Epidemiological Cardiology Research Center

Wake Forest, NC, United States

Epidemiological Cardiology Research Center

Wake Forest, NC, United States
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Kamel H.,New York Medical College | Okin P.M.,New York Medical College | Loehr L.R.,University of North Carolina at Chapel Hill | Alonso A.,University of Minnesota | Soliman E.Z.,Epidemiological Cardiology Research Center
Annals of Neurology | Year: 2015

Objective The aim of this study was to assess the relationship between abnormally increased P-wave terminal force in lead V1, an electrocardiographic (ECG) marker of left atrial abnormality, and incident ischemic stroke subtypes. We hypothesized that associations would be stronger with nonlacunar stroke, given that we expected left atrial abnormality to reflect the risk of thromboembolism rather than in situ cerebral small-vessel occlusion. Methods Our cohort comprised 14,542 participants 45 to 64 years of age prospectively enrolled in the Atherosclerosis Risk in Communities study and free of clinically apparent atrial fibrillation (AF) at baseline. Left atrial abnormality was defined as PTFV1 >4,000μV∗ms. Outcomes were adjudicated ischemic stroke, nonlacunar (including cardioembolic) ischemic stroke, and lacunar stroke. Results During a median follow-up period of 22 years (interquartile range, 19-23 years), 904 participants (6.2%) experienced a definite or probable ischemic stroke. A higher incidence of stroke occurred in those with baseline left atrial abnormality (incidence rate per 1,000 person-years, 6.3; 95% confidence interval [CI]: 5.4-7.4) than in those without (incidence rate per 1,000 person-years, 2.9; 95% CI: 2.7-3.1; p < 0.001). In Cox regression models adjusted for potential confounders and incident AF, left atrial abnormality was associated with incident ischemic stroke (hazard ratio [HR]: 1.33; 95% CI: 1.11-1.59). This association was limited to nonlacunar stroke (HR, 1.49; 95% CI: 1.07-2.07) as opposed to lacunar stroke (HR, 0.89; 95% CI: 0.57-1.40). Interpretation We found an association between ECG-defined left atrial abnormality and subsequent nonlacunar ischemic stroke. Our findings suggest that an underlying atrial cardiopathy may cause left atrial thromboembolism in the absence of recognized AF. © 2015 American Neurological Association.


Soliman E.Z.,Epidemiological Cardiology Research Center | Lopez F.,University of Minnesota | Chen L.Y.,University of Minnesota | Bengtson L.,Epidemiological Cardiology Research Center | And 4 more authors.
Circulation | Year: 2015

Background: It has recently been reported that atrial fibrillation (AF) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association is currently unknown. Further study of the relationship of AF with the type of MI (ST-segment-elevation MI [STEMI] versus non-ST-segment-elevation MI [NSTEMI]) might shed light on the potential mechanisms. Methods and Results: We examined the association between AF and incident MI in 14 462 participants (mean age, 54 years; 56% women; 26% blacks) from the Atherosclerosis Risk in Communities (ARIC) study who were free of coronary heart disease at baseline (1987-1989) with follow-up through December 31, 2010. AF cases were identified from study visit ECGs and by review of hospital discharge records. Incident MI and its types were ascertained by an independent adjudication committee. Over a median follow-up of 21.6 years, 1374 MI events occurred (829 NSTEMIs, 249 STEMIs, 296 unclassifiable MIs). In a multivariable-adjusted model, AF (n=1545) as a time-varying variable was associated with a 63% increased risk of MI (hazard ratio,1.63; 95% confidence interval, 1.32-2.02). However, AF was associated with NSTEMI (hazard ratio, 1.80; 95% confidence interval, 1.39-2.31) but not STEMI (hazard ratio, 0.49; 95% confidence interval, 0.18-1.34; P for hazard ratio comparison=0.004). Combining the unclassifiable MI group with either STEMI or NSTEMI did not change this conclusion. The association between AF and MI, total and NSTEMI, was stronger in women than in men (P for interaction <0.01 for both). Conclusions: AF is associated with an increased risk of incident MI, especially in women. However, this association is limited to NSTEMI. © 2015 American Heart Association, Inc.


Soliman E.Z.,Epidemiological Cardiology Research Center | Lopez F.,University of Minnesota | Chen L.Y.,University of Minnesota | Bengtson L.,University of Minnesota | And 4 more authors.
Circulation | Year: 2015

Background-It has recently been reported that atrial fibrillation (AF) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association is currently unknown. Further study of the relationship of AF with the type of MI (ST-segment-elevation MI [STEMI] versus non-ST-segment-elevation MI [NSTEMI]) might shed light on the potential mechanisms. Methods and Results-We examined the association between AF and incident MI in 14 462 participants (mean age, 54 years; 56% women; 26% blacks) from the Atherosclerosis Risk in Communities (ARIC) study who were free of coronary heart disease at baseline (1987-1989) with follow-up through December 31, 2010. AF cases were identified from study visit ECGs and by review of hospital discharge records. Incident MI and its types were ascertained by an independent adjudication committee. Over a median follow-up of 21.6 years, 1374 MI events occurred (829 NSTEMIs, 249 STEMIs, 296 unclassifiable MIs). In a multivariable-adjusted model, AF (n=1545) as a time-varying variable was associated with a 63% increased risk of MI (hazard ratio, 1.63; 95% confidence interval, 1.32-2.02). However, AF was associated with NSTEMI (hazard ratio, 1.80; 95% confidence interval, 1.39-2.31) but not STEMI (hazard ratio, 0.49; 95% confidence interval, 0.18-1.34; P for hazard ratio comparison=0.004). Combining the unclassifiable MI group with either STEMI or NSTEMI did not change this conclusion. The association between AF and MI, total and NSTEMI, was stronger in women than in men (P for interaction <0.01 for both). Conclusions-AF is associated with an increased risk of incident MI, especially in women. However, this association is limited to NSTEMI. © 2015 American Heart Association, Inc.


Soliman E.Z.,Epidemiological Cardiology Research Center | Safford M.M.,University of Alabama at Birmingham | Muntner P.,University of Alabama at Birmingham | Khodneva Y.,University of Alabama at Birmingham | And 7 more authors.
JAMA Internal Medicine | Year: 2014

IMPORTANCE Myocardial infarction (MI) is an established risk factor for atrial fibrillation (AF). However, the extent to which AF is a risk factor for MI has not been investigated. OBJECTIVE To examine the risk of incident MI associated with AF. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort of 23 928 participants residing in the continental United States and without coronary heart disease at baseline were enrolled from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort between 2003 and 2007, with follow-up through December 2009. MAIN OUTCOMES AND MEASURES Expert-adjudicated total MI events (fatal and nonfatal). RESULTS Over 6.9 years of follow-up (median 4.5 years), 648 incident MI events occurred. In a sociodemographic- adjusted model, AF was associated with about 2-fold increased risk of MI (hazard ratio [HR], 1.96 [95% CI, 1.52-2.52]). This association remained significant (HR, 1.70 [95% CI, 1.26-2.30]) after further adjustment for total cholesterol, high-density lipoprotein cholesterol, smoking status, systolic blood pressure, blood pressure-lowering drugs, body mass index, diabetes, warfarin use, aspirin use, statin use, history of stroke and vascular disease, estimated glomerular filtration rate, albumin to creatinine ratio, and C-reactive protein level. In subgroup analysis, the risk of MI associated with AF was significantly higher in women (HR, 2.16 [95% CI, 1.41-3.31]) than in men (HR, 1.39 [95% CI, 0.91-2.10]) and in blacks (HR, 2.53 [95% CI, 1.67-3.86]) than in whites (HR, 1.26 [95% CI, 0.83-1.93]); for interactions, P =.03 and P =.02, respectively. On the other hand, there were no significant differences in the risk of MI associated with AF in older (≥75 years) vs younger (<75 years) participants (HR, 2.00 [95% CI, 1.16-3.35] and HR, 1.60 [95% CI, 1.11-2.30], respectively); for interaction, P =.44. CONCLUSIONS AND RELEVANCE AF is independently associated with an increased risk of incident MI, especially in women and blacks. These findings add to the growing concerns of the seriousness of AF as a public health burden: in addition to being a well-known risk factor for stroke, AF is also associated with increased risk of MI. Copyright 2014 American Medical Association. All rights reserved.


Soliman E.Z.,Epidemiological Cardiology Research Center | Howard G.,University of Alabama at Birmingham | Cushman M.,University of Vermont | Kissela B.,University of Cincinnati | And 5 more authors.
Journal of the American College of Cardiology | Year: 2012

Objectives: The purpose of this study was to examine the association between prolongation of QT interval corrected for heart rate (QTc) with incident stroke. Background: Unlike cardiovascular morbidity and mortality, little is known about the relationship between QTc and risk of stroke. Methods: A total of 27,411 participants age 45 years and older without previous stroke from the REGARDS (REasons for Geographic and Racial Differences in Stroke) study were included in this analysis. QTc was calculated using Framingham formula (QTc Fram) . Stroke cases were identified and adjudicated during up to 8.2 years of follow-up (median, 5.1 years). Results: The risk of incident stroke in study participants with prolonged QTc Fram was almost 3 times the risk in those with normal QTc Fram (hazard ratio [HR] [95% confidence interval (CI)]: 2.88 [2.12 to 3.92], p < 0.0001). After adjustment for demographics (age, race, and sex), traditional stroke risk factors (antihypertensive medication use, systolic blood pressure, current smoking, diabetes, left ventricular hypertrophy, atrial fibrillation, and previous cardiovascular disease), warfarin use, aspirin use, QRS duration and use of QTc-prolonging drugs, the risk of stroke remained significantly high (HR [95% CI]: 1.67 [1.16 to 2.41], p = 0.0061) and was consistent across several subgroups of REGARDS study participants. Similar results were obtained when the risk of stroke was estimated per 1-SD increase in QTc Fram, (HR [95% CI]: 1.12 [1.03 to 1.21], p = 0.0053 in multivariable-adjusted model) and when other QTc correction formulas including those of Hodge, Bazett, and Fridericia were used. Conclusions: QTc prolongation is associated with a significantly increased risk of incident stroke independent of traditional stroke risk factors. Examining the risk of stroke associated with QTc-prolonging drugs may be warranted. © 2012 American College of Cardiology Foundation.


Agarwal S.K.,Johns Hopkins University | Soliman E.Z.,Epidemiological Cardiology Research Center
Expert Review of Cardiovascular Therapy | Year: 2013

In this review, the authors discuss the role of ECG in prediction of stroke. ECG plays an important role in detection of several stroke risk factors/predictors including atrial fibrillation and left ventricular hypertrophy; both are components of the Framingham Stroke Risk Score. Multiple other ECG traits have also emerged as potential predictors of stroke, namely cardiac electrical/structural remodeling - Q wave, QRS/QT duration, bundle blocks, P wave duration/amplitude/dispersion, other waveform angles and slopes; higher automaticity - ectopic beats; and re-entry - atrial tachyarrhythmia; and higher vulnerability to arrhythmia - heart rate and its variability. Most of these predictors are not ready for prime time yet; however, further research focusing on their role in risk stratification and prevention of stroke may be useful. In this article, the authors discuss the prevalence, mechanisms and clinical applications of traditional and novel ECG markers in the prevention and treatment of stroke. © 2013 Informa UK Ltd.


Rautaharju P.M.,Epidemiological Cardiology Research Center | Soliman E.Z.,Epidemiological Cardiology Research Center
Journal of Electrocardiology | Year: 2014

This review covers selected electrocardiographic left ventricular hypertrophy (ECG-LVH) studies which have evaluated their prognostic value for adverse cardiovascular (CVD) events. Most ECG-LVH studies have used echocardiographic left ventricular mass (Echo-LVM) as the gold standard for evaluating ECG-LVH criteria. More recently, LVM from magnetic resonance imaging (MRI-LVM) has evolved as the new gold standard. The reported risk of adverse CVD events is generally highest for ECG-LVH criteria which combine high amplitude QRS criteria with repolarization abnormalities such as in LV strain pattern. Evolving coronary heart disease (CHD) may account in part for the increased risk for ECG-LVH. However, one large coronary arteriography study found that 5-year survival was significantly lower in coronary artery disease (CAD) patients with ECG-LVH than without LVH regardless of CAD status. The utility of Echo-LVH as a standard is limited by the large intra- and inter-reader variability and the lack of standardization of allometric formulations for adjustment of LVM to body size. Newer evaluation data with MRI-LVM as the standard show that for most ECG criteria CVD event rates are significantly higher for study subgroups with ECG-LVH than those without ECG-LVH. However, the performance results differ when comparing the risk for CVD events from those for the overall LVH classification accuracy according to sensitivity and specificity. Large short-term variability of ECG amplitudes due to electrode placement variability is a common limiting factor for ECG-LVH criteria performance regardless of the gold standard. Clinical trials for hypertension control rely largely on monitoring Echo-LVH rather than ECG-LVH. © 2014 Elsevier Inc.


Soliman E.Z.,Epidemiological Cardiology Research Center | Cammarata M.,Section on Cardiology | Li Y.,Epidemiological Cardiology Research Center
Heart Rhythm | Year: 2014

Background There is a strong interest in PR interval as a predictor for adverse outcomes. However, inconsistent reports have emerged. Objective The purpose of this study was to test the hypothesis that the significance of PR interval as a predictor depends on the level of contribution of P duration to its length, a contribution that varies across populations. Methods We tested our hypothesis in 7501 participants from the Third National Health and Nutrition Examination Survey (NHANES III). Participants were divided into two subgroups based on the median P-duration contribution to PR interval (P duration/PR interval* 100). The risk of mortality associated with prolonged (>200 ms) and short (<120 ms) PR interval compared with normal PR interval was examined in all participants and each subgroup. Results P-duration contribution to the length of PR interval ranged from 30% to 90% (median 70%). During median follow-up of 13.8 years, 2541 deaths occurred. In a multivariable adjusted model, short but not prolonged PR interval was associated with mortality (hazard ratio [HR], (95% confidence interval [CI]): 1.54 (1.18, 2.00) and 1.02 (0.90, 1.16), respectively). However, in a stratified analysis by P-duration contribution to PR interval, both short and prolonged PR interval were associated with mortality in participants with high P-duration contribution (HR (95% CI):1.46 (1.10, 1.94) and 2.00 (1.34, 2.99), respectively) but not in participants with low P-duration contribution (HR (95% CI):1.53 (0.68, 3.41) and 0.99 (0.87, 1.13), respectively); interaction P =.008. Conclusion PR-interval associations with outcomes are dictated by the level of contribution of P duration to its length, a contribution that has a wide range and is expected to vary across populations. These findings could explain the inconsistent reports of PR-interval associations in different studies and call for caution when using PR interval in risk prediction models. © 2014 Heart Rhythm Society. All rights reserved.


Soliman E.Z.,Epidemiological Cardiology Research Center | Prineas R.J.,Epidemiological Cardiology Research Center
Journal of Electrocardiology | Year: 2014

The reported lower prevalence and incidence of atrial fibrillation (AF) despite the higher prevalence of AF risk factors in African Americans compared to Caucasian whites has been referred to as the paradox of AF in African Americans. In this report we highlight this paradox and address potential explanations using data from several US populations studies. These possible explanations include limited methodology to detect AF patterns that are harder to detect (e.g. paroxysmal/intermittent AF or atrial flutter) coupled with the possibility of African Americans having more of these patterns, differential access to health care with African Americans having less access and subsequently less detected AF, survival bias with Caucasian whites living longer and subsequently having more AF, and finally differential impact of AF risk factors with Caucasian whites being more affected or African Americans less affected by AF risk factors whether this is genetically determined or via other unknown predispositions. © 2014 Elsevier Inc. All rights reserved.


Soliman E.Z.,Epidemiological Cardiology Research Center | Shah A.J.,Emory University | Boerkircher A.,Wake Forest Baptist Medical Center | Li Y.,Epidemiological Cardiology Research Center | Rautaharju P.M.,Epidemiological Cardiology Research Center
Circulation: Arrhythmia and Electrophysiology | Year: 2014

Background-Prolonged-QT commonly coexists in the ECG with left ventricular hypertrophy (ECG-LVH). However, it is unclear whether to what extent QT prolongation coexisting with ECG-LVH can explain the prognostic signifcance of ECG-LVH, and whether prolonged-QT coexisting with ECG-LVH should be considered as an innocent consequence of ECG-LVH. Methods and Results-The study population consisted of 7506 participants (mean age, 59.4±13.3 years; 49% whites; and 47% men) from the US Third National Health and Nutrition Examination Survey. ECG-LVH was defned by Cornell voltage criteria. Prolonged heart-rate-adjusted QT (prolonged-QTa) was defned as QTa≥460 ms in women or 450 ms in men. Cox proportional hazards analysis was used to calculate the hazard ratios with 95% confdence intervals for the risk of all-cause mortality for various combinations of ECG-LVH and prolonged-QTa. ECG-LVH was present in 4.2% (N=312) of the participants, of whom 16.4% had prolonged-QTa. In a multivariable-adjusted model and compared with the group without ECG-LVH or prolonged-QTa, mortality risk was highest in the group with concomitant ECG-LVH and prolonged-QTa (hazard ratio, 1.63; 95% confdence interval, 1.12-2.36), followed by isolated ECG-LVH (1.48; 1.24-1.77), and then isolated prolonged-QTa (1.27; 1.12-1.46). In models with similar adjustment where ECG-LVH and prolonged-QTa were entered as 2 separate variables and subsequently additionally adjusted for each other, the mortality risk was essentially unchanged for both variables. Conclusions-Although prolonged-QT commonly coexists with LVH, both are independent markers of poor prognosis. Concomitant presence of prolonged-QT and ECG-LVH carries a higher risk than either predictor alone. © 2014 American Heart Association, Inc.

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