Gutierrez Jose, Goldman James, Dwork Andrew J, Elkind Mitchell S V, Marshall Randolph S, Morgello Susan
From the Departments of Neurology (J.G., M.S.V.E., R.S.M.), Pathology and Cell Biology (J.G., A.J.D.), Psychiatry (A.J.D.), and Epidemiology (M.S.V.E.), Columbia University Medical Center; and the Departments of Neurology, Neuroscience, and Pathology (S.M.), Icahn School of Medicine at Mount Sinai Medical Center, New York, NY.
Neurology. 2015 Sep 29;85(13):1139-45. doi: 10.1212/WNL.0000000000001976. Epub 2015 Aug 28.
Cerebrovascular disease is a cause of morbidity in HIV-infected populations. The relationship among HIV infection, brain arterial remodeling, and stroke is unclear.
Large brain arteries (n = 1,878 segments) from 284 brain donors with and without HIV were analyzed to obtain media and wall thickness and lumen-to-wall ratio, and to determine the presence of atherosclerosis and dolichoectasia (arterial remodeling extremes). Neuropathologic assessment was used to characterize brain infarcts. Multilevel models were used to assess for associations between arterial characteristics and HIV. Associations between arterial characteristics and brain infarcts were examined in HIV+ individuals only.
Adjusting for vascular risk factors, HIV infection was associated with thicker arterial walls and smaller lumen-to-wall ratios. Cerebral atherosclerosis accounted for one-quarter of the brain infarcts in HIV+ cases, and was more common with aging, diabetes, a lower CD4 nadir, and a higher antemortem CD4 count. In contrast, a higher lumen-to-wall ratio was the only arterial predictor of unexplained infarcts in HIV+ cases. Dolichoectasia was more common in HIV+ cases with smoking and media thinning, and with protracted HIV infection and a detectable antemortem viral load.
HIV infection may predispose to inward remodeling compared to uninfected controls. However, among HIV+ cases with protracted immunosuppression, outward remodeling is the defining arterial phenotype. Half of all brain infarcts in this sample were attributed to the extremes of brain arterial remodeling: atherosclerosis and dolichoectasia. Understanding the mechanisms influencing arterial remodeling will be important in controlling cerebrovascular disease in the HIV-infected population.
脑血管疾病是HIV感染人群发病的一个原因。HIV感染、脑动脉重塑和中风之间的关系尚不清楚。
对284名有或没有HIV感染的脑供体的大脑大动脉(共1878段)进行分析,以获取中膜厚度、管壁厚度和管腔与管壁比值,并确定动脉粥样硬化和动脉扩张(动脉重塑的极端情况)的存在。采用神经病理学评估来描述脑梗死特征。使用多级模型评估动脉特征与HIV之间的关联。仅在HIV阳性个体中检查动脉特征与脑梗死之间的关联。
在调整血管危险因素后,HIV感染与较厚的动脉壁和较小的管腔与管壁比值相关。脑动脉粥样硬化占HIV阳性病例中脑梗死的四分之一,在老年人、糖尿病患者、最低CD4细胞计数较低以及死前CD4细胞计数较高的患者中更为常见。相比之下,较高的管腔与管壁比值是HIV阳性病例中不明原因梗死的唯一动脉预测因素。动脉扩张在有吸烟史、中膜变薄、长期HIV感染且死前病毒载量可检测到的HIV阳性病例中更为常见。
与未感染的对照组相比,HIV感染可能易导致内向型重塑。然而,在长期免疫抑制的HIV阳性病例中,外向型重塑是典型的动脉表型。该样本中所有脑梗死的一半归因于脑动脉重塑的极端情况:动脉粥样硬化和动脉扩张。了解影响动脉重塑的机制对于控制HIV感染人群的脑血管疾病至关重要。