Short-term repeatability of the peguero-lo presti electrocardiographic left ventricular hypertrophy criteria.

BACKGROUND: Electrocardiographic left ventricular hypertrophy (ECG-LVH) represents preclinical cardiovascular disease and predicts cardiovascular disease morbidity and mortality. While the newly developed Peguero-Lo Presti ECG-LVH criteria have greater sensitivity for LVH than the Cornell voltage and Sokolow-Lyon criteria, its short-term repeatability is unknown. Therefore, we characterized the short-term repeatability of Peguero-Lo Presti ECG-LVH criteria and evaluate its agreement with Cornell voltage and Sokolow-Lyon ECG-LVH criteria. METHODS: Participants underwent two resting, standard, 12-lead ECGs at each of two visits one week apart (n = 63). We defined a Peguero-Lo Presti index as a sum of the deepest S wave amplitude in any single lead and lead V4 (i.e., SD  + SV4 ) and defined Peguero-Lo Presti LVH index as ≥ 2,300 µV among women and ≥ 2,800 µV among men. We estimated repeatability as an intraclass correlation coefficient (ICC), agreement as a prevalence-adjusted bias-adjusted kappa coefficient (κ), and precision using 95% confidence intervals (CIs). RESULTS: The Peguero-Lo Presti index was repeatable: ICC (95% CI) = 0.94 (0.91-0.97). Within-visit agreement of Peguero-Lo Presti LVH was high at the first and second visits: κ (95% CI) = 0.97 (0.91-1.00) and 1.00 (1.00-1.00). Between-visit agreement of the first and second measurements at each visit was comparable: κ (95% CI) = 0.90 (0.80-1.00) and 0.93 (0.85-1.00). Agreement of Peguero-Lo Presti and Cornell or Sokolow-Lyon LVH on any one of the four ECGs was slightly lower: κ (95% CI) = 0.71 (0.54-0.89). CONCLUSION: The Peguero-Lo Presti index and LVH have excellent repeatability and agreement, which support their use in clinical and epidemiological studies.

Effect of Intensive Blood Pressure Lowering on the Risk of Atrial Fibrillation.

It remains uncertain whether intensive control of blood pressure (BP) results in a lower risk of atrial fibrillation (AF) in patients with hypertension. Using data from SPRINT (Systolic Blood Pressure Intervention Trial), which enrolled participants with hypertension at increased risk of cardiovascular disease, we examined whether intensive BP lowering (target systolic BP [SBP] <120 mm Hg), compared with standard BP lowering (target SBP<140 mm Hg), results in a lower risk of AF. This analysis included 8022 participants (4003 randomized to the intensive arm and 4019 to standard BP arm) who were free of AF at the time of enrollment and with available baseline and follow-up electrocardiographic data. AF was ascertained from standard 12-lead electrocardiograms recorded at biannual study examinations and an exit visit. During up to 5.2 years of follow-up and a total of 28 322 person-years, 206 incident AF cases occurred; 88 in the intensive BP-lowering arm and 118 in the standard BP-lowering arm. Intensive BP lowering was associated with a 26% lower risk of developing new AF (hazard ratio, 0.74 [95% CI, 0.56-0.98]; P=0.037). This effect was consistent among prespecified subgroups of SPRINT participants stratified by age, sex, race, SBP tertiles, prior cardiovascular disease, and prior chronic kidney disease when interactions between treatment effect and these subgroups were assessed using Hommel adjusted P values. In conclusion, intensive treatment to a target of SBP <120 mm Hg in patients with hypertension at high risk of cardiovascular disease has the potential to reduce the risk of AF. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

Genome-wide association study and meta-analysis identify loci associated with ventricular and supraventricular ectopy.

The genetic basis of supraventricular and ventricular ectopy (SVE, VE) remains largely uncharacterized, despite established genetic mechanisms of arrhythmogenesis. To identify novel genetic variants associated with SVE/VE in ancestrally diverse human populations, we conducted a genome-wide association study of electrocardiographically identified SVE and VE in five cohorts including approximately 43,000 participants of African, European and Hispanic/Latino ancestry. In thirteen ancestry-stratified subgroups, we tested multivariable-adjusted associations of SVE and VE with single nucleotide polymorphism (SNP) dosage. We combined subgroup-specific association estimates in inverse variance-weighted, fixed-effects and Bayesian meta-analyses. We also combined fixed-effects meta-analytic t-test statistics for SVE and VE in multi-trait SNP association analyses. No loci reached genome-wide significance in trans-ethnic meta-analyses. However, we found genome-wide significant SNPs intronic to an apoptosis-enhancing gene previously associated with QRS interval duration (FAF1; lead SNP rs7545860; effect allele frequency = 0.02; P = 2.0 × 10-8) in multi-trait analysis among European ancestry participants and near a locus encoding calcium-dependent glycoproteins (DSC3; lead SNP rs8086068; effect allele frequency = 0.17) in meta-analysis of SVE (P = 4.0 × 10-8) and multi-trait analysis (P = 2.9 × 10-9) among African ancestry participants. The novel findings suggest several mechanisms by which genetic variation may predispose to ectopy in humans and highlight the potential value of leveraging pleiotropy in future studies of ectopy-related phenotypes.

Silent Myocardial Infarction and Long-Term Risk of Heart Failure: The ARIC Study.

BACKGROUND: Although silent myocardial infarction (SMI) accounts for about one-half of the total number of myocardial infarctions (MIs), the risk of heart failure (HF) among patients with SMI is not well established. OBJECTIVES: The purpose of this study was to examine the association of SMI and clinically manifested myocardial infarction (CMI) with HF, as compared with patients with no MI. METHODS: This analysis included 9,243 participants from the ARIC (Atherosclerosis Risk In Communities) study who were free of cardiovascular disease at baseline (ARIC visit 1: 1987 to 1989). SMI was defined as electrocardiographic evidence of MI without CMI after the baseline until ARIC visit 4 (1996 to 1998). HF events were ascertained starting from ARIC visit 4 until 2010 in individuals free of HF before that visit. RESULTS: Between ARIC visits 1 and 4, 305 SMIs and 331 CMIs occurred. After ARIC visit 4 and during a median follow-up of 13.0 years, 976 HF events occurred. The incidence rate of HF was higher in both CMI and SMI participants than in those without MI (incidence rates per 1,000 person-years were 30.4, 16.2, and 7.8, respectively; p < 0.001). In a model adjusted for demographics and HF risk factors, both SMI (hazard ratio [HR]: 1.35; 95% confidence interval [CI]: 1.02 to 1.78) and CMI (HR: 2.85; 95% CI: 2.31 to 3.51) were associated with increased risk of HF compared with no MI. These associations were consistent in subgroups of participants stratified by several HF risk predictors. However, the risk of HF associated with SMI was stronger in those younger than the median age (53 years) (HR: 1.66; 95% CI: 1.00 to 2.75 vs. HR: 1.19; 95% CI: 0.85 to 1.66, respectively; overall interaction p by MI type <0.001). CONCLUSIONS: SMI is associated with an increased risk of HF. Future research is needed to examine the cost effectiveness of screening for SMI as part of HF risk assessment, and to identify preventive therapies to improve the risk of HF among patients with SMI.

Distribution and determinants of QRS rotation of black and white persons in the general population.

BACKGROUND: The prevalence and determinants of QRS transition zones are not well established. METHODS: We examined the distributions of Normal, clockwise (CW) and counterclockwise (CCW)) QRS transition zones and their relations to disease, body size and demographics in 4624 black and white men and women free of cardiovascular disease and major ECG abnormalities enrolled in the NHANES-III survey. RESULTS: CW transition zones were least observed (6.2%) and CCW were most prevalent (60.1%) with Normal in an intermediate position (33.7%). In multivariable logistic regression analysis, the adjusted, significant predictors for CCW compared to Normal were a greater proportion of blacks and women, fewer thin people (BMI<20, thin), a greater ratio of chest depth to chest width, and an LVMass index <80g. By contrast, CW persons were older, had larger QRS/T angles, smaller ratio of chest depth to chest width, had a greater proportion of subjects with low voltage QRS, more pulmonary disease, a greater proportion with high heart rates, shorter QRS duration and were more obese (BMI≥30). CONCLUSIONS: Normal rather than being the most prevalent transition zone was intermediate in frequency between the most frequently encountered CCW and the least frequently encountered transition zone CW. Differences in the predictors of CW and CCW exist. This requires further investigation to examine how far these differences explain the differences in the published prognostic differences between CW and CCW.

Erratum: "Genome-wide Association Study of Susceptibility to Particulate Matter-Associated QT Prolongation".

[This corrects the article DOI: 10.1289/EHP347.].

Fifteen Genetic Loci Associated With the Electrocardiographic P Wave.

BACKGROUND: The P wave on an ECG is a measure of atrial electric function, and its characteristics may serve as predictors for atrial arrhythmias. Increased mean P-wave duration and P-wave terminal force traditionally have been used as markers for left atrial enlargement, and both have been associated with increased risk of atrial fibrillation. Here, we explore the genetic basis of P-wave morphology through meta-analysis of genome-wide association study results for P-wave duration and P-wave terminal force from 12 cohort studies. METHODS AND RESULTS: We included 44 456 individuals, of which 6778 (16%) were of African ancestry. Genotyping, imputation, and genome-wide association study were performed at each study site. Summary-level results were meta-analyzed centrally using inverse-variance weighting. In meta-analyses of P-wave duration, we identified 6 significant (P<5×10-8) novel loci and replicated a prior association with SCN10A. We identified 3 loci at SCN5A, TBX5, and CAV1/CAV2 that were jointly associated with the PR interval, PR segment, and P-wave duration. We identified 6 novel loci in meta-analysis of P-wave terminal force. Four of the identified genetic loci were significantly associated with gene expression in 329 left atrial samples. Finally, we observed that some of the loci associated with the P wave were linked to overall atrial conduction, whereas others identified distinct phases of atrial conduction. CONCLUSIONS: We have identified 6 novel genetic loci associated with P-wave duration and 6 novel loci associated with P-wave terminal force. Future studies of these loci may aid in identifying new targets for drugs that may modify atrial conduction or treat atrial arrhythmias.

Comparison of Risk of Atrial Fibrillation Among Employed Versus Unemployed (from the REasons for Geographic and Racial Differences in Stroke Study).

Involuntary unemployment due to job loss has been associated with increased risk of cardiovascular events. Whether it also is associated with increased risk of atrial fibrillation (AF) is currently unknown. Therefore, we examined this association in 8,812 participants residing mainly in the Southeastern United States (mean age 58.1 ± 7.8 years; 63.2%; women; 43.2% black) with data on employment status who were enrolled in the REasons for Geographic And Racial Differences in Stroke study between 2003 and 2007 after excluding those with voluntary unemployment (retiree, homemakers, and students). AF was identified by electrocardiogram and past medical history at the same period. The cross-sectional association between status and type of unemployment with AF was examined in multivariable logistic regression models. Additional analysis in 4,273 participants without baseline AF and with data on incident AF collected in a follow-up visit occurred after a median of 9.4 years from baseline was also conducted. In a model adjusted for socio-demographics, health insurance, income, perceived stress, and cardiovascular risk factors, unemployment was associated with 60% increased odds of AF (odds ratio [95% confidence interval] 1.60 (1.24, 2.07)). This association was consistent in subgroups stratified by median age, gender, race, education, income, and health insurance status. Similarly, unemployment was associated with AF in those without AF at baseline who developed incident AF (odds ratio [95% confidence interval] 1.54 (1.04, 2.37)). In conclusion, involuntary unemployment is associated with increased risk of AF. This may call for considering socioeconomic determinants such as unemployment as part of the preventive strategies for AF.

Genome-wide Association Study of Susceptibility to Particulate Matter-Associated QT Prolongation.

BACKGROUND: Ambient particulate matter (PM) air pollution exposure has been associated with increases in QT interval duration (QT). However, innate susceptibility to PM-associated QT prolongation has not been characterized. OBJECTIVE: To characterize genetic susceptibility to PM-associated QT prolongation in a multi-racial/ethnic, genome-wide association study (GWAS). METHODS: Using repeated electrocardiograms (1986­2004), longitudinal data on PM<10 µm in diameter (PM10), and generalized estimating equations methods adapted for low-prevalence exposure, we estimated approximately 2.5×106 SNP×PM10 interactions among nine Women's Health Initiative clinical trials and Atherosclerosis Risk in Communities Study subpopulations (n=22,158), then combined subpopulation-specific results in a fixed-effects, inverse variance-weighted meta-analysis. RESULTS: A common variant (rs1619661; coded allele: T) significantly modified the QT-PM10 association (p=2.11×10−8). At PM10 concentrations >90th percentile, QT increased 7 ms across the CC and TT genotypes: 397 (95% confidence interval: 396, 399) to 404 (403, 404) ms. However, QT changed minimally across rs1619661 genotypes at lower PM10 concentrations. The rs1619661 variant is on chromosome 10, 132 kilobase (kb) downstream from CXCL12, which encodes a chemokine, stromal cell-derived factor 1, that is expressed in cardiomyocytes and decreases calcium influx across the L-type Ca2+ channel. CONCLUSIONS: The findings suggest that biologically plausible genetic factors may alter susceptibility to PM10-associated QT prolongation in populations protected by the U.S. Environmental Protection Agency's National Ambient Air Quality Standards. Independent replication and functional characterization are necessary to validate our findings. https://doi.org/10.1289/EHP347

Genome-wide association study of heart rate and its variability in Hispanic/Latino cohorts.

BACKGROUND: Although time-domain measures of heart rate variability (HRV) are used to estimate cardiac autonomic tone and disease risk in multiethnic populations, the genetic epidemiology of HRV in Hispanics/Latinos has not been characterized. OBJECTIVE: The purpose of this study was to conduct a genome-wide association study of heart rate (HR) and its variability in the Hispanic Community Health Study/Study of Latinos, Multi-Ethnic Study of Atherosclerosis, and Women's Health Initiative Hispanic SNP-Health Association Resource project (n = 13,767). METHODS: We estimated HR (bpm), standard deviation of normal-to-normal interbeat intervals (SDNN, ms), and root mean squared difference in successive, normal-to-normal interbeat intervals (RMSSD, ms) from resting, standard 12-lead ECGs. We estimated associations between each phenotype and 17 million genotyped or imputed single nucleotide polymorphisms (SNPs), accounting for relatedness and adjusting for age, sex, study site, and ancestry. Cohort-specific estimates were combined using fixed-effects, inverse-variance meta-analysis. We investigated replication for select SNPs exceeding genome-wide (P <5 × 10-8) or suggestive (P <10-6) significance thresholds. RESULTS: Two genome-wide significant SNPs replicated in a European ancestry cohort, 1 one for RMSSD (rs4963772; chromosome 12) and another for SDNN (rs12982903; chromosome 19). A suggestive SNP for HR (rs236352; chromosome 6) replicated in an African-American cohort. Functional annotation of replicated SNPs in cardiac and neuronal tissues identified potentially causal variants and mechanisms. CONCLUSION: This first genome-wide association study of HRV and HR in Hispanics/Latinos underscores the potential for even modestly sized samples of non-European ancestry to inform the genetic epidemiology of complex traits.

Effect of Intensive Blood Pressure Lowering on Left Ventricular Hypertrophy in Patients With Hypertension: SPRINT (Systolic Blood Pressure Intervention Trial).

BACKGROUND: It is currently unknown whether intensive blood pressure (BP) lowering beyond that recommended would lead to more lowering of the risk of left ventricular hypertrophy (LVH) in patients with hypertension and whether reducing the risk of LVH explains the reported cardiovascular disease (CVD) benefits of intensive BP lowering in this population. METHODS: This analysis included 8164 participants (mean age, 67.9 years; 35.3% women; 31.2% blacks) with hypertension but no diabetes mellitus from the SPRINT trial (Systolic Blood Pressure Intervention Trial): 4086 randomly assigned to intensive BP lowering (target SBP <120 mm Hg) and 4078 assigned to standard BP lowering (target SBP <140 mm Hg). Progression and regression of LVH as defined by Cornell voltage criteria derived from standard 12-lead ECGs recorded at baseline and biannually were compared between treatment arms during a median follow-up of 3.81 years. The effect of intensive (versus standard) BP lowering on the SPRINT primary CVD outcome (a composite of myocardial infarction, acute coronary syndrome, stroke, heart failure, and CVD death) was compared before and after adjustment for LVH as a time-varying covariate. RESULTS: Among SPRINT participants without baseline LVH (n=7559), intensive (versus standard) BP lowering was associated with a 46% lower risk of developing LVH (hazard ratio=0.54; 95% confidence interval, 0.43-0.68). Similarly, among SPRINT participants with baseline LVH (n=605, 7.4%), those assigned to the intensive (versus standard) BP lowering were 66% more likely to regress/improve their LVH (hazard ratio=1.66; 95% confidence interval, 1.31-2.11). Adjustment for LVH as a time-varying covariate did not substantially attenuate the effect of intensive BP therapy on CVD events (hazard ratio of intensive versus standard BP lowering on CVD, 0.76 [95% confidence interval, 0.64-0.90] and 0.77 [95% confidence interval, 0.65-0.91] before and after adjustment for LVH as a time-varying covariate, respectively). CONCLUSIONS: Among patients with hypertension but no diabetes mellitus, intensive BP lowering (target systolic BP <120 mm Hg) compared with standard BP lowering (target systolic BP <140 mm Hg) resulted in lower rates of developing new LVH in those without LVH and higher rates of regression of LVH in those with existing LVH. This favorable effect on LVH did not explain most of the reduction in CVD events associated with intensive BP lowering in the SPRINT trial. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062.

Electrocardiographic QRS-T angle and the risk of incident silent myocardial infarction in the Atherosclerosis Risk in Communities study.

BACKGROUND: Silent myocardial infarction (SMI) accounts for about half of the total number of MIs, and is associated with poor prognosis as is clinically documented MI (CMI). The electrocardiographic (ECG) spatial QRS/T angle has been a strong predictor of cardiovascular outcomes. Whether spatial QRS/T angle also is predictive of SMI, and the easy-to-obtain frontal QRS/T angle will show similar association are currently unknown. METHODS: We examined the association between the spatial and frontal QRS/T angles, separately, with incident SMI among 9498 participants (mean age 54years, 57% women, and 20% African-American), who were free of cardiovascular disease at baseline (visit 1, 1987-1989) from the Atherosclerosis Risk in Communities (ARIC) study. Incident SMI was defined as MI occurring after the baseline until visit 4 (1996-1998) without CMI. The frontal plane QRS/T angle was defined as the absolute difference between QRS axis and T axis. Values greater than the sex-specific 95th percentiles of the QRS/T angles were considered wide (abnormal). RESULTS: A total of 317 (3.3%) incident SMIs occurred during a 9-year median follow-up. In a model adjusted for demographics, cardiovascular risk factors and potential confounders, both abnormal frontal (HR 2.28, 95% CI 1.58-3.29) and spatial (HR 2.10, 95% CI 1.44-3.06) QRS/T angles were associated with an over 2-fold increased risk of incident SMI. Similar patterns of associations were observed when the results were stratified by sex. CONCLUSIONS: Both frontal and spatial QRS/T angles are predicative of SMI suggesting a potential use for these markers in identifying individuals at risk.

Relation of Higher Resting Heart Rate to Risk of Cardiovascular Versus Noncardiovascular Death.

Higher resting heart rate (RHR) is associated with increased risk of all-cause and cardiovascular mortality, with some reports showing the magnitude of association with all-cause mortality being stronger than that with cardiovascular mortality. This suggests that RHR association with mortality may not be limited to cardiovascular death. We compared the association between RHR with cardiovascular and noncardiovascular mortality in 6,743 participants (mean age 58.7 years, 52% women, 48% non-Hispanic whites) from the Third National Health and Nutrition Examination Survey (NHANES-III) after excluding those on antiarrhythmic drugs or with missing data. RHR data were obtained from standard 12-lead electrocardiogram recorded on the NHANES participants during a physical examination. National Death Index was used to identify the date and cause of death. Multivariable Cox proportional hazards analysis was used to calculate the hazard ratios (HRs) and 95% CIs for cardiovascular mortality and noncardiovascular mortality, separately, associated with 10 beats/min increase in RHR. During a median follow-up of 13.9 years, 906 cardiovascular deaths and 1,306 noncardiovascular deaths occurred. In models adjusted for age, gender, race, hypertension, diabetes, obesity, dyslipidemia, previous cardiovascular disease, smoking, cancer, chronic obstructive airway disease, thyroid disease, and serum creatinine, higher RHR was associated with increased risk of both cardiovascular mortality and noncardiovascular mortality with a relatively similar magnitude of risk (HR 1.19, 95% CI 1.12 to 1.26 and HR 1.23, 95% CI 1.17 to 1.29, respectively). In conclusion, higher RHR is associated with both cardiovascular mortality and noncardiovascular mortality suggesting that RHR is probably a marker of overall well-being rather than a marker of cardiovascular health.

Usefulness of Maintaining a Normal Electrocardiogram Over Time for Predicting Cardiovascular Health.

We hypothesized that maintaining a normal electrocardiogram (ECG) status over time is associated with low cardiovascular (CV) disease in a dose-response fashion and subsequently could be used to monitor programs aimed at promoting CV health. This analysis included 4,856 CV disease-free participants from the Atherosclerosis Risk in Communities study who had a normal ECG at baseline (1987 to 1989) and complete electrocardiographic data in subsequent 3 visits (1990 to 1992, 1993 to 1995, and 1996 to 1998). Participants were classified based on maintaining their normal ECG status during these 4 visits into "maintained," "not maintained," or "inconsistent" normal ECG status as defined by the Minnesota ECG classification. CV disease events (coronary heart disease, heart failure, and stroke) were adjudicated from Atherosclerosis Risk in Communities visit-4 through 2010. Over a median follow-up of 13.2 years, 885 CV disease events occurred. The incidence rate of CV disease events was lowest among study participants who maintained a normal ECG status, followed by those with an inconsistent pattern, and then those who did not maintain their normal ECG status (trend p value <0.001). Similarly, the greater the number of visits with a normal ECG status, the lower was the incidence rate of CV disease events (trend p value <0.001). Maintaining (vs not maintaining) a normal ECG status was associated with a lower risk of CV disease, which was lower than that observed in those with inconsistent normal ECG pattern (trend p value <0.01). In conclusion, maintaining a normal ECG status over time is associated with low risk of CV disease in a dose-response fashion, suggesting its potential use as a monitoring tool for programs promoting CV health.

Frontal QRS-T Angle and the Risk of Atrial Fibrillation in the Elderly.

BACKGROUND: Frontal QRS-T angle reflects changes in regional action potential duration and the direction of repolarization. Although it has been suggested that abnormal ventricular repolarization predisposes to atrial arrhythmias, it is unknown whether abnormal frontal QRS-T angle is associated with an increased risk of atrial fibrillation (AF). METHODS: We examined the association between frontal QRS-T angle and AF in 4282 participants (95% white; 41% male) from the Cardiovascular Health Study (CHS). QRS-T angle was computed from baseline electrocardiogram data. Abnormal QRS-T angle was defined as values greater than the sex-specific 95th percentile (men >131°; women: >104°). AF cases were identified from study electrocardiograms and from hospitalization discharge data through December 31, 2010. Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association between abnormal QRS-T angle and AF. RESULTS: Over a median follow-up of 12.1 years, a total of 1276 (30%) participants developed AF. In a Cox regression model, adjusted for socio-demographics and known AF risk factors, abnormal QRS-T angle was associated with a 55% increased risk of AF (HR = 1.55, 95%CI = 1.23, 1.97). When QRS-T angle was examined as a continuous variable, each 10° increase was associated with a 3% increased risk of AF (HR = 1.03, 95%CI = 1.01, 1.05). This finding was consistent in subgroups stratified by age, sex, and race. CONCLUSION: Our findings suggest that an abnormal frontal QRS-T angle on the electrocardiogram provides important prognostic information regarding AF risk in the elderly, and further implicate ventricular repolarization abnormalities in the pathogenesis of AF.

Electrocardiographic J Wave and Cardiovascular Outcomes in the General Population (from the Atherosclerosis Risk In Communities Study).

The association between the J wave, a key component of the early repolarization pattern, and adverse cardiovascular outcomes remains unclear. Inconsistencies have stemmed from the different methods used to measure the J wave. We examined the association between the J wave, detected by an automated method, and adverse cardiovascular outcomes in 14,592 (mean age = 54 ± 5.8 years; 56% women; 26% black) participants from the Atherosclerosis Risk In Communities (ARIC) study. The J wave was detected at baseline (1987 to 1989) and during follow-up study visits (1990 to 1992, 1993 to 1995, and 1996 to 1998) using a fully automated method. Sudden cardiac death, coronary heart disease death, and cardiovascular mortality were ascertained from hospital discharge records, death certificates, and autopsy data through December 31, 2010. A total of 278 participants (1.9%) had evidence of a J wave. Over a median follow-up of 22 years, 4,376 of the participants (30%) died. In a multivariable Cox regression analysis adjusted for demographics, cardiovascular risk factors, and potential confounders, the J wave was not associated with an increased risk of sudden cardiac death (hazard ratio [HR] 0.74, 95% CI 0.36 to 1.50), coronary heart disease death (HR 0.72, 95% CI 0.40 to 1.32), or cardiovascular mortality (HR 1.16, 95% CI 0.87 to 1.56). An interaction was detected for cardiovascular mortality by gender with men (HR 1.54, 95% CI 1.09 to 2.19) having a stronger association than women (HR 0.74, 95% CI 0.43 to 1.25; P-interaction = 0.030). In conclusion, our findings suggest that the J wave is a benign entity that is not associated with an increased risk for sudden cardiac arrest in middle-aged adults in the United States.

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.

Race and Sex Differences in the Incidence and Prognostic Significance of Silent Myocardial Infarction in the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Race and sex differences in silent myocardial infarction (SMI) are not well established. METHODS AND RESULTS: The analysis included 9498 participants from the Atherosclerosis Risk in Communities (ARIC) study who were free of cardiovascular disease at baseline (visit 1, 1987-1989). Incident SMI was defined as ECG evidence of MI without clinically documented MI (CMI) after the baseline until ARIC visit 4 (1996-1998). Coronary heart disease and all-cause deaths were ascertained starting from ARIC visit 4 until 2010. During a median follow-up of 8.9 years, 317 participants (3.3%) developed SMI and 386 (4.1%) developed CMI. The incidence rates of both SMI and CMI were higher in men (5.08 and 7.96 per 1000-person years, respectively) than in women (2.93 and 2.25 per 1000-person years, respectively; P<0.0001 for both). Blacks had a nonsignificantly higher rate of SMI than whites (4.45 versus 3.69 per 1000-person years; P=0.217), but whites had higher rate of CMI than blacks (5.04 versus 3.24 per 1000-person years; P=0.002). SMI and CMI (compared with no MI) were associated with increased risk of coronary heart disease death (hazard ratio, 3.06 [95% confidence interval, 1.88-4.99] and 4.74 [95% confidence interval, 3.26-6.90], respectively) and all-cause mortality (hazard ratio, 1.34 [95% confidence interval, 1.09-1.65] and 1.55 [95% confidence interval, 1.30-1.85], respectively). However, SMI and CMI were associated with increased mortality among both men and women, with potentially greater increased risk among women (interaction P=0.089 and 0.051, respectively). No significant interactions by race were detected. CONCLUSIONS: SMI represents >45% of incident MIs and is associated with poor prognosis. Race and sex differences in the incidence and prognostic significance of SMI exist that may warrant considering SMI in personalized assessments of coronary heart disease risk.

Electrocardiographic Advanced Interatrial Block and Atrial Fibrillation Risk in the General Population.

Although advanced interatrial block (aIAB) is an established electrocardiographic phenotype, its prevalence, incidence, and prognostic significance in the general population are unclear. We examined the prevalence, incidence, and prognostic significance of aIAB in 14,625 (mean age = 54 ± 5.8 years; 26% black; 55% female) participants from the Atherosclerosis Risk in Communities (ARIC) study. aIAB was detected from digital electrocardiograms recorded during 4 study visits (1987 to 1989, 1990 to 1992, 1993 to 1995, and 1996 to 1998). Risk factors for the development of aIAB were examined using multivariable Poisson regression models with robust variance estimates. Cox regression was used to compute hazard ratios and 95% CIs for the association between aIAB, as a time-dependent variable, and atrial fibrillation (AF). AF was ascertained from study electrocardiogram data, hospital discharge records, and death certificates thorough 2010. A total of 69 participants (0.5%) had aIAB at baseline, and 193 (1.3%) developed aIAB during follow-up. The incidence for aIAB was 2.27 (95% CI 1.97 to 2.61) per 1,000 person-years. Risk factors for aIAB development included age, male gender, white race, antihypertensive medication use, low-density lipoprotein cholesterol, body mass index, and systolic blood pressure. In a Cox regression analysis adjusted for sociodemographics, cardiovascular risk factors, and potential confounders, aIAB was associated with an increased risk for AF (hazard ratio 3.09, 95% CI 2.51 to 3.79). In conclusion, aIAB is not uncommon in the general population. Risk factors for developing aIAB are similar to those for AF, and the presence of aIAB is associated with an increased risk for AF.