Comorbidities associated with different levels of total cholesterol in male and female acute ischemic stroke patients.
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ABSTRACT: Abstract
Men and women differ in their clinical risk factors with respect to various predictors of severity in acute ischemic stroke (AIS). High cholesterol is a risk factor for AIS and the mechanism by which high cholesterol levels lead to an AIS is well established. However, the specific relationship between demographic, clinical risk factors, total cholesterol, and the resulting gender difference in AIS patients is yet to be investigated. This study recruited AIS patients between January 2000 and June 2016 classified into normal, borderline or high total cholesterol (TC). Normal was defined as ?200?mg/dl, borderline 200 to 239?mg/dl and high ?240?mg/dl based on Adult Treatment Panel III (ATP III) Guidelines for the classification of TC levels. The logistic regression model was used to predict clinical risk factors associated within men and women AIS patients with different levels of TC. A total of 3532 AIS patients presented with normal TC, 760 patients with borderline TC and 427 patients with high TC. The high total cholesterol group was more likely to be women with increasing age (OR?=?1.028, 95% CI, 1.006-1.052, P?=?.014), body mass index (BMI) (OR?=?1.052, 95% CI, 1.004-1.102, P?=?.033), and high-density lipoprotein cholesterol (HDL-C) (OR?=?1.039, 95% CI, 1.019-1.060, P?
SUBMITTER: Brechtel L
PROVIDER: S-EPMC7769330 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
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Comorbidities associated with different levels of total cholesterol in male and female acute ischemic stroke patients.
Brechtel Leanne L Poupore Nicolas N Stoikov Teodora T Roley Laurie Theriot LT Emerson John F JF Nathaniel Thomas T
Medicine 20201201 52
<h4>Abstract</h4>Men and women differ in their clinical risk factors with respect to various predictors of severity in acute ischemic stroke (AIS). High cholesterol is a risk factor for AIS and the mechanism by which high cholesterol levels lead to an AIS is well established. However, the specific relationship between demographic, clinical risk factors, total cholesterol, and the resulting gender difference in AIS patients is yet to be investigated. This study recruited AIS patients between Janu ...[more]
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2020-11-25 | GSE162072 | GEO
Project description:BackgroundStroke is the second leading cause of death and the third leading cause of disability worldwide, with ischemic stroke (IS) being the most prevalent. A substantial number of irreversible brain cell death occur in the short term, leading to impairment or death in IS. Limiting the loss of brain cells is the primary therapy target and a significant clinical issue for IS therapy. Our study aims to establish the gender specificity pattern from immune cell infiltration and four kinds of cell-death perspectives to improve IS diagnosis and therapy.MethodsCombining and standardizing two IS datasets (GSE16561 and GSE22255) from the GEO database, we used the CIBERSORT algorithm to investigate and compare the immune cell infiltration in different groups and genders. Then, ferroptosis-related differently expressed genes (FRDEGs), pyroptosis-related DEGs (PRDEGs), anoikis-related DEGs (ARDEGs), and cuproptosis-related DEGs (CRDEGs) between the IS patient group and the healthy control group were identified in men and women, respectively. Machine learning (ML) was finally used to generate the disease prediction model for cell death-related DEGs (CDRDEGs) and to screen biomarkers related to cell death involved in IS.ResultsSignificant changes were observed in 4 types of immune cells in male IS patients and 10 types in female IS patients compared with healthy controls. In total, 10 FRDEGs, 11 PRDEGs, 3 ARDEGs, and 1 CRDEG were present in male IS patients, while 6 FRDEGs, 16 PRDEGs, 4 ARDEGs, and 1 CRDEG existed in female IS patients. ML techniques indicated that the best diagnostic model for both male and female patients was the support vector machine (SVM) for CDRDEG genes. SVM's feature importance analysis demonstrated that SLC2A3, MMP9, C5AR1, ACSL1, and NLRP3 were the top five feature-important CDRDEGs in male IS patients. Meanwhile, the PDK4, SCL40A1, FAR1, CD163, and CD96 displayed their overwhelming influence on female IS patients.ConclusionThese findings contribute to a better knowledge of immune cell infiltration and their corresponding molecular mechanisms of cell death and offer distinct clinically relevant biological targets for IS patients of different genders.
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Project description:Background and Purpose: Compared with one single measurement, dynamic change of lipid parameter calculated by repeated measurements has been recognized as a potential biometric to make stroke risk assessments. Total cholesterol (TC) is an important risk factor for stroke, but the relationship between TC change and incident stroke has not been investigated thoroughly. We thus aimed to explore the association between 2-year TC change and the risk of incident stroke, both ischemic and hemorrhagic, in the general population. Methods: From June 2006 to October 2007, a total of 70,999 participants with complete TC value at baseline (2006-2007) and the second examination (2008-2009) were included in our study. The change of TC was calculated as the 2-year follow-up TC subtracting baseline TC. Cox proportional hazards regression analysis was used to evaluate the association between the tertile of TC change and risk of incident stroke and stroke subtypes. Results: A total of 2,815 cases of stroke events were identified with a median follow-up period of 9.0 years. After adjusting for baseline TC and confounding factors, 2-year TC change was independently associated with increased risk of total stroke (HR 1.07, 95% CI 1.02-1.12) and ischemic stroke (HR 1.08, 95% CI 1.03-1.13) per SD (1.04 mmol/L) increase, while no significant association was obtained between TC change and intracerebral hemorrhage (p = 0.659). Conclusions: Increased 2-year TC change is associated with an elevated risk of incident total stroke and ischemic stroke, irrespective of the baseline TC value. Maintaining a sustained ideal level of TC is important for stroke prevention.
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Project description:Background: Ischemic stroke causes increased blood-brain barrier permeability and release of markers of axonal damage and inflammation. To investigate diagnostic and prognostic roles of neurofilament light chain (NF-L), we assessed levels of NF-L, S100B, interleukin-6 (IL-6), E-selectin, vascular endothelial growth factor-A (VEGF-A), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in patients with acute ischemic stroke or transient ischemic attack (TIA) and healthy controls. Methods: We studied neurofilament (NF) expression in 2 cases of human postmortem ischemic stroke, representing infarcts aged 3- to >7-days. In a prospective study, we measured plasma NF-L and inflammatory markers <8 h of symptom onset and at 72 h in acute ischemic stroke (n = 31), TIA (n = 9), and healthy controls (n = 29). We assessed whether NF-L, S100B, and IL-6 were associated with clinical severity on admission (Scandinavian Stroke Scale, SSS), diagnosis of ischemic stroke vs. TIA, and functional outcome at 3 months (modified Rankin Scale, mRS). Results: NF expression increased in ischemic neurons and in the infarcted brain parenchyma after stroke. Plasma NF-L levels were higher in stroke patients than in TIA patients and healthy controls, but IL-6 levels were similar. Higher acute NF-L levels were associated with lower SSS scores at admission and higher mRS scores at 3 months. No correlation was observed between NF-L and S100B, NF-L and IL-6, nor between S100B or IL-6 and SSS or mRS. Compared to controls, stroke patients had significantly higher VEGF-A and VCAM-1 at <8 h that remained elevated at 72 h, with significantly higher VEGF-A at <8 h; ICAM-1 was significantly increased at <8 h, while S100B and E-selectin were unchanged. Conclusions: Plasma NF-L levels, but not IL-6 and S100B, were significant predictors of clinical severity on admission and functional outcome at 3 months. Plasma NF-L is a promising biomarker of functional outcome after ischemic stroke.
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