S-EPMC9469171 - Stroke incidence and cognitive outcomes of intracranial atherosclerotic stenosis: study protocol for a multicenter, prospective, observational cohort study. - OmicsDI

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Dataset Information

Stroke incidence and cognitive outcomes of intracranial atherosclerotic stenosis: study protocol for a multicenter, prospective, observational cohort study.

ABSTRACT:

Background

Intracranial atherosclerotic stenosis (ICAS) is one of the leading causes of stroke worldwide. Current diagnostic evaluations and treatments remain insufficient to assess the vulnerability of intracranial plaques and reduce the recurrence of stroke in symptomatic ICAS. On the other hand, asymptomatic ICAS is associated with an increased risk of cognitive impairment. The pathogenesis of ICAS related cognitive decline is largely unknown. The aim of SICO-ICAS study (stroke incidence and cognitive outcomes of ICAS) is to elucidate the pathophysiology of stroke and cognitive impairment in ICAS population, comprehensively evaluating the complex interactions among life-course exposure, genomic variation, vascular risk factors, cerebrovascular burden and coexisting neurodegeneration.

Methods

SICO-ICAS is a multicenter, prospective, observational cohort study. We aim to recruit 3,000 patients with symptomatic or asymptomatic ICAS (>50% or occlusion) who will be followed up for ≥12 months. All participants will undergo pre-designed magnetic resonance imaging packages, blood biomarkers testing, as well as detailed cognitive domains assessment. All participants will undergo clinical visits every 6 months and telephone interviews every 3 months. The primary outcome measurement is ischemic stroke or cognitive impairment within 12 months after enrollment.

Discussion

This study will establish a large prospective ICAS cohort, hopefully discover new biomarkers associated with vulnerable intracranial plaques, identify subjects at high risk for incident ischemic stroke or cognitive impairment, and eventually propose a precise diagnostic and treatment strategy for ICAS population.

Trial registration

Chinese Clinical Trials Register ChiCTR2200061938.

SUBMITTER: Si Q

PROVIDER: S-EPMC9469171 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Stroke incidence and cognitive outcomes of intracranial atherosclerotic stenosis: study protocol for a multicenter, prospective, observational cohort study.

Si Qianqian Q Teng Yuming Y Liu Caiyan C Yuan Weizhuang W Fan Xiaoyuan X Zhang Xiaoqian X Zhang Zongmuyu Z Li Mingli M Liu Qing Q Wang Peng P Yan Zhongrui Z Wu Bo B Liu Qiang Q Li Hangjuan H Ji Yan Y Ran Yuncai Y Song Bo B Zhu Shiguang S Li Hongyan H Guan Jingxia J Zhao Manli M Hao Yonggang Y Wang Pengfei P Bian Hong H Wang Ningfen N Wang Yulin Y Pan Yuning Y An Hongwei H Guo Rong R Han Cong C Zhang Junshi J Wang Hebo H You Yong Y Jiang Hongquan H Liu Zifan Z Liu Jingli J Tao Dingbo D Piao Xiangyu X Zhang Jiangtao J Wang Pei P Yang Shen S Liu Zhou Z Wei Xiue X Han Kai K Shi Zhimin Z Liu Aihua A Zhang Zuowen Z Ma Chunye C Wang Baichen B Zhang Gejuan G Song Chengguang C Zhang Guilian G Yang Xiao X Chen Bing B Lu Baoquan B Chen Beilei B Zuo Meng M Han Kun K Zhang Xiaodan X Cao Wenfeng W Wu Lingfeng L Li Qi Q Geng Xiaokun X Zhou Junshan J Zhong Mengfei M Wang Minghua M Chen Yangmei Y Liu Jiachun J Wang Tingrui T Deng Youqing Y Xu Weihai W

Annals of translational medicine 20220801 16

<h4>Background</h4>Intracranial atherosclerotic stenosis (ICAS) is one of the leading causes of stroke worldwide. Current diagnostic evaluations and treatments remain insufficient to assess the vulnerability of intracranial plaques and reduce the recurrence of stroke in symptomatic ICAS. On the other hand, asymptomatic ICAS is associated with an increased risk of cognitive impairment. The pathogenesis of ICAS related cognitive decline is largely unknown. The aim of SICO-ICAS study (stroke incide ...[more]

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Project description:ObjectiveTo develop and validate a radiomics nomogram for predicting stroke recurrence in symptomatic intracranial atherosclerotic stenosis (SICAS).MethodsThe data of 156 patients with SICAS were obtained from the hospital database. Those with and without stroke recurrence were identified. The 156 patients were separated into a training cohort (n = 110) and a validation cohort (n = 46). Baseline clinical data were collected from our medical records, and plaque radiological features were extracted from vascular wall high-resolution imaging (VW-HRMRI). The imaging sequences included 3D-T1WI-VISTA, T2WI, and 3D-T1WI-VISTA-enhanced imaging. Least absolute shrinkage and selection operator (LASSO) analysis were used to select the radiomics features associated with stroke recurrence. Then, multiple logistic regression analysis of clinical risk factors, radiological features, and radiomics signatures were performed, and a predictive nomogram was constructed to predict the probability of stroke recurrence in SICAS. The performance of the nomogram was evaluated.ResultsDiabetes mellitus, plaque burden, and enhancement ratio were independent risk factors for stroke recurrence [odds ratio (OR) = 1.24, 95% confidence interval (CI): 1.04-3.79, p = 0.018; OR = 1.76, per 10% increase, 95% CI, 1.28-2.41, p < 0.001; and OR = 1.94, 95% CI: 1.27-3.09, p < 0.001]. Five features of 3D-T1WI-VISTA, six features of T2WI, and nine features of 3D-T1WI-VISTA-enhanced images were associated with stroke recurrence. The radiomics signature in 3D-T1WI-VISTA-enhanced images was superior to the radiomics signature of the other two sequences for predicting stroke recurrence in both the training cohort [area under the curve (AUC), 0.790, 95% CI: 0.669-0.894] and the validation cohort (AUC, 0.779, 95% CI: 0.620-0.853). The combination of clinical risk factors, radiological features, and radiomics signature had the best predictive value (AUC, 0.899, 95% CI: 0.844-0.936 in the training cohort; AUC, 0.803, 95% CI: 0.761-0.897 in the validation cohort). The C-index of the nomogram was 0.880 (95% CI: 0.805-0.934) and 0.817 (95% CI: 0.795-0.948), respectively, in the training and validation cohorts. The decision curve analysis further confirmed that the radiomics nomogram had good clinical applicability with a net benefit of 0.458.ConclusionThe radiomics features were helpful to predict stroke recurrence in patients with SICAS. The nomogram constructed by combining clinical high-risk factors, plaque radiological features, and radiomics features is a reliable tool for the individualized risk assessment of predicting the recurrence of SICAS stroke.

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Project description:Objective Acute ischemic stroke is a group of diseases characterized by high morbidity, high disability, high mortality, and high recurrence, and most patients are left with varying degrees of sequelae. Symptomatic intracranial atherosclerotic stenosis (sICAS) is a major cause of acute ischemic stroke pathogenesis, and its formation and progression are influenced by a combination of pathways including lipid metabolism and inflammatory response. sICAS has a high risk of clinical recurrence. Therefore, timely and effective assessment of intracranial vascular stenosis in acute ischemic stroke is particularly important for the diagnosis of sICAS, the treatment of stroke and the prevention of stroke recurrence.Method The aim of this study was to screen for unique differential proteins that are closely associated with sICAS in patients with acute ischemic stroke. Fourteen patients with acute ischemic stroke were included and divided into stenosis and control groups according to whether the intracranial vessels were stenosed or not. First, mass spectrometry was applied to all patients included using 4D Label-free proteome quantification technology to obtain the differential proteins between the two groups. Secondly, functional enrichment analysis using GO classification, KEGG pathway, Domain and other bioinformatics libraries were used to obtain differential protein-related enrichment trends. Then, the STRING (v.11.5) protein interaction network database was applied for comparison to obtain the differential protein interactions and corresponding target proteins. Finally, PRM was applied to validate the selected target proteins.Result 1096 proteins were obtained by mass spectrometry, of which the number of quantitatively comparable proteins was 991. When P value<0.05, a change in differential expression of more than 1.3 was used as the change threshold for significant up-regulation and less than 1/1.3 was used as the change threshold for significant down-regulation, resulting in a total of 46 differential proteins screened, of which 24 proteins were significantly up-regulated and 22 proteins were significantly down-regulated. In PRM experiments, five proteins involved in lipid metabolism and inflammatory response have been validated, namely A2M ,LBP, CTSG,CST3,FABP1.Conclusion By detecting the changes of these five proteins in acute ischemic stroke patients, we can provide a basis for the diagnosis of sICAS, the treatment of stroke and the prevention of stroke recurrence, and also help to promote the development of drugs for the prevention of acute ischemic stroke recurrence by combining Chinese and Western medicine.