Atherosclerosis is the process underlying heart attack and stroke. A characteristic feature of the atherosclerotic plaque is the accumulation of apoptotic cells in the necrotic core. Pro-phagocytic Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Atherosclerosis is the process underlying heart attack and stroke. Despite decades of research, its pathogenesis remains unclear. Dogma suggests that atherosclerotic plaques expand primarily via the accumulation of cholesterol and inflammatory cells. However, recent evidence suggests that a substantial portion of the plaque may arise from a subset of “dedifferentiated” vascular smooth muscle cells (SMCs) which proliferate in a clonal fashion. Herein we use multicolor lineage-tracing models to confirm that the mature SMC can give rise to a hyperproliferative cell which appears to promote inflammation via elaboration of complement-dependent anaphylatoxins. Despite being extensively opsonized with prophagocytic complement fragments, we find that this cell also escapes immune surveillance by neighboring macrophages, thereby exacerbating its relative survival advantage. Mechanistic studies indicate this phenomenon results from a generalized opsonin-sensing defect acquired by macrophages during polarization. This defect coincides with the noncanonical up-regulation of so-called don’t eat me molecules on inflamed phagocytes, which reduces their capacity for programmed cell removal (PrCR). Knockdown or knockout of the key antiphagocytic molecule CD47 restores the ability of macrophages to sense and clear opsonized targets in vitro, allowing for potent and targeted suppression of clonal SMC expansion in the plaque in vivo. Because integrated clinical and genomic analyses indicate that similar pathways are active in humans with cardiovascular disease, these studies suggest that the clonally expanding SMC may represent a translational target for treating atherosclerosis.

Background-Associations between hospital volume and the risk of stroke or death following carotid endarterectomy (CEA) and carotid artery stenting (CAS) on a national level in Germany were analyzed. Methods and Results-Secondary data analysis using microdata from the nationwide statutory German quality assurance database on all surgical or endovascular carotid interventions on the extracranial carotid artery between 2009 and 2014. Hospitals were categorized into empirically determined quintiles according to the annual case volume. The resulting volume thresholds were 10, 25, 46, and 79 for CEA and 2, 6, 12, and 26 for CAS procedures. The primary outcome was any stroke or death before hospital discharge. For risk-adjusted analyses, a multilevel regression model was applied. The analysis included 161 448 CEA and 17 575 CAS procedures. In CEA patients, the crude risk of stroke or death decreased monotonically from 4.2% (95% confidence interval, 3.6%-4.9%) in low-volume hospitals (first quintile 1-10 CEA per year) to 2.1% (2.0%-2.2%) in hospitals providing ≥80 CEA per year (fifth quintile; P<0.001 for trend). The overall risk of any stroke or death in CAS patients was 3.7% (3.5%-4.0%), but no trend on annual volume was seen (P=0.304). Riskadjusted analyses confirmed a significant inverse relationship between hospital volume (categorized or continuous) and the risk of stroke or death after CEA but not CAS procedures. Conclusions-An inverse volume-outcome relationship in CEA-treated patients was demonstrated. No significant association between hospital volume and the risk of stroke or death was found for CAS. (Circ Cardiovasc Interv. 2016;9:e004171.

T he short-term risk of stroke or death of surgically treated patients having a symptomatic carotid stenosis has been shown to be similar in younger and older patients (<70 years [5.7%] versus ≥70 years [5.9%]).1 In contrast, a meta-analysis of 3 large randomized controlled trials (EVA-3S, SPACE, ICSS) revealed that the risk of stroke or death after carotid artery stenting increases significantly with age (<70 years [5.8%] versus ≥70 years [12.0%]).1 A similar trend (although not significant) has also been found in asymptomatic patients, particularly when sex was taken into account. 2 These observations might be explained by embolism derived from ruptured plaques or sheared-off arterial calcifications caused by guidewire manipulations during carotid artery stenting procedures. 3,4 In addition, multivariable analyses of pooled randomized controlled trial data on symptomatic patients showed that men have had a higher risk of stroke or death when treated with carotid artery stenting compared with carotid endarterectomy (9.0% versus 5.5%, respectively).1 In contrast, no significant differences were found in women. 1 This discrepancy in the available data raises the question of whether age and sex are associated with differences in plaque morphology or plaque composition.The pathophysiological development of an atherosclerotic plaque is a long-lasting and dynamic process. 5 The development of atherosclerosis begins already at an early age. However, the incidence of clinically apparent atherosclerosisrelated cardiovascular events increases only at an advanced age. [6][7][8][9][10] In Germany, the prevalence of extracranial carotid artery stenosis (>50%) is ≈6.9% in patients aged >65 years but increases further with age. 4,11 Among all ischemic stroke events, ≈15% were caused by arterioarterial embolization from extracranial atherosclerotic carotid artery stenosis. 4 InBackground and Purpose-The purpose of this study was to analyze the association between morphological characteristics of human carotid plaques and patient's sex, age, and history of neurological symptoms. Methods-The study included 763 atherosclerotic plaques from patients treated surgically for carotid stenosis between 2004 and 2013. Histological analyses of carotid plaques were performed to assess the type of plaque (American Heart Association classification), the stability of the plaque, the extent of calcification, inflammation, and neovascularization, as well as the deposition of collagen and elastin. According to the scale of outcome measurement, logistic regression, ordinal regression, and multinomial regression analyses were applied. All results were adjusted for common risk factors of atherosclerosis. contrast, in coronary arteries, acute angina underlies the consequences of rupture or erosion of the plaque surface and subsequent luminal thrombus formation. 12,13 It is also known from coronary artery disease that fibrous plaques are mainly associated with stable syndromes, whereas atheromatous plaques are more often related to unstable ...

Local anesthesia, patch plasty compared with primary closure, intraoperative completion studies by duplex ultrasound or angiography, and perioperative antiplatelet medication were independently associated with lower in-hospital stroke or death rates after carotid endarterectomy.

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BackgroundGuideline recommendations on carotid endarterectomy are based predominantly on randomized, controlled trials, in which women or elderly patients are often under‐represented. This study analyzed the association of age and sex with the risk of in‐hospital stroke or death following carotid endarterectomy under routine conditions in Germany.Methods and ResultsSecondary data analysis using the Statutory German Quality Assurance Database on all carotid endarterectomy procedures (n=142 074) performed between 2009 and 2014. Primary outcome was any stroke or death until discharge; secondary outcomes were any in‐hospital stroke (alone), and death (alone). Descriptive statistics and multilevel multivariable regression analyses were applied. Patients were predominately male (68%), with mean age 71 years. Carotid stenosis was symptomatic in 40%. Primary outcome occurred in 1.8% of women and 1.9% of men. Multivariable regression analysis revealed that more‐advanced age was associated with a higher primary outcome rate (relative risk [RR] per 10‐year increase: 1.19; 95% CI, 1.14–1.24). Risk of death (alone) was associated with age (RR, 1.68; 95% CI, 1.54–1.84). Age was associated with the risk of stroke (alone; RR, 1.05; 95% CI, 1.00–1.11). Sex was not associated with primary outcome rate (1.01; 95% CI, 0.93–1.10), nor did it significantly modify the age effect.ConclusionsThis study shows that increasing age, but not sex, is associated with a higher risk of in‐hospital stroke or death following carotid endarterectomy under everyday conditions in Germany. Whereas the risk of death (alone) is significantly associated with age, the association between age and the risk of stroke (alone) can be considered of minor importance.

The use of an embolic protection device was independently associated with lower in-hospital risk for stroke or death, major stroke or death, and stroke.