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 ◽  
...  

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.

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.


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.


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.


Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Markus Degirmenci ◽  
Peter W Callas ◽  
Suzanne E Judd ◽  
Virginia Howard ◽  
Nancy S Jenny ◽  
...  

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.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Nancy S Jenny ◽  
Peter Callas ◽  
Neil A Zakai ◽  
Leslie McClure ◽  
Suzanne Judd ◽  
...  

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.


Stroke ◽  
2019 ◽  
Vol 50 (Suppl_1) ◽  
Author(s):  
George Howard ◽  
Mary Cushman ◽  
Maciej Banach ◽  
Brett M Kissela ◽  
Dawn O Kleindorfer ◽  
...  

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
George Howard ◽  
Mary Cushman ◽  
Maciej Banach ◽  
Brett M Kissela ◽  
David C Goff ◽  
...  

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.


2019 ◽  
Vol 4 (7) ◽  

Introduction: Patients undergoing hemodialysis are at increased risk of stroke. However, less known about the impact of some of the stroke risk factors, and the value of stroke risk scores in determining the risk in those patients. Our main goal. To assess the risk factors for stroke in hemodialysis patients and the use of the new CHA2DS2-VASc score for stroke assessment. Methods: Single center, retrospective cohort study of 336 patients undergoing hemodialysis from June 24, 2018, to September 6, 2018, was recruited. Baseline demographics, clinical, and laboratory data were collected. We calculated the CHA2 DS2 -VASc score for stroke assessment in all patients and categorized them into high, moderate and low risk patients according to CHA2 DS2 - VASc score and subcategorized them to two groups atrial fibrillation (AFib) and Non- Atrial fibrillation (Non AFib) patients. Results: 336 patients were included in our study; the majority of patients were at high risk with a CHA2 DS2 -VASc Score mean of 2.9± 1.5, although history of stroke was observed only in 15 patients (4.46%). According to CHA2 DS2 - VASc score, 280 patients were at high risk, 172 (51.19%) were high-risk patients on treatment (anticoagulant or antiplatelet) and 108(32.14%) patients were high risk patients not on treatment 48 were at moderate risk (14.28%) and 8 were at low risk (2.38 %). Patients were divided into subgroups as non-AFib and AFib. In non-AFib patients 320 (95.23%), high-risk patients 103 (32.18%) were not treated; high-risk patients with treatment are 162 (50.62%), moderate patients were 47 (14.68%), 8(2.5%) was in low risk. AFib patients were 16 with a mean CHA2 DS2 -VASc score of 4.4±1.1. Patients with AFib were all at high risk except 1 was at moderate risk (6.25%). There were 11 (68.75%) patients on treatment and 5 (31.25%) patients not on treatment. The risk factors for stroke that were statistically significant in increasing score risk for all patients were: age > 65 (95% CI, -2.04– -1.29; p = 0.000), being female (95% CI, -1.36– -0.68; p = 0.000) hypertension (95% CI, -2.59– -1.37; p = 0.000), diabetes (95% CI, -2.10– -1.50; p = 0.000), CVD (95% CI, -2.07– -1.24; p=0.000), history of stroke or TIA (95% CI, -3.70– -2.03; p = 0.000), CHF or LVEF (95% CI, -2.28– - 0.91; p = 0.000). Conclusions: The risk of stroke in hemodialysis patients is significant according to the use of CHA2 DS2 -VASc score in Non-AFib hemodialysis patients shows supportive evidence of increased risk of stroke in those patients, which suggest the importance of close monitoring of patients with stroke risk factors by the nephrologist and the stroke team which will lead to the initiation of early prophylaxis in those patients.


2019 ◽  
Vol 5 (4) ◽  
pp. 343-351
Author(s):  
Zaid I Almarzooq ◽  
Lisandro D Colantonio ◽  
Peter M Okin ◽  
Joshua S Richman ◽  
Todd M Brown ◽  
...  

Abstract Aims A recently described phenomenon is that of myocardial infarction (MI) events that meet criteria for MI, but that have very low peak troponin elevations, so-called ‘microsize MI’. These events are very common and associated with increased risk of all-cause mortality. Our aim is to compare risk factors for microsize MI vs. usual MI events. Methods and results Among 24 470 participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort free of coronary heart disease at baseline, heart-related hospitalizations were expert adjudicated for MI using published guidelines. Myocardial infarctions were classified as microsize MI (peak troponin <0.5 ng/mL) or usual MI (peak troponin ≥0.5 ng/mL). Competing risk analyses assessed associations between baseline risk factors and incident microsize vs. usual MI. Between 2003 and 2013 there were 891 MIs; 279 were microsize MI and 612 were usual MI. Risk factors for both usual MI and microsize MI include age, gender, diabetes, and urinary albumin to creatinine ratio. Risk factors for only usual MI include Residence in the Stroke Belt and Buckle regions and current smoking. Black race was associated with a uniquely lower risk of usual MI. Conclusion The similarities in risk profiles suggest a possible common aetiology and should encourage clinicians to both treat reversible risk factors for microsize MI and to initiate secondary prevention strategies following these events until this emerging clinical entity is better understood. Future studies should further assess the clinical outcomes of these two entities and their effect on future management.


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