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Wu ZP, Wei W, Liu S, Hu MD, Zhao H, Li XF, Chen X. The effect of hypertension, obesity, and type 2 diabetes on lacunar stroke: A network Mendelian randomization study. Nutr Metab Cardiovasc Dis 2025; 35:103974. [PMID: 40189994 DOI: 10.1016/j.numecd.2025.103974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 03/03/2025] [Accepted: 03/04/2025] [Indexed: 04/29/2025]
Abstract
BACKGROUND AND AIMS Previous studies have reported an association of lacunar stroke with hypertension, obesity, and type 2 diabetes (T2D). The aim of this study was to investigate whether the association was causal and whether body mass index mediated the effect of hypertension on lacunar stroke. METHODS AND RESULTS The independence and causal association of hypertension, obesity, and T2D with lacunar stroke were assessed by multivariate Mendelian randomization (MVMR) and network Mendelian randomization (NMR) with inverse variance weighting (IVW). The reliability of the results was increased by sensitivity analyses including MR-Egger, Cochrane's Q test, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and leave-one-out. MVMR analysis found that genetically predicted hypertension had a 42 % higher lacunar stroke risk (OR: 1.42, 95 % CI: 1.29-1.56, P < 0.001) when adjusted for obesity and T2D, genetically predicted T2D had a 9 % higher lacunar stroke risk (OR: 1.09, 95 % CI: 1.03-1.16, P < 0.004) when adjusted for hypertension and obesity, and genetically predicted obesity had a 15 % lower lacunar stroke risk (OR: 0.85, 95 % CI: 0.77-0.93, P < 0.001) when adjusted for hypertension and T2D. NMR found that 44 % of the association between hypertension and lacunar stroke risk was mediated by obesity. CONCLUSION This genetic association study found novel independent genetic associations between hypertension and T2D with high risk of lacunar stroke, whereas obesity attenuated the risk of lacunar stroke. The findings emphasize the importance of individualized lacunar stroke prevention strategies rather than uniform weight management optimize medical care in high-risk populations.
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Affiliation(s)
- Zhi-Ping Wu
- Department of Epidemiology, School of Public Health, Dalian Medical University, Dalian, China
| | - Wei Wei
- Department of Neurosurgery, Central Hospital of Dalian University of Technology, Dalian, China
| | - Shan Liu
- Department of Epidemiology, School of Public Health, Dalian Medical University, Dalian, China; Emergency Department, Dalian Center for Disease Control and Prevention, Dalian, China
| | - Meng-Die Hu
- Department of Epidemiology, School of Public Health, Dalian Medical University, Dalian, China
| | - Heng Zhao
- Department of Epidemiology, School of Public Health, Dalian Medical University, Dalian, China
| | - Xiao-Feng Li
- Department of Epidemiology, School of Public Health, Dalian Medical University, Dalian, China
| | - Xin Chen
- Department of Epidemiology, School of Public Health, Dalian Medical University, Dalian, China.
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Zhang Y, Yang S, Wang S, Zou X, Tang L, Chen L, Ma J, Li Y, Yao T, Zhang X, Tang R, Tang L, Zhang F, Zhou H, Xu L, Tang Q, Ma S, Yi Y, Liu R, Bai G, Zeng Y, Zhou Y, Zhao Y, Wang Y, Yang Q, Wang D, Shen M, Zhang L. Prevalence and 10-Year Risk of Intracerebral Hemorrhage in Central China Using Estimates From the 1 Million Cross-Sectional Study. Neurology 2025; 104:e213545. [PMID: 40258204 DOI: 10.1212/wnl.0000000000213545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 02/11/2025] [Indexed: 04/23/2025] Open
Abstract
BACKGROUND AND OBJECTIVES Intracerebral hemorrhage (ICH) is a common and fatal type of stroke, especially in central China. However, recent epidemiologic data are scarce. The study aimed to investigate the latest prevalence of ICH in central China and assess the risk of ICH in the next 10 years based on the Resident Health Records (RHR) data. METHODS First, this cross-sectional study was based on a large-scale face-to-face investigation of ICH, which was launched on residents aged 20 years or older from January 1, 2021, to December 31, 2021, and estimated the prevalence of ICH in Hunan, a representative province in central China. Then, based on the RHR database, we assessed the ICH risk, population attributable fraction (PAF), and effects of ICH prevention under different risk factor control scenarios over the next decade by the China Kadoorie Biobank (CKB)-cardiovascular disease (CVD) model. RESULTS In 2021, 1.78 million participants enrolled in the investigation (mean age = 50.1 years; 51% male). The age-standardized prevalence rate of ICH was 159.2 (95% CI 153.7-164.9) per 100,000. The prevalence rate of ICH in men was 193.6 (95% CI 185.2-202.5) per 100,000, while in women was 124.0 (95% CI 117.1-131.3) per 100,000, and it increased with age. Spatial aggregation was observed, with the peak prevalence rate of ICH at 327.3 (95% CI 293.1-365.5) per 100,000 in Zhuzhou, followed by Changsha was 215.8 (95% CI 190.6-243.9) per 100,000, while Shaoyang had the lowest rate was 62.8 (95% CI 51.2-77.1) per 100,000. For the assessment of 10-year ICH risk, we included a total of 8.36 million participants aged 30-79 with the RHR database into the CKB-CVD model. We found that there will be 354,146 cases (ICH risk: 4.2%) of ICH among the participants in the next decade. Controlling hypertension showed the highest potential for ICH prevention, with a PAF of 8.6%. By controlling hypertension, smoking, waist circumference, and diabetes, 56,673 ICH cases (PAF 19.1%) can be avoided in the next decade. DISCUSSION The ICH prevalence in central China remained high. Strict blood pressure control could significantly reduce the risk of ICH in the next 10 years. It is important to continually improve ICH prevention strategies in the general population.
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Affiliation(s)
- Yupeng Zhang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Songchun Yang
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China
| | - Sai Wang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Xuelun Zou
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Li Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Lei Chen
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Junyi Ma
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Ye Li
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Tianxing Yao
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Xiangbin Zhang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Rongmei Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Lei Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Feng Zhang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Hunan, Changsha, China
| | - Huifang Zhou
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Lianxu Xu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Qiaoling Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Siyuan Ma
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Yexiang Yi
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Ran Liu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
| | - Genghuai Bai
- School of Computer Science and Engineering, Central South University, Changsha, Hunan, China
| | - Yi Zeng
- Department of Geriatrics, Second Xiangya Hospital, Central South University, Changsha, China
| | - Yanhong Zhou
- Cancer Research Institute, Basic School of Medicine, Central South University, Changsha, Hunan, China
| | - Ying Zhao
- School of Computer Science and Engineering, Central South University, Changsha, Hunan, China
| | - Yang Wang
- Institute of Integrative Chinese Medicine, Department of Integrated Chinese Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Qidong Yang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Duolao Wang
- Department of Clinical Sciences, Liverpool School of Tropical Medicine, United Kingdom
| | - Minxue Shen
- Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, China
| | - Le Zhang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Multi-Modal Monitoring Technology for Severe Cerebrovascular Disease of Human Engineering Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Brain Health Center of Hunan Province, Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, Hunan, China
- Human Brain Disease Biological Resources Platform of Hunan Province, Changsha, China; and
- FuRong Laboratory, Changsha, Hunan, China
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Cheng Y, Valdés Hernández MDC, Xu M, Zhang S, Pan X, An B, Wardlaw JM, Liu M, Wu B. Differential risk factor profile and neuroimaging markers of small vessel disease between lacunar ischemic stroke and deep intracerebral hemorrhage. Ther Adv Neurol Disord 2024; 17:17562864241253901. [PMID: 38799702 PMCID: PMC11119384 DOI: 10.1177/17562864241253901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 04/22/2024] [Indexed: 05/29/2024] Open
Abstract
Background Lacunar ischemic stroke (LIS) and deep intracerebral hemorrhage (dICH) are two stroke phenotypes of deep perforator arteriopathy. It is unclear what factors predispose individuals with deep perforator arteriopathy to either ischemic or hemorrhagic events. Objectives We aimed to investigate risk factors and neuroimaging features of small vessel disease (SVD) associated with LIS versus dICH in a cross-sectional study. Methods We included patients with clinically presenting, magnetic resonance imaging-confirmed LIS or dICH from two tertiary hospitals between 2010 and 2021. We recorded vascular risk factors and SVD markers, including lacunes, white matter hyperintensities (WMH), perivascular spaces (PVS), and cerebral microbleeds (CMB). Logistic regression modeling was used to determine the association between vascular risk factors, SVD markers, and stroke phenotype. We further created WMH probability maps to compare WMH distribution between LIS and dICH. Results A total of 834 patients with LIS (mean age 61.7 ± 12.1 years) and 405 with dICH (57.7 ± 13.2 years) were included. Hypertension was equally frequent between LIS and dICH (72.3% versus 74.8%, p = 0.349). Diabetes mellitus, hyperlipidemia, smoking, and prior ischemic stroke were more associated with LIS [odds ratio (OR) (95% confidence interval (CI)), 0.35 (0.25-0.48), 0.32 (0.22-0.44), 0.31 (0.22-0.44), and 0.38 (0.18-0.75)]. Alcohol intake and prior ICH were more associated with dICH [OR (95% CI), 2.34 (1.68-3.28), 2.53 (1.31-4.92)]. Lacunes were more prevalent in LIS [OR (95% CI) 0.23 (0.11-0.43)], while moderate-to-severe basal-ganglia PVS and CMB were more prevalent in dICH [OR (95% CI) 2.63 (1.35-5.27), 4.95 (2.71-9.42)]. WMH burden and spatial distribution did not differ between groups. Conclusion The microangiopathy underlying LIS and dICH reflects distinct risk profiles and SVD features, hence possibly SVD subtype susceptibility. Prospective studies with careful phenotyping and genetics are needed to clarify the mechanisms underlying this difference.
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Affiliation(s)
- Yajun Cheng
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | | | - Mangmang Xu
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Shuting Zhang
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaohua Pan
- Department of Neurology, Baotou Eighth Hospital, Baotou, China
| | - Baoqiang An
- Department of Neurology, Baotou Central Hospital, Baotou, China
- Center of Cerebrovascular Disease, Inner Mongolia AeroSpace Hospital, Hohhot, China
| | - Joanna M. Wardlaw
- Centre for Clinical Brain Sciences, UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK
| | - Ming Liu
- Department of Neurology, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu 610041, China
| | - Bo Wu
- Department of Neurology, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu 610041, China
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Sun H, Zhong Y, Liao L, Wu J, Xu H, Ma J. Obesity and hypertension mediate the effect of education on deep intracerebral hemorrhage: A Mendelian randomization study. J Stroke Cerebrovasc Dis 2024; 33:107758. [PMID: 38710461 DOI: 10.1016/j.jstrokecerebrovasdis.2024.107758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 03/12/2024] [Accepted: 05/03/2024] [Indexed: 05/08/2024] Open
Abstract
BACKGROUND Educational attainment (EA) as a stable indicator of socioeconomic status has been confirmed to affect intracerebral hemorrhage (ICH), but the mechanism relating EA and ICH is still unknown. AIM To explore the causal relationship between EA and ICH through a bidirectional and two-step Mendelian randomization (MR) study. METHODS Using summary-level Genome-wide Association Study using GWAS data FROM CASES AND CONTROLS of European ancestry, we performed bidirectional and two-step MR analyses to explore the causal relationship between educational attainment and ICH to understand the mediating influence of risk factors in this process. We also carried out subgroup analysis according to the different sites (deep and lobar) of ICH. A set of sensitivity analyses were performed to test valid MR assumptions. RESULTS Bidirectional MR analysis consistently demonstrated a unidirectional causal effect, revealing that higher EA had a protective influence on ICH. Each additional 1-standard deviation (SD) increase in genetically predicted years of schooling was associated with a reduced risk of all ICH (inverse variance weighted (IVW) OR: 0.381 [95 %CI: 0.264-0.549]), deep ICH (OR: 0.334 [95 %CI: 0.216-0.517]), and lobar ICH (OR: 0.422 [95 %CI: 0.261-0.682]). The mediating effect of EA on all ICH was mediated via systolic blood pressure (SBP) (6.93 % [1.20-13.45 %]) and body mass index (BMI) (17.87 % [3.92-34.64 %]), and the mediating effect of EA on deep ICH was also mediated via SBP (7.85 % [1.55-15.07 %]) and BMI (18.63 % [4.02-36.26 %]). CONCLUSION This study provides robust genetic evidence for supporting the protective effect of EA on ICH risk, with further evidence that the effect of EA on deep ICH is partially mediated through hypertension and obesity. Further validation is needed to ascertain whether these findings are applicable to other racial or general population groups.
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Affiliation(s)
- Hao Sun
- Neurointensive Care Unit, the First Affiliated Hospital of Shantou University Medical College, Shantou, PR China
| | - Yuan Zhong
- Department of Neurosurgery, the First Affiliated Hospital of Shantou University Medical College, Shantou, PR China
| | - Lixian Liao
- Intensive Care Unit, Huizhou Third People's Hospital, Guangzhou Medical University, Huizhou, PR China
| | - Jujiang Wu
- Neurointensive Care Unit, the First Affiliated Hospital of Shantou University Medical College, Shantou, PR China
| | - Hongwu Xu
- Department of Neurosurgery, the First Affiliated Hospital of Shantou University Medical College, Shantou, PR China
| | - Junqiang Ma
- Neurointensive Care Unit, the First Affiliated Hospital of Shantou University Medical College, Shantou, PR China; Department of Population Medicine, Shantou University Medical College, Shantou, PR China.
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Gao Y, Zong C, Liu H, Zhang K, Yang H, Wang Y, Li Y, Song B, Xu Y. Clinical features and associated factors of coexisting intracerebral hemorrhage in patients with cerebral small vessel disease: a cross-sectional study. Sci Rep 2024; 14:5596. [PMID: 38454101 PMCID: PMC10920749 DOI: 10.1038/s41598-024-55968-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 02/29/2024] [Indexed: 03/09/2024] Open
Abstract
Intracerebral hemorrhage (ICH) is generally considered to be closely related to cerebral small vessel disease (CSVD), leading to a poor prognosis. However, the coexistence of ICH in general CSVD patients and related factors remain underreported. In our cross-sectional study, we screened 414 CSVD patients from a database at the Department of Neurology, First Affiliated Hospital of Zhengzhou University (September 2018 to April 2022). Imaging biomarkers of CSVD and coexisting ICH lesion were assessed. Factors associated with coexisting ICH in CSVD were determined using multivariate logistic regression analysis. ICH was observed in 59 patients (14.3%). Multivariate logistic regression showed that previous history of ischemic stroke or transient ischemic attack (OR 5.189, 95%CI 2.572-10.467, P < 0.001), high-grade perivascular space in the basal ganglia (n > 10) (OR 2.051, 95%CI 1.044-4.027, P = 0.037) and low adjusted calcium-phosphorus product (OR 0.728 per 1 [mmol/L]2 increase, 95%CI 0.531-0.998, P = 0.049) were associated with coexisting ICH in CSVD patients. The considerable proportion of coexisting ICH and revelation of associated factors in general CSVD patients alert physicians of the potential risk of the reoccurrence of ICH, and might have a significant impact on therapeutic strategies.
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Affiliation(s)
- Yuan Gao
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Erqi District, Zhengzhou, 450052, Henan Province, China
| | - Ce Zong
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Erqi District, Zhengzhou, 450052, Henan Province, China
| | - Hongbing Liu
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Erqi District, Zhengzhou, 450052, Henan Province, China
| | - Ke Zhang
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Erqi District, Zhengzhou, 450052, Henan Province, China
| | - Hongxun Yang
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Erqi District, Zhengzhou, 450052, Henan Province, China
| | - Yunchao Wang
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Erqi District, Zhengzhou, 450052, Henan Province, China
| | - Yusheng Li
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Erqi District, Zhengzhou, 450052, Henan Province, China
| | - Bo Song
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Erqi District, Zhengzhou, 450052, Henan Province, China
| | - Yuming Xu
- Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Erqi District, Zhengzhou, 450052, Henan Province, China.
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Crispino P. Hemorrhagic Coagulation Disorders and Ischemic Stroke: How to Reconcile Both? Neurol Int 2023; 15:1443-1458. [PMID: 38132972 PMCID: PMC10745771 DOI: 10.3390/neurolint15040093] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Revised: 11/22/2023] [Accepted: 11/28/2023] [Indexed: 12/23/2023] Open
Abstract
Coagulation and fibrinolytic system disorders are conditions in which the blood's ability to clot is impaired, resulting in an increased risk of thrombosis or bleeding. Although these disorders are the expression of two opposing tendencies, they can often be associated with or be a consequence of each other, contributing to making the prognosis of acute cerebrovascular events more difficult. It is important to recognize those conditions that are characterized by dual alterations in the coagulation and fibrinolytic systems to reduce the prognostic impact of clinical conditions with difficult treatment and often unfortunate outcomes. Management of these individuals can be challenging, as clinicians must balance the need to prevent bleeding episodes with the potential risk of clot formation. Treatment decisions should be made on an individual basis, considering the specific bleeding disorder, its severity, and the patient's general medical condition. This review aims to deal with all those forms in which coagulation and fibrinolysis represent two sides of the same media in the correct management of patients with acute neurological syndrome. Precision medicine, personalized treatment, advanced anticoagulant strategies, and innovations in bleeding control represent future directions in the management of these complex pathologies in which stroke can be the evolution of two different acute events or be the first manifestation of an occult or unknown underlying pathology.
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Affiliation(s)
- Pietro Crispino
- Medicine Unit, Santa Maria Goretti Hospital, Via Scaravelli Snc, 04100 Latina, Italy
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Lee PN, Coombs KJ, Hamling JS. Evidence relating cigarettes, cigars and pipes to cardiovascular disease and stroke: Meta-analysis of recent data from three regions. World J Meta-Anal 2023; 11:290-312. [DOI: 10.13105/wjma.v11.i6.290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 08/14/2023] [Accepted: 08/21/2023] [Indexed: 09/13/2023] Open
Abstract
BACKGROUND More recent data are required relating to disease risk for use of various smoked products and of other products containing nicotine. Earlier we published meta-analyses of recent results for chronic obstructive pulmonary disease and lung cancer on the relative risk (RR) of current compared to never product use for cigarettes, cigars and pipes based on evidence from North America, Europe and Japan. We now report corresponding up-to-date evidence for acute myocardial infarction (AMI), ischaemic heart disease (IHD) and stroke.
AIM To estimate, using recent data, AMI, IHD and stroke RRs by region for current smoking of cigarettes, cigars and pipes.
METHODS Publications in English from 2015 to 2020 were considered that, based on epidemiological studies in the three regions, estimated the current smoking RR of AMI, IHD or stroke for one or more of the three products. The studies should involve at least 100 cases of stroke or cardiovascular disease (CVD), not be restricted to populations with specific medical conditions, and should be of cohort or nested case-control study design or randomized controlled trials. A literature search was conducted on MEDLINE, examining titles and abstracts initially, and then full texts. Additional papers were sought from reference lists of selected papers, reviews and meta-analyses. For each study identified, we entered the most recent available data on current smoking of each product, as well as the characteristics of the study and the RR estimates. Combined RR estimates were derived using random-effects meta-analysis for stroke and, in the case of CVD, separately for IHD and AMI. For cigarette smoking, where far more data were available, heterogeneity was studied by a wide range of factors. For cigar and pipe smoking, a more limited heterogeneity analysis was carried out. A more limited assessment of variation in risk by daily number of cigarettes smoked was also conducted. Results were compared with those from previous meta-analyses published since 2000.
RESULTS Current cigarette smoking: Ten studies gave a random-effects RR for AMI of 2.72 [95% confidence interval (CI): 2.40-3.08], derived from 13 estimates between 1.47 and 4.72. Twenty-three studies gave an IHD RR of 2.01 (95%CI: 1.84-2.21), using 28 estimates between 0.81 and 4.30. Thirty-one studies gave a stroke RR of 1.62 (95%CI: 1.48-1.77), using 37 estimates from 0.66 to 2.91. Though heterogeneous, only two of the overall 78 RRs were below 1.0, 71 significantly (P < 0.05) exceeding 1.0. The heterogeneity was only partly explicable by the factors studied. Estimates were generally higher for females and for later-starting studies. They were significantly higher for North America than Europe for AMI, but not the other diseases. For stroke, the only endpoint with multiple Japanese studies, RRs were lower there than for Western studies. Adjustment for multiple factors tended to increase RRs. Our RR estimates and the variations by sex and region are consistent with earlier meta-analyses. RRs generally increased with amount smoked. Current cigar and pipe smoking: No AMI data were available. One North American study reported reduced IHD risk for non-exclusive cigar or pipe smoking, but considered few cases. Two North American studies found no increased stroke risk with exclusive cigar smoking, one reporting reduced risk for exclusive pipe smoking (RR 0.24, 95%CI: 0.06-0.91). The cigar results agree with an earlier review showing no clear risk increase for IHD or stroke.
CONCLUSION Current cigarette smoking increases risk of AMI, IHD and stroke, RRs being 2.72, 2.01 and 1.62. The stroke risk is lower in Japan, no increase was seen for cigars/pipes.
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Affiliation(s)
- Peter Nicholas Lee
- Medical Statistics and Epidemiology, P.N.Lee Statistics and Computing Ltd., Sutton SM2 5DA, Surrey, United Kingdom
| | - Katharine J Coombs
- Medical Statistics and Epidemiology, P.N.Lee Statistics and Computing Ltd., Sutton SM2 5DA, Surrey, United Kingdom
| | - Jan S Hamling
- Medical Statistics and Epidemiology, P.N.Lee Statistics and Computing Ltd., Sutton SM2 5DA, Surrey, United Kingdom
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8
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Tsuji H, Shiojima I. Elevated Aminotransferase Levels and Intracerebral Hemorrhage Deaths in a General Japanese Population. Int Heart J 2023; 64:678-683. [PMID: 37518349 DOI: 10.1536/ihj.23-027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/01/2023]
Abstract
Although chronic liver disease has been associated with cardiovascular disease, to which metabolic syndrome might be related, intracerebral hemorrhage (ICH) generally has not been focused. Associations of chronic liver disease assessed by aspartate (AST) and alanine (ALT) aminotransferase levels with ICH deaths were examined using 15,952 subjects without a history of cardiovascular disease who underwent annual health checkups in 1997 in Japan. Proportional hazards regression analyses adjusted for age, sex, hypertension, current smoking, diabetes mellitus, drinking habits, excess body weight, and hypercholesterolemia were performed. During a mean follow-up of 18.6 ± 7.2 years, there were 227 stroke deaths (including 124 ischemic and 60 ICH deaths) and 135 coronary deaths. Elevated aminotransferase levels, defined as a serum AST or ALT level of ≥ 30 IU/L were significantly associated with ICH deaths (hazard ratio (HR) = 2.72, 95% confidence interval (CI) = 1.56-4.73, P = 0.0004). Because elevated aminotransferase levels are frequently observed in alcoholic or metabolic liver diseases, additional analyses were performed to examine the effect of drinking habits and/or metabolic syndrome on the association of elevated aminotransferase levels with ICH deaths. After exclusion of subjects with any drinking habit (n = 9,941), elevated aminotransferase levels were significantly associated with ICH deaths (HR = 2.88, 95%CI = 1.44-5.76, P = 0.0028). After exclusion of subjects with at least one metabolic syndrome component (n = 5,672), elevated aminotransferase levels were significantly associated with ICH deaths (HR = 6.47, 95% CI = 1.85-22.6, P = 0.0035). Elevated aminotransferase levels were not associated with ischemic stroke or coronary deaths in any models. Elevated aminotransferase levels were significantly associated with ICH deaths, independent of drinking habits, or metabolic syndrome.
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Affiliation(s)
- Hisako Tsuji
- Health Examination Center of Moriguchi-City
- Department of Internal Medicine II, Kansai Medical University
| | - Ichiro Shiojima
- Department of Internal Medicine II, Kansai Medical University
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9
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Association of Left Ventricular Hypertrophy and Atrial Fibrillation with Hemorrhagic Evolution of Small Vessel Disease. J Stroke Cerebrovasc Dis 2021; 30:105946. [PMID: 34214964 DOI: 10.1016/j.jstrokecerebrovasdis.2021.105946] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 06/02/2021] [Accepted: 06/06/2021] [Indexed: 11/20/2022] Open
Abstract
OBJECTIVES Cerebral small vessel disease (SVD) is often associated with hypertension and may evolve towards intracerebral hemorrhage (ICH) or lacunar ischemic stroke. However, the factors favoring the evolution towards ICH or lacunar stroke are not well understood. MATERIALS AND METHODS This retrospective study included 326 consecutive patients (71.1±13.2 years, 38% women): 143 with deep ICH and 183 with lacunar lesions (LL) <2 cm, which were visible in a deep location on brain CT scan. Among LL patients, 143 had a small-artery occlusion (SAO) stroke according to the TOAST classification. Clinical characteristics plus laboratory and neuroradiological variables of these patients had been prospectively collected and a subgroup underwent echocardiography. RESULTS In multivariate analysis, ICH patients (97% hypertensive), compared to SAO patients (89% hypertensive), had greater left ventricular wall thickness (LVWT; OR 4.15, 95%CI 1.64-10.53, for those with LVWT ≥ 1.4 cm, 70% of whom were hemorrhagic) and lower prevalence of white matter lesions (OR 0.30, 95%CI 0.13-0.70), ever smokers (OR 0.39, 95%CI 0.18-0.82) and diabetics (OR 0.29, 95% CI 0.10-0.84). Moreover, ICH patients had a greater prevalence of atrial fibrillation than LL patients (OR 3.14, 95%CI 1.11-8.93), and so they were more often anticoagulated. CONCLUSIONS Most SVD patients were hypertensive, but those evolving towards ICH were characterized by organ damage at the cardiac level (increase in LVWT and atrial fibrillation), while those evolving towards lacunar stroke were characterized by a higher prevalence of smokers and diabetics, and by organ damage at the cerebral level (white matter lesions).
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10
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Bernal M, Escarcena P, Arboix A, Garcia-Eroles L, Vergés E, Díez L, Massons J. Differential Characteristics of Ischemic and Hemorrhagic Stroke in Patients with Cerebral Small Vessel Disease. Neurol India 2021; 69:85-90. [PMID: 33642276 DOI: 10.4103/0028-3886.310106] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Background Small vessel disease (SVD) is the underlying anatomical substrate for both lacunar infarction and subcortical hemorrhage. Aim To assess predictive factors of ischemic or hemorrhagic stroke in patients with cerebral SVD. Materials and Methods Prospective hospital-based stroke registry ("The Sagrat Cor Hospital of Barcelona Stroke Registry") in an acute-care teaching hospital in Barcelona, Spain. From 4597 acute stroke patients included in the stroke registry over a 24-year period, 440 cases of lacunar stroke and 210 of subcortical intracerebral hemorrhage were selected. Demographics, clinical characteristics, risk factors, and early outcome were compared. Predictors of lacuna versus subcortical hemorrhage were assessed by multivariate analyses. Results In a logistic regression model based on demographics, risk factors, clinical features and outcome, dyslipidemia (odds ratio [OR] 2.06 (95% confidence interval (CI) 1.17-3.62) and diabetes (OR 1.97, 95% CI 1.19-3.26) were independent risk factors for lacunar infarction. Anticoagulation therapy (OR 0.05, 95% CI 0.01-0.28), sudden onset (OR 0.51, 95% CI 0.33-0.78), motor symptoms (OR 0.44, 95% CI 0.26-0.76), headache (OR 0.23, 95% CI 0.12-0.41), altered consciousness (OR 0.10, 95% CI 0.05-0.21), respiratory complications (OR 0.19, 95% CI 0.08-0.46), and in-hospital death (OR 0.08, 95% CI 0.02-0.36) were predictors of subcortical hemorrhage. Conclusion Identification of differential clinical and prognostic profile between ischemic and hemorrhagic consequences of underlying cerebral SVD is useful for risk stratification in the current process pursuing precision medicine.
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Affiliation(s)
- Mireia Bernal
- Cerebrovascular Division, Department of Neurology, Hospital Universitari del Sagrat Cor, Universitat de Barcelona, Barcelona, Catalonia, Spain
| | - Paula Escarcena
- Cerebrovascular Division, Department of Neurology, Hospital Universitari del Sagrat Cor, Universitat de Barcelona, Barcelona, Catalonia, Spain
| | - Adrià Arboix
- Cerebrovascular Division, Department of Neurology, Hospital Universitari del Sagrat Cor, Universitat de Barcelona, Barcelona, Catalonia, Spain
| | - Lluis Garcia-Eroles
- Director d'Organització i Sistemes d'Informació, Gerència Territorial Metropolitana Nord, Institut Català de la Salut, Barcelona, Catalonia, Spain
| | - Enric Vergés
- Cerebrovascular Division, Department of Neurology, Hospital Universitari del Sagrat Cor, Universitat de Barcelona, Barcelona, Catalonia, Spain
| | - Laura Díez
- Cerebrovascular Division, Department of Neurology, Hospital Universitari del Sagrat Cor, Universitat de Barcelona, Barcelona, Catalonia, Spain
| | - Joan Massons
- Cerebrovascular Division, Department of Neurology, Hospital Universitari del Sagrat Cor, Universitat de Barcelona, Barcelona, Catalonia, Spain
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11
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Stanton R, Demel SL, Flaherty ML, Antzoulatos E, Gilkerson LA, Osborne J, Behymer TP, Moomaw CJ, Sekar P, Langefeld C, Woo D. Risk of intracerebral haemorrhage from hypertension is greatest at an early age. Eur Stroke J 2021; 6:28-35. [PMID: 33817332 DOI: 10.1177/2396987321994296] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 01/17/2021] [Indexed: 11/16/2022] Open
Abstract
Introduction The risk of intracerebral haemorrhage (ICH) associated with hypertension (HTN) is well documented. While the prevalence of HTN increases with age, the greatest odds ratio (OR) for HTN as a risk for ischemic stroke is at an early age. We sought to evaluate if the risk for ICH from HTN was higher in the youngest patients of each race. Patients and methods The Ethnic/Racial Variations of ICH (ERICH) study is a prospective multicenter case-control study of ICH among whites, blacks, and Hispanics. Participants were divided into age groups based on race-specific quartiles. Cases in each race/age group were compared to controls using logistic regression (i.e., cases and controls unmatched). The probability of ICH among cases and controls for each race were compared against independent variables of HTN, quartile of age and interaction of quartile and age also using logistic regression. Results Overall, 2033 non-lobar ICH cases and 2060 controls, and 913 lobar ICH cases with 927 controls were included. ORs were highest in the youngest age quartile for non-lobar haemorrhage for blacks and Hispanics and highest in the youngest quartile for lobar haemorrhage for all races. The formal test of interaction between age and HTN was significant in all races for all locations with the exception of lobar ICH in whites (p = 0.2935). Discussion Hypertension is a strong independent risk factor for ICH irrespective of location among persons of younger age, consistent with the hypothesis that first exposure to HTN is a particularly sensitive time for all locations of ICH.
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Affiliation(s)
- Robert Stanton
- Department of Neurology & Rehabilitation Medicine, University of Cincinnati, OH, USA
| | - Stacie L Demel
- Department of Neurology & Rehabilitation Medicine, University of Cincinnati, OH, USA
| | - Matthew L Flaherty
- Department of Neurology & Rehabilitation Medicine, University of Cincinnati, OH, USA
| | - Eleni Antzoulatos
- Department of Neurology & Rehabilitation Medicine, University of Cincinnati, OH, USA
| | - Lee A Gilkerson
- Department of Neurology & Rehabilitation Medicine, University of Cincinnati, OH, USA
| | - Jennifer Osborne
- Department of Neurology & Rehabilitation Medicine, University of Cincinnati, OH, USA
| | - Tyler P Behymer
- Department of Neurology & Rehabilitation Medicine, University of Cincinnati, OH, USA
| | - Charles J Moomaw
- Department of Neurology & Rehabilitation Medicine, University of Cincinnati, OH, USA
| | - Padmini Sekar
- Department of Neurology & Rehabilitation Medicine, University of Cincinnati, OH, USA
| | - Carl Langefeld
- Department of Biostatistical Sciences, Wake Forest University, Winston-Salem, NC, USA
| | - Daniel Woo
- Department of Neurology & Rehabilitation Medicine, University of Cincinnati, OH, USA
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12
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Reinert NJ, Patel BM, Al-Robaidi K, Gao X, Fabio A, Jadhav A, Muluk VS, Esper SA, Zuckerbraun BS, Thirumala PD. Perioperative stroke-related mortality after non-cardiovascular, non-neurological procedures: A retrospective risk factor evaluation of common surgical comorbidities. J Perioper Pract 2021; 31:80-88. [PMID: 32301383 DOI: 10.1177/1750458920911830] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
BACKGROUND Perioperative stroke-related mortality in the non-cardiovascular, non-neurological surgery population is an uncommon, yet devastating outcome. A combination of emboli and hypoperfusion may cause large vessel occlusions leading to perioperative strokes and mortality. Identifying independent risk factors for perioperative stroke-related mortality may enhance risk-stratification algorithms and preventative therapies. OBJECTIVES This study utilised cause-of-death data to determine independent risk scores for common surgical comorbidities that may lead to perioperative stroke-related mortality, including atrial fibrillation and asymptomatic carotid stenosis. METHODS This retrospective, IRB-exempt, case-control study evaluated non-cardiovascular, non-neurological surgical patients in a claims-based database. ICD-10-CM and ICD-9-CM codes identified cause of death and comorbidity incidences, respectively. A multivariate regression analysis then established adjusted independent risk scores of each comorbidity in relation to perioperative stroke-related mortality. RESULTS Patients with atrial fibrillation were more likely (1.7 aOR, 95% CI (1.1, 2.8) p = 0.02) to die from perioperative stroke-related mortality than from other causes. No association was found with asymptomatic carotid stenosis. Further, in-hospital strokes (25.9 aOR, 95% CI (16.0, 41.8) p < 0.001) or diabetes (1.8 aOR, 95% CI (1.1, 2.9) p = 0.02) may increase perioperative stroke-related mortality risk. CONCLUSIONS Atrial fibrillation, diabetes and in-hospital strokes may be independent risk factors for perioperative stroke-related mortality in the non-cardiovascular, non-neurological surgery population.
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Affiliation(s)
- Nathan J Reinert
- Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Neurosurgery, University of Pittsburgh, Pittsburgh, PA, USA
| | - Bansri M Patel
- Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Neurosurgery, University of Pittsburgh, Pittsburgh, PA, USA
| | - Khaled Al-Robaidi
- Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Xiaotian Gao
- Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA
| | - Anthony Fabio
- Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA
| | - Ashutosh Jadhav
- Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Visala S Muluk
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Stephen A Esper
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Brian S Zuckerbraun
- Department of General Surgery, University of Pittsburgh, Pittsburgh, PA, USA
| | - Parthasarathy D Thirumala
- Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Neurosurgery, University of Pittsburgh, Pittsburgh, PA, USA
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13
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Mukaz DK, Zakai NA, Cruz-Flores S, McCullough LD, Cushman M. Identifying Genetic and Biological Determinants of Race-Ethnic Disparities in Stroke in the United States. Stroke 2020; 51:3417-3424. [PMID: 33104469 PMCID: PMC7594163 DOI: 10.1161/strokeaha.120.030425] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
In the United States, causes of racial differences in stroke and its risk factors remain only partly understood, and there is a long-standing disparity in stroke incidence and mortality impacting Black Americans. Only half of the excess risk of stroke in the United States Black population is explained by traditional risk factors, suggesting potential effects of other factors including genetic and biological characteristics. Here, we nonsystematically reviewed candidate laboratory biomarkers for stroke and their relationships to racial disparities in stroke. Current evidence indicates that IL-6 (interleukin-6), a proinflammatory cytokine, mediates racial disparities in stroke through its association with traditional risk factors. Only one reviewed biomarker, Lp(a) (lipoprotein[a]), is a race-specific risk factor for stroke. Lp(a) is highly genetically determined and levels are substantially higher in Black than White people; clinical and pharmaceutical ramifications for stroke prevention remain uncertain. Other studied stroke risk biomarkers did not explain racial differences in stroke. More research on Lp(a) and other biological and genetic risk factors is needed to understand and mitigate racial disparities in stroke.
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Affiliation(s)
- Debora Kamin Mukaz
- Department of Medicine, Vermont Center on Cardiovascular and Brain Health, Larner College of Medicine at the University of Vermont, Burlington, VT
| | - Neil A. Zakai
- Department of Medicine, Vermont Center on Cardiovascular and Brain Health, Larner College of Medicine at the University of Vermont, Burlington, VT
- Department of Pathology & Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington, VT
| | - Salvador Cruz-Flores
- Department of Neurology, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso
| | - Louise D. McCullough
- Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX
| | - Mary Cushman
- Department of Medicine, Vermont Center on Cardiovascular and Brain Health, Larner College of Medicine at the University of Vermont, Burlington, VT
- Department of Pathology & Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington, VT
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14
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Marini S, Merino J, Montgomery BE, Malik R, Sudlow CL, Dichgans M, Florez JC, Rosand J, Gill D, Anderson CD. Mendelian Randomization Study of Obesity and Cerebrovascular Disease. Ann Neurol 2020; 87:516-524. [PMID: 31975536 PMCID: PMC7392199 DOI: 10.1002/ana.25686] [Citation(s) in RCA: 96] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 01/19/2020] [Accepted: 01/20/2020] [Indexed: 01/05/2023]
Abstract
OBJECTIVE To systematically investigate causal relationships between obesity and cerebrovascular disease and the extent to which hypertension and hyperglycemia mediate the effect of obesity on cerebrovascular disease. METHODS We used summary statistics from genome-wide association studies for body mass index (BMI), waist-to-hip ratio (WHR), and multiple cerebrovascular disease phenotypes. We explored causal associations with 2-sample Mendelian randomization (MR) accounting for genetic covariation between BMI and WHR, and we assessed what proportion of the association between obesity and cerebrovascular disease was mediated by systolic blood pressure (SBP) and blood glucose levels, respectively. RESULTS Genetic predisposition to higher BMI did not increase the risk of cerebrovascular disease. In contrast, for each 10% increase in WHR there was a 75% increase (95% confidence interval [CI] = 44-113%) in risk for large artery ischemic stroke, a 57% (95% CI = 29-91%) increase in risk for small vessel ischemic stroke, a 197% increase (95% CI = 59-457%) in risk of intracerebral hemorrhage, and an increase in white matter hyperintensity volume (β = 0.11, 95% CI = 0.01-0.21). These WHR associations persisted after adjusting for genetic determinants of BMI. Approximately one-tenth of the observed effect of WHR was mediated by SBP for ischemic stroke (proportion mediated: 12%, 95% CI = 4-20%), but no evidence of mediation was found for average blood glucose. INTERPRETATION Abdominal adiposity may trigger causal pathological processes, partially independent from blood pressure and totally independent from glucose levels, that lead to cerebrovascular disease. Potential targets of these pathological processes could represent novel therapeutic opportunities for stroke. ANN NEUROL 2020;87:516-524.
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Affiliation(s)
- Sandro Marini
- Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
- Department of Neurology, Boston University Medical Center, Boston, MA, USA
| | - Jordi Merino
- Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
- Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA
- Department of Medicine, Harvard Medical School, Boston, MA, USA
- Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, Sant Joan University Hospital, Universitat Rovira i Virgili, IISPV, CIBERDEM, Reus, Spain
| | | | - Rainer Malik
- Institute for Stroke and Dementia Research (ISD), University Hospital of Ludwig-Maximilians-University (LMU), Munich, Germany
| | - Catherine L. Sudlow
- Centre for Medical Informatics, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom
| | - Martin Dichgans
- Institute for Stroke and Dementia Research (ISD), University Hospital of Ludwig-Maximilians-University (LMU), Munich, Germany
- Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
- German Centre for Neurodegenerative Diseases (DZNE), Munich, Germany
| | - Jose C. Florez
- Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
- Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA
- Department of Medicine, Harvard Medical School, Boston, MA, USA
- Programs in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA
| | - Jonathan Rosand
- Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
- Programs in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA
- Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
- Henry and Allison McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA
| | - Dipender Gill
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Christopher D. Anderson
- Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
- Programs in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA
- Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
- Henry and Allison McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA
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15
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Chen Z, Mo J, Xu J, Qin H, Zheng H, Pan Y, Meng X, Jing J, Xiang X, Wang Y. Risk Profile of Ischemic Stroke Caused by Small-Artery Occlusion vs. Deep Intracerebral Hemorrhage. Front Neurol 2019; 10:1213. [PMID: 31827458 PMCID: PMC6890715 DOI: 10.3389/fneur.2019.01213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Accepted: 10/30/2019] [Indexed: 11/13/2022] Open
Abstract
Background: Small-artery occlusion (SAO) subtype accounts for a quarter of the cases of ischemic stroke and is mainly caused by pathological changes in cerebral small vessels, which also involve in deep intracerebral hemorrhage (dICH). However, the factors that drive some cases to SAO and others to dICH remained incompletely defined. Material and Methods: This study is a cross-sectional study from the China National Stroke Registry that included consecutive patients with ischemic stroke or intracerebral hemorrhage between August 2007 and September 2008. We compared the risk profile between the two subgroups using multivariable logistic regression. Results: A total of 1,135 patients with SAO stroke and 1,125 dICH patients were included for analyses. Generally, patients with SAO stroke were more likely to be male (odds ratio = 0.74, confidence interval = 0.58-0.94) and have diabetes (0.30, 0.22-0.40), higher atherogenic lipid profiles, higher body mass index (0.96, 0.94-0.99), higher waist/height ratio (0.12, 0.03-0.48), higher platelet count (0.84, 0.77-0.91), and higher proportion of abnormal estimated glomerular filtration rate (<90, ml/min/1.73 m2) (0.77, 0.62-0.95). Conversely, patients with dICH were more likely to have higher blood pressure parameters, inflammation levels (white blood cell count: 1.61, 1.48-1.76; high sensitivity C-reactive protein: 2.07, 1.36-3.16), and high-density lipoprotein-c (1.57, 1.25-1.98). Conclusions: The risk profile between SAO stroke and dICH were different. Furthermore, despite of traditional indexes, waist/height ratio, platelet count, inflammation levels, lipid profile, and estimated glomerular filtration rate also play important roles in driving arteriolosclerosis into opposite ends.
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Affiliation(s)
- Zimo Chen
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Jinglin Mo
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Jie Xu
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Haiqiang Qin
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Huaguang Zheng
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Yuesong Pan
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Xia Meng
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Jing Jing
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Xianglong Xiang
- China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Yongjun Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
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Park YS, Chung MS, Choi BS. MRI Assessment of Cerebral Small Vessel Disease in Patients with Spontaneous Intracerebral Hemorrhage. Yonsei Med J 2019; 60:774-781. [PMID: 31347333 PMCID: PMC6660438 DOI: 10.3349/ymj.2019.60.8.774] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Revised: 05/28/2019] [Accepted: 06/04/2019] [Indexed: 11/27/2022] Open
Abstract
PURPOSE Cerebral small vessel disease (SVD) is known to be associated with ischemic stroke, intracerebral hemorrhage (ICH), and cognitive impairment. In this retrospective observational study, we explored SVD markers on MRI relevant to spontaneous ICH. MATERIALS AND METHODS The ICH group consisted of 150 consecutive patients with a first primary parenchymal ICH, and the control group consisted of 271 age- and sex-matched individuals who underwent brain MRI in a health care center. We compared cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), enlarged perivascular space (EPVS), and lacunae in the ICH and control groups. RESULTS A total of 1278 CMB lesions were identified in 121 of the 150 patients in the ICH group (80.6%), while 77 CMB lesions were found in 32 of the 271 individuals in the control group (11.8%). WMH and EPVS were more severe and lacunae were more frequent in the ICH patients than in the control group. When receiver operating characteristic (ROC) curves were plotted, number of CMBs most significantly predicted ICH. All imaging markers were significantly associated with ICH in every age group. The location of CMBs coincided with the location of ICH, and ICH volume correlated with CMB count. CONCLUSION All MRI markers for SVD were worse in ICH patients than in healthy controls, and these markers were prominent even in young ICH patients. Lacunae, WMH, EPVS, and CMB should be considered as factors related with spontaneous ICH.
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Affiliation(s)
- Yong Sook Park
- Department of Neurosurgery, Chung-Ang University College of Medicine, Seoul, Korea.
| | - Mi Sun Chung
- Department of Radiology, Chung-Ang University College of Medicine, Seoul, Korea
| | - Byung Sun Choi
- Department of Preventive Medicine, Chung-Ang University College of Medicine, Seoul, Korea
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Arnoldussen IAC, Gustafson DR, Leijsen EMC, de Leeuw FE, Kiliaan AJ. Adiposity is related to cerebrovascular and brain volumetry outcomes in the RUN DMC study. Neurology 2019; 93:e864-e878. [PMID: 31363056 DOI: 10.1212/wnl.0000000000008002] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Accepted: 04/08/2019] [Indexed: 01/07/2023] Open
Abstract
OBJECTIVE Adiposity predictors, body mass index (BMI), waist circumference (WC), and blood leptin and total adiponectin levels were associated with components of cerebral small vessel disease (CSVD) and brain volumetry in 503 adults with CSVD who were ≥50 years of age and enrolled in the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC). METHODS RUN DMC participants were followed up for 9 years (2006-2015). BMI, WC, brain imaging, and dementia diagnoses were evaluated at baseline and follow-up. Adipokines were measured at baseline. Brain imaging outcomes included CSVD components, white matter hyperintensities, lacunes, microbleeds, gray and white matter, hippocampal, total brain, and intracranial volumes. RESULTS Cross-sectionally among men at baseline, higher BMI, WC, and leptin were associated with lower gray matter and total brain volumes, and higher BMI and WC were associated with lower hippocampal volume. At follow-up 9 years later, higher BMI was cross-sectionally associated with lower gray matter volume, and an obese WC (>102 cm) was protective for ≥1 lacune or ≥1 microbleed in men. In women, increasing BMI and overweight or obesity (BMI ≥25 kg/m2 or WC >88 cm) were associated with ≥1 lacune. Longitudinally, over 9 years, a baseline obese WC was associated with decreasing hippocampal volume, particularly in men, and increasing white matter hyperintensity volume in women and men. CONCLUSIONS Anthropometric and metabolic adiposity predictors were differentially associated with CSVD components and brain volumetry outcomes by sex. Higher adiposity is associated with a vascular-neurodegenerative spectrum among adults at risk for vascular forms of cognitive impairment and dementias.
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Affiliation(s)
- Ilse A C Arnoldussen
- From the Departments of Anatomy (I.A.C.A., A.J.K.) and Neurology (E.M.C.L., F.-E.d.L.), Donders Institute for Brain, Cognition and Behaviour, and Radboud Alzheimer Center (I.A.C.A., A.J.K.), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Neurology (D.R.G.), The State University of New York Downstate Health Sciences University, Brooklyn; and Department of Health and Education (D.R.G.), University of Skövde, Sweden
| | - Deborah R Gustafson
- From the Departments of Anatomy (I.A.C.A., A.J.K.) and Neurology (E.M.C.L., F.-E.d.L.), Donders Institute for Brain, Cognition and Behaviour, and Radboud Alzheimer Center (I.A.C.A., A.J.K.), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Neurology (D.R.G.), The State University of New York Downstate Health Sciences University, Brooklyn; and Department of Health and Education (D.R.G.), University of Skövde, Sweden.
| | - Esther M C Leijsen
- From the Departments of Anatomy (I.A.C.A., A.J.K.) and Neurology (E.M.C.L., F.-E.d.L.), Donders Institute for Brain, Cognition and Behaviour, and Radboud Alzheimer Center (I.A.C.A., A.J.K.), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Neurology (D.R.G.), The State University of New York Downstate Health Sciences University, Brooklyn; and Department of Health and Education (D.R.G.), University of Skövde, Sweden
| | - Frank-Erik de Leeuw
- From the Departments of Anatomy (I.A.C.A., A.J.K.) and Neurology (E.M.C.L., F.-E.d.L.), Donders Institute for Brain, Cognition and Behaviour, and Radboud Alzheimer Center (I.A.C.A., A.J.K.), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Neurology (D.R.G.), The State University of New York Downstate Health Sciences University, Brooklyn; and Department of Health and Education (D.R.G.), University of Skövde, Sweden
| | - Amanda J Kiliaan
- From the Departments of Anatomy (I.A.C.A., A.J.K.) and Neurology (E.M.C.L., F.-E.d.L.), Donders Institute for Brain, Cognition and Behaviour, and Radboud Alzheimer Center (I.A.C.A., A.J.K.), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Neurology (D.R.G.), The State University of New York Downstate Health Sciences University, Brooklyn; and Department of Health and Education (D.R.G.), University of Skövde, Sweden
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18
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Regenhardt RW, Das AS, Ohtomo R, Lo EH, Ayata C, Gurol ME. Pathophysiology of Lacunar Stroke: History's Mysteries and Modern Interpretations. J Stroke Cerebrovasc Dis 2019; 28:2079-2097. [PMID: 31151839 DOI: 10.1016/j.jstrokecerebrovasdis.2019.05.006] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Revised: 04/13/2019] [Accepted: 05/04/2019] [Indexed: 01/13/2023] Open
Abstract
Since the term "lacune" was adopted in the 1800s to describe infarctions from cerebral small vessels, their underlying pathophysiological basis remained obscure until the 1960s when Charles Miller Fisher performed several autopsy studies of stroke patients. He observed that the vessels displayed segmental arteriolar disorganization that was associated with vessel enlargement, hemorrhage, and fibrinoid deposition. He coined the term "lipohyalinosis" to describe the microvascular mechanism that engenders small subcortical infarcts in the absence of a compelling embolic source. Since Fisher's early descriptions of lipohyalinosis and lacunar stroke (LS), there have been many advancements in the understanding of this disease process. Herein, we review lipohyalinosis as it relates to modern concepts of cerebral small vessel disease (cSVD). We discuss clinical classifications of LS as well as radiographic definitions based on modern neuroimaging techniques. We provide a broad and comprehensive overview of LS pathophysiology both at the vessel and parenchymal levels. We also comment on the role of biomarkers, the possibility of systemic disease processes, and advancements in the genetics of cSVD. Lastly, we assess preclinical models that can aid in studying LS disease pathogenesis. Enhanced understanding of this highly prevalent disease will allow for the identification of novel therapeutic targets capable of mitigating disease sequelae.
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Affiliation(s)
- Robert W Regenhardt
- Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Alvin S Das
- Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Ryo Ohtomo
- Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Eng H Lo
- Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Cenk Ayata
- Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Mahmut Edip Gurol
- Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
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Lin TC, Lin YK, Chen CI, Chan L, Chi NF, Yuan RY, Sheu JJ, Wei CR, Tsai JP, Yeh TH. Serum lipid level is not associated with symptomatic intracerebral hemorrhage after intravenous thrombolysis for acute ischemic stroke. PeerJ 2018; 6:e6021. [PMID: 30505640 PMCID: PMC6254245 DOI: 10.7717/peerj.6021] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Accepted: 10/29/2018] [Indexed: 11/20/2022] Open
Abstract
Background This study assessed whether serum lipid levels are associated with the risk of symptomatic intracerebral hemorrhage (sICH) and functional outcomes in patients with acute ischemic stroke after receiving intravenous thrombolysis. Methods We retrospectively analyzed consecutive ischemic stroke patients who were treated with intravenous tissue plasminogen activator between January 2007 and January 2017. Lipid levels on admission, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels, as well as potential predictors of sICH were tested using univariate and multivariate analyses. Results Of the 229 enrolled patients (100 women, aged 68 ± 13 years), 14 developed sICH and 103 (45%) had favorable functional outcomes at 3 months. The patients with sICH more often had diabetes mellitus (71% vs. 26%, P = 0.01) and had more severe stroke (mean National Institutes of Health Stroke Scale [NIHSS] score of 16 vs. 13, P = 0.045). Regarding lipid subtype, total cholesterol, LDL-C, HDL-C, and triglyceride levels were not associated with sICH or functional outcomes. According to the results of multivariate analysis, the frequency of sICH was independently associated with diabetes mellitus (odds ratio [OR] = 6.04; 95% CI [1.31-27.95]; P = 0.02) and the NIHSS score (OR = 1.12; 95% CI [1.02-1.22]; P = 0.01). A higher NIHSS score was independently associated with unfavorable functional outcomes (OR = 0.86; 95% CI [0.81-0.91]; P < 0.001). Conclusions Serum lipid levels on admission, including total cholesterol, LDL-C, HDL-C, and triglyceride levels, were not associated with sICH or 3-month functional outcomes after intravenous thrombolysis for acute ischemic stroke.
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Affiliation(s)
- Ting-Chun Lin
- Department of Neurology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
| | - Yen-Kuang Lin
- Research Center of Biostatistics, Taipei Medical University, Taipei, Taiwan
| | - Chin-I Chen
- Department of Neurology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Lung Chan
- Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
| | - Nai-Fang Chi
- Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
| | - Rey-Yue Yuan
- Department of Neurology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
| | - Jau-Jiuan Sheu
- Department of Neurology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
| | - Chun-Ren Wei
- Department of Neurology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
| | - Jui-Ping Tsai
- Department of Neurology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
| | - Tu-Hsueh Yeh
- Department of Neurology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
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20
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The frontal skull Hounsfield unit value can predict ventricular enlargement in patients with subarachnoid haemorrhage. Sci Rep 2018; 8:10178. [PMID: 29977066 PMCID: PMC6033863 DOI: 10.1038/s41598-018-28471-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Accepted: 06/22/2018] [Indexed: 12/24/2022] Open
Abstract
Hydrocephalus is a common complication following subarachnoid haemorrhage (SAH) arising from spontaneous aneurysm rupture. The Hounsfield unit (HU) value from computed tomography scans may reflect bone mineral density, which correlates with body mass index, which in turn is related to post-SAH ventricle size changes. We herein investigated potential associations between frontal skull HU values and ventricle size changes after SAH. HU values from four different areas in the frontal bone were averaged to minimize measurement errors. The bicaudate index and Evans ratio were measured using both baseline and follow-up CT images. CT images with bicaudate index >0.2 and Evans ratio >0.3 simultaneously were defined as indicating ventriculomegaly. We included 232 consecutive patients with SAH due to primary spontaneous aneurysm rupture, who underwent clipping over almost a 9-year period at a single institution. The first tertile of frontal skull HU values in older patients (≥55 years) was an independent predictor of ventriculomegaly after SAH, as compared to the third tertile in younger patients (hazard ratio, 4.01; 95% confidence interval 1.21-13.30; p = 0.023). The lower frontal skull HU value independently predicted ventricular enlargement post-SAH, due to the potential weak integrity of subarachnoid trabecular structures in younger patients.
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Suo Y, Chen W, Pan Y, Peng Y, Yan H, Li W, Liu G, Wang Y. Magnetic Resonance Imaging Markers of Cerebral Small Vessel Disease in Hematoma Expansion of Intracerebral Hemorrhage. J Stroke Cerebrovasc Dis 2018; 27:2006-2013. [PMID: 29605289 DOI: 10.1016/j.jstrokecerebrovasdis.2018.02.066] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Revised: 02/19/2018] [Accepted: 02/28/2018] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Hematoma expansion is an independent risk factor of unfavorable outcome after intracerebral hemorrhage (ICH), which always occurs in the early phase after symptoms onset. The relationship between underlying small vessel disease (SVD) and hematoma expansion was inconsistent in patients with ICH. We aimed to investigate the relationship between magnetic resonance (MR) characteristics of SVD and hematoma expansion in patients with ICH within 72 hours after symptoms onset. METHODS Data were derived from a cohort of biological sample collection from April 2014 to April 2016. We recruited patients aged 18 years or older with a baseline and follow-up computed tomography within 72 hours after symptom onset, as well as an MR imaging within 3 months before or after ICH. Hematoma expansion was defined as an increase in volume between baseline and final hematoma volume exceeding 6 mL or 33% of the baseline volume. Multivariate logistic regression was used to explore the association between clinical characteristics, imaging markers, total SVD score, and hematoma expansion in patients with ICH. RESULTS A total of 103 patients experienced hematoma expansion among the 263 enrolled patients (mean age 53.4 ± 14.0 years, 76.4% male). Electrocardiogram abnormal rhythm, fewer non-lobar microbleeds, lower plasma homocysteine concentration, and smaller baseline hematoma volume independently predicted the risk of hematoma expansion (P = .004, .021, .001, and .024, respectively). Odds ratios ranged from 1.02 to 3.72. CONCLUSIONS Our study suggested that the use of MR markers revealing underlying SVD may help to identify patients with ICH with potential hematoma expansion.
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Affiliation(s)
- Yue Suo
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Weiqi Chen
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Yuesong Pan
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China; Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China
| | - Yujing Peng
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China; Department of Neurology and Institute of Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Hongyi Yan
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Wei Li
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China; Monogenic Disease Research Center for Neurological Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Gaifen Liu
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.
| | - Yongjun Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.
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Cappellari M, Zivelonghi C, Turcato G, Forlivesi S, Micheletti N, Tomelleri G, Bovi P, Bonetti B. A nomogram to predict the probability of mortality after first-ever acute manifestations of cerebral small vessel disease. J Neurol Sci 2018; 385:92-95. [DOI: 10.1016/j.jns.2017.12.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Revised: 11/23/2017] [Accepted: 12/17/2017] [Indexed: 10/18/2022]
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Factors Predicting Ventricle Volume Increase After Aneurysmal Clipping in Patients with Subarachnoid Hemorrhage. World Neurosurg 2017; 108:859-868.e4. [PMID: 28842230 DOI: 10.1016/j.wneu.2017.08.076] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Revised: 08/09/2017] [Accepted: 08/11/2017] [Indexed: 11/23/2022]
Abstract
OBJECTIVE Although many studies have evaluated risk factors associated with hydrocephalus after aneurysmal subarachnoid hemorrhage, specific ventricle volume changes after subarachnoid hemorrhage have not been evaluated. We sought to evaluate factors predicting ventricle volume enlargement in patients with aneurysmal subarachnoid hemorrhage by measuring ventricle volume with a validated, semiautomated tool. METHODS Uni- and multivariable linear regression analyses were conducted with the follow-up ventricle volume as the dependent variable and the duration between subarachnoid hemorrhage occurrence and follow-up imaging as the independent variable, classified by the use of various predictive factors. A logistic regression model was used to calculate the odds ratio for the greater ventricle volume group compared with the lower ventricle volume group based on predictive factors. RESULTS We included 173 participants with a mean age of 55.5 years. Overall, an approximate increase in ventricle volume of 1.1 mL was observed daily within 60 days of clipping due to subarachnoid hemorrhage. In the multivariate logistic regression analysis, patients in the first and second tertile groups for body mass index showed approximately a 5.9- and 4.1-fold increased risk of greater follow-up ventricle volume, respectively, compared with the third tertile group for body mass index within 60 days of subarachnoid hemorrhage. CONCLUSIONS We found that greater body mass index independently predicted suppression of ventricle volume growth, owing to maintenance of subarachnoid trabeculae structures after subarachnoid hemorrhage. Further studies are needed to confirm our findings.
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