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Background: In people with atrial fibrillation (AF), periods of sinus rhythm present an opportunity to detect prothrombotic atrial remodeling through measurement of P-wave indices (PWIs)-prolonged P-wave duration, abnormal P-wave axis, advanced interatrial block, and abnormal P-wave terminal force in lead V1. We hypothesized that the addition of PWIs to the CHA 2 DS 2 -VASc score would improve its ability to predict AF-related ischemic stroke., Methods: We included 2229 participants from the ARIC study (Atherosclerosis Risk in Communities) and 700 participants from MESA (Multi-Ethnic Study of Atherosclerosis) with incident AF who were not on anticoagulants within 1 year of AF diagnosis. PWIs were obtained from study visit ECGs before development of AF. AF was ascertained using study visit ECGs and hospital records. Ischemic stroke cases were based on physician adjudication of hospital records. We used Cox proportional hazards models to estimate hazard ratios and 95% CIs of PWIs for ischemic stroke. Improvement in 1-year stroke prediction was assessed by C-statistic, categorical net reclassification improvement, and relative integrated discrimination improvement., Results: Abnormal P-wave axis was the only PWI associated with increased ischemic stroke risk (hazard ratio, 1.84; 95% CI, 1.33-2.55) independent of CHA 2 DS 2 -VASc variables, and that resulted in meaningful improvement in stroke prediction. The β estimate was approximately twice that of the CHA 2 DS 2 -VASc variables, and thus abnormal P-wave axis was assigned 2 points to create the P 2 -CHA 2 DS 2 -VASc score. This improved the C-statistic (95% CI) from 0.60 (0.51-0.69) to 0.67 (0.60-0.75) in ARIC and 0.68 (0.52-0.84) to 0.75 (0.60-0.91) in MESA (validation cohort). In ARIC and MESA, the categorical net reclassification improvements (95% CI) were 0.25 (0.13-0.39) and 0.51 (0.18-0.86), respectively, and the relative integrated discrimination improvement (95% CI) were 1.19 (0.96-1.44) and 0.82 (0.36-1.39), respectively., Conclusions: Abnormal P-wave axis-an ECG correlate of left atrial abnormality- improves ischemic stroke prediction in AF. Compared with CHA 2 DS 2 -VASc, the P 2 -CHA 2 DS 2 -VASc is a better prediction tool for AF-related ischemic stroke.

Rationale: Blacks compared with whites have a greater risk of adverse cardiovascular outcomes. Impaired regenerative capacity, measured as lower levels of circulating progenitor cells (CPCs), is a novel determinant of adverse outcomes; however, little is known about racial differences in CPCs., Objective: To investigate the number of CPCs, PC-mobilizing factors, PC mobilization during acute myocardial infarction and the predictive value of CPC counts in blacks compared with whites., Methods and Results: CPCs were enumerated by flow cytometry as CD45med + blood mononuclear cells expressing CD34+, CD133+, VEGF2R+, and CXCR4+ epitopes in 1747 subjects, mean age 58.4±13, 55% male, and 26% self-reported black. Patients presenting with acute myocardial infarction (n=91) were analyzed separately. Models were adjusted for relevant clinical variables. SDF-1α (stromal cell-derived factor-1α), VEGF (vascular endothelial growth factor), and MMP-9 (matrix metallopeptidase-9) levels were measured (n=561), and 623 patients were followed for median of 2.2 years for survival analysis. Blacks were younger, more often female, with a higher burden of cardiovascular risk, and lower CPC counts. Blacks had fewer CD34+ cells (-17.6%; [95% confidence interval (CI), -23.5% to -11.3%]; P<0.001), CD34+/CD133+ cells (-15.5%; [95% CI, -22.4% to -8.1%]; P<0.001), CD34+/CXCR4+ cells (-17.3%; [95% CI, -23.9% to -10.2%]; P<0.001), and CD34+/VEGF2R+ cells (-27.9%; [95% CI, -46.9% to -2.0%]; P=0.04) compared with whites. The association between lower CPC counts and black race was not affected by risk factors or cardiovascular disease. Results were validated in a separate cohort of 411 patients. Blacks with acute myocardial infarction had significantly fewer CPCs compared with whites ( P=0.02). Blacks had significantly lower plasma MMP-9 levels ( P<0.001) which attenuated the association between low CD34+ and black race by 19% (95% CI, 13%-33%). However, VEGF and SDF-1α levels were not significantly different between the races. Lower CD34+ counts were similarly predictive of mortality in blacks (hazard ratio, 2.83; [95% CI, 1.12-7.20]; P=0.03) and whites (hazard ratio, 1.79; [95% CI, 1.09-2.94]; P=0.02) without significant interaction., Conclusions: Black subjects have lower levels of CPCs compared with whites which is partially dependent on lower circulating MMP-9 levels. Impaired regenerative capacity is predictive of adverse outcomes in blacks and may partly account for their increased risk of cardiovascular events.

Background: Limited information exists on the lifetime risk of atrial fibrillation (AF) in African Americans and by socioeconomic status., Methods: We studied 15 343 participants without AF at baseline from the ARIC (Atherosclerosis Risk in Communities) cohort recruited in 1987 to 1989 from 4 communities in the United States when they were 45 to 64 years of age. Participants have been followed through 2014. Incidence rates of AF were calculated dividing the number of new cases by person-years of follow-up. Lifetime risk of AF was estimated by a modified Kaplan-Meier method considering death as a competing risk. Participants' family income and education were obtained at baseline., Results: We identified 2760 AF cases during a mean follow-up of 21 years. Lifetime risk of AF was 36% (95% confidence interval, 32%-38%) in white men, 30% (95% confidence interval, 26%-32%) in white women, 21% (95% confidence interval, 13%-24%) in African American men, and 22% (95% confidence interval, 16%-25%) in African American women. Regardless of race and sex, incidence rates of AF decreased from the lowest to the highest categories of income and education. In contrast, lifetime risk of AF increased in individuals with higher income and education in most sex-race groups. Cumulative incidence of AF was lower in those with higher income and education compared with their low socioeconomic status counterparts through earlier life but was reversed after age 80., Conclusions: Lifetime risk of AF in the ARIC cohort was ≈1 in 3 among whites and 1 in 5 among African Americans. Socioeconomic status was inversely associated with cumulative incidence of AF before the last decades of life., (© 2018 American Heart Association, Inc.)

Rationale: Circulating progenitor cells (CPCs) mobilize in response to ischemic injury, but their predictive value remains unknown in acute coronary syndrome (ACS)., Objective: We aimed to investigate the number of CPCs in ACS compared with those with stable coronary artery disease (CAD), relationship between bone marrow PCs and CPCs, and whether CPC counts predict mortality in patients with ACS., Methods and Results: In 2028 patients, 346 had unstable angina, 183 had an acute myocardial infarction (AMI), and the remaining 1499 patients had stable CAD. Patients with ACS were followed for the primary end point of all-cause death. CPCs were enumerated by flow cytometry as mononuclear cells expressing a combination of CD34+, CD133+, vascular endothelial growth factor receptor 2+, or chemokine (C-X-C motif) receptor 4+. CPC counts were higher in subjects with AMI compared those with stable CAD even after adjustment for age, sex, race, body mass index, renal function, hypertension, diabetes mellitus, hyperlipidemia, and smoking; CD34+, CD34+/CD133+, CD34+/CXCR4+, and CD34+/VEGFR2+ CPC counts were 19%, 25%, 28%, and 142% higher in those with AMI, respectively, compared with stable CAD. There were strong correlations between the concentrations of CPCs and the PC counts in bone marrow aspirates in 20 patients with AMI. During a 2 (interquartile range, 1.31-2.86)-year follow-up period of 529 patients with ACS, 12.4% died. In Cox regression models adjusted for age, sex, body mass index, heart failure history, estimated glomerular filtration rate, and AMI, subjects with low CD34+ cell counts had a 2.46-fold (95% confidence interval, 1.18-5.13) increase in all-cause mortality, P =0.01. CD34+/CD133+ and CD34+/CXCR4+, but not CD34+/VEGFR2+ PC counts, had similar associations with mortality. Results were validated in a separate cohort of 238 patients with ACS., Conclusions: CPC levels are significantly higher in patients after an AMI compared with those with stable CAD and reflect bone marrow PC content. Among patients with ACS, a lower number of hematopoietic-enriched CPCs are associated with a higher mortality., (© 2018 American Heart Association, Inc.)

Background: Several reports have demonstrated that prolongation of the QT interval is associated with sudden cardiac death (SCD). However, it is unknown whether any of the components within the QT interval are responsible for its association with SCD., Methods and Results: We examined the association of the individual QT-interval components (R-wave onset to R-peak, R-peak to R-wave end, ST-segment, T-wave onset to T-peak, and T-peak to T-wave end) with SCD in 12 241 participants (54±5.7 years; 26% black; 55% women) from the ARIC study (Atherosclerosis Risk in Communities). The QT interval and its components were measured at baseline (1987-1989) from 12-lead ECGs. SCD cases were adjudicated by a group of physicians through December 31, 2012. During a median follow-up of 23.6 years, a total of 346 cases of SCD were identified. Although prolongation of the QT interval was associated with a 49% increased risk of SCD (hazard ratio, 1.49; 95% confidence interval, 1.01-2.18), only the T-wave onset to T-peak component (per 1-SD increase: hazard ratio, 1.19; 95% confidence interval, 1.06-1.34) was associated with SCD and not any of the other components in separate models. When all of the QT-interval components were included in the same model, T-wave onset to T-peak remained the strongest predictor of SCD (per 1-SD increase: hazard ratio, 1.21; 95% confidence interval, 1.06-1.37)., Conclusions: The risk of SCD with the QT interval is driven by prolongation of the T-wave onset to T-peak component. This suggests that shifting the focus from the overall QT interval to its individual components will refine SCD prediction in the community., (© 2017 American Heart Association, Inc.)

Background and Purpose: Abnormal P-wave axis (aPWA) has been linked to incident atrial fibrillation and mortality; however, the relationship between aPWA and stroke has not been reported. We hypothesized that aPWA is associated with ischemic stroke independent of atrial fibrillation and other stroke risk factors and tested our hypothesis in the ARIC study (Atherosclerosis Risk In Communities), a community-based prospective cohort study., Methods: We included 15 102 participants (aged 54.2±5.7 years; 55.2% women; 26.5% blacks) who attended the baseline examination (1987-1989) and without prevalent stroke. We defined aPWA as any value outside 0 to 75° using 12-lead ECGs obtained during study visits. Each case of incident ischemic stroke was classified in accordance with criteria from the National Survey of Stroke by a computer algorithm and adjudicated by physician review. Multivariable Cox regression was used to estimate hazard ratios and 95% confidence intervals for the association of aPWA with stroke., Results: During a mean follow-up of 20.2 years, there were 657 incident ischemic stroke cases. aPWA was independently associated with a 1.50-fold (95% confidence interval, 1.22-1.85) increased risk of ischemic stroke in the multivariable model that included atrial fibrillation. When subtyped, aPWA was associated with a 2.04-fold (95% confidence interval, 1.42-2.95) increased risk of cardioembolic stroke and a 1.32-fold (95% confidence interval, 1.03-1.71) increased risk of thrombotic stroke., Conclusions: aPWA is independently associated with ischemic stroke. This association seems to be stronger for cardioembolic strokes. Collectively, our findings suggest that alterations in atrial electric activation may predispose to cardiac thromboembolism independent of atrial fibrillation., (© 2017 American Heart Association, Inc.)

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., (© 2016 American Academy of Neurology.)

Aims: The aim of this study was to examine the bidirectional association between atrial fibrillation and congestive heart failure (CHF) in older adults., Methods: We studied the association of atrial fibrillation at entry with incident CHF (N = 5281; 85% white, 42% male) and the association of CHF at entry with incident atrial fibrillation (N = 5233; 85% white, 42% male) in the Cardiovascular Health Study (CHS). Baseline atrial fibrillation was identified during the study electrocardiogram and by self-reported history, and incident cases were identified during subsequent study electrocardiograms and hospitalization data. Baseline CHF was identified by self-reported history and adjudication of medical records, and incident cases were identified using hospitalization data. Cox regression was used to compute hazard ratios and 95% confidence intervals (CIs) for the association between atrial fibrillation and incident CHF, and CHF and incident atrial fibrillation, separately., Results: Over a median follow-up of 12.6 years, 534 (10%) participants developed atrial fibrillation. CHF was associated with an increased risk of atrial fibrillation (hazard ratio 2.0, 95% CI 1.4, 3.0). A total of 1692 (32%) participants developed CHF over a median follow-up of 11.7 years and atrial fibrillation was associated with an increased risk of CHF (hazard ratio 1.9, 95% CI 1.5, 2.2)., Conclusion: Our results suggest that a bidirectional relationship exists between atrial fibrillation and CHF, with each condition influencing the development of the other.

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., (© 2015 American Heart Association, Inc.)

Objective: This study examines the association between environmental tobacco smoke (ETS) exposure and atrial fibrillation (AF)., Methods: We examined the cross-sectional association between ETS exposure and AF in 12,021 participants (mean age: 65 ± 9.9 years; 60% women; 40% blacks) from the REasons for Geographic And Racial Differences in Stroke study who self-identified as never smokers between 2003 and 2007., Results: A total of 2503 (21%) participants reported ETS exposure. In a multivariate logistic regression model adjusted for sociodemographics and potential confounders, ETS exposure was significantly associated with AF (odds ratio = 1.27, 95% confidence interval = 1.08, 1.50)., Conclusions: Our findings suggest that the harmful effects of ETS exposure extend to sustained arrhythmias such as AF.

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.)

Race and sex disparities are believed to play an important role in heart disease. The purpose of this study was to examine the association between race, sex, and number of diseased vessels at the time of coronary artery bypass grafting (CABG), and subsequent postoperative outcomes. The 13,774 patients undergoing first-time, isolated CABG between 1992 and 2011 were included. Trend in the number of diseased vessels between black and white patients, stratified by sex, were analyzed using a Cochran-Armitage trend test. Models were adjusted for age, procedural status (elective vs. nonelective), and payor type (private vs. nonprivate insurance). Black female CABG patients presented with an increasingly greater number of diseased vessels than white female CABG patients (adjusted P(trend) = 0.0021). A similar trend was not observed between black and white male CABG patients (adjusted P(trend) = 0.18). Black female CABG patients were also more likely to have longer intensive care unit and hospital lengths of stay than other race-sex groups.Our findings suggest that black female CABG patients have more advanced coronary artery disease than white female CABG patients. Further research is needed to determine the benefit of targeted preventive care and preoperative workup for this high-risk group.

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., (© 2014 American Heart Association, Inc.)

Aims: Conditional survival is defined as the probability of surviving an additional number of years beyond that already survived. The aim of this study was to estimate conditional survival in heart failure patients after coronary artery bypass grafting (CABG)., Methods: Heart failure patients with multivessel coronary artery disease undergoing first-time, isolated CABG between 1992 and 2011 were included in this study. Conditional survival estimates were computed for 1, 5, and 10 years after already surviving 0.5, 1, 2, 3, 4, and 5 years., Results: Compared with traditional survival estimates, conditional survival was consistently higher at all time periods. The overall 2-year adjusted survival estimate was 84% compared with the 1-year conditional survival rate of 95% for 1-year survivors. Similarly, the overall 10-year adjusted survival rate was 36% from the time of surgery compared with the 5-year conditional survival of 54% for patients who had survived 5 years., Conclusion: Conditional survival provides a more accurate estimate of long-term survival in heart failure patients who have already survived for a certain amount of time after CABG. This information is useful for patients and physicians who manage their long-term care.