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 ...

Little is known about changes in carotid plaque morphology during aging and the possible impact on cardiovascular events. Only few studies addressed so far age-related modifications within atherosclerotic lesions. Therefore, in this work we endeavored to summarize the current knowledge about changing of plaque composition in elderly. The data from hitherto existing studies confirm that atherosclerotic plaques undergo distinct alternations with advanced age. However, the results are often ambiguous and the changes do not seem to be as disastrous as expected. Interestingly, none of the studies could definitely evidence increased plaque vulnerability with advanced age. Nevertheless, based on the previous work showing decrease in elastin fibers, fibroatheroma, SMCs, overall cellularity and increase in the area of lipid core, hemorrhage, and calcification, the plaque morphology appears to transform toward unstable plaques. Otherwise, even if inflammatory cells often accumulate in plaques of younger patients, their amount is reduced in the older age and so far no clear association has been observed between thin fibrous cap and aging. Thus, the accurate contribution of age-related changes in plaque morphology to cardiovascular events has yet to be elucidated. KEY MESSAGES Composition of carotid atherosclerotic lesions changes during aging. These alternations are however, just moderate and depend upon additional variables, such as life style, accompanying disease, genetics, and other factors that have yet to be determined. Based on the current data, the age-associated plaque morphology seems to transform toward vulnerable plaques. However, the changes do not seem to be as disastrous as expected.

IntroductionStroke is one of the leading causes of death and disability in western societies and a prevalent public health concern worldwide [1]. Extracranial carotid artery stenosis due to atherosclerotic plaque burden is one of the major risk factors of forthcoming stroke [2]. Epidemiologic data document that ischemic stroke attributable to a diseased carotid artery corresponds with up to 18 % of all incidents leading to neurological events [3,4]. Furthermore, the prevalence of a cervical internal carotid artery stenosis increases with age and can be found in 6.9 % of the elderly population (> 65 years) [5]. Large randomized clinical trials (the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST)) have provided clear evidence of the usefulness of surgical treatment of patients with neurological symptoms for a degree of stenosis > 50 % in NAS-CET and > 70 % in ECST [6,7]. In contrast, the benefi t of carotid endarterectomy (CEA) for asymptomatic patients is less clear. Large multicenter randomized studies for asymptomatic carotid artery disease (the Asymptomatic Carotid Surgery Trial (ACST) and the Asymptomatic Carotid Atherosclerosis Study (ACAS)) demonstrated a small reduction in secondary stroke risk using CEA compared to medical treatment [8,9]. However, the absolute risk reduction was rather small [10,11].Epidemiological studies have already revealed that aging and sex are independent risk factors for cardiovascular disease [12,13]. However, the question as to how far potential changes in carotid plaque morphology might contribute to ischemic stroke during aging, especially due to unstable atherosclerotic lesions, has not yet been elucidated. Interestingly, very few studies have focused so far on lesion morphology and instability as a function of age, sex, or patient symptomatology [14 -20]. The data suggest that especially neurological symptoms are often caused by critical changes in carotid plaque morphology, leading to lesion instability. Consequently, unfavorable alterations in the pathophysiology of atherosclerotic plaques in asymptomatic patients might cause an increased risk of stroke.The aim of the current study was therefore to analyze plaque instability as a function of age and sex in patients with asymptomatic carotid artery stenosis by means of his- 2004 -2013) at the Munich Vascular Biobank were analyzed. Ascertainment of lesion stability/instability was performed on formalin-fi xed paraffi n-embedded tissue samples using hematoxylin-eosin and elastic van Gieson staining. Unstable plaques were considered lesions with a fi brous cap < 200 μm overlaying lipid-rich atheroma. Results: The average age of the patients was 69.3 ± 8.2 years. Independent of age, asymptomatic men had in total more frequently unstable plaques in contrast to women (41 % versus 52%, p = 0.042). No differences were found in plaque instability between age-related quartiles (< 65, 65-69, 70 -74, > 74 years) for female sex (p = 0.422). In men, a continuous increase ...

Objectives: Instable plaques are more common in patients with symptomatic carotid stenosis compared to asymptomatic patients. Clinically symptomatic patients are at high risk for a recurrent stroke in the first days after a neurologic index event. Histopathologic plaque stabilisation or remodelling mechanisms of symptomatic plaques are unclear. Therefore, our study aimed to find changes of plaque morphology in dependence of time interval between neurologic index event and plaque removal. Methods: Plaques of patients that were removed from surgically treated patients with symptomatic carotid stenosis between 2004 and 2016 were included. Histological analyses of those carotid plaques were performed to assess the type of plaque (American Heart Association classification), the stability of plaque (thickness of the fibrous cap </>200μm), the extent of calcification, inflammation, neovascularization and the deposition of collagen and elastin. Statistical analysis was applied in form of an ordinal regression analysis, adjusted for common risk factors of atherosclerosis. Results: Out of 348 included plaques, the patients’ median age was 71 (Q1-Q3, 65 - 77) years and 69% were male. Median time interval between index event and plaque removal was 10 days (Q1-Q3, 4-28 days). Most common index event was a transient ischemic attack with 37% (128 of 348), followed by stroke in 28% (97 of 348), amaurosis fugax in 22% (76 of 348) and instable symptoms (crescendo transient ischemic attack, stroke in evolution) in 12% (43 of 348), respectively. The ordinal regression analysis revealed, that the time interval as continuous independent variable had no significant influence on plaque type, plaque stability, extent of calcification, inflammation or neovascularization and the deposition of collagen and elastin. Conclusions: The examined plaque morphology features of patients with symptomatic carotid stenosis showed no differences in relation to the time interval between neurologic index event and plaque removal. To find potential symptomatic plaque remodelling mechanisms, currently ongoing molecular and histomorphological analysis aim at identifying novel markers of apoptosis and cell fate-driven mechanisms in fibrous cap-enriched vascular smooth cells.