Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events.

BACKGROUND: Childhood cardiovascular risk factors predict subclinical adult cardiovascular disease, but links to clinical events are unclear. METHODS: In a prospective cohort study involving participants in the International Childhood Cardiovascular Cohort (i3C) Consortium, we evaluated whether childhood risk factors (at the ages of 3 to 19 years) were associated with cardiovascular events in adulthood after a mean follow-up of 35 years. Body-mass index, systolic blood pressure, total cholesterol level, triglyceride level, and youth smoking were analyzed with the use of i3C-derived age- and sex-specific z scores and with a combined-risk z score that was calculated as the unweighted mean of the five risk z scores. An algebraically comparable adult combined-risk z score (before any cardiovascular event) was analyzed jointly with the childhood risk factors. Study outcomes were fatal cardiovascular events and fatal or nonfatal cardiovascular events, and analyses were performed after multiple imputation with the use of proportional-hazards regression. RESULTS: In the analysis of 319 fatal cardiovascular events that occurred among 38,589 participants (49.7% male and 15.0% Black; mean [±SD] age at childhood visits, 11.8±3.1 years), the hazard ratios for a fatal cardiovascular event in adulthood ranged from 1.30 (95% confidence interval [CI], 1.14 to 1.47) per unit increase in the z score for total cholesterol level to 1.61 (95% CI, 1.21 to 2.13) for youth smoking (yes vs. no). The hazard ratio for a fatal cardiovascular event with respect to the combined-risk z score was 2.71 (95% CI, 2.23 to 3.29) per unit increase. The hazard ratios and their 95% confidence intervals in the analyses of fatal cardiovascular events were similar to those in the analyses of 779 fatal or nonfatal cardiovascular events that occurred among 20,656 participants who could be evaluated for this outcome. In the analysis of 115 fatal cardiovascular events that occurred in a subgroup of 13,401 participants (31.0±5.6 years of age at the adult measurement) who had data on adult risk factors, the adjusted hazard ratio with respect to the childhood combined-risk z score was 3.54 (95% CI, 2.57 to 4.87) per unit increase, and the mutually adjusted hazard ratio with respect to the change in the combined-risk z score from childhood to adulthood was 2.88 (95% CI, 2.06 to 4.05) per unit increase. The results were similar in the analysis of 524 fatal or nonfatal cardiovascular events. CONCLUSIONS: In this prospective cohort study, childhood risk factors and the change in the combined-risk z score between childhood and adulthood were associated with cardiovascular events in midlife. (Funded by the National Institutes of Health.).

Obesity during childhood is associated with higher cancer mortality rate during adulthood: the i3C Consortium.

BACKGROUND: In high-income countries, cancer is the leading cause of death among middle-aged adults. Prospective data on the effects of childhood risk exposures on subsequent cancer mortality are scarce. METHODS: We examined whether childhood body mass index (BMI), blood pressure, glucose and lipid levels were associated with adult cancer mortality, using data from 21,012 children enrolled aged 3-19 years in seven prospective cohort studies from the U.S., Australia, and Finland that have followed participants from childhood into adulthood. Cancer mortality (cancer as a primary or secondary cause of death) was captured using registries. RESULTS: 354 cancer deaths occurred over the follow-up. In age-, sex, and cohort-adjusted analyses, childhood BMI (Hazard ratio [HR], 1.13; 95% confidence interval [CI] 1.03-1.24 per 1-SD increase) and childhood glucose (HR 1.22; 95%CI 1.01-1.47 per 1-SD increase), were associated with subsequent cancer mortality. In a multivariable analysis adjusted for age, sex, cohort, and childhood measures of fasting glucose, total cholesterol, triglycerides, and systolic blood pressure, childhood BMI remained as an independent predictor of subsequent cancer mortality (HR, 1.24; 95%CI, 1.03-1.49). The association of childhood BMI and subsequent cancer mortality persisted after adjustment for adulthood BMI (HR for childhood BMI, 1.35; 95%CI 1.12-1.63). CONCLUSIONS: Higher childhood BMI was independently associated with increased overall cancer mortality.

Childhood BMI and Fasting Glucose and Insulin Predict Adult Type 2 Diabetes: The International Childhood Cardiovascular Cohort (i3C) Consortium.

OBJECTIVE: To examine childhood BMI, fasting glucose, and insulin in relation to incident adult type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: We used data from the International Childhood Cardiovascular Cohort (i3C) Consortium. Data included childhood (age 3-19 years) measurements obtained during the 1970s-1990s; a health questionnaire, including self-report of adult T2DM (occurrence age, medication use) obtained at mean age 40 years; and a medical diagnosis registry (Finland). RESULTS: The sample included 6,738 participants. Of these, 436 (6.5%) reported onset of T2DM between ages 20 and 59 (mean 40.8) years, and 86% of them reported use of a confirmed antidiabetic medication. BMI and glucose (age and sex standardized) were associated with incident T2DM after adjustment for cohort, country, sex, race, age, and calendar year of measurement. Increasing levels of childhood BMI and glucose were related to an incrementally increased risk of T2DM beginning at age 30 years, beginning at cut points <95th percentile for BMI and <100 mg/dL for glucose. Insulin was positively associated with adult T2DM after adjustment for BMI and glucose and added to T2DM discrimination. CONCLUSIONS: Childhood BMI and glucose are predictors of adult T2DM at levels previously considered to be within the normal range. These easy-to-apply measurements are appealing from a clinical perspective. Fasting insulin has the potential to be an additional predictor.

Childhood/Adolescent Smoking and Adult Smoking and Cessation: The International Childhood Cardiovascular Cohort (i3C) Consortium.

Background Despite declining US adolescent smoking prevalence from 40% among 12th graders in 1995 to around 10% in 2018, adolescent smoking is still a significant problem. Using the International Childhood Cardiovascular Cohort (i3C) Consortium, which includes 7 international cohorts recruited in childhood and followed into adulthood, the present study was designed to confirm the important relation between adolescent smoking and daily adult smoking and present new data on adult smoking into the forties and comparison of smoking in the United States, Finland, and Australia. Methods and Results Childhood smoking experience during ages 6 to 19 in the 1970s and 1980s was classifiable in 6687 i3C participants who also provided smoking status in their twenties and forties through 2011-2018. Prevalence of daily smoking in their twenties was directly related to degree of smoking during adolescence and inversely related to the age at which that smoking experience occurred (P trend, <0.001). Similar patterns were observed for prediction of smoking during age forties. Among the 2465 smokers in their twenties, cessation by their forties was generally inverse to degree of smoking in ages 6 to 19 (P trend, <0.001). Prevalence of smoking during adolescence and adulthood was similar among US, Finnish, and Australian participants. Conclusions These long-term follow-up data show that smoking intensity increased throughout adolescence. Prevalence of adult smoking and cessation by the forties were both correlated with levels of childhood smoking intensity. These data lend support to preventive strategies designed to reduce, delay, or eliminate any youth access to cigarettes.

Prediction of adult class II/III obesity from childhood BMI: the i3C consortium.

BACKGROUND AND OBJECTIVES: Adult class II/III obesity (BMI ≥ 35 kg/m2) has significant adverse health outcomes. Early prevention and treatment are critical, but prospective childhood risk estimates are lacking. This study aimed to define the prospective risk of adult class II/III obesity, using childhood BMI. METHODS: Children ages 3-19 years enrolled in cohorts of the International Childhood Cardiovascular Cohort (i3C) consortium with measured BMI assessments in childhood and adulthood were included. Prospective risk of adult class II/III obesity was modeled based on childhood age, sex, race, and BMI. RESULTS: A total of 12,142 individuals (44% male, 85% white) were assessed at median age 14 [Interquartile range, IQR: 11, 16] and 33 [28, 39] years. Class II/III adult obesity developed in 6% of children with normal weight; 29% of children with overweight; 56% of children with obesity; and 80% of children with severe obesity. However, 38% of the 1440 adults with class II/III obesity (553/1440) were normal weight as children. Prospective risk of adult class II/III obesity varied by age, sex, and race within childhood weight status classifications, and is notably higher for girls, black participants, and those in the United States. The risk of class II/III obesity increased with older adult age. CONCLUSIONS: Children with obesity or severe obesity have a substantial risk of adult class II/III obesity, and observed prospective risk estimates are now presented by age, sex, race, and childhood BMI. Clinical monitoring of children's BMI for adult class II/III obesity risk may be especially important for females and black Americans.

Predicting overweight and obesity in young adulthood from childhood body-mass index: comparison of cutoffs derived from longitudinal and cross-sectional data.

BACKGROUND: Historically, cutoff points for childhood and adolescent overweight and obesity have been based on population-specific percentiles derived from cross-sectional data. To obtain cutoff points that might better predict overweight and obesity in young adulthood, we examined the association between childhood body-mass index (BMI) and young adulthood BMI status in a longitudinal cohort. METHODS: In this study, we used data from the International Childhood Cardiovascular Cohort (i3C) Consortium (which included seven childhood cohorts from the USA, Australia, and Finland) to establish childhood overweight and obesity cutoff points that best predict BMI status at the age of 18 years. We included 3779 children who were followed up from 1970 onwards, and had at least one childhood BMI measurement between ages 6 years and 17 years and a BMI measurement specifically at age 18 years. We used logistic regression to assess the association between BMI in childhood and young adulthood obesity. We used the area under the receiver operating characteristic curve (AUROC) to assess the ability of fitted models to discriminate between different BMI status groups in young adulthood. The cutoff points were then compared with those defined by the International Obesity Task Force (IOTF), which used cross-sectional data, and tested for sensitivity and specificity in a separate, independent, longitudinal sample (from the Special Turku Coronary Risk Factor Intervention Project [STRIP] study) with BMI measurements available from both childhood and adulthood. FINDINGS: The cutoff points derived from the longitudinal i3C Consortium data were lower than the IOTF cutoff points. Consequently, a larger proportion of participants in the STRIP study was classified as overweight or obese when using the i3C cutoff points than when using the IOTF cutoff points. Especially for obesity, i3C cutoff points were significantly better at identifying those who would become obese later in life. In the independent sample, the AUROC values for overweight ranged from 0·75 (95% CI 0·70-0·80) to 0·88 (0·84-0·93) for the i3C cutoff points, and the corresponding values for the IOTF cutoff points ranged from 0·69 (0·62-0·75) to 0·87 (0·82-0·92). For obesity, the AUROC values ranged from 0·84 (0·75-0·93) to 0·90 (0·82-0·98) for the i3C cutoff points and 0·57 (0·49-0·66) to 0·76 (0·65-0·88) for IOTF cutoff points. INTERPRETATION: The childhood BMI cutoff points obtained from the i3C Consortium longitudinal data can better predict risk of overweight and obesity in young adulthood than can standards that are currently used based on cross-sectional data. Such cutoff points should help to more accurately identify children at risk of adult overweight or obesity. FUNDING: None.

Periprocedural Stroke and Myocardial Infarction as Risks for Long-Term Mortality in CREST.

BACKGROUND: The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) previously reported increased mortality in patients who sustained a periprocedural stroke or cardiac event (myocardial infarction [MI] or biomarker only) in follow-up to 4 years. We now extend these observations to 10 years. METHODS AND RESULTS: CREST is a randomized controlled trial designed to compare the outcomes of carotid stenting versus carotid endarterectomy. Proportional hazards models were used to assess the association between mortality and periprocedural stroke, MI, or biomarker-only events. For 10-year follow-up, patients with periprocedural stroke were at 1.74× the risk of death compared with those without stroke (adjusted hazard ratio [HR]=1.74; 95% CI, 1.21-2.50; P<0.003). This increased risk was driven by increased early (between 0 and 90 days) mortality (adjusted HR=14.41; 95% CI, 5.33-38.94; P<0.0001), with no significant increase in late (between 91 days and 10 years) mortality (adjusted HR=1.40; 95% CI, 0.93-2.10; P=0.11). Patients with a protocol MI were at 3.61× increased risk of death compared with those without MI (adjusted HR=3.61; 95% CI, 2.28-5.73; P<0.0001), with an increased hazard both early (adjusted HR=8.20; 95% CI, 1.86-36.2; P=0.006) and late (adjusted HR=3.40; 95% CI, 2.09-5.53; P<0.0001). Patients with a biomarker-only event were at 2.04× increased risk overall (adjusted HR=2.04; 95% CI, 1.09-3.84; P=0.03) than those without MI, with an increased early hazard (adjusted HR=8.44; 95% CI, 1.09-65.5; P=0.04) and a suggestive but nonsignificant association toward higher 91-day to 10-year risk (1.88; 95% CI, 0.97-3.64; P=0.062) contributing to the increased risk. CONCLUSIONS: In the CREST trial, patients with periprocedural events demonstrate a substantial increase in future mortality to 10 years. For stroke, this risk is largely confined to an early time frame while periprocedural MI or biomarker-only events confer a continuous increased mortality for 10 years. Strategies to reduce periprocedural events and to optimize the evaluation and management of patients with cardiac events should be considered in efforts to reduce not only early but also long-term mortality. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00004732.

A comprehensive evaluation of the genetic architecture of sudden cardiac arrest.

Aims: Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA. Methods and results: We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk. Conclusions: Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.

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.

Antihypertensive Therapies and Left Ventricular Hypertrophy.

PURPOSE OF REVIEW: It is widely accepted that successful lowering of blood pressure (BP) in patients with hypertension leads to regression of left ventricular hypertrophy (LVH). However, whether differences exist among pharmacological BP-lowering therapies is debated. In this report, we discuss these differences in light of recent literature and the position of extant practice guidelines. RECENT FINDINGS: Studies comparing the effects of antihypertensive classes on LVH regression reached different conclusions, but the overall direction which is reflected in current society guidelines is that successful lowering of BP is more important than selection of an individual antihypertensive class. Nevertheless, some practice guidelines added statements about considering a specific antihypertensive class for its potential benefit such as angiotensin-converting enzyme inhibitors and/or excluding a class such as direct vasodilators. On the other hand, reports have been consistent about the more favorable effect of intensive BP-lowering strategy (target systolic BP < 120 mmHg) compared to standard BP lowering (target systolic BP > 140 mmHg), which is not yet discussed in the current practice guidelines. Successful lowering of BP leads to LVH regression. While reports have been inconsistent about differences among antihypertensive classes, lowering BP beyond currently recommended levels has consistently showed a greater effect on LVH regression.

The Metabolic Syndrome and Risk of Sudden Cardiac Death: The Atherosclerosis Risk in Communities Study.

BACKGROUND: Prior studies have demonstrated a link between the metabolic syndrome and increased risk of cardiovascular mortality. Whether the metabolic syndrome is associated with sudden cardiac death is uncertain. METHODS AND RESULTS: We characterized the relationship between sudden cardiac death and metabolic syndrome status among participants of the ARIC (Atherosclerosis Risk in Communities) Study (1987-2012) free of prevalent coronary heart disease or heart failure. Among 13 168 participants, 357 (2.7%) sudden cardiac deaths occurred during a median follow-up of 23.6 years. Participants with the metabolic syndrome (n=4444) had a higher cumulative incidence of sudden cardiac death than those without it (n=8724) (4.1% versus 2.3%, P<0.001). After adjustment for participant demographics and clinical factors other than components of the metabolic syndrome, the metabolic syndrome was independently associated with sudden cardiac death (hazard ratio, 1.70, 95% confidence interval, 1.37-2.12, P<0.001). This relationship was not modified by sex (interaction P=0.10) or race (interaction P=0.62) and was mediated by the metabolic syndrome criteria components. The risk of sudden cardiac death varied according to the number of metabolic syndrome components (hazard ratio 1.31 per additional component of the metabolic syndrome, 95% confidence interval, 1.19-1.44, P<0.001). Of the 5 components, elevated blood pressure, impaired fasting glucose, and low high-density lipoprotein were independently associated with sudden cardiac death. CONCLUSIONS: We observed that the metabolic syndrome was associated with a significantly increased risk of sudden cardiac death irrespective of sex or race. The risk of sudden cardiac death was proportional to the number of metabolic syndrome components.

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.

Electrocardiographic measures of left ventricular hypertrophy in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

Left ventricular hypertrophy (LVH) predicts cardiovascular risk in hypertensive patients. We analyzed baseline/follow-up electrocardiographies in 26,376 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial participants randomized to amlodipine (A), lisinopril (L), or chlorthalidone (C). Prevalent/incident LVH was examined using continuous and categorical classifications of Cornell voltage. At 2 and 4 years, prevalence of LVH in the C group (5.57%; 6.14%) was not statistically different from A group (2 years: 5.47%; P = .806, 4 years: 6.54%; P = .857) or L group (2 years: 5.64%; P = .857, 4 years: 6.50%; P = .430). Incident LVH followed similarly, with no difference at 2 years for C (2.99%) compared to A (2.57%; P = .173) or L (3.16%; P = .605) and at 4 years (C = 3.52%, A = 3.29%, L = 3.71%; P = .521 C vs. A, P = .618 C vs. L). Mean Cornell voltage decreased comparably across treatment groups (Δ baseline, 2 years = +3 to -27 µV, analysis of variance P = .8612; 4 years = +10 to -17 µV, analysis of variance P = .9692). We conclude that risk reductions associated with C treatment in secondary end points of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial cannot be attributed to differential improvements in electrocardiography LVH.

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.

Bundle branch blocks and the risk of mortality in the Atherosclerosis Risk in Communities study.

AIMS: The main objective of our study was to evaluate the associations between different categories of bundle branch blocks (BBBs) and mortality and to consider possible impact of QRS prolongation in these associations. METHODS: This analysis included 15 408 participants (mean age 54 years, 55.2% women, and 26.9% blacks) from the Atherosclerosis Risk in Communities study. We used Cox regression to examine associations between left BBB (LBBB), right BBB (RBBB) and indetermined type of ventricular conduction defect [intraventricular conduction defect (IVCD)] with coronary heart disease (CHD) death and all-cause mortality. RESULTS: During a mean 21 years of follow-up, 4767 deaths occurred; of these, 728 were CHD deaths. Compared to No-BBB, LBBB and IVCD were strongly associated with increased CHD death (hazard ratios 4.11 and 3.18, respectively; P < 0.001 for both). Furthermore, compared to No-BBB with QRS duration less than 100 ms, CHD mortality risk was increased 1.33-fold for the No-BBB group with QRS duration 100-109 ms, and 1.48-fold with QRS duration 110-119 ms, 3.52-fold for pooled LBBB-IVCD group with QRS duration less than 140 ms and 4.96-fold for pooled LBBB-IVCD group with QRS duration at least 140 ms (P < 0.001). However, mortality risk was not significantly increased for lone RBBB. For all-cause mortality, trends similar to those for CHD death were observed within the BBB groups, although at lower levels of risk. CONCLUSION: Prevalent LBBB and IVCD, but not RBBB, are associated with increased risk of CHD death and all-cause mortality. Mortality risk is further increased as the QRS duration is prolonged above 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.

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.

Childhood wrist circumference is not a predictor of insulin resistance in adulthood.

We sought to determine whether childhood wrist circumference predicts insulin resistance in adulthood. Measures were taken in prepubertal children and then approximately 30 years later in the same subjects as adults. Our findings suggest that wrist circumference in childhood is not a predictor of insulin resistance in adulthood.

The paradox of atrial fibrillation in African Americans.

The reported lower prevalence and incidence of atrial fibrillation (AF) despite the higher prevalence of AF risk factors in African Americans compared to Caucasian whites has been referred to as the paradox of AF in African Americans. In this report we highlight this paradox and address potential explanations using data from several US populations studies. These possible explanations include limited methodology to detect AF patterns that are harder to detect (e.g. paroxysmal/intermittent AF or atrial flutter) coupled with the possibility of African Americans having more of these patterns, differential access to health care with African Americans having less access and subsequently less detected AF, survival bias with Caucasian whites living longer and subsequently having more AF, and finally differential impact of AF risk factors with Caucasian whites being more affected or African Americans less affected by AF risk factors whether this is genetically determined or via other unknown predispositions.