Abstract P418: Increased Pro-neurotensin/neuromedin N is Associated With Incident Ischemic Stroke

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.

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Premature Atrial Contractions on the Screening Electrocardiogram and Risk of Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study

Neuroepidemiology ◽

10.1159/000448619 ◽

2016 ◽

Vol 47 (1) ◽

pp. 53-58 ◽

Cited By ~ 13

Author(s):

Wesley T. O'Neal ◽

Hooman Kamel ◽

Dawn Kleindorfer ◽

Suzanne E. Judd ◽

George Howard ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Racial Differences ◽

Stroke Risk ◽

Cox Regression ◽

Stroke Risk Factors ◽

Stroke Study ◽

Increased Risk ◽

Study Participants ◽

The Relationship

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.

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Pro-neurotensin/neuromedin N and risk of ischemic stroke: The REasons for Geographic And Racial Differences in Stroke (REGARDS) study

Vascular Medicine ◽

10.1177/1358863x20957406 ◽

2020 ◽

Vol 25 (6) ◽

pp. 534-540

Author(s):

Charles D Nicoli ◽

Nicholas Wettersten ◽

Suzanne E Judd ◽

George Howard ◽

Virginia J Howard ◽

...

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Ischemic Stroke ◽

Racial Differences ◽

Stroke Risk ◽

Cox Proportional Hazards Model ◽

Demographic Model ◽

Stroke Risk Factors ◽

Regards Study ◽

Neuromedin N

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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Inflammatory cytokines and ischemic stroke risk

Neurology ◽

10.1212/wnl.0000000000007416 ◽

2019 ◽

Vol 92 (20) ◽

pp. e2375-e2384 ◽

Cited By ~ 13

Author(s):

Nancy Swords Jenny ◽

Peter W. Callas ◽

Suzanne E. Judd ◽

Leslie A. McClure ◽

Brett Kissela ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Racial Differences ◽

Racial Disparity ◽

Stroke Risk ◽

Black Population ◽

Sample Mean ◽

Stroke Incidence ◽

Stroke Risk Factors ◽

Ischemic Stroke Risk

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.

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Abstract MP88: Dehydroepiandrosterone (DHEAS) and Risk of Stroke in Black and White Americans: The Reasons for Geographic and Racial Differences in Stroke Cohort (REGARDS)

Circulation ◽

10.1161/circ.131.suppl_1.mp88 ◽

2015 ◽

Vol 131 (suppl_1) ◽

Author(s):

Markus Degirmenci ◽

Peter W Callas ◽

Suzanne E Judd ◽

Virginia Howard ◽

Nancy S Jenny ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Racial Differences ◽

Stroke Risk ◽

Inverse Association ◽

Baseline Serum ◽

Men And Women ◽

Black And White ◽

Stroke Risk Factors ◽

Increased Risk

Introduction: The association of DHEAS with coronary risk has been extensively studied, but little information is available on stroke risk. DHEAS levels are lower with stroke risk factors such as atrial fibrillation, arterial stiffness and atherosclerosis, but only one paper evaluated stroke risk and showed an inverse association of DHEAS and stroke risk in female nurses. Hypothesis: We assessed the hypothesis that lower DHEAS level is associated with increased ischemic stroke risk. Methods: REGARDS enrolled 30,239 US participants aged 45 and older in 2003-07 (41% black, 59% white, 55% living in the southeastern stroke belt). Baseline serum DHEAS was measured in 1,578 participants; 963 in a cohort random sample and 544 with first-time ischemic stroke during 5.4 years of follow up. Cox proportional hazard models with weights to account for the case cohort design were used to calculate hazard ratios (HR) of stroke by quartiles of DHEAS levels. Results: DHEAS was significantly lower with older age, white race, female sex, and history of heart disease. DHEAS in the first compared to the fourth quartile was associated with increased risk of stroke (HR 1.7, CI: 1.2-2.4), although this association was not present after adjusting for age (or other stroke risk factors: HR 1.0, CI: 0.7-1.6). These findings were similar in men and women. Stratifying on age, as shown in the table, in those <65 at baseline, lower DHEAS was associated with increased stroke after adjustment for sex, race, and Framingham stroke risk factors (HR 3.1, CI: 1.3-7.6), but there was no association in those >65 years (HR 0.8, CI: 0.5-1.4). Conclusion: There was no overall association of lower DHEAS and stroke risk in this bi-racial cohort of men and women from across the US, although a possible difference by age was observed. More research is needed to determine association of DHEAS with stroke risk.

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Abstract T P153: Women and Men with Ischemic Stroke in SiGN Have Different Subtype Distributions and Risk Factors

Stroke ◽

10.1161/str.45.suppl_1.tp153 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Kathryn M Rexrode ◽

Braxton D Mitchell ◽

Kathleen A Ryan ◽

Steven J Kittner ◽

Hakan Ay ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Stroke Risk ◽

Cardioembolic Stroke ◽

Relative Distribution ◽

Large Artery ◽

Stroke Risk Factors ◽

Stroke Subtypes ◽

Small Artery Occlusion ◽

Ischemic Stroke Risk

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.

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Chapter 1. Transient Ischemic Attack, Traumatic Brain Injury, and Ischemic Stroke: Risk Factors and Treatments

Acute Brain Impairment - Drug Discovery ◽

10.1039/9781788012539-00001 ◽

2017 ◽

pp. 1-14

Author(s):

Philip V. Peplow ◽

Jacqueline J. T. Liaw

Keyword(s):

Risk Factors ◽

Traumatic Brain Injury ◽

Ischemic Stroke ◽

Brain Injury ◽

Transient Ischemic Attack ◽

Stroke Risk ◽

Stroke Risk Factors ◽

Ischemic Stroke Risk ◽

Ischemic Attack

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Arterial Ischemic Stroke in the Pediatric Population

Neurographics ◽

10.3174/ng.1900026 ◽

2019 ◽

Vol 9 (6) ◽

pp. 395-404

Author(s):

R. González‐Odriozola ◽

E. Rawie ◽

H.A. Parmar ◽

F. Rivas‐Rodriguez

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Stroke Risk ◽

Pediatric Population ◽

Arterial Ischemic Stroke ◽

Stroke Risk Factors ◽

Multiple Risk Factors ◽

Ischemic Stroke Risk ◽

High Level ◽

Neuroimaging Techniques

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.

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Abstract WMP54: ABO Blood Type and Incident Stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Stroke ◽

10.1161/str.44.suppl_1.awmp54 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Neil A Zakai ◽

Suzanne E Judd ◽

Leslie A McClure ◽

Brett M Kissela ◽

George Howard ◽

...

Keyword(s):

Risk Factors ◽

Racial Differences ◽

Stroke Risk ◽

Blood Type ◽

Stroke Risk Factors ◽

Increased Risk ◽

Cox Proportional Hazard Models ◽

Regards Study ◽

Type Ab ◽

Von Willebrand

Background: Non-O blood type is associated with higher procoagulant proteins and potentially stroke. Prior studies may overestimate the association due to lack of control for race and stroke risk factors as there are known racial differences in blood type, conventional stroke risk factors, and stroke risk. Methods: REGARDS recruited 30,239 participants in their homes between 2003-07 from the continental US; 55% were female, 41% were black, and 56% lived in the southeast (by design). Using a case-cohort design, 553 participants with incident stroke and 991 participants without baseline stroke were genotyped to determine blood type. Cox proportional hazard models adjusting for race and Framingham or ARIC stroke risk factors were used to determine the association of blood type with incident stroke. Results: Blacks had a higher frequency of blood type B (17% vs. 10%) and AB (5% vs. 2%) and a lower frequency of blood type O (31% vs. 42%) than whites (p <0.001) (Table). Except for diabetes (OR 4.1 95% CI 2.1, 7.9) and higher systolic blood pressure (7.5 mm hg higher, p = 0.01) for blood type AB vs. O, stroke risk factors did not differ by blood type. Over 4.5 years of follow-up, neither blood types A or B were associated with incident stroke accounting for race and traditional stroke risk factors (Table). Blood type AB was associated with a marginally increased risk of stroke after adjusting for race and Framingham (HR 1.8; 95% CI 1.0, 3.4) or ARIC (HR 1.8; 95% CI 1.0, 3.3) stroke risk factors (Table). Discussion: Blood type AB is associated with an increased risk of stroke which is not mediated by conventional stroke risk factors. This association could relate to increased factor VIII or von Willebrand factor in individuals with non-O blood type but this does not explain the unique association of blood type AB with stroke. Whether blood type should be incorporated into clinical stroke risk models is unknown.

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