BACKGROUND AND PURPOSE Atrial fibrillation (AF) is associated with dementia independent of clinical stroke. The mechanisms underlying this association remain unclear. In a community-based cohort, the ARIC study, we evaluated: (1) the longitudinal association of incident AF and (2) the cross-sectional association of prevalent AF with brain MRI abnormalities. METHODS The longitudinal analysis included 963 participants (mean age, 73±4.4 years, 62% women, 51% black) without prevalent stroke or AF who underwent a brain MRI in 1993–1995 and a second MRI in 2004–2006 (mean, 10.6±0.8 years). Outcomes included subclinical cerebral infarctions (SCI), sulcal size, ventricular size, and, for the cross-sectional analysis, white matter hyperintensity (WMH) volume and total brain volume (TBV). RESULTS In the longitudinal analysis, 29 (3.0%) participants developed AF after the first brain MRI. Those who developed AF had higher odds of increase in SCIs (OR, 3.08; 95% CI, 1.39–6.83), worsening sulcal grade (OR, 3.56; 95% CI, 1.04–12.2), and worsening ventricular grade (OR, 9.34; 95% CI 1.24–70.2). In cross-sectional analysis, of 969 participants, 35 (3.6%) had prevalent AF at the time of the 2004–2006 MRI scan. Those with AF had greater odds of higher sulcal (OR, 3.9; 95% CI, 1.7–9.1) and ventricular grade (OR, 2.4; 95% CI, 1.0–5.7) after multivariable adjustment, and no difference in WMH or TBV. CONCLUSION AF is independently associated with increase in SCI and worsening sulcal and ventricular grade—morphological changes associated with aging and dementia. More research is needed to define the mechanisms underlying AF-related neurodegeneration.

BACKGROUND: The American Heart Association set 2020 Strategic Impact Goals that defined cardiovascular risk factors to be included in the concept of ideal cardiovascular health (ICH). The prevalence of ICH among differing levels of adiposity in youth, especially severe obesity, is uncertain. METHODS AND RESULTS: The cross-sectional study measured ICH metrics in 300 children and adolescents stratified by adiposity: normal weight, overweight/obese, and severely obese. ICH incorporates 7 behavioral and health metrics, and was characterized as poor, intermediate, or ideal. Individual ICH metrics were transformed into standardized sample z-scores; a summary ICH sample z-score was also calculated. Multivariable linear regression models were used to estimate differences in ICH sample z-scores by adiposity status. Of the 300 participants, 113 were classified as having normal weight, 87 as having overweight/obesity, and 100 as having severe obesity (mean age 12.8 years, SD 2.7; 48% female). No participants met the criteria for ICH; 80% of those classified as having normal weight, 81% of those with overweight/obesity, and all of those with severe obesity were in poor cardiovascular health. After multivariable adjustment, those with overweight/obesity (sample z-score: -1.35; 95% confidence interval, -2.3, -1.1) and severe obesity (sample z-score: -1.45; 95% confidence interval, -2.9, -0.92) had lower overall ICH sample z-scores compared with participants with normal weight. Results were similar for individual ICH metrics. CONCLUSIONS: Poor cardiovascular health was highly prevalent in youth; ICH sample z-scores increased across levels of adiposity. Youth with obesity, particularly those with severe obesity, remain a rich target for primary prevention efforts. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01508598.

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.

BACKGROUND: Although peripheral artery disease as defined by ankle-brachial index (ABI) is associated with incident atrial fibrillation (AF), questions remain about the risk of AF in borderline ABI (>0.90 to <1.0) or noncompressible arteries (>1.4). We evaluated the association of borderline ABI and ABI >1.4 in the ARIC (Atherosclerosis Risk in Communities) study, a population-based prospective cohort study. METHODS AND RESULTS: We included 14 794 participants (age, 54.2±5.8 years, 55% women, 26% blacks) with ABI measured at the baseline (1987-1989) and without AF. AF was identified from hospital records, death certificates, and ECGs. Using Cox proportional hazards, we evaluated the association between ABI and AF. During a median follow-up of 23.3 years, there were 2288 AF cases. After adjustment for cardiovascular risk factors, hazard ratio (HR) (95% confidence interval) for AF among individuals with ABI <1.0 compared with ABI 1.0 to 1.4, was 1.13 (1.01-1.27). ABI >1.4 was not associated with increased AF risk. ABI ≤0.9 and borderline ABI were associated with a higher risk of AF compared with ABI 1.0 to 1.4. Demographics-adjusted HRs (95% confidence interval) were 1.43 (1.17-1.75) and 1.32 (1.16-1.50), respectively. However, the associations of ABI ≤0.9 and borderline ABI with AF were attenuated after adjusting for cardiovascular risk factors (HR [95% confidence interval], 1.10 [0.90-1.34] and 1.14 [1.00-1.30]), respectively. CONCLUSIONS: Peripheral artery disease indicated by low ABI, including borderline ABI, is a weak risk factor for AF. ABI >1.4 is not associated with an increased AF risk. The relationship between peripheral artery disease and AF appears to be mostly explained by traditional atherosclerotic risk factors.

Background Multiple prospective studies have established an association between inflammation and higher risk of atrial fibrillation (AF), but the association between lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) mass and activity and incident AF has not been extensively evaluated. Methods Using data from 10,794 Atherosclerosis Risk In Communities (ARIC) study participants aged 53-75 years, 5,181 Cardiovascular Health Study (CHS) participants aged 65 to 100 years, and 5,425 Multi-Ethnic Study of Atherosclerosis (MESA) participants aged 45-84 years, we investigated the association between baseline Lp-PLA 2 levels and the risk of developing AF. Incident AF was identified in each cohort by follow-up visit electrocardiograms, hospital discharge coding of AF, or Medicare claims data. Results Over a mean of 13.1, 11.5, and 10.0 years of follow-up, 1,439 (13%), 2,084 (40%), and 615 (11%) incident AF events occurred in ARIC, CHS, and MESA, respectively. In adjusted analyses, each SD increment in Lp-PLA 2 activity was associated with incident AF in both ARIC (hazard ratio [HR] 1.13, 95% CI 1.06-1.20) and MESA (HR 1.24, 95% CI 1.05-1.46). Each SD increment in Lp-PLA 2 mass was also associated with incident AF in MESA (HR 1.25, 95% CI 1.11-1.41). No significant associations were observed among CHS participants. Conclusions Although higher Lp-PLA 2 mass and activity were associated with development of AF in ARIC and MESA, this relationship was not observed in CHS, a cohort of older individuals.

Background: Blood pressure (BP) and cholesterol are major modifiable risk factors for cardiovascular disease (CVD), but effects of exposures during young adulthood on later life CVD risk have not been well quantified. Objective: The authors sought to evaluate the independent associations between young adult exposures to risk factors and later life CVD risk, accounting for later life exposures. Methods: The authors pooled data from 6 U.S. cohorts with observations spanning the life course from young adulthood to later life, and imputed risk factor trajectories for low-density lipoprotein (LDL) and high-density lipoprotein cholesterols, systolic and diastolic BP starting from age 18 years for every participant. Time-weighted average exposures to each risk factor during young (age 18 to 39 years) and later adulthood (age ≥40 years) were calculated and linked to subsequent risks of coronary heart disease (CHD), heart failure (HF), or stroke. Results: A total of 36,030 participants were included. During a median follow-up of 17 years, there were 4,570 CHD, 5,119 HF, and 2,862 stroke events. When young and later adult risk factors were considered jointly in the model, young adult LDL ≥100 mg/dl (compared with <100 mg/dl) was associated with a 64% increased risk for CHD, independent of later adult exposures. Similarly, young adult SBP ≥130 mm Hg (compared with <120 mm Hg) was associated with a 37% increased risk for HF, and young adult DBP ≥80 mm Hg (compared with <80 mm Hg) was associated with a 21% increased risk. Conclusions: Cumulative young adult exposures to elevated systolic BP, diastolic BP and LDL were associated with increased CVD risks in later life, independent of later adult exposures.

Background and aims: Individuals with atherosclerosis and stiffness often have increased abdominal aortic diameters, but prospective evidence linking them to the risk of abdominal aortic aneurysm (AAA) is limited. Methods: We prospectively examined the relationship of carotid atherosclerosis and stiffness with future risk of AAA in ARIC. At Visits 1 (1987–89) or 2 (1990–1992), we assessed carotid atherosclerosis (represented by greater carotid intima-media thickness [cIMT] or presence of atherosclerotic plaque) and lower carotid distensibility (reflected by a higher carotid Beta Index). We identified incident, clinical AAAs during follow-up through 2011 using hospital discharge codes, Medicare outpatient diagnoses, or death certificates. Results: Participants’ mean age at baseline was 54.2 years (SD 5.8), 45% were male and 73% white. During a median of 22.5 years of follow-up, 542 clinical AAAs were ascertained. After multivariable adjustment, the presence of carotid atherosclerotic plaque at baseline was associated with 1.31 (95% CI: 1.10–1.57; p = 0.003) times higher risk of clinical AAA. Greater cIMT and Beta Index were also associated with clinical AAA with a dose-response across quartiles (p trend for both: 0.006; hazard ratios [95% CI] for the highest vs. lowest quartiles: 1.55 [1.13–2.11] and 1.68 [1.16–2.43], respectively). The associations of cIMT and Beta Index with AAA were independent of each other. Conclusions: This prospective population-based study found that indices of greater carotid atherosclerosis and lower carotid distensibility are markers of increased AAA risk.

Background: The purpose of this study was to characterize the repeatability of ectopic beats, defined by premature atrial contractions (PACs) and premature ventricular contractions (PVCs), on ambulatory electrocardiogram (aECG) monitoring and evaluate the effect of length of aECG monitoring on the repeatability estimates. Methods: This analysis includes 95 randomly selected participants from the Atherosclerosis Risk in Communities Study (ARIC; 2011–2013). The participants wore a Holter monitor for two, 48-hr periods separated by a mean of 38 days following an identical, standardized protocol. We divided each 48-hr recording into 3-, 6-, 12-, and 24-hr recording periods and calculated intraclass correlation coefficients (ICCs) for PACs and PVCs and also as a percentage of the corresponding total of recorded beats per hour among these periods. Results: All participants had ≥1 PAC during the 48-hr recordings, and only two participants had no PVCs. ICCs were >0.83 for all indices and recording lengths ≥12 hrs. ICCs were intermediate for 6-hr recordings (range 0.80–0.83) and lower for 3-hr recordings (range 0.74–0.80). The ratio of the between- to within-participant variation increased with recording length. Conclusion: Repeatability of PACs and PVCs was excellent for recording lengths of 6–24 hr and fair for 3 hr. Repeatability varies over shorter duration recordings within the 48-hr recording period, and thus the present results have implications for detection algorithms for ectopic beats and can facilitate epidemiologic and clinical applications in which knowledge of measurement variability and misclassification are needed.

Introduction Although it has been suggested that increased concentrations of activated platelet biomarkers are associated with increased risk of incident cardiovascular disease (CVD) in the general population, evidence for this association is still controversial. Thus, we tested the hypothesis that activated platelets, measured by higher concentrations of β-thromboglobulin, are associated with increased risk of incident CVD (coronary heart disease, heart failure ischemic stroke, and atrial fibrillation). Materials and methods We prospectively followed a cohort random sample of the Atherosclerosis Risk in Communities (ARIC) cohort, aged 45–64 years, and free of CVD at baseline who had previous measurements of plasma β-thromboglobulin. We identified incident CVD from 1987 through 2013, and used a weighted Cox proportional hazard models to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs). Results During the 14,387 person-years of follow-up for the 746 participants, we identified 140 coronary heart diseases, 123 heart failures, 54 ischemic strokes, and 126 atrial fibrillations. The age-, sex-, and race-adjusted model showed no association between plasma β-thromboglobulin and CVD, regardless of subtypes. After further adjustment for other CVD risk factors, including antiplatelet agent use, β-thromboglobulin remained unassociated with CVD risk. Conclusions In the prospective population-based ARIC cohort, β-thromboglobulin was not associated with CVD risk. Our results do not support the hypothesis that a blood marker of higher platelet activity reflects increased future risk of CVD in the general population.