Proximal Region of Carotid Atherosclerotic Plaque Shows More Intraplaque Hemorrhage: The Plaque at Risk Study.

BACKGROUND AND PURPOSE: Intraplaque hemorrhage contributes to lipid core enlargement and plaque progression, leading to plaque destabilization and stroke. The mechanisms that contribute to the development of intraplaque hemorrhage are not completely understood. A higher incidence of intraplaque hemorrhage and thin/ruptured fibrous cap (upstream of the maximum stenosis in patients with severe [≥70%] carotid stenosis) has been reported. We aimed to noninvasively study the distribution of intraplaque hemorrhage and a thin/ruptured fibrous cap in patients with mild-to-moderate carotid stenosis. MATERIALS AND METHODS: Eighty-eight symptomatic patients with stroke (<70% carotid stenosis included in the Plaque at Risk study) demonstrated intraplaque hemorrhage on MR imaging in the carotid artery plaque ipsilateral to the side of TIA/stroke. The intraplaque hemorrhage area percentage was calculated. A thin/ruptured fibrous cap was scored by comparing pre- and postcontrast black-blood TSE images. Differences in mean intraplaque hemorrhage percentages between the proximal and distal regions were compared using a paired-samples t test. The McNemar test was used to reveal differences in proportions of a thin/ruptured fibrous cap. RESULTS: We found significantly larger areas of intraplaque hemorrhage in the proximal part of the plaque at 2, 4, and 6 mm from the maximal luminal narrowing, respectively: 14.4% versus 9.6% (P = .04), 14.7% versus 5.4% (P < .001), and 11.1% versus 2.2% (P = .001). Additionally, we found an increased proximal prevalence of a thin/ruptured fibrous cap on MR imaging at 2, 4, 6, and 8 mm from the MR imaging section with the maximal luminal narrowing, respectively: 33.7% versus 18.1%, P = .007; 36.1% versus 7.2%, P < .001; 33.7% versus 2.4%, P = .001; and 30.1% versus 3.6%, P = .022. CONCLUSIONS: We demonstrated that intraplaque hemorrhage and a thin/ruptured fibrous cap are more prevalent on the proximal side of the plaque compared with the distal side in patients with mild-to-moderate carotid stenosis.

Apolipoprotein D: a potential biomarker for cerebral amyloid angiopathy.

AIMS: We investigated the potential of apolipoprotein D (apoD) as cerebrospinal fluid (CSF) biomarker for cerebral amyloid angiopathy (CAA) after confirmation of its association with CAA pathology in human brain tissue. METHODS: The association of apoD with CAA pathology was analysed in human occipital lobe tissue of CAA (n = 9), Alzheimer's disease (AD) (n = 11) and healthy control cases (n = 11). ApoD levels were quantified in an age- and sex-matched CSF cohort of CAA patients (n = 31), AD patients (n = 27) and non-neurological controls (n = 67). The effects of confounding factors (age, sex, serum levels) on apoD levels were studied using CSF of non-neurological controls (age range 16-85 years), and paired CSF and serum samples. RESULTS: ApoD was strongly associated with amyloid deposits in vessels, but not with parenchymal plaques in human brain tissue. CSF apoD levels correlated with age and were higher in men than women in subjects >50 years. The apoD CSF/serum ratio correlated with the albumin ratio. When controlling for confounding factors, CSF apoD levels were significantly lower in CAA patients compared with controls and compared with AD patients (P = 0.0008). CONCLUSIONS: Our data show that apoD is specifically associated with CAA pathology and may be a CSF biomarker for CAA, but clinical application is complicated due to dependency on age, sex and blood-CSF barrier integrity. Well-controlled follow-up studies are required to determine whether apoD can be used as reliable biomarker for CAA.

Association between fibrinogen and fibrinogen γ' and atherosclerotic plaque morphology and composition in symptomatic carotid artery stenosis: Plaque-At-RISK study.

INTRODUCTION: Von Willebrand Factor (VWF), ADAMTS13, fibrinogen and fibrinogen γ' are associated with an increased risk of ischemic stroke. Carotid atherosclerosis is an important risk factor for ischemic stroke. Characteristics of the vulnerable plaque; intraplaque hemorrhage (IPH), plaque ulceration and lipid-rich necrotic core (LRNC) can be visualized with imaging techniques. Since atherosclerosis might attribute to the association between coagulation factors and ischemic stroke risk, the aim of this study is to investigate the association between coagulation factors and atherosclerotic plaque characteristics in more detail. MATERIALS AND METHODS: In 182 patients of the Plaque-At-RISK study (prospective multicenter cohort study) with a recent transient ischemic attack (TIA) or ischemic stroke and a symptomatic mild-to-moderate carotid artery stenosis, we measured VWF antigen (VWF:Ag), ADAMTS13 activity, fibrinogen (Clauss), and fibrinogen γ'. Presence of plaque ulceration, IPH volume and LRNC volume were determined by Multidetector-Row Computed Tomography (MDCTA, n = 160) and Magnetic Resonance Imaging (MRI, n = 172). Linear regression analysis was used to assess the association between imaging biomarkers and coagulation factors. RESULTS: VWF:Ag or ADAMTS13 levels were not significantly associated with plaque ulceration, IPH and LRNC. We found an inverse association between fibrinogen and fibrinogen γ' and IPH volume (B = -23.40 mm3/g/L, p = 0.01 and B = -161.73 mm3/g/L, p = 0.01) and between fibrinogen and fibrinogen γ' and LRNC volume (B = -38.89 mm3 g/L, p < 0.01 and B = -227.06 mm3 g/L, p = 0.01). Additional adjustments for C-reactive protein (CRP) did not change the results. CONCLUSIONS: Fibrinogen and fibrinogen γ' are inversely associated with IPH volume and LRNC volume, independent of inflammation. CLINICAL TRIAL REGISTRATION: clinicaltrials.govNCT01208025.

Orthogonal B-Mode Evaluation of Common Carotid Artery Plaques Reveals the Absence of Outward Remodeling.

To properly assess morphologic and dynamic parameters of arteries and plaques, we propose the concept of orthogonal distance measurements, that is, measurements made perpendicular to the local lumen axis rather than along the ultrasound beam (vertical direction for a linear array). The aim of this study was to compare orthogonal and vertical artery and lumen diameters at the site of a plaque in the common carotid artery (CCA). Moreover, we investigated the interrelationship of orthogonal diameters and plaque size and the association of artery parameters with plaque echogenicity. In 29 patients, we acquired a longitudinal B-mode ultrasound recording of plaques at the posterior CCA wall. After semi-automatic segmentation of end-diastolic frames, diameters were extracted orthogonally along the lumen axis. To establish inter-observer variability of diameters obtained at the location of maximal plaque thickness, a second observer repeated the analysis (subset N = 21). Orthogonal adventitia-adventitia and lumen diameters could be determined with good precision (coefficient of variation: 1%-5%. However, the precision of the change in lumen diameter from diastole to systole (distension) at the site of the plaque was poor (21%-50%). The orthogonal lumen diameter was significantly smaller than the vertical lumen diameter (p <0.001). Surprisingly, the plaques did not cause outward remodeling, that is, a local increase in adventitia-adventitia distance at the site of the plaque. The intra- and inter-observer precision of diastolic-systolic plaque compression was poor and of the same order as the standard deviation of plaque compression. The orthogonal relative lumen distension was significantly lower for echogenic plaques, indicating a higher stiffness, than for echolucent plaques (p <0.01). In conclusion, we illustrated the feasibility of extracting orthogonal CCA and plaque dimensions, albeit that the proposed approach is inadequate to quantify plaque compression.

Association between eye position on brain scan and hospital mortality in acute intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Conjugate eye deviation (CED) and horizontal skew deviation are often seen in patients with intracerebral hemorrhage (ICH), but its prognostic significance is unclear. In this study, the association between brain scan assessed eye position and hospital mortality in patients with supratentorial ICH was tested. METHODS: A retrospective analysis was performed in 316 patients with supratentorial ICH. Eye position was measured on first brain computed tomography or magnetic resonance imaging. Patients with CED, horizontal skew deviation or no deviation were distinguished. The association between eye position and hospital mortality was assessed using logistic regression analysis. RESULTS: Conjugate eye deviation was present in 96 (30.4%), skew deviation in 44 (13.9%) and no deviation in 176 (55.7%) patients. In patients with CED, 81.3% had an eye position to the ipsilateral side of the hemorrhage. In univariable regression analysis, skew deviation was associated with mortality (odds ratio 3.10, 95% confidence interval 1.57-6.11; P = 0.001). In multivariable regression analysis, adjusting for age, ICH volume, intraventricular extension and Glasgow Coma Scale, eye position was not independently associated with mortality. CONCLUSION: Horizontal skew eyes were found to be an unfavorable prognostic factor. However, this was not independent of other important predictors of ICH mortality and is most probably explained by its association with worse initial clinical presentation.

Plaque At RISK (PARISK): prospective multicenter study to improve diagnosis of high-risk carotid plaques.

BACKGROUND: Patients with symptomatic carotid artery stenosis are at high risk for recurrent stroke. To date, the decision to perform carotid endarterectomy in patients with a recent cerebrovascular event is mainly based on degree of stenosis of the ipsilateral carotid artery. However, additional atherosclerotic plaque characteristics might be better predictors of stroke, allowing for more precise selection of patients for carotid endarterectomy. AIMS AND HYPOTHESIS: We investigate the hypothesis that the assessment of carotid plaque characteristics with magnetic resonance imaging, multidetector-row computed tomography angiography, ultrasonography, and transcranial Doppler, either alone or in combination, may improve identification of a subgroup of patients with < 70% carotid artery stenosis with an increased risk of recurrent stroke. METHODS: The Plaque At RISK (PARISK) study is a prospective multicenter cohort study of patients with recent (<3 months) neurological symptoms due to ischemia in the territory of the carotid artery and < 70% ipsilateral carotid artery stenosis who are not scheduled for carotid endarterectomy or stenting. At baseline, 300 patients will undergo magnetic resonance imaging, multidetector-row computed tomography angiography, and ultrasonography examination of the carotid arteries. In addition, magnetic resonance imaging of the brain, ambulatory transcranial Doppler recording of the middle cerebral artery and blood withdrawal will be performed. After two-years, imaging will be repeated in 150 patients. All patients undergo a follow-up brain magnetic resonance imaging, and there will be regular clinical follow-up until the end of the study. STUDY OUTCOMES: The combined primary end-point contains ipsilateral recurrent ischemic stroke or transient ischemic attack or new ipsilateral ischemic brain lesions on follow-up brain magnetic resonance imaging.