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 ◽  
...  

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.


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.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Mahdi Habibi-koolaee ◽  
Leila Shahmoradi ◽  
Sharareh R. Niakan Kalhori ◽  
Hossein Ghannadan ◽  
Erfan Younesi

Background. Stroke is a leading cause of death and disability worldwide. According to the Iranian Ministry of Medical Health and Education, out of 100,000 stroke incidents in the country, 25,000 lead to death. Thus, identifying risk factors of stroke can help healthcare providers to establish prevention strategies. This study was conducted to investigate the prevalence of stroke risk factors and their distribution based on stroke subtypes in Sayad Shirazi Hospital, Gorgan, Northeastern Iran. Material and Methods. A retrospective hospital-based study was conducted at Sayad Shirazi Hospital in Gorgan, the only referral university hospital for stroke patients in Gorgan city. All medical records with a diagnosis of stroke were identified based on the International Classification of Diseases, Revision 10, from August 23, 2015, to August 22, 2016. A valid and reliable data gathering form was used to capture data about demographics, diagnostics, lifestyle, risk factors, and medical history. Results. Out of 375 cases, two-thirds were marked with ischemic stroke with mean ages (standard deviation) of 66.4 (14.2) for men and 64.6 (14.2) for women. The relationship between stroke subtypes and age groups (P=0.008) and hospital outcome (P=0.0001) was significant. Multiple regression analysis showed that hypertension (Exp. (B) =1.755, P=0.037), diabetes mellitus (Exp. (B) =0.532, P=0.021), and dyslipidemia (Exp. (B) =2.325, P=0.004) significantly increased the risk of ischemic stroke. Conclusion. Overall, hypertension, diabetes mellitus, and dyslipidemia were the major risk factors of stroke in Gorgan. Establishment of stroke registry (population- or hospital-based) for the province is recommended.


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.


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 ◽  
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 ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Urvish K Patel ◽  
Priti Poojary ◽  
Vishal Jani ◽  
Mandip S Dhamoon

Background: There is limited recent population-based data of trends in acute ischemic stroke (AIS) hospitalization rates among young adults (YA). Rising prevalence of stroke risk factors may increase stroke rates in YA. We hypothesized that 1) stroke hospitalizations and mortality among YA are increasing over time (2000-2011), 2) besides traditional stroke risk factors, non-traditional factors are associated with stroke in YA, 3) stroke hospitalization among YA is associated with higher mortality, length of stay (LOS), and cost. Methods: In the Nationwide Inpatient Sample database (years 2000-2011), adult hospitalizations for AIS and concurrent diagnoses were identified by ICD-9-CM codes; the analytic cohort constituted all AIS hospitalizations. We performed weighted analysis using chi-square, t-test, and Jonckheere trend test. Multivariable survey regression models evaluated interactions between age group (18-45 vs. >45 years) and traditional and non-traditional risk factors, with outcomes including mortality, LOS, and cost. Models were adjusted for race, sex, Charlson’s Comorbidity Index, primary payer, location and teaching status of hospital, and admission day. Results: Among 5220960 AIS hospitalizations, 231858 (4.4%) were YA. On trend analysis, proportion of YA amongst AIS increased from 3.6% in 2000 to 4.7% in 2011 (p<0.0001) but mortality in YA decreased from 3.7% in 2000 to 2.6% in 2011, compared to 7.1% in 2000 to 4.6% in 2011 (p<0.0001) among older adults. Non-traditional, especially behavioral, risk factors were more common among YA, and LOS and cost were higher (Table). Conclusion: There was a trend for higher proportion of YA among AIS hospitalizations, though there was a decreasing mortality trend over 10 years. Behavioral risk factors were more common among YA, and there was an increased length of stay and cost. AIS in YA may require different preventive approaches compared to AIS among older adults.


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