Publications by authors named "Elsayed Z Soliman"

542 Publications

Associations of High-Sensitivity Troponin and Natriuretic Peptide Levels With Outcomes After Intensive Blood Pressure Lowering: Findings From the SPRINT Randomized Clinical Trial.

JAMA Cardiol 2021 Sep 1. Epub 2021 Sep 1.

Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas.

Importance: Elevated high-sensitivity cardiac troponin T (hscTnT) and N-terminal pro-B-type natriuretic peptide (NTproBNP) levels are associated with risk of heart failure (HF) and mortality among individuals in the general population. However, it is unknown if this risk is modifiable.

Objective: To test the hypothesis that elevated hscTnT and NTproBNP levels would identify individuals with the greatest risk for mortality and HF and the largest benefit associated with intensive systolic blood pressure (SBP) lowering.

Design, Setting, And Participants: This is a nonprespecified post hoc analysis of the multicenter, prospective, randomized clinical Systolic Blood Pressure Intervention Trial (SPRINT), conducted from October 20, 2010, to August 20, 2015. A total of 9361 patients without diabetes with increased risk for cardiovascular disease were randomized to receive intensive vs standard SBP lowering. Statistical analysis was performed on an intention-to-treat basis from September 30, 2019, to July 29, 2021.

Interventions: Participants were randomized to undergo intensive (<120 mm Hg) or standard (<140 mm Hg) SBP lowering. High-sensitivity cardiac troponin T and NTproBNP levels were measured from stored specimens collected at enrollment, with elevated levels defined as 14 ng/L or more for hscTnT (to convert to micrograms per liter, multiply by 0.001) and 125 pg/mL or more for NTproBNP (to convert to nanograms per liter, multiply by 1.0).

Main Outcomes And Measures: The primary outcome of this ancillary study was HF and mortality.

Results: Of the 9361 participants enrolled in SPRINT, 8828 (5578 men [63.2%]; mean [SD] age, 68.0 [9.5] years) had measured hscTnT levels and 8836 (5585 men [63.2%]; mean [SD] age, 68.0 [9.5] years) had measured NTproBNP levels; 2262 of 8828 patients (25.6%) had elevated hscTnT levels, 3371 of 8836 patients (38.2%) had elevated NTproBNP, and 1411 of 8828 patients (16.0%) had both levels elevated. Randomization to the intensive SBP group led to a 4.9% (95% CI, 1.7%-7.5%) absolute risk reduction (ARR) over 4 years in death and HF (421 events) for those with elevated hscTnT and a 1.7% (95% CI, 0.7%-2.5%) ARR for those without elevated levels. Similarly, for those with elevated NTproBNP, the ARR for death and HF over 4 years was 4.6% (95% CI, 2.3%-6.5%) vs 1.8% (95% CI, 0.9%-2.5%) in those without elevated levels. For those with elevated levels of both biomarkers, the ARR for death and HF over 4 years was 7.8% (95% CI, 3.3%-11.3%) vs 1.7% (95% CI, 0.8%-2.3%) in those with neither biomarker elevated. No significant treatment group by biomarker category interactions were detected.

Conclusions And Relevance: Intensive SBP control led to large absolute differences in death and HF among patients with abnormal hscTnT and NTproBNP levels. These findings demonstrate that risk associated with elevation of these biomarkers is modifiable with intensive BP control. A prospective, randomized clinical trial is needed to evaluate whether these biomarkers may help guide selection of patients for intensive SBP lowering.

Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.
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http://dx.doi.org/10.1001/jamacardio.2021.3187DOI Listing
September 2021

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

Am J Cardiol 2021 Aug 28. Epub 2021 Aug 28.

Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota.

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.
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http://dx.doi.org/10.1016/j.amjcard.2021.07.043DOI Listing
August 2021

Association between human immunodeficiency virus serostatus and the prevalence of atrial fibrillation.

Medicine (Baltimore) 2021 Jul;100(29):e26663

Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.

Abstract: Atrial fibrillation (AF) leads to increased risk for stroke. Human immunodeficiency virus (HIV) is associated with cardiovascular disease (CVD), although it is unclear if HIV is associated with AF. The purpose of this study was to evaluate the association between HIV serostatus and the prevalence of AF in the Multicenter AIDS Cohort Study.A cross sectional study was conducted among 1674 HIV-infected (HIV+) and uninfected (HIV-) men who completed resting 12-lead electrocardiograms, and/or ambulatory electrocardiogram monitoring. Multivariable logistic regression was used to evaluate the association between AF, defined as the presence of either AF or atrial flutter, and HIV+ serostatus. Associations were adjusted for demographic variables, and then also for CVD risk factors.HIV+ men were younger than HIV- men (median 55.5 vs 61.7 years, P < .001) and were more frequently African-American (30.5% vs 17.8%, P < .001). Most HIV+ men (81%) had undetectable viral load. The age and race adjusted prevalence of AF was 3.0% in HIV+ and 3.3% in HIV- men. There was only 1 case of AF among African-American men. There were no associations between AF and HIV serostatus after adjusting for demographic factors (odds ratio 0.76; 95% CI 0.37 to -1.58; P = .47) or after further adjustment for CVD risk factors (odds ratio 0.84; 95% CI 0.39 to -1.81; P = .66).We found no association between HIV and AF in this cohort in which viral replication among the HIV+ men is generally suppressed. The overall prevalence of AF was low and was rare in African-American men.
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http://dx.doi.org/10.1097/MD.0000000000026663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294896PMC
July 2021

Development and optimization of an in vivo electrocardiogram recording method and analysis program for adult zebrafish.

Dis Model Mech 2021 08 11;14(8). Epub 2021 Aug 11.

McKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Clinically pertinent electrocardiogram (ECG) data from model systems, such as zebrafish, are crucial for illuminating factors contributing to human cardiac electrophysiological abnormalities and disease. Current zebrafish ECG collection strategies have not adequately addressed the consistent acquisition of high-quality traces or sources of phenotypic variation that could obscure data interpretation. Thus, we developed a novel platform to ensure high-quality recording of in vivo subdermal adult zebrafish ECGs and zebrafish ECG reading GUI (zERG), a program to acquire measurements from traces that commercial software cannot examine owing to erroneous peak calling. We evaluate normal ECG trait variation, revealing highly reproducible intervals and wave amplitude variation largely driven by recording artifacts, and identify sex and body size as potential confounders to PR, QRS and QT intervals. With this framework, we characterize the effect of the class I anti-arrhythmic drug flecainide acetate on adults, provide support for the impact of a Long QT syndrome model, and establish power calculations for this and other studies. These results highlight our pipeline as a robust approach to evaluate zebrafish models of human cardiac electrophysiological phenotypes.
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http://dx.doi.org/10.1242/dmm.048827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380046PMC
August 2021

Effect of intensive blood pressure lowering on left atrial remodeling in the SPRINT.

Hypertens Res 2021 Aug 6. Epub 2021 Aug 6.

Epidemiological Cardiology Research Center, Department of Epidemiology and Prevention, Division of Public Health Sciences and Department of Medicine, Section on Cardiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.

Upstream therapy of atrial remodeling may decrease atrial fibrillation and associated thromboembolism. We examined the impact of intensive BP lowering on ECG-defined left atrial abnormalities in the SPRINT. SPRINT was a randomized clinical trial comparing outcomes when a systolic BP of <120 mmHg (standard treatment) was the target. We included SPRINT participants without baseline atrial fibrillation who had a technically interpretable baseline ECG and at least one follow-up ECG. The primary outcome was incident left atrial abnormality, defined as P-wave terminal force in V (PTFV) > 4000 μV × ms. Secondary outcomes were regression of the left atrial abnormality and the change in PTFV from baseline across follow-up ECGs. Cox regression was used to examine the associations between treatment assignment and incident left atrial abnormality and its regression. We used linear mixed models to examine the changes in PTFV. Of 9361 SPRINT participants, 7738 qualified for this analysis, of whom 5544 did not have baseline left atrial abnormalities. Intensive BP management was not associated with incident left atrial abnormality (HR, 0.96; 95% CI, 0.87-1.07) or regression of the baseline left atrial abnormality (HR, 1.09; 95% CI, 0.98-1.21). The change in PTFV from baseline through follow-up did not differ significantly between treatment groups (difference in μV × ms per year, 6; 95% CI, -67 to 79). Thus, among patients in a randomized clinical trial, we found no difference in the progression or regression of ECG-defined left atrial abnormalities with intensive BP management compared to standard BP management.
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http://dx.doi.org/10.1038/s41440-021-00713-2DOI Listing
August 2021

Higher Serum Urate Levels Are Associated With an Increased Risk for Sudden Cardiac Death.

J Rheumatol 2021 Jun 15. Epub 2021 Jun 15.

This research project is supported by cooperative agreement U01 NS041588 co-funded by the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute on Aging (NIA), National Institutes of Health, Department of Health and Human Service. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NINDS or the NIA. Representatives of the NINDS were involved in the review of the manuscript but were not directly involved in the collection, management, analysis or interpretation of the data. Additional funding was provided by grants R01 HL080477 and K24 HL111154 from the National Heart, Lung, and Blood Institute (NHLBI) and grant P50AR060772 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Representatives from the NHLBI or the NIAMS did not have any role in the design and conduct of the study, the collection, management, analysis, and interpretation of the data, or the preparation or approval of the manuscript. L.D. Colantonio, MD, PhD, N.S. Chaudhary, MBBS, MPH, N.D. Armstrong, PhD, P. Muntner, PhD, M.R. Irvin, PhD, Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA; R.J. Reynolds, PhD, K.G. Saag, MD, MSc, Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA; T.R. Merriman, PhD, Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA, and Department of Biochemistry, University of Otago, Dunedin, New Zealand; A. Gaffo, MD, MSPH, Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, and Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, USA; J.A. Singh, MD, MPH, Department of Epidemiology, University of Alabama at Birmingham, Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, and Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, USA; T.B. Plante, MD, MHS, Department of Medicine, Larner College of Medicine at the University of Vermont, Burlington, Vermont, USA; E.Z. Soliman, MD, MSc, MS, Epidemiological Cardiology Research Center (EPICARE), Wake Forest School of Medicine, Winston-Salem, North Carolina, USA; J.R. Curtis, MD, MS, MPH, Department of Epidemiology, University of Alabama at Birmingham, and Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA; S.L. Bridges Jr., MD, PhD, Department of Medicine, Division of Rheumatology, Hospital for Special Surgery, and Joan and Sanford I. Weill Department of Medicine, Division of Rheumatology, Weill Cornell Medicine, New York, New York, USA; L. Lang, PhD, Department of Medicine, University of Colorado Denver, Denver, Colorado, USA; G. Howard, DrPH, Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, USA; M.M. Safford, MD, Department of Medicine, Weill Cornell Medical College, New York, New York, USA. LDC receives research support from Amgen. AG receives research support from Amgen and honoraria from UpToDate. JAS receives consultant fees from Crealta/Horizon, Medisys, Fidia, UBM LLC, Medscape, WebMD, Clinical Care Options, Clearview Healthcare Partners, Putnam Associates, Spherix, Trio Health, Focus Forward, Navigant Consulting, Practice Point Communications, Simply Speaking, the National Institutes of Health, and the American College of Rheumatology; is a member of the Executive Committee of Outcome Measures in Rheumatology (OMERACT), and is a stockholder of Amarin Pharmaceuticals and Viking Therapeutics. MMS receives research support from Amgen. PM receives research support from Amgen and serves as a consultant for Amgen. KGS receives research support from Horizon, Takeda, Sobi, and Shanton; and serves as a consultant/advisor for Arthrosi, Atom Bioscience, LG Pharma, Mallinkrodt, Sobi, Horizon, and Takeda. The remaining authors have no conflicts of interest relevant to this article. Address correspondence to Dr. L.D. Colantonio, 1720 2nd Ave South, RPHB 527C, Birmingham, AL 35294-0013, USA. Email: Accepted for publication June 2, 2021.

Objective: To determine the association of serum urate (SU) levels with sudden cardiac death and incident coronary heart disease (CHD), separately, among adults without a history of CHD.

Methods: We conducted a case-cohort analysis of Black and White participants aged ≥ 45 years enrolled in the REason for Geographic And Racial Differences in Stroke (REGARDS) study without a history of CHD at baseline between 2003 and 2007. Participants were followed for sudden cardiac death or incident CHD (i.e., myocardial infarction [MI] or death from CHD excluding sudden cardiac death) through December 31, 2013. Baseline SU was measured in a random sample of participants (n = 840) and among participants who experienced sudden cardiac death (n = 235) or incident CHD (n = 851) during follow-up.

Results: Participants with higher SU levels were older and more likely to be male or Black. The crude HR (95% CI) per 1 mg/dL higher SU level was 1.26 (1.14-1.40) for sudden cardiac death and 1.17 (1.09-1.26) for incident CHD. After adjustment for age, sex, race, and cardiovascular risk factors, the HR (95% CI) per 1 mg/dL higher SU level was 1.19 (1.03-1.37) for sudden cardiac death and 1.05 (0.96-1.15) for incident CHD. HRs for sudden cardiac death were numerically higher among participants aged 45-64 vs ≥ 65 years, without vs with diabetes, and among those of White vs Black race, although values for effect modification were all ≥ 0.05.

Conclusion: Higher SU levels were associated with an increased risk for sudden cardiac death but not with incident CHD.
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http://dx.doi.org/10.3899/jrheum.210139DOI Listing
June 2021

The role of traditional risk factors in explaining the social disparities in cardiovascular death: The national health and Nutrition Examination Survey III (NHANES III).

Am J Prev Cardiol 2020 Dec 15;4:100094. Epub 2020 Oct 15.

Department of Internal Medicine, Section on Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.

Objective: ─ To assess the role of traditional risk factors in explaining the association between cumulative social risk exposure and disparities in CVD death among US adults.

Methods: ─ The study included 15,906 participants from the Third National Health and Nutrition Examination Survey III who were CVD-free at enrollment. Baseline social risk factors (minority race, poverty-income ratio<1, education<12 grade, and living single) were used to create a cumulative social risk score (0 to ≥3). CVD death served as the primary outcome. We assessed the contribution of each major CVD risk factor to the link between cumulative social risk exposure and CVD death.

Results: ─ During a median follow-up of 14 years, 1309 CVD deaths occurred. Participants with elevated cumulative social risk score were at increased risk of CVD death, with hazard ratio 1.19(95%CI 1.01-1.41), 1.52(95%CI 1.28-1.79), and 1.46 (95%CI 1.23-1.74) in individuals with score 1, 2 and ​≥ ​3 respectively, compared with individuals with score of 0. Traditional CVD risk factors explained about one third of the disparities in CVD death in individuals with the elevated social risk exposure. Among the one third effect by combined CVD risk factors, current smoking contributed the largest proportion, accounting for approximately one half of the combined risk factors effect, followed by obesity and diabetes.

Conclusions: ─Among the traditional risk factors, control of smoking appears to be the greatest opportunity to attenuate the social disparities in CVD death. While these findings call for further studies to identify other pathways that explain the elevated CVD mortality in socially disadvantaged population.
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http://dx.doi.org/10.1016/j.ajpc.2020.100094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315458PMC
December 2020

Multiple Blood Biomarkers and Stroke Risk in Atrial Fibrillation: The REGARDS Study.

J Am Heart Assoc 2021 Aug 30;10(15):e020157. Epub 2021 Jul 30.

Departments of Medicine and Pathology & Laboratory Medicine Larner College of Medicine at the University of Vermont Burlington VT.

Background Atrial fibrillation is associated with increased stroke risk; available risk prediction tools have modest accuracy. We hypothesized that circulating stroke risk biomarkers may improve stroke risk prediction in atrial fibrillation. Methods and Results The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a prospective cohort study of 30 239 Black and White adults age ≥45 years. A nested study of stroke cases and a random sample of the cohort included 175 participants (63% women, 37% Black adults) with baseline atrial fibrillation and available blood biomarker data. There were 81 ischemic strokes over 5.2 years in these participants. Adjusted for demographics, stroke risk factors, and warfarin use, the following biomarkers were associated with stroke risk (hazard ratio [HR]; 95% CI for upper versus lower tertile): cystatin C (3.16; 1.04-9.58), factor VIII antigen (2.77; 1.03-7.48), interleukin-6 (9.35; 1.95-44.78), and NT-proBNP (N-terminal B-type natriuretic peptide) (4.21; 1.24-14.29). A multimarker risk score based on the number of blood biomarkers in the highest tertile was developed; adjusted HRs of stroke for 1, 2, and 3+ elevated blood biomarkers, compared with none, were 1.75 (0.57-5.40), 4.97 (1.20-20.5), and 9.51 (2.22-40.8), respectively. Incorporating the multimarker risk score to the CHADSVASc score resulted in a net reclassification improvement of 0.34 (95% CI, 0.04-0.65). Conclusions Findings in this biracial cohort suggested the possibility of substantial improvement in stroke risk prediction in atrial fibrillation using blood biomarkers or a multimarker risk score.
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http://dx.doi.org/10.1161/JAHA.120.020157DOI Listing
August 2021

Rare Coding Variants Associated With Electrocardiographic Intervals Identify Monogenic Arrhythmia Susceptibility Genes: A Multi-Ancestry Analysis.

Circ Genom Precis Med 2021 Aug 28;14(4):e003300. Epub 2021 Jul 28.

Regeneron Genetics Center, Tarrytown, NY. Departments of Medicine, Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (S.R.).

Background: Alterations in electrocardiographic (ECG) intervals are well-known markers for arrhythmia and sudden cardiac death (SCD) risk. While the genetics of arrhythmia syndromes have been studied, relations between electrocardiographic intervals and rare genetic variation at a population level are poorly understood.

Methods: Using a discovery sample of 29 000 individuals with whole-genome sequencing from Trans-Omics in Precision Medicine and replication in nearly 100 000 with whole-exome sequencing from the UK Biobank and MyCode, we examined associations between low-frequency and rare coding variants with 5 routinely measured electrocardiographic traits (RR, P-wave, PR, and QRS intervals and corrected QT interval).

Results: We found that rare variants associated with population-based electrocardiographic intervals identify established monogenic SCD genes (, , and ), a controversial monogenic SCD gene (), and novel genes ( and ) involved in cardiac conduction. Loss-of-function and pathogenic variants, carried by 0.1% of individuals, were associated with a nearly 6-fold increased odds of the first-degree atrioventricular block (=8.4×10). Similar variants in and (0.2% of individuals) were associated with a 23-fold increased odds of marked corrected QT interval prolongation (=4×10), a marker of SCD risk. Incomplete penetrance of such deleterious variation was common as over 70% of carriers had normal electrocardiographic intervals.

Conclusions: Our findings indicate that large-scale high-depth sequence data and electrocardiographic analysis identifies monogenic arrhythmia susceptibility genes and rare variants with large effects. Known pathogenic variation in conventional arrhythmia and SCD genes exhibited incomplete penetrance and accounted for only a small fraction of marked electrocardiographic interval prolongation.
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http://dx.doi.org/10.1161/CIRCGEN.120.003300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373440PMC
August 2021

Utility of using electrocardiogram measures of heart rate variability as a measure of cardiovascular autonomic neuropathy in type 1 diabetes patients.

J Diabetes Investig 2021 Jul 26. Epub 2021 Jul 26.

Epidemiological Cardiology Research Center (EPICARE), Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.

Aims/introduction: Cardiovascular autonomic neuropathy (CAN) is a predictor of cardiovascular disease and mortality. Cardiovascular reflex tests (CARTs) are the gold standard for the diagnosis of CAN, but might not be feasible in large research cohorts or in clinical care. We investigated whether measures of heart rate variability obtained from standard electrocardiogram (ECG) recordings provide a reliable measure of CAN.

Materials And Methods: Standardized CARTs (R-R response to paced breathing, Valsalva, postural changes) and digitized 12-lead resting ECGs were obtained concomitantly in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications participants (n = 311). Standard deviation of normally conducted R-R intervals (SDNN) and the root mean square of successive differences between normal-to-normal R-R intervals (rMSSD) were measured from ECG. Sensitivity, specificity, probability of correct classification and Kappa statistics evaluated the agreement between ECG-derived CAN and CARTs-defined CAN.

Results: Participants with CARTs-defined CAN had significantly lower SDNN and rMSSD compared with those without CAN (P < 0.001). The optimal cut-off points of ECG-derived CAN were <17.13 and <24.94 ms for SDNN and rMSSD, respectively. SDNN plays a dominant role in defining CAN, with an area under the curve of 0.73, indicating fair test performance. The Kappa statistic for SDNN was 0.41 (95% confidence interval 0.30-0.51) for the optimal cut-off point, showing fair agreement with CARTs-defined CAN. Combining SDNN and rMSSD optimal cut-off points does not provide additional predictive power for CAN.

Conclusions: These analyses are the first to show the agreement between indices of heart rate variability derived from ECGs and the gold standard CARTs, thus supporting potential use as a measure of CAN in clinical research and clinical care.
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http://dx.doi.org/10.1111/jdi.13635DOI Listing
July 2021

Rural/urban differences in the prevalence of stroke risk factors: A cross-sectional analysis from the REGARDS study.

J Rural Health 2021 Jul 16. Epub 2021 Jul 16.

Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Purpose: We previously described the magnitude of rural-urban differences in the prevalence of stroke risk factors and stroke mortality. In this report, we sought to extend the understanding of rural-urban differences in the prevalence of stroke risk factors by using an enhanced definition of rural-urban status and assessing the impact of neighborhood socioeconomic status (nSES) on risk factor differences.

Methods: This analysis included 28,242 participants without a history of stroke from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. Participants were categorized into the 6-level ordinal National Center for Health Statistics Urban-Rural Classification Scheme. The prevalence of stroke risk factors (hypertension, diabetes, smoking, atrial fibrillation, left ventricular hypertrophy, and heart disease) was assessed across the rural-urban scale with adjustment for demographic characteristics and further adjustment for nSES score.

Findings: Hypertension, diabetes, and heart disease were more prevalent in rural than urban regions. Higher odds were observed for these risk factors in the most rural compared to the most urban areas (odds ratios [95% CI]: 1.25 [1.11-1.42] for hypertension, 1.15 [0.99-1.33] for diabetes, and 1.19 [1.02-1.39] for heart disease). Adjustment for nSES score partially attenuated the odds of hypertension and heart disease with rurality, completely attenuated the odds of diabetes, and unmasked an association of current smoking.

Conclusions: Some of the higher stroke mortality in rural areas may be due to the higher burden of stroke risk factors in rural areas. Lower nSES contributed most notably to rural-urban differences for diabetes and smoking.
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http://dx.doi.org/10.1111/jrh.12608DOI Listing
July 2021

Association of heart failure subtypes and atrial fibrillation: Data from the Atherosclerosis Risk in Communities (ARIC) study.

Int J Cardiol 2021 Sep 8;339:47-53. Epub 2021 Jul 8.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA. Electronic address:

Aims: To determine the prevalence and incidence of AF among HF subtypes in a biracial community-based cohort.

Methods: We studied 6496 participants in the Atherosclerosis Risk in Community study (mean age, 75.8 ± 5.3, 59% women, 23% black) who attended the 2011-2013 visit. HF was identified from physician adjudicated diagnosis, hospital discharges, and self-report. HF subtypes were based on echocardiography. A left ventricular ejection fraction <40% represents HF with reduced ejection fraction (HFrEF), 40%-49% for HF with midrange ejection fraction (HFmEF), and ≥ 50% for HF with preserved ejection fraction (HFpEF). AF was ascertained through 2017 from study electrocardiograms, hospital discharges, and death certificates. Confounder-adjusted logistic regression and Cox models were used to estimate associations of HF subtype with prevalent and incident AF.

Results: Among eligible participants, 393 had HF (HFpEF = 232, HFmEF = 41, HFrEF = 35 and unclassified HF = 85) and 735 had AF. Compared to those without HF, all HF subtypes were more likely to have prevalent AF [odds ratio (95% confidence interval (CI)) 7.4 (5.6-9.9) for HFpEF, 8.1 (4.3-15.3) for HFmEF, 10.0 (5.0-20.2) for HFrEF, 8.8 (5.6-14.0) for unclassified HF]. Among participants without AF at baseline (n = 5761), 610 of them developed AF. Prevalent HF was associated with increased risk of AF [hazard ratio (95%CI) 2.3 (1.6-3.2) for HFpEF, 5.0 (2.7-9.3) for HFmEF, 3.5 (1.7-7.6) for HFrEF, 1.9 (0.9-3.7) for unclassified HF].

Conclusion: AF and HF frequently co-occur, with small differences by HF subtype, underscoring the importance of understanding the interplay of these two epidemics and evaluating shared preventive and therapeutic strategies.
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http://dx.doi.org/10.1016/j.ijcard.2021.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419094PMC
September 2021

Exposure to secondhand smoke is associated with increased left ventricular mass.

Tob Induc Dis 2021 4;19:43. Epub 2021 Jun 4.

Institute of Global Health and Human Ecology, School of Sciences and Engineering, The American University in Cairo, New Cairo, Egypt.

Introduction: Chronic hypertension is associated with left ventricular hypertrophy. Recent evidence suggests that secondhand smoke (SHS) exposure is associated with chronic hypertension, so we sought to examine the relationship between secondhand smoke exposure and electrocardiographic left ventricular (LV) mass among non-smokers.

Methods: This analysis included 4982 non-smoker participants from the Third National Health and Nutrition Examination (NHANES-III). Non-smoking was defined by self-report and serum cotinine ≤10 ng/mL, a biomarker for tobacco exposure. SHS exposure was defined as serum cotinine level ≥1 ng/mL. LV mass was estimated using an electrocardiographic model developed and applied in NHANES-III then validated in the Cardiovascular Health Study. Multivariable linear regression was used to examine the cross-sectional association between SHS exposure (vs no exposure) with estimated LV mass index. In similar models, we also examined the associations of LV mass index across quartiles of serum cotinine (reference group, 1st quartile) and in subgroups stratified by age, race, sex, hypertension, and obesity.

Results: About 9.8% (n=489) of the participants were exposed to SHS. Exposure to SHS was associated with an estimated 2.9 g/m increase in LV mass index, with a dose-response relationship between higher serum cotinine and LV mass index. These results were consistent in men and women, Whites and non-Whites, elderly and non-elderly, and those with and without hypertension. Significant effect modification was present among obese individuals with an estimated 4.8 g/m increase in LV mass index (interaction p=0.01).

Conclusions: In a racially diverse sample of non-smokers, SHS is associated with increased LV mass with a dose-response relationship between level of exposure and LV mass. Effect modification was present among obese individuals. These findings underscore the harmful effect of passive smoking on the cardiovascular system and highlight the need for more restrictions on smoking in public areas, especially in countries or regions with less-stringent public health policies.
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http://dx.doi.org/10.18332/tid/136415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176893PMC
June 2021

Electrocardiogram machine learning for detection of cardiovascular disease in African Americans: the Jackson Heart Study.

Eur Heart J Digit Health 2021 Mar 20;2(1):137-151. Epub 2021 Jan 20.

Department of Medicine, Knight Cardiovascular Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, UHN62, Portland, OR 97239, USA.

Aims: Almost half of African American (AA) men and women have cardiovascular disease (CVD). Detection of prevalent CVD in community settings would facilitate secondary prevention of CVD. We sought to develop a tool for automated CVD detection.

Methods And Results: Participants from the Jackson Heart Study (JHS) with analysable electrocardiograms (ECGs) (=3679; age, 6212 years; 36% men) were included. Vectorcardiographic (VCG) metrics QRS, T, and spatial ventricular gradient vectors magnitude and direction, and traditional ECG metrics were measured on 12-lead ECG. Random forests, convolutional neural network (CNN), lasso, adaptive lasso, plugin lasso, elastic net, ridge, and logistic regression models were developed in 80% and validated in 20% samples. We compared models with demographic, clinical, and VCG input (43 predictors) and those after the addition of ECG metrics (695 predictors). Prevalent CVD was diagnosed in 411 out of 3679 participants (11.2%). Machine learning models detected CVD with the area under the receiver operator curve (ROC AUC) 0.690.74. There was no difference in CVD detection accuracy between models with VCG and VCG + ECG input. Models with VCG input were better calibrated than models with ECG input. Plugin-based lasso model consisting of only two predictors (age and peak QRS-T angle) detected CVD with AUC 0.687 [95% confidence interval (CI) 0.6250.749], which was similar (=0.394) to the CNN (0.660; 95% CI 0.5970.722) and better (<0.0001) than random forests (0.512; 95% CI 0.4930.530).

Conclusions: Simple model (age and QRS-T angle) can be used for prevalent CVD detection in limited-resources community settings, which opens an avenue for secondary prevention of CVD in underserved communities.
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http://dx.doi.org/10.1093/ehjdh/ztab003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139412PMC
March 2021

Silent Myocardial Infarction and Subsequent Ischemic Stroke in the Cardiovascular Health Study.

Neurology 2021 08 24;97(5):e436-e443. Epub 2021 May 24.

From the Clinical and Translational Neuroscience Unit (A.E.M., H.K.), Feil Family Brain and Mind Research Institute (A.E.M., H.K.), and Departments of Neurology (A.E.M., H.K.) and Medicine (P.M.O., M.M.S.), Weill Cornell Medical College, New York, NY; Department of Biostatistics (T.M.B.), Cardiovascular Health Research Unit (B.M.P.), and Departments of Medicine (B.M.P.), Epidemiology (B.M.P., W.T.L.), Health Services (B.M.P.), and Neurology (W.T.L.), University of Washington, Seattle; Epidemiological Cardiology Research Center (E.Z.S.), Wake Forest University School of Medicine, Winston-Salem, NC; Department of Epidemiology (V.H.), School of Public Health, University of Alabama at Birmingham; Kaiser Permanente Washington Health Research Institute (B.M.P.), Seattle; and Department of Neurology, Vagelos College of Physicians and Surgeons (M.S.V.E.), and Department of Epidemiology (M.S.V.E.), Mailman School of Public Health, Columbia University, New York, NY.

Objective: To test the hypothesis that silent myocardial infarction (MI) is a risk factor for ischemic stroke, we evaluated the association between silent MI and subsequent ischemic stroke in the Cardiovascular Health Study.

Methods: The Cardiovascular Health Study prospectively enrolled community-dwelling individuals ≥65 years of age. We included participants without prevalent stroke or baseline evidence of MI. Our exposures were silent and clinically apparent, overt MI. Silent MI was defined as new evidence of Q-wave MI, without clinical symptoms of MI, on ECGs performed during annual study visits from 1989 to 1999. The primary outcome was incident ischemic stroke. Secondary outcomes were ischemic stroke subtypes: nonlacunar, lacunar, and other/unknown. Cox proportional hazards analysis was used to model the association between time-varying MI status (silent, overt, or no MI) and stroke after adjustment for baseline demographics and vascular risk factors.

Results: Among 4,224 participants, 362 (8.6%) had an incident silent MI, 421 (10.0%) an incident overt MI, and 377 (8.9%) an incident ischemic stroke during a median follow-up of 9.8 years. After adjustment for demographics and comorbidities, silent MI was independently associated with subsequent ischemic stroke (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.03-2.21). Overt MI was associated with ischemic stroke both in the short term (HR, 80; 95% CI, 53-119) and long term (HR, 1.60; 95% CI, 1.04-2.44). In secondary analyses, the association between silent MI and stroke was limited to nonlacunar ischemic stroke (HR, 2.40; 95% CI, 1.36-4.22).

Conclusion: In a community-based sample, we found an association between silent MI and ischemic stroke.
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http://dx.doi.org/10.1212/WNL.0000000000012249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356380PMC
August 2021

Atrial fibrillation and risk of incident heart failure with reduced versus preserved ejection fraction.

Heart 2021 May 24. Epub 2021 May 24.

Epidemiological Cardiology Research Center (EPICARE), Department of Epidemiology, Division of Public Health, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.

Objective: Associations between atrial fibrillation (AF) and heart failure (HF) have been established. We compared the extent to which AF is associated with each primary subtype of HF, with reduced (HFrEF) versus preserved ejection fraction (HFpEF).

Methods: We included 25 787 participants free of baseline HF from the REGARDS (REasons for Geographic And Racial Differences in Stroke) cohort. Baseline AF was ascertained from ECG and self-reported history of physician diagnosis. Incident HF events were determined from physician-adjudicated review of hospitalisation medical records and HF deaths. Based on left ventricular ejection fraction (LVEF) at the time of HF event, HFrEF, HFpEF, and mid-range HF were defined as LVEF <40%, ≥50% and 40%-49%, respectively. Multivariable Cox proportional-hazards models examined the association between AF and HF. The Lunn-McNeil method was used to compare associations of AF with incident HFrEF versus HFpEF.

Results: Over a median of 9 years of follow-up, 1109 HF events occurred (356 HFpEF, 388 HFrEF, 77 mid-range and 288 unclassified). In a model adjusted for sociodemographics, cardiovascular risk factors, and incident coronary heart disease, AF was associated with increased risk of all HF events (HR 1.67, 95% CI 1.38 to 2.01). The associations of AF with HFrEF versus HFpEF events did not differ significantly (HR 1.87 (95% CI 1.38 to 2.54) and HR 1.65 (95% CI 1.20 to 2.28), respectively; p value for difference=0.581). These associations were consistent in sex and race subgroups.

Conclusions: AF is associated with both HFrEF and HFpEF events, with no significant difference in the strength of association among these subtypes.
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http://dx.doi.org/10.1136/heartjnl-2021-319122DOI Listing
May 2021

Cannabis Use and Electrocardiographic Myocardial Injury.

Am J Cardiol 2021 07 21;151:100-104. Epub 2021 May 21.

Cardiovascular Medicine Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston Salem, North Carolina; Institute of Global Health and Human Ecology, School of Sciences and Engineering, American University in Cairo, New Cairo, Egypt.

Multiple observational studies have demonstrated an association with cannabis use and acute myocardial infarction, especially among young adults. However, little is known about the connection with subclinical or electrocardiographic myocardial injury. We hypothesized that cannabis use would be associated with an increased risk of myocardial injury as defined by the cardiac infarction and/or injury score (CIIS). This analysis included 3,634 (age 48.0 ± 5.9 years, 47.1% male, 68.7% Caucasians) participants from the Third National Health and Examination Survey. Cannabis use was defined by self-report. Those with history of cardiovascular disease were excluded. Myocardial injury was defined as electrocardiographic CIIS ≥ 10. Multivariable logistic regression was used to examine the association between cannabis use and myocardial injury. The consistency of this association was tested among subgroups stratified by race, gender, tobacco smoking status, and comorbidities. About 26.0% (n = 900) of participants were ever-cannabis users and 15.5% (n = 538) had myocardial injury. In a model adjusted for potential confounders, ever-cannabis users had 43% increased odds of myocardial injury compared to never users (Odds ratio (95% confidence interval): 1.43 (1.14, 1.80); p = 0.002). This association was stronger among participants with a history of hypertension versus those without (Odds ratio (95% confidence interval): 1.83 (1.36, 2.47) vs 1.17 (0.83, 1.64), respectively; interaction p value 0.04). Cannabis use is associated with an increased risk of myocardial injury among those without cardiovascular disease with effect modification by co-existent hypertension. These novel findings underscore the harmful effects of cannabis use on cardiovascular health and also merit a personalized risk assessment when counseling patients with hypertension on its use.
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http://dx.doi.org/10.1016/j.amjcard.2021.03.058DOI Listing
July 2021

Associations of anger, vital exhaustion, anti-depressant use, and poor social ties with incident atrial fibrillation: The Atherosclerosis Risk in Communities Study.

Eur J Prev Cardiol 2021 05;28(6):633-640

Department of Epidemiology, Emory University, USA.

Background: We examined the relationships of anger, vital exhaustion, anti-depressant use, and poor social ties with incident atrial fibrillation in a biracial cohort of middle and older-aged adults.

Methods: This analysis included 11,445 Atherosclerosis Risk in Communities Study participants who were free of atrial fibrillation at baseline in 1990-1992. Vital exhaustion was assessed at baseline and defined as a score in the highest quartile on the 21-item Vital Exhaustion Questionnaire. Baseline anti-depressant use was self-reported. The Spielberger Trait Anger Scale to assess anger and both the Interpersonal Support Evaluation List and the Lubben Social Network Scale to assess social ties were also administered at baseline. The primary outcome was incident atrial fibrillation throughout 2016, identified by electrocardiogram, hospital discharge coding of atrial fibrillation, and death certificates.

Results: A total of 2220 incident atrial fibrillation cases were detected over a median follow-up of 23.4 years. After adjusting for age, race-center, sex, education, and height, participants in the 4th Vital Exhaustion Questionnaire quartile (referent = 1st Vital Exhaustion Questionnaire quartile) and those reporting anti-depressant use were at increased risk for atrial fibrillation (hazard ratio = 1.45, 95% confidence interval 1.29-1.64 for Vital Exhaustion Questionnaire; hazard ratio = 1.37, 95% confidence interval 1.11-1.69 for anti-depressant use). The increased atrial fibrillation risk observed for 4th Vital Exhaustion Questionnaire quartile participants remained significant after additional adjustment for relevant comorbidities (hazard ratio = 1.20; confidence interval 1.06-1.35). No significant associations were observed for anger or poor social ties with development of atrial fibrillation.

Conclusions: Vital exhaustion is associated with an increased risk of incident atrial fibrillation.
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http://dx.doi.org/10.1177/2047487319897163DOI Listing
May 2021

Association of arterial stiffness with incident atrial fibrillation: a cohort study.

BMC Cardiovasc Disord 2021 05 20;21(1):247. Epub 2021 May 20.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.

Background: Stiff arteries increase left ventricular (LV) end-systolic workload, leading over time to left atrial and ventricular remodeling, and providing the substrate for atrial fibrillation (AF) development. We investigated if carotid femoral pulse wave velocity (cfPWV), a measure of central arterial stiffness, is associated with incident AF.

Methods: In 2011-2013, cfPWV was measured in 3882 participants of the Atherosclerosis Risk in Communities Cohort Study (ARIC) without prevalent AF. Participants were followed through 2017 for the incidence of AF. Individuals were categorized in cfPWV quartiles based on visit measurements. Multivariable Cox regression models were used to evaluate the association of cfPWV with incident AF.

Results: Mean age was 75 years (SD 5), 60% were female and 20% were African American. Over a median follow-up of 5.5 years we identified 331 incident cases of AF. cfPWV demonstrated U-shaped associations with AF risk. In models adjusted for age, race, center, sex, education levels, and hemodynamic and clinical factors, hazard ratios (HR) of AF for participants in the first, third and fourth quartiles were 1.49 (95% CI 1.06, 2.10), 1.59 (1.14, 2.10), and 1.56(1.10, 2.19), respectively, compared to those in the second quartile.

Conclusion: Among community-dwelling older adults, low and high central arterial stiffness is associated with AF risk.
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http://dx.doi.org/10.1186/s12872-021-02057-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139144PMC
May 2021

Longitudinal Measures of Blood Pressure and Subclinical Atrial Arrhythmias: The MESA and the ARIC Study.

J Am Heart Assoc 2021 Jun 20;10(11):e020260. Epub 2021 May 20.

Cardiovascular Division Department of Medicine University of Minnesota Medical School Minneapolis MN.

Background High blood pressure (BP) is a well-known risk factor for atrial fibrillation (AF), but a single BP measurement may provide limited information about AF risk in older adults. Methods and Results This study included 1256 MESA (Multi-Ethnic Study of Atherosclerosis) and 1948 ARIC (Atherosclerosis Risk in Communities) study participants who underwent extended ambulatory electrocardiographic monitoring and who were free of clinically detected cardiovascular disease, including AF. Using BP measurements from 6 examinations (2000-2018 in MESA and 1987-2017 in ARIC study), we calculated individual long-term mean, trend, and detrended visit-to-visit variability in systolic BP and pulse pressure for each participant. Outcomes, assessed at examination 6, included subclinical AF and supraventricular ectopy. Results from each study were combined with inverse variance-weighted meta-analysis. At examination 6, the mean age was 73 years in MESA and 79 years in ARIC study, and 4% had subclinical AF. Higher visit-to-visit detrended variability in systolic BP was associated with a greater prevalence of subclinical AF (odds ratio [OR], 1.20; 95% CI, 1.02-1.38) and with more premature atrial contractions/hour (geometric mean ratio, 1.08; 95% CI, 1.01-1.15). For pulse pressure as well, higher visit-to-visit detrended variability was associated with a greater prevalence of AF (OR, 1.18; 95% CI, 1.00-1.37). In addition, higher long-term mean pulse pressure was associated with a greater prevalence of subclinical AF (OR, 1.36; 95% CI, 1.08-1.70). Conclusions Antecedent visit-to-visit variability in systolic BP and pulse pressure, but not current BP, is associated with a higher prevalence of subclinical atrial arrhythmias. Prior longitudinal BP assessment, rather than current BP, may be more helpful in identifying older adults who are at higher risk of atrial arrhythmias.
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http://dx.doi.org/10.1161/JAHA.120.020260DOI Listing
June 2021

P-wave signal-averaged electrocardiography: Reference values, clinical correlates, and heritability in the Framingham Heart Study.

Heart Rhythm 2021 Sep 11;18(9):1500-1507. Epub 2021 May 11.

National Heart, Lung, and Blood Institute and Boston University's Framingham Heart Study, Framingham, Massachusetts; Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.

Background: P-wave signal-averaged electrocardiography (P-SAECG) quantifies atrial electrical activity. P-SAECG measures and their clinical correlates and heritability have had limited characterization in community-based cohorts.

Objective: The purpose of this study was to (1) establish reference values; (2) identify clinical risk factors associated with P-SAECG; and (3) estimate genetic heritability for P-SAECG traits.

Methods: We performed P-SAECG in 2 generations of Framingham Heart Study participants. We performed backward elimination regression models to assess associations of clinical factors with each SAECG trait (P-wave [PW] duration, root mean square voltage in terminal 40 ms [RMS40], terminal 30 ms RMS30, terminal 20 ms RMS20, RMS PW, and PW integral). We estimated the adjusted genetic heritability of P-SAECG measures using the Sequential Oligogenic Linkage Analysis Routines (SOLAR) program.

Results: We included 4307 participants (age 55 ± 14 years; 56% female). The reference values were derived from 1752 participants without cardiovascular risk factors. Median (2.5th percentile; 97.5th percentile) total PW duration was 118 ms (93; 146) in women and 128 ms (104; 158) in men in the reference sample, and 121 ms (94; 151) in women and 129 ms (103; 159) in the entire study cohort (broad sample). In the broad sample, after adjusting for age and sex, total PW duration was positively associated with height, weight, prevalent heart failure, history of atrial fibrillation (AF), and atrioventricular node blockers, and negatively associated with smoking, waist circumference, heart rate, and diabetes. The estimated heritability of P-SAECG traits was moderate, ranging from 11.9% for RMS30 to 24.9% for PW integral.

Conclusion: P-SAECG traits are associated with multiple AF-related risk factors and are moderately heritable.
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http://dx.doi.org/10.1016/j.hrthm.2021.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419007PMC
September 2021

Artificial Intelligence-Assisted Prediction of Late-Onset Cardiomyopathy Among Childhood Cancer Survivors.

JCO Clin Cancer Inform 2021 04;5:459-468

Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN.

Purpose: Early identification of childhood cancer survivors at high risk for treatment-related cardiomyopathy may improve outcomes by enabling intervention before development of heart failure. We implemented artificial intelligence (AI) methods using the Children's Oncology Group guideline-recommended baseline ECG to predict cardiomyopathy.

Material And Methods: Seven AI and signal processing methods were applied to 10-second 12-lead ECGs obtained on 1,217 adult survivors of childhood cancer prospectively followed in the St Jude Lifetime Cohort (SJLIFE) study. Clinical and echocardiographic assessment of cardiac function was performed at initial and follow-up SJLIFE visits. Cardiomyopathy was defined as an ejection fraction < 50% or an absolute drop from baseline ≥ 10%. Genetic algorithm was used for feature selection, and extreme gradient boosting was applied to predict cardiomyopathy during the follow-up period. Model performance was evaluated by five-fold stratified cross-validation.

Results: The median age at baseline SJLIFE evaluation was 31.7 years (range 18.4-66.4), and the time between baseline and follow-up evaluations was 5.2 years (0.5-9.5). Two thirds (67.1%) of patients were exposed to chest radiation, and 76.6% to anthracycline chemotherapy. One hundred seventeen (9.6%) patients developed cardiomyopathy during follow-up. In the model based solely on ECG features, the cross-validation area under the curve (AUC) was 0.87 (95% CI, 0.83 to 0.90), whereas the model based on clinical features had an AUC of 0.69 (95% CI, 0.64 to 0.74). In the model based on ECG and clinical features, the cross-validation AUC was 0.89 (95% CI, 0.86 to 0.91), with a sensitivity of 78% and a specificity of 81%.

Conclusion: AI using ECG data may assist in the identification of childhood cancer survivors at increased risk for developing future cardiomyopathy.
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http://dx.doi.org/10.1200/CCI.20.00176DOI Listing
April 2021

Frequent Premature Atrial Contractions Are Associated With Poorer Cognitive Function in the Atherosclerosis Risk in Communities (ARIC) Study.

Mayo Clin Proc 2021 05 9;96(5):1147-1156. Epub 2021 Apr 9.

Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, MN.

Objective: To evaluate the association of premature atrial contraction (PAC) frequency with cognitive test scores and prevalence of dementia or mild cognitive impairment (MCI).

Materials And Methods: 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% to <5%, 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1016/j.mayocp.2021.01.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106627PMC
May 2021

Relation of Atrial Fibrillation to Cognitive Decline (from the REasons for Geographic and Racial Differences in Stroke [REGARDS] Study).

Am J Cardiol 2021 06 6;148:60-68. Epub 2021 Mar 6.

Department of Epidemiology & Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina; Department of Internal Medicine, Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina. Electronic address:

The association of atrial fibrillation (AF) with cognitive function remains unclear, especially among racially/geographically diverse populations. This analysis included 25,980 black and white adults, aged 48+, from the national REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, free from cognitive impairment and stroke at baseline. Baseline AF was identified by self-reported medical history or electrocardiogram (ECG). Cognitive testing was conducted yearly with the Six Item Screener (SIS) to define impairment and at 2-year intervals to assess decline on: animal naming and letter fluency, Montreal Cognitive Assessment (MoCA), Word List Learning (WLL) and Delayed Recall tasks (WLD). Multivariable regression models estimated the relationships between AF and baseline impairment and time to cognitive impairment. Models were adjusted sequentially for age, sex, race, geographic region, and education, then cardiovascular risk factors and finally incident stroke. AF was present in 2,168 (8.3%) participants at baseline. AF was associated with poorer baseline performance on measures of: semantic fluency (p<0.01); global cognitive performance (MoCA, p<0.01); and WLD (p<0.01). During a mean follow-up of 8.06 years, steeper declines in list learning were observed among participants with AF (p<0.03) which remained significant after adjusting for cardiovascular risk factors (p<0.04) and incident stroke (p<0.03). Effect modification by race, sex and incident stroke on AF and cognitive decline were also detected. In conclusion, AF was associated with poorer baseline cognitive performance across multiple domains and incident cognitive impairment in this bi-racial cohort. Additional adjustment for cardiovascular risk factors attenuated these relations with the exception of learning.
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http://dx.doi.org/10.1016/j.amjcard.2021.02.036DOI Listing
June 2021

Life's Simple 7 cardiovascular health score and premature atrial contractions: The atherosclerosis risk in communities (ARIC) study.

Int J Cardiol 2021 06 4;332:70-77. Epub 2021 Mar 4.

Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, United States of America.

Background: Premature atrial contractions (PACs) are associated with increased risk of atrial fibrillation (AF) and ischemic stroke. Although lifestyle and risk factor modification reduces AF incidence, their relationship to PACs frequency is unclear. We assessed the association of Life's Simple 7 (LS7) and individual LS7 factors in midlife with PACs frequency in late life in the Atherosclerosis Risk in Communities (ARIC) Study.

Methods: We followed 1924 participants from ARIC clinic Visit 3 (1993--95) to Visit 6 (2016-17) when a 2-week continuous heart rhythm monitor (Zio®XT Patch) was applied. LS7 factors were assessed at Visit 3 and a composite score was calculated. PACs frequency was categorized as minimal (<0.1%), occasional (≥0.1%-5%) and frequent (>5%). Logistic regression was used to evaluate the association of LS7 score and individual factors with PACs frequency.

Results: Each 1-point LS7 score increase was associated with lower odds of frequent PACs vs. no PACs (OR [95% CI]: 0.87 [0.78, 0.98]) and frequent PACs vs. occasional PACs (OR [95% CI]: 0.88 [0.79, 0.98]). Of the individual LS7 factors, compared with ideal physical activity, poor physical activity was associated with 81% higher odds of frequent PACs vs. no PACs. Compared with ideal BMI, poor BMI was associated with 41% higher odds of occasional PACs vs. no PACs.

Conclusion: Lifestyle risk factors, particularly physical activity and BMI, are associated with higher odds of PACs frequency. More research is needed to determine whether modifying these risk factors in midlife would prevent frequent PACs, and thereby prevent AF and stroke in older age.
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http://dx.doi.org/10.1016/j.ijcard.2021.02.083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164708PMC
June 2021

Subclinical myocardial injury and cardiovascular mortality: Racial differences in prevalence and risk (from the third National Health and Nutrition Examination survey).

Ann Noninvasive Electrocardiol 2021 07 6;26(4):e12827. Epub 2021 Mar 6.

Department of Internal Medicine, Division of Cardiology, University of Pittsburgh School of Medicine and Heart & Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Background: Subclinical myocardial injury (SCMI) determined from the Electrocardiographic Cardiac Infarction/Injury Score (CIIS) is associated with increased risk of cardiovascular disease and mortality. We hypothesized that SCMI prevalence and association with mortality would differ by race, categorized as non-Hispanic White (White), non-Hispanic Black (Black), and Mexican American.

Methods: Our analysis included 5,852 participants (age 58.5 ± 13.2 years; 54% women, 52% Whites, 23% Blacks, and 25% Mexican American participants) from the National Health and Nutrition Examination Survey (NHANES III, 1988-94) who were free of cardiovascular disease at the time of enrollment. SCMI was defined as the presence of CIIS ≥ 10 score points on the 12-lead ECG. Prevalence of SCMI and its association with cardiovascular mortality were examined in each race/ethnic group in models adjusted for sociodemographics and common cardiovascular risk factors.

Results: SCMI prevalence was 23.4% in Whites, 21.8% in Blacks, and 18.0% in Mexican Americans. Compared to Whites, Blacks were as likely to have SCMI (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.80-1.13), while Mexican Americans were less likely (OR 0.74, 95% CI 0.62-0.88). SCMI was not associated with increased risk of cardiovascular mortality in either Whites (hazard ratio [HR] 1.18, 95% CI 0.95-1.48) or Blacks (HR 1.19, 95% CI 0.79-1.80). In contrast, SCMI in Mexican Americans was associated with increased risk of cardiovascular mortality (HR 1.74, 95% CI 1.13-2.67, p < .05).

Conclusion: Mexican Americans had a lower prevalence of SCMI, but increased risk of cardiovascular mortality. Screening for SCMI may identify individuals at increased risk and improve targeted prevention efforts.
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http://dx.doi.org/10.1111/anec.12827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293602PMC
July 2021

Comparison of the Relation of Carotid Intima-Media Thickness With Incident Heart Failure With Reduced Versus Preserved Ejection Fraction (from the Multi-Ethnic Study of Atherosclerosis [MESA]).

Am J Cardiol 2021 06 3;148:102-109. Epub 2021 Mar 3.

Section of Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina; Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins School of Medicine, Baltimore, Maryland; Department of Pediatrics, Saint Joseph University Medical Center, Paterson, New Jersey; Department of Medicine, Lundquist Institute, Torrance, California; Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA; Kaiser Permanente Health Research Institute, Seattle, Washington; Johns Hopkins University School of Medicine, Baltimore, Maryland; Ultrasound Reading Center, Tufts Medical Center, Boston, Massachusetts; National University of Ireland and National Institute for Prevention and Cardiovascular Health, Galway, Ireland.

Increased carotid intima-media thickness (cIMT) is associated with heart failure (HF) in previous studies, but it is not known whether the association of cIMT differs between HF with reduced (HFrEF) versus preserved ejection fraction (HFpEF). We studied 6699 participants (mean age 62 ± 10 years, 47% male, and 38% white) from the Multi-Ethnic Study of Atherosclerosis (MESA) with baseline cIMT measurements. We classified HF events as HFrEF (EF <50%) or HFpEF (EF ≥ 50%) at the time of diagnosis. Cox proportional hazard regression was used to compute hazard ratios (HR), and 95% confidence intervals (CI) for the association between the IMT Z-score (measured maximum IMT of Internal Carotid (IC) and Common Carotid (CC) sites as the mean of the maximum IMT of the near and far walls of right and left sides), and incident HFrEF or HFpEF. Models were adjusted for covariates and interim coronary artery disease (CAD) events. A total of 191 HFrEF and 167 HFpEF events occurred during follow-up. In multivariable analysis, each 1 standard deviation increase in the measured maximum IMT (Z-score) was associated with both HFrEF and HFpEF in the unadjusted and demographically adjusted models [HR, 95% CI 1.57 (1.43 to 1.73)] and [HR, 95% CI 1.61 (1.47 to 1.77)] but not in the fully adjusted models [HR, 95% CI 1.11 (0.96 to 1.28)] and [HR, 95% CI 1.13 (0.98 to 1.30)]. In conclusion, cIMT was significantly associated with incident HF, but the association is partially attenuated with adjustment for demographic factors and becomes non-significant after adjustment for other traditional heart failure risk factors and interim CAD events. There was no difference in the association of IMT measures with HFrEF versus HFpEF.
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http://dx.doi.org/10.1016/j.amjcard.2021.02.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113133PMC
June 2021

Risk Factors for Longitudinal Resting Heart Rate and Its Associations With Cardiovascular Outcomes in the DCCT/EDIC Study.

Diabetes Care 2021 May 25;44(5):1125-1132. Epub 2021 Feb 25.

University of Tennessee Health Science Center, Memphis, TN.

Objective: Individuals with diabetes have higher resting heart rate compared with those without, which may be predictive of long-term cardiovascular disease (CVD) risk. Using data from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study, we evaluated whether the beneficial effect of intensive versus conventional diabetes therapy on heart rate persisted, the factors mediating the differences in heart rate between treatment groups, and the effects of heart rate on future CVD risk.

Research Design And Methods: Longitudinal changes in heart rate, from annual electrocardiograms over 22 years of EDIC follow-up, were evaluated in 1,402 participants with type 1 diabetes. Linear mixed models were used to assess the effect of DCCT treatment group on mean heart rate over time, and Cox proportional hazards models were used to estimate the effect of heart rate on CVD risk during DCCT/EDIC.

Results: At DCCT closeout, 52% of participants were male and mean ± SD age was 33 ± 7 years, diabetes duration 12 ± 5 years, and HbA 7.4 ± 1.2% (intensive) and 9.1 ± 1.6% (conventional). Through EDIC, participants in the intensive group had significantly lower heart rate in comparison with the conventional group. While significant group differences in heart rate were fully attenuated by DCCT/EDIC mean HbA, higher heart rate predicted CVD and major adverse cardiovascular events independent of other risk factors.

Conclusions: After 22 years of follow-up, former intensive versus conventional therapy remained significantly associated with lower heart rate, consistent with the long-term beneficial effects of intensive therapy on CVD. DCCT treatment group effects on heart rate were explained by differences in DCCT/EDIC mean HbA.
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http://dx.doi.org/10.2337/dc20-2387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132325PMC
May 2021

Association of Psychosocial Factors With Short-Term Resting Heart Rate Variability: The Atherosclerosis Risk in Communities Study.

J Am Heart Assoc 2021 02 26;10(5):e017172. Epub 2021 Feb 26.

Department of Medicine School of Medicine Emory University Atlanta GA.

Background Psychosocial factors predict heart disease risk, but our understanding of underlying mechanisms is limited. We sought to evaluate the physiologic correlates of psychosocial factors by measuring their relationships with heart rate variability (HRV), a measure of autonomic health, in the ARIC (Atherosclerosis Risk in Communities) study. We hypothesize that increased psychosocial stress associates with lower HRV. Methods and Results We studied 9331 participants in ARIC with short-term HRV data at visits 2 and 4. The mean (SD) age was 54.4 (5.7) years, 55% were women, and 25% were Black. Psychosocial factors included: (1) vital exhaustion (VE), (2) anger proneness, a personality trait, and (3) perceived social support. Linear models adjusted for sociodemographic and cardiovascular risk factors. Low frequency HRV (ln ms) was significantly lower in the highest versus lowest quartiles of VE (B=-0.14, 95% CI, -0.24 to -0.05). When comparing this effect to age (B=-0.04, 95% CI, -0.05 to -0.04), the difference was equivalent to 3.8 years of accelerated aging. Perceived social support associated with lower time-domain HRV. High VE (versus low VE) also associated with greater decreases in low frequency over time, and both anger and VE associated with greater increases in resting heart rate over time. Survival analyses were performed with Cox models, and no evidence was found that HRV explains the excess risk found with high VE and low perceived social support. Conclusions Vital exhaustion, and to a lesser extent anger and social support, were associated with worse autonomic function and greater adverse changes over time.
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http://dx.doi.org/10.1161/JAHA.120.017172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174247PMC
February 2021

Association of P-Wave Abnormalities With Sudden Cardiac and Cardiovascular Death: The ARIC Study.

Circ Arrhythm Electrophysiol 2021 02 16;14(2):e009314. Epub 2021 Feb 16.

Department of Medicine (L.Y.C.), University of Minnesota, Minneapolis.

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http://dx.doi.org/10.1161/CIRCEP.120.009314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109763PMC
February 2021
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