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 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.

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.

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.

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 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.

Atrial Fibrillation and Risk of ST-Segment-Elevation Versus Non-ST-Segment-Elevation Myocardial Infarction: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: It has recently been reported that atrial fibrillation (AF) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association is currently unknown. Further study of the relationship of AF with the type of MI (ST-segment-elevation MI [STEMI] versus non-ST-segment-elevation MI [NSTEMI]) might shed light on the potential mechanisms. METHODS AND RESULTS: We examined the association between AF and incident MI in 14 462 participants (mean age, 54 years; 56% women; 26% blacks) from the Atherosclerosis Risk in Communities (ARIC) study who were free of coronary heart disease at baseline (1987-1989) with follow-up through December 31, 2010. AF cases were identified from study visit ECGs and by review of hospital discharge records. Incident MI and its types were ascertained by an independent adjudication committee. Over a median follow-up of 21.6 years, 1374 MI events occurred (829 NSTEMIs, 249 STEMIs, 296 unclassifiable MIs). In a multivariable-adjusted model, AF (n=1545) as a time-varying variable was associated with a 63% increased risk of MI (hazard ratio,1.63; 95% confidence interval, 1.32-2.02). However, AF was associated with NSTEMI (hazard ratio, 1.80; 95% confidence interval, 1.39-2.31) but not STEMI (hazard ratio, 0.49; 95% confidence interval, 0.18-1.34; P for hazard ratio comparison=0.004). Combining the unclassifiable MI group with either STEMI or NSTEMI did not change this conclusion. The association between AF and MI, total and NSTEMI, was stronger in women than in men (P for interaction <0.01 for both). CONCLUSIONS: AF is associated with an increased risk of incident MI, especially in women. However, this association is limited to NSTEMI.

Individual components of the Romhilt-Estes left ventricular hypertrophy score differ in their prediction of cardiovascular events: The Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The Romhilt-Estes left ventricular hypertrophy score and its components predict all-cause mortality in the general population.

BACKGROUND: The same electrocardiographic (ECG) criteria that have been used for detection of left ventricular hypertrophy (LVH) have recently been recognized as predictors of adverse clinical outcomes, but this predictive ability is inadequately explored and understood. METHODS: A total of 14,984 participants from the ARIC study were included in this analysis. Romhilt-Estes (R-E) LVH score was measured from the automatically processed baseline (1987-1989) ECG data. All-cause mortality was ascertained up to December 2010. Cox proportional hazard models were used to examine the association between baseline R-E score, overall and each of its 6 individual components separately, with all-cause mortality. The associations between change in R-E score between baseline and first follow-up visit with mortality were also examined. RESULTS: During a median follow-up of 21.7 years, 4,549 all-cause mortality events occurred during follow-up. In multivariable-adjusted models, increasing levels of the R-E score was associated with increasing risk of mortality both as a baseline finding and as a change between the baseline and the first follow-up visit. Of the 6 ECG components of the score, 4 were predictive of all-cause mortality (P-terminal force, QRS amplitude, LV strain, and intrinsicoid deflection), whereas 2 of the components were not (left axis deviation and prolonged QRS duration). Differences in the strengths of the associations between the individual components of the score and mortality were observed. CONCLUSIONS: The R-E score, traditionally used for detection of LVH, could be used as a useful tool for predication of adverse outcomes.

Ventricular conduction defects and the risk of incident heart failure in the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: We evaluated the risk of incident heart failure (HF) associated with various categories of ventricular conduction defects (VCDs) and examined the impact of QRS duration on the risk of HF. METHODS AND RESULTS: This analysis included 14,478 participants from the Atherosclerosis Risk in Communities (ARIC) study who were free of HF at baseline. VCDs (n = 377) were categorized into right and left bundle branch blocks (RBBB and LBBB, respectively), bifascicular BBB (RBBB with fascicular block), indeterminate-type VCD (IVCD), and pooled VCD group excluding lone RBBB. During an average of 18 years' follow-up, 1,772 participants were hospitalized for incident HF. Compared with no VCD, LBBB and pooled VCD were strongly associated with increased risk of incident HF (multivariable hazard ratios 2.87 and 2.29, respectively). Compared with no VCD with QRS duration <100 ms, HF risk was 1.17-fold for the no VCD group with QRS duration 100-119 ms, 1.97-fold for the pooled VCD group with QRS duration 120-139 ms, and 3.25-fold for the pooled VCD group with QRS duration ≥140 ms. HF risk for the pooled VCD group remained significant (1.74-fold for QRS duration 120-139 ms and 2.81-fold for QRS duration ≥140 ms) in the subgroup free from cardiovascular disease at baseline. Lone RBBB was not associated with incident HF. CONCLUSIONS: VCDs except for isolated RBBB are strong predictors of incident HF, and HF risk is further increased as the QRS duration is prolonged >140 ms.

A wide QRS/T angle in bundle branch blocks is associated with increased risk for coronary heart disease and all-cause mortality in the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Repolarization abnormality in bundle branch blocks (BBB) is traditionally ignored. This study evaluated the prognostic value of QRS/T angle for mortality in the presence and absence of BBB. METHODS AND RESULTS: Total 15,408 participants (mean age 54 years, 55.2% women, 26.9% blacks, 2.8% with BBB) were from the Arteriosclerosis Risk in Communities Study. Sex stratified Cox regression models were used to compute hazard ratios (HRs) with 95% confidence intervals (CIs) for coronary heart disease (CHD) and all-cause mortality for wide spatial QRS/T angle with and without BBB including right BBB (RBBB), left BBB (LBBB) and indetermined-type ventricular conduction defect (IVCD) and RBBB combined with left anterior fascicular block. During a median 22-year follow-up, 4767 deaths occurred, 728 of them CHD deaths. Using the No-BBB with QRS/T angle below median value as gender-specific reference groups, the mortality risk increase was significant for both women and men with No-BBB and QRS/T angle above the median value. In the pooled ICVD/LBBB group, the risk for CHD death was increased 15.9-fold in women and 6.04 fold in men, and for all-cause deaths 3.01-fold in women and 1.84-fold in men. However, the mortality risk in isolated RBBB group was only significantly increased in women but not in men. CONCLUSION: A wide spatial QRS/T angle in BBB is associated with increased risk for CHD and all-cause mortality over and above the predictive value for BBB alone. The risk for women is as high as or higher than that in men.

Electrocardiographic repolarization-related predictors of coronary heart disease and sudden cardiac deaths in men and women with cardiovascular disease in the Atherosclerosis Risk in Communities (ARIC) study.

INTRODUCTION: We evaluated repolarization-related predictors of coronary heart disease (CHD) death and sudden cardiac death (SCD) in men and women with cardiovascular disease (CVD) in the Atherosclerosis Risk in Communities (ARIC) study. METHODS AND RESULTS: Hazard ratios (HR) from Cox regression were computed for 11 ECG measures of repolarization in 1384 subjects (50% women) 45 to 65years of age. The average follow-up was 14years. Based on electrophysiological considerations the spatial angle between Tpeak and normal repolarization reference vector [Ѳ(Tp|Tref)], STJV6 amplitude, QRS duration and Tonset and Tpeak vector magnitude ratio (ToV/TpV) were considered as primary candidates for independent mortality predictors, and as an alternative set TaVR and TV1 amplitudes and the spatial angle between the initial and terminal T vectors [Ѳ(Tinit|Tterm)]. From the primary set [Ѳ(Tp|Tref)] was a strong independent predictor for CHD death (nearly 4-fold increased risk in men and 2-fold increased risk in women) and for SCD [Ѳ(Tinit|Tterm)] in men (3.4-fold increased risk) and (ToV/TpV) in women (7.76-fold increased risk). From the alternative set of independent predictors TaVR amplitude negativity reduced to less than 150µV (1.5mm) was a strong mortality predictor with an approximately 3-fold increased risk for CHD death and SCD in men and women. CONCLUSIONS: The strongest independent predictors of CHD death were [Ѳ(Tp|Tref)] in men and TaVR in women and of SCD were [Ѳ(Tp|Tref)] in men and ToV/TpV in women. Overall, TaVR amplitude negativity reduced to less than 150µV (1.5mm) was the most consistent mortality predictor in all subgroups. These ECG variables may warrant consideration for identification of high risk men and women for more intense preventive intervention.

Race- and sex-associated differences in rate-adjusted QT, QTpeak, ST elevation and other regional measures of repolarization: the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Data are limited about race-and sex-associated differences in prognostically important ECG measures of regional repolarization. METHODS AND RESULTS: The normal reference group from the Atherosclerosis Risk in Communities (ARIC) study included 8,676 white and African-American men and women aged 40-65 years. Exclusion criteria included cardiovascular disease, hypertension, diabetes and major ECG abnormalities. Notable sex differences (p<0.001) were observed in the upper 98% limits for rate-adjusted QTend (QTea) which was 435 ms in white and African-American men and 445 ms in white and African-American women, and for left ventricular epicardial repolarization time (RTepi) which was 345 ms in white and African-American men and 465 ms in white and African-American women. These sex differences reflect earlier onset and end of repolarization in men than in women. Upper normal limits for STJ amplitude in V2-V3 were 100 µV in white and African-American women, 150 µV in white men and 200 µV in African-American men (p<0.001 for sex differences), and for other chest leads, aVL and aVF 50 µV in white women, 100 µV in African-American women, 100 µV in white men and 150 µV in African-American men (p<0.001 for sex and race differences). CONCLUSIONS: Shorter QTea and RTepi in men than in women reflect earlier onset and end of repolarization in men. STJ amplitudes in African-American men were higher than in other subgroups by race and sex. These sex and race differences need to be considered in clinical and epidemiological applications of normal standards.

Determinants of developing widened spatial QRS-T angle in HIV-infected individuals: results from the Strategies for Management of Antiretroviral Therapy [SMART] Study.

BACKGROUND: A widened electrocardiographic spatial QRS-T angle has been shown to be predictive of cardiovascular disease in HIV-infected individuals. However, determinants and risk factors of developing widened QRS-T angle over time in this population remain unknown. METHODS AND RESULTS: Spatial QRS-T angle was automatically measured from standard electrocardiogram of 1444 HIV-infected individuals without baseline widened spatial QRS-T angle from the Strategies for Management of Antiretroviral Therapy [SMART], a clinical trial comparing two antiretroviral treatment strategies [Drug Conservation (DC) vs. Viral Suppression (VS)]. Conditional logistic regression analysis was used to examine the association between baseline characteristics and incident widened spatial QRS-T angle (a new angle>93° in males and>74° in females). During 2544 person-years of follow-up, 199 participants developed widened angle at a rate of 7.8 per 100 person-years. In unadjusted models, female sex, black race (vs. white), DC treatment strategy, current and past smokers (vs. never), history of alcohol abuse, greater body mass index, history of diabetes and higher levels of hs-C-reactive protein were associated with incident widened spatial QRS-T angle. When these variables were entered together in the same model with adjustment for demographics and treatment strategy, DC treatment strategy [OR (95% CI): 1.50 (1.09, 2.07)], female gender [1.69 (1.17, 2.45)], current and past smoking (vs. never) [2.49 (1.63, 3.81) and 1.93 (1.21, 3.09), respectively], and diabetes [2.28 (1.33, 3.91)] predicted incident widened spatial QRS-T angle. CONCLUSIONS: Drug conservation treatment strategy, female gender, smoking, and diabetes are independently predictive of incident widened spatial QRS-T angle in HIV-infected individuals.

Normal standards for computer-ECG programs for prognostically and diagnostically important ECG variables derived from a large ethnically diverse female cohort: the Women's Health Initiative (WHI).

BACKGROUND: Substantial new information has emerged recently about the prognostic value for a variety of new ECG variables. The objective of the present study was to establish reference standards for these novel risk predictors in a large, ethnically diverse cohort of healthy women from the Women's Health Initiative (WHI) study. METHODS AND RESULTS: The study population consisted of 36,299 healthy women. Racial differences in rate-adjusted QT end (QT(ea)) and QT peak (QT(pa)) intervals as linear functions of RR were small, leading to the conclusion that 450 and 390 ms are applicable as thresholds for prolonged and shortened QT(ea) and similarly, 365 and 295 ms for prolonged and shortened QT(pa), respectively. As a threshold for increased dispersion of global repolarization (T(peak)T(end) interval), 110 ms was established for white and Hispanic women and 120 ms for African-American and Asian women. ST elevation and depression values for the monitoring leads of each person with limb electrodes at Mason-Likar positions and chest leads at level of V1 and V2 were first computed from standard leads using lead transformation coefficients derived from 892 body surface maps, and subsequently normal standards were determined for the monitoring leads, including vessel-specific bipolar left anterior descending, left circumflex artery and right coronary artery leads. The results support the choice 150 µV as a tentative threshold for abnormal ST-onset elevation for all monitoring leads. Body mass index (BMI) had a profound effect on Cornell voltage and Sokolow-Lyon voltage in all racial groups and their utility for left ventricular hypertrophy classification remains open. CONCLUSIONS: Common thresholds for all racial groups are applicable for QT(ea), and QT(pa) intervals and ST elevation. Race-specific normal standards are required for many other ECG parameters.

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.

Ethnic distribution of ECG predictors of atrial fibrillation and its impact on understanding the ethnic distribution of ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND PURPOSE: The paradox of the reported low prevalence of atrial fibrillation (AF) in blacks compared with whites despite higher stroke rates in the former could be related to limitations in the current methods used to diagnose AF in population-based studies. Hence, this study aimed to use the ethnic distribution of ECG predictors of AF as measures of AF propensity in different ethnic groups. METHODS: The distribution of baseline measures of P-wave terminal force, P-wave duration, P-wave area, and PR duration (referred to as AF predictors) were compared by ethnicity in 15 429 participants (27% black) from the Atherosclerosis Risk in Communities (ARIC) study by unpaired t test, chi(2), and logistic-regression analysis, as appropriate. Cox proportional-hazards analysis was used to separately examine the association of AF predictors with incident AF and ischemic stroke. RESULTS: Whereas AF was significantly less common in blacks compared with whites (0.24% vs 0.95%, P<0.0001), similar to what has been reported in previous studies, blacks had significantly higher and more abnormal values of AF predictors (P<0.0001 for all comparisons). Black ethnicity was significantly associated with abnormal AF predictors compared with whites; odds ratios for different AF predictors ranged from 2.1 to 3.1. AF predictors were significantly and independently associated with AF and ischemic stroke with no significant interaction between ethnicity and AF predictors, findings that further justify using AF predictors as an earlier indicator of future risk of AF and stroke. CONCLUSIONS: There is a disconnect between the ethnic distribution of AF predictors and the ethnic distribution of AF, probably because the former, unlike the latter, do not suffer from low sensitivity. These results raise the possibility that blacks might actually have a higher prevalence of AF that might have been missed by previous studies owing to limited methodology, a difference that could partially explain the greater stroke risk in blacks.

Synergistic effect of polymorphisms of paraoxonase gene cluster and arsenic exposure on electrocardiogram abnormality.

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 sensitivity of the method used to detect atrial fibrillation in population studies affects group-specific prevalence estimates: ethnic and regional distribution of atrial fibrillation in the REGARDS study.

BACKGROUND: Among African-Americans, and in southern US states, the rates of stroke are high but the reported prevalences of atrial fibrillation (AF) are low. We hypothesized that the reported ethnic and regional distributions of AF are affected by the sensitivity of the methods that were used to detect AF in previous reports. METHODS: A total of 18,833 black and white participants from the US national REasons For Geographic And Racial Differences In Stroke (REGARDS) study were included in this analysis. Levels of sensitivity to detect AF, from least to most sensitive, were created for combinations of self-report (SR) and ECG methods, as follows: (1) SR plus ECG, (2) ECG alone, (3) SR alone, and (4) SR or ECG. Geographic regions were dichotomized as Stroke Belt (the southern US states) and non-Stroke Belt. Logistic regression analysis estimated the odd ratios of AF associated with the Stroke Belt and black ethnicity for each diagnostic combination. RESULTS: Residence in the Stroke Belt was significantly associated with AF when diagnosed by SR plus ECG (multivariable-adjusted OR, 0.66; 95% CI, 0.47 to 0.92), but not when diagnosed with SR or ECG (OR, 0.95; 95% CI, 0.85 to 1.06). Similarly, for the 4 methods used to detect AF, the strength of the association between black ethnicity and AF progressively decreased with increasing test sensitivity (ORs: 0.20, 0.40, 0.70, 0.71, respectively). CONCLUSIONS: The association of AF with residence in the Stroke Belt and black ethnicity was inversely related to the sensitivity of the method used to detect AF: as test sensitivity increased, the association became attenuated. This may partially explain the lower reported prevalence of AF in populations and regions with higher stroke rates.

Ambient particulate air pollution and ectopy--the environmental epidemiology of arrhythmogenesis in Women's Health Initiative Study, 1999-2004.

The relationships between ambient PM(2.5) and PM(10) and arrhythmia and the effect modification by cigarette smoking were investigated. Data from U.S. Environmental Protection Agency (EPA) air quality monitors and an established national-scale, log-normal kriging method were used to spatially estimate daily mean concentrations of PM at addresses of 57,422 individuals from 59 examination sites in 24 U.S. states in 1999-2004. The acute and subacute exposures were estimated as mean, geocoded address-specific PM concentrations on the day of, 0-2 d before, and averaged over 30 d before the electrocardiogram (ECG) (Lag(0); Lag(1); Lag(2); Lag(1-30)). At the time of standard 12-lead resting ECG, the mean age (SD) of participants was 67.5 (6.9) yr (84% non-Hispanic White; 6% current smoker; 15% with coronary heart disease; 5% with ectopy). After the identification of significant effect modifiers, two-stage random-effects models were used to calculate center-pooled odds ratios and 95% confidence intervals (OR, 95% CI) of arrhythmia per 10 mug/m(3) increase in PM concentrations. Among current smokers, Lag(0) and Lag(1) PM concentrations were significantly associated ventricular ectopy (VE)-the OR (95% CI) for VE among current smokers was 2 (1.32-3.3) and 1.32 (1.07-1.65) at Lag(1) PM(2.5) and PM(10), respectively. The interactions between current smoking and acute exposures (Lag(0); Lag(1); Lag(2)) were significant in relationship to VE. Acute exposures were not significantly associated with supraventricular ectopy (SVE), or with VE among nonsmokers. Subacute (Lag(1-30)) exposures were not significantly associated with arrhythmia. Acute PM(2.5) and PM(10) exposure is directly associated with the odds of VE among smokers, suggesting that they are more vulnerable to the arrhythmogenic effects of PM.