Zhu-ming Zhang

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. 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. 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. 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 participa...

The prevalence and determinants of QRS transition zones are not well established. 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. 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 h...

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.

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. To characterize genetic susceptibility to PM-associated QT prolongation in a multi-racial/ethnic, genome-wide association study (GWAS). Using repeated electrocardiograms (1986-2004), longitudinal data on in diameter (), and generalized estimating equations methods adapted for low-prevalence exposure, we estimated approximately interactions among nine Women's Health Initiative clinical trials and Atherosclerosis Risk in Communities Study subpopulations (), then combined subpopulation-specific results in a fixed-effects, inverse variance-weighted meta-analysis. A common variant (rs1619661; coded allele: T) significantly modified the association (). At concentrations percentile, QT increased 7 ms across the CC and TT genotypes: 397 (95% confidence interval: 396, 399) to 404...

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74<rg<-0.55) and blood pressure…

Although time-domain measures of heart rate variability (HRV) are used to estimate cardiac autonomic tone and disease risk in multi-ethnic populations, the genetic epidemiology of HRV in Hispanics/Latinos has not been characterized. Conduct a genome-wide association study (GWAS) 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). We estimated HR (beats/min), the standard deviation of normal-to-normal inter-beat intervals (SDNN, ms), and the root mean squared difference in successive, normal-to-normal inter-beat intervals (RMSSD, ms) from resting, standard twelve-lead electrocardiograms. 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 e...

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 n...

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 o...

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 regr...

The electrocardiographic QRS duration, a measure of ventricular depolarization and conduction, is associated with cardiovascular mortality. While genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with QRS duration at 22 loci among those of European descent, the genetic architecture of QRS duration in non-European populations is largely unknown. We therefore performed a GWAS meta-analysis of QRS duration in 13,031 African Americans from ten cohorts and a transethnic GWAS meta-analysis with additional results from populations of European descent. In the African American GWAS, a single genome-wide significant SNP association was identified (rs3922844, P=4x10(-14)) in intron 16 of SCN5A, a voltage-gated cardiac sodium channel gene. The QRS-prolonging rs3922844 C allele was also associated with decreased SCN5A RNA expression in human atrial tissue (P=1.1x10(-4)). High density genotyping revealed that the SCN5A association region in A...

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). 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. Over a median follow-up of 12.1 years, a total of 1276 (30%...

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. 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 (ARIC) Study. 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. 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 th...

The electrocardiogram (ECG) is an objective tool for cardiovascular disease (CVD) risk assessment. We evaluated distribution of ECG abnormalities and risk factors for developing new abnormalities in 1314 patients with type 1 diabetes (T1D) from the Epidemiology of Diabetes Interventions and Complications (EDIC) study. Annual ECGs were centrally read. ECG abnormalities were classified as major and minor according to the Minnesota ECG Classification. At EDIC year 1 (baseline), 356 (27.1%) of the participants had at least 1 ECG abnormality (major or minor) whereas 26 (2%) had at least one major abnormality. During 16 years of follow-up, 1016 (77.3%) participants developed at least 1 new ECG abnormality (major or minor), whereas 172 (13.1%) developed at least 1 new major abnormality. Independent risk factors for developing new major ECG abnormalities were: age, current smoking, increased systolic blood pressure, and higher glycosylated hemoglobin (hazard ratio [HR] [95% CI]: 1.04 [1.02-...

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 basel...

It has been recently reported that the Romhilt-Estes (R-E) score, originally proposed for detection of left ventricular hypertrophy from the electrocardiogram, is a strong predictor of all-cause mortality. Whether the R-E score is also predictive of cardiovascular disease (CVD) and whether its individual components differ in their ability to predict different CVD outcomes are not well established. This analysis includes 13,261 participants from the ARIC study who were free of CVD at baseline (1987-1989). Incident CVD, coronary heart disease (CHD), heart failure (HF), and stroke were ascertained by an adjudication committee through December 2010. The R-E left ventricular hypertrophy score was measured from automatically processed baseline electrocardiogram data. Cox proportional hazard models were used to examine the association between baseline the R-E overall score (overall) and each of its 6 individual components separately, with each of the CVD outcomes. During a median follow-up of 21.8 years, 3,579, 2,205, 1,814, and 731 CVD, CHD, HF, and stroke events, respectively, occurred. In multivariable adjusted models, R-E score ≥4 points (compared with 0 points) was associated with increased risk of CVD, CHD, HF, and stroke (hazard ratio [95% CI] 1.66 [1.41-1.96], 1.66 [1.34-2.07], 1.97 [1.60-2.43], and 1.49 [1.07-2.07], respectively). The 6 component of the R-E score varied in their relationship to different CVD outcomes. The R-E score is predictive of CVD outcomes. The 6 R-E score components differ in their associations with different CVD outcomes, indicating that they may be electrical biomarkers of different physiological events within the myocardium.

There are no proven strategies to prevent atrial fibrillation (AF) in patients with type 2 diabetes (T2DM). We compared standard blood pressure (BP) lowering vs. intensive BP lowering in reducing incidence of AF or P-wave indices (PWI-ECG markers of left atrial abnormality that are considered intermediate phenotypes of AF) in patients with T2DM. We analyzed data from the ACCORD BP trial-a randomized controlled nonblinded trial (2001-2009) which randomized patients with T2DM and systolic BP (SBP) 130-180mm Hg on ≤3 antihypertensive medications aged 40-79 years with cardiovascular disease (CVD) or aged 55-79 years with subclinical CVD or ≥2 CVD risk factors to standard BP lowering (SBP <140mm Hg) vs. intensive BP lowering (SBP <120mm Hg). The primary outcome was a composite of incident AF and PWI. Data from 3,087 participants (mean age, 62.2 years; women, 48.2%; non-White, 39.2%) were analyzed. During a mean follow-up of 4.4 years, the primary outcome occurred in 1,063 participa...

The body acts as a large conductor of electrical currents generated by heart. To record, these currents require that only any two points on the body be connected to the electrocardiograph. This establishes the necessary completion of an electrical circuit and is done by means of electrodes attached to the limbs or the chest, each pair of attachments being one “lead.” The ECG leads generally used are I, II, III, aVR, aVL, aVF, V1, V2, V3, V4, V5, and V6.

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. AF is associated with MI in older adults. A total of 4608 participants (85% white, 40% male) from the Cardiovascular Health Study without evidence of baseline coronary heart disease were included in this analysis. AF cases were identified during the yearly study electrocardiogram, a self-reported history of a physician diagnosis, or by hospitalization data. Incident MI was identified using medical records with local and central adjudication. Cox regression was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between AF and incident MI. A total of 434 (9.4%) participants had evidence of AF before incident MI. Over a median follow-up of 12.2 years, a total of 797 (17.3%) participants developed MI. In a multivar...

Although current evidence suggests that the spatial T wave axis captures important information about ventricular repolarization abnormalities, there are only a few and discordant epidemiologic studies addressing the ability of the spatial T wave axis to predict coronary heart disease (CHD) occurrence. This prospective study analyzed data from 12,256 middle-aged African American and white men and women, from the Atherosclerosis Risk in Communities Study (ARIC). Following a standardized protocol, resting standard 12-lead, 10-second electrocardiograms were digitized and analyzed with the Marquette GE program. The median follow-up time was 12.1 years; incident coronary heart disease comprised fatal and non-fatal CHD events. The incidence rate of CHD was 4.26, 4.18, 4.28 and 5.62 per 1000 person-years respectively, across the spatial T wave axis quartiles. Among women for every 10 degrees increase in the spatial T wave axis deviation, there was an estimated increase in the risk of CHD of...

Arsenic has been linked to increased prevalence of cancer and cardiovascular disease (CVD), but the long-term impact of arsenic exposure remains unclear. Human paraoxonase (PON1) is a high-density lipoprotein-associated antioxidant enzyme which hydrolyzes oxidized lipids and is thought to be protective against atherosclerosis, but evidence remains limited to case-control studies. Only recently have genes encoding enzymes responsible for arsenic metabolism, such as AS3MT and GSTO, been cloned and characterized. This study was designed to evaluate the synergistic interaction of genetic factors and arsenic exposure on electrocardiogram abnormality. A total of 216 residents from three tap water implemented villages of previous arseniasis-hyperendemic regions in Taiwan were prospectively followed for an average of 8 years. For each resident, a 12-lead conventional electrocardiogram (ECG) was recorded and coded by Minnesota Code standard criteria. Eight functional polymorphisms of PON1, PON2, AS3MT, GSTO1, and GSTO2 were examined for genetic susceptibility to ECG abnormality. Among 42 incident cases with ECG deterioration identified among 121 baseline-normal subjects, arsenic exposure was significantly correlated with incidence of ECG abnormality. In addition, polymorphisms in two paraoxonase genes were also found associated with the incidence of ECG abnormality. A haplotype R-C-S constituted by polymorphisms of PON1 Q192R, -108C/T and PON2 C311S was linked to the increased risk. Subjects exposed to high levels of As (cumulative As exposure >14.7 ppm-year or drinking artesian well water >21 years) and carrying the R-C-S haplotype had significantly increased risks for ECG abnormality over those with only one risk factor. Results of this study showed a long-term arsenic effect on ECG abnormality and significant gene-gene and gene-environment interactions linked to the incidence of CVD. This finding might have important implications for a novel and potentially useful biomarker of arsenic risk.

The spatial QRS/T angle has been identified as a strong predictor of adverse cardiac events. Mean QRS and T amplitudes from X, Y, and Z leads generated by a matrix transformation method are often used to calculate the QRS/T angle (QRS/T(matrix)). Many investigators find this procedure cumbersome. We used electrocardiographic data files of 14881 men and women aged 45 to 65 years from the Atherosclerosis in Communities study to derive a simple formula for estimated spatial QRS/T angle (QRS/T(simple)). QRS/T(simple) is calculated as the inverse cosine between the mean QRS and T vectors, which are approximated by 3 QRS(net) and T(net) amplitudes for each vector. QRS/T(simple) explained 79% of the variance of QRS/T(matrix) (r = 0.89). Using sex-specific thresholds, QRS/T(simple) detected abnormally wide QRS/T(matrix) values with a sensitivity of 91% and specificity of 88%. It is concluded that this simple method may provide a satisfactory substitute for QRS/T from the matrix transformation method.

Widening of the electrocardiographic (ECG) spatial QRS-T angle has been predictive of cardiovascular disease (CVD) events in the general population. However, its prognostic significance in human immunodeficiency virus (HIV)-infected patients remains unknown. The spatial QRS-T angle was derived from the baseline resting 12-lead electrocardiogram of 4,453 HIV-infected patients aged 43.5 ± 9.3 years from the Strategies for Management of Antiretroviral Therapy (SMART) trial. CVD events were identified during a median follow-up of 28.7 months. Quartiles of the spatial QRS-T angle was calculated for men and women separately, and values in the upper quartile were considered as a widened angle (values >74° for women and >93° for men). A multivariate Cox proportional hazards analysis was used to examine the association between a widened baseline spatial QRS-T angle and incident CVD events. During 11,965 person-years of follow-up, 152 CVD events occurred at a rate of 1.27 events/100 person-years. The rate of CVD events in those with a widened spatial QRS-T angle was almost double the rate in those with a normal spatial QRS-T angle (rate ratio 1.94, 95% confidence interval 1.40 to 2.69; p <0.001). In a model adjusted for study treatment arm, demographics, CVD risk factors, HIV characteristics, inflammatory markers, and other ECG abnormalities, a widened spatial QRS-T angle was associated with a >50% increased risk of CVD events compared to a normal spatial QRS-T angle (hazard ratio 1.53, 95% confidence interval 1.07 to 2.17; p = 0.02). No interaction was seen by SMART trial arm (p value for interaction = 0.37) or gender (p value for interaction = 0.84). In conclusion, a widened spatial QRS-T angle was independently predictive of CVD events in HIV-infected patients receiving antiretroviral therapy. This highlights the potential role of routine electrocardiography as a simple noninvasive CVD risk-screening tool in HIV-infected patients.

T-axis shift has been reported to be an indicator of increased mortality risk. We evaluated the association of spatial T-axis deviation with incident coronary heart disease (CHD) events in older men and women free from clinically overt CHD. Spatial T-axis deviation was measured ...

We evaluated the risk of incident heart failure (HF) associated with bundle-branch blocks (BBBs) in postmenopausal women. Cox's regression was used to evaluate hazard ratios with 95% confidence intervals for HF among 65975 participants of the Women's Health Initiative (WHI) study during an average follow-up of 14 years. BBBs observed in 1676 women at baseline were categorized into left, right, and indetermined-type BBBs (LBBB, RBBB, and intraventricular conduction defect, respectively). Compared with women with no BBB, LBBB, and intraventricular conduction defect were strong predictors of incident HF in multivariable-adjusted risk models (hazard ratio, 3.79; confidence interval, 2.95-4.87 for LBBB and hazard ratio, 3.53; confidence interval, 2.14-5.81 for intraventricular conduction defect). RBBB was not a significant predictor of incident HF in multivariable-adjusted risk model, but the combination of RBBB and left anterior fascicular block was a strong predictor (hazard ra...

Among 35,192 postmenopausal, predominantly white women in Iowa age 55-69 years and free of cancer, we collected baseline history, dietary information, and anthropometric data by mail in 1986. We ascertained the 8-year incidence (62 new cases) of renal cell carcinoma using the Iowa Surveillance, Epidemiology, and End Results (SEER) register, the National Death Index, and mail follow-up. Risk factors for renal cell carcinoma included increasing age, increasing weight (either current, maximum adult weight, or weight at ages 18, 30, or 50 years), greater waist-to-hip ratio, and a history of blood transfusion. Total dietary calcium was associated independently with a reduced risk of renal cell carcinoma. No other dietary micro- or macronutrients or food groups were predictive of the development of renal cell carcinoma. Other previously identified risk factors were not confirmed: most notably, there was no increased risk from a history of hypertension, after adjustment for diuretic use. History of ever-use of diuretics was associated with a twofold increased risk of renal cancer, although the strength of association was markedly reduced after adjustment for age, weight, waist-to-hip ratio, and calcium intake.

Electrocardiographic bundle branch block (BBB) has higher cardiac and all-cause death. However, reports on the association between BBBs and mortality in the general populations are conflicting. The aim of this study was to evaluate the risk for coronary heart disease (CHD) and all-cause death associated with left BBB (LBBB) and right BBB (RBBB) during 14 years of follow-up in 66,450 participants from the Women's Health Initiative (WHI) study. Cox proportional-hazards regression was performed for mortality risk in Women with LBBB (n = 714) and those with RBBB (n = 832). In risk models adjusted for demographic and clinical risk factors in women with cardiovascular disease (CVD), hazard ratios for CHD death were 2.92 (95% confidence interval 2.08 to 4.08, p <0.001) for LBBB and 1.62 (95% confidence interval 1.08 to 2.43, p <0.05) for RBBB, and only LBBB was a significant predictor of all-cause death (hazard ratio 1.43, 95% confidence interval 1.11 to 1.83, p <0.01). In CVD-free women, only LBBB was a significant predictor of CHD death (fully adjusted hazard ratio 2.17, 95% confidence interval 1.37 to 3.43, p <0.01), and neither blocks was predictive of all-cause death. From several repolarization variables that were significant mortality predictors in univariate risk models, after adjustment for other electrocardiographic covariates and risk factors, ST J-point depression in lead aVL ≤-30 μV in women with LBBB was an independent predictor of CHD death, with a more than fivefold increase in risk. None of the repolarization variables were independent predictors in women with RBBB. In conclusion, prevalent LBBB in CVD-free women and LBBB and RBBB in women with CVD were significant predictors of CHD death. In women with LBBB, ST J-point depression in lead aVL was a strong independent predictor of CHD death.