Modeling Vascular Risk Factors for the Development of Ischemic Stroke Therapies

Background: Atherosclerotic stenosis of large IC arteries is an important cause of stroke. The prevalence of ICS in stroke population differs by ethnicity.We report the frequency of ICS among a global sample of patients with non-lacunar cryptogenic ischemic stroke (NLCIS) who did not have another identifiable cause for stroke i.e. cardioembolic, extracranial LAD, or other specific causes. Hypothesis: We hypothesized that the prevalence rates of ICS will differ according to global regions. Methods: Consecutive patients with recent ischemic stroke were retrospectively surveyed at 19 stroke centers in 19 countries to identify the frequency of IC imaging and its yield. Countries were grouped by World Bank regions. ICS was considered to be significant if there was >50% stenosis in the arteries proximal to the index stroke evidenced by MRA, CTA or TCD. Results: We identified a total of 2145 consecutive ischemic stroke patients among which 475 had NLCIS. IC arterial imaging was carried-out,on average, in 87% of patients. Of these 414 patients, 15% had stenosis proximal to the area of brain ischemia. The frequency of ICS among NLCIS patients was highest in East Asia (27%) and lowest in Pacific (4%). Patients with ICS in Latin America were significantly younger when compared to other 4 regions. Conclusion: IC arterial imaging is carried out in majority of stroke centers in patients with NLCIS, among whom the fraction of IS associated with ICS is substantial throughout the world, averaging about 15%. MRA / CTA had a higher yield than TCD. On average these patients have traditional vascular risk factors except for Latin American patients who are significantly younger with no vascular risk factors.

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Sex differences in vascular risk factors, in‐hospital management, and outcomes of patients with acute ischemic stroke in China

European Journal of Neurology ◽

10.1111/ene.15124 ◽

2021 ◽

Author(s):

Hong‐Qiu Gu ◽

Chun‐Juan Wang ◽

Xin Yang ◽

Chelsea Liu ◽

Xia Wang ◽

...

Keyword(s):

Risk Factors ◽

Sex Differences ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Hospital Management ◽

Vascular Risk Factors ◽

Vascular Risk

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Abstract WMP53: Traditional Vascular Risk Factors Account for Different Proportions of Ischemic Stroke Within Different Gender and Race Groups

Stroke ◽

10.1161/str.51.suppl_1.wmp53 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Elizabeth M Aradine ◽

Yan Hou ◽

Kathleen A Ryan ◽

Prachi Mehndiratta ◽

Michael S Phipps ◽

...

Keyword(s):

Risk Factors ◽

Young Adults ◽

Ischemic Stroke ◽

Black Men ◽

White Men ◽

Vascular Risk Factors ◽

Vascular Risk ◽

Odds Ratios ◽

Stroke In Young Adults ◽

Stroke In Young

Introduction: Few studies have compared the proportion of ischemic strokes attributable to traditional vascular risk factors (population-attributable risk percent or PAR%) between genders and races. The PAR% is a function of the population prevalence and strength of association of a risk factor. Methods: A population-based case-control study of ischemic stroke in young adults ages 18-49 in the Baltimore-Washington region was used to study the prevalence, odds ratios, and PAR% of hypertension, diabetes, and smoking among blacks and whites. Logistic regression was used to calculate age-adjusted odds ratios. All analyses were stratified by gender. Results: There were 1044 cases and 1099 controls. Of the cases, 47% were black, 54% were women. Roughly a quarter to a third of all strokes in women were attributable to smoking. Due to the higher prevalence of hypertension and a higher odds ratio for hypertension in black men (OR 3.9, 95% CI 2.6-5.9) compared to white men (OR 1.8, 95% CI 1.3-2.6), there was a much higher PAR% for hypertension among black men than white men. See Table 1 for prevalence and Table 2 for PAR% stratified by gender and race. Conclusion: Traditional vascular risk factors have the potential to explain a high proportion of ischemic stroke in young adults. The high proportion of strokes in women attributable to smoking underscores the need for targeted smoking cessation interventions in this population. Diabetes and, especially, hypertension are important contributors to the excess population burden of ischemic stroke among blacks. These findings support the value of early screening and treatment for hypertension in young blacks.

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Abstract TMP58: Determinants of White Matter Hyperintensity in Acute Ischemic Stroke Patients: The MRI-GENIE Study

Stroke ◽

10.1161/str.48.suppl_1.tmp58 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Anne-Katrin Giese ◽

Markus D Schirmer ◽

Adrian V Dalca ◽

Ramesh Sridharan ◽

Lisa Cloonan ◽

...

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Ischemic Stroke ◽

White Matter ◽

Stroke Risk ◽

Smoking Status ◽

Vascular Risk Factors ◽

White Matter Hyperintensity ◽

Vascular Risk ◽

Prior Stroke

Introduction: White matter hyperintensity (WMH) is a highly heritable trait and a significant contributor to stroke risk and severity. Vascular risk factors contribute to WMH severity; however, knowledge of the determinants of WMH in acute ischemic stroke (AIS) is still limited. Hypothesis: WMH volume (WMHv) varies across AIS subtypes and is modified by vascular risk factors. Methods: We extracted WMHv from the clinical MRI scans of 2683 AIS subjects from the MRI-Genetics Interface Exploration (MRI-GENIE) study using a novel fully-automated, volumetric analysis pipeline. Demographic data, stroke risk factors and stroke subtyping for the Causative Classification of Stroke (CCS) were performed at each of the 12 international study sites. WMHv was natural log-transformed for linear regression analyses. Results: Median WMHv was 5.7cm 3 (interquartile range (IQR): 2.2-12.8cm 3 ). In univariable analysis, age (63.1 ± 14.7 years, β=0.04, SE=0.002), prior stroke (10.2%, β=0.66, SE=0.08), hypertension (65.4%, β=0.75, SE=0.05), diabetes mellitus (23.1%, β=0.35, SE=0.06), coronary artery disease (17.6%, β=0.04, SE=0.002), and atrial fibrillation (14.6%, β=0.48, SE=0.07) were significant predictors of WMHv (all p<0.0001), as well as smoking status (52.2%, β=0.15, SE=0.05, p=0.005), race (16.5% Non-Caucasian, β=0.25, SE=0.07) and ethnicity (8.2% Hispanic, β=0.30, SE=0.11) (all p<0.01). In multivariable analysis, age (β=0.04, SE=0.002), prior stroke (β=0.56, SE=0.08), hypertension (β=0.33, SE=0.05), smoking status (β=0.16, SE=0.05), race (β=0.42, SE=0.06), and ethnicity (β=0.34, SE=0.09) were independent predictors of WMHv (all p<0.0001), as well as diabetes mellitus (β=0.13, SE=0.06, p=0.02). WMHv differed significantly (p<0.0001, unadjusted) across CCS stroke subtypes: cardioembolic stroke (8.0cm 3 , IQR: 4.2-15.4cm 3 ), large-artery stroke (6.9cm 3 , IQR: 3.1-14.7cm 3 ), small-vessel stroke (5.8cm 3 , IQR: 2.5-13.5cm 3 ), stroke of undetermined (4.7cm 3 , IQR: 1.6-11.0cm 3 ) or other (2.55cm 3 , IQR: 0.9-8.8cm 3 ) causes. Conclusion: In this largest-to-date, multicenter hospital-based cohort of AIS patients with automated WMHv analysis, common vascular risk factors contribute significantly to WMH burden and WMHv varies by CCS subtype.

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Traditional Vascular Risk Factors Account for Different Proportions of Ischemic Stroke Within Different Gender and Race Groups

Journal of Stroke and Cerebrovascular Diseases ◽

10.1016/j.jstrokecerebrovasdis.2020.104729 ◽

2020 ◽

Vol 29 (5) ◽

pp. 104729

Author(s):

Elizabeth Aradine

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Vascular Risk Factors ◽

Vascular Risk ◽

Gender And Race

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Diabetic patients with ischemic stroke have higher frequency of comorbid vascular risk factors and poor discharge outcomes

Journal of the Neurological Sciences ◽

10.1016/j.jns.2019.10.471 ◽

2019 ◽

Vol 405 ◽

pp. 27-28

Author(s):

B. Homoud ◽

A. Hakami ◽

M. AlMalki ◽

M. Shaheen ◽

A. Althuabiti ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Vascular Risk Factors ◽

Diabetic Patients ◽

Vascular Risk ◽

Discharge Outcomes

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Characteristics of first ever ischemic stroke in the very elderly: Profile of vascular risk factors and clinical outcome

Clinical Neurology and Neurosurgery ◽

10.1016/j.clineuro.2011.05.011 ◽

2011 ◽

Vol 113 (8) ◽

pp. 654-657 ◽

Cited By ~ 13

Author(s):

E. Auriel ◽

A.Y. Gur ◽

O. Uralev ◽

S. Brill ◽

L. Shopin ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Clinical Outcome ◽

Vascular Risk Factors ◽

Vascular Risk ◽

Very Elderly

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Extracranial carotid atherosclerosis and vascular risk factors in different types of ischemic stroke in Taiwan.

Stroke ◽

10.1161/01.str.25.10.1989 ◽

1994 ◽

Vol 25 (10) ◽

pp. 1989-1993 ◽

Cited By ~ 34

Author(s):

J S Jeng ◽

M Y Chung ◽

P K Yip ◽

B S Hwang ◽

Y C Chang

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Carotid Atherosclerosis ◽

Vascular Risk Factors ◽

Vascular Risk ◽

Different Types

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Ischemic Stroke, Inflammation, and Endotheliopathy in COVID-19 Patients

Stroke ◽

10.1161/strokeaha.120.031971 ◽

2021 ◽

Author(s):

Lindsay S. McAlpine ◽

Adeel S. Zubair ◽

Ilavarasy Maran ◽

Pola Chojecka ◽

Paul Lleva ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Endothelial Activation ◽

Vascular Risk Factors ◽

Interquartile Range ◽

Stroke Onset ◽

Vascular Risk ◽

Stroke Patients ◽

Markers Of Inflammation ◽

Von Willebrand

Background and Purpose: Reports indicate an increased risk of ischemic stroke during coronavirus disease 2019 (COVID-19) infection. We aimed to identify patients with COVID-19 and ischemic stroke and explore markers of inflammation, hypercoagulability, and endotheliopathy, a structural and functional disturbance of the vascular endothelium due to a stressor. Methods: This was a retrospective, observational cohort study comparing acute ischemic stroke patients with and without COVID-19 across 3 hospitals. Timing of stroke onset during COVID-19 course and markers of inflammation, hypercoagulability, and endothelial activation were evaluated by COVID-19 status and stroke cause. Results: Twenty-one patients with ischemic stroke were diagnosed with COVID-19 during the study period. Patients with COVID-19 had a similar age and burden of vascular risk factors compared with the control cohort (n=168). We identified a temporal correlation between stroke onset and the peak of acute phase reactants, including CRP (C-reactive protein), ferritin, and d-dimer. In subsets of patients with labs available, embolic stroke of undetermined source was associated with elevated IL (interleukin)-6 (median, 171 [interquartile range, 13–375] versus 8 [4–11], P <0.01) and sIL (soluble IL)-2 receptor (1972 [1525–4720] versus 767 [563–1408.5], P =0.05) levels. Stroke patients with COVID-19 demonstrated elevated levels of endothelial activation markers compared with non-COVID-19 stroke controls (median von Willebrand activity 285.0% [interquartile range, 234%–382%] versus 150% [128%–183%], P =0.034; von Willebrand antigen 330.0% [265%–650%] versus 152% [130%–277%], P =0.007, and factor VIII 301% [289%–402%] versus 49% [26%–94%], P <0.001). Conclusions: Ischemic stroke in patients with COVID-19 is associated with endotheliopathy and a systemic inflammatory response in patients with vascular risk factors. Further research evaluating endothelial and inflammatory markers in the setting of ischemic stroke and COVID-19 in larger, prospective cohorts is needed to validate the findings.

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Cancer-Related Ischemic Stroke Has a Distinct Blood mRNA Expression Profile

Stroke ◽

10.1161/strokeaha.119.026143 ◽

2019 ◽

Vol 50 (11) ◽

pp. 3259-3264 ◽

Cited By ~ 1

Author(s):

Babak B. Navi ◽

Ryna Mathias ◽

Carla P. Sherman ◽

Julia Wolfe ◽

Hooman Kamel ◽

...

Keyword(s):

Gene Expression ◽

Risk Factors ◽

Ischemic Stroke ◽

Mrna Expression ◽

Expression Profile ◽

Vascular Risk Factors ◽

Differentially Expressed ◽

Cancer Type ◽

Vascular Risk ◽

Stroke Group

Background and Purpose— Comorbid cancer is common in patients with acute ischemic stroke (AIS). As blood mRNA profiles can distinguish AIS mechanisms, we hypothesized that cancer-related AIS would have a distinctive gene expression profile. Methods— We evaluated 4 groups of 10 subjects prospectively enrolled at 3 centers from 2009 to 2018. This included the group of interest with active solid tumor cancer and AIS and 3 control groups with active cancer only, AIS only, or vascular risk factors only. Subjects in the AIS-only and cancer-only groups were matched to subjects in the cancer-stroke group by age, sex, and cancer type (if applicable). Subjects in the vascular risk factor group were matched to subjects in the cancer-stroke and stroke-only groups by age, sex, and vascular risk factors. Blood was drawn 72 to 120 hours after stroke. Total RNA was processed using 3′ mRNA sequencing. ANOVA and Fisher least significant difference contrast methods were used to estimate differential gene expression between groups. Results— In the cancer-stroke group, 50% of strokes were cryptogenic. All groups had differentially expressed genes that could distinguish among them. Comparing the cancer-stroke group to the stroke-only group and after accounting for cancer-only genes, 438 genes were differentially expressed, including upregulation of multiple genes/pathways implicated in autophagy signaling, immunity/inflammation, and gene regulation, including IL (interleukin)-1, interferon, relaxin, mammalian target of rapamycin signaling, SQSTMI1 (sequestosome-1), and CREB1 (cAMP response element binding protein-1). Conclusions— This study provides evidence for a distinctive molecular signature in blood mRNA expression profiles of patients with cancer-related AIS. Future studies should evaluate whether blood mRNA can predict detection of occult cancer in patients with AIS. Clinical Trial Registration— URL: https://clinicaltrials.gov . Unique identifier: NCT02604667.

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