SECONDARY PREVENTION IN SMALL SUBCORTICAL STROKES (SPS3)

小的皮质下中风（S3），也称为腔隙性脑梗死，占脑梗死的近25%，是血管性痴呆的先兆，在墨西哥裔美国人中尤为常见。氯吡格雷加阿司匹林联合抗血小板治疗和强化降压可显著减少S3患者的主要血管事件和认知能力下降。然而，需要一项大型随机临床试验来确定这些干预措施的有效性和安全性，特别是在推定为小血管疾病的S3患者中。本建议是一项初步研究，目的是：确定S3幸存者最低可耐受、可实现的目标血压。2. 评估最低可耐受血压与标准目标之间的差异是否足以影响随后中风和认知能力下降的发生。3. 通过系列MRI定量评估S3患者的白质异常，并将其与患者特征、认知状态、血压控制和抗血小板治疗相关联。4. 评估墨西哥裔美国人种族与血压干预、抗血小板治疗耐受性、白质异常的程度和进展以及认知状态的关系，并修改和评估现有的以西班牙语为主的认知状态筛查试验。由小血管疾病引起的S3患者将随机接受阿司匹林（650mg/d）或阿司匹林加氯吡格雷（75mg/d）治疗（双盲），而有高血压病史的患者将随机接受三种不同的降压目标水平（非盲法）。每个目标水平的耐受性和达到的血压将是主要结果，抗血小板治疗的耐受性和副作用也将被评估。定量MRI将在入组时和平均一年后进行，与认知状态、干预和种族相关。没有临床试验评估过S3的二级预防，S3是墨西哥裔美国人最常见的中风类型，在美国每年约有15万例中风。虽然这项初步研究是进行更大规模、更明确的临床试验的必要的第一步，但关于中风后血压控制和墨西哥裔美国人中风预防相关问题的有价值和独特的信息将会出现。

Small subcortical strokes (S3), also known as lacunar infarcts, comprise nearly 25 percent of brain infarcts, are harbingers of vascular dementia, and are particularly frequent in Mexican- Americans. Combination antiplatelet therapy using clopidogrel plus aspirin and intensive lowering of blood pressure could substantially reduce major vascular events and cognitive decline in S3 patients. However, a large randomized clinical trial is required to define the efficacy and safety of these interventions specifically in patients with S3 due to presumed small vessel disease. This proposal is for a pilot study to: 1. Determine the lowest tolerable, achievable target blood pressures among survivors of S3. 2. To assess whether the difference between the lowest tolerable blood pressures are sufficiently different from that achieved by standard targets to substantially impact the occurrence of subsequent stroke and cognitive decline. 3. To quantitatively assess white matter abnormalities in S3 patient by serial MRI, correlating these with patient features, cognitive status, blood pressure control and antiplatelet treatment. 4. To assess the relationship of Mexican-American ethnicity to blood pressure interventions, tolerance of antiplatelet therapy, extent and progression of white matter abnormalities, and cognitive status, as well as to modify and assess existing screening tests of cognitive status for those who primarily speak Spanish. Participants with S3 attributed to small vessel disease will be randomized to treatment with aspirin (650mg/d) or aspirin plus clopidogrel (75mg/d) (double-blind), while those with a history of hypertension will additionally be randomized to three different target levels of blood pressure lowering (not blinded). The tolerance and achieved blood pressures in each target level will be the primary outcome, with tolerance and side-effects of antiplatelet therapy also assessed. Quantitative MRI will be done at entry and after a mean of one year, correlated with cognitive status, interventions and ethnicity. No clinical trials have assessed secondary prevention in S3, the most common type of stroke in Mexican Americans and accounting for about 150,000 strokes yearly in the US. While this pilot study is a necessary first-step for a larger, definitive clinical trial, valuable and unique information about blood pressure control after stroke and about issues relevant to stroke prevention in Mexican-Americans will emerge.