AGE-RELATED DIFFERENCES IN STROKE RISK FACTORS: INSIGHTS FROM THE REASONS FOR GEOGRAPHIC AND RACIAL DIFFERENCES IN STROKE (REGARDS) STUDY

2017 ◽  
Author(s):  
George Howard
Keyword(s):  
Risk Factors ◽  
Racial Differences ◽  
Stroke Risk ◽  
Stroke Risk Factors ◽  
Age Related ◽  
Regards Study

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

Stroke ◽  
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.

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

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.

Abstract P351: Inflammation and Stroke Risk in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Nancy S Jenny ◽  
Peter Callas ◽  
Neil A Zakai ◽  
Leslie McClure ◽  
Suzanne Judd ◽  
...  
Keyword(s):  
Risk Factors ◽  
Racial Differences ◽  
Stroke Risk ◽  
Proportional Hazards ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Stroke Patients ◽  
Stroke Risk Factors ◽  
Cox Proportional Hazards Models ◽  
Regards Study

Background: Levels of the pro-inflammatory cytokines interleukin (IL)-6 and IL-8 and the anti-inflammatory cytokine IL-10 are altered in acute stroke patients compared to controls. However, results for IL-10 are inconsistent (higher in stroke patients compared to controls in some studies and decreased in others) and very few studies have examined associations of these biomarkers with risk of incident stroke. Methods: We examined associations of baseline levels of IL-6, IL-8 and IL-10 with stroke risk factors and risk of incident stroke in 1,572 white and black men and women from the REGARDS Study; an observational cohort of 30,239 adults followed for 5 years. Among those without prebaseline stroke, stroke cases (n=592, 53% men, 59% white, mean age 70 years) were compared to a cohort random sample (n=980, 44% men, 58% white, mean age 65 years). We used Cox proportional hazards models to examine associations of biomarkers with incident stroke. Hazard ratios (HR; 95% confidence intervals) for highest compared to lowest quartile for each biomarker are presented. Results: Baseline IL-6 was significantly higher in incident stroke cases compared to the cohort sample (p<0.001) while IL-8 and IL-10 levels did not vary significantly (p>0.05 for both). Adjusting for age, sex and race, IL-6 was higher in blacks compared to whites and higher in current smokers compared to never/former smokers (all p≤0.01). IL-6 was inversely associated with physical activity, alcohol use and education (all p≤0.01). IL-8 and IL-10 did not vary significantly with the risk factors examined. Adjusting for age, sex and race, the HR for risk of incident stroke in those in the highest compared to lowest quartile of IL-6 was 2.4 (1.6-3.4). HRs for IL-8 and IL-10 were 1.5 (1.0-2.1) and 1.4 (1.0-1.9), respectively. Adjusting for Framingham stroke risk factors and history of coronary heart disease, only IL-6 remained significantly associated with stroke risk (HR 2.0; 1.3-3.2). HRs for IL-8 and IL-10 were 1.1 (0.7-1.6) and 1.2 (0.8-1.8), respectively. IL-6 remained significantly associated with stroke risk when C-reactive protein was added to the model (HR 1.7; 1.1-2.7). Associations did not differ by race. Conclusions: In this population-based sample of US black and white adults, IL-6, but not IL-8 or IL-10, was associated with stroke risk factors and risk of incident stroke. Further study is needed on the clinical utility of IL-6 measurement in stroke risk assessment.

Abstract WP214: Differential Impact of Stroke Risk Factors Across the Age Spectrum: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Stroke ◽  
2019 ◽  
Vol 50 (Suppl_1) ◽  
Author(s):  
George Howard ◽  
Mary Cushman ◽  
Maciej Banach ◽  
Brett M Kissela ◽  
Dawn O Kleindorfer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Racial Differences ◽  
Stroke Risk ◽  
Differential Impact ◽  
Stroke Risk Factors ◽  
Regards Study

Abstract T P136: Potential Contributors to the Declining Impact of Stroke Risk Factors with Age: Implications for Stroke Epidemiology in the Elderly

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
George Howard ◽  
Mary Cushman ◽  
Maciej Banach ◽  
Brett M Kissela ◽  
David C Goff ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Stroke Risk ◽  
Multivariable Analysis ◽  
The Elderly ◽  
Stroke Risk Factors ◽  
Age Related ◽  
Increased Risk ◽  
The Impact ◽  
Age Related Changes

Purpose: The importance of stroke research in the elderly is increasing as America is “graying.” For most risk factors for most diseases (including stroke), the magnitude of association with incident events decreases at older ages. Potential changes in the impact of risk factors could be a “true” effect, or could be due to methodological issues such as age-related changes in residual confounding. Methods: REGARDS followed 27,748 stroke-free participants age 45 and over for an average of 5.3 years, during which 715 incident strokes occurred. The association of the “Framingham” risk factors (hypertension [HTN], diabetes, smoking, AFib, LVH and heart disease) with incident stroke risk was assessed in age strata of 45-64 (Young), 65-74 (Middle), and 75+ (Old). For those with and without an “index” risk factor (e.g., HTN), the average number of “other” risk factors was calculated. Results: With the exception of AFib, there was a monotonic decrease in the magnitude of the impact across the age strata, with HTN, diabetes, smoking and LVH even becoming non-significant in the elderly (Figure 1). However, for most factors, the increasing prevalence of other risk factors with age impacts primarily those with the index risk factor absent (Figure 2, example HTN as the “index” risk factor). Discussion: The impact of stroke risk factors substantially declined at older ages. However, this decrease is partially attributable to increases in the prevalence of other risk factors among those without the index risk factor, as there was little change in the prevalence of other risk factors in those with the index risk factor. Hence, the impact of the index risk factor is attenuated by increased risk in the comparison group. If this phenomenon is active with latent risk factors, estimates from multivariable analysis will also decrease with age. A deeper understanding of age-related changes in the impact of risk factors is needed.

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

2016 ◽  
Vol 47 (1) ◽  
pp. 53-58 ◽  
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.

scholarly journals An Examination of Stroke-Related Knowledge in Male Stroke Survivors Living in the South Carolina Stroke Belt

2014 ◽  
Vol 8 (6) ◽  
pp. 532-537 ◽  
Author(s):  
Charles Ellis
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Risk Factor ◽  
Racial Differences ◽  
Stroke Prevention ◽  
Stroke Risk ◽  
Stroke Survivors ◽  
Stroke Risk Factor ◽  
Stroke Risk Factors ◽  
Stroke Knowledge

Racial differences have been observed in stroke-related knowledge and knowledge of specific stroke risk factors and stroke prevention practices. Using data from 134 male stroke survivors, racial differences in overall knowledge, risk factor knowledge, and stroke prevention practices were examined using the Stroke Knowledge Test. Knowledge that diabetes doubles ones risk of stroke was present in 48% of the participants, while knowledge of aspirin in the prevention of stroke by stopping blood clot formation was reported in 83% of the participants. Findings indicate participants were knowledgeable that obesity increased risk of stroke (71%) and high blood pressure was the most important stroke risk factor (70%). Participants indicated knowledge that diet, exercise, and controlling blood pressure and cholesterol reduces risk of stroke (86%). In regression models, there were no significant race differences in overall stroke knowledge or the odds of knowledge of information related to stroke risk factors and stroke prevention practices after adjusting for age, education, and marital status. Although stroke-related knowledge did not differ by race, stroke survivors exhibited gaps in stroke knowledge particularly of knowledge of common risk factors. These factors should be considered in approaches to improve stroke-related knowledge in all stroke survivors.

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

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Charles D Nicoli ◽  
Nicholas Wettersten ◽  
George Howard ◽  
Virginia J Howard ◽  
Suzanne E Judd ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Racial Differences ◽  
Hemorrhagic Stroke ◽  
Stroke Risk ◽  
Disease Risk ◽  
Stroke Risk Factors ◽  
Increased Risk ◽  
Ischemic Stroke Risk ◽  
Neuromedin N

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.

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 ◽  
...  
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.

Abstract P216: Fatty Liver Index and Stroke Risk: the Reasons for Geographic and Racial Differences in Stroke Study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Kristine S Alexander ◽  
Neil A Zakai ◽  
Steven D Lidofsky ◽  
Peter W Callas ◽  
Suzanne E Judd ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Fatty Liver ◽  
Racial Differences ◽  
Stroke Risk ◽  
Stroke Risk Factors ◽  
Liver Index ◽  
Fatty Liver Index ◽  
Negative Score ◽  
Positive Score

Background: Nonalcoholic fatty liver disease (NAFLD) is a common condition driven by the obesity epidemic. It is associated with cardiometabolic risk factors including diabetes, obesity, and hyperlipidemia, but also cardiovascular disease events, independent of these factors. No prospective studies have investigated the association of NAFLD with stroke risk. Hypothesis: NAFLD is associated with the risk of stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) case-cohort study. Methods: The REGARDS study recruited 30,239 participants from the contiguous U.S., in order to study the reasons for regional and racial differences in stroke mortality. The REGARDS case-cohort study consists of 569 cases of incident stroke with 5.4 years follow up and a cohort random sample of 1,104. The Fatty Liver Index (FLI) was used a surrogate marker for NAFLD. It is calculated as e X /(1 + e X ) x 100, where x = 0.953*log(triglycerides) + 0.139*BMI + 0.718*log(γ-glutamyltransferase) + 0.053*waist circumference - 15.745. An FLI >60 is considered a positive score, 20-60 an intermediate score, and <20 a negative score. After excluding 68 participants who reported heavy alcohol consumption and 87 with baseline stroke, Cox proportional hazards models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) of stroke for FLI category, adjusting for age, race, sex, and the Framingham stroke risk factors and stratified by body mass index (BMI). Results: In the cohort sample, 44% of participants had NAFLD based on the FLI and 19% had a negative score. Compared to those without NAFLD, individuals with a positive score were more likely to be male (51% vs. 28%), have hypertension (69% vs. 40%), dyslipidemia (68% vs. 37%) diabetes (35% vs. 8%), and higher BMI (mean 33.7 vs. 23.0 kg/m 2 ; all p<0.001). No participant with BMI < 20 kg/m 2 had NAFLD by FLI. NAFLD was not associated with risk of stroke in a model adjusted for age, race and sex; HR 1.00 (95% CI 0.69-1.46), or a model further adjusted for Framingham stroke risk factors; HR 0.71 (95% CI 0.45-1.11). Stratifying by BMI group (20-30 kg/m 2 ), there was no association between NAFLD and stroke risk in those with BMI 20-<25 or 25-30 kg/m 2 . We were unable to analyze NAFLD in the BMI >30 group, due to low number of negative scores. When analyzed as a continuous variable among those with BMI 30 kg/m 2 , the HRs for a 10 unit higher FLI score were 0.92 (95% CI 0.84-1.01) and 1.17 (95% CI 0.97-1.42), respectively, adjusted for age, sex, race, and stroke risk factors. Discussion: NAFLD, as determined by a positive FLI score, was not associated with risk of stroke although FLI score was borderline associated with stroke risk in those with a BMI >30. Results raise the possibility that NAFLD represents end organ damage from an adverse metabolic profile, and is not a mediator of stroke risk.

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