Wesley T. O’Neal

Brachial Flow-Mediated Dilation and Incident Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis

Objective— It is unknown whether endothelial dysfunction precedes atrial fibrillation (AF) development. The objective of this study was to examine the association of brachial flow-mediated dilation (FMD) with incident AF. Approach and Results— A total of 2936 participants (mean age, 61±9.9 years; 50% women; 66% nonwhites) from the Multi-Ethnic Study of Atherosclerosis with available ultrasound brachial FMD measurements who were free of baseline AF were included in this analysis. Baseline (2000–2002) FMD was computed from the percentage difference (%FMD) in brachial artery diameter and maximum diameter during measured vasodilator response. AF was ascertained from hospitalization data including Medicare claims during a median follow-up of 8.5 years. Probability-weighted Cox proportional-hazards regression was used to compute hazard ratios and 95% confidence intervals for the association between FMD as a continuous variable (%FMD values per 1-SD increase) and incident AF. Incident AF was detected in 137 (4.7%) participants. Those with %FMD values below the sex-specific median value (median %FMD; men, 3.6%; women, 4.2%; incidence rate per 1000 person-years, 7.3; 95% confidence interval, 5.9–9.0) were more likely to develop AF than people whose %FMD values were above the median value (incidence rate per 1000 person-years, 4.5; 95% confidence interval, 3.4–5.8; log-rank P=0.0043). In a multivariable Cox regression analysis, each 1-SD increase in %FMD values (SD, 2.8%) was associated with less incident AF (hazard ratio, 0.84; 95% confidence interval, 0.70–0.99). These results were consistent across subgroups stratified by age, sex, and race/ethnicity. Conclusions— Smaller brachial FMD values are associated with higher rates of AF, suggesting a role for endothelial dysfunction in AF pathogenesis.Objective— It is unknown whether endothelial dysfunction precedes atrial fibrillation (AF) development. The objective of this study was to examine the association of brachial flow-mediated dilation (FMD) with incident AF. Approach and Results— A total of 2936 participants (mean age, 61±9.9 years; 50% women; 66% nonwhites) from the Multi-Ethnic Study of Atherosclerosis with available ultrasound brachial FMD measurements who were free of baseline AF were included in this analysis. Baseline (2000–2002) FMD was computed from the percentage difference (%FMD) in brachial artery diameter and maximum diameter during measured vasodilator response. AF was ascertained from hospitalization data including Medicare claims during a median follow-up of 8.5 years. Probability-weighted Cox proportional-hazards regression was used to compute hazard ratios and 95% confidence intervals for the association between FMD as a continuous variable (%FMD values per 1-SD increase) and incident AF. Incident AF was detected in 137 (4.7%) participants. Those with %FMD values below the sex-specific median value (median %FMD; men, 3.6%; women, 4.2%; incidence rate per 1000 person-years, 7.3; 95% confidence interval, 5.9–9.0) were more likely to develop AF than people whose %FMD values were above the median value (incidence rate per 1000 person-years, 4.5; 95% confidence interval, 3.4–5.8; log-rank P =0.0043). In a multivariable Cox regression analysis, each 1-SD increase in %FMD values (SD, 2.8%) was associated with less incident AF (hazard ratio, 0.84; 95% confidence interval, 0.70–0.99). These results were consistent across subgroups stratified by age, sex, and race/ethnicity. Conclusions— Smaller brachial FMD values are associated with higher rates of AF, suggesting a role for endothelial dysfunction in AF pathogenesis. # Significance {#article-title-23}

The Effect of Race and Chronic Obstructive Pulmonary Disease on Long-Term Survival after Coronary Artery Bypass Grafting

Background: Chronic obstructive pulmonary disease (COPD) is a known predictor of decreased long-term survival after coronary artery bypass grafting (CABG). Differences in survival by race have not been examined. Methods: A retrospective cohort study was conducted of CABG patients between 2002 and 2011. Long-term survival was compared in patients with and without COPD and stratified by race. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. Results: A total of 984 (20%) patients had COPD (black n = 182; white n = 802) at the time of CABG (N = 4,801). The median follow-up for study participants was 4.4 years. COPD was observed to be a statistically significant predictor of decreased survival independent of race following CABG (no COPD: HR = 1.0; white COPD: adjusted HR = 1.9, 95% CI = 1.7–2.3; black COPD: adjusted HR = 1.6, 95% CI = 1.1–2.2). Conclusion: Contrary to the expected increased risk of mortality among black COPD patients in the general population, a similar survival disadvantage was not observed in our CABG population.

Heart rate and the risk of adverse outcomes in patients with heart failure with preserved ejection fraction

Background Although high resting heart rates are associated with adverse outcomes in heart failure with reduced ejection, the reports for heart failure with preserved ejection fraction (HFpEF) are conflicting. Design A secondary analysis was conducted in order to examine the relationship between resting heart rate and adverse outcomes in 2705 patients (mean age = 68 ± 10 years; 47% men; 88% white) with HFpEF who were in sinus rhythm from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT). Methods Baseline heart rate was obtained from baseline electrocardiogram data. Outcomes were adjudicated by a clinical end-point committee and included the following factors: hospitalisation, hospitalisation for heart failure, death and cardiovascular death. Results Over a median follow-up of 3.4 years (25th–75th percentiles = 2.0–4.9 years), a total of 1157 hospitalisations, 311 hospitalizations for heart failure, 369 deaths and 233 cardiovascular deaths occurred. An increased risk (per 5-beats per minute [bpm] increase) for hospitalisation (hazard ratio [HR] = 1.03, 95% confidence interval [CI] = 1.004–1.060), hospitalisation for heart failure (HR = 1.10, 95% CI = 1.05–1.15), death (HR = 1.10, 95% CI = 1.06–1.16) and cardiovascular death (HR = 1.13, 95% CI = 1.07–1.19) was observed. When the analysis was limited to those who did not report the use of β-blockers, the magnitude of the association for each outcome (per 5-bpm increase) was not materially altered (hospitalisation: HR = 1.03, 95% CI = 0.97–1.09; hospitalisation for heart failure: HR = 1.12, 95% CI = 0.98–1.27; death: HR = 1.16, 95% CI = 1.05–1.28; cardiovascular death: HR = 1.12, 95% CI = 0.99–1.27). Conclusion High resting heart rate is a risk factor for adverse outcomes in patients with HFpEF, and future studies are needed in order to determine whether reducing heart rate improves outcomes in HFpEF.

The Impact of Prior Percutaneous Coronary Intervention on Long-Term Survival after Coronary Artery Bypass Grafting

BACKGROUND Previous studies examining the influence of prior percutaneous coronary intervention (PCI) on long-term survival after coronary artery bypass grafting (CABG) have reported conflicting results. The purpose of this study was to further examine the influence of prior PCI on long-term survival after CABG at a large tertiary referral heart institute. METHODS Long-term survival between 1992 and 2011 was compared in non-emergent CABG cases with and without prior PCI. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. RESULTS A total of 2532 (19%) patients had prior PCI before CABG (n=13,354). The median follow-up for study participants was 8.1 years. The median survival for patients with and without prior PCI was 15 years and 14 years, respectively (p<0.0001). Long-term survival was similar between patients with and without prior PCI after adjusting for age, sex, race, hypertension, coronary artery disease severity, congestive heart failure, and prior stroke (adjusted HR=0.99, 95%CI=0.91-1.06). CONCLUSION Findings from outcomes research are important in the planning of appropriate postoperative patient care. Our study provides additional evidence that prior PCI is not a significant predictor of long-term survival after CABG.

Ephrin-Eph signaling as a potential therapeutic target for the treatment of myocardial infarction

Although numerous strategies have been developed to reduce the initial ischemic insult and cellular injury that occurs during myocardial infarction (MI), few have progressed into the clinical arena. The epidemiologic and economic impact of MI necessitates the development of innovative therapies to rapidly and effectively reduce the initial injury and subsequent cardiac dysfunction. The Eph receptors and their cognate ligands, the ephrins, are the largest family of receptor tyrosine kinases, and their signaling has been shown to play a diverse role in various cellular processes. The recent advances in the study of ephrin-Eph signaling have shown promising progress in many fields of medicine. They have been implicated in the pathophysiology of various cancers and in the regulation of inflammation and apoptosis. Recent studies have shown that manipulation of ephrin-Eph cell signaling can favorably influence cardiomyocyte viability and ultimately preserve cardiac function post-MI. In this article, we explore the hypothesis that manipulation of ephrin-Eph signaling may potentially be a novel therapeutic target in the treatment of MI through alteration of the cellular processes that govern injury and wound healing.

Brachial Flow-Mediated Dilation and Incident Atrial Fibrillation

Objective— It is unknown whether endothelial dysfunction precedes atrial fibrillation (AF) development. The objective of this study was to examine the association of brachial flow-mediated dilation (FMD) with incident AF. Approach and Results— A total of 2936 participants (mean age, 61±9.9 years; 50% women; 66% nonwhites) from the Multi-Ethnic Study of Atherosclerosis with available ultrasound brachial FMD measurements who were free of baseline AF were included in this analysis. Baseline (2000–2002) FMD was computed from the percentage difference (%FMD) in brachial artery diameter and maximum diameter during measured vasodilator response. AF was ascertained from hospitalization data including Medicare claims during a median follow-up of 8.5 years. Probability-weighted Cox proportional-hazards regression was used to compute hazard ratios and 95% confidence intervals for the association between FMD as a continuous variable (%FMD values per 1-SD increase) and incident AF. Incident AF was detected in 137 (4.7%) participants. Those with %FMD values below the sex-specific median value (median %FMD; men, 3.6%; women, 4.2%; incidence rate per 1000 person-years, 7.3; 95% confidence interval, 5.9–9.0) were more likely to develop AF than people whose %FMD values were above the median value (incidence rate per 1000 person-years, 4.5; 95% confidence interval, 3.4–5.8; log-rank P=0.0043). In a multivariable Cox regression analysis, each 1-SD increase in %FMD values (SD, 2.8%) was associated with less incident AF (hazard ratio, 0.84; 95% confidence interval, 0.70–0.99). These results were consistent across subgroups stratified by age, sex, and race/ethnicity. Conclusions— Smaller brachial FMD values are associated with higher rates of AF, suggesting a role for endothelial dysfunction in AF pathogenesis.Objective— It is unknown whether endothelial dysfunction precedes atrial fibrillation (AF) development. The objective of this study was to examine the association of brachial flow-mediated dilation (FMD) with incident AF. Approach and Results— A total of 2936 participants (mean age, 61±9.9 years; 50% women; 66% nonwhites) from the Multi-Ethnic Study of Atherosclerosis with available ultrasound brachial FMD measurements who were free of baseline AF were included in this analysis. Baseline (2000–2002) FMD was computed from the percentage difference (%FMD) in brachial artery diameter and maximum diameter during measured vasodilator response. AF was ascertained from hospitalization data including Medicare claims during a median follow-up of 8.5 years. Probability-weighted Cox proportional-hazards regression was used to compute hazard ratios and 95% confidence intervals for the association between FMD as a continuous variable (%FMD values per 1-SD increase) and incident AF. Incident AF was detected in 137 (4.7%) participants. Those with %FMD values below the sex-specific median value (median %FMD; men, 3.6%; women, 4.2%; incidence rate per 1000 person-years, 7.3; 95% confidence interval, 5.9–9.0) were more likely to develop AF than people whose %FMD values were above the median value (incidence rate per 1000 person-years, 4.5; 95% confidence interval, 3.4–5.8; log-rank P =0.0043). In a multivariable Cox regression analysis, each 1-SD increase in %FMD values (SD, 2.8%) was associated with less incident AF (hazard ratio, 0.84; 95% confidence interval, 0.70–0.99). These results were consistent across subgroups stratified by age, sex, and race/ethnicity. Conclusions— Smaller brachial FMD values are associated with higher rates of AF, suggesting a role for endothelial dysfunction in AF pathogenesis. # Significance {#article-title-23}

Coronary Artery Calcium Progression and Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis

Background— Coronary artery calcium (CAC) measured at a single time point has been associated with an increased risk for atrial fibrillation (AF). It is unknown whether CAC progression over time carries a similar risk. Methods and Results— This analysis included 5612 participants (mean age: 62±10; 52% women; 39% whites; 27% blacks; 20% Hispanics; 12% Chinese Americans) from the Multi-Ethnic Study of Atherosclerosis. Phantom-adjusted Agatston scores for baseline and follow-up measurements were used to compute change in CAC per year (≤0, 1–100, 101–300, and >300 U/year). AF was ascertained by review of hospital discharge records and from Medicare claims data through December 31, 2010. Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association between CAC progression and AF. Over a median follow-up of 5.6 years (25th, 75th percentiles=5.1, 6.8), a total of 203 (3.6%) incident AF cases were detected. Any CAC progression (>0/year) was associated with an increased risk for AF (HR=1.55, 95% CI=1.10, 2.19), and the risk increased with higher levels of CAC progression (≤0/year: HR=1.0 [reference]; 1–100/year: HR=1.47, 95% CI=1.03, 2.09; 101–300/year: HR=1.92, 95%CI=1.15, 3.20; >300/year: HR=3.23, 95%CI=1.48, 7.05). An interaction was observed by age with the association of CAC progression with AF being stronger for younger (<61 years: HR=3.53, 95% CI=1.29, 9.69) compared with older (≥61 years: HR=1.42, 95% CI=0.99, 2.04) participants ( P interaction=0.037). Conclusions— CAC progression during an average of 5 to 6 years of follow-up is associated with an increased risk for AF.Background—Coronary artery calcium (CAC) measured at a single time point has been associated with an increased risk for atrial fibrillation (AF). It is unknown whether CAC progression over time carries a similar risk. Methods and Results—This analysis included 5612 participants (mean age: 62±10; 52% women; 39% whites; 27% blacks; 20% Hispanics; 12% Chinese Americans) from the Multi-Ethnic Study of Atherosclerosis. Phantom-adjusted Agatston scores for baseline and follow-up measurements were used to compute change in CAC per year (⩽0, 1–100, 101–300, and >300 U/year). AF was ascertained by review of hospital discharge records and from Medicare claims data through December 31, 2010. Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association between CAC progression and AF. Over a median follow-up of 5.6 years (25th, 75th percentiles=5.1, 6.8), a total of 203 (3.6%) incident AF cases were detected. Any CAC progression (>0/year) was associated with an increased risk for AF (HR=1.55, 95% CI=1.10, 2.19), and the risk increased with higher levels of CAC progression (⩽0/year: HR=1.0 [reference]; 1–100/year: HR=1.47, 95% CI=1.03, 2.09; 101–300/year: HR=1.92, 95%CI=1.15, 3.20; >300/year: HR=3.23, 95%CI=1.48, 7.05). An interaction was observed by age with the association of CAC progression with AF being stronger for younger (<61 years: HR=3.53, 95% CI=1.29, 9.69) compared with older (≥61 years: HR=1.42, 95% CI=0.99, 2.04) participants (P interaction=0.037). Conclusions—CAC progression during an average of 5 to 6 years of follow-up is associated with an increased risk for AF.

Electrocardiographic Left Atrial Abnormality and Stroke Subtype in ARIC

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.

Race, insurance type, and stage of presentation among lung cancer patients

The purpose of this study was to determine whether African-American lung cancer patients are diagnosed at a later stage than white patients, regardless of insurance type. The relationship between race and stage at diagnosis by insurance type was assessed using a Poisson regression model, with relative risk as the measure of association. The setting of the study was a large tertiary care cancer center located in the southeastern United States. Patients who were diagnosed with lung cancer between 2001 and 2010 were included in the study. A total of 717 (31%) African-American and 1,634 (69%) white lung cancer patients were treated at our facility during the study period. Adjusting for age, sex, and smoking-related histology, African-American patients were diagnosed at a statistically significant later stage (III/IV versus I/II) than whites for all insurance types, with the exception of Medicaid. Our results suggest that equivalent insurance coverage may not ensure equal presentation of stage between African-American and white lung cancer patients. Future research is needed to determine whether other factors such as treatment delays, suboptimal preventive care, inappropriate specialist referral, community segregation, and a lack of patient trust in health care providers may explain the continuing racial disparities observed in the current study.

Sex hormones and the risk of atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis (MESA)

PurposeAtrial fibrillation is more prevalent in men than women. Due to these sex differences in atrial fibrillation susceptibility, we examined whether sex hormones have differing associations with atrial fibrillation risk in men and women.MethodsThis analysis included 4883 (mean age = 63 ± 10 years; 39% women; 64% non-white) participants from the Multi-Ethnic Study of Atherosclerosis. Sex hormones (total testosterone, bioavailable testosterone, estradiol, and sex hormone binding globulin) were measured at baseline (2000-2002) for all male and all postmenopausal female participants. Atrial fibrillation was ascertained by hospital discharge records, Medicare claims data, and study electrocardiograms through December 31, 2012.ResultsOver a median follow-up of 10.9 years, a total of 613 (13%) atrial fibrillation cases were detected. A higher incidence rate of atrial fibrillation was observed for males (n = 385, age-standardized incidence rate per 1000 person-years = 12.3, 95%CI = 11.1, 13.6) than females (n = 228, age-standardized incidence rate per 1000 person-years = 9.0, 95%CI = 7.9, 10.3). In men, higher bioavailable testosterone levels were associated with increased atrial fibrillation risk (HR = 1.32, 95%CI = 1.01, 1.74; p = 0.044; comparing 3rd to 1st tertile), while an association in the opposite direction was observed for women (HR = 0.81, 95%CI = 0.58, 1.13; p = 0.22; comparing 3rd to 1st tertile). Other hormones were not associated with atrial fibrillation in men or women.ConclusionHigher levels of endogenous bioavailable testosterone contribute to atrial fibrillation development in men. The combination of endogenous bioavailable testosterone and other risk factors potentially are important for atrial fibrillation development in men.