Joint Association of Albuminuria and Left Ventricular Hypertrophy With Incident Heart Failure in Adults at High Risk With Hypertension: A Systolic Blood Pressure Intervention Trial Substudy.

Albuminuria and left ventricular hypertrophy (LVH) are independent predictors of heart failure (HF); however, to the best of our knowledge, their combined effect on the risk of HF has not yet been explored. Therefore, we examined the joint associations of albuminuria and electrocardiographic-LVH with incident acute decompensated HF (ADHF), and whether albuminuria/LVH combinations modified the effects of blood pressure control strategy in reducing the risk of ADHF. A total of 8,511 participants from the Systolic Blood Pressure Intervention Trial (SPRINT) were included. Electrocardiographic-LVH was present if any of the following criteria were present: Cornell voltage, Cornell voltage product, or Sokolow-Lyon. Albuminuria was defined as urine albumin/creatinine ratio ≥30 mg/g. ADHF was defined as hospitalization or emergency department visit for ADHF. Cox proportional hazard models were used to examine the association of neither LVH nor albuminuria (reference), either LVH or albuminuria, and both (LVH + albuminuria) with incident ADHF. Over a median follow-up of 3.2 years, 182 cases of ADHF occurred. In adjusted models, concomitant albuminuria and LVH were associated with greater risk of ADHF than either albuminuria or LVH in isolation (hazard ratio [95% confidence interval]: 4.95 [3.22 to 7.62], 2.04 [1.39 to 3.00], and 1.47 [0.93 to 2.32], respectively, additive interaction p = 0.01). The effect of intensive blood pressure in reducing ADHF was attenuated in participants with coexisting albuminuria and LVH without any interaction between treatment group assignment and albuminuria/LVH categories (interaction p = 0.26). In conclusion, albuminuria and LVH are additive predictors of ADHF. The effect of intensive blood pressure control in reducing ADHF risk did not vary significantly across albuminuria/LVH combinations.

Joint Association of Albuminuria and Left Ventricular Hypertrophy with Incident Heart Failure in High-Risk Adults with Hypertension: a SPRINT substudy.

Background: Albuminuria and left ventricular hypertrophy (LVH) are independent predictors of heart failure (HF), however their combined effect on risk of HF has not been explored previously. Objectives: To examine the joint associations of albuminuria and electrocardiographic (ECG) LVH with incident acute decompensated HF (ADHF), and whether albuminuria/LVH combinations modified the effects of blood pressure control strategy in reducing the risk of ADHF. Methods: 8,511 participants from the SPRINT (Systolic Blood Pressure Intervention Trial) were included. ECG-LVH was present if any of the following criteria: Cornell voltage, Cornell voltage product, or Sokolow Lyon were present. Albuminuria was defined as urine albumin-creatinine ratio (UACR) ≥30 mg/g. ADHF was defined as hospitalization or emergency visit for ADHF. Cox proportional hazard models were used to examine the association of neither LVH, nor albuminuria (reference), either LVH or albuminuria, and both (LVH + albuminuria) with incident ADHF. Results: Over a median follow-up of 3.2 years, 182 cases of ADHF occurred. In adjusted models, concomitant albuminuria and LVH were associated with higher risk of ADHF than either albuminuria or LVH in isolation (HR (95% CI): 4.95 (3.22-7.62), 2.04 (1.39-3.00), and 1.47 (0.93-2.32), respectively (additive interaction p=0.01). The effect of intensive blood pressure in decreasing ADHF attenuated among participants with co-existing albuminuria and LVH without any interaction between treatment group assignment and albuminuria/LVH categories (interaction p-value= 0.26). Conclusions: Albuminuria and LVH are additive predictors of ADHF. The effect of intensive blood pressure control in decreasing ADHF risk did not vary significantly across albuminuria/LVH combinations.

Electrocardiographic markers of atrial cardiomyopathy and risk of heart failure in the multi-ethnic study of atherosclerosis (MESA) cohort.

Background: The association of electrocardiographic (ECG) markers of atrial cardiomyopathy with heart failure (HF) and its subtypes is unclear. Methods: This analysis included 6,754 participants free of clinical cardiovascular disease (CVD), including atrial fibrillation (AF), from the Multi-Ethnic Study of Atherosclerosis. Five ECG markers of atrial cardiomyopathy (P-wave terminal force in V1 [PTFV1], deep-terminal negativity in V1 [DTNV1], P-wave duration [PWD], P-wave axis [PWA], advanced intra-atrial block [aIAB]) were derived from digitally recorded electrocardiograms. Incident HF events through 2018 were centrally adjudicated. An ejection fraction (EF) of 50% at the time of HF was used to classify HF as HF with reduced EF (HFrEF), HF with preserved EF (HFpEF), or unclassified HF. Cox proportional hazard models were used to examine the associations of markers of atrial cardiomyopathy with HF. The Lunn-McNeil method was used to compare the associations in HFrEF vs. HFpEF. Results: 413 HF events occurred over a median follow-up of 16 years. In adjusted models, abnormal PTFV1 (HR (95%CI): 1.56(1.15-2.13), abnormal PWA (HR (95%CI):1.60(1.16-2.22), aIAB (HR (95%CI):2.62(1.47-4.69), DTNPV1 (HR (95%CI): 2.99(1.63-7.33), and abnormal PWD (HR (95%CI): 1.33(1.02-1.73), were associated with increased HF risk. These associations persisted after further adjustments for intercurrent AF events. No significant differences in the strength of association of each ECG predictor with HFrEF and HFpEF were noted. Conclusions: Atrial cardiomyopathy defined by ECG markers is associated with HF, with no differences in the strength of association between HFrEF and HFpEF. Markers of atrial Cardiomyopathy may help identify individuals at risk of developing HF.

Interrelations between albuminuria, electrocardiographic left atrial abnormality, and incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.

BACKGROUND: The objective of the study was to examine the joint associations of albuminuria and electrocardiographic left atrial abnormality (ECG-LAA) with incident atrial fibrillation (AF) and whether this relationship varies by race. METHODS: This analysis included 6670 participants free of clinical cardiovascular disease (CVD), including atrial fibrillation (AF), from the Multi-Ethnic Study of Atherosclerosis. ECG-LAA was defined as P-wave terminal force in V1 [PTFV1] >5000 µV × ms. Albuminuria was defined as urine albumin-creatinine ratio (UACR) ≥30 mg/g. Incident AF events through 2015 were ascertained from hospital discharge records and study-scheduled electrocardiograms. Cox proportional hazard models were used to examine the association of "no albuminuria + no ECG-LAA (reference)", "isolated albuminuria", "isolated ECG-LAA" and "albuminuria + ECG-LAA" with incident AF. RESULTS: Over a median follow-up of 13.8 years, 979 incident cases of AF occurred. In adjusted models, the concomitant presence of ECG-LAA and albuminuria was associated with a higher risk of AF than either ECG-LAA or albuminuria in isolation (HR (95% CI): 2.43 (1.65-3.58), 1.33 (1.05-1.69), and 1.55 (1.27-1.88), respectively (interaction p-value = 0.50). Effect modification by race was observed with a 4-fold greater AF risk in Black participants with albuminuria + ECG-LAA (HR (95%CI): 4.37 (2.38-8.01) but no significant association in White participants (HR (95% CI) 0.60 (0.19-1.92) respectively; (interaction p-value for race x albuminuria-ECG-LAA combination = 0.05). CONCLUSIONS: Concomitant presence of ECG-LAA and albuminuria confers a higher risk of AF compared to either one in isolation with a stronger association in Blacks than Whites.

Relationship Between High Blood Pressure, Atrial Cardiopathy, and Mortality in the General Population.

BACKGROUND: Atrial cardiopathy is associated with an increased risk of mortality. However, it is unclear whether this association is modified by hypertension, a risk factor for both atrial cardiopathy and mortality. METHODS: This analysis included 8,023 participants from the Third National Health and Nutrition Examination Survey. Electrocardiographic deep terminal negativity of P-wave in V1 ≥100 µV defined atrial cardiopathy. National Death Index was used to identify the date and cause of death. Cox proportional hazard analysis was used to examine the association of atrial cardiopathy with mortality among participants stratified by hypertension status. RESULTS: In total 2.7% of the participants had atrial cardiopathy. Over a median follow-up of 14 years, 2,922 all-cause deaths occurred, of which 1,058 were CVD. All-cause death rates were almost double among participants with concomitant atrial cardiopathy and elevated blood pressure (BP) (120-129/<80), stage 1 (130-139/80-89), or stage 2 hypertension (≥140/≥90) compared to their counterparts in the same hypertension stages without atrial cardiopathy (47.8, 61.3, and 80.2 vs. 23, 24.7, and 44.8 per 1,000 person-years (PY), respectively). In multivariable-adjusted models, a stronger association between atrial cardiopathy and all-cause mortality was observed in the presence compared to the absence of hypertension (HR (95% CI): 1.59 (1.25-2.01) vs. 0.67 (0.41-1.10), respectively, interaction P-value = 0.009). Similarly, an association between atrial cardiopathy and cardiovascular disease (CVD) mortality was observed in the presence compared to the absence of hypertension (HR (95% CI): 1.64 (1.08-2.47) vs. 0.63 (0.20-2.00), respectively, interaction P-value = 0.20). CONCLUSIONS: Concomitant presence of high BP and atrial cardiopathy carries a higher risk of mortality, and the risk increases with higher BP levels.

Association of physical activity with the incidence of atrial fibrillation in persons > 65 years old: the Atherosclerosis Risk in Communities (ARIC) study.

AIMS: To evaluate the association of physical activity (PA) with atrial fibrillation (AF) incidence in an elderly population. METHODS: We studied 5166 participants of the Atherosclerosis Risk in Communities cohort examined in 2011-2013 free of AF. Self-reported PA was evaluated with a validated questionnaire. Weekly minutes of leisure-time moderate to vigorous physical activity (MVPA) were calculated and categorized using the 2018 Physical Activity Guidelines for Americans (no activity [0 min/week], low [> 0- < 150 min/week], adequate [150- < 300 min/week], high [≥ 300 min/week]). Incident AF through 2019 was ascertained from hospital discharges and death certificates. Cox models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for AF by levels of physical activity adjusting for potential confounders. RESULTS: The mean (SD) age for the sample was 75 (5) years (59% female, 22% Black). During a mean (SD) follow-up time of 6.3 (2.0) years, 703 AF events were identified. The association of MVPA with AF incidence showed a U-shaped relationship. Compared to those not engaging in MVPA, individuals with low MVPA had a 23% lower hazard of AF (HR = 0.77; 95% CI 0.61, 0.96), while those with adequate MVPA had a 14% lower hazard (HR 0.86; 95% CI 0.69, 1.06). High levels of MVPA were not associated with AF risk (HR 0.97; 95% CI 0.78, 1.20). CONCLUSION: This study suggests that being involved in low to moderate levels of MVPA is associated with lower AF risk, with no evidence of increased risk of AF in those with higher levels of MVPA.

Risk Factors for Dementia in Patients With Atrial Fibrillation.

Although dementia and atrial fibrillation (AF) are common in older adults, risk factors for dementia have not been sufficiently characterized in patients with AF. We studied 621,773 patients with AF without dementia at the time of AF diagnosis who were enrolled in the MarketScan Commercial and Medicare Supplemental databases from 2007 to 2015. Dementia incidence and presence of predictors at the time of AF diagnosis (cardiometabolic conditions, mental and neurologic disorders, and other chronic conditions) were based on International Classification of Diseases, Ninth Revision, Clinical Modification codes in outpatient and inpatient claims, whereas medication usage was based on outpatient pharmacy claims. A frailty score was calculated using a previously established algorithm. The associations between the predictors of interest and dementia were assessed with multivariable Cox models. Patients had a mean age of 68 years (SD 14 years) and 41% were women. During a mean follow-up of 2.0 years, there were 16,073 cases of dementia. The strongest predictors of dementia were frailty (hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.40 to 1.45, per 1-SD increase in the score), cognitive impairment (HR 1.50, 95% CI 1.36 to 1.65), mood disorders (HR 1.49, 95% CI 1.32 to 1.70), schizophrenia (HR 1.86, 95% CI 1.75 to 1.98), and substance abuse (HR 1.58, 95% CI 1.39 to 1.80). Among cardiometabolic conditions, only stroke (HR 1.17, 95% CI 1.13 to 1.22) and diabetes mellitus (HR 1.14, 95% CI 1.11 to 1.18) were associated with small increases in dementia risk after adjusting for demographics, frailty, co-morbidities, and medications. We have identified several risk factors for dementia in patients with AF.

Reliability and Validity of the Composite Activity-Related Fall Risk Scale.

Introduction: The newly developed Composite Activity-related Risk of Falls Scale (CARFS) is designed to measure composite activity-related risk of falls (CARF) in relation to the activity-specific fear of falling and physical behavior. This study tested the reliability and validity of the CARFS in older people with various health statuses and persons with stroke or spinal cord injury. Methods: Participants included 70 older adults, 38 persons with stroke, and 18 with spinal cord injury. They were first surveyed using a combined questionnaire including the CARFS and activity-specific balance confidence (ABC) scale in addition to items asking for personal and disease-related information, fall history, walking independence levels for examining internal consistency, ceiling and floor effects, and convergent validity in each participant group. One week after the initial survey, 33 older participants were reexamined using the CARFS to analyze test-retest reliability, where a minimal detectable change was found. Significance was set at α = 0.05 for all analyses. Results: The CARFS showed excellent test-retest reliability in the dimensions of fear of falling, physical behavior, and CARF [ICC (3,1) = 0.972, 0.994, and 0.994, respectively for their overall score], with a minimal detectable change of 3.944 in the older population. The internal consistency of CARFS items was excellent in the older participants, good in participants with stroke or spinal cord injury (Cronbach's alpha = 0.945, 0.843, 0.831 in each participant group, respectively). No ceiling and floor effects were demonstrated in the wide range of people. For the convergent validity, overall CARF score was significantly correlated with the average ABC score in each participant group (rho = -0.824, -0.761, and -0.601, respectively; p < 0.01), and was significantly correlated with walking independence levels in each participant group (rho = -0.636, -0.423, and -0.522, respectively; p < 0.01). It showed weak correlation with the number of previous falls only in participants with stroke (rho = 0.291, p = 0.076). Conclusion: The CARFS is a reliable and valid tool for measuring fall risk in older people and persons with stroke or spinal cord injury.

Association of Brain Volumes and White Matter Injury With Race, Ethnicity, and Cardiovascular Risk Factors: The Multi-Ethnic Study of Atherosclerosis.

Background Cardiovascular risk factors are associated with cognitive decline and dementia. Magnetic resonance imaging provides sensitive measurement of brain morphology and vascular brain injury. However, associations of risk factors with brain magnetic resonance imaging findings have largely been studied in White participants. We investigated associations of race, ethnicity, and cardiovascular risk factors with brain morphology and white matter (WM) injury in a diverse population. Methods and Results In the Multi-Ethnic Study of Atherosclerosis, measures were made in 2018 to 2019 of total brain volume, gray matter and WM volume, and WM injury, including WM hyperintensity volume and WM fractional anisotropy. We assessed cross-sectional associations of race and ethnicity and of cardiovascular risk factors with magnetic resonance imaging measures. Magnetic resonance imaging data were complete in 1036 participants; 25% Black, 15% Chinese-American, 19% Hispanic, and 41% White. Mean (SD) age was 72 (8) years and 53% were women. Although WM injury was greater in Black than in White participants in a minimally adjusted model, additional adjustment for cardiovascular risk factors and socioeconomic status each attenuated this association, rendering it nonsignificant. Overall, greater average WM hyperintensity volume was associated with older age and current smoking (69% greater vs never smoking); lower fractional anisotropy was additionally associated with higher diastolic blood pressure, use of antihypertensive medication, and diabetes. Conclusions We found no statistically significant difference in measures of WM injury by race and ethnicity after adjustment for cardiovascular risk factors and socioeconomic status. In all racial and ethnic groups, older age, current smoking, hypertension, and diabetes were strongly associated with WM injury.

Identification of Incident Atrial Fibrillation From Electronic Medical Records.

Background Electronic medical records are increasingly used to identify disease cohorts; however, computable phenotypes using electronic medical record data are often unable to distinguish between prevalent and incident cases. Methods and Results We identified all Olmsted County, Minnesota residents aged ≥18 with a first-ever International Classification of Diseases, Ninth Revision (ICD-9) diagnostic code for atrial fibrillation or atrial flutter from 2000 to 2014 (N=6177), and a random sample with an International Classification of Diseases, Tenth Revision (ICD-10) code from 2016 to 2018 (N=200). Trained nurse abstractors reviewed all medical records to validate the events and ascertain the date of onset (incidence date). Various algorithms based on number and types of codes (inpatient/outpatient), medications, and procedures were evaluated. Positive predictive value (PPV) and sensitivity of the algorithms were calculated. The lowest PPV was observed for 1 code (64.4%), and the highest PPV was observed for 2 codes (any type) >7 days apart but within 1 year (71.6%). Requiring either 1 inpatient or 2 outpatient codes separated by >7 days but within 1 year had the best balance between PPV (69.9%) and sensitivity (95.5%). PPVs were slightly higher using ICD-10 codes. Requiring an anticoagulant or antiarrhythmic prescription or electrical cardioversion in addition to diagnostic code(s) modestly improved the PPVs at the expense of large reductions in sensitivity. Conclusions We developed simple, exportable, computable phenotypes for atrial fibrillation using structured electronic medical record data. However, use of diagnostic codes to identify incident atrial fibrillation is prone to some misclassification. Further study is warranted to determine whether more complex phenotypes, including unstructured data sources or using machine learning techniques, may improve the accuracy of identifying incident atrial fibrillation.

Activities-specific performance frequency can accurately detect fallers in elderly populations: an alternative method for quantifying activity restrictions.

BACKGROUND: The high prevalence of falling among older adults constitutes a major public and clinical health concern. Many elderly persons may develop activities-specific restriction due to the risk of falling. This highlights the need for relevant evaluative tools. METHODS: This cross-sectional study used activities-specific performance frequency indicators to quantify activity restrictions in elderly participants, with all measures based on items from the Activities-Specific Balance Confidence (ABC) scale. Specifically, we tested for correlations between activities-specific performance frequency and balance confidence, functional balance/mobility, and fall history. There were 88 elderly participants, including 28 with stroke, 30 with Parkinson's disease, and 30 with no neurological diseases. In addition to their activities-specific performance frequency measures, we collected a series of demographic and health-related characteristics from each participant. We analyzed between-group differences in activities-specific performance frequency and other demographic and health-related characteristics via the one-way analysis of variance and Kruskal-Wallis test. Next, we used the Spearman's rank correlation test and binary logistic regression to investigate the correlations between activities-specific performance frequency and demographic/other health-related characteristics. RESULTS: There were significant group differences in performance frequency for all ABC activity items except for walking around the house, average ABC scores, and functional balance/mobility among normal older adults, participants with strokes and those with Parkinson's disease. Activities-specific performance frequency showed stronger correlations with activities-relevant functional mobility (r=0.250-0.713 for 15 items with significant correlations, 13 activity items with r≧0.4) than with balance confidence (r=0.279-0.668 for 13 items with significant correlations, 10 activity items with r≧0.4). The performance frequency of walking in crowds/bumped was the most sensitive measure for predicting fallers (odd ratio=3.310, p<0.05). CONCLUSIONS: This study proposed and validated the usage of activities-specific performance frequency as an alternative method for quantifying activity restrictions among older adults.

Associations Between Atrial Arrhythmias and Brain Amyloid Deposition: The ARIC-PET Study.

The aim of this study is to determine if there is an association between atrial arrhythmias and brain amyloid-ß (Aß), measured on florbetapir (FBP) PET. 346 nondemented participants from the Atherosclerosis Risk in Communities study underwent FBP-PET, 185 also wore Zio® XT Patch. The associations between global cortical Aß (> 1.2 standardized uptake value ratio) and history of atrial fibrillation, zio-defined atrial tachycardia and premature atrial contractions, each, were evaluated. Among nondemented community-dwelling older adults, we did not find an association between atrial arrhythmias and Aß. Other brain pathology may underlie the association described between atrial arrhythmias and cognition.

Direct Oral Anticoagulants and Warfarin for Atrial Fibrillation Treatment: Rural and Urban Trends in Medicare Beneficiaries.

BACKGROUND: Data are needed on the use of oral anticoagulation in patients with atrial fibrillation (AF) in rural versus urban areas, including the initiation of direct oral anticoagulants (DOACs). OBJECTIVE: We used Medicare data to examine rural/urban differences in anticoagulation use in patients with AF. METHODS: We identified incident AF in a 20% sample of fee-for-service Medicare beneficiaries (aged ≥ 65 years) from 2011 to 2016 and collected ZIP code and covariates at the time of AF. We identified the first anticoagulant prescription filled, if any, following AF diagnosis. We categorized beneficiaries into four rural/urban areas using rural-urban commuting area codes and used Poisson regression models to compare anticoagulant use. RESULTS: We included 447,252 patients with AF (mean age 79 ± 8 years), of which 82% were urban, 9% large rural, 5% small rural, and 4% isolated. The percentage who initiated an anticoagulant rose from 34% in 2011 to 53% in 2016, paralleling the uptake of DOACs. In a multivariable-adjusted analysis, those in rural areas (vs. urban) were more likely to initiate an anticoagulant. However, rural beneficiaries (vs. urban) were less likely to initiate a DOAC; those in isolated areas were 17% less likely (95% confidence interval [CI] 13-20), those in small rural areas were 12% less likely (95% CI 9-15), and those in large rural areas were 10% less likely (95% CI 8-12). CONCLUSION: Among Medicare beneficiaries with AF, anticoagulation use was low but increased over time with the introduction of DOACs. Rural beneficiaries were less likely to receive a DOAC.

Sex differences in treatment strategy and adverse outcomes among patients 75 and older with atrial fibrillation in the MarketScan database.

BACKGROUND: Women with atrial fibrillation (AF) experience greater symptomatology, worse quality of life, and have a higher risk of stroke as compared to men, but are less likely to receive rhythm control treatment. Whether these differences exist in elderly patients with AF, and whether sex modifies the effectiveness of rhythm versus rate control therapy has not been assessed. METHODS: We studied 135,850 men and 139,767 women aged ≥ 75 years diagnosed with AF in the MarketScan Medicare database between 2007 and 2015. Anticoagulant use was defined as use of warfarin or a direct oral anticoagulant. Rate control was defined as use of rate control medication or atrioventricular node ablation. Rhythm control was defined by use of anti-arrhythmic medication, catheter ablation or cardioversion. We used multivariable Poisson and Cox regression models to estimate the association of sex with treatment strategy and to determine whether the association of treatment strategy with adverse outcomes (bleeding, heart failure and stroke) differed by sex. RESULTS: At the time of AF, women were on average (SD) 83.8 (5.6) years old and men 82.5 (5.2) years, respectively. Compared to men, women were less likely to receive an anticoagulant or rhythm control treatment. Rhythm control (vs. rate) was associated with a greater risk for heart failure with a significantly stronger association in women (HR women = 1.41, 95% CI 1.34-1.49; HR men = 1.21, 95% CI 1.15-1.28, p < 0.0001 for interaction). No sex differences were observed for the association of treatment strategy with the risk of bleeding or stroke. CONCLUSION: Sex differences exist in the treatment of AF among patients aged 75 years and older. Women are less likely to receive an anticoagulant and rhythm control treatment. Women were also at a greater risk of experiencing heart failure as compared to men, when treated with rhythm control strategies for AF. Efforts are needed to enhance use AF therapies among women. Future studies will need to delve into the mechanisms underlying these differences.

Shared Decision Making in Cardiac Electrophysiology Procedures and Arrhythmia Management.

Shared decision making (SDM) has been advocated to improve patient care, patient decision acceptance, patient-provider communication, patient motivation, adherence, and patient reported outcomes. Documentation of SDM is endorsed in several society guidelines and is a condition of reimbursement for selected cardiovascular and cardiac arrhythmia procedures. However, many clinicians argue that SDM already occurs with clinical encounter discussions or the process of obtaining informed consent and note the additional imposed workload of using and documenting decision aids without validated tools or evidence that they improve clinical outcomes. In reality, SDM is a process and can be done without decision tools, although the process may be variable. Also, SDM advocates counter that the low-risk process of SDM need not be held to the high bar of demonstrating clinical benefit and that increasing the quality of decision making should be sufficient. Our review leverages a multidisciplinary group of experts in cardiology, cardiac electrophysiology, epidemiology, and SDM, as well as a patient advocate. Our goal is to examine and assess SDM methodology, tools, and available evidence on outcomes in patients with heart rhythm disorders to help determine the value of SDM, assess its possible impact on electrophysiological procedures and cardiac arrhythmia management, better inform regulatory requirements, and identify gaps in knowledge and future needs.

Proteomics and Risk of Atrial Fibrillation in Older Adults (From the Atherosclerosis Risk in Communities [ARIC] Study).

Plasma proteomic profiling may aid in the discovery of novel biomarkers upstream of the development of atrial fibrillation (AF). We used data from the Atherosclerosis Risk in Communities study to examine the relation between large-scale proteomics and incident AF in a cohort of older-aged adults in the United States. We quantified 4,877 plasma proteins in Atherosclerosis Risk in Communities participants at visit 5 (2011-2013) using an aptamer-based proteomic profiling platform. We used Cox proportional hazards models to assess the association between protein levels and incident AF, and explored relation of selected protein biomarkers using annotated pathway analysis. Our study included 4,668 AF-free participants (mean age 75 ± 5 years; 59% female; 20% Black race) with proteomic measures. A total of 585 participants developed AF over a mean follow-up of 5.7 ± 1.7 years. After adjustment for clinical factors associated with AF, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with the risk of incident AF (hazard ratio, 1.82; 95% CI, 1.68 to 1.98; p, 2.91 × 10-45 per doubling of NT-proBNP). In addition, 36 other proteins were also significantly associated with incident AF after Bonferroni correction. We further adjusted for medication use and estimated glomerular filtration rate and found 17 proteins, including angiopoietin-2 and transgelin, that remained significantly associated with incident AF. Pathway analyses implicated the inhibition of matrix metalloproteases as the top canonical pathway in AF pathogenesis. In conclusion, using a large-scale proteomic platform, we identified both novel and established proteins associated with incident AF and explored mechanistic pathways of AF development.

Association of Proton Pump Inhibitors With Higher Risk of Cardiovascular Disease and Heart Failure.

OBJECTIVE: To examine associations of cumulative exposure to proton pump inhibitors (PPIs) with total cardiovascular disease (CVD; composed of stroke, coronary heart disease, and heart failure [HF]) and HF alone in a cohort study of White and African American participants of the Atherosclerosis Risk in Communities (ARIC) study. METHODS: Use of PPIs was assessed by pill bottle inspection at visit 1 (January 1, 1987 to 1989) and up to 10 additional times before baseline (visit 5; 2011 to 2013). We calculated cumulative exposure to PPIs as days of use from visit 1 to baseline. Participants (n=4346 free of total CVD at visit 5; mean age, 75 years) were observed for incident total CVD and HF events through December 31, 2016. We used Cox regression to measure associations of PPIs with total CVD and HF. RESULTS: After adjustment for potential confounding variables, participants with a cumulative exposure to PPIs of more than 5.1 years had a 2.02-fold higher risk of total CVD (95% CI, 1.50 to 2.72) and a 2.21-fold higher risk of HF (95% CI, 1.51 to 3.23) than nonusers. CONCLUSION: Long-term PPI use was associated with twice the risk of total CVD and HF compared with nonusers. Our findings are in concordance with other research and suggest another reason to be cautious of PPI overuse.

Differences in Left Atrial Size and Function and Supraventricular Ectopy Between Black and White Participants in the ARIC Study.

Background Black Americans have more atrial fibrillation risk factors but lower atrial fibrillation risk than White Americans. Left atrial (LA) enlargement and/or dysfunction, frequent atrial tachycardia (AT), and premature atrial contractions (PAC) are associated with increased atrial fibrillation risk. Racial differences in these factors may exist that could explain the difference in atrial fibrillation risk. Methods and Results We included 2133 ARIC (Atherosclerosis Risk in Communities) study participants (aged 74±4.5 years[mean±SD], 59% women, 27% Black participants) who had echocardiograms in 2011 to 2013 and wore the Zio XT Patch (a 2-week continuous heart monitor) in 2016 to 2017. Linear regression was used to analyze (1) differences in AT/day or PAC/hour between Black and White participants, (2) differences in LA measures between Black and White participants, and (3) racial differences in the association of LA measures with AT or PAC frequency. Compared with White participants, Black participants had a higher prevalence of cardiovascular risk factors and disease, lower AT frequency, greater LA size, and lower LA function. After multivariable adjustments, Black participants had 37% (95% CI, 24%-47%) fewer AT runs/day than White participants. No difference in PAC between races was noted. Greater LA size and reduced LA function are associated with more AT and PAC runs; however, no race interaction was present. Conclusions Differences in LA measures are unlikely to explain the difference in atrial fibrillation risk between Black and White individuals. Despite more cardiovascular risk factors and greater atrial remodeling, Black participants have lower AT frequency than White participants. Future research is needed to elucidate the protective mechanisms that confer resilience to atrial arrhythmias in Black individuals.

6-year change in high sensitivity cardiac troponin T and the risk of atrial fibrillation in the Atherosclerosis Risk in Communities cohort.

BACKGROUND: Circulating high sensitivity cardiac troponin T (hs-cTnT) is associated with incidence of atrial fibrillation (AF), but the association of changes in hs-cTnT over time on incident AF has not been explored. HYPOTHESIS: Six-year increase in circulating hs-cTnT will be associated with increased risk of AF and will contribute to improved prediction of incident AF. METHODS: We conducted a prospective cohort analysis of 8431 participants from the Atherosclerosis Risk in Communities (ARIC) study. hs-cTnT change was categorized at visit 2 and 4 as undetectable (<5 ng/L), detectable (≥5 ng/L, <14 ng/L), or elevated (≥14 ng/L). We used Cox regression to examine the association between the combination of hs-cTnT categories at two visits and incident AF. We also assessed the impact of adding absolute hs-cTnT change on risk discrimination for AF by C-statistics and net reclassification improvement (NRI). RESULTS: Over a mean follow-up of 16.5 years, 1629 incident AF cases were diagnosed. Among participants with undetectable hs-cTnT at visit 2, the multivariable HR of AF was 1.28 (95% CI 1.12-1.48) among those with detectable or elevated hs-cTnT at visit 4 compared to those in which hs-cTnT remained undetectable. Among those with detectable hs-cTnT at visit 2, compared to those who remained in the detectable hs-cTnT group, reduction to undetectable at visit 4 was associated with lower risk of AF (HR 0.74, 95% CI 0.59-0.94), while increment to elevated was associated with higher AF risk (HR 1.30, 95% CI 1.01-1.68). Adding hs-cTnT change to our main model with baseline hs-cTnT did not result in significant improvement in the C-statistic or substantial NRI. CONCLUSION: Six-year increase in circulating hs-cTnT was associated with elevated risk of incident AF.

Association of Longitudinal Changes in Cardiac Biomarkers With Atrial and Ventricular Arrhythmias (from the Atherosclerosis Risk in Communities [ARIC] Study).

We evaluated the association of longitudinal changes in circulating levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin T (hs-cTnT) with the burden of arrhythmias as captured by 2-week ambulatory ECG monitoring. This study included 1,930 Atherosclerosis Risk in Communities Study participants who wore a leadless, ambulatory ECG monitor (Zio XT Patch) at visit 6 (2016 to 2017) and had cardiac biomarkers measured at visit 6 and visit 4 (median of 19 years earlier). The mean age of participants at V6 was 79 ± 5 years, 41% were men, and 22% were black. Adjusting for demographics, body mass index, smoking, diabetes, hypertension, stroke, left ventricular mass, cardiac medications, patch wear time, visit 4 levels of NT-proBNP and hs-cTnT, and relative change in hs-cTnT, each log-transformed unit relative increase in NT-proBNP was associated with a higher likelihood of nonsustained ventricular tachycardia (odds ratio 1.29, 95% confidence interval [CI] 1.12 to 1.48), a higher number of daily atrial tachycardia episodes (geometric mean ratio [GMR] 1.16, 95% CI 1.10 to 1.21), and a higher daily ectopic burden (premature ventricular contractions -GMR 1.42, 95% CI 1.25 to 1.62; premature atrial contractions -GMR 1.40, 95% CI 1.25 to 1.57). In fully adjusted analyses, each log-transformed unit relative increase in hs-cTnT was only found to be weakly associated with a higher daily premature ventricular contraction burden (GMR 1.31, 95% CI 1.01 to 1.70). In conclusion, longitudinal change in NT-proBNP was associated with an increased atrial and ventricular arrhythmia burden.