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 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.

Eyewitness to history: Landmarks in the development of computerized electrocardiography.

The use of digital computers for ECG processing was pioneered in the early 1960s by two immigrants to the US, Hubert Pipberger, who initiated a collaborative VA project to collect an ECG-independent Frank lead data base, and Cesar Caceres at NIH who selected for his ECAN program standard 12-lead ECGs processed as single leads. Ray Bonner in the early 1970s placed his IBM 5880 program in a cart to print ECGs with interpretation, and computer-ECG programs were developed by Telemed, Marquette, HP-Philips and Mortara. The "Common Standards for quantitative Electrocardiography (CSE)" directed by Jos Willems evaluated nine ECG programs and eight cardiologists in clinically-defined categories. The total accuracy by a representative "average" cardiologist (75.5%) was 5.8% higher than that of the average program (69.7, p<0.001). Future comparisons of computer-based and expert reader performance are likely to show evolving results with continuing improvement of computer-ECG algorithms and changing expertise of ECG interpreters.

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.

Electrocardiographic left ventricular hypertrophy and the risk of adverse cardiovascular events: a critical appraisal.

This review covers selected electrocardiographic left ventricular hypertrophy (ECG-LVH) studies which have evaluated their prognostic value for adverse cardiovascular (CVD) events. Most ECG-LVH studies have used echocardiographic left ventricular mass (Echo-LVM) as the gold standard for evaluating ECG-LVH criteria. More recently, LVM from magnetic resonance imaging (MRI-LVM) has evolved as the new gold standard. The reported risk of adverse CVD events is generally highest for ECG-LVH criteria which combine high amplitude QRS criteria with repolarization abnormalities such as in LV strain pattern. Evolving coronary heart disease (CHD) may account in part for the increased risk for ECG-LVH. However, one large coronary arteriography study found that 5-year survival was significantly lower in coronary artery disease (CAD) patients with ECG-LVH than without LVH regardless of CAD status. The utility of Echo-LVH as a standard is limited by the large intra- and inter-reader variability and the lack of standardization of allometric formulations for adjustment of LVM to body size. Newer evaluation data with MRI-LVM as the standard show that for most ECG criteria CVD event rates are significantly higher for study subgroups with ECG-LVH than those without ECG-LVH. However, the performance results differ when comparing the risk for CVD events from those for the overall LVH classification accuracy according to sensitivity and specificity. Large short-term variability of ECG amplitudes due to electrode placement variability is a common limiting factor for ECG-LVH criteria performance regardless of the gold standard. Clinical trials for hypertension control rely largely on monitoring Echo-LVH rather than ECG-LVH.

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.

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.

Heart rate adjustment of PR interval in middle-aged and older adults.

Prolonged PR interval has been associated with adverse cardiac events. Consequently, the scientific community and regulatory agencies have become concerned about PR interval prolongation induced by cardioactive agents. We evaluated PR dependence on heart rate (HR) in 5757 men and women aged 40 years and older from the US third National Health and Nutrition Survey with the objective to determine if rate adjustment for the PR interval is warranted as is the case with QT interval. Electrocardiograms were computer-processed in a central electrocardiogram laboratory. There was a statistically significant negative correlation between PR and HR (r = -0.15; P < .001); notably weaker than that between QT and HR (r = -0.76; P < .001). Evaluation of subgroups stratified by sex, race, and age revealed a significant interaction between PR and HR with age (P = .006). A subsequent search for optimal rate-adjusted PR (PRa) formula that eliminates PR dependence on HR within each age group produced the formula: PRa = PR + 0.26 (HR - 70) for age group younger than 60 years and PRa = PR + 0.42 (HR - 70) for age group 60 years or older. The application of this formula in the study population effectively made the PR interval rate-invariant (residual slope of regression, -0.0054; 95% confidence interval, -0.064 to 0.053; P = .86). Based on the distribution of PRa, the 98th percentile limit of 220 milliseconds would be a reasonable overall threshold for defining first-degree AV block, with the 95th percentile limit of 205 as a threshold for borderline PR prolongation. In conclusion, the association between PR and HR is age- and rate-dependent and a separate rate-adjustment formula is needed for adults in younger and older age groups. The prognostic significance of the rate-adjusted PR needs to be investigated.

Isolated negative T waves as independent predictors of short-term and long-term coronary heart disease mortality in men free of manifest heart disease in the Seven Countries Study.

Isolated T-wave findings are generally considered of little importance in clinical electrocardiogram (ECG) interpretation, although a few studies have associated them with excess mortality risk. We used Cox regression models to evaluate coronary heart disease (CHD) mortality risk for isolated inverted T waves in 8713 men in the Seven Countries Study with no manifest cardiac diseases at baseline. The study population was stratified into 3 mutually exclusive groups: (1) isolated inverted T waves in the absence of other codable ECG findings according to the Minnesota Code; (2) other ECG findings with or without negative T waves; and (3) no codable ECG findings, used as the reference group. Mortality follow-up of the entire cohort was performed at 5, 10, 20, 30, and 40 years. The prevalence of isolated negative T waves at baseline was low, 1.6%, in these men from working populations. The hazard ratio (HR) for CHD mortality risk after 5 years in the isolated T-wave inversion group was more than 3 times greater than that in the reference group after adjusting for age, body mass index, cigarette smoking, systolic blood pressure, serum cholesterol and cohort (HR 3.68, 95% confidence interval [1.44-9.37]). Hazard ratio declined gradually with the length of follow-up but was still at 50% excess risk at 40-year follow-up (HR 1.51, 95% confidence interval [1.12-2.05]). T waves in the isolated T-wave inversion group were "flat" or less negative than 1mm (-100 µV) in the majority (86%) of inverted T waves. We conclude that inverted T waves with even a minor degree of negativity as an isolated ECG finding in men with no evidence of heart disease predict an excess short-term and long-term risk of CHD death.

Electrocardiographic estimates of action potential durations and transmural repolarization time gradients in healthy subjects and in acute coronary syndrome patients--profound differences by sex and by presence vs absence of diagnostic ST elevation.

Action potential duration (APD) changes increasing repolarization time (RT) dispersion are potentially arrhythmogenic. A repolarization model developed from electrocardiographic data of 5376 healthy men and women was used to derive parameter estimates for APD and RT and their transmural gradients (RT(grad) and APD(grad), respectively) in myocardial infarction patients, 126 with and 658 without diagnostic ST elevation (STEMI and NSTEMI, respectively). The model uses, as covariates, rate-adjusted QT and QT peak intervals (QT(a) and QT(pa), respectively) and diagonal crossmural RT(grad) derived as T(p)-T(xd), the interval from T(p) to the inflection point at descending limb of global T wave. An additional parameter is Θ(T|T(ref)), the spatial angle between a subject's T vector and the average T vector of the normal reference group. If Θ(T|T(ref)) >0, QT(pa) is assigned to RT(epi) and QT(pa) + RT(grad) to RT(endo), with RT(epi) and RT(endo) assignments reversed if Θ(T|T(ref)) ≤0. Parameter estimates for APD(epi) and APD(endo) were shorter in men than in women (by 17 ms and 14 ms, respectively, P < .001 for both). Compared to the reference group, RT(epi) in the STEMI group was shortened by 14 ms in men and by 18 ms in women (P < .001 for both) with a lesser decrease in RT(endo) suggesting predominantly subepicardial ischemia. In NSTEMI only RT(endo) was shortened, by 6 ms in males (P < .01) and 10 ms in females (P < .001), suggesting subendocardial ischemia. RT(grad) signifying local crossmural RT dispersion was prolonged in STEMI by 8 ms in men and by 11 ms in men (P < .001 for both). RT(grad) was not changed significantly in NSTEMI. Rate-adjusted T(p)-T(e) interval signifying global RT dispersion was increased in both MI and in both sex groups (P <.001 for all). In conclusion, QT prolongation observed in NSTEMI without prolongation of RT(grad) and APD(epi) suggests a delay during terminal repolarization, and in contrast, in STEMI, QT is not changed significantly in spite of prolonged RT(grad) because of shortened APD(epi) and RT(epi). These repolarization abnormalities are not revealed by QT alone but readily by the repolarization model.

Electrocardiographic estimates of regional action potential durations and repolarization time subintervals reveal ischemia-induced abnormalities in acute coronary syndrome not evident from global QT.

We evaluated electrocardiogram estimates of repolarization times (RTs) and action potential durations (APD) separately for initial and terminal repolarization periods in a reference group of 5376 healthy men and women and in 125 acute coronary syndrome patients with and 657 without diagnostic ST elevation (ST-elevation myocardial infarction [STEMI] and non-STEMI [NSTEMI], respectively). Two key covariates in the model are the rate-adjusted QT peak interval (QT(pa)), assigned to earliest epicardial RT (RT(epi)), and (T(p)-T(xd)), the rate-invariant interval from T(p) to the inflection point (T(xd)) at T wave downstroke. (T(p)-T(xd)) defines the crossmural RT gradient (XMRT(grad)). Transmural RT(grad) (TMRT(grad)) is obtained as CosΘ(R(max)|T(max))*XMRT(grad), where Θ is the spatial angle between the maximal QRS and T vectors. Derived endocardial variables are the XMRT(endo), equal to QT(pa) + XMRT(grad) and TMRT(endo), equal to QT(pa) + TMRT(grad). Noting that excitation time (ET) and RT define APD, APD(epi) = RT(epi) - QR(p) in V6 and TMAPD(endo) = TMRT(endo)--10 milliseconds. Compared to the reference group, the estimates for APD(epi) and TMAPD(endo) were shortened in STEMI by 20 and 31 milliseconds, respectively, (p < 0.001 for both) signifying transmural ischemia. In contrast, in NSTEMI, TMAPD(endo) was shortened by 28 milliseconds (P < 0.001) with a lesser, 5 millisecond shortening of APD(epi), signifying subendocardial ischemia. QT was prolonged by 6 milliseconds in STEMI (P < 0.05) and by 8 milliseconds in NSTEMI (P < 0.001). Prolonged QT with shortened APD(epi) suggests that prolonged repolarization in terminal possibly non-ischemic regions accounts for QT prolongation in both myocardial infarction groups. These substantial differences in ischemia-induced regional manifestations of repolarization abnormalities revealed by the repolarization model were not evident from evaluation of the global QT.

Premature ventricular complexes and the risk of incident stroke: the Atherosclerosis Risk In Communities (ARIC) Study.

BACKGROUND AND PURPOSE: Premature ventricular complexes (PVCs) on a 2-minute electrocardiogram are a common, largely asymptomatic finding associated with increased risk of coronary heart disease and death. They may reflect atherosclerosis or other pathogenic pathways that predispose to arrhythmias and stroke. METHODS: We conducted a prospective evaluation of the Atherosclerosis Risk In Communities Study cohort (n=14,783) of middle-aged men and women to assess whether the presence of PVCs at study baseline (1987 to 1989) influenced the risk of incident stroke through December 31, 2004. RESULTS: PVCs were seen in 6.1% of the participants at baseline, and 729 (4.9%) had incident stroke. The unadjusted cumulative proportion of incident stroke in individuals with any PVC was 6.6% compared with 4.1% in those without PVC. The unadjusted hazard ratio of incident stroke in individuals with any PVC compared with those without any PVCs was 1.71 (95% CI, 1.33 to 2.20). Among individuals without hypertension and diabetes at baseline, PVCs were independently associated with incident stroke (hazard ratio: 1.72; 95% CI: 1.14 to 2.59). Among those with either diabetes or hypertension, the presence of any PVCs did not increase the risk of stroke. The association was stronger for noncarotid embolic stroke than for thrombotic stroke and its magnitude increased with higher frequency of PVCs. CONCLUSIONS: Frequent PVCs are associated with risk of incident stroke in participants free of hypertension and diabetes. This suggests that PVCs may contribute to atrioventricular remodeling or may be a risk marker for incident stroke, particularly embolic stroke.

Electrocardiographic abnormalities that predict coronary heart disease events and mortality in postmenopausal women: the Women's Health Initiative.

BACKGROUND: Information is limited about the independent prognostic value of repolarization abnormalities in women. METHODS AND RESULTS: We evaluated hazard ratios for ECG variables for combined fatal and nonfatal coronary heart disease (CHD) events and for CHD mortality using Cox regression in 38,283 Women's Health Initiative (WHI) participants during up to 9.2 years of follow-up. All risk models were adjusted for demographic, clinical, and therapeutic variables. Evaluated as single ECG variables, wide QRS/T angle and ECG-demonstrated myocardial infarction (ECG-MI) were the strongest predictors of CHD events, with hazard ratios (95% CI) of 1.90 (1.50 to 2.42) and 1.62 (1.29 to 2.03), respectively. Six other repolarization variables were also significant, strong predictors of CHD events. Wide QRS/T angle, ECG-MI, and QT prolongation appeared as dominant predictors when evaluated simultaneously with other ECG variables in a multiadjusted risk model. QRS/T angle, ECG-MI, and high QRS nondipolar voltage were the strongest predictors of CHD mortality, with hazard ratios of 2.70, 2.41, and 2.18, respectively. The risk increase ranged from 63% to 95% for the other 4 significant predictors. Five ECG abnormalities were identified as dominant mortality risk predictors: wide QRS/T angle, ECG-MI, high QRS nondipolar voltage, reduced heart rate variability, and QT prolongation (in the cardiovascular disease-free group only). CONCLUSIONS: Ventricular repolarization abnormalities in postmenopausal women are as important predictors of CHD events and CHD mortality as ECG-MI and other QRS abnormalities. Repolarization variables and QRS nondipolar voltage warrant attention in future investigations.

Electrocardiographic predictors of incident congestive heart failure and all-cause mortality in postmenopausal women: the Women's Health Initiative.

BACKGROUND: Information is limited about ECG predictors of the risk of incident congestive heart failure (CHF), particularly in women without overt manifestations of cardiovascular disease (CVD). METHODS AND RESULTS: We evaluated hazard ratios for incident CHF and all-cause mortality using Cox regression in 38,283 participants of the Women's Health Initiative (WHI) during a 9-year follow-up. All risk models were adjusted for demographic and available clinical and therapeutic variables (multivariable-adjusted models). A backward selection procedure was used to identify dominant predictors among those that were significant as individual ECG predictors. Eleven ECG variables were significant predictors of incident CHF, with none of them having a significant interaction with baseline CVD status. From 6 dominant ECG predictors, wide QRS/T angle had a nearly 3-fold increased risk in multivariable-adjusted single ECG variable models. Two other repolarization variables, STV5 depression and high TV1 amplitude, and 2 QRS-related variables, QRS non-dipolar voltage and myocardial infarction (MI) by ECG, were all associated with &2-fold increase of incident CHF risk. Overall, 11 of the 12 ECG variables were significant predictors of all-cause mortality. Four variables had a significant interaction with CVD status requiring stratification. Three among these 4 were strong, dominant predictors in the CVD group: ECG MI, wide QRS/T angle, and low TV5 amplitude had risk increase from >2-fold to 3-fold, with considerably lower risks in the CVD-free group. CONCLUSIONS: Several repolarization variables in postmenopausal women are predictors of the risk of incident CHF and all-cause mortality as important as old ECG MI.

Alcohol consumption and risk and prognosis of atrial fibrillation among older adults: the Cardiovascular Health Study.

BACKGROUND: The relationship of alcohol consumption with risk of atrial fibrillation (AF) is inconsistent in previous studies, and its relationship with prognosis of AF is undetermined. METHODS: As part of the Cardiovascular Health Study, a population-based cohort of adults 65 years and older from 4 US communities, 5609 participants reported their use of beer, wine, and spirits yearly. We identified cases of AF with routine study electrocardiograms and validated discharge diagnoses from hospitalizations. RESULTS: A total of 1232 cases of AF were documented during a mean of 9.1 years of follow-up. Compared with long-term abstainers, the multivariable-adjusted hazard ratios were 1.25 (95% CI, 1.02-1.54) among former drinkers, 1.09 (95% CI, 0.94-1.28) among consumers of less than 1 drink per week, 1.00 (95% CI, 0.84-1.19) among consumers of 1 to 6 drinks per week, 1.06 (95% CI, 0.82-1.37) among consumers of 7 to 13 drinks per week, and 1.09 (95% CI, 0.88-1.37) among consumers of 14 or more drinks per week (P trend = 0.64). In analyses of mortality among participants with AF, the hazard ratios were 1.27 (95% CI, 1.06-1.52) among former drinkers, 0.94 (95% CI, 0.76-1.18) among consumers of less than 1 drink per week, 0.98 (95% CI, 0.78-1.23) among consumers of 1 to 6 drinks per week, 0.73 (95% CI, 0.51-1.03) among consumers of 7 to 13 drinks per week, and 0.81 (95% CI, 0.59-1.11) among consumers of 14 or more drinks per week (P trend = 0.12). CONCLUSIONS: Current moderate alcohol consumption is not associated with risk of AF or with risk of death after diagnosis of AF, but former drinking identifies individuals at higher risk.

Comparison of the prognostic significance of the electrocardiographic QRS/T angles in predicting incident coronary heart disease and total mortality (from the atherosclerosis risk in communities study).

Spatial QRS/T angle and spatial T-wave axis were shown to be strong independent predictors of incident coronary heart disease (CHD) and total mortality, but they are not routinely available. We evaluated whether frontal plane QRS/T angle, easily obtained as the difference between frontal plane axes of QRS and T, provides a suitable substitute for spatial QRS/T angle as a risk predictor. Our study consisted of 13,973 participants from the ARIC Study. Outcome variables were incident CHD and total mortality during a median follow-up of 14 years. Electrocardiographic variables were categorized as abnormal (>/=95th percentile), borderline (>/=75th and <95th percentile), and normal (<75th percentile) separately for men and women. Cox regression was used to assess the effect of electrocardiographic variables on risk of each outcome. The normal category was considered the reference cell. With adjustment for demographic and clinical characteristics, both QRS/T angles were approximately equally strong predictors of total mortality with >50% increased risk. Spatial QRS/T angle was a stronger predictor of incident CHD in women, with a 114% increased risk, but it was not significantly associated with risk of incident CHD in men. Similarly, frontal plane QRS/T angle was statistically significant for only women with a 74% increased risk of incident CHD. In conclusion, frontal plane QRS/T angle as an easily derived risk measure is a suitable clinical substitute for spatial QRS/T angle for risk prediction.

Electrocardiographic predictors of new-onset heart failure in men and in women free of coronary heart disease (from the Atherosclerosis in Communities [ARIC] Study).

We compared the prognostic value of 12 electrocardiographic (ECG) variables in predicting risk of new-onset heart failure (HF) in a subgroup of 13,555 participants of the Atherosclerosis Risk in Communities (ARIC) study who were considered free of coronary heart disease at the onset of the study. Cox proportional hazards models were used to evaluate risk of HF for the highest decile of the distribution of each ECG variable (lowest decile for ST and T amplitudes in lead V(5)), with the remaining deciles as reference groups. Risk models were adjusted for demographic and clinical variables. In univariate Cox regression models, in men 11 and in women 8 of the 12 ECG variables were significant, strong predictors of risk of new-onset HF. Subsequently, 8 ECG variables with low mutual correlations were entered simultaneously into a multivariate Cox regression model. In men, large left ventricular mass by electrocardiogram, QT prolongation, and increased heart rate were the strongest independent predictors of new-onset HF, each with a twofold increased risk. Other independent predictors in men were ST depression in lead V(5), wide QRS/T angle, and old (silent) myocardial infarction, each with a >50% increased risk of incident HF. In women, QRS nondipolar voltage was associated with an 87% increased risk of incident HF, and other independent predictors, as in men, were wide QRS/T angle and increased heart rate. In conclusion, several ECG abnormalities are manifestations of evolving HF in men and women considered free of coronary heart disease.