Evans Tavia E, O'Sullivan Michael J, de Groot Marius, Niessen Wiro J, Hofman Albert, Krestin Gabriel P, van der Lugt Aad, Portegies Marileen L P, Koudstaal Peter J, Bos Daniel, Vernooij Meike W, Ikram M Arfan
From the Department of Epidemiology (T.E.E., M.d.G., A.H., M.L.P.P., D.B., M.W.V., M.A.I.), Department of Radiology and Nuclear Medicine (T.E.E., M.d.G., W.J.N., G.P.K., A.v.d.L., D.B., M.W.V., M.A.I.), Department of Medical Informatics (M.d.G., W.J.N.), and Department of Neurology (M.L.P.P., P.J.K., M.A.I.), Erasmus MC, Rotterdam, The Netherlands; Department of Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, United Kingdom (T.E.E., M.J.O.); Imaging Physics, Faculty of Applied Sciences, Delft University of Technology, The Netherlands (W.J.N.); and Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H., D.B.).
Stroke. 2016 Nov;47(11):2756-2762. doi: 10.1161/STROKEAHA.116.014651. Epub 2016 Oct 4.
The presence of subclinical vascular brain disease, including white matter lesions and lacunar infarcts, substantially increases the risk of clinical stroke. White matter microstructural integrity is considered an earlier, potentially better, marker of the total burden of vascular brain disease. Its association with risk of stroke, a focal event, remains unknown.
From the population-based Rotterdam Study, 4259 stroke-free participants (mean age: 63.6 years, 55.6% women) underwent brain magnetic resonance imaging, including diffusion magnetic resonance imaging, between 2006 and 2011. All participants were followed up for incident stroke until 2013. Cox proportional hazards models were used to associate markers of the microstructure of normal-appearing white matter with risk of stroke, adjusting for age, sex, white matter lesion volume, lacunar infarcts, and additionally for cardiovascular risk factors. Finally, we assessed the predictive value of white matter microstructural integrity for stroke beyond the Framingham Stroke Risk Profile.
During 18 476 person-years of follow-up, 58 people experienced a stroke. Both lower fractional anisotropy and higher MD increased risk of stroke, independent of age, sex, cardiovascular risk factors, white matter lesion volume, and lacunar infarcts (hazard ratio per SD increase in: fractional anisotropy: 0.75 [95% confidence interval, 0.57-0.98] and MD: 1.50 [95% confidence interval, 1.08-2.09]). MD improved stroke prediction beyond the Framingham Stroke Risk Profile (continuous net reclassification improvement: 0.52 [95% confidence interval, 0.24-0.81]).
Future stroke is predicted not only by prevalent vascular lesions but also by subtle alterations in the microstructure of normal-appearing white matter. Inclusion of this effect in risk prediction models produces a significant advantage in stroke prediction compared with the existing Framingham Stroke Risk Profile.
亚临床血管性脑疾病的存在，包括白质病变和腔隙性梗死，会大幅增加临床卒中的风险。白质微观结构完整性被认为是血管性脑疾病总负担的一个更早出现、可能更好的标志物。其与作为局灶性事件的卒中风险之间的关联尚不清楚。
在基于人群的鹿特丹研究中，4259名无卒中参与者（平均年龄：63.6岁，55.6%为女性）在2006年至2011年间接受了脑磁共振成像检查，包括扩散磁共振成像。所有参与者随访至2013年以观察卒中发生情况。采用Cox比例风险模型将正常白质微观结构标志物与卒中风险相关联，并对年龄、性别、白质病变体积、腔隙性梗死以及心血管危险因素进行校正。最后，我们评估了白质微观结构完整性在弗明汉姆卒中风险评估之外对卒中的预测价值。
在18476人年的随访期间，58人发生了卒中。较低的分数各向异性和较高的平均扩散率均增加了卒中风险，且独立于年龄、性别、心血管危险因素、白质病变体积和腔隙性梗死（分数各向异性每增加1个标准差的风险比：0.75[95%置信区间，0.57 - 0.98]；平均扩散率：1.50[95%置信区间，1.08 - 2.09]）。平均扩散率在弗明汉姆卒中风险评估之外改善了卒中预测（连续净重新分类改善：0.52[95%置信区间，0.24 - 0.81]）。
未来卒中不仅可由现有的血管病变预测，还可由正常白质微观结构的细微改变预测。与现有的弗明汉姆卒中风险评估相比，在风险预测模型中纳入这一因素在卒中预测方面具有显著优势。
