Association of psychosocial factors with short-term resting heart rate variability: The atherosclerosis risk in communities study

BACKGROUND: Psychosocial factors predict heart disease risk, but our understanding of underlying mechanisms is limited. We sought to evaluate the physiologic correlates of psychosocial factors by measuring their relationships with heart rate variability (HRV), a measure of autonomic health, in the ARIC (Atherosclerosis Risk in Communities) study. We hypothesize that increased psychosocial stress associates with lower HRV. METHODS AND RESULTS: We studied 9331 participants in ARIC with short-term HRV data at visits 2 and 4. The mean (SD) age was 54.4 (5.7) years, 55% were women, and 25% were Black. Psychosocial factors included: (1) vital exhaustion (VE), (2) anger proneness, a personality trait, and (3) perceived social support. Linear models adjusted for sociodemographic and cardiovascular risk factors. Low frequency HRV (ln ms2) was significantly lower in the highest versus lowest quartiles of VE (B=−0.14, 95% CI, −0.24 to −0.05). When comparing this effect to age (B=−0.04, 95% CI, −0.05 to −0.04), the difference was equivalent to 3.8 years of accelerated aging. Perceived social support associated with lower time-domain HRV. High VE (versus low VE) also associated with greater decreases in low frequency over time, and both anger and VE associated with greater increases in resting heart rate over time. Survival analyses were performed with Cox models, and no evidence was found that HRV ex-plains the excess risk found with high VE and low perceived social support. CONCLUSIONS: Vital exhaustion, and to a lesser extent anger and social support, were associated with worse autonomic function and greater adverse changes over time

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

Electrocardiographic intervals associated with incident atrial fibrillation: Dissecting the QT interval

Background Prolongation of the QT interval has been associated with an increased risk of developing atrial fibrillation (AF), but the responsible mechanism remains unknown. Objectives The aims of this study were to subdivide the QT interval into its components and identify the resultant electrocardiographic interval(s) responsible for the association with AF. Methods Predefined QT-interval components were assessed for association with incident AF in the Atherosclerosis Risk in Communities study using Cox proportional hazards models. Hazard ratios (HRs) were calculated per 1-SD increase in each component. Among QT-interval components exhibiting significant associations, additional analyses evaluating long extremes, defined as greater than the 95th percentile, were performed. Results Of the 14,625 individuals, 1505 (10.3%) were diagnosed with incident AF during a mean follow-up period of 17.6 years. After multivariable adjustment, QT-interval components involved in repolarization, but not depolarization, exhibited significant associations with incident AF, including a longer ST segment (HR 1.27; 95% confidence interval [CI] 1.14–1.41; P <.001) and a prolonged T-wave onset to T-wave peak (T-onset to T-peak) (HR 1.13; 95% CI 1.07–1.20; P <.001). Marked prolongation of the ST segment (HR 1.31; 95% CI 1.04–1.64; P =.022) and T-onset to T-peak (HR 1.36; 95% CI 1.09–1.69; P =.006) was also associated with an increased risk of incident AF. Conclusion The association between a prolonged QT interval and incident AF is primarily explained by components involved in ventricular repolarization: prolongation of the ST segment and T-onset to T-peak. These observations suggest that prolongation of phases 2 and 3 of the cardiac action potential drives the association between the QT interval and AF risk

Association of Sleep Apnea, Diagnosed by Self-Reported Physician Diagnosis or Hospital Discharge Codes, With Atrial Fibrillation and Ectopy Using Ambulatory Electrocardiogram in the ARIC Study

Sleep apnea is associated with cardiac arrhythmias1 such as atrial fibrillation (AF), premature ventricular contractions (PVC), and premature atrial contractions (PAC). Mechanisms that may explain this association include autonomic imbalance, hypertension, intermittent hypoxia, and atrial remodeling. However, prior studies of sleep apnea and cardiac arrhythmias relied on a single ten second,12-lead electrocardiogram, and/or hospital medical records, which would miss paroxysmal, asymptomatic, and intermittent arrhythmias. The Reveal XT-SA study reported that using a medically implanted device for cardiac monitoring in patients with severe obstructive SA may help to identify newly detected AF, however application of this study’s findings to our work was limited as the Reveal XT-SA study used a small sample size in a clinical population.4 Our study overcomes these limitations by adding standardized 48-hour continuous ambulatory ECG (aECG) monitoring to the population-based Atherosclerosis Risk in Communities (ARIC) study to examine the association between sleep apnea and AF, PACs, and PVCs

American Heart Association's Life Simple 7 and risk of atrial fibrillation in a population without known cardiovascular disease: The ARIC (Atherosclerosis risk in communities) study

Background-The American Heart Association has defined metrics of ideal cardiovascular health known as Life's Simple 7 (LS7) to prevent cardiovascular disease. We examined the association between LS7 and incident atrial fibrillation (AF) in a biracial cohort of middle- and older-aged adults without known cardiovascular disease. Methods and Results-This analysis included 13 182 ARIC (Atherosclerosis Risk in Communities) study participants (mean baseline age=54±5.7 years; 56% women; 25% black) free of AF and cardiovascular disease. An overall LS7 score was calculated as the sum of the LS7 component scores and classified as inadequate (0-4), average (5-9), or optimal (10-14) cardiovascular health. The primary outcome was incident AF, identified primarily by ECG and hospital discharge coding of AF through December 31, 2014. A total of 2266 (17%) incident AF cases were detected over a median follow-up of 25.1 years. Compared with the inadequate category (n=1057), participants in the average (n=8629) and optimal (n=3496) categories each had a lower risk of developing AF in a multivariable Cox proportional hazards model (hazard ratio 0.59, 95% confidence interval 0.51, 0.67 for average; and hazard ratio 0.38, 95% confidence interval 0.32, 0.44 for optimal). In a similar model, a 1-point-higher LS7 score was associated with a 12% lower risk of incident AF (hazard ratio 0.88, 95% confidence interval 0.86, 0.89). Conclusions-A higher LS7 score is strongly associated with a lower risk of AF in individuals without baseline cardiovascular disease. Determining whether interventions that improve the population's cardiovascular health also reduce AF incidence is needed

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

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

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

Serum Metabolomics and Incidence of Atrial Fibrillation (from the Atherosclerosis Risk in Communities Study)

We have previously identified associations of 2 circulating secondary bile acids (glycocholenate and glycolithocolate sulfate) with atrial fibrillation (AF) risk in 1,919 blacks in the Atherosclerosis Risk in Communities cohort. We aimed to replicate these findings in an independent sample of 2,003 white and black Atherosclerosis Risk in Communities participants, and performed a new metabolomic analysis in the combined sample of 3,922 participants, followed between 1987 and 2013. Metabolomic profiling was done in baseline serum samples using gas and liquid chromatography mass spectrometry. AF was ascertained from electrocardiograms, hospitalizations, and death certificates. We used multivariable Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) of AF by 1 standard deviation difference of metabolite levels. Over a mean follow-up of 20 years, 608 participants developed AF. Glycocholenate sulfate was associated with AF in the replication and combined samples (HR 1.10, 95% CI 1.00, 1.21 and HR 1.13, 95% CI 1.04, 1.22, respectively). Glycolithocolate sulfate was not related to AF risk in the replication sample (HR 1.02, 95% CI 0.92, 1.13). An analysis of 245 metabolites in the combined cohort identified 3 additional metabolites associated with AF after multiple-comparison correction: pseudouridine (HR 1.18, 95% CI 1.10, 1.28), uridine (HR 0.86, 95% CI 0.79, 0.93) and acisoga (HR 1.17, 95% CI 1.09, 1.26). In conclusion, we replicated a prospective association among a previously identified secondary bile acid, glycocholenate sulfate, and AF incidence, and identified new metabolites involved in nucleoside and polyamine metabolism as markers of AF risk

Lifetime Risk of Atrial Fibrillation by Race and Socioeconomic Status: ARIC Study (Atherosclerosis Risk in Communities)

Background: Limited information exists on the lifetime risk of atrial fibrillation (AF) in African Americans and by socioeconomic status. Methods: We studied 15 343 participants without AF at baseline from the ARIC (Atherosclerosis Risk in Communities) cohort recruited in 1987 to 1989 from 4 communities in the United States when they were 45 to 64 years of age. Participants have been followed through 2014. Incidence rates of AF were calculated dividing the number of new cases by person-years of follow-up. Lifetime risk of AF was estimated by a modified Kaplan-Meier method considering death as a competing risk. Participants' family income and education were obtained at baseline. Results: We identified 2760 AF cases during a mean follow-up of 21 years. Lifetime risk of AF was 36% (95% confidence interval, 32%-38%) in white men, 30% (95% confidence interval, 26%-32%) in white women, 21% (95% confidence interval, 13%-24%) in African American men, and 22% (95% confidence interval, 16%-25%) in African American women. Regardless of race and sex, incidence rates of AF decreased from the lowest to the highest categories of income and education. In contrast, lifetime risk of AF increased in individuals with higher income and education in most sex-race groups. Cumulative incidence of AF was lower in those with higher income and education compared with their low socioeconomic status counterparts through earlier life but was reversed after age 80. Conclusions: Lifetime risk of AF in the ARIC cohort was ≈1 in 3 among whites and 1 in 5 among African Americans. Socioeconomic status was inversely associated with cumulative incidence of AF before the last decades of life

Relationship between QRS duration and incident atrial fibrillation

Background: QRS duration (QRSd), a measure of ventricular conduction, has been associated with adverse cardiovascular outcomes, but its relationship with incident atrial fibrillation (AF) is poorly understood. Methods and results: This study included 15,314 participants from the Atherosclerosis Risk in Communities (ARIC) study who were free of AF at baseline. QRSd was automatically measured from resting 12-lead electrocardiograms (ECGs) at baseline. Incident AF cases were systematically ascertained using ECGs, hospital discharge diagnoses and death certificates. Multivariable adjusted Cox regression analyses were performed to investigate the relationship between QRSd and incident AF. Mean age of our population was 54 ± 6 years (55% females). During a median follow-up of 21.2 years, 2041 confirmed incident AF cases occurred. In multivariable adjusted Cox models, a 1-SD increase in QRSd was associated with a hazard ratio (HR) (95% CI) for AF of 1.05 (1.01; 1.10), p = 0.01. This relationship was significant among women (HR per 1-SD increase in QRSd (95% CI) 1.13 (1.06; 1.20), p < 0.001), but not among men (1.00 (0.95; 1.06), p = 0.97) (p for interaction 0.005). Compared to individuals with a QRSd <100 ms, the HRs for incident AF in individuals with a QRSd of 100–119 and ≥120 ms were 1.13 (1.02; 1.26) and 1.35 (1.08; 1.68), respectively (p for trend 0.002). Again, this relationship was significant among women (p for trend <0.001) but not among men (p for trend 0.23). Conclusion: In this large population-based study, QRSd was an independent predictor of incident AF among women, but not in men. Further studies are needed to better understand the underlying mechanisms