Wesley T. O'Neal

Atrial fibrillation and risk of ST-segment-elevation versus non-ST-segment-elevation myocardial infarction the Atherosclerosis Risk in Communities (ARIC) study

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.

Electrocardiographic left atrial abnormality and stroke subtype in the atherosclerosis risk in communities study

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.

Monoamine Oxidase is a Major Determinant of Redox Balance in Human Atrial Myocardium and is Associated With Postoperative Atrial Fibrillation

Background Onset of postoperative atrial fibrillation (POAF) is a common and costly complication of heart surgery despite major improvements in surgical technique and quality of patient care. The etiology of POAF, and the ability of clinicians to identify and therapeutically target high‐risk patients, remains elusive. Methods and Results Myocardial tissue dissected from right atrial appendage (RAA) was obtained from 244 patients undergoing cardiac surgery. Reactive oxygen species (ROS) generation from multiple sources was assessed in this tissue, along with total glutathione (GSHt) and its related enzymes GSH‐peroxidase (GPx) and GSH‐reductase (GR). Monoamine oxidase (MAO) and NADPH oxidase were observed to generate ROS at rates 10‐fold greater than intact, coupled mitochondria. POAF risk was significantly associated with MAO activity (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=1.8, 95% confidence interval [CI]=0.84 to 4.0; Q3: ARR=2.1, 95% CI=0.99 to 4.3; Q4: ARR=3.8, 95% CI=1.9 to 7.5; adjusted Ptrend=0.009). In contrast, myocardial GSHt was inversely associated with POAF (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=0.93, 95% confidence interval [CI]=0.60 to 1.4; Q3: ARR=0.62, 95% CI=0.36 to 1.1; Q4: ARR=0.56, 95% CI=0.34 to 0.93; adjusted Ptrend=0.014). GPx also was significantly associated with POAF; however, a linear trend for risk was not observed across increasing levels of the enzyme. GR was not associated with POAF risk. Conclusions Our results show that MAO is an important determinant of redox balance in human atrial myocardium, and that this enzyme, in addition to GSHt and GPx, is associated with an increased risk for POAF. Further investigation is needed to validate MAO as a predictive biomarker for POAF, and to explore this enzymes potential role in arrhythmogenesis.

Atrial Fibrillation and Incident Myocardial Infarction in the Elderly

Atrial fibrillation (AF) has been shown to be independently associated with an increased risk of myocardial infarction (MI) in a predominantly middle‐aged population; however, this association has not been examined in older populations.

Advanced interatrial block and ischemic stroke The Atherosclerosis Risk in Communities Study

Objective: Given that recent reports have suggested left atrial disease to be an independent risk factor for ischemic stroke, we sought to examine if advanced interatrial block (aIAB) is an independent stroke risk factor. Methods: We examined the association between aIAB and incident ischemic stroke in 14,716 participants (mean age 54 ± 5.8 years; 55% female; 26% black) from the Atherosclerosis Risk in Communities Study (ARIC). Cases of aIAB were identified from digital ECGs recorded during the baseline ARIC visit (1987–1989) and the first 3 follow-up study visits (1990–1992, 1993–1995, and 1996–1998). Adjudicated ischemic stroke events were ascertained through December 31, 2010. Results: There were 266 (1.8%) participants who had evidence of aIAB. Over a median follow-up of 22 years, 916 (6.2%) ischemic stroke events were detected. The incidence rate (per 1,000 person-years) of ischemic stroke among those with aIAB (incidence rate 8.05, 95% confidence interval [CI] 5.7, 11.4) was more than twice the rate in those without aIAB (incidence rate 3.14, 95% CI 2.94, 3.35). In a multivariable Cox regression analysis adjusted for stroke risk factors and potential confounders, aIAB was associated with an increased risk of ischemic stroke (hazard ratio 1.63, 95% CI 1.13, 2.34). The results were consistent across subgroups of participants stratified by age, sex, and race. Conclusions: In the ARIC, aIAB was associated with incident ischemic stroke, which strengthens the hypothesis that left atrial disease should be considered an independent stroke risk factor.

Relation Between Cancer and Atrial Fibrillation (from the REasons for Geographic And Racial Differences in Stroke Study)

Atrial fibrillation (AF) is common in patients with life-threatening cancer and those undergoing active cancer treatment. However, data from subjects with a history of non-life-threatening cancer and those who do not require active cancer treatment are lacking. A total of 15,428 (mean age 66 ± 8.9 years; 47% women; 45% blacks) participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study with baseline data on previous cancer diagnosis and AF were included. Participants with life-threatening cancer and active cancer treatment within 2 years of study enrollment were excluded. History of cancer was identified using computer-assisted telephone interviews. AF cases were identified from baseline electrocardiogram data and by a self-reported history of a previous diagnosis. Logistic regression was used to examine the cross-sectional association between cancer diagnosis and AF. A total of 2,248 (15%) participants had a diagnosis of cancer and 1,295 (8.4%) had AF. In a multivariable logistic regression model adjusted for sociodemographic characteristics (age, gender, race, education, income, and region of residence) and cardiovascular risk factors (systolic blood pressure, high-density lipoprotein cholesterol, total cholesterol, C-reactive protein, body mass index, smoking, diabetes, antihypertensive and lipid-lowering agents, left ventricular hypertrophy, and cardiovascular disease), those with cancer were more likely to have prevalent AF than those without cancer (odds ratio 1.19, 95% confidence interval 1.02 to 1.38). Subgroup analyses by age, sex, race, cardiovascular disease, and C-reactive protein yielded similar results. In conclusion, AF was more prevalent in participants with a history of non-life-threatening cancer and those who did not require active cancer treatment in REGARDS.

Peripheral Arterial Disease and Risk of Atrial Fibrillation and Stroke: The Multi‐Ethnic Study of Atherosclerosis

Background Peripheral arterial disease (PAD) shares several risk factors with atrial fibrillation (AF), and persons with PAD have an increased risk of stroke. It is unclear if PAD is associated with an increased risk for AF and whether this potential association explains the increased risk of stroke observed in those with PAD. Methods and Results We examined the association between PAD, measured by ankle‐brachial index (ABI), and incident AF and incident stroke, separately, in 6568 participants (mean age 62±10 years, 53% women, 62% nonwhite) from the Multi‐Ethnic Study of Atherosclerosis (MESA). ABI values <1.0 or >1.4 defined PAD. AF was ascertained through review of hospital discharge records and from Medicare claims data until December 31, 2010. An independent adjudication committee ascertained stroke events. Cox regression was used to estimate hazard ratios and 95% CIs for the association between PAD and AF and stroke. Over a median follow‐up of 8.5 years, 301 (4.6%) participants developed AF and 140 (2.1%) developed stroke. In a model adjusted for sociodemographics, cardiovascular risk factors, and potential confounders, PAD was associated with an increased risk of AF (hazard ratio 1.5, 95% CI 1.1 to 2.0). In a similar model, PAD was associated with incident stroke (hazard ratio 1.7, 95% CI 1.1 to 2.5), and the magnitude of risk was not different after inclusion of AF as a time‐dependent covariate (hazard ratio 1.7, 95% CI 1.1 to 2.5). Conclusions PAD is associated with an increased risk of AF and stroke in MESA. Potentially, the relationship between PAD and stroke is not mediated by AF.

Coronary Artery Calcium and Risk of Atrial Fibrillation (From the Multi-Ethnic Study of Atherosclerosis)

Calcified coronary arteries are associated with the development of cardiovascular disease and stroke. It is currently unknown whether coronary artery calcium (CAC) is associated with an increased risk for atrial fibrillation (AF). The aim of this study was to address this question in 6,641 participants (mean age 62 ± 10 years, 53% women, 62% nonwhites) from the Multi-Ethnic Study of Atherosclerosis (MESA) who were free of baseline clinical cardiovascular disease and AF. CAC measurements were assessed by cardiac computed tomography at study baseline. AF was ascertained by review of hospital discharge records and from Medicare claims data until December 31, 2010. Cox regression was used to compute hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between CAC and AF. During a median follow-up period of 8.5 years, 308 participants (4.6%) developed AF. In a model adjusted for sociodemographics, cardiovascular risk factors, and potential confounders, higher CAC scores were associated with increased risk for AF (CAC = 0: HR 1.0, referent; CAC = 1 to 100: HR 1.4, 95% CI 1.01 to 2.0; CAC = 101 to 300: HR 1.6, 95% CI 1.1 to 2.4; CAC >300: HR 2.1, 95% CI 1.4 to 2.9). The addition of CAC to the Framingham Heart Study and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) AF risk scores yielded integrated discrimination improvement of 0.0033 (95% CI 0.0015 to 0.0066) and 0.0028 (95% CI 0.0012 to 0.0057), with relative integrated discrimination improvement of 0.10 (95% CI 0.061 to 0.15) and 0.077 (95% CI 0.040 to 0.11), respectively. In conclusion, CAC is independently associated with increased risk for AF.

Effect of Peripheral Arterial Disease and Race on Survival After Coronary Artery Bypass Grafting

BACKGROUND Although peripheral arterial disease (PAD) is more prevalent among blacks, the effect of race on long-term survival after coronary artery bypass grafting (CABG) has not been examined in this population. METHODS A retrospective cohort study was conducted of CABG patients between 1992 and 2011. Long-term survival was compared in patients with and without PAD and stratified by race. Hazard ratios (HR) and 95% confidence intervals were computed using a Cox regression model. RESULTS Of 13,053 patients who underwent CABG, 1,501 (11%) had PAD, comprising 311 blacks and 1,190 whites. Median follow-up was 8.3 years. Long-term survival differed by race (no PAD: HR, 1.0; white PAD: adjusted HR, 1.5, 95% confidence interval, 1.4 to 1.6; black PAD: adjusted HR, 2.1, 95% confidence interval, 1.8 to 2.5; p < 0.0001 for trend). CONCLUSIONS Risk of death after CABG was comparatively higher among black PAD patients. This finding provides useful outcome information for surgeons and their patients.

Electrocardiographic and Echocardiographic Left Ventricular Hypertrophy in the Prediction of Stroke in the Elderly.

INTRODUCTION It is unclear whether left ventricular hypertrophy (LVH) detected by electrocardiography (ECG-LVH) is equally predictive of heart failure as LVH detected by echocardiography (echo-LVH). METHODS This analysis included 4,008 white participants (41% men) aged 65 years or older from the Cardiovascular Health Study who were free of stroke and major intraventricular conduction defects. ECG-LVH was defined by the Cornell criteria from baseline ECG data and echo-LVH was calculated from baseline echocardiography measurements. Cox regression was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between ECG-LVH and echo-LVH and adjudicated incident stroke events, separately. Harrells concordance indices (C-index) were calculated for the Framingham Stroke Risk Score with inclusion of ECG-LVH and echo-LVH, separately. RESULTS ECG-LVH was detected in 136 (3.4%) participants and echo-LVH was present in 208 (5.2%) participants. Over a median follow-up of 13 years, a total of 769 (19%; incidence rate = 15.4 per 1000 person-years) strokes occurred. In a multivariable Cox regression analysis adjusted for stroke risk factors and potential confounders, ECG-LVH (HR = 1.68; 95% CI = 1.23, 2.28) and echo-LVH (HR = 1.58; 95% CI = 1.17, 2.14) were associated with an increased risk of stroke. Similar values were obtained for the C-index when either ECG-LVH (C-index = .786) or echo-LVH (C-index = .786) were included in the Framingham Stroke Risk Score. CONCLUSION ECG-LVH and echo-LVH are able to be used interchangeably in stroke risk scores.