Large-vessel Atherosclerotic Disease Research Articles

The Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE): protocol for a randomised, double-blind, placebo-controlled trial

BackgroundInflammation is a key mediator in the development and progression of the atherosclerotic disease process as well as its resultant complications, like myocardial infarction (MI), stroke and cardiovascular (CV) death,...

An In-Depth Analysis of Medullary Strokes at a Tertiary Care Stroke Center: Incidence, Clinical and Radiological Characteristics, Etiology, Treatment, and Prognosis.

Introduction Medullary infarctions (MI) are a rare medical entity that is classified mainly as the more commonly lateral medullary infarcts (LMI) and the less common medial medullary infarcts (MMI). Lateral medullary syndrome, also known as Wallenberg syndrome, results when the medulla oblongata is affected and predominantly occurs secondary to atherosclerotic occlusion of the vertebrobasilar arteries. Previous studies have focused more on the anatomical, clinical, and topographical aspects of medullary infarcts. We describe the incidence of their presentation, radiological findings, etiology, treatment, and outcome at our comprehensive stroke center. Material and method This is a retrospective cohort study of 108 medullary stroke patients with confirmed clinical and radiological diagnoses of MI at Hamad General Hospital, Doha, between January 1, 2018 and December 31, 2020. We evaluated the electronic medical records of all stroke patients. Result During the selected period, a total of 2,912 ischemic strokes were reported. Of these, 843 (28.8%) were posterior circulation strokes. Only 108 (3.7%) patients had medullary strokes. Commonly encountered neurological features were dizziness (94.4%), limb ataxia (84.3%), dysarthria (44.4%), ipsilateral facial sensory loss (32.4%), headache (32.4%), contralateral limb sensory loss (25%), ipsilateral hemiparesis (24%), dysphagia (19.4%), and hiccups (13%). Most strokes reported were either minor (73% with National Institutes of Health Stroke Scale [NIHSS] 1-4) or moderate (26% with NIHSS 5-15). LMIs (87.9%) were the most common, followed by medial paramedian MI (10%). Twenty-five percent had extramedullary involvement, predominantly of the cerebellum (17.6%). Out of the total number of patients, 44 (40.7%) had large vessel atherosclerotic disease, followed by 41 (37.6%) whose stroke was due to small vessel disease, 15 (13.8 %) due to undetermined etiology, and 6 (5.5%) due to arterial dissection. Twenty-eight patients (25.4%) underwent 48-hour Holter monitoring, which detected atrial fibrillation in two patients (1.85%). The majority of patients (98.2%, or 106 patients) received antiplatelet therapy, while 68.5% (74 patients) received single antiplatelet therapy (SAPT), and 29.6% (32 patients) received dual antiplatelet therapy (DAPT). Noteworthy is that only 2.7% (three patients) received thrombolysis as an acute reperfusion therapy. Forty-seven percent (51 patients) were discharged home (mRS 0-2), and 51.9% (56 patients) were transferred to rehabilitation facilities. Follow-up assessments were performed at the stroke clinic for 57.4% (62) of the patients. The assessments found that 46 of the follow-up patients were functionally independent at that time (mRS 0-2). Conclusion This is the first large local study of medullary strokes to determine their frequency, presentation, etiology, treatment, and clinical outcome. Medullary strokes represent 3.7% of total ischemic strokes at our comprehensive stroke center. MI is rare and could present with a variety of neurological and non-specific symptoms that mimic common benign conditions. Prompt and early recognition with a high index of suspicion, the use of posterior NIHSS (POST-NIHSS), and urgent MRI-diffusion-weighted imaging (DWI) of the brain in acute settings can improve early diagnosis and the rate of reperfusion therapy. Further studies are needed to enable the early recognition and treatment of medullary infarcts.

The role of cross-sectional imaging of the extracranial and intracranial vasculature in embolic stroke of undetermined source.

Despite an extensive workup, nearly one third of ischemic strokes are defined as Embolic Stroke of Undetermined Source (ESUS), indicating that no clear etiologic cause has been identified. Since large vessel atherosclerotic disease is a major cause of ischemic stroke, we focus on imaging of large vessel atherosclerosis to identify further sources of potential emboli which may be contributing to ESUS. For a stroke to be considered ESUS, both the extracranial and intracranial vessels must have <50% stenosis. Given the recent paradigm shift in our understanding of the role of plaque vulnerability in ischemic stroke risk, we evaluate the role of imaging specific high-risk extracranial plaque features in non-stenosing plaque and their potential contributions to ESUS. Further, intracranial vessel-wall MR is another potential tool to identify non-stenosing atherosclerotic plaques which may also contribute to ESUS. In this review, we discuss the role of cross-sectional imaging of the extracranial and intracranial arteries and how imaging may potentially uncover high risk plaque features which may be contributing to ischemic strokes.

O16: TARGETING THE LOX-1 SCAVENGER RECEPTOR ATTENUATES ATHEROSCLEROSIS AND NEOINTIMAL HYPERPLASIA IN APO-E NULL TRANSGENIC MICE

Abstract Introduction The clinical consequences of atherosclerosis and post-procedure neointimal hyperplasia (NIH) represent a significant proportion of the vascular surgeon's workload. Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) is a class E scavenger receptor expressed in endothelial cells implicated in atherosclerosis and NIH. This study aims to demonstrate the therapeutic potential of LOX-1 targeting using a transgenic mouse model and LOX-1-specific non-antibody synthetic protein scaffolds called affimers. Method Apolipoprotein-E (APO-E) null and APO-E/LOX-1 double-null transgenic mice were fed a high cholesterol western diet for 12 weeks. One group of APO-E null mice was treated subcutaneously with LOX-1 affimer. All mice underwent unilateral common femoral artery wire injury at week 8. Mice were culled and tissues harvested for evaluation of atherosclerotic burden and femoral artery NIH. Studies were carried out with Home Office approval. Result Compared with APO-E null controls, carotid and femoral bifurcation atherosclerosis (p&amp;lt;0.05) and total aortic plaque coverage (p&amp;lt;0.01) were significantly reduced in APO-E/LOX-1 double-null mice. Reductions were observed in APO-E null mice treated with LOX-1 affimer, however these were non-significant. Femoral artery NIH was reduced by 16% in APO-E/LOX-1 double null and 11% in LOX-1 affimer treated APO-E null mice compared with untreated APO-E controls, however these reductions were non-significant. Conclusion This study demonstrates the therapeutic potential of LOX-1 targeting in large vessel atherosclerotic disease and NIH. Knockout of the LOX-1 transgene produced promising results, while results following LOX-1 affimer therapy were less impressive. Improvements in affimer pharmacokinetics and drug delivery optimisation are avenues for future studies. Take-home message The LOX-1 scavenger receptor is a potential novel therapeutic target in large-vessel atherosclerosis and neointimal hyperplasia.

Alternative Splicing of Putative Stroke/Vascular Risk Factor Genes Expressed in Blood Following Ischemic Stroke Is Sexually Dimorphic and Cause-Specific.

Genome-wide association studies have identified putative ischemic stroke risk genes, yet, their expression after stroke is unexplored in spite of growing interest in elucidating their specific role and identifying candidate genes for stroke treatment. Thus, we took an exploratory approach to investigate sexual dimorphism, alternative splicing, and etiology in putative risk gene expression in blood following cardioembolic, atherosclerotic large vessel disease and small vessel disease/lacunar causes of ischemic stroke in each sex compared to controls. Whole transcriptome arrays assessed 71 putative stroke/vascular risk factor genes for blood RNA expression at gene-, exon-, and alternative splicing-levels. Male (n = 122) and female (n = 123) stroke and control volunteers from three university medical centers were matched for race, age, vascular risk factors, and blood draw time since stroke onset. Exclusion criteria included: previous stroke, drug abuse, subarachnoid or intracerebral hemorrhage, hemorrhagic transformation, infection, dialysis, cancer, hematological abnormalities, thrombolytics, anticoagulants or immunosuppressants. Significant differential gene expression (fold change > |1.2|, p < 0.05, partial correlation > |0.4|) and alternative splicing (false discovery rate p < 0.3) were assessed. At gene level, few were differentially expressed: ALDH2, ALOX5AP, F13A1, and IMPA2 (males, all stroke); ITGB3 (females, cardioembolic); ADD1 (males, atherosclerotic); F13A1, IMPA2 (males, lacunar); and WNK1 (females, lacunar). GP1BA and ITGA2B were alternatively spliced in both sexes (all patients vs. controls). Six genes in males, five in females, were alternatively spliced in all stroke compared to controls. Alternative splicing and exon-level analyses associated many genes with specific etiology in either sex. Of 71 genes, 70 had differential exon-level expression in stroke patients compared to control subjects. Among stroke patients, 24 genes represented by differentially expressed exons were male-specific, six were common between sexes, and two were female-specific. In lacunar stroke, expression of 19 differentially expressed exons representing six genes (ADD1, NINJ2, PCSK9, PEMT, SMARCA4, WNK1) decreased in males and increased in females. Results demonstrate alternative splicing and sexually dimorphic expression of most putative risk genes in stroke patients' blood. Since expression was also often cause-specific, sex, and etiology are factors to consider in stroke treatment trials and genetic association studies as society trends toward more personalized medicine.

Opportunities to explore the physiology of arterial insufficiency and claudication

Walking dysfunction in patients with intermittent claudication is now understood to result from the complex interplay of large vessel atherosclerotic disease and responses/concomitant processes in small vessels/capillaries as well as in muscle tissue itself.1,2 The ankle-brachial index with toe pressures (with or without treadmill exercise) has been our primary physiologic diagnostic modality both in the clinic and research space. The clinical usefulness of the ankle-brachial index in patients with claudication is limited by its poor relationship to ambulatory capacity and limb pain symptoms.

Carotid Atherosclerotic Disease and Risk Factors in Patients with Ischemic Stroke – Study Report –

Abstract Ischemic stroke (IS) is the second frequent vascular disease after myocardial infarction, with different clinical and etiological aspects and various risk factors. Large vessel atherosclerotic disease is the most frequent IS causing pathology, followed by cerebral microangiopathy and cardioembolic events. Cervical arteries Doppler ultrasonography helps identifying the subtype of IS, and by revealing the vascular status of the patient, guides the therapeutic decision and secondary IS prevention. The aim of this paper is to present the results of an observational, retrospective, analytical study on a number of 174 patients with acute IS evaluated by Doppler carotid ultrasound in CVASIC Research Centre of Academic Emergency Hospital of Sibiu from January to December 2018. Materials and methods: All patients with IS admitted in our centre received a Doppler carotid ultrasound evaluation. We observed the degree of carotid stenosis, presence of atherosclerotic risk factors and their influence. Results: The mean age of patients was 71.3 years (36 to 92 years range). 16 (9.19%) patients presented occlusion of internal carotid artery (ICA) on the same side as stroke, 37 (21.26%) had severe carotid stenosis (&gt;70%), 31 (17.81%) presented moderate stenosis (50-70%), the remaining patients had mild or no stenosis. 129 (74,13%) patients presented arterial hypertension, 51 (29.31%) patients had diabetes mellitus, 14 (8.04%) were smokers, 81 (46.56%) had dyslipidemia. Conclusions: A large number of patients had severe carotid stenosis and occlusion. The most common risk factor was arterial hypertension, followed by dyslipidemia and diabetes mellitus. Continuous medical education of population at risk regarding good nutrition principles and healthy lifestyle are needed to reduce the social costs of ischemic stroke.

Association between blood pressure components and the presence of carotid plaque among adults aged 45 years and older: a population-based cross-sectional study in rural China.

Pulse pressure is strongly associated with the early development of large-vessel atherosclerotic disease. However, the relationship between pulse pressure and carotid plaque in China is unknown. Thus, we investigated the associations of pulse pressure and mean arterial pressure with the presence of carotid plaques in a low-income population in rural China. Residents, aged ≥45 years, without histories of stroke or cardiovascular disease were enrolled. Participant demographics, previous medical histories, and lifestyle information were collected; anthropometric measures, serum profiles, and B-mode ultrasonographic investigations were also performed. The mean age of participants (n = 3789) was 59.9 years overall (men 61.1 years; women, 59.1 years). The mean SBP (146.42 mmHg) and DBP (86.81 mmHg), pulse pressures (59.61 mmHg), and mean arterial pressures (106.68 mmHg) were high in this population. The odds ratio (95% confidence interval) for the association of pulse pressure with the presence of carotid plaques was 1.028 (1.023-1.033), in the univariate analysis. After gradual adjustment for demographic features, risk factors, and serum profile measurements, this positive association remained statistically significant (all, P < 0.001). However, there was no significant relationship between mean arterial pressure and the presence of carotid plaques. These findings suggest that an elevated pulse pressure is an independent risk factor for the presence of carotid plaque. These results suggest that enhanced monitoring of blood pressure components, among low-income residents, is crucial for decreasing the risk of stroke and other cardiovascular disease in China.

Whole-brain magnetic resonance imaging of plaque burden and lenticulostriate arteries in patients with different types of stroke.

Background:Large-vessel atherosclerotic disease is an important pathogenesis of deep-perforator infarction (DPI). However, altered vessel walls of intracranial large arteries and distribution of small arteries in DPI are unclear because of the limited resolution of current imaging techniques. In this study the intracranial plaque burden and lenticulostriate artery (LSA) distribution in patients with recent DPI and non-DPI using whole-brain vessel-wall imaging (WB-VWI) were investigated.Methods:A total of 44 patients with recent DPI (23 patients) or non-DPI (21 patients) due to intracranial atherosclerotic disease were prospectively enrolled. WB-VWI was performed in all the patients using a three-dimensional T1-weighted vessel-wall magnetic resonance technique. Hemispheres with DPI and non-DPI were considered as the DPI group and non-DPI group, respectively. Hemispheres without a history of stroke were the control group. The intracranial plaque burden was compared between the DPI and non-DPI groups. The number and length of visualized LSA branches among DPI, non-DPI, and control groups were also evaluated.Results:A total of 77 hemispheres were analyzed (23 in the DPI group, 21 in the non-DPI group, and 33 in the control group). Plaque burden was lower (p = 0.047) in the DPI group (82.0 ± 45.9 mm3) compared with the non-DPI group (130.9 ± 90.3 mm3). There was a significant reduction (p = 0.002) in length of visualized LSA branches in the DPI group (74.1 ± 21.7 mm) compared with the control group (104.6 ± 33.3 mm).Conclusions:WB-VWI enables the combination of vessel-wall and LSA imaging in one image setting, which can provide information about plaque burden and LSA distribution.

Influence of hemodynamics on enlarged perivascular spaces in atherosclerotic large vessel disease

ABSTRACTObjectives: Enlarged perivascular spaces (EPVS) are often observed in small vessel disease on T2-weighted images. However, their role in ischemic conditions caused by cerebral large vessel disease remains unclear. We evaluated EPVS in patients with hemodynamic compromise associated with atherosclerotic large vessel disease and aimed to identify the pathophysiology of EPVS.Methods: We examined 28 adults with atherosclerotic large vessel disease. EPVS numbers in the basal ganglia and the centrum semiovale were assessed. For each affected hemisphere, the total numbers of EPVS were compared with those on the unaffected side. EPVS in the impaired hemodynamics group were compared with those in the unimpaired hemodynamics group. Moreover, EPVS were compared in the presence/absence of large stroke.Results: The number of EPVS was significantly increased on the affected side in the centrum semiovale (p = 0.023), particularly in the impaired hemodynamics group (p = 0.006). Moreover, in the small stroke subgroup of the impaired hemodynamics group, the number of EPVS was significantly increased on the affected side (p = 0.002), although this number was insignificant in the large ischemic stroke subgroup.Conclusions: The number of EPVS was increased in patients with atherosclerotic large vessel disease with hemodynamic compromise and decreased in the presence of a large stroke. EPVS might act as fluid absorbers in a hemodynamically compromised state until the occurrence of an ischemic stroke.

Large Artery Atherosclerosis: Extracranial and Intracranial.

AbstractLarge vessel atherosclerotic disease (affecting both intracranial and extracranial arteries) is a highly prevalent cause of stroke. In this review, the authors describe the epidemiology, evaluation, diagnosis, and therapeutic aspects of large-vessel atherosclerotic disease. Endarterectomy and stenting have proven to be effective methods for carotid artery revascularization and stroke prevention, although some of the clinical trials demonstrating this benefit predated the advances in modern medical therapy. Randomized clinical trials comparing aggressive management with surgical and endovascular stenting plus aggressive medical management have shown medical management alone to be safer and more effective for preventing stroke in intracranial and vertebrobasilar stenosis.

Does stroke etiology play a role in predicting outcome of acute stroke patients who underwent endovascular treatment with stent retrievers?

AimsThe goal of the study was to identify whether the stroke etiology play a role in the recanalization and outcome of patients who underwent mechanical thrombectomy with stent retrievers. Methods and resultsA retrospective analysis of a prospectively collected database included consecutive patients treated with stent retrievers. We included patients with cardioembolic stroke and large vessel atherosclerotic disease and compared risk factors for stroke, baseline NIHSS and Alberta Stroke Program Early CT scores (ASPECTS), stroke outcome, recanalization rate, onset-to-recanalization, onset-to-groin puncture time and the procedural time between two groups. Male sex was statistically more common in patients with large vessel atherosclerotic disease. Mean time from symptom onset- to the achievement of recanalization in patients with LVAD was 242±72.4 compared with cardioembolic stroke patients (301±70.7; p=0.014). Time for groin puncture to recanalization was longer in patients with cardioembolic stroke compared to LVAD group (97.5±44.3 vs 58.2±21.8; p=0.002). Time for microcatheter to successful recanalization or procedural termination was longer in patients with cardioembolic stroke compared to LVAD group (63.6±30.2 vs 34.2±19.4; p<0.001) with cardioembolic stroke had significantly worse long-term outcome (mRS 3–6) compared to those with LVAD (60.6% vs 26.3%; p=0.036). ConclusionStroke etiology may play a role in the outcome of acute stroke patients who underwent endovascular stroke therapy. Cardioembolic strokes may be more resistant to endovascular acute stroke treatment.

Antiplatelet Treatment in Stroke: New Insights.

Stroke is a feared vascular event among healthy people and those with cardiovascular disease, and holds a leading position as a cause of disability and death worldwide. Antiplatelet therapy is central in the management of patients with ischemic nonembolic stroke and transient ischemic attacks. In this narrative review, we provide an overview and update of evidence regarding antiplatelet treatment in the primary and secondary prevention of stroke. Aspirin, clopidogrel and aspirin plus dipyridamole are the mainstays of antiplatelet treatment post-stroke, while promising agents include triflusal, cilostazol and ticagrelor. Available data are in favor of dual antiplatelet treatment in the early treatment of atherosclerotic large vessel disease. Long-term dual antiplatelet treatment should be individualized keeping in mind the higher rates of bleeding complications. Treatment with an antiplatelet agent is recommended to reduce recurrent stroke and death in patients with a non-cardioembolic ischemic stroke or transient ischemic attack. Moreover, clinicians should carefully assess the pros and cons in each case and individualize the need for prolonged dual antiplatelet therapy.

Morphological and functional carotid vessel wall properties in relation to cerebral white matter lesions in myocardial infarction patients.

ObjectiveAtherosclerotic large vessel disease is potentially involved in the pathogenesis of cerebral small vessel disease related to occurrence of white matter lesions (WMLs) in the brain. We aimed to assess morphological and functional carotid vessel wall properties in relation to WML using magnetic resonance imaging (MRI) in myocardial infarction (MI) patients.Materials and methodsA total of 20 MI patients (90 % male, 61 ± 11 years) underwent carotid artery and brain MRI. Carotid vessel wall thickness (VWT) was assessed, by detecting lumen and outer wall contours. Carotid pulse wave velocity (PWV), a measure of elasticity, was determined using the transit-time method. Patients were divided according to the median VWT into two groups. Brain MRI allowed for the WML score.ResultsMean VWT was 1.41 ± 0.29 mm and mean carotid PWV was 7.0 ± 2.2 m/s. A significant correlation (Pearson r = 0.45, p = 0.046) between VWT and PWV was observed. Furthermore, in the group of high VWT, the median WML score was higher as compared with the group with lower VWT (4.0 vs 3.0, p = 0.035).ConclusionsCarotid artery morphological and functional alterations are correlated in MI patients. Patients with high VWT showed a higher amount of periventricular WMLs. These findings support the hypothesis that atherosclerotic large vessel disease is potentially involved in the pathogenesis of cerebral small vessel disease.

Homocysteine, small-vessel disease, and atherosclerosis: an MRI study of 825 stroke patients.

We evaluated the relationship between hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and small-vessel disease (SVD) and atherosclerotic large-vessel disease (LVD) in stroke patients. A total of 825 noncardioembolic ischemic stroke patients whose plasma concentrations of total homocysteine were measured and whose MTHFR C677T polymorphism status was identified were included in this retrospective study. MRI of the brain and magnetic resonance angiography of the intracranial and extracranial cerebral arteries had been performed. SVD and LVD were assessed by the Scheltens scale (the SVD score) and by the number of atherosclerotic steno-occlusive arteries (the LVD score), respectively. The TT genotype of the MTHFR C677T polymorphism was associated with hyperhomocysteinemia (p < 0.001), but not with SVD (p = 0.182) or LVD (p = 0.988) scores. Multiple logistic regression analysis showed that hyperhomocysteinemia was associated with SVD (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.01-1.07; p = 0.005) and LVD (OR 1.02; 95% CI 1.00-1.05; p = 0.041) scores. Hyperhomocysteinemia was related to the LVD score of extracranial arteries (p = 0.008), but not to the LVD score of intracranial arteries (p = 0.730). In multiple logistic regression analysis, however, hyperhomocysteinemia was not related to the LVD score of extracranial arteries (p = 0.255). Hyperhomocysteinemia was associated with SVD of the brain and LVD of cerebral arteries. The MTHFR C677T polymorphism was not related to SVD and LVD, although the TT genotype was an important determinant of hyperhomocysteinemia.

Abstract 2668: Lacunar Strokes In Patients With Symptomatic Intracranial Stenosis

Background and Purpose: Lacunar strokes are conventionally attributed to a distinct microvascular pathophysiology, but the “lacunar hypothesis” has been challenged since some small deep infarcts are identified in patients with sources of cardioembolism or large vessel atherosclerotic disease. We hypothesized that patients with intracranial stenosis with a lacunar stroke presentation would have a lower risk of recurrent stroke than those with an index non-lacunar stroke, and that their recurrent strokes would predominantly be lacunar. Methods: We analyzed subjects enrolled with an index stroke into the Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial. The index and endpoint strokes were classified as lacunar or non-lacunar by central adjudication. The primary endpoint was recurrent ischemic stroke. Cox proportional hazard models were generated with stratification for severity of stenosis. Results: 347 subjects were enrolled after an index stroke, 38 were lacunar and 309 were non-lacunar. Over a mean follow-up of 1.8 years there was no significant difference in stroke recurrence between patients whose index stroke was lacunar (7/38; 18%) vs. non-lacunar (69/309; 22%) (HR 0.79, 95%CI: 0.36-1.71). Further, no significant differences were found when groups were stratified by 50-69% stenosis (HR 0.50, 95%CI:0.12-2.1) and ≥70% stenosis (HR 0.87, 95%CI: 0.34-2.2) but power was limited. Of the 7 recurrent strokes in patients whose index stroke was lacunar, all 7 were non-lacunar and 3 were in the territory of the stenotic artery. Of the 69 recurrent strokes in patients whose index stroke was non-lacunar, 6 (9%) were lacunar of which 4 were in the territory of the stenotic artery. Conclusions: The risk of recurrent stroke due to intracranial stenosis was similar in patients who presented with lacunar vs. non-lacunar strokes, and all recurrent strokes in patients presenting with lacunar stroke were non-lacunar. These findings suggest that the pathophysiology of index and recurrent strokes in patients presenting with a lacunar stroke and intracranial stenosis is related to the stenosis and not microvascular disease. Therefore, patients with intracranial stenosis who present with lacunar strokes should be included in future trials investigating secondary stroke prevention for symptomatic intracranial stenosis.

The Diagnosis of Vertebrobasilar Insufficiency Using Transcranial Doppler Ultrasound

Background. Vertebrobasilar insufficiency (VBI) is a hemodynamic posterior circulation transient ischemic attack (TIA) caused by intermittent vertebral artery occlusion that is induced by a head rotation or extension. VBI may result from large vessel atherosclerotic disease, dissection, cervical compressive lesions, and subclavian steal phenomenon. Diagnostic transcranial Doppler (TCD) of VBI disease and hemodynamic posterior circulation TCD monitoring in symptomatic positions might prove a useful tool in establishing the diagnosis. Patient and Material/Method. A 50-year-old Caucasian man presented with a one-year history of episodic positional vertigo and ataxic gait that were induced by a neck extension and resolved by an upright position or a neck flexion. Computed tomography angiogram (CTA) and TCD confirmed the presence of VBI where no blood flow was detected through posterior cerebral arteries in the symptomatic position (head extension position). Conclusion. TCD is a promising noninvasive technique that might have a role as a diagnostic test in VBI.

Peripheral Artery Disease and Glaucoma

To examine the relationship between peripheral artery disease (PAD) and glaucoma. As part of a population-based study of 3280 persons of Malay descent (78.7% response) aged 40 to 80 years examined between August 1, 2004, and June 30, 2006, the ankle-brachial index (ABI) was assessed in all persons with known diabetes mellitus and every fifth systematically sampled participant without diabetes. Peripheral artery disease was deemed present if the ABI was 0.9 or less. Glaucoma was diagnosed using International Society of Geographical and Epidemiological Ophthalmology criteria. Of the 922 participants who had ABI measured, 79 (8.6%) had PAD and 42 (4.6%) had glaucoma. Persons with PAD were more likely to have glaucoma (11.4% vs 3.9%; age- and sex-adjusted odds ratio [OR], 2.80; 95% confidence interval [CI], 1.26-6.24), higher intraocular pressure (age- and sex-adjusted mean, 16.4 vs 15.5; P = .05), and a larger vertical cup-disc ratio (age- and sex-adjusted mean, 0.45 vs 0.40; P = .02). The association of PAD with glaucoma persisted while controlling for hypertension, diabetes, body mass index, serum triglyceride levels, and beta-blocker use (multivariable-adjusted OR, 2.55; 95% CI, 1.09-5.98) and was stronger in people with diabetes (multivariable-adjusted OR, 2.91; 95% CI, 1.14-7.44). Peripheral artery disease was related to glaucoma, supporting an association between large-vessel atherosclerotic disease and glaucoma. However, because the study sample included a high proportion of persons with diabetes, further research is needed to determine the relevance of these results to the general population.

Atherosclerotic Peripheral Vascular Disease Symposium II

The primary goal of this American Heart Association renal intervention writing group was to discuss current controversies related to renal interventions and to recommend important areas of clinical research and advocacy initiatives in this peripheral arterial bed. The 4 areas covered in this section include (1) management of asymptomatic renal artery disease, (2) treatment of ischemic nephropathy, (3) prevention and treatment of atheroembolism in renal artery interventions, and (4) treatment of renal in-stent restenosis (ISR). Atherosclerotic renal artery disease is an often unrecognized contributor to refractory hypertension, renal insufficiency, and increased risk of cardiovascular death.1,2 Renal artery disease is associated with increased cardiovascular events (myocardial infarction, stroke, and death), and when associated with symptomatic coronary artery disease, it independently doubles the risk of death.3 Additionally, the presence of bilateral renal artery stenoses is associated with a reduced 4-year survival rate when compared with unilateral disease (47% versus 59%, P <0.001).3 Hypertension, renal insufficiency, and multisystem atherosclerosis are common entities, and the independent occurrence of these conditions is frequent. Thus, the physician must distinguish between association and causation in the evaluation of patients with atherosclerotic renal artery disease and critically appraise the potential for clinical improvement in selecting patients for renal artery intervention. In contrast to other regional manifestations of atherosclerosis, it is impractical to classify patients with atherosclerotic renal artery disease into symptomatic or asymptomatic categories. Two of the cardinal manifestations of renal artery disease, hypertension and renal insufficiency, are frequently “silent” with regard to clinical manifestations until end-organ damage or uremia occurs. Thus, the majority of patients may be deemed asymptomatic. A more appropriate classification of patients with atherosclerotic renal artery disease may be to classify them in relation to potential clinical consequences. We propose the following classification scheme in patients with renal artery disease:

Abstract 3077: Cross-Sectional Associations of Arterial Stiffness Measures and Ankle-Brachial Index: The Multi-Ethnic Study of Atherosclerosis (MESA)

The association between tonometry-derived measures of arterial stiffness and peripheral arterial disease (PAD) is unclear. Using baseline data from 2847 female and 2614 male participants of the NHLBI-funded MESA study, we conducted linear regression analyses adjusted for age, demographics and risk factors. Ankle-brachial index (ABI) was the dependent variable and measures of large (C1) and small artery elasticity (C2) and total vascular impedance (TVI), all measured from radial artery tonometry, were the independent variables in separate models. In men and women, lower C1 and C2 values were associated with lower ABI. Higher TVI was associated with lower ABI in men and women [P&lt;0.001]. Significant trends for C1, C2 and TVI were observed across clinical strata of ABI (Table ). In pairwise analyses, compared with participants with a normal ABI (1.1 to &lt;1.3), those with ABI &lt;1.1 tended to have significantly lower C2. Additionally, women with high ABI (1.3–1.5) tended to have significantly higher C2 values. Pairwise comparisons of lower and higher ABI groups compared with normal groups did not yield consistent findings for C1. Significantly higher TVI levels with lower ABI group were noted mostly in women (Table ). We observed a continuum of arterial mechanical characteristics across clinical ABI values, indicating that measures of arterial stiffness are significantly associated with ABI and severity of PAD. These results suggest that changes in C2 occur in patients with advanced lower extremity large-vessel atherosclerotic disease. Of note, female participants with high ABI between 1.3–1.5 had a significantly higher C2, arguing against the accepted “non-compressible” or “calcified arterial disease” explanation for high ABI in women. Associations Between ABI and Pulse Wave Analysis Measurements when adjusted for age, cigarette smoking, diabetes, hypertension, and creatinine level