scholarly journals Inflammatory cytokines and ischemic stroke risk

Neurology ◽  
2019 ◽  
Vol 92 (20) ◽  
pp. e2375-e2384 ◽  
Author(s):  
Nancy Swords Jenny ◽  
Peter W. Callas ◽  
Suzanne E. Judd ◽  
Leslie A. McClure ◽  
Brett Kissela ◽  
...  

ObjectiveWe studied circulating interleukin (IL)–6, IL-8, and IL-10 concentrations and incident ischemic stroke risk in a biracial cohort, and determined if these cytokines mediated the racial disparity in stroke incidence affecting the black population.MethodsThe Reasons for Geographic and Racial Differences in Stroke study enrolled 30,237 black and white men and women age ≥45 in 2003-2007. We measured baseline IL-6, IL-8, and IL-10 in a case–cohort study of 557 participants with incident stroke over 5.4 years and 951 participants in a cohort sample.ResultsIL-6, but not IL-8 or IL-10, was higher in cases compared to the cohort sample (mean 4.5 vs 3.7 ng/mL; p < 0.001). Only IL-6 was associated with stroke risk factors. Adjusting for age, sex, and race, the hazard ratio (HR; 95% confidence interval) for incident stroke for the highest vs lowest quartile of IL-6 was 2.4 (1.6–3.4). HRs for the highest vs lowest quartiles of IL-8 and IL-10 were 1.5 (1.0–2.1) and 1.4 (1.0–1.9), respectively. After additional adjustment for stroke risk factors, only higher IL-6 remained associated with stroke risk (HR 2.0; 1.2–3.1). Associations did not differ by race. Mediation analyses showed that IL-6 mediated the black–white disparity in stroke risk, but mediation was via IL-6 associations with stroke risk factors.ConclusionsIn this biracial population-based sample, IL-6 was strongly associated with risk of incident stroke and mediated the racial disparity in stroke via inflammatory effects of risk factors. Further study on the clinical utility of IL-6 measurement in stroke risk assessment would be helpful.

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Charles D Nicoli ◽  
Nicholas Wettersten ◽  
George Howard ◽  
Virginia J Howard ◽  
Suzanne E Judd ◽  
...  

Introduction: The neuropeptide neurotensin (NT) has been linked to cardiovascular and metabolic disease risk. Through measurement of its stable equimolar precursor, pro-neurotensin/neuromedin N (pro-NT/NMN), hyperactivity of NT has been associated with aggregate cardiovascular outcomes that include stroke. However, the exclusive association of pro-NT/NMN with incident ischemic or hemorrhagic stroke has not been studied. Hypothesis: Higher serum pro-NT/NMN is associated with incident ischemic and hemorrhagic stroke. Methods: Prospective case-cohort study in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. From 2003-2007, REGARDS enrolled 30,239 White or Black adults aged ≥45. Pro-NT/NMN was measured by immunoassay in 464 ischemic stroke cases, 49 hemorrhagic stroke cases, and 800 non-cases from a random cohort. Cox proportional-hazards models were used to calculate hazard ratios (HR) of stroke by pro-NT/NMN quartiles and per standard deviation (SD) of log pro-NT/NMN. Model 1 (both stroke types) included demographic factors as covariates, Model 2A (ischemic only) added ischemic stroke risk factors, and Model 2B (hemorrhagic only) added hemorrhagic stroke risk factors. Results: The table shows an increased HR of ischemic stroke for those in the 4th vs 1st-quartile pro-NT/NMN in Model 1 with a trend of increased risk across quartiles; this was attenuated in Model 2A. Prebaseline diabetes and coronary artery disease were the largest confounders of ischemic stroke risk, with each accounting for 19% of the association observed in Model 1. There was no association of pro-NT/NMN with hemorrhagic stroke in either model. There were no interactions of race or sex with log pro-NT/NMN. Conclusions: Higher pro-NT/NMN is associated with increased risk of ischemic stroke after adjusting for demographics, but this was not independent of stroke risk factors. No significant association with hemorrhagic stroke was observed; this analysis was limited by a small number of events.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Kathryn M Rexrode ◽  
Braxton D Mitchell ◽  
Kathleen A Ryan ◽  
Steven J Kittner ◽  
Hakan Ay ◽  
...  

Introduction: The relative distribution of stroke risk factors, as well as ischemic stroke subtypes, in women compared with men is not well described. Hypothesis: We hypothesized that the distribution of ischemic stroke risk factors and subtypes would differ by sex, with a later onset in women and greater proportion of comorbidities. Methods: The NINDS Stroke Genetics Network (SiGN) consortium was established to evaluate genetic risk factors for ischemic stroke. A total of 23 separate studies performed Causative Classification of Stroke (CCS) typing using standardized criteria on ischemic stroke cases and contributed data on risk factors. We compared the distribution of ischemic stroke risk factors and CCS phenotypes between men and women with ischemic stroke. Results: Of the 16,228 ischemic strokes in SiGN, 8005 (49.3%) occurred in women. Median age at stroke was older in female than male stroke cases (73 vs. 66 years) (p=<0.0001). Among stroke cases, women were more likely than men cases to have hypertension or atrial fibrillation and less likely to have diabetes or coronary artery disease, or to smoke (p <0.003 for all). The distribution of stroke subtypes also differed by sex, with women less likely than men to have large artery infarction and small artery occlusion, and more likely to have cardioembolic stroke and undetermined stroke due to incomplete work-up (p values all <0.0001; see Table). Results were similar when the distribution of stroke subtypes was examined for those <70 years and ≥70 years, except for cardioembolic stroke remaining more common only among women ≥70. Conclusions: In this large group of carefully phenotyped ischemic strokes, the distribution of ischemic stroke subtypes and risk factor profiles differ significantly by sex. Evaluation of the causes of these differences may highlight areas for improved prevention and risk reduction in both genders.


2016 ◽  
Vol 47 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Wesley T. O'Neal ◽  
Hooman Kamel ◽  
Dawn Kleindorfer ◽  
Suzanne E. Judd ◽  
George Howard ◽  
...  

Background: It is currently unknown if premature atrial contractions (PACs) detected on the routine screening electrocardiogram are associated with an increased risk of ischemic stroke. Methods: We examined the association between PACs and ischemic stroke in 22,975 (mean age 64 ± 9.2; 56% women; 40% black) participants from the Reasons for Geographic and Racial Differences in Stroke study. Participants who were free of stroke at baseline were included. PACs were detected from centrally read electrocardiograms at baseline. Cox regression was used to examine the association between PACs and ischemic stroke events through March 31, 2014. Results: PACs were present in 1,687 (7.3%) participants at baseline. In a Cox regression model adjusted for stroke risk factors and potential confounders, PACs were associated with an increased risk of ischemic stroke (hazards ratio (HR) 1.34, 95% CI 1.04-1.74). The relationship was limited to non-lacunar infarcts (HR 1.42, 95% CI 1.08-1.87), and not lacunar strokes (HR 1.01, 95% CI 0.51-2.03). An interaction by sex was detected, with the association between PACs and ischemic stroke being stronger among women (HR 1.82, 95% CI 1.29-2.56) than men (HR 1.03, 95% CI 0.69-1.52; p-interaction = 0.0095). Conclusion: PACs detected on the routine electrocardiogram are associated with an increased risk for non-lacunar ischemic strokes, especially in women.


Cephalalgia ◽  
2015 ◽  
Vol 35 (14) ◽  
pp. 1252-1260 ◽  
Author(s):  
Amy A Gelfand ◽  
Heather J Fullerton ◽  
Alice Jacobson ◽  
Stephen Sidney ◽  
Peter J Goadsby ◽  
...  

Importance Our understanding of risk factors for childhood stroke is incomplete. In adults, migraine with aura is associated with a two-fold increase in ischemic stroke risk. Objective In this cohort study we examine the association between migraine and stroke among children in Kaiser Permanente Northern California (KPNC). Design, setting, and participants Children ages 2–17 years who were members of KPNC for ≥6 months between 1997 and 2007 were included. Migraine cohort members had one or more of: an ICD-9 code for migraine, migraine listed as a significant health problem, or a prescription for a migraine-specific medication. The comparison group was children with no evidence of headache. Main outcome measures Main outcome measures included stroke incidence rates and incidence rate ratios (IR). Results Among the 1,566,952 children within KPNC during the study period, 88,164 had migraine, and 1,323,142 had no evidence of headache. Eight migraineurs had a stroke (three (38%) hemorrhagic; five (63%) ischemic). Eighty strokes occurred in children without headache (53 (66%) hemorrhagic; 27 (34%) ischemic). The ischemic stroke incidence rate was 0.9/100,000 person-years in migraineurs vs. 0.4/100,000 person-years in those without headache; IR 2.0 (95% CI 0.8–5.2). A post-hoc analysis of adolescents (12–17 years) showed an increased risk of ischemic stroke among those with migraine; IR 3.4 (95% CI 1.2–9.5). The hemorrhagic stroke incidence rate was 0.5/100,000 person-years in migraineurs and 0.9/100,000 person-years in those without headache; IR 0.6 (95% CI 0.2–2.0). Conclusions There was no statistically significant increase in hemorrhagic or ischemic stroke risk in pediatric migraineurs in this cohort study. A post-hoc analysis found that ischemic stroke risk was significantly elevated in adolescents with migraine. Future studies should focus on identifying risk factors for ischemic stroke among adolescent migraineurs. Based on adult data, we recommend that migraine aura status should be studied as a possible risk factor for ischemic stroke among adolescent migraineurs.


Neurographics ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 395-404
Author(s):  
R. González‐Odriozola ◽  
E. Rawie ◽  
H.A. Parmar ◽  
F. Rivas‐Rodriguez

Recognizing childhood arterial ischemic stroke risk factors and presentation are extremely important for a prompt diagnosis and administration of hyperacute treatment requiring a high level of clinical suspicion. Stroke presentation in the pediatric population is not very specific, yet it is imperative to distinguish it from other mimics that may require different medical management. Vascular imaging studies, including MRA, CTA, and advanced neuroimaging techniques (eg, arterial wall imaging and CT/MR perfusion images) are extremely useful in the diagnosis of arterial ischemic stroke. This article offers a review of arterial pediatric ischemic stroke risk factors, clinical presentation, and the imaging appearance of the most common arterial ischemic stroke etiologies.Learning Objective: To recognize multiple risk factors, etiologies, and imaging presentations of pediatric arterial ischemic strokes.


2011 ◽  
Vol 69 (1) ◽  
pp. 130-140 ◽  
Author(s):  
Mark T. Mackay ◽  
Max Wiznitzer ◽  
Susan L. Benedict ◽  
Katherine J. Lee ◽  
Gabrielle A. deVeber ◽  
...  

2001 ◽  
Vol 50 (2) ◽  
pp. 163-168 ◽  
Author(s):  
Meredith R. Golomb ◽  
Daune L. MacGregor ◽  
Trish Domi ◽  
Derek C. Armstrong ◽  
Brian W. McCrindle ◽  
...  

2020 ◽  
Vol 25 (6) ◽  
pp. 534-540
Author(s):  
Charles D Nicoli ◽  
Nicholas Wettersten ◽  
Suzanne E Judd ◽  
George Howard ◽  
Virginia J Howard ◽  
...  

The tridecapeptide neurotensin has been implicated in the pathogenesis of cardiometabolic disease. Its stable precursor, pro-neurotensin/neuromedin N (pro-NT/NMN), has been associated with composite cardiovascular outcomes including coronary heart disease (CHD) and stroke. The exclusive association of pro-NT/NMN with ischemic stroke has not been evaluated. We conducted a prospective case-cohort study in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. From 2003 to 2007, REGARDS enrolled 30,239 white or black adults aged ⩾ 45 years. Baseline fasting pro-NT/NMN was measured by immunoassay in the analytic sample including 448 incident ischemic stroke cases and 818 random cohort sample participants. A total of 464 ischemic strokes occurred. Risk of stroke was assessed with a Cox proportional-hazards model incorporating demographic covariates and a second adding stroke risk factors. Increased pro-NT/NMN was associated with ischemic stroke in the demographic model overall (hazard ratio (HR) per standard deviation (SD) pro-NT/NMN 1.16, 95% confidence interval (CI) 1.01–1.33) and in men (HR per SD pro-NT/NMN 1.25, 95% CI 1.04–1.50); HRs were attenuated in the risk factor model. Pre-existing diabetes mellitus and CHD were the largest confounders of ischemic stroke risk, each accounting for an estimated 19% of the association of pro-NT/NMN with ischemic stroke observed in the demographic model. There were no significant interactions of race or sex with pro-NT/NMN. Further research on associations of pro-NT/NMN with stroke risk factors such as diabetes mellitus is indicated.


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