See related article, p 90

Covert brain infarcts (CBI) are predominantly small ischemic cerebral lesions that are detected on magnetic resonance imaging (MRI) in the absence of stroke events.¹ They have been repeatedly reported using MRI in large population-based cohorts as well as in stroke patients in association with symptomatic ischemic or hemorrhagic lesions. Their prevalence increases considerably with aging. Previous reports suggest that the lack of acute clinical manifestations in CBI might be related to their location in the brain,² associated lesions, or sex^2,3 but not to the underlying lesion type itself or cause. CBI were initially described as silent infarcts in the literature, but the term silent was rapidly challenged and is progressively abandoned after subtle but true clinical effects were depicted at their occurrence.^1,4 In the most severe forms of cerebral small vessel disease, accumulation of CBI has been shown to participate in cognitive and motor decline of progressive appearance.⁵ Therefore, there is no doubt that CBIs should not be considered as benign MRI markers but are true focal tissue injuries with serious potential consequences.

The risk factors associated with CBIs appear very similar to those associated with stroke events.⁶ In previous large population-based studies, their presence or number on MRI are found strongly associated with an increased risk of incident stroke, cognitive decline, or dementia.⁷ Covert cerebral infarcts are also associated with a higher risk of incident cerebral lesions accumulating in the brain along aging.⁶ Accumulating evidence suggests that these different risks could be modulated by the number or severity of vascular risk factors and by their control.^8,9 However, in clinical practice, the fact remains that no strong recommendation can be proposed today to an individual with an isolated covert infarct, whereas the same lesion associated with acute neurological manifestations will lead to a large etiological work-up and strong therapeutic recommendations. To date, there is not a single preventive trial in stroke-free patients who present only with covert cerebral infarcts on their MRI.

In our aging countries, these questions are, however, crucial for preventing stroke, disability, and dementia. The number of individuals asking for an advice after the discovery of CBIs is increasing with improving access to MRI investigations, particularly in elderly people. Numerous practical questions are often raised by these incidental findings. Should we perform MRI in patients at risk of developing CBI? Should we follow them and control all their potential risk factors? Which preventive strategy should we adopt in presence of 1, 2, or several CBIs? Should we use statins, antiplatelets, or antihypertensive agents? We have not yet the answers to these questions. However, we learned from the literature that the risk associated with CBI considerably varies according to the population, age, risk factors, severity of associated cerebral lesions, and the underlying pathology. It is, therefore, crucial to delineate the group of individuals with the highest risk for testing innovative preventive strategies and treatments in the next future.

In the NOMAS (Northern Manhattan Study), a population-based cohort study of stroke-free individuals aged >40 years, 1287 stroke-free subjects of median age 70 years participated in a large MRI substudy. Wright et al¹⁰ already showed that the NOMAS participants with subclinical cerebral infarcts on MRI had a greater risk of all stroke types (hazard ratio, 1.9 [95% CI, 1.1–3.3]). The highest risk corresponded to the occurrence of lacunar strokes (hazard ratio, 4.0 [95% CI, 1.3–12.3]) or of cryptogenic strokes (hazard ratio 3.6 [95% CI, 1.0–12.7]). An increased risk of mortality among Hispanic participants harboring CBI was also detected (hazard ratio 2.9 [95% CI, 1.4–5.8]).¹⁰ Interestingly, Wright et al¹⁰ showed that covert ischemic lesions with cavitation between 3 and 15 mm in diameter actually increased the risk of incident stroke but not the other small cerebral cavities observed on MRI. Their data emphasized the risk related to CBI may vary according to different cerebral small vessel lesions subtypes and ethnicity.¹⁰ In the present study of Gutierez et al¹¹ in the journal Stroke, also obtained in the NOMAS cohort, special efforts were first made to improve the diagnosis of CBIs and to segregate them from perivascular spaces on MRI.¹² Thus, voids in the brain stem were considered as covert infarcts whatever their aspects but the presence of an hyperintense rim was needed for defining covert infarcts in the subinsular cortex, infraputaminal regions, or in the cerebellum. Gutierez et al¹¹ showed that CBIs thus defined were more frequent in the right hemisphere and smaller than lesions related to clinical stroke. They also confirmed that the presence of CBI is associated with an increased risk of any stroke, myocardial infarction, and death. But their main findings is that these different risks largely vary among subjects with CBI according to the following categorization: (1) a positive history of atrial fibrillation, congestive heart failure, or valvulopathy; (2) the presence of a stenosis of the ipsilateral extracranial or intracranial large artery; (3) irregularities or stenosis of the corresponding penetrating intracranial artery; (4) the total absence of all these potential sources of embolism.¹¹ The risk of ischemic stroke, myocardial infarction, and that of death increased particularly in patients with either a significant stenosis of extracranial or intracranial artery or in the absence of any detectable source of embolism. The highest risk was clearly driven by the presence of stenosis of the ipsilateral extra or intracranial arteries (>50%) associated with a crude incidence rate of about 2.2%/y for stroke events, 3.2% for myocardial infarction, and 6.9% for death.¹¹

These results are important. They further confirm that CBIs are not benign lesions. They suggest that a work-up as performed in stroke patients may help to select individuals exposed to the highest risk of stroke, myocardial infarction, or death. They indicate that individuals with CBIs and significant stenosis of extra or intracranial arteries are at increased risk of stroke, myocardial infarction, or death. Finally, these findings will certainly help determining the best population of individuals with CBI for testing future preventive strategies.

The status of the cerebrovascular network clearly matters for estimating the risk associated with CBIs. Thus, look at magnetic resonance angiography when MRI shows such lesions.

The research of Dr Chabriat on imaging biomarkers in cerebral small vessel disease is funded by ANR - RHU TRT_cSVEV.

Dr Chabriat declares to have received fees from Servier and Hovid Companies for participating in a steering committee during the past 5 years. This work was unrelated to the content of the present article.

The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.

Guest Editor for this article was Emmanuel Touzé, PhD.

请参阅相关文章，第90页

隐性脑梗死（CBI）主要是小的缺血性脑病变，可在没有中风事件的情况下通过磁共振成像（MRI）检测到。^[1] MRI已经在基于人群的队列研究中以及在有症状的缺血性或出血性病变的中风患者中反复报道。随着年龄的增长，它们的患病率大大增加。先前的报告表明，CBI缺乏急性临床表现可能与它们在大脑中的位置，^2个相关病变或性别^2,3有关。但不适用于潜在病变类型本身或原因。CBI最初在文献中被描述为沉默性梗死，但是沉默一词很快受到了挑战，在描述了微妙但真实的临床效果后逐渐被放弃。^1,4在最严重的脑小血管疾病形式中，CBI的积累已被证明参与认知和运动能力的下降。⁵因此，毫无疑问，CBI不应被视为良性MRI标记，而应是真正的局灶性组织损伤，可能会带来严重的潜在后果。

与CBI相关的危险因素看起来与与中风事件相关的危险因素非常相似。⁶在先前的大型人群研究中，发现其在MRI上的存在或数量与发生中风，认知能力下降或痴呆的风险增加密切相关。⁷隐性脑梗塞还伴随着随着年龄增长而在大脑中累积的突发性脑部病变风险更高。⁶越来越多的证据表明，这些不同的风险可以通过血管危险因素的数量或严重程度以及对其的控制来调节。^8,9然而，在临床实践中，仍然存在这样的事实，即今天不能向患有隐蔽性梗塞的个体提出强烈的建议，而与急性神经系统表现有关的同一病变将导致大量的病因检查和强有力的治疗建议。迄今为止，尚无一项针对仅在MRI上表现为隐性脑梗塞的无中风患者的预防性试验。

但是，在我们这些老龄化的国家，这些问题对于预防中风，残疾和痴呆症至关重要。发现CBI后寻求咨询意见的人数正在增加，尤其是在老年人中，获得MRI检查的机会越来越多。这些偶然发现常常提出许多实际问题。我们应该对有发展为CBI风险的患者进行MRI检查吗？我们是否应该关注它们并控制它们的所有潜在风险因素？在有1个，2个或几个CBI的情况下，我们应采用哪种预防策略？我们应该使用他汀类药物，抗血小板药物或抗高血压药吗？我们还没有这些问题的答案。但是，我们从文献中了解到，与CBI相关的风险会因人群，年龄，风险因素，相关的脑部病变的严重程度而异，以及潜在的病理。因此，至关重要的是要划定在未来的将来测试创新的预防策略和治疗方法风险最高的人群。

在NOMAS（北曼哈顿研究）中，一项基于人群的年龄大于40岁的无中风个体队列研究，中年年龄为70岁的1287个无中风受试者参加了一项大型MRI研究。Wright等[ ^10]已经表明，患有亚临床脑梗塞的MRI的NOMAS参与者对所有中风类型的风险更高（危险比为1.9 [95％CI，1.1-3.3]）。最高风险对应于腔隙性中风（危险比4.0 [95％CI，1.3-12.3]）或隐源性中风（危险比3.6 [95％CI，1.0-12.7]）的发生。在携带CBI的西班牙裔参与者中，死亡风险也有所增加（危险比2.9 [95％CI，1.4-5.8]）。¹⁰有趣的是，赖特（Wright）等人¹⁰研究表明，直径为3至15毫米的隐性缺血性病变的空化实际上增加了发生中风的风险，但MRI上观察到的其他小脑腔则没有增加。他们的数据强调与CBI相关的风险可能会因脑小血管病变亚型和种族的不同而有所差异。¹⁰在本研究中Gutierez等¹¹在杂志行程，在NOMAS队列也获得特别的努力首次作出改善CBIS的诊断，并从MRI血管周围间隙隔离他们。¹²因此，脑干中的空隙无论其形态如何都被认为是隐蔽性梗塞，但是需要一个高强度的边缘来定义岛下皮层，腹膜下区域或小脑中的隐蔽性梗塞。古铁雷斯（Gutierez）等人¹¹结果表明，与临床卒中相关的病变相比，如此定义的CBI在右半球更常见且更小。他们还证实，CBI的存在与中风，心肌梗塞和死亡的风险增加有关。但是他们的主要发现是，根据以下分类，这些不同的风险在患有CBI的受试者之间差异很大：（1）房颤，充血性心力衰竭或瓣膜病的阳性病史；（2）同侧颅外或颅内大动脉狭窄；（3）相应的颅内动脉不规则或狭窄；（4）完全没有所有这些可能的栓塞来源。¹¹缺血性中风，心肌梗塞和死亡的风险增加，尤其是在颅外或颅内动脉明显狭窄或没有任何可检测到的栓塞来源的患者中。最高风险显然是由同侧外或颅内动脉狭窄（> 50％）引起的，卒中事件的年发生率约为每年2.2％，心肌梗塞的发生率约为3.2％，死亡的发生率约为6.9％ 。¹¹

这些结果很重要。他们进一步证实CBI不是良性病变。他们建议对中风患者进行的检查可能有助于选择暴露于中风，心肌梗塞或死亡风险最高的个体。他们表明患有CBIs且颅外或颅内动脉明显狭窄的个体患中风，心肌梗塞或死亡的风险增加。最后，这些发现无疑将有助于确定患有CBI的最佳人群，以测试未来的预防策略。

脑血管网络的状态对于评估与CBI相关的风险显然很重要。因此，当MRI显示此类病变时，请查看磁共振血管造影。

Chabriat博士对脑小血管疾病的成像生物标志物的研究由ANR-RHU TRT_cSVEV资助。

Chabriat博士宣布在过去5年中因参加指导委员会而从Servier和Hovid公司收取了费用。这项工作与本文的内容无关。

本文表达的观点不一定是编辑者或美国心脏协会的观点。

本文的客座编辑是伊曼纽尔·图泽（EmmanuelTouzé）博士。