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Although advanced interatrial block (aIAB) is an established electrocardiographic phenotype, its prevalence, incidence, and prognostic significance in the general population are unclear. We examined the prevalence, incidence, and prognostic significance of aIAB in 14,625 (mean age = 54 ± 5.8 years; 26% black; 55% female) participants from the Atherosclerosis Risk in Communities (ARIC) study. aIAB was detected from digital electrocardiograms recorded during 4 study visits (1987 to 1989, 1990 to 1992, 1993 to 1995, and 1996 to 1998). Risk factors for the development of aIAB were examined using multivariable Poisson regression models with robust variance estimates. Cox regression was used to compute hazard ratios and 95% CIs for the association between aIAB, as a time-dependent variable, and atrial fibrillation (AF). AF was ascertained from study electrocardiogram data, hospital discharge records, and death certificates thorough 2010. A total of 69 participants (0.5%) had aIAB at baseline, and 193 (1.3%) developed aIAB during follow-up. The incidence for aIAB was 2.27 (95% CI 1.97 to 2.61) per 1,000 person-years. Risk factors for aIAB development included age, male gender, white race, antihypertensive medication use, low-density lipoprotein cholesterol, body mass index, and systolic blood pressure. In a Cox regression analysis adjusted for sociodemographics, cardiovascular risk factors, and potential confounders, aIAB was associated with an increased risk for AF (hazard ratio 3.09, 95% CI 2.51 to 3.79). In conclusion, aIAB is not uncommon in the general population. Risk factors for developing aIAB are similar to those for AF, and the presence of aIAB is associated with an increased risk for AF.

Background Silent myocardial infarction (SMI) frequently goes undetected, yet it is associated with increased cardiovascular morbidity and mortality. The impact of intensive systolic blood pressure (SBP) lowering on the risk of SMI in those with hypertension remains uncertain. Methods In this post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), participants with serial electrocardiograms (ECGs) during the trial were included. SPRINT investigated the benefit of intensive SBP lowering, aiming for < 120 mmHg compared to the standard SBP goal of < 140 mmHg. Incident SMI was defined as evidence of new MI on an ECG without adjudicated recognized myocardial infarction (RMI). Results During a median follow‐up of 3.9 years, a total of 234 MI events (55 SMI and 179 RMI) occurred. Intensive, compared to standard, SBP lowering resulted in a lower rate of SMI (incidence rate 1.1 vs. 2.3 cases per 1000 person‐years, respectively; HR [95% CI]: 0.48 [0.27–0.84]). Similarly, intensive, compared to standard, BP lowering reduced the risk of RMI (incidence rate 4.6 vs. 6.5 cases per 1000 person‐years, respectively; HR [95% CI]: 0.71 [0.52–0.95]). No significant differences were noted between the strength of the association of intensive BP control on lowering the risk of SMI and RMI (p‐value for HR differences = 0.23). Conclusions This study shows that in adults with hypertension, the benefits of intensive SBP lowering, compared with standard BP lowering, go beyond the prevention of RMI to include the prevention of SMI. Trial Registration ClinicalTrials.gov Identifier: NCT01206062. In this post hoc analysis of the SPRINT trial, intensive systolic blood pressure (SBP) lowering in individuals with high‐risk hypertension was associated with a reduced the risk of ECG‐based silent myocardial infarction (MI) compared to standard SBP lowering. This demonstrates additional benefits of intensive SBP treatment beyond preventing clinically recognized MI.

We recently described the association between periodontal disease (PD) and stroke risk. The purpose of this study was to test the association between PD, dental care utilization and incident atrial fibrillation (AF), as well as AF as a mediator to PD- stroke association. In dental cohort of the Atherosclerosis Risk in Communities Study (ARIC), participants without prior AF underwent full-mouth periodontal measurements. PD was defined on an ordinal scale as healthy (referent), mild, moderate and severe. In ARIC main cohort, participants were classified as regular or episodic dental care users. These patients were followed for AF, over 17 years. Cox proportional hazards models adjusted for AF risk factors were used to study relationships between PD severity, dental care utilization and AF. Mediation analysis was used to test if AF mediated the PD- stroke association. In dental ARIC cohort, 5,958 were assessed without prior AF, 754 were found to have AF. Severe PD was associated with AF on both univariable (crude HR, 1.54; 95% CI, 1.26-1.87) and multivariable (adjusted HR, 1.31, 95% CI, 1.06-1.62) analyses. Mediation analysis suggested AF mediates the association between PD and stroke. In the main ARIC cohort, 9,666 participants without prior AF were assessed for dental care use, 1558 were found to have AF. Compared with episodic users, regular users had a lower risk for AF on univariable (crude HR, 0.82, 95% CI, 0.74-0.90) and multivariable (adjusted HR, 0.88, 95% CI, 0.78-0.99) analyses. PD is associated with AF. The association may explain the PD-stroke risk. Regular users had a lower risk of incident AF compared with episodic users. [Display omitted]

Low heart rate variability (HRV) has been linked to increased total mortality in the general population; however, the relationship between low HRV and sudden cardiac death (SCD) is less well-characterized. The goal of this study was to evaluate the relationship between low HRV and SCD in a community-based cohort. Our cohort consisted of 12,543 participants from the Atherosclerosis Risk in Communities (ARIC) study. HRV measures were derived from 2-minute electrocardiogram recordings obtained during the baseline exam (1987-89). Time domain measurements included the standard deviation of all normal RR intervals (SDNN) and the root mean squared successive difference (r-MSSD). Frequency domain measurements included low frequency power (LF) and high frequency (HF) power. During a median follow-up of 13 years, 215 SCDs were identified from physician adjudication of all coronary heart disease deaths through 2001. In multivariable adjusted Cox proportional hazards models, each standard deviation decrement in SDNN, LF, and HF were associated with 24%, 27% and 16% increase in SCD risk, respectively. Low HRV is independently associated with increased risk of SCD in the general population.

Although current alcohol consumption is a risk factor for incident atrial fibrillation (AF), the more clinically relevant question may be whether alcohol cessation is associated with a reduced risk. We studied participants enrolled in the Atherosclerosis Risk in Communities Study (ARIC) between 1987 and 1989 without prevalent AF. Past and current alcohol consumption were ascertained at baseline and at 3 subsequent visits. Incident AF was ascertained via study ECGs, hospital discharge ICD-9 codes, and death certificates. Of 15,222 participants, 2,886 (19.0%) were former drinkers. During a median follow-up of 19.7 years, there were 1,631 cases of incident AF, 370 occurring in former consumers. Former drinkers had a higher rate of AF compared to lifetime abstainers and current drinkers. After adjustment for potential confounders, every decade abstinent from alcohol was associated with an approximate 20% (95% CI 11-28%) lower rate of incident AF; every additional decade of past alcohol consumption was associated with a 13% (95% CI 3-25%) higher rate of AF; and every additional drink per day during former drinking was associated with a 4% (95% CI 0-8%) higher rate of AF. Among former drinkers, the number of years of drinking and the amount of alcohol consumed may each confer an increased risk of AF. Given that a longer duration of abstinence was associated with a decreased risk of AF, earlier modification of alcohol use may have a greater influence on AF prevention.

Prolonged P-wave duration, a marker of left atrial abnormality, is associated with myocardial fibrosis, atrial fibrillation, and all-cause death. It is not known if prolonged P-wave duration is associated with sudden cardiac death (SCD) in the general population. We aimed to evaluate whether prolonged P-wave duration is independently associated with SCD risk in the Atherosclerosis Risk in Communities Study, a community-based prospective cohort study. We included 15,321 participants in our analysis (age 54.2 ± 5.7 years, 55.2% women, 26.4% black). Prolonged P-wave duration was defined as maximum P-wave duration >120 ms and was determined from 12-lead electrocardiograms obtained during 4 exams (1987 to 1999). SCD was physician adjudicated and defined as a sudden, pulseless condition in a previously stable patient without evidence for noncardiac cause of death. We used Cox proportional hazard models to assess the association between prolonged P-wave duration and SCD, adjusting for cardiovascular risk factors and conditions including atrial fibrillation. During a mean follow-up of 12.5 years (1987 to 2001), 268 SCDs were identified. The multivariable hazard ratio (95% confidence interval) of prolonged P-wave duration for SCD was 1.70 (1.31 to 2.20). This association was attenuated but remained significant after updating covariates to the end of follow-up with a hazard ratio of 1.35 (1.04 to 1.76). In conclusion, prolonged P-wave duration is independently associated with an increased risk of SCD in the general population. This association is independent of atrial fibrillation and is only partially mediated by shared cardiovascular risk factors.

Sick sinus syndrome (SSS) is a common indication for pacemaker implantation. Limited information exists on the association of sick sinus syndrome (SSS) with mortality and cardiovascular disease (CVD) in the general population. We studied 19,893 men and women age 45 and older in the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS), two community-based cohorts, who were without a pacemaker or atrial fibrillation (AF) at baseline. Incident SSS cases were validated by review of medical charts. Incident CVD and mortality were ascertained using standardized protocols. Multivariable Cox models were used to estimate the association of incident SSS with selected outcomes. During a mean follow-up of 17 years, 213 incident SSS events were identified and validated (incidence, 0.6 events per 1,000 person-years). After adjustment for confounders, SSS incidence was associated with increased mortality (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.14-1.70), coronary heart disease (HR 1.72, 95%CI 1.11-2.66), heart failure (HR 2.87, 95%CI 2.17-3.80), stroke (HR 1.56, 95%CI 0.99-2.46), AF (HR 5.75, 95%CI 4.43-7.46), and pacemaker implantation (HR 53.7, 95%CI 42.9-67.2). After additional adjustment for other incident CVD during follow-up, SSS was no longer associated with increased mortality, coronary heart disease, or stroke, but remained associated with higher risk of heart failure (HR 2.00, 95%CI 1.51-2.66), AF (HR 4.25, 95%CI 3.28-5.51), and pacemaker implantation (HR 25.2, 95%CI 19.8-32.1). Individuals who develop SSS are at increased risk of death and CVD. The mechanisms underlying these associations warrant further investigation.

Atrial fibrillation (AF) is associated with an increased risk of ischemic stroke and cardiovascular (CV) death. Whether modifiable lifestyle risk factors are associated with these CV outcomes in AF is unknown. Among Atherosclerosis Risk in Communities (ARIC) study and Cardiovascular Health Study (CHS) participants with incident AF, we estimated the risk of composite endpoint of ischemic stroke or CV death associated with candidate modifiable risk factor (smoking, heavy alcohol consumption, or high body mass index [BMI]), and computed the C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) of incorporating each factor into the CHA2DS2-VASc. Among 1222 ARIC (mean age: 63.4) and 756 CHS (mean age: 79.1) participants with incident AF, during mean follow-up of 6.9 years and 5.7 years, there were 332 and 335 composite events respectively. Compared with never smokers, current smokers had a higher incidence of the composite endpoint in ARIC [HR: 1.65 (1.21-2.26)] but not in CHS [HR: 1.05 (0.69-1.61)]. In ARIC, the addition of current smoking did not improve risk prediction over and above the CHA2DS2-VASc. No significant associations were observed with alcohol consumption or BMI with CVD outcomes in AF patients from either cohort. Smoking is associated with an increased risk of ischemic stroke or CV death in ARIC, which comprised mostly middle-aged to young-old (65-74 years), but not in CHS, which comprised mostly middle-old or oldest-old (≥75 years) adults with AF. However, addition of smoking to the CHA2DS2-VASc score did not improve risk prediction of these outcomes.

Reports on the association between the PR-interval and atrial fibrillation (AF) are conflicting. We hypothesized that inconsistencies stem from that fact that the PR-interval represents a composite of several distinct components. We examined the associations of the PR-interval and its components (P-wave onset to P-wave peak duration, P-wave peak to P-wave end duration, and PR-segment) with incident AF in 14,924 participants (mean age 54 ± 5.8 years; 26% black; 55% women) from the Atherosclerosis Risk In Communities study. The PR-interval and its components were automatically measured at baseline (1987 to 1989) from standard 12-lead electrocardiograms. PR-interval >200 ms was considered prolonged and values above the ninety-fifth percentile defined abnormal PR-interval components. AF was ascertained during follow-up through December 31, 2010. Over a median follow-up of 21.2 years, 1,985 participants (13%) developed AF. Prolonged PR-interval was associated with an increased risk of AF (hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.02 to 1.40). However, PR-interval components showed varying levels of association with AF (P-wave onset to P-wave peak duration: HR 1.57, 95% CI 1.31 to 1.88; P-wave peak to P-wave end duration: HR 1.20, 95% CI 0.99 to 1.46; and PR-segment: HR 1.05, 95% CI 0.85 to 1.29). In addition, the components of the PR-interval had weak-to-moderate correlation with each other (correlation r ranged from −0.44 to 0.06). In conclusion, our findings suggest the PR-interval represents a composite of distinct components that are not uniformly associated with AF. Without considering the contribution of each component, inconsistent associations between the PR-interval and AF are inevitable.

No scores presently exist to predict bleeding in atrial fibrillation (AF) populations using direct oral anticoagulants (DOACs). We used data from two independent healthcare claims databases to develop and validate a predictive model of major bleeding in a contemporary AF population. Patients with non-valvular AF initiating oral anticoagulation were identified in the MarketScan databases from 2007-2014. Using Cox regression models in 1000 bootstrapped samples, we developed a model that selected variables predicting major bleeding in the first year after anticoagulant initiation. The final model was validated in patients with non-valvular AF in the Optum Clinformatics database in the period 2009-2015. The discriminative ability of existing bleeding scores were individually evaluated and compared with the new bleeding model termed Anticoagulation-specific Bleeding Score (ABS) in both MarketScan and Optum. Among 119,083 patients with AF initiating oral anticoagulation in the derivation cohort, 4,030 experienced a bleeding event. The variable selection model identified 15 variables (including individual type of oral anticoagulant) associated with major bleeding. Discrimination of the model was modest [c-statistic 0.68, 95% confidence interval (CI) 0.67-0.69]. The model was subsequently applied to 81,285 AF patients in the validation data set (3,238 bleeding events), showing similar discrimination (c-statistic 0.68, 95% CI 0.67-0.69). In both cohorts, the predictive performance of the ABS was better than the existing models for bleeding prediction in AF. We developed a model that uses administrative healthcare data for the identification of AF patients at higher risk of bleeding after initiation of oral anticoagulation, taking into account the lower bleeding risk in DOAC compared to warfarin users.