Gastrointestinal Disorders and Risk of First-Ever Ischemic Stroke

Background and Purpose: Recent studies suggest that alteration of the normal gut microbiome contributes to atherosclerotic burden and cardiovascular disease. While many gastrointestinal diseases are known to cause disruption of the normal gut microbiome in humans, the clinical impact of gastrointestinal diseases on subsequent cerebrovascular disease remains unknown. We conducted an exploratory analysis evaluating the relationship between gastrointestinal diseases and ischemic stroke. Methods: We performed a retrospective cohort study using claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. We included only beneficiaries ≥66 years of age. We used previously validated diagnosis codes to ascertain our primary outcome of ischemic stroke. In an exploratory manner, we categorized gastrointestinal disorders by anatomic location, disease chronicity, and disease mechanism. We used Cox proportional hazards models to examine associations of gastrointestinal disorder categories and ischemic stroke with adjustment for demographics and established vascular risk factors. Results: Among a mean of 1 725 246 beneficiaries in each analysis, several categories of gastrointestinal disorders were associated with an increased risk of ischemic stroke after adjustment for established stroke risk factors. The most notable positive associations included disorders of the stomach (hazard ratio, 1.17 [95% CI, 1.15–1.19]) and functional (1.16 [95% CI, 1.15–1.17]), inflammatory (1.13 [95% CI, 1.12–1.15]), and infectious gastrointestinal disorders (1.13 [95% CI, 1.12–1.15]). In contrast, we found no associations with stroke for diseases of the anus and rectum (0.97 [95% CI, 0.94–1.00]) or neoplastic gastrointestinal disorders (0.97 [95% CI, 0.94–1.00]). Conclusions: In exploratory analyses, several categories of gastrointestinal disorders were associated with an increased risk of future ischemic stroke after adjustment for demographics and established stroke risk factors.

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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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Electrocardiographic ST-T Abnormities Are Associated With Stroke Risk in the REGARDS Study

Stroke ◽

10.1161/strokeaha.119.028069 ◽

2020 ◽

Vol 51 (4) ◽

pp. 1100-1106

Author(s):

Mitsuaki Sawano ◽

Ya Yuan ◽

Shun Kohsaka ◽

Taku Inohara ◽

Takeki Suzuki ◽

...

Keyword(s):

Ischemic Stroke ◽

Racial Differences ◽

Stroke Risk ◽

Proportional Hazards ◽

The United States ◽

Incidence Rates ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Common Finding ◽

Increased Risk

Background and Purpose— In previous studies, isolated nonspecific ST-segment and T-wave abnormalities (NSSTTAs), a common finding on ECGs, were associated with greater risk for incident coronary artery disease. Their association with incident stroke remains unclear. Methods— The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a population-based, longitudinal study of 30 239 white and black adults enrolled from 2003 to 2007 in the United States. NSSTTAs were defined from baseline ECG using the standards of Minnesota ECG Classification (Minnesota codes 4-3, 4-4, 5-3, or 5-4). Participants with prior stroke, coronary heart disease, and major and minor ECG abnormalities other than NSSTTAs were excluded from analysis. Multivariable Cox proportional hazards regression was used to examine calculate hazard ratios of incident ischemic stroke by presence of baseline NSSTTAs. Results— Among 14 077 participants, 3111 (22.1%) had NSSTTAs at baseline. With a median of 9.6 years follow-up, 106 (3.4%) with NSSTTAs had ischemic stroke compared with 258 (2.4%) without NSSTTAs. The age-adjusted incidence rates (per 1000 person-years) of stroke were 2.93 in those with NSSTTAs and 2.19 in those without them. Adjusting for baseline age, sex, race, geographic location, and education level, isolated NSSTTAs were associated with a 32% higher risk of ischemic stroke (hazard ratio, 1.32 [95% CI, 1.05–1.67]). With additional adjustment for stroke risk factors, the risk of stroke was increased 27% (hazard ratio, 1.27 [95% CI, 1.00–1.62]) and did not differ by age, race, or sex. Conclusions— Presence of NSSTTAs in persons with an otherwise normal ECG was associated with a 27% increased risk of future ischemic stroke.

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Abstract 140: Association Between Epilepsy and the Risk of Ischemic Stroke or Myocardial Infarction

Stroke ◽

10.1161/str.48.suppl_1.140 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Matthew A Mercuri ◽

Alexander E Merkler ◽

Neal S Parikh ◽

Michael E Reznik ◽

Hooman Kamel

Keyword(s):

Risk Factors ◽

Myocardial Infarction ◽

Ischemic Stroke ◽

Elderly Patients ◽

Proportional Hazards ◽

Predictor Variable ◽

Cox Proportional Hazards ◽

Vascular Events ◽

Increased Risk ◽

Acute Mi

Background: Vascular brain injury can result in epilepsy. It is posited that seizures in elderly patients might reflect subclinical vascular disease and thus herald future clinical vascular events. Hypothesis: Seizures in elderly patients are associated with an increased risk of ischemic stroke or myocardial infarction (MI). Methods: We obtained inpatient and outpatient claims data from 2008-2014 on a 5% sample of Medicare beneficiaries ≥66 years of age. The predictor variable was epilepsy, defined as two or more inpatient or outpatient claims with a diagnosis of seizure. The primary outcome was a composite of ischemic stroke or acute MI. The predictors and outcomes were all ascertained with previously validated ICD-9-CM code algorithms. Survival statistics and Cox proportional hazards models were used to assess the relationship between epilepsy and incident ischemic stroke or MI while adjusting for demographic characteristics and vascular risk factors. Patients were censored at the first occurrence of a stroke or MI, at the time of death, or on December 31, 2014. Results: Among 1,548,556 beneficiaries with a mean follow-up of 4.4 (±1.8) years, 15,055 (1.0%) developed epilepsy and 121,866 (7.9%) experienced an ischemic stroke or acute MI. Patients with seizures were older (76.1 versus 73.7 years) and had a significantly higher burden of vascular comorbidities than the remainder of the cohort. The annual incidence of stroke or acute MI was 3.28% (95% confidence interval [CI], 3.10-3.47%) in those with seizures versus 1.79% (95% CI, 1.78-1.80%) in those without (unadjusted hazard ratio [HR], 1.89; 95% CI, 1.78-2.00). After adjustment for demographics and risk factors, epilepsy had a weak association with the composite outcome (adjusted HR, 1.36; 95% CI, 1.29-1.44), a stronger association with ischemic stroke (adjusted HR, 1.77; 95% CI, 1.65-1.90), and no association with acute MI (adjusted HR, 0.95; 95% CI, 0.86-1.04). Conclusions: We found an association between epilepsy in elderly patients and future ischemic stroke but not acute MI. Therefore, seizures might signify occult cerebrovascular disease but not necessarily occult disease in other vascular beds.

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Abstract WP213: Association Between Thoracic Aorta Surgery and Long Term Risk of Stroke in Adults

Stroke ◽

10.1161/str.51.suppl_1.wp213 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Tashfin Huq ◽

Marialaura Simonetto ◽

Babak B Navi ◽

Hooman Kamel

Keyword(s):

Ischemic Stroke ◽

Thoracic Aorta ◽

Stroke Risk ◽

Proportional Hazards ◽

Perioperative Period ◽

Cox Proportional Hazards ◽

Medicare Beneficiaries ◽

Increased Risk ◽

Nationally Representative

Introduction: Thoracic aorta surgery carries a risk of perioperative stroke, but the long-term incidence of stroke after the perioperative period in these patients remains unclear. We therefore assessed the long-term risk of stroke in patients who underwent thoracic aorta repair. Methods: We performed a retrospective cohort study using 2008-2015 claims data from a nationally representative 5% sample of Medicare beneficiaries. Our exposure of interest was thoracic aorta surgery, defined using ICD-9-CM hospital procedure codes for endovascular graft implantation (39.73) or surgical resection and replacement (38.45). Our primary outcome was ischemic stroke, defined using previously validated ICD-9-CM diagnosis codes. Patients with stroke during the index surgical hospitalization were excluded, since our focus was on long-term stroke risk after the perioperative period . Cox proportional hazards analysis was used to examine the association between thoracic aorta surgery and stroke risk after adjustment for demographics and vascular risk factors. Given a clear violation of the proportional hazards assumption, we calculated period-specific risk estimates. Results: Among 1,751,719 beneficiaries (mean age 73 ±8 years), 1,402 underwent thoracic aorta repair. During 4.6 ±2.2 years of follow-up, 62,702 patients were diagnosed with ischemic stroke. The incidence of stroke was 1.24% (95% CI, 0.93-1.66%) per year after thoracic aorta repair compared to 0.77% (95% CI, 0.76-0.78%) per year in patients without thoracic aorta surgery. In adjusted models, there was an increased risk of stroke in the first 120 days after discharge from thoracic aorta surgery (HR, 2.1; 95% CI, 1.2-3.7), but no heightened risk was seen beyond 120 days after discharge from surgery (HR, 0.7; 95% CI, 0.5-1.0). Conclusions: In a large sample of Medicare beneficiaries, thoracic aorta surgery was associated with an increased risk of ischemic stroke in the first 120 days after hospital discharge, but there was no excess risk beyond that time point.

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

Circulation ◽

10.1161/circ.141.suppl_1.p418 ◽

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.

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Increased One-Year Recurrent Ischemic Stroke after First-Ever Ischemic Stroke in Males with Benign Prostatic Hyperplasia

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17155360 ◽

2020 ◽

Vol 17 (15) ◽

pp. 5360 ◽

Cited By ~ 1

Author(s):

Chun-Gu Cheng ◽

Hsin Chu ◽

Jiunn-Tay Lee ◽

Wu-Chien Chien ◽

Chun-An Cheng

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Benign Prostatic Hyperplasia ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Prostatic Hyperplasia ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Increased Risk ◽

One Year

(1) Background: Patients with benign prostatic hyperplasia (BPH) were questioned about quality of life and sleep. Most BPH patients were treated with alpha-1 adrenergic receptor antagonists, which could improve cerebral blood flow for 1–2 months. Patients with ischemic stroke (IS) could experience cerebral autoregulation impairment for six months. The relationship between BPH and recurrent IS remains unclear. The aim of this study was to determine the risk of one-year recurrent IS conferred by BPH. (2) Methods: We used data from the Taiwanese National Health Insurance Database to identify newly diagnosed IS cases entered from 1 January 2008 to 31 December 2008. Patients were followed until the recurrent IS event or 365 days after the first hospitalization. The risk factors associated with one-year recurrent IS were assessed using Cox proportional hazards regression. (3) Results: Patients with BPH had a higher risk of recurrent IS (12.11% versus 8.15%) (adjusted hazard ratio (HR): 1.352; 95% confidence interval (CI): 1.028–1.78, p = 0.031). Other risk factors included hyperlipidemia (adjusted HR: 1.338; 95% CI: 1.022–1.751, p = 0.034), coronary artery disease (adjusted HR: 1.487; 95% CI: 1.128–1.961, p = 0.005), chronic obstructive pulmonary disease (adjusted HR: 1.499; 95% CI: 1.075–2.091, p = 0.017), and chronic kidney disease (adjusted HR: 1.523; 95% CI: 1.033–2.244, p = 0.033). (4) Conclusion: Patients with BPH who had these risk factors had an increased risk of one-year recurrent IS. The modification of risk factors may prevent recurrent IS.

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Abstract TP159: Risk of Ischemic Stroke in Patients with Atrial Flutter

Stroke ◽

10.1161/str.48.suppl_1.tp159 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Mais Al-Kawaz ◽

Setareh Salehi Omran ◽

Neal S Parikh ◽

Mitchell S Elkind ◽

Elsayed Z Soliman ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Lower Risk ◽

Stroke Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Administrative Claims ◽

Primary Analysis ◽

Stroke Incidence ◽

The Difference

Introduction: Guidelines advise anticoagulation for patients with both atrial fibrillation (AF) and flutter (AFL). However, the risk of stroke associated with these two conditions has not been robustly compared. Methods: Using inpatient and outpatient Medicare administrative claims data from 2008-2014 for a 5% sample of all beneficiaries ≥66 years of age, we identified all patients diagnosed with AFL or AF. Patients with prior stroke were excluded. The primary outcome was ischemic stroke. Predictors and the outcome were ascertained by validated ICD-9-CM diagnosis codes. Patients were censored at the time of ischemic stroke, death, or last available follow-up. In the primary analysis, patients with AFL were censored upon diagnosis of AF. Survival statistics were used to compare stroke incidence in patients with AF versus AFL. We used Cox proportional hazards analysis to compare the associations of AFL and AF with ischemic stroke after adjustment for demographics and risk factors. In a secondary analysis, patients with AFL were not censored upon diagnosis of AF because the natural history of AFL frequently features the development of AF. Results: We identified 16,441 patients with AFL and 338,726 with AF. Patients with AFL were less often female (42.4% versus 53.0%), but other baseline characteristics, including mean CHA 2 DS 2 -VASc scores (3.9), were similar between groups. Over 2.4 (±2.0) years, 16,451 ischemic strokes were identified. The annual incidence of ischemic stroke in patients with AFL was 0.60% (95% confidence interval [CI], 0.48-0.75%), whereas it was 2.00% (95% CI, 1.96-2.02%) in patients with AF. After adjustment for demographics and vascular risk factors, AFL was associated with a lower risk of ischemic stroke than AF (hazard ratio [HR], 0.30; 95% CI, 0.24-0.37). Within 1 year, 64.9% (95% CI, 64.1-65.6%) of patients with AFL received a diagnosis of AF. The difference between stroke risk in AFL compared to AF was attenuated (HR, 0.85; 95% CI, 0.79-0.92) when patients with AFL were not censored upon diagnosis of AF. Conclusions: Patients with AFL may face a lower risk of ischemic stroke than patients with AF. However, AF often develops in those with AFL, and taking this into account, the difference in stroke risk between the two conditions grows smaller.

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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 11900: Influence of Competing Risks on the Association Between Warfarin and Ischemic Stroke in Atrial Fibrillation: The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study

Circulation ◽

10.1161/circ.132.suppl_3.11900 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Jeffrey M Ashburner ◽

Alan S Go ◽

Yuchiao Chang ◽

Margaret C Fang ◽

Lisa Fredman ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Ischemic Stroke ◽

Competing Risks ◽

Stroke Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Subdistribution Hazard ◽

Risk Of Death

Introduction: Studies examining the association between warfarin therapy and incidence of ischemic stroke in adults with atrial fibrillation (AF) have not accounted for patients who die of non-stroke causes. Hypothesis: Accounting for the competing risk of death may provide greater understanding of the “real world” impact of warfarin on stroke risk during multiyear follow-up in a large, diverse cohort of AF patients. Methods: We assessed this association in the ATRIA community-based cohort of AF patients (n=13,559; study years 1996-2003), with thromboembolic (>90% ischemic stroke) events (TEE) being clinician-adjudicated. Extended Cox proportional hazards regression with time-varying warfarin exposure estimated the cause-specific hazard ratio (HR) for TEE while adjusting for stroke risk factors. Fine and Gray subdistribution regression was used to estimate this association while also accounting for competing death events. Results: Patients using warfarin were younger, more likely to have had a prior stroke, and to have known diabetes, coronary disease, and heart failure, and also had higher mean CHA2DS2VASc scores (3.68 vs. 3.22). The death rate was much higher in the non-warfarin group (8.1 deaths/100 person-years; 2637 deaths vs. 5.5 deaths/100 person-years; 1777 deaths on warfarin). The cause-specific HR indicated a large reduction in TE with warfarin use (adjusted HR: 0.57, 95% CI: 0.50-0.65). In subdistribution hazard models accounting for competing death events over the full follow-up of 6 years, this association was substantially attenuated (adjusted HR: 0.87, 95% CI: 0.77-0.99). In analyses limited to 1-year follow-up with only 648 competing death events, the results without accounting for competing risks (adjusted cause-specific HR: 0.55, 95% CI: 0.43-0.71) were similar to the results that did account for competing risks (adjusted subdistribution HR: 0.59, 95% CI: 0.46-0.75). Conclusions: By accounting for competing death events, our results reflect a more realistic estimate of the multi-year stroke prevention benefits of warfarin for patients with AF. Many old/frail individuals with AF will not live long enough to gain substantial benefit from warfarin.

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

Circulation ◽

10.1161/circ.129.suppl_1.p351 ◽

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.

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