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

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 P089: Adiposity and risk of stroke: body shape matters more than body weight

Circulation ◽

10.1161/circ.129.suppl_1.p089 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Suzanne E Judd ◽

Virginia J Howard ◽

George Howard ◽

Susan Lakoski ◽

Mary Cushman ◽

...

Keyword(s):

Racial Differences ◽

Stroke Risk ◽

Proportional Hazards ◽

Obesity Paradox ◽

The United States ◽

Cox Proportional Hazards ◽

Stroke Risk Factor ◽

Medical Risk ◽

Increased Risk ◽

History Of

Background: Higher body mass index (BMI) and larger waist circumference (WC), characteristics of increased adiposity, are associated with greater risk of cardiovascular disease (CVD). However, an obesity paradox (improved survival in those with history of stroke) has been observed in some populations. We hypothesized that BMI would be associated with decreased risk of stroke but that this association would be attenuated after accounting for WC. Methods: The REasons for Geographic and Racial Differences in Stroke (REGARDS) study recruited 30,239 black and white participants age 45 years and older from across the United States between 2003 and 2007. WC, height and weight were measured during a baseline in home visit and participants were followed every 6 months. Strokes were adjudicated by physicians after review of medical records. Cox proportional hazards models were used to assess stroke risk. BMI and WC were modeled in quintiles. Results: We observed 1047 incident and recurrent strokes over a mean of 6.3 years. Higher BMI and lower WC were associated with decreased risk of stroke after adjustment for demographic and medical risk factors (Table). Having both BMI and WC in the model dramatically increased the strength of association for the other variable. Collinearity was not present. The observed association was consistent across race, sex, age, WC, and history of stroke (all p for interaction >0.20). Conclusion: Increased BMI, the main measure used to define obesity, was not a stroke risk factor. Increased risk of stroke was observed in WC less than the current recommendations of 88 cm for women and 102 cm for men. Smaller waist sizes and maintenance of lean mass are important targets for stroke prevention.<br

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Metabolic Syndrome and Risk of Ischemic Stroke in Atrial Fibrillation

Stroke ◽

10.1161/strokeaha.119.025376 ◽

2019 ◽

Vol 50 (11) ◽

pp. 3045-3050 ◽

Cited By ~ 2

Author(s):

Joseph J. Decker ◽

Faye L. Norby ◽

Mary R. Rooney ◽

Elsayed Z. Soliman ◽

Pamela L. Lutsey ◽

...

Keyword(s):

Atrial Fibrillation ◽

Metabolic Syndrome ◽

Ischemic Stroke ◽

Stroke Risk ◽

Proportional Hazards ◽

International Diabetes Federation ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Increased Risk ◽

Low Hdl

Background and Purpose— Metabolic syndrome (MetS), a prothrombotic state, is associated with an increased risk of atrial fibrillation (AF) and stroke. The CHA 2 DS 2 -VASc score does not account for the MetS components of prehypertension, prediabetes mellitus, abdominal obesity, elevated triglycerides, and low HDL (high-density lipoprotein). Data are limited on the association of MetS with stroke in AF, independent of CHA 2 DS 2 -VASc variables. Our aim was to identify MetS components associated with ischemic stroke in participants with AF in the ARIC study (Atherosclerosis Risk in Communities). Methods— We included 1172 participants with incident AF within 5 years of measurement of MetS components. MetS was defined by ATP criteria and International Diabetes Federation criteria. Incident ischemic stroke was physician adjudicated. Multivariable Cox proportional hazards regression was used to assess the association of MetS components with stroke. Results— After a median follow-up of 14.8 years, there were 113 ischemic stroke cases. Of the individual MetS components, low HDL was borderline associated with increased stroke risk (hazard ratio, 1.48 [95% CI, 0.99–2.21]) after adjustment for CHA 2 DS 2 -VASc variables while the remaining MetS variables were not associated with stroke risk. The presence of ≥3 components of MetS was not significantly associated with ischemic stroke after adjustment for CHA 2 DS 2 -VASc variables (hazard ratio, 1.38 [95% CI, 0.91–2.11]). The risk of stroke increased by 13% for each additional component of MetS; however, this association was borderline significant (hazard ratio, 1.13 [95% CI, 0.99–1.28]). Conclusions— The presence of MetS was not significantly associated with ischemic stroke after adjustment for CHA 2 DS 2 -VASc variables. Consideration of MetS is unlikely to improve stroke prediction in AF.

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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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Gastrointestinal Disorders and Risk of First-Ever Ischemic Stroke

Stroke ◽

10.1161/strokeaha.120.030643 ◽

2020 ◽

Vol 51 (12) ◽

pp. 3577-3583

Author(s):

William H. Roth ◽

Anna Cai ◽

Cenai Zhang ◽

Monica L. Chen ◽

Alexander E. Merkler ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Gut Microbiome ◽

Stroke Risk ◽

Proportional Hazards ◽

Gastrointestinal Diseases ◽

Cox Proportional Hazards ◽

Gastrointestinal Disorders ◽

Stroke Risk Factors ◽

Increased Risk

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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Abstract 19554: Lipoprotein(a) and Risk of Ischemic Stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Circulation ◽

10.1161/circ.132.suppl_3.19554 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Kristine S Alexander ◽

Neil A Zakai ◽

Fred Unverzagt ◽

Virginia Wadley ◽

Brett M Kissela ◽

...

Keyword(s):

Ischemic Stroke ◽

Racial Differences ◽

Stroke Risk ◽

Proportional Hazards ◽

Continuous Variable ◽

Cox Proportional Hazards ◽

Stroke Incidence ◽

Lipoprotein A ◽

Cox Proportional Hazards Models ◽

Regards Study

Background: Increased lipoprotein (a) (Lp(a)) is associated with coronary risk, but links with stroke have been less consistent. Blacks have 2-4-fold higher Lp(a) levels than whites, and have higher stroke incidence than whites, but have been under-represented in studies of Lp(a) and stroke to date. Hypothesis: Lp(a) is a risk factor for ischemic stroke, and this risk differs by race. Methods: REGARDS recruited 30,239 black and white U.S. men and women in 2003-7 to study regional and racial differences in stroke mortality. We measured Lp(a) by immunonepholometric assay in 572 cases of incident ischemic stroke and a 1,104-person cohort random sample. The hazard ratio of stroke by baseline Lp(a) was calculated using Cox proportional hazards models, stratified by race. Lp(a) was modeled both as a continuous variable (per sex- and race-specific SD) and in sex- and race-specific quartiles, given known differences in distributions by race and sex. Results: As shown in the Figure, being in the 4 th vs 1 st Lp(a) quartile was associated with ischemic stroke in black but not white participants, adjusted for age and sex (Model 1). The HRs were essentially unchanged with added adjustment for stroke risk factors (Model 2). There was no significant association between Lp(a) as a continuous variable and stroke, though race-specific patterns were similar. There remained no association between Lp(a) and stroke in whites when we used the sex- and race-specific 90 th percentile as a cut-off (HR: 0.91 95% CI: 0.52, 1.60). Discussion: Lp(a) was associated with ischemic stroke risk in black but not white REGARDS participants, this might partly explain the black/white disparity in stroke. Further studies in racially diverse groups are necessary to confirm these findings. Figure 1. Hazard ratios for Lp(a) and stroke in blacks and whites, per quartile (compared with first quartile) and SD.

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Migraine with visual aura is a risk factor for incident atrial fibrillation

Neurology ◽

10.1212/wnl.0000000000006650 ◽

2018 ◽

Vol 91 (24) ◽

pp. e2202-e2210 ◽

Cited By ~ 24

Author(s):

Souvik Sen ◽

X. Michelle Androulakis ◽

Viktoriya Duda ◽

Alvaro Alonso ◽

Lin Yee Chen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Confidence Interval ◽

Stroke Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Visual Aura ◽

Atherosclerosis Risk In Communities ◽

Increased Risk ◽

Atherosclerosis Risk

ObjectiveMigraine with visual aura is associated with cardioembolic stroke risk. The aim of this study was to test association between migraine with visual aura and atrial fibrillation (AF), in the Atherosclerosis Risk in Communities study.MethodsIn the Atherosclerosis Risk in Communities study, a longitudinal, community-based cohort study, participants were interviewed for migraine history in 1993–1995 and were followed for incident AF through 2013. AF was adjudicated using ECGs, discharge codes, and death certificates. Multivariable Cox proportional hazards models were used to study the relation between migraine and its subtypes with incident AF, compared with controls without headaches. Mediation analysis was conducted to test whether AF was a mediator of migraine with visual aura-associated stroke risk.ResultsOf 11,939 participants assessed for headache and without prior AF or stroke, 426 reported migraines with visual aura, 1,090 migraine without visual aura, 1,018 nonmigraine headache, and 9,405 no headache. Over a 20-year follow-up period, incident AF was noted in 232 (15%) of 1,516 with migraine and 1,623 (17%) of 9,405 without headache. After adjustment for multiple confounders, migraine with visual aura was associated with increased risk of AF compared to no headache (hazard ratio 1.30, 95% confidence interval 1.03–1.62) as well as when compared to migraine without visual aura (hazard ratio 1.39, 95% confidence interval 1.05–1.83). The data suggest that AF may be a potential mediator of migraine with visual aura–stroke risk.ConclusionsMigraine with aura was associated with increased risk of incident AF. This may potentially lead to ischemic strokes.

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Race and Ethnic Disparities in Stroke Incidence in the Northern Manhattan Study

Stroke ◽

10.1161/strokeaha.119.028806 ◽

2020 ◽

Vol 51 (4) ◽

pp. 1064-1069 ◽

Cited By ~ 1

Author(s):

Hannah Gardener ◽

Ralph L. Sacco ◽

Tatjana Rundek ◽

Valeria Battistella ◽

Ying Kuen Cheung ◽

...

Keyword(s):

Incidence Rate ◽

Low Socioeconomic Status ◽

Proportional Hazards ◽

Ethnic Disparities ◽

Population Based ◽

Incidence Rates ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Stroke Incidence ◽

Increased Risk

Background and Purpose— An excess incidence of strokes among blacks versus whites has been shown, but data on disparities related to Hispanic ethnicity remain limited. This study examines race/ethnic differences in stroke incidence in the multiethnic, largely Caribbean Hispanic, NOMAS (Northern Manhattan Study), and whether disparities vary by age. Methods— The study population included participants in the prospective population-based NOMAS, followed for a mean of 14±7 years. Multivariable-adjusted Cox proportional hazards models were constructed to estimate the association between race/ethnicity and incident stroke of any subtype and ischemic stroke, stratified by age. Results— Among 3298 participants (mean baseline age 69±10 years, 37% men, 24% black, 21% white, 52% Hispanic), 460 incident strokes accrued (400 ischemic, 43 intracerebral hemorrhage, 9 subarachnoid hemorrhage). The most common ischemic subtype was cardioembolic, followed by lacunar infarcts, then cryptogenic. The greatest incidence rate was observed in blacks (13/1000 person-years), followed by Hispanics (10/1000 person-years), and lowest in whites (9/1000 person-years), and this order was observed for crude incidence rates until age 75. By age 85, the greatest incidence rate was in Hispanics. Blacks had an increased risk of stroke versus whites overall in multivariable models that included sociodemographics (hazard ratio, 1.51 [95% CI, 1.13–2.02]), and stratified analyses showed that this disparity was driven by women of age ≥70. The increased rate of stroke among Hispanics (age/sex-adjusted hazard ratio, 1.48 [95% CI, 1.13–1.93]) was largely explained by education and insurance status (a proxy for socieoeconomic status; hazard ratio after further adjusting for these variables, 1.17 [95% CI, 0.85–1.62]) but remained significant for women age ≥70. Conclusions— This study provides novel data regarding the increased stroke risk among Caribbean Hispanics in this elderly population. Results highlight the need to create culturally tailored campaigns to reach black and Hispanic populations to reduce race/ethnic stroke disparities and support the important role of low socioeconomic status in driving an elevated risk among Caribbean Hispanics.

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Risk of Ischemic Stroke Increases Over the Spectrum of Metabolic Syndrome Severity

Stroke ◽

10.1161/strokeaha.120.028944 ◽

2020 ◽

Vol 51 (8) ◽

pp. 2548-2552 ◽

Cited By ~ 1

Author(s):

Mark D. DeBoer ◽

Stephanie L. Filipp ◽

Mario Sims ◽

Solomon K. Musani ◽

Matthew J. Gurka

Keyword(s):

Metabolic Syndrome ◽

Ischemic Stroke ◽

Stroke Risk ◽

Proportional Hazards ◽

Lifestyle Modification ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

The Metabolic Syndrome ◽

Cox Proportional Hazards Models ◽

Ischemic Stroke Risk

Background and Purpose: Ischemic stroke is associated with the metabolic syndrome (MetS) as diagnosed using dichotomous criteria; however, these criteria exhibit racial/ethnic discrepancies. Our goal was to assess whether ischemic stroke risk extended over the spectrum of worsening MetS severity using a sex- and race/ethnicity-specific MetS-severity Z score. Methods: We used Cox-proportional hazards models to assess the relationship between baseline MetS- Z score and incident ischemic stroke among participants of the Atherosclerosis Risk in Communities study and Jackson Heart Study who were free from diabetes, coronary heart disease or stroke at baseline, evaluating 13 141 white and black individuals with mean follow-up of 18.6 years. Results: We found that risk of ischemic stroke increased consistently with MetS severity, with a hazard ratio of 1.75 (95% CI, 1.35–2.27) for those >75th percentile compared to those <25th percentile. This risk was highest for white females (hazard ratio, 2.63 [CI, 1.70–4.07]) though without significant interaction by sex and race. Relationships between stroke and all the individual components of MetS were only noted for white females, though again without sex-race interactions. Hazard ratio’s for systolic blood pressure and stroke were significant among all sex/racial subgroups. Conclusions: Ischemic stroke risk increased over the spectrum of MetS severity in the absence of baseline diabetes mellitus, further implicating potential etiologic risks from processes underlying MetS. Individuals with elevated MetS severity should be counselled toward lifestyle modification to lower ischemic stroke risk.

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Factors that contribute to urban–rural gradients in risk of schizophrenia: Comparing Danish and Western Australian registers

Australian & New Zealand Journal of Psychiatry ◽

10.1177/00048674211009615 ◽

2021 ◽

pp. 000486742110096

Author(s):

Oleguer Plana-Ripoll ◽

Patsy Di Prinzio ◽

John J McGrath ◽

Preben B Mortensen ◽

Vera A Morgan

Keyword(s):

Confidence Interval ◽

Western Australia ◽

Urban Areas ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Indigenous Status ◽

Increased Risk ◽

The Relationship ◽

Western Australian

Introduction: An association between schizophrenia and urbanicity has long been observed, with studies in many countries, including several from Denmark, reporting that individuals born/raised in densely populated urban settings have an increased risk of developing schizophrenia compared to those born/raised in rural settings. However, these findings have not been replicated in all studies. In particular, a Western Australian study showed a gradient in the opposite direction which disappeared after adjustment for covariates. Given the different findings for Denmark and Western Australia, our aim was to investigate the relationship between schizophrenia and urbanicity in these two regions to determine which factors may be influencing the relationship. Methods: We used population-based cohorts of children born alive between 1980 and 2001 in Western Australia ( N = 428,784) and Denmark ( N = 1,357,874). Children were categorised according to the level of urbanicity of their mother’s residence at time of birth and followed-up through to 30 June 2015. Linkage to State-based registers provided information on schizophrenia diagnosis and a range of covariates. Rates of being diagnosed with schizophrenia for each category of urbanicity were estimated using Cox proportional hazards models adjusted for covariates. Results: During follow-up, 1618 (0.4%) children in Western Australia and 11,875 (0.9%) children in Denmark were diagnosed with schizophrenia. In Western Australia, those born in the most remote areas did not experience lower rates of schizophrenia than those born in the most urban areas (hazard ratio = 1.02 [95% confidence interval: 0.81, 1.29]), unlike their Danish counterparts (hazard ratio = 0.62 [95% confidence interval: 0.58, 0.66]). However, when the Western Australian cohort was restricted to children of non-Aboriginal Indigenous status, results were consistent with Danish findings (hazard ratio = 0.46 [95% confidence interval: 0.29, 0.72]). Discussion: Our study highlights the potential for disadvantaged subgroups to mask the contribution of urban-related risk factors to risk of schizophrenia and the importance of stratified analysis in such cases.

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Abstract 187: Electrocardiographic Heart Rate-corrected Qt Interval And Risk Of Stroke In The REasons For Geographic And Racial Differences In Stroke (REGARDS) Study

Stroke ◽

10.1161/str.43.suppl_1.a187 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Elsayed Z Soliman ◽

George Howard ◽

Mary Cushman ◽

Brett Kissela ◽

...

Keyword(s):

Heart Rate ◽

Racial Differences ◽

Qt Interval ◽

Proportional Hazards ◽

Left Ventricular ◽

Cox Proportional Hazards ◽

Corrected Qt Interval ◽

Cardiovascular Morbidity And Mortality ◽

Increased Risk ◽

Regards Study

Background: Prolongation of heart rate-corrected QT interval (QTc) is a well established predictor of cardiovascular morbidity and mortality. Little is known, however, about the relationship between this simple electrocardiographic (ECG) marker and risk of stroke. Methods: A total of 27,411 participants aged > 45 years without prior stroke from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study were included in this analysis. QTc was calculated using Framingham formula (QTcFram). Stroke cases were identified and adjudicated during an up to 7 years of follow-up (median 2.7 years). Cox proportional hazards analysis was used to estimate the hazard ratios for incident stroke associated with prolonged QTcFram interval (vs. normal) and per 1 standard deviation (SD) increase, separately, in a series of incremental models. Results: The risk of incident stroke in the study participants with baseline prolonged QTcFram was almost 3 times the risk in those with normal QTcFram [HR (95% CI): 2.88 (2.12, 3.92), p<0.0001]. After adjustment for age, race, sex, antihypertensive medication use, systolic blood pressure, current smoking, diabetes, left ventricular hypertrophy, atrial fibrillation, prior cardiovascular disease, QRS duration, warfarin use, and QT-prolonging drugs (full model), the risk of stroke remained significantly high [HR (95% CI): 1.67 (1.16, 2.41), p=0.0060)], and was consistent across several subgroups of REGARDS participants. When the risk of stroke was estimated per 1 SD increase in QTcFram, a 24% increased risk was observed [HR (95% CI): 1.24 (1.16, 1.33), p<0.0001)]. This risk remained significant in the fully adjusted model [HR (95% CI): 1.12 (1.03, 1.21), p=0.0055]. Similar results were obtained when other QTc correction formulas including Hodge’s, Bazett’s and Fridericia’s were used. Conclusions: QTc prolongation is associated with a significantly increased risk of incident stroke independently from known stroke risk factors. In light of our results, examining the risk of stroke associated with QT-prolonging drugs may be warranted.

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