Cloonan Lisa, Fitzpatrick Kaitlin M, Kanakis Allison S, Furie Karen L, Rosand Jonathan, Rost Natalia S
J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA; Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
Atherosclerosis. 2015 May;240(1):149-53. doi: 10.1016/j.atherosclerosis.2015.02.052. Epub 2015 Mar 2.
Increasing white matter hyperintensity (WMH) burden is linked to risk of stroke and poor post-stroke outcomes. While the biology of WMH remains ill-defined, several lines of evidence implicate endothelial dysfunction. In this study, we sought to assess the association between metabolic markers of endothelial dysfunction and WMH severity in patients with acute ischemic stroke (AIS).
In this retrospective study, consecutive subjects, ≥18 years of age, admitted to our ED with AIS, brain MRI, and blood homocysteine (Hcy) and hemoglobin A1c (HgbA1c) measurements were eligible for this analysis. WMH volume (WMHV) was quantified using a validated semi-automated algorithm and log-transformed for linear regression analyses.
There were 809 AIS subjects included (mean age 65.57±14.7, median WMHV 6.25 cm3 (IQR 2.8-13.1)). In univariate analysis, age, female gender, race, ethnicity, systolic blood pressure, history of hypertension, atrial fibrillation, coronary artery disease, prior stroke, and current alcohol and tobacco use (all p<0.05), as well as Hcy (p<0.0001) and HgbA1c levels (p=0.0005) were associated with WMHV. However, only Hcy (β=0.11, p=0.003) and HgbA1c levels (β=0.1, p=0.008) independently predicted WMHV in the multivariate model, along with age (β=0.03, p<0.0001), race (β=0.39, p=0.01), ethnicity (β=-0.11, p=0.03), and current alcohol use (β=0.26, p=0.002).
Elevated levels of Hcy and HgbA1c have been previously linked to endothelial dysfunction related to oxidative stress. The association between Hcy and HgbA1c and WMH burden in AIS suggests that the degree of endothelial dysfunction may be greater in patients with increased WMHV, and may in part explain the relationship between WMHV and poor post-stroke outcomes.
白质高信号（WMH）负担增加与中风风险及中风后不良预后相关。虽然WMH的生物学机制仍不明确，但有几条证据表明内皮功能障碍与之有关。在本研究中，我们试图评估急性缺血性中风（AIS）患者内皮功能障碍的代谢标志物与WMH严重程度之间的关联。
在这项回顾性研究中，年龄≥18岁、因AIS入住我们急诊科且进行了脑部MRI以及血液同型半胱氨酸（Hcy）和糖化血红蛋白（HgbA1c）测量的连续受试者符合本分析条件。使用经过验证的半自动算法对WMH体积（WMHV）进行量化，并进行对数转换以进行线性回归分析。
共纳入809例AIS受试者（平均年龄65.57±14.7岁，WMHV中位数为6.25 cm³（四分位间距2.8 - 13.1））。在单因素分析中，年龄、女性性别、种族、族裔、收缩压、高血压病史、心房颤动、冠状动脉疾病、既往中风以及当前饮酒和吸烟情况（均p<0.05），以及Hcy（p<0.0001）和HgbA1c水平（p=0.0005）均与WMHV相关。然而，在多变量模型中，只有Hcy（β=0.11，p=0.003）和HgbA1c水平（β=0.1，p=0.008）独立预测WMHV，同时还有年龄（β=0.03，p<0.0001）、种族（β=0.39，p=0.01）、族裔（β=-0.11，p=0.03）和当前饮酒情况（β=0.26，p=0.002）。
Hcy和HgbA1c水平升高先前已与氧化应激相关的内皮功能障碍有关。AIS中Hcy和HgbA1c与WMH负担之间的关联表明，WMHV增加的患者内皮功能障碍程度可能更大，这可能部分解释了WMHV与中风后不良预后之间的关系。
