Modifiable predictors of ventricular ectopy in the community

Background Premature ventricular contractions (PVCs) predict heart failure and death. Data regarding modifiable risk factors for PVCs are scarce. Methods and Results We studied 1424 Cardiovascular Health Study participants randomly assigned to 24-hour Holter monitoring. Demographics, comorbidities, habits, and echocardiographic measurements were examined as predictors of PVC frequency and, among 845 participants, change in PVC frequency 5 years later. Participants exhibited a median of 0.6 (interquartile range, 0.1-7.1) PVCs per hour. Of the more directly modifiable characteristics and after multivariable adjustment, every SD increase in systolic blood pressure was associated with 9% more PVCs (95% confidence interval [CI], 2%-17%; P=0.01), regularly performing no or low-intensity exercise compared with more physical activity was associated with ≈15% more PVCs (95% CI, 3-25%; P=0.02), and those with a history of smoking exhibited an average of 18% more PVCs (95% CI, 3-36%; P=0.02) than did never smokers. After 5 years, PVC frequency increased from a median of 0.5 (IQR, 0.1-4.7) to 1.2 (IQR, 0.1-13.8) per hour ( P<0.0001). Directly modifiable predictors of 5-year increase in PVCs, described as the odds per each quintile increase in PVCs, included increased diastolic blood pressure (odds ratio per SD increase, 1.16; 95% CI, 1.02-1.31; P=0.02) and a history of smoking (OR, 1.31; 95% CI, 1.02-1.68; P=0.04). Conclusions Enhancing physical activity, smoking cessation, and aggressive control of blood pressure may represent fruitful strategies to mitigate PVC frequency and PVC-associated adverse outcomes

Body size measures, hemostatic and inflammatory markers and risk of venous thrombosis: The Longitudinal Investigation of Thromboembolism Etiology

Obesity is an important venous thrombosis (VT) risk factor but the reasons for this are unclear

Alcohol consumption and leukocyte telomere length.

The relationship between alcohol consumption and mortality generally exhibits a U-shaped curve. The longevity observed with moderate alcohol consumption may be explained by other confounding factors, and, if such a relationship is present, the mechanism is not well understood. Indeed, the optimal amount of alcohol consumption for health has yet to be determined. Leukocyte telomere length is an emerging quantifiable marker of biological age and health, and a shorter telomere length is a predictor of increased mortality. Because leukocyte telomere length is a quantifiable and objectively measurable biomarker of aging, we sought to identify the amount of alcohol consumption associated with the longest telomere length and least telomere length attrition. Among over 2,000 participants from two distinct cohort studies, we found no pattern of alcohol consumption that was associated with longer telomere length or less telomere length attrition over time. Binge drinking may reduce telomere length. Using telomere length as a marker of age and health, these data fail to demonstrate any benefits of alcohol consumption, even when consumed in moderation

Incidence of and Risk Factors for Sick Sinus Syndrome in the General Population

AbstractBackgroundLittle is known about the incidence of and risk factors for sick sinus syndrome (SSS), a common indication for pacemaker implantation.ObjectivesThis study sought to describe the epidemiology of SSS.MethodsThis analysis included 20,572 participants (mean baseline age 59 years, 43% male) in the ARIC (Atherosclerosis Risk In Communities) study and the CHS (Cardiovascular Health Study), who at baseline were free of prevalent atrial fibrillation and pacemaker therapy, had a heart rate of ≥50 beats/min unless using beta blockers, and were identified as of white or black race. Incident SSS cases were identified by hospital discharge International Classification of Disease-revision 9-Clinical Modification code 427.81 and validated by medical record review.ResultsDuring an average 17 years of follow-up, 291 incident SSS cases were identified (unadjusted rate 0.8 per 1,000 person-years). Incidence increased with age (hazard ratio [HR]: 1.73; 95% confidence interval [CI]: 1.47 to 2.05 per 5-year increment), and blacks had a 41% lower risk of SSS than whites (HR: 0.59; 95% CI: 0.37 to 0.98). Incident SSS was associated with greater baseline body mass index, height, N-terminal pro–B-type natriuretic peptide, and cystatin C, with longer QRS interval, with lower heart rate, and with prevalent hypertension, right bundle branch block, and cardiovascular disease. We project that the annual number of new SSS cases in the United States will increase from 78,000 in 2012 to 172,000 in 2060.ConclusionsBlacks have a lower risk of SSS than whites, and several cardiovascular risk factors were associated with incident SSS. With the aging of the population, the number of Americans with SSS will increase dramatically over the next 50 years

Brachial Flow-Mediated Dilation and Incident Atrial Fibrillation The Multi-Ethnic Study of Atherosclerosis

Objective—It is unknown whether endothelial dysfunction precedes atrial fibrillation (AF) development. The objective of this study was to examine the association of brachial flow-mediated dilation (FMD) with incident AF. Approach and Results—A total of 2936 participants (mean age, 61±9.9 years; 50% women; 66% nonwhites) from the Multi-Ethnic Study of Atherosclerosis with available ultrasound brachial FMD measurements who were free of baseline AF were included in this analysis. Baseline (2000–2002) FMD was computed from the percentage difference (%FMD) in brachial artery diameter and maximum diameter during measured vasodilator response. AF was ascertained from hospitalization data including Medicare claims during a median follow-up of 8.5 years. Probability-weighted Cox proportional-hazards regression was used to compute hazard ratios and 95% confidence intervals for the association between FMD as a continuous variable (%FMD values per 1-SD increase) and incident AF. Incident AF was detected in 137 (4.7%) participants. Those with %FMD values below the sex-specific median value (median %FMD; men, 3.6%; women, 4.2%; incidence rate per 1000 person-years, 7.3; 95% confidence interval, 5.9–9.0) were more likely to develop AF than people whose %FMD values were above the median value (incidence rate per 1000 person-years, 4.5; 95% confidence interval, 3.4–5.8; log-rank P=0.0043). In a multivariable Cox regression analysis, each 1-SD increase in %FMD values (SD, 2.8%) was associated with less incident AF (hazard ratio, 0.84; 95% confidence interval, 0.70–0.99). These results were consistent across subgroups stratified by age, sex, and race/ethnicity. Conclusions—Smaller brachial FMD values are associated with higher rates of AF, sugge

Ectopy on a single 12‐lead ECG, incident cardiac myopathy, and death in the community

BackgroundAtrial fibrillation and heart failure are 2 of the most common diseases, yet ready means to identify individuals at risk are lacking. The 12-lead ECG is one of the most accessible tests in medicine. Our objective was to determine whether a premature atrial contraction observed on a standard 12-lead ECG would predict atrial fibrillation and mortality and whether a premature ventricular contraction would predict heart failure and mortality.Methods and resultsWe utilized the CHS (Cardiovascular Health) Study, which followed 5577 participants for a median of 12 years, as the primary cohort. The ARIC (Atherosclerosis Risk in Communities Study), the replication cohort, captured data from 15 792 participants over a median of 22 years. In the CHS, multivariable analyses revealed that a baseline 12-lead ECG premature atrial contraction predicted a 60% increased risk of atrial fibrillation (hazard ratio, 1.6; 95% CI, 1.3-2.0; P<0.001) and a premature ventricular contraction predicted a 30% increased risk of heart failure (hazard ratio, 1.3; 95% CI, 1.0-1.6; P=0.021). In the negative control analyses, neither predicted incident myocardial infarction. A premature atrial contraction was associated with a 30% increased risk of death (hazard ratio, 1.3; 95% CI, 1.1-1.5; P=0.008) and a premature ventricular contraction was associated with a 20% increased risk of death (hazard ratio, 1.2; 95% CI, 1.0-1.3; P=0.044). Similarly statistically significant results for each analysis were also observed in ARIC.ConclusionsBased on a single standard ECG, a premature atrial contraction predicted incident atrial fibrillation and death and a premature ventricular contraction predicted incident heart failure and death, suggesting that this commonly used test may predict future disease

Prehospital Systolic Blood Pressure Thresholds: A Community‐based Outcomes Study

Objectives Emergency medical services (EMS) personnel commonly use systolic blood pressure ( sBP ) to triage and treat acutely ill patients. The definition of prehospital hypotension and its associated outcomes are poorly defined. The authors sought to determine the discrimination of prehospital sBP thresholds for 30‐day mortality and to compare patient classification by best‐performing thresholds to traditional cutoffs. Methods In a community‐based cohort of adult, nontrauma, noncardiac arrest patients transported by EMS between 2002 and 2006, entries to state hospital discharge data and death certificates were linked. Prehospital sBP thresholds between 40 and 140 mm Hg in derivation ( n =  132,624) and validation ( n =  22,020) cohorts and their discrimination for 30‐day mortality, were examined. Cutoffs were evaluated using the 0/1 distance, Youden index, and adjusted Z‐statistics from multivariable logistic regression models. Results In the derivation cohort, 1,594 (1.2%) died within 24 hours, 7,404 (6%) were critically ill during hospitalization, and 6,888 (5%) died within 30 days. The area under the receiver operating characteristic (ROC) curve for sBP was 0.60 (95% confidence interval [CI] = 0.59, 0.61) for 30‐day mortality and 0.64 (95% CI = 0.62 0.66) for 24‐hour mortality. The 0/1 distance, Youden index, and adjusted Z‐statistics found best‐performing sBP thresholds between 110 and 120 mm Hg. When compared to an sBP ≤ 90 mm Hg, a cutoff of 110 mm Hg would identify 17% ( n =  137) more deaths at 30 days, while overtriaging four times as many survivors. Conclusions Prehospital sBP is a modest discriminator of clinical outcomes, yet no threshold avoids substantial misclassification of 30‐day mortality among noninjured patients. Resumen Los Umbrales de la Presión Arterial Sistólica Prehospitalaria: Un Estudio de Base Comunitaria Acerca de la Evolución de los Pacientes Objetivos El personal de los sistemas de emergencias médicas ( SEM ) usa frecuentemente la presión arterial sistólica ( PAS ) para clasificar y tratar a los pacientes agudos. Las definiciones de hipotensión prehospitalaria y sus resultados asociados están pobremente definidos. Se determinó la discriminación de los umbrales de PAS prehospitalaria para la mortalidad a los 30 días, y se comparó la clasificación del paciente por los mejores umbrales con los puntos de corte tradicionales. Metodología Estudio de cohorte de base comunitaria de pacientes adultos no traumatológicos ni con paradas cardiorrespiratorias transportados por los SEM entre 2002 y 2006, cuyas historias estaban vinculadas con los datos de alta hospitalaria y los certificados de mortalidad. Se examinaron los umbrales de PAS prehospitalaria entre 40 mm Hg y 140 mm Hg en las cohortes de derivación ( n =  132.624), y validación ( n =  22,020), y su discriminación para la mortalidad a los 30 días. Los puntos de corte se evaluaron usando la distancia 0/1, el índice de Youden y los estadísticos Z ajustados de los modelos de regresión logística multivariable. Resultados: En la cohorte de derivación, 1.594 (1,2%) fallecieron en las primeras 24 horas, 7.404 (6%) estuvieron críticamente enfermos durante el ingreso y 6.888 (5%) fallecieron en los 30 primeros días. El área bajo la curva de la ROC para PAS fue 0,60 ( IC 95% = 0,59–0,61) para la mortalidad a los 30 días y 0,64 ( IC 95% = 0,62–0,66) para la mortalidad a las 24 horas. La distancia 0/1, el índice de Youden y las estadísticas Z ajustadas hallaronque los mejores umbrales de PAS estaban entre 110 y 120 mm Hg. Cuando se comparó con una PAS ≤ 90 mm Hg, un punto de corte de 110 mm Hg identificaría un 17% ( n =  137) más de muertes a los 30 días, mientras que sobreclasificaría cuatro veces más a los supervivientes. Conclusiones La presión arterial sistólica es un discriminador modesto de resultados clínicos. No obstante, ningún umbral evita una mala clasificación de la mortalidad a los 30 días entre los pacientes no traumatológicos.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/1/acem12142-sup-0002-DataSupplementS2_FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/2/acem12142-sup-0007-DataSupplementS7_FigS4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/3/acem12142-sup-0006-DataSupplementS6_FigS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/4/acem12142-sup-0009-DataSupplementS9_TableS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/5/acem12142-sup-0003-DataSupplementS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/6/acem12142-sup-0008-DataSupplementS8_TableS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/7/acem12142-sup-0004-DataSupplementS4_TableS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/8/acem12142-sup-0001-DataSupplementS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/9/acem12142.pd

Incremental value of rare genetic variants for the prediction of multifactorial diseases

Background: It is often assumed that rare genetic variants will improve available risk prediction scores. We aimed to estimate the added predictive ability of rare variants for risk prediction of common diseases in hypothetical scenarios.Methods: In simulated data, we constructed risk models with an area under the ROC curve (AUC) ranging between 0.50 and 0.95, to which we added a single variant representing the cumulative frequency and effect (odds ratio, OR) of multiple rare variants. The frequency of the rare variant ranged between 0.0001 and 0.01 and the OR between 2 and 10. We assessed the resulting AUC, increment in AUC, integrated discrimination improvement (IDI), net reclassification improvement (NRI(>0.01)) and categorical NRI. The analyses were illustrated by a simulation of atrial fibrillation risk prediction based on a published clinical risk model.Results: We observed minimal improvement in AUC with the addition of rare variants. All measures increased with the frequency and OR of the variant, but maximum increment in AUC remained below 0.05. Increment in AUC and NRI(>0.01) decreased with higher AUC of the baseline model, w

Peripheral Arterial Disease and Risk of Atrial Fibrillation and Stroke: The Multi�Ethnic Study of Atherosclerosis

Background Peripheral arterial disease (PAD) shares several risk factors with atrial fibrillation (AF), and persons with PAD have an increased risk of stroke. It is unclear if PAD is associated with an increased risk for AF and whether this potential association explains the increased risk of stroke observed in those with PAD. Methods and Results We examined the association between PAD, measured by ankle�brachial index (ABI), and incident AF and incident stroke, separately, in 6568 participants (mean age 62±10 years, 53% women, 62% nonwhite) from the Multi�Ethnic Study of Atherosclerosis (MESA). ABI values 1.4 defined PAD. AF was ascertained through review of hospital discharge records and from Medicare claims data until December 31, 2010. An independent adjudication committee ascertained stroke events. Cox regression was used to estimate hazard ratios and 95% CIs for the association between PAD and AF and stroke. Over a median follow�up of 8.5 years, 301 (4.6%) participants developed AF and 140 (2.1%) developed stroke. In a model adjusted for sociodemographics, cardiovascular risk factors, and potential confounders, PAD was associated with an increased risk of AF (hazard ratio 1.5, 95% CI 1.1 to 2.0). In a similar model, PAD was associated with incident stroke (hazard ratio 1.7, 95% CI 1.1 to 2.5), and the magnitude of risk was not different after inclusion of AF as a time�dependent covariate (hazard ratio 1.7, 95% CI 1.1 to 2.5). Conclusions PAD is associated with an increased risk of AF and stroke in MESA. Potentially, the relationship between PAD and stroke is not mediated by AF

DEEPMIR: A DEEP neural network for differential detection of cerebral Microbleeds and IRon deposits in MRI

Lobar cerebral microbleeds (CMBs) and localized non-hemorrhage iron deposits in the basal ganglia have been associated with brain aging, vascular disease and neurodegenerative disorders. Particularly, CMBs are small lesions and require multiple neuroimaging modalities for accurate detection. Quantitative susceptibility mapping (QSM) derived from in vivo magnetic resonance imaging (MRI) is necessary to differentiate between iron content and mineralization. We set out to develop a deep learning-based segmentation method suitable for segmenting both CMBs and iron deposits. We included a convenience sample of 24 participants from the MESA cohort and used T2-weighted images, susceptibility weighted imaging (SWI), and QSM to segment the two types of lesions. We developed a protocol for simultaneous manual annotation of CMBs and non-hemorrhage iron deposits in the basal ganglia. This manual annotation was then used to train a deep convolution neural network (CNN). Specifically, we adapted the U-Net model with a higher number of resolution layers to be able to detect small lesions such as CMBs from standard resolution MRI. We tested different combinations of the three modalities to determine the most informative data sources for the detection tasks. In the detection of CMBs using single class and multiclass models, we achieved an average sensitivity and precision of between 0.84-0.88 and 0.40-0.59, respectively. The same framework detected non-hemorrhage iron deposits with an average sensitivity and precision of about 0.75-0.81 and 0.62-0.75, respectively. Our results showed that deep learning could automate the detection of small vessel disease lesions and including multimodal MR data (particularly QSM) can improve the detection of CMB and non-hemorrhage iron deposits with sensitivity and precision that is compatible with use in large-scale research studies