Relationship of Hematocrit to Ischemic Stroke Outcome

描述(由申请人提供)：这项研究的目的是检验基线红细胞压积(HCT)水平、卒中严重程度和缺血性卒中后预后之间的关系。红细胞压积是决定血液携氧能力和血液粘度的主要因素。由于血液粘度的增加和脑血流量的减少，高红细胞压积时中枢神经系统(CNS)的氧运输减少。低Hct水平时，由于血液含氧量低，氧传输也会减少。几项研究发现，缺血性中风在红细胞压积水平较高的人群中更为普遍。使用局灶性缺血动物模型的研究表明，随着实验中Hct降低到30%至35%的水平，脑梗塞面积缩小，脑氧流量增加。然而，基于这些动物研究，使用血液稀释技术的多中心临床试验旨在将Hct降低到类似的目标水平，但未能证明临床有益，在某些情况下导致了更糟糕的结果。初步研究表明，大约45%的Hct水平可能与人类最佳的中风结局有关，这个值比动物模型所建议的要高得多。包括卒中亚型和合并症在内的临床变量可能会显著影响这种关系。这项研究涉及对现有临床数据库的重新分析，即甲磺酸替拉扎特治疗急性卒中的随机试验(RANTTAS)。具体目的是：(1)研究卒中后Hct水平与NIHSS、B1和COS评分之间的关系；(2)评估Hct水平与预后之间的关系是否受卒中亚型的影响；(3)检验某些协变量是否影响这种关系；(4)以梗死体积作为次要指标，进一步研究Hct水平与预后之间的关系。将使用统计建模技术对RANTTAS数据集进行严格的统计评估。这些模型允许评估HCT对急性缺血性卒中的影响，调整其他可能的影响，并比较HCT在不同卒中亚型中的效果。提出了一些模型，每个模型都旨在评估在这一背景下HCT的影响的不同方面。拟合这些模型将导致对红细胞压积和卒中结局之间的关联有更全面的了解。这些发现可能会导致开发新的干预措施来改善中风的结局。

DESCRIPTION (provided by applicant): The purpose of this study is to examine the association between baseline hematocrit (HCT) level, stroke severity, and outcome following ischemic stroke. HCT is the main determinant of blood oxygen carrying capacity and blood viscosity. Central Nervous System (CNS) oxygen transport diminishes at high HCT levels due to increased blood viscosity and reduced cerebral blood flow. Oxygen transport is also reduced at low HCT levels due to low blood oxygen content. Several studies have found ischemic stroke more prevalent among persons with high HCT levels. Studies employing animal models of focal ischemia have shown a reduction in infarct size and increase in cerebral oxygen flow with experimental reductions in HCT to levels of 30 to 35%. Yet, multicenter clinical trials using hemodilution techniques designed to reduce HCT to similar target levels based on these animal studies have failed to demonstrate a clinical benefit and in some instances has resulted in worse outcome. Preliminary research suggests that HCT levels around 45% may be associated with optimal stroke outcome in humans, a value considerably higher than suggested by animal models. Clinical variables including stroke subtype and comorbidities may significantly influence this relationship. This study involves reanalysis of an existing clinical database, the Randomized Trial of Tirilazad Mesylate in Acute Stroke (RANTTAS). Specific aims are (1) to examine the association between initial HCT level and clinical/functional outcome as measured by NIHSS, Bl and COS scores following stroke; (2) to assess whether the association between HCT level and outcome is influenced by stroke subtype; (3) to examine whether certain co-variables influence this relationship; (4) to further study the association between HCT level and outcome using infarct volume as a secondary outcome measure. Rigorous statistical evaluation of the RANTTAS dataset will be carried out using statistical modeling techniques. These models allow for the evaluation of the effect of HCT in acute ischemic stroke adjusting for other possible effects, and for comparing the effect of HCT in different stroke subtypes. A number of models are proposed, each of which is intended to assess different aspects of the effect of HCT in this setting. Fitting these models will result in a more complete understanding of the association between HCT and stroke outcome. Findings could lead to the development of new interventions to improve stroke outcome.