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To evaluate the association of premature atrial contraction (PAC) frequency with cognitive test scores and prevalence of dementia or mild cognitive impairment (MCI).We conducted a cross-sectional analysis using Atherosclerosis Risk in Communities study visit 6 (January 1, 2016, through December 31, 2017) data. We included 2163 participants without atrial fibrillation (AF) (age mean ± SD, 79±4 years; 1273 (58.9%) female; and 604 (27.97.0% Black) who underwent cognitive testing and wore a leadless, ambulatory electrocardiogram monitor for 14 days. We categorized PAC frequency based on the percent of beats: less than 1%, minimal; 1% to5%, occasional; greater than or equal to 5%, frequent. We derived cognitive domain-specific factor scores (memory, executive function, language, and global z-score). Dementia and MCI were adjudicated.During a mean analyzable time of 12.6±2.6 days, 339 (15.7%) had occasional PACs and 107 (4.9%) had frequent PACs. Individuals with frequent PACs (vs minimal) had lower executive function factor scores by 0.30 (95% CI, -0.46 to -0.14) and lower global factor scores by 0.20 (95% CI, -0.33 to -0.07) after multivariable adjustment. Individuals with frequent PACs (vs minimal) had higher odds of prevalent dementia or MCI after multivariable adjustment (odds ratio, 1.74; 95% CI, 1.09 to 2.79). These associations were unchanged with additional adjustment for stroke.In community-dwelling older adults without AF, frequent PACs were cross-sectionally associated with lower executive and global cognitive function and greater prevalence of dementia or MCI, independently of stroke. Our findings lend support to the notion that atrial cardiomyopathy may be a driver of AF-related outcomes. Further research to confirm these associations prospectively and to elucidate underlying mechanisms is warranted.

Background: Low levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the low physiologic range, surrogate markers for reduced liver metabolic function, are associated with cerebral hypometabolism, impairment in neurotransmitter production and synaptic maintenance, and a higher prevalence of dementia. It is unknown whether a prospective association exists between low liver enzyme levels and incident dementia. Objective: To determine whether low levels of ALT and AST are associated with higher risk of incident dementia. Methods: Plasma ALT and AST were measured on 10,100 study participants (mean age 63.2 years, 55% female, 22% black) in 1996–1998. Dementia was ascertained from comprehensive neuropsychological assessments, annual contact, and medical record surveillance. Cox proportional hazards regression was used to estimate the association. Results: During a median follow-up of 18.3 years (maximum 21.9 years), 1,857 individuals developed dementia. Adjusted for demographic factors, incidence rates of dementia were higher at the lower levels of ALT and AST. Compared to the second quintile, ALT values

The relationship between body weight and lung function is complex. Using a dyadic multilevel linear modeling approach, treating body mass index (BMI; weight (kg)/height (m)2) and lung function as paired, within-person outcomes, we tested the hypothesis that persons with more rapid increase in BMI exhibit more rapid decline in lung function, as measured by forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and their ratio (FEV1:FVC). Models included random intercepts and slopes and adjusted for sociodemographic and smoking-related factors. A sample of 9,115 adults with paired measurements of BMI and lung function taken at ≥3 visits were selected from a pooled set of 5 US population-based cohort studies (1983–2018; mean age at baseline = 46 years; median follow-up, 19 years). At age 46 years, average annual rates of change in BMI, FEV1, FVC, and FEV1:FVC ratio were 0.22 kg/m2/year, −25.50 mL/year, −21.99 mL/year, and −0.24%/year, respectively. Persons with steeper BMI increases had faster declines in FEV1 (r = −0.16) and FVC (r = −0.26) and slower declines in FEV1:FVC ratio (r = 0.11) (all P values

Faster rates of age-related cognitive decline might result in early onset of cognitive impairment and dementia. The relationship between ethanol intake and cognitive decline, although studied extensively, remains poorly understood. Previous studies used single measurements of ethanol, and few were conducted in diverse populations. We assessed the association of 9-year trajectories of ethanol intake (1987–1998) with 15-year rate of decline in cognitive performance from mid- to late life (1996–2013) among 2,169 Black and 8,707 White participants of the US Atherosclerosis Risk in Communities study using multivariable linear regression models. We hypothesized that stable, low to moderate drinking would be associated with lesser 15-year cognitive decline, and stable, heavy drinking with greater 15-year cognitive decline. Stable, low to moderate drinking (for Blacks, adjusted mean difference (MD) = 0.03 (95% confidence interval (CI): −0.13, 0.19); for Whites, adjusted MD = 0.02 (95% CI: −0.05, 0.08)) and stable, heavy drinking (for Blacks, adjusted MD = 0.08 (95% CI: −0.34, 0.50); for Whites, adjusted MD = −0.03 (95% CI: −0.18, 0.11)) in midlife compared with stable never-drinking were not associated with 15-year decline in general cognitive function from mid- to late life. No association was observed for the stable former and “mostly” drinking trajectories with 15-year cognitive decline. Stable low, low to moderate, and stable heavy drinking in midlife are not associated with lesser and greater cognitive decline, respectively, from mid- to late life among Black and White adults.

Summary Background Former smokers now outnumber current smokers in many developed countries, and current smokers are smoking fewer cigarettes per day. Some data suggest that lung function decline normalises with smoking cessation; however, mechanistic studies suggest that lung function decline could continue. We hypothesised that former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers, including among those without prevalent lung disease. Methods We used data on six US population-based cohorts included in the NHLBI Pooled Cohort Study. We restricted the sample to participants with valid spirometry at two or more exams. Two cohorts recruited younger adults (≥17 years), two recruited middle-aged and older adults (≥45 years), and two recruited only elderly adults (≥65 years) with examinations done between 1983 and 2014. FEV1 decline in sustained former smokers and current smokers was compared to that of never-smokers by use of mixed models adjusted for sociodemographic and anthropometric factors. Differential FEV1 decline was also evaluated according to duration of smoking cessation and cumulative (number of pack-years) and current (number of cigarettes per day) cigarette consumption. Findings 25 352 participants (ages 17–93 years) completed 70 228 valid spirometry exams. Over a median follow-up of 7 years (IQR 3–20), FEV1 decline at the median age (57 years) was 31·01 mL per year (95% CI 30·66–31·37) in sustained never-smokers, 34·97 mL per year (34·36–35·57) in former smokers, and 39·92 mL per year (38·92–40·92) in current smokers. With adjustment, former smokers showed an accelerated FEV1 decline of 1·82 mL per year (95% CI 1·24–2·40) compared to never-smokers, which was approximately 20% of the effect estimate for current smokers (9·21 mL per year; 95% CI 8·35–10·08). Compared to never-smokers, accelerated FEV1 decline was observed in former smokers for decades after smoking cessation and in current smokers with low cumulative cigarette consumption ( Interpretation Former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers. These results suggest that all levels of smoking exposure are likely to be associated with lasting and progressive lung damage. Funding National Institutes of Health, National Heart Lung and Blood Institute, and US Environmental Protection Agency.

BackgroundInsulin resistance may contribute to aortic stiffening that leads to end-organ damage. We examined the cross-sectional association and prospective association of insulin resistance and aortic stiffness in older adults without diabetes.MethodsWe analyzed 2571 men and women at Visit 5 (in 2011–2013), and 2350 men and women at repeat examinations from baseline at Visit 1 (in 1987–1989) to Visit 5 (in 2011–2013). Linear regression was used to estimate the difference in aortic stiffness per standard unit of HOMA-IR, TG/HDL-C, and TyG at Visit 5. Linear mixed effects were used to assess if high, as opposed to non-high, aortic stiffness (> 75th percentile) was preceded by a faster annual rate of change in log-HOMA-IR, log-TG/HDL-C, and log-TyG from Visit 1 to Visit 5.ResultsThe mean age of participants was 75 years, 37% (n = 957) were men, and 17% (n = 433) were African American. At Visit 5, higher HOMA-IR, higher TG/HDL-C, and higher TyG were associated with higher aortic stiffness (16 cm/s per SD (95% CI 6, 27), 29 cm/s per SD (95% CI 18, 40), and 32 cm/s per SD (95% CI 22, 42), respectively). From Visit 1 to Visit 5, high aortic stiffness, compared to non-high aortic stiffness, was not preceded by a faster annual rate of change in log-HOMA-IR from baseline to 9 years (0.030 (95% CI 0.024, 0.035) vs. 0.025 (95% CI 0.021, 0.028); p = 0.15) or 9 years onward (0.011 (95% CI 0.007, 0.015) vs. 0.011 (95% CI 0.009, 0.013); p = 0.31); in log-TG/HDL-C from baseline to 9 years (0.019 (95% CI 0.015, 0.024) vs. 0.024 (95% CI 0.022, 0.026); p = 0.06) or 9 years onward (− 0.007 (95% CI − 0.010, − 0.005) vs. − 0.009 (95% CI − 0.010, − 0.007); p = 0.08); or in log-TyG from baseline to 9 years (0.002 (95% CI 0.002, 0.003) vs. 0.003 (95% CI 0.003, 0.003); p = 0.03) or 9 years onward (0 (95% CI 0, 0) vs. 0 (95% CI 0, 0); p = 0.08).ConclusionsAmong older adults without diabetes, insulin resistance was associated with aortic stiffness, but the putative role of insulin resistance in aortic stiffness over the life course requires further study.

Introduction: Circulating metabolome profiling holds promise in predicting HF risk, but its prediction performance among older adults is not well established. Hypothesis: We hypothesize that metabolic signatures are associated with the risk of HF and its subtypes (HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF)), and they can improve HF risk prediction beyond established risk factors. Methods: We measured 828 serum metabolites among 4,030 African and European Americans free of HF from the Atherosclerosis Risk in Communities (ARIC) study visit 5 (2011-2013). We regressed incident HF on each metabolite using Cox proportional hazards models. A metabolite risk score (MRS) was derived by summing individual metabolite levels weighted by beta coefficients estimated from least absolute shrinkage and selection operator (LASSO) regularized regressions. We regressed incident HF, HFpEF and HFrEF on the MRS. Harrell’s C-statistics were calculated to evaluate risk discrimination. We replicated the association between MRS and HF in 3,697 independent ARIC participants with metabolite measured at visit 1 (1987-1989). Results: Among 4,030 participants, the mean (SD) age was 76 (5) years. Adjusting for HF risk factors, 302 metabolites were associated with incident HF (false discovery rate < 0.05). One SD increase of the MRS, constructed from 51 metabolites selected by LASSO, was associated with two to three-fold high risk of HF, HFpEF and HFrEF in the fully adjusted models ( Table ). Five-year risk prediction analysis showed that C statistics improved from 0.850 to 0.884 by adding MRS over ARIC HF risk factors, kidney function and NT-proBNP (ΔC (95%CI) = 0.034 (0.017,0.052)). In the replication analysis, a more parsimonious MRS constructed using 15 metabolites, was associated with incident HF ( Table ). Conclusions: We identified a metabolic signature that was associated with the risk of HF and improved HF risk prediction. Our findings may shed light on pathways in HF development and at-risk populations.

Background A lower prevalence of atrial fibrillation (AF), but paradoxically higher burden of cardiovascular disease risk factors, has been observed among African Americans compared to Whites in studies of AF identified by mostly 12-lead electrocardiograms (ECGs) and clinically. Methods We performed 48-hour ambulatory electrocardiography (aECG) in a biracial sample of 1,193 participants in the Atherosclerosis Risk in Communities (ARIC) (mean age = 78 years, 62% African Americans, 64% female). Atrial fibrillation was identified from aECG, study visit ECGs, and discharge codes from cohort hospitalizations. We used covariate-adjusted logistic regression to estimate prevalence odds ratios (ORs) for AF in African Americans versus Whites, with adjustment for sampling and nonresponse. Results African Americans were more likely than Whites to have hypertension and diabetes but less likely to have coronary heart disease. The prevalence of AF detected by aECG or ARIC study ECG (adjusted for age and coronary heart disease) was lower in African Americans than Whites (2.7% vs 5.0%). White men had a higher (although not significant) AF prevalence of 7.8% compared to the other race and gender groups at 2.3%-2.8%. The adjusted OR for AF was 0.49 (0.24-0.99) comparing African Americans to Whites. Findings were similar when AF was defined to include prior AF hospitalizations (OR = 0.42, 0.25-0.72). There were no significant differences by race for asymptomatic or paroxysmal AF. Conclusions Atrial fibrillation was less prevalent in African American than white older adults, regardless of detection method. Although overall detection of new AF cases with aECG was low, future studies should consider longer-term monitoring to characterize AF by race.

Introduction: Age and vitamin D levels may affect symptom burden in chronic obstructive pulmonary disease (COPD). We used the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) to determine independent associations between vitamin D levels and COPD symptoms in different age strata. Methods: Serum 25-hydroxy (OH)-vitamin D levels were modeled continuously and categorically (65 years old), multivariable modeling was performed to identify relationships between 25-OH-vitamin D levels and the COPD Assessment Test (CAT), the modified Medical Research Council score (mMRC), the St George’s Respiratory Questionnaire (SGRQ) total and subdomain scores, the Veterans’ Specific Activity Questionnaire, and the 6-minute walk test distance. Results: In the middle-aged group, each 5 ng/ml higher 25-OH-vitamin D level was independently associated with more favorable CAT score (-0.35 [-0.67 to -0.03], P=0.03), total SGRQ (-0.91 [-1.65 to -0.17]; P=0.02), and the SGRQ subdomains (Symptoms:-1.07 [-1.96 to -0.18], P=0.02; Impact: -0.77 [-1.53 to -0.003], P=0.049; Activity: -1.07 [-1.96 to -0.18], P=0.02). These associations persisted after the addition of comorbidity score, reported vitamin D supplementation, outdoor time, or season of blood draw to models. No associations were observed between 25-OH-vitamin D levels and symptom scores in the older age group. Discussion: When controlled for clinically relevant covariates, higher 25-OH-vitamin D levels are associated with more favorable respiratory-specific symptoms and quality-of-life assessments in middle-age but not older COPD individuals. Study of the role of vitamin D supplementation in the symptom burden of younger COPD patients is needed.

Background: Hispanic/Latino individuals are less likely to receive optimal treatment for chronic kidney disease (CKD) than non-Hispanic whites. This may be particularly detrimental for women of reproductive age as CKD may increase risk for infertility, menstrual irregularities, and pregnancy loss. While these maternal outcomes have been associated with advanced CKD, their occurrence in mild to moderate CKD is unclear. Methods: Using baseline (2008-2011) and second study visit (2014-2017) data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we assessed the association between CKD and self-reported infertility, cessation of menses, hysterectomy, and nonviable pregnancy loss (experienced at less than 24 weeks gestation) in women of reproductive age (18-45 years). Multivariable survey logistic regression analyses were used to compute prevalence odds ratios with 95% confidence intervals (OR, 95% CI). Results: Of the 2,589 women included (mean age 31.4 years), 4.6% were considered to have CKD. In adjusted analyses, women with CKD did not have a significantly increased odds of infertility (OR 1.02, 95% CI 0.42 - 2.49), cessation of menses (OR 1.25, 95% CI 0.52 - 3.04) or hysterectomy (OR 1.17, 95% CI 0.61 - 2.25) compared to those without CKD. In those with CKD, the adjusted odds of a nonviable pregnancy loss was increased when considering pregnancies occurring after baseline visit (OR 2.11, 95% CI 0.63 - 7.02) but not statistically significance. Conclusion: In our Hispanic/Latino cohort, the presence of mild to moderate CKD did not confer an additional risk of our outcomes of interest. Examining nonviable pregnancy loss after CKD diagnosis in a larger sample warrants further study.

Not available.

Background Heart failure with preserved ejection fraction (HFpEF) accounts for half of heart failure hospitalizations, with limited data on predictors of mortality by sex and race. We evaluated for differences in predictors of all‐cause mortality by sex and race among hospitalized patients with HFpEF in the ARIC (Atherosclerosis Risk in Communities) Community Surveillance Study. Methods and Results Adjudicated HFpEF hospitalization events from 2005 to 2013 were analyzed from the ARIC Community Surveillance Study, comprising 4 US communities. Comparisons between clinical characteristics and mortality at 1 year were made by sex and race. Of 4335 adjudicated acute decompensated heart failure cases, 1892 cases (weighted n=8987) were categorized as HFpEF. Men had an increased risk of 1‐year mortality compared with women in adjusted analysis (hazard ratio [HR], 1.27; 95% CI, 1.06–1.52 [ P =0.01]). Black participants had lower mortality compared with White participants in unadjusted and adjusted analyses (HR, 0.79; 95% CI, 0.64–0.97 [ P =0.02]). Age, heart rate, worsening renal function, and low hemoglobin were associated with increased mortality in all subgroups. Higher body mass index was associated with improved survival in men, with borderline interaction by sex. Higher blood pressure was associated with improved survival among all groups, with significant interaction by race. Conclusions In a diverse HFpEF population, men had worse survival compared with women, and Black participants had improved survival compared with White participants. Age, heart rate, and worsening renal function were associated with increased mortality across all subgroups; high blood pressure was associated with decreased mortality with interaction by race. These insights into sex‐ and race‐based differences in predictors of mortality may help strategize targeted management of HFpEF.

Background: The number of current smokers has reached its lowest level to date in the US but the proportion of smokers smoking Aim: To assess relative risks of respiratory and lung cancer mortality in low-intensity smokers. Methods: Data from 4 US general population cohorts were harmonized and pooled. Current smokers were categorized by self-reported CPD ( Results: Of 18,730 participants (mean age 61 yrs, 56% women, 69% white, 13% current smokers, 17 yrs median follow-up), 649 (IDR=20/10,000 person-years) died from respiratory causes while 560 (IDR=17) died from lung cancer. Compared to never smokers, those with Conclusions: Risk of respiratory and lung cancer deaths among low-intensity current smokers vs never smokers, is non-trivial: in this study, this risk was equivalent to at least half that seen in those with 20+CPD.

Background Prior studies have shown insulin resistance is associated with reduced cardiac autonomic function measured at rest, but few studies have determined whether insulin resistance is associated with reduced cardiac autonomic function measured during daily activities. Methods We examined older adults without diabetes with 48-h ambulatory electrocardiography (n = 759) in an ancillary study of the Atherosclerosis Risk in Communities Study. Insulin resistance, the exposure, was defined by quartiles for three indexes: 1) the homeostatic model assessment of insulin resistance (HOMA-IR), 2) the triglyceride and glucose index (TyG), and 3) the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C). Low heart rate variability, the outcome, was defined by Results The average age was 78 years, 66% (n = 497) were women, and 58% (n = 438) were African American. Estimates of association were not robust at all levels of HOMA-IR, TyG, and TG/HDL-C, but suggest that high indexes were associated consistently with indicators of vagal activity. High HOMA-IR, high TyG, and high TG/HDL-C were consistently associated with low RMSSD (OR: 1.68 (1.00, 2.81), OR: 2.03 (1.21, 3.39), and OR: 1.73 (1.01, 2.91), respectively). High HOMA-IR, high TyG, and high TG/HDL-C were consistently associated with low HF (OR: 1.90 (1.14, 3.18), OR: 1.98 (1.21, 3.25), and OR: 1.76 (1.07, 2.90), respectively). Conclusions In older adults without diabetes, insulin resistance was associated with reduced cardiac autonomic function – specifically and consistently for indicators of vagal activity – measured during daily activities. Primary prevention of insulin resistance may reduce the related risk of cardiac autonomic dysfunction.

ObjectiveWe performed a cross-sectional analysis to determine whether nonsustained ventricular tachycardia (NSVT) and premature ventricular contractions (PVCs) were associated with dementia in a population-based study.MethodsWe included 2,517 (mean age 79 years, 26% Black) participants who wore a 2-week ambulatory continuous ECG recording device in 2016 to 2017. NSVT was defined as a wide-complex tachycardia ≥4 beats with a rate >100 bpm. We calculated NSVT and PVC burden as the number of episodes per day. Dementia was adjudicated by experts. We used logistic regression to assess the associations of NSVT and PVCs with dementia.ResultsThe mean recording time of the Zio XT Patch was 12.6 ± 2.6 days. There were 768 (31%) participants with NSVT; prevalence was similar in White and Black participants. There were 134 (6.5%) dementia cases (5% in White, 10% in Black participants). After multivariable adjustment, there was no overall association between NSVT and dementia; however, there was a significant race interaction (p < 0.001). In Black participants, NSVT was associated with a 3.67 times higher adjusted odds of dementia (95% confidence interval [CI] 1.92–7.02) compared to those without NSVT, whereas in White participants NSVT was not associated with dementia (odds ratio [95% CI] 0.64 [0.37–1.10]). In Black participants only, a higher burden of PVCs was associated with dementia.ConclusionsPresence of NSVT and a higher burden of NSVT and PVCs are associated with dementia in elderly Black people. Further research to confirm this novel finding and to elucidate the underlying mechanisms is warranted.

Background Goal‐striving stress (GSS), the stress from striving for goals, is associated with poor health. Less is known about its association with cardiovascular disease (CVD). Methods and Results We used data from the JHS (Jackson Heart Study), a study of CVD among blacks (21–95 years old) from 2000 to 2015. Participants free of CVD at baseline (2000–2004) were included in this analysis (n=4648). GSS was examined in categories (low, moderate, high) and in SD units. Incident CVD was defined as fatal or nonfatal stroke, coronary heart disease (CHD), and/or heart failure. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident CVD by levels of GSS, adjusting for demographics, socioeconomic status, health behaviors, risk factors, and perceived stress. The distribution of GSS categories was as follows: 40.77% low, 33.97% moderate, and 25.26% high. Over an average of 12 years, there were 140 incident stroke events, 164 CHD events, and 194 heart failure events. After full adjustment, high (versus low) GSS was associated with a lower risk of stroke (HR, 0.38; 95% CI, 0.17–0.83) and a higher risk of CHD (HR, 1.91; 95% CI, 1.10–3.33) among women. A 1‐standard deviation unit increase in GSS was associated with a 31% increased risk of CHD (HR, 1.31; 95% CI, 1.10–1.56) among women. Conclusions Higher GSS may be a risk factor for developing CHD among women; however, it appears to be protective of stroke among women. These analyses should be replicated in other samples of black individuals.

Introduction: Low levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) among older adults are associated with mortality, and reportedly with lower cognitive performance, biomarkers of neurodegeneration, and dementia. We tested the associations of liver enzymes with cognition in ARIC-NCS. Methods: We studied 3191 participants (mean age 79 years, 59% female, 23% black) free of chronic liver disease and cirrhosis, and with AST:ALT ratio ≤2 at visit in 2016-2017. Serum ALT and AST were examined continuously and by quintiles, with the 3 rd quintile as the distribution-based modal reference range. Cognitive status (normal, mild cognitive impairment [MCI], dementia) was ascertained by an expert adjudication panel. A composite global cognition score was estimated from memory, executive function, and language tests. We used demographic and ApoE4 adjusted multinomial logistic and linear regressions. Results: Participants were classified as cognitively unimpaired (2375), MCI (602) or dementia (214). Lower levels of ALT and AST, and a higher AST:ALT ratio were associated with higher prevalence of dementia and lower global cognition scores ( Figure ). The prevalence odds ratio of dementia and MCI for the 1 st quintile, vs 3 rd quintile of ALT, were 1.73 (95% CI:1.06-2.81) and 1.27 (0.92-1.76), respectively. The corresponding estimates for AST were 1.71 (1.03-2.84) and 1.17 (0.87-1.59). Global cognition scores were lower in the 1 st vs 3 rd quintiles of ALT and AST by 0.13 (0.06-0.21) and 0.08 (0-0.15) standard deviation units, respectively. Additional adjustment for alcohol intake did not change the results. Conclusions: Liver hypometabolism is linked to reduced brain glucose metabolism, impaired production of neurotransmitters and synaptic maintenance, systemic insulin resistance and inflammation, while hepatic metabolite profiles are altered in dementia. Prospective assessments are warranted to characterize the role of hepatic metabolic dysfunction in cognitive impairment among older adults.

Background: Community trends of acute decompensated heart failure (ADHF) in diverse populations may differ by race and sex. Methods: The ARIC study (Atherosclerosis Risk in Communities) sampled heart failure-related hospitalizations (≥55 years of age) in 4 US communities from 2005 to 2014 using International Classification of Diseases, Ninth Revision, Clinical Modification codes. ADHF hospitalizations were validated by standardized physician review and computer algorithm, yielding 40 173 events after accounting for sampling design (unweighted n=8746). Results: Of the ADHF hospitalizations, 50% had reduced ejection fraction, and 39% had preserved EF (HFpEF). HF with reduced ejection fraction was more common in black men and white men, whereas HFpEF was most common in white women. Average age-adjusted rates of ADHF were highest in blacks (38.1 per 1000 black men, 30.5 per 1000 black women), with rates differing by HF type and sex. ADHF rates increased over the 10 years (average annual percentage change: black women +4.3%, black men +3.7%, white women +1.9%, white men +2.6%), mostly reflecting more acute HFpEF. Age-adjusted 28-day and 1-year case fatality proportions were ≈10% and 30%, respectively, similar across race-sex groups and HF types. Only blacks showed decreased 1-year mortality over time (average annual percentage change: black women –5.4%, black men –4.6%), with rates differing by HF type (average annual percentage change: black women HFpEF –7.1%, black men HF with reduced ejection fraction –4.7%). Conclusions: Between 2005 and 2014, trends in ADHF hospitalizations increased in 4 US communities, primarily driven by acute HFpEF. Survival at 1 year was poor regardless of EF but improved over time for black women and black men.

Chronic lower respiratory diseases (CLRDs) are the fourth leading cause of death in the United States. To support investigations into CLRD risk determinants and new approaches to primary prevention, we aimed to harmonize and pool respiratory data from US general population-based cohorts. Data were obtained from prospective cohorts that performed prebronchodilator spirometry and were harmonized following 2005 ATS/ERS standards. In cohorts conducting follow-up for noncardiovascular events, CLRD events were defined as hospitalizations/deaths adjudicated as CLRD-related or assigned relevant administrative codes. Coding and variable names were applied uniformly. The pooled sample included 65,251 adults in 9 cohorts followed-up for CLRD-related mortality over 653,380 person-years during 1983-2016. Average baseline age was 52 years; 56% were female; 49% were never-smokers; and racial/ethnic composition was 44% white, 22% black, 28% Hispanic/Latino, and 5% American Indian. Over 96% had complete data on smoking, clinical CLRD diagnoses, and dyspnea. After excluding invalid spirometry examinations (13%), there were 105,696 valid examinations (median, 2 per participant). Of 29,351 participants followed for CLRD hospitalizations, median follow-up was 14 years; only 5% were lost to follow-up at 10 years. The NHLBI Pooled Cohorts Study provides a harmonization standard applied to a large, US population-based sample that may be used to advance epidemiologic research on CLRD.

Background Research suggests antihypertensive medications are associated with fractures in older adults, however results are inconsistent and few have examined how the association varies over time. We sought to examine the association between antihypertensive class and incident non-vertebral fractures among older adults initiating monotherapy according to time since initiation. Methods We used a new-user cohort design to identify Medicare beneficiaries (≥ 65 years of age) initiating antihypertensive monotherapy during 2008–2011 using a 20% random sample of Fee-For-Service Medicare beneficiaries enrolled in parts A (inpatient services), B (outpatient services), and D (prescription medication) coverage. Starting the day after the initial antihypertensive prescription, we followed beneficiaries for incident non-vertebral fractures. We used multinomial logistic regression models to estimate propensity scores for initiating each antihypertensive drug class. Using these propensity scores, we weighted beneficiaries to achieve the same baseline covariate distribution as beneficiaries initiating with angiotensin-converting enzyme inhibitors. Lastly, we used weighted Cox proportional hazard models to estimate hazard ratios (HRs) of having an incident fractures according to antihypertensive class and time since initiation. Results During 2008–2011, 122,629 Medicare beneficiaries initiated antihypertensive monotherapy (mean age 75, 61% women, 86% White). Fracture rates varied according to days since initiation and antihypertensive class. Beneficiaries initiating with thiazides had the highest fracture rate in the first 14 days following initiation (438 per 10,000 person-years, 95% confidence interval (CI): 294–628; HR: 1.40, 0.78–2.52). However, beneficiaries initiating with calcium channel blockers had the highest fracture rate during the 15–365 days after initiation (435 per 10,000 person-years, 95% CI: 404–468; HR: 1.11, 1.00–1.24). Beneficiaries initiating with angiotensin-receptor blockers had the lowest fracture rates during the initial 14 days (333 per 10,000 person-years, 190–546, HR: 0.92, 0.49–1.75) and during 15–365 days after initiation (321 per 10,000 person-years, 287–358, HR: 0.96, 0.84–1.09). Conclusion The association between antihypertensives and fractures varied according to class and time since initiation. Results suggest that when deciding upon antihypertensive therapy, clinicians may want to consider possible fracture risks when choosing between antihypertensive drug classes. Electronic supplementary material The online version of this article (10.1186/s40621-017-0125-8) contains supplementary material, which is available to authorized users.

BackgroundPatient-reported outcomes and epidemiological studies in adults with tetralogy of Fallot are lacking. Recruitment and longitudinal follow-up investigation across institutions is particularly challenging. Objectives of this study were to assess the feasibility of recruiting adult patients with tetralogy of Fallot for a patient-reported outcomes study, describe challenges for recruitment, and create an interactive, online tetralogy of Fallot registry.MethodsAdult patients living with tetralogy of Fallot, aged 18–58 years, at the University of North Carolina were identified using diagnosis code query. A survey was designed to collect demographics, symptoms, history, and birth mother information. Recruitment was attempted by phone (Part I, n=20) or by email (Part II, n=20). Data analysis included thematic grouping of recruitment challenges and descriptive statistics. Feasibility threshold was 75% for recruitment and for data fields completed per patient.ResultsIn Part I, 60% (12/20) were successfully contacted and eight (40%) were enrolled. Demographics and birth mother information were obtained for all enrolled patients. In Part II, 70% (14/20) were successfully contacted; 30% (6/20) enrolled and completed all data fields linked to REDCap database; the median time for survey completion was 8 minutes. Half of the patients had cardiac operations/procedures performed at more than one hospital. Automatic electronic data entry from the online survey was uncomplicated.ConclusionsAlthough recruitment (54%) fell below our feasibility threshold, enrolled individuals were willing to complete phone or online surveys. Incorrect contact information, privacy concerns, and patient-reported time constraints were challenges for recruitment. Creating an online survey and linked database is technically feasible and efficient for patient-reported outcomes research.

Background Cardiac autonomic perturbations frequently antecede onset of paroxysmal atrial fibrillation (AF). Interventions that influence autonomic inputs to myocardium may prevent AF. However, whether low heart rate or heart rate variability (HRV), which are noninvasive measures of cardiac autonomic dysfunction, are associated with AF incidence is unclear. Objectives This study sought to study the association between HRV and risk of AF. Methods This study included 11,715 middle-aged adults in the ARIC (Atherosclerosis Risk In Communities) cohort with heart rate and HRV measures obtained from 2-min electrocardiogram recordings performed at baseline (1987 to 1989). These measures included SD of normal-to-normal RR intervals, high-frequency (HF) (0.15 to 0.40 Hz), low-frequency (0.04 to 0.15 Hz), and the low-frequency/HF ratio (denoting a greater sympathetic to parasympathetic dominance). Incident AF cases were ascertained by electrocardiogram at ARIC follow-up visits, hospital discharge diagnosis, or death certificates through 2011. Results During an average follow-up of 19.4 years, 1,580 or 13.5% of participants developed AF. A baseline heart rate Conclusions Cardiac autonomic dysfunction denoted by low resting short-term HRV was associated with higher AF incidence. A low heart rate may be associated with higher AF risk. Further studies are needed to determine whether interventions in the general population to restore autonomic balance may prevent AF.

Background: The prevalence of subclinical atrial fibrillation (AF) in the elderly general population is unclear. We sought to define the prevalence of subclinical AF in a community-based elderly population and to characterize subclinical AF and the incremental diagnostic yield of 4 versus 2 weeks of continuous ECG monitoring. Methods: We conducted a cross-sectional analysis within the community-based multicenter observational ARIC study (Atherosclerosis Risk in Communities) using visit 6 (2016–2017) data. The 2616 ARIC study participants who wore a leadless, ambulatory ECG monitor (Zio XT Patch) for up to 2 weeks were aged 79±5 years, 42% men, and 26% black. In a subset, 386 participants without clinically recognized AF wore the monitor twice, each time for up to 2 weeks. We characterized the prevalence of subclinical AF (ie, AF detected on the Zio XT Patch without clinically recognized AF) over 2 weeks of monitoring and the diagnostic yield of 4 versus 2 weeks of monitoring. Results: The prevalence of subclinical AF was 2.5%; the prevalence of subclinical AF was 3.3% among white men, 2.5% among white women, 2.1% among black men, and 1.6% among black women. Subclinical AF was mostly intermittent (75%). Among those with intermittent subclinical AF, 91% had AF burden ≤10% during the monitoring period. In a subset of 386 participants without clinical AF, 78% more subclinical AF was detected by 4 weeks versus 2 weeks of ECG monitoring. Conclusions: In our study, the prevalence of subclinical AF was lower than previously reported and monitoring beyond 2 weeks provided substantial incremental diagnostic yield. Future studies should focus on individuals with higher risk to increase diagnostic yield and consider continuous monitoring duration longer than 2 weeks.

Context Polycystic ovary syndrome (PCOS), a condition of androgen excess in women, is associated with cardiometabolic risk factors; however, this association is not fully characterized in a population-based sample of premenopausal women and high-risk groups such as Hispanics/Latinas. Objective We examined the association of PCOS signs and metabolic syndrome (MetS) in premenopausal Hispanic/Latina women. Methods This cross-sectional analysis includes 1427 women age 24 to 44 years from the Hispanic Community Health Study/Study of Latinos. PCOS signs included menstrual cycle greater than 35 days or irregular, self-reported PCOS, and oral contraceptive use to regulate periods or acne, and a composite of 1 or more PCOS signs. We calculated odds ratios (OR) and 95% CI for MetS, accounting for sociodemographic factors and the complex survey design; an additional model included body mass index (BMI). Results The mean age was 34 years and 30% reported any PCOS sign. The odds of MetS were higher in women reporting cycles greater than 35 days or irregular (OR 1.63; CI: 1.07-2.49) vs cycles 24 to 35 days, self-reported PCOS (OR 2.49; CI: 1.38-4.50) vs no PCOS, and any PCOS sign (OR 1.58; CI: 1.10-2.26) vs none. We found no association between OC use to regulate periods or acne and MetS (OR 1.1; CI: 0.6-1.8). When adjusting for BMI, only the association of self-reported PCOS and MetS was attenuated (OR 1.78; CI: 0.92-3.44). Conclusions In Hispanic/Latina women, irregular menstrual cycles, self-reported PCOS, and any PCOS sign were associated with MetS and could indicate women at metabolic disease risk.

Background: Several heart failure (HF) risk factors, including hypertension, diabetes mellitus, obesity, and physical activity, are well described. However, the degree to which optimization of these modifiable risk factors might impact the incidence of HF is not yet fully defined. Hypothesis: We hypothesized more optimal control of major modifiable HF risk factors is associated with progressively lower HF risk. Methods: We performed a prospective analysis of 13,534 ARIC participants (mean age 57, 55% female), examining HF risk associations of different cutpoints of glycemia (HbA1c), systolic blood pressure (SBP), body mass index (BMI) and physical activity (assessed at Visit 2 [1990-92], except for physical activity assessed at Visit 1 (1987-89]). Optimal risk factor control was defined as HbA1c < 7%, SBP < 120 mmHg, BMI 18.5-25 kg/m 2 , and AHA-recommended activity levels. Severely uncontrolled risk factors were defined as HbA1c > 8%, SBP > 160 mmHg, BMI > 35 kg/m 2 and no exercise physical activity. Intermediate values were considered mild to moderately uncontrolled. Cox models simultaneously including all risk factors were constructed to assess associations of risk factor levels with incident HF (by discharge codes) after Visit 2 through 2016. Results: There were 2,827 HF events over a median 24 years of follow-up. Risk gradations were seen across categorizations of each risk factor (Table). In the full model, relative to optimal control, HRs were 2.06 for BMI ≥ 35 kg/m 2 , 1.16 for poor physical activity, 2.31 for HbA1c > 8% and 1.80 for SBP ≥ 160 mmHg. No risk gradient was seen from SBP < 120 to 140 mmHg among hypertensives. Incidence rates (per 1000 PYs) were 7.9 for all optimally controlled risk factors, 14.5 for 3-4 mild to moderately uncontrolled risk factors and 39.5 for 3-4 severely uncontrolled risk factors. Conclusion: Optimal control of modifiable risk factors is strongly linked to lower HF risk. Our findings suggest prioritizing optimization of existing risk factors may be central to successful strategies to prevent HF onset.

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.

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.

Estimates of the numbers and rates of acute decompensated heart failure (ADHF) hospitalization are central to understanding health-care utilization and efforts to improve patient care. We comprehensively estimated the frequency, rate, and trends of ADHF hospitalization in the United States. Based on Atherosclerosis Risk in Communities (ARIC) Study surveillance adjudicating 12,450 eligible hospitalizations during 2005–2010, we developed prediction models for ADHF separately for 3 International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 428 discharge diagnosis groups: 428 primary, 428 nonprimary, or 428 absent. We applied the models to data from the National Inpatient Sample (11.5 million hospitalizations of persons aged ≥55 years with eligible ICD-9-CM codes), an all-payer, 20% probability sample of US community hospitals. The average estimated number of ADHF hospitalizations per year was 1.76 million (428 primary, 0.80 million; 428 nonprimary, 0.83 million; 428 absent, 0.13 million). During 1998–2004, the rate of ADHF hospitalization increased by 2.0%/year (95% confidence interval (CI): 1.8, 2.5) versus a 1.4%/year (95% CI: 0.8, 2.1) increase in code 428 primary hospitalizations (P < 0.001). In contrast, during 2005–2011, numbers of ADHF hospitalizations were stable (−0.5%/year; 95% CI: −1.4, 0.3), while the numbers of 428-primary hospitalizations decreased by −1.5%/year (95% CI: −2.2, −0.8) (P for contrast = 0.03). In conclusion, the estimated number of hospitalizations with ADHF is approximately 2 times higher than the number of hospitalizations with ICD-9-CM code 428 in the primary position. The trend increased more steeply prior to 2005 and was relatively flat after 2005.

Background: Limited data suggest normalization of lung function decline with smoking cessation and slower decline with smoking reduction; yet, mechanistic studies suggest ongoing risk. Aims: To test whether former and “light” smoking are associated with accelerated lung function decline compared to never smoking. Methods: The NHLBI Pooled Cohorts Study harmonized spirometry and other measures from US population-based cohorts. Smoking status was self-reported as never, former, or current at each exam. Light current smoking was defined as Results: 25,552 participants from 6 cohorts (mean age 53 years) contributed 70,411 spirometry exams over a median of 7 years. Forty percent were never smokers (NS), 28% sustained former smokers (FS), 10% sustained current smokers (CS), and 23% reported variable status. In adjusted models, compared to NS, FS demonstrated 1.8 mL/year faster FEV1 decline (95% CI, 1.3-2.4) and 19% faster FEV1/FVC decline (95% CI, 14%-24%); these were 20% and 25% of effect sizes for CS. Lung function decline was faster in current light smokers than NS or FS (P Conclusions: Former and light smoking were associated with faster lung function decline than never smoking.

We have previously identified associations of two circulating secondary bile acids (glycocholenate and glycolithocolate sulfate) with atrial fibrillation (AF) risk among blacks. We aimed to replicate these findings in an independent sample including both whites and blacks, and performed a new metabolomic analysis in the combined sample. We studied 3,922 participants from the ARIC cohort followed between 1987 and 2013. Of these, 1,919 had been included in the prior analysis and 2,003 were new samples. 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 one 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 three 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). To conclude, we replicated a prospective association between 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.

Background Previous studies are inconclusive on the shape of the relationship between parity and cardiovascular disease, with few evaluating a range of cardiovascular outcomes. It is also unclear if any relationship between parity and cardiovascular disease is independent of breastfeeding. We examined the associations between parity and cardiovascular outcomes, including adjustment for breastfeeding duration. Methods Data were from 8,609 Caucasian and African-American women, aged 45–64 years, participating in the Atherosclerosis Risk in Communities Study, a prospective epidemiological study with 24 years of follow-up. Cardiovascular outcomes [coronary heart disease (CHD); myocardial infarction (MI); heart failure; stroke] were identified through annual follow-up phone interviews and community-wide hospital surveillance and ascertained through 2012. At baseline and follow-up, parity and total duration of breastfeeding were self-reported. Cox proportional hazards regression models were used to estimate hazard ratios (HR) for the association between parity and cardiovascular outcomes, adjusting for baseline sociodemographic, clinical and lifestyle factors, and breastfeeding duration. Results Women reported never being pregnant (6.0%), or having none (1.6%), 1–2 (36.0%), 3–4 (36.4%), or 5+ (19.7%) live births. During 26 years follow-up, there were the following numbers of incident events: 1,196 CHDs, 733 MIs, 635 strokes and 1321 heart failure events. Compared with women with 1–2 prior births, those with prior pregnancies and no live births had a higher risk of both incident CHD (HR=1.68, 95% CI:1.14–2.47) and heart failure (1.51, 1.07–2.14), after adjustment for baseline characteristics. Women with 5+births had a higher risk of incident CHD (1.30, 1.10–1.55) and hospitalised MI (1.40, 1.13–1.74), after adjustment for baseline characteristics and breastfeeding duration. Conclusions In a diverse cohort of U.S. women, a history of 5+live births is associated with future risk of CHD, specifically, MI, independent of breastfeeding. Having a prior pregnancy and no live birth is associated with a greater risk of CHD and heart failure. Future studies should address whether the increased cardiovascular risk from multiparity arises from biological or lifestyle factors.

Background The American Heart Association has defined metrics of ideal cardiovascular health known as Life's Simple 7 ( LS 7) to prevent cardiovascular disease. We examined the association between LS 7 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 LS 7 score was calculated as the sum of the LS 7 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 LS 7 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 LS 7 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 Previous studies have reported that atrial fibrillation ( AF ) is associated with cognitive decline and dementia. These studies, however, had limited follow‐up, were based mostly on white and highly selected populations, and did not account for attrition. We evaluated the association of incident AF with 20‐year change in cognitive performance (accounting for attrition) and incident dementia in the ARIC (Atherosclerosis Risk in Communities) Study. Methods and Results We analyzed data from 12 515 participants (mean age, 56.9 [ SD , 5.7] years in 1990–1992; 56% women and 24% black) from 1990 to 1992 through 2011 to 2013. Incident AF was ascertained from study ECG s and hospital discharge codes. Cognitive tests were performed in 1990 to 1992, 1996 to 1998, and 2011 to 2013. Incident dementia was clinician adjudicated. We used generalized estimating equations and Cox proportional hazards models to assess the association of time‐dependent AF with change in Z scores of cognitive tests and incident dementia, respectively. During 20 years, 2106 participants developed AF and 1157 participants developed dementia. After accounting for cardiovascular risk factors, including ischemic stroke, the average decline over 20 years in global cognitive Z score was 0.115 (95% confidence interval, 0.014–0.215) greater in participants with AF than in those without AF . Further adjustment for attrition by multiple imputation by chained equations strengthened the association. In addition, incident AF was associated with an increased risk of dementia (hazard ratio, 1.23; 95% confidence interval, 1.04–1.45), after adjusting for cardiovascular risk factors, including ischemic stroke. Conclusions AF is associated with greater cognitive decline and increased risk of dementia, independent of ischemic stroke. Because cognitive decline is a precursor to dementia, our findings prompt further investigation to identify specific treatments for AF that will delay the trajectory of cognitive decline and, thus, prevent dementia in patients with AF.

Introduction: Sleep apnea (SA) is associated with burden of atrial fibrillation (AF), but studies of SA and ectopic beats, potential triggers of AF, are sparse. Our study contributes by examining the association of SA with AF, premature atrial contractions (PACs), and premature ventricular contractions (PVCs) from 48-hour continuous ambulatory electrocardiogram (aECG) monitoring. Methods: The study population includes 716 black and 438 white participants from the ARIC 48-hour aECG ancillary study, after excluding those with a paced rhythm (n=43) or poor quality measures (n=8). SA was defined as self-reported physician diagnosis or hospital discharge records with ICD-9-CM codes for SA. Prevalent AF was defined using 48-hour aECG monitoring, study visit ECGs, or hospital discharge code (427.3) since study baseline in 1986-1987. PACs and PVCs were defined if ectopy was present 1-5% (occasional) and >5% (frequent) of the recording time versus Results: Participants with SA (unweighted N=217) were more likely to be female (55%), white race (52%), current smokers (57%), have hypertension (82%), and be obese (57%). Participants with SA were 7.3 (95% CI: 3.7, 14.5) times more likely to have AF compared to those without SA after adjusting for covariates. Compared to participants without SA, the relative odds of occasional and frequent PACs versus the referent was increased by 20% and 50% respectively among participants with SA after adjusting for confounders, although not statistically significant. The association was similar and not statistically significant for frequent PVCs. Conclusions: In a community-based population using standardized 48-hour aECG monitoring, SA was associated with prevalent AF, but not significantly associated with PACs or PVCs. Further study is needed to establish mechanisms that link SA and cardiac arrhythmias.

Introduction: Lower heart rate variability (HRV) is an indicator of cardiac autonomic dysfunction which is associated with cardiovascular disease in diabetes. Whether pre-diabetes insulin resistance contributes to lower HRV is not clear; insulin resistance (IR) indexes reflect different aspects of IR, including dysregulation of glucose, insulin, and lipids. We hypothesized that IR indexes are inversely associated with HRV. Methods: We analyzed 48-hour ambulatory electrocardiograms on 759 adults in a sample of the ARIC Study, excluding diabetes, antiarrhythmic medications, and missing/poor quality recordings. Insulin resistance indexes were defined as quartiles for the homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride to HDL-C ratio (TG/HDL-C), and triglyceride-glucose index (TyG). Low HRV was defined as th percentile for time domain measures -- including the standard deviation of all NN intervals (SDNN) and square root of the mean squared differences of successive NN intervals (RMSSD), and frequency domain measures -- including the high-frequency (HF) and low-frequency (LF) spectral components. Logistic regression with weights for sampling and nonresponse was used to estimate odds ratios and 95% confidence intervals (OR, 95% CI). Results: Mean age was 75 years [993 (63%) women, 688 (43%) African American]. The following results are reported for TyG. For time domain measures, high IR indexes were significantly associated with low SDNN (OR 1.83, 95% CI 1.09, 3.07), but not with low RMSSD (OR 1.48, 95% CI 0.89, 2.46). For frequency domain measures, high IR indexes were not associated with low HF (OR 1.62, 95% CI 0.96, 2.74), but significantly associated with low LF (OR 1.95, 95% CI 1.15, 3.30). Although results for other indexes were in the same direction, most were not statistically significant. Conclusions: Insulin resistance indexes may be inversely associated with HRV. An understanding of this relationship informs public health strategies for prevention of cardiovascular risk.

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.

Background Reduced estimated glomerular filtration rate ( eGFR ) and elevated urinary albumin‐to‐creatinine ratio ( ACR ) individually increase risk of cardiovascular disease ( CVD ). We hypothesized that these associations are stronger among people with abnormal (both low and high) hemoglobin levels. Methods and Results Using 5801 participants with available hemoglobin measures of the ARIC (Atherosclerosis Risk in Community) study in 1996–1998, we explored the cross‐sectional association of eGFR and ACR with hemoglobin levels and their longitudinal associations with CVD (heart failure, coronary heart disease, and stroke) risk through 2013. At baseline, 8.8% had anemia (eGFR 30 to 59 compared with ≥90 mL/min per 1.73 m 2 and 1.45 (1.07–1.95) for ACR ≥30 compared with ACR ≥30 mg/g was also associated with high hemoglobin (prevalence ratio, 1.57 [1.12–2.19] compared with CVD s among 5098 CVD ‐free participants at baseline. In multivariable Cox models, lower eGFR , higher ACR , and anemia were each independently associated with CVD risk, with the association of low eGFR being slightly stronger in anemia ( P ‐for‐interaction, 0.072). There was no hemoglobin‐ ACR interaction; however, when CVD subtypes were analyzed separately, risk of coronary heart disease and stroke associated with high ACR was slightly stronger in high hemoglobin ( P ‐for‐interaction, 0.074). Conclusions Kidney function, albuminuria, and anemia were correlated and independently associated with CVD risk. Correlation and potential interaction for atherosclerotic CVD between albuminuria and high hemoglobin deserve further investigation.

Reports on the burden of heart failure (HF) have largely omitted HF diagnosed in outpatient settings. We quantified annual incidence rates ([IR] per 1,000 person years) of HF identified in ambulatory clinics, emergency departments (EDs), and during hospital stays in a national probability sample of Medicare beneficiaries from 2008 to 2014, by age and race/ethnicity. A 20% random sample of Medicare beneficiaries ages ≥65 years with continuous Medicare Parts A, B, and D coverage was used to estimate annual IRs of HF identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Of the 681,487 beneficiaries with incident HF from 2008 to 2014, 283,451 (41%) presented in ambulatory clinics, 76,919 (11%) in EDs, and 321,117 (47%) in hospitals. Overall, incidence of HF in ambulatory clinics decreased from 2008 (IR 22.2, 95% confidence interval [CI] 22.0, 22.4) to 2014 (IR 15.0, 95% CI 14.8, 15.1). Similarly, incidence of HF-related ED visits without an admission to the hospital decreased somewhat from 2008 (IR 5.5, 95% CI 5.4, 5.6) to 2012 (IR 4.2, 95% CI 4.1, 4.3) and stabilized from 2013 to 2014. Similar to previous reports, HF hospitalizations, both International Classification of Diseases, Ninth Revision, Clinical Modification code 428.x in the primary and any position, decreased over the study period. More than half of all new cases of HF in Medicare beneficiaries presented in an ambulatory clinic or ED. The overall incidence of HF decreased from 2008 to 2014, regardless of health-care setting. In conclusion, consideration of outpatient HF is warranted to better understand the burden of HF and its temporal trends.

CONTEXT: The homeostatic model assessment of insulin resistance (HOMA-IR) and triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) are insulin resistance indexes routinely used in clinical and population-based studies; however, their short-term repeatability is not well characterized. OBJECTIVE: To quantify the short-term repeatability of insulin resistance indexes and their analytes, consisting of fasting glucose and insulin for HOMA-IR and TG and HDL-C for TG/HDL-C. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 102 adults 68 to 88 years old without diabetes attended an initial examination and repeated examination (mean, 46 days; range, 28 to 102 days). Blood samples were collected, processed, shipped, and assayed following a standardized protocol. MAIN OUTCOME MEASURES: Repeatability was quantified using the intraclass correlation coefficient (ICC) and within-person coefficient of variation (CV). Minimum detectable change (MDC(95)) and minimum detectable difference with 95% confidence (MDD(95)) were quantified. RESULTS: For HOMA-IR, insulin, and fasting glucose, the ICCs were 0.70, 0.68, and 0.70, respectively; their respective within-person CVs were 30.4%, 28.8%, and 5.6%. For TG/HDL-C, TG, and HDL-C, the ICCs were 0.80, 0.68, and 0.91, respectively; their respective within-person CVs were 23.0%, 20.6%, and 8.2%. The MDC(95) was 2.3 for HOMA-IR and 1.4 for TG/HDL-C. The MDD(95) for a sample of n = 100 was 0.8 for HOMA-IR and 0.6 for TG/HDL-C. CONCLUSIONS: Short-term repeatability was fair to good for HOMA-IR and excellent for TG/HDL-C according to suggested benchmarks, reflecting the short-term variability of their analytes. These measurement properties can inform the use of these indexes in clinical and population-based studies.

Objective The aim of this study was to assess the relationship between abnormally increased P-wave terminal force in lead V1, an electrocardiographic (ECG) marker of left atrial abnormality, and incident ischemic stroke subtypes. We hypothesized that associations would be stronger with nonlacunar stroke, given that we expected left atrial abnormality to reflect the risk of thromboembolism rather than in situ cerebral small-vessel occlusion. Methods Our cohort comprised 14,542 participants 45 to 64 years of age prospectively enrolled in the Atherosclerosis Risk in Communities study and free of clinically apparent atrial fibrillation (AF) at baseline. Left atrial abnormality was defined as PTFV1 >4,000μV*ms. Outcomes were adjudicated ischemic stroke, nonlacunar (including cardioembolic) ischemic stroke, and lacunar stroke. Results During a median follow-up period of 22 years (interquartile range, 19–23 years), 904 participants (6.2%) experienced a definite or probable ischemic stroke. A higher incidence of stroke occurred in those with baseline left atrial abnormality (incidence rate per 1,000 person-years, 6.3; 95% confidence interval [CI]: 5.4–7.4) than in those without (incidence rate per 1,000 person-years, 2.9; 95% CI: 2.7–3.1; p < 0.001). In Cox regression models adjusted for potential confounders and incident AF, left atrial abnormality was associated with incident ischemic stroke (hazard ratio [HR]: 1.33; 95% CI: 1.11–1.59). This association was limited to nonlacunar stroke (HR, 1.49; 95% CI: 1.07–2.07) as opposed to lacunar stroke (HR, 0.89; 95% CI: 0.57–1.40). Interpretation We found an association between ECG-defined left atrial abnormality and subsequent nonlacunar ischemic stroke. Our findings suggest that an underlying atrial cardiopathy may cause left atrial thromboembolism in the absence of recognized AF. Ann Neurol 2015;78:Ann Neurol 2015;78:679–696

Background/objectives Empirical investigation of the adequacy of metabolic syndrome (MetS) diagnostic criteria, and whether meaningful subtypes of MetS exist, is needed among Hispanics/Latinos. Methods In 15,825 US Hispanics/Latinos from HCHS/SOL, latent class analysis of MetS components (waist circumference, systolic and diastolic blood pressure, HDL cholesterol, triglycerides, glucose, and antihypertensive, lipid- and glucose-lowering medication use) was used to investigate (1) whether distinct subtypes of MetS could be identified, and how component levels differed between them, and (2) how identified subtypes related to covariates and cardiovascular disease (CVD) prevalence. Results Two latent clusters emerged in both men (n=6317) and women (n=9508): one characterized by relatively healthy mean levels (Non-MetS cluster, 77.1% of men and 67.1% of women) and the other by clinically elevated mean levels (MetS cluster, 22.9% of men and 32.9% of women) across most MetS components. These clusters showed expected associations with covariates and CVD prevalence. Notable results suggest that (1) HDL cholesterol may poorly differentiate between US Hispanics/Latinos with and without MetS (mean=45.4 vs. 44.6mg/dL for men and 51.3 vs. 52.0mg/dL for women in the MetS vs. Non-MetS clusters, respectively) and (2) the NCEP-ATP III 88cm waist circumference cutoff for US females may not optimize diagnosis among Hispanic/Latino women (MetS cluster mean waist circumference=102.5cm). Conclusions Beyond classification into having MetS or not, additional subtypes of MetS do not clearly emerge in US Hispanics/Latinos. Current diagnostic cutoffs for some components may not optimize MetS identification among this population.

Anemia is associated with poor prognosis in patients hospitalized with acute decompensated heart failure (ADHF). Whether the impact of anemia differs by heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction (HFrEF) is uncertain. We examined hospital surveillance data captured by the Atherosclerosis Risk in Communities Study from January 1, 2005, to December 31, 2010. Diagnoses of ADHF were validated by standardized physician review of the medical record. Anemia was classified using the World Health Organization criteria (12 g/dl for women and13 g/dl for men), and HF type was determined by the ejection fraction (40% for HFrEF and ≥40% for HFpEF). Hospital length of stay and 1-year mortality outcomes were analyzed by multivariable regression, weighted to account for the sampling design, and adjusted for demographics and clinical covariates. Over 6 years, 15,461 (weighted) hospitalized events for ADHF (59% HFrEF) occurred in the catchment of the Atherosclerosis Risk in Communities, based on 3,309 sampled events. Anemia was associated with a mortality hazard ratio of 2.1 (95% confidence interval [CI] 1.6 to 2.7) in patients classified with HFpEF and 1.4 (95% CI 1.1 to 1.7) in those with HFrEF; p for interaction = 0.05. The mean increase in length of hospital stay associated with anemia was 3.5 days (95% CI 3.4 to 3.6) for patients with HFpEF, compared with 1.8 days (95% CI 1.7 to 1.9) for those with HFrEF; p for interaction0.0001. In conclusion, the incremental risks of death and lengthened hospital stay associated with anemia are more pronounced in ADHF patients classified with HFpEF than HFrEF.

Introduction: Chronic lower respiratory disease (CLRD) mortality has not dropped, despite less smoking in the US. Reliable trend data on CLRD incidence are needed. Aim: To compare incidence of severe obstructive lung events (SOLE) vs major adverse cardiac events (MACE) in US population-based cohorts. Methods: The NHLBI Pooled Cohorts Study harmonized data from 4 US cohorts. We excluded those with prevalent clinical CLRD or prior myocardial infarction (MI) and analyzed only incident/first events, 1987-2016. SOLE were defined as hospitalizations/deaths with CLRD (ICD9 491-493, 496; ICD10 J40-46) as 1 ◦ discharge diagnosis or underlying cause of death; MACE were MD-adjudicated MI, cardiac arrest, and CHD death. Incidence density rates (IDRs) were calculated per 1000 person-years adjusting for age, sex, race and cohort. Results: 22,413 adults contributed 353,954 person-years (mean age 61); 738 participants had incident SOLE and 3,746 had incident MACE; 208 had both. IDRs for MACE declined 6-fold (14.6 to 2.6) over 3 decades, while IDRs for SOLE were relatively stable (0.7 to 0.5). MACE and SOLE IDRs converged in both current and never-smokers. Conclusions: In contrast to large reductions in incident cardiovascular events, incident respiratory event rates remained stable over the last 3 decades in US cohorts, despite decreased smoking, highlighting the public health importance of and need for preventive approaches to CLRD.

Background Ceruloplasmin (CP) may promote structural changes in the atrium making it more arrhythmogenic. We assessed the associations between CP, CP-associated genetic variants, and incident atrial fibrillation (AF) in the Atherosclerosis Risk in Communities (ARIC) study. Methods and results We studied 10,059 men and women without prevalent AF aged 53 to 75years in 1996–1998 and followed through 2012. Circulating CP was measured in stored blood samples obtained in 1996–1998. Polymorphisms rs11708215 and rs13072552, previously associated with CP concentrations, were measured in 10,059 and 8829 participants respectively. AF was ascertained from study electrocardiograms, hospital discharge codes, and death certificates. Multivariable Cox models were run to study the association between circulating CP, CP-associated polymorphisms, and the incidence of AF. Over 10.5years of mean follow-up, 1357 cases of AF were identified. After adjusting for traditional risk factors and biomarkers, higher levels of circulating CP were associated with incident AF (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.11, 1.61 comparing top to bottom quartiles). Both rs11708215 and rs13072552 were significantly associated with CP levels. Presence of the CP-increasing alleles in rs11708215 and rs13072552, however, were significantly associated with lower risk of AF in whites (HR 0.84, 95%CI 0.76, 0.94, p =0.002 and HR 0.83; 95%CI 0.69, 0.99, p =0.043 respectively per CP-increasing allele in the final adjusted model) but not in African Americans. Conclusions Even though higher CP concentrations were associated with increased AF risk, genetic variants associated with higher CP decreased the risk of AF in whites. Our results suggest that circulating CP levels may not be causally related to risk of incident AF.

Objectives The aim of this study was to describe the relationship between ankle brachial index (ABI) and the risk for heart failure (HF). Background The ABI is a simple, noninvasive measure associated with atherosclerotic cardiovascular disease and death; however, the relationship between ABI and risk for HF is less well characterized. Methods Between 1987 and 1989 in the ARIC (Atherosclerosis Risk In Communities) study, an oscillometric device was used to measure blood pressure in a single upper and randomly chosen lower extremity to determine the ABI. Incident HF events were defined by the first hospitalization with an International Classification of Diseases, Ninth Revision, code of 428.x through 2008. The risk for HF was assessed across the ABI range using restricted cubic splines and Cox proportional hazards models. Results ABI was available in 13,150 participants free from prevalent HF. Over a mean 17.7 years of follow-up, 1,809 incident HF events occurred. After adjustment for traditional HF risk factors, prevalent coronary heart disease, subclinical carotid atherosclerosis, and interim myocardial infarction, compared with an ABI of 1.01 to 1.40, participants with ABIs ≤0.90 were at increased risk for HF (hazard ratio: 1.40; 95% confidence interval: 1.12 to 1.74), as were participants with ABIs of 0.91 to 1.00 (hazard ratio: 1.36; 95% confidence interval: 1.17 to 1.59). Conclusions In a middle-age community cohort, an ABI ≤1.00 was significantly associated with an increased risk for HF, independent of traditional HF risk factors, prevalent coronary heart disease, carotid atherosclerosis, and interim myocardial infarction. Low ABI may reflect not only overt atherosclerosis but also pathologic processes in the development of HF beyond epicardial atherosclerotic disease and myocardial infarction alone. A low ABI, as a simple, noninvasive measure, may be a risk marker for HF.