65 %; p < 0.0001), coronary heart disease (14 % versus 40 %; p < 0.0001), and a lower mean Charlson co-morbidity index (CCI), (0.18 versus 0.84; p < 0.0001). Tobacco use was more prevalent in the young (39 % versus 26 %; P < 0.0001). Large artery disease (2 % versus 21 %; p < 0.0001), small artery disease (3 % versus 12 %; p = 0.0019) and atrial fibrillation (1 % versus 17 %; p = 0.001) were less common in young patients, while other etiologies (31 % versus 9 %; p < 0.0001), patent foramen ovale or atrial septal defect (44 % versus 26 %; p < 0.0001), and cervical artery dissection (26 % versus 7 %; p < 0.0001) were more frequent. A favorable outcome (mRS 0 or 1) was more common (57.4 % versus 46.9 %; p = 0.023), and mortality (5.1 % versus 12 %; p = 0.009) was lower in the young. After regression analysis, there was no independent association between age and outcome (p = 0.206) or mortality (p = 0.073). Baseline NIHSS score (p < 0.0001), diabetes (p = 0.041), and CCI (p = 0.002) independently predicted an unfavorable outcome. Younger patients were more likely to be female, had different risk factors and etiologies and fewer co-morbidities. There was no independent association between age and clinical outcome or mortality.

Prevention of aortic fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in angiotensin II-induced hypertension

Fibrosis is an important component of large conduit artery disease in hypertension. The endogenous tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) has anti-inflammatory and antifibrotic effects in the heart and kidney. However, it is not known whether Ac-SDKP has an anti-inflammatory and antifibrotic effect on conduit arteries such as the aorta. We hypothesize that in ANG II-induced hypertension Ac-SDKP prevents aortic fibrosis and that this effect is associated with decreased protein kinase C (PKC) activation, leading to reduced oxidative stress and inflammation and a decrease in the profibrotic cytokine transforming growth factor-beta1 (TGF-beta1) and phosphorylation of its second messenger Smad2. To test this hypothesis we used rats with ANG II-induced hypertension and treated them with either vehicle or Ac-SDKP. In this hypertensive model we found an increased collagen deposition and collagen type I and III mRNA expression in the aorta. These changes were associated with increased PKC activation, oxidative stress, intercellular adhesion molecule (ICAM)-1 mRNA expression, and macrophage infiltration. TGF-beta1 expression and Smad2 phosphorylation also increased. Ac-SDKP prevented these effects without decreasing blood pressure or aortic hypertrophy. Ac-SDKP also enhanced expression of inhibitory Smad7. These data indicate that in ANG II-induced hypertension Ac-SDKP has an aortic antifibrotic effect. This effect may be due in part to inhibition of PKC activation, which in turn could reduce oxidative stress, ICAM-1 expression, and macrophage infiltration. Part of the effect of Ac-SDKP could also be due to reduced expression of the profibrotic cytokine TGF-beta1 and inhibition of Smad2 phosphorylation.

Diabetes increases large artery diseases, but not small artery diseases in the brain

It is established that diabetes causes various systemic micro- and macro-vascular complications. Little has been, however, studied on the differential effects of diabetes on the large artery diseases (LAD) or small artery disease (SAD) in the brain. The purpose of this study was to examine an association of diabetes on the incidence of underlying LAD versus SAD in ischemic stroke patients. We prospectively collected 523 acute ischemic stroke patients without cardioembolic causes or other determined causes of stroke. Using brain MRI, the cerebral LAD (extracranial and intracranial arterial stenosis of 50 % or more) and the cerebral SAD (old lacunar infarction, microbleeds and leukoaraiosis) findings were assessed. Information regarding vascular risk factor was also collected. Among the patients (male, n = 342; diabetes, n = 200), diabetes was not associated with the presence of LADs or SADs in female subjects, but strongly with the presence of intracranial LAD in male subjects (p < 0.01). The association remained significant (OR 2.09, 95 %CI 1.25-3.51) after adjusting for major confounders. A similar association was also found in intracranial LAD and insulin resistance. There was, however, no significant association of diabetes with SAD in male nor in female patients. Our results showed that diabetes is associated with the frequency of intracranial LAD, especially in males. Out study may be regarded as evidence of differential biological effects of diabetes on cerebral vasculature.

Transient Ischemic Attack Etiologic Subtype and Early Risk of Stroke

To the Editor: Although clinical features help stratify stroke risk after transient ischemic attack (TIA), the novel study by Purroy et al1 on predictors of early recurrent ischemia according to etiologic subtype of the index TIA emphasizes additional variables we must consider in our prognostication algorithms. We wish to discuss some issues raised in the article which we felt merited further exploration. The study found a very low recurrent event rate in the small-vessel disease (SVD) group (1.5%, or 1 event/68 patients). Transient lacunar events due to SVD are commonly thought to have a relatively benign prognosis, and these results support such an assertion. However, in our experience, lacunar events can often progress after a seemingly transient onset, and others have shown that lacunar …

Guest Editorial: are diabetes‐related wounds and amputations worse than cancer?

Certainly one of the most feared complications of diabetes is the lower extremity amputation 1. This fear is not unwarranted. Diabetes-related ulcer and amputation may be associated with surprisingly high 5-year mortality. Moulik et al.2 reported a 5-year mortality of 45%, 18% and 55% for neuropathic, neuroischaemic and ischaemic ulcers, respectively. As expected, mortality was higher in ischaemic ulcers than neuropathic ulcers. However, it is fairly evident based on these data that all types of diabetic foot ulcers are associated with high morbidity and mortality. Similarly, approximately half the persons receiving a diabetes-related amputation will not be alive in 5 years. Certainly, peripheral vascular disease may be implicated as a significant factor associated with shorter life span. Criqui reported the 10-year mortality in patients with peripheral arterial disease and found a substantially higher risk of mortality among patients with large vessel peripheral arterial disease – a factor that may be even more profound today than when it was reported in the early 1990s 3, 4. Faglia et al. related this high mortality with the absence of revascularisation, citing a 1.7-fold greater risk for death in ischaemic subjects who might have benefited from intervention 5. How do these data compare with other serious medical conditions, such as cancer? If one reviews Figure 1, one might conclude that persons with lower extremity complications of diabetes have 5-year mortality rates similar or worse than many common types of cancer 6-10. In fact, some high-risk subgroups such as persons with renal disease requiring distal bypass may have 5-year mortality rates approaching 95% 10. Five-year mortality (%). Perhaps now is the time to change our discussion with health-care administrators, policy makers and especially ourselves. The disease state that many of us treat routinely is, quite literally, killing our patients at a rate comparable to cancer. Addressing this issue aggressively may alter this and make a difference for millions of people worldwide.

Response to Letter by Sheikh

Response: We appreciate the comments by Dr Sheikh. In our research letter,1 we studied the prevalence and associations of intracranial large-artery disease (ICLAD) among ethnic South Asians in Singapore. The cited reference “Global burden of intracranial atherosclerosis”2 for the statement reading “ICLAD is the most common vascular lesion in stroke worldwide” was published in the International Journal of Stroke , the official journal of the World Stroke Organization (WSO), edited by Prof Geoffrey Donnan, current president of the WSO. It is not registered with PubMed Central as its first issue was only published in February …

Prevalence of Intracranial Atherosclerosis and Coexistent Conditions in Ethnic South Asians

To the Editor: Although the objectives of their study were not stated, De Silva et al1 used clinical data on 200 acute ischemic stroke patients admitted in a hospital in Singapore to determine the prevalence of intracranial large-artery disease (ICLAD) and its risk factors. The study subjects were selected on the basis of their origin of the Indian subcontinent (ethnic South Asians). The authors declared that “ICLAD is the most common vascular lesion in stroke worldwide”. To justify their declaration, they cited a reference (Reference 2 in their article1) to an article published in Int J Stroke . This publication was not found in PubMed Central. The authors found that 54% of stroke patients had ICLAD and they pronounced it as “high burden of …