A human brain vascular atlas reveals diverse mediators of Alzheimer's risk.

The human brain vasculature is of great medical importance: its dysfunction causes disability and death1, and the specialized structure it forms-the blood-brain barrier-impedes the treatment of nearly all brain disorders2,3. Yet so far, we have no molecular map of the human brain vasculature. Here we develop vessel isolation and nuclei extraction for sequencing (VINE-seq) to profile the major vascular and perivascular cell types of the human brain through 143,793 single-nucleus transcriptomes from 25 hippocampus and cortex samples of 9 individuals with Alzheimer's disease and 8 individuals with no cognitive impairment. We identify brain-region- and species-enriched genes and pathways. We reveal molecular principles of human arteriovenous organization, recapitulating a gradual endothelial and punctuated mural cell continuum. We discover two subtypes of human pericytes, marked by solute transport and extracellular matrix (ECM) organization; and define perivascular versus meningeal fibroblast specialization. In Alzheimer's disease, we observe selective vulnerability of ECM-maintaining pericytes and gene expression patterns that implicate dysregulated blood flow. With an expanded survey of brain cell types, we find that 30 of the top 45 genes that have been linked to Alzheimer's disease risk by genome-wide association studies (GWASs) are expressed in the human brain vasculature, and we confirm this by immunostaining. Vascular GWAS genes map to endothelial protein transport, adaptive immune and ECM pathways. Many are microglia-specific in mice, suggesting a partial evolutionary transfer of Alzheimer's disease risk. Our work uncovers the molecular basis of the human brain vasculature, which will inform our understanding of overall brain health, disease and therapy.

Physiological blood-brain transport is impaired with age by a shift in transcytosis.

The vascular interface of the brain, known as the blood-brain barrier (BBB), is understood to maintain brain function in part via its low transcellular permeability1-3. Yet, recent studies have demonstrated that brain ageing is sensitive to circulatory proteins4,5. Thus, it is unclear whether permeability to individually injected exogenous tracers-as is standard in BBB studies-fully represents blood-to-brain transport. Here we label hundreds of proteins constituting the mouse blood plasma proteome, and upon their systemic administration, study the BBB with its physiological ligand. We find that plasma proteins readily permeate the healthy brain parenchyma, with transport maintained by BBB-specific transcriptional programmes. Unlike IgG antibody, plasma protein uptake diminishes in the aged brain, driven by an age-related shift in transport from ligand-specific receptor-mediated to non-specific caveolar transcytosis. This age-related shift occurs alongside a specific loss of pericyte coverage. Pharmacological inhibition of the age-upregulated phosphatase ALPL, a predicted negative regulator of transport, enhances brain uptake of therapeutically relevant transferrin, transferrin receptor antibody and plasma. These findings reveal the extent of physiological protein transcytosis to the healthy brain, a mechanism of widespread BBB dysfunction with age and a strategy for enhanced drug delivery.

Evaluating Screening Tests for Depression in Post-Stroke Older Adults.

BACKGROUND: Uncertainty surrounds which screening test to use in older patients with poststroke depression, in whom symptoms of depression are more complex and often occur in conjunction with other comorbidities. We evaluated screening tests for depression among a cohort of older ambulatory individuals with comorbid ischemic heart disease and prior stroke. METHODS: We administered 4 depression screening instruments to 148 participants with ischemic heart disease and self-reported stroke from The Heart and Soul Study. Instruments included the 10-item Center for Epidemiologic Studies Depression Scale (CES-D), 9-item and 2-item versions of the Patient Health Questionnaire (PHQ-9 and PHQ-2), and the Whooley questions, a 2-item yes/no questionnaire. We administered the computerized version of the National Institute of Mental Health Diagnostic Interview Schedule as a gold standard. RESULTS: Of the 148 participants, 35 (24%) had major depression. The Whooley questions demonstrated the highest sensitivity for detection (89%), followed by the CES-D (80%), PHQ-2 with cut point ≥2 (79%), PHQ-9 (51%), and PHQ-2 with cut point ≥3 (32%). The Whooley questions had a specificity of 0.66, a positive likelihood ratio of 2.61, and a negative likelihood ratio of 0.82. We observed no significant difference in the area under the receiver operating characteristic curve across the 4 instruments. CONCLUSION: In a cohort of ambulatory older adults with coronary heart disease and prior stroke, depression occurred in a fourth of the participants. The simple Whooley questions screening instrument can efficiently detect depression with a high sensitivity in this population, one representative of older patients commonly encountered within a primary care setting.

Evaluation of URO17® to improve non-invasive detection of bladder cancer.

BACKGROUND: The gold standard for detecting bladder cancer is cystoscopy with biopsy or transurethral resection confirming histologic diagnosis. URO17® employs a chromogenically labeled monoclonal antibody to keratin 17 (k17), an intermediate filament cytoskeleton molecule associated with bladder, pancreatic, and cervical cancers. Preliminary studies evaluating k17 demonstrated a high sensitivity and specificity for the detection of bladder cancer, supporting the need for further study. OBJECTIVE: To evaluate the sensitivity and specificity of URO17. METHODS: This is a cross-sectional study of participants undergoing urologic procedures between July 6, 2018 and July 17, 2019 at a single institution. Patients undergoing cystectomy, endoscopic bladder and/or upper tract procedure for probable urothelial carcinoma comprised cases; patients undergoing urologic procedures for other reasons comprised the control group (i.e. prostatectomy, nephrectomy, etc.). Voided urine samples were at the time of procedure; a minority of participants underwent multiple resections in the study period, thus, as many as three urine samples were taken from any given participant. Samples were distributed for blinded testing with URO17. Sensitivity and specificity were calculated. RESULTS: In 152 participants and 167 samples, URO17 demonstrated an overall sensitivity of 90% and 92% and a specificity of 88% and 87%, respectively. In 76 participants and 91 samples from patients with suspected urothelial carcinoma, the sensitivity was 90% and 92%, and the specificity was 50% and 54%, respectively. No controls demonstrated a positive URO17 result, and URO17 superseded urine cytology detection of low-grade and high-grade Ta. False positive results were associated with inflamed tissue or urothelial atypia on histology; the large majority had a history of intravesical therapy. CONCLUSION: Limitations include cross-sectional design and convenience sampling. URO17 may improve sensitivity of urine cytology in the detection of urothelial cancer, though further study is required to refine the application of this biomarker in clinical practice.

Wake-Up Call to Address Sleep Health in Non-Muscle Invasive Bladder Cancer: Underappreciated Contributor to Poor Quality of Life.

BACKGROUND: Few studies have specifically examined sleep health in patients with non-muscle invasive bladder cancer (NMIBC). Further study is warranted to inform future strategies in patients with NMIBC. OBJECTIVE: We aim to describe sleep health in a cohort of patients with NMIBC, and its relationship with quality of life (QOL). METHODS: We conducted an observational cross-sectional study in patients undergoing surveillance for NMIBC. The validated Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep health (scores from 0-21) in the overall study population as well as stratified. We assessed QOL among participants with and without poor sleep quality using the SF-12 and QLQ-NMIBC-24. RESULTS: In a cohort of 94 NMIBC patients, median age was 67 years (IQR: 58, 72) and median time since initial diagnosis was 27 months (IQR: 9, 41). The mean PSQI score was 6.3 (SD: 3.8) and 64% percent of participants met or exceeded the PSQI cut-off score of 5, with a score of 5 or more indicating overall poor sleep quality. In those with poor sleep quality, there were statistically significant detriments in multiple QOL domains. CONCLUSIONS: In patients undergoing surveillance for NMIBC, there is a substantial burden of sleep disturbances and resulting decrements in QOL. These data support the need for future interventions to support sleep quality and highlight the importance of addressing sleep health as part of NMIBC survivorship care to improve QOL in patients with NMIBC.

Engaging Men of Diverse Racial and Ethnic Groups With Advanced Prostate Cancer in the Design of an mHealth Diet and Exercise Intervention: Focus Group Study.

BACKGROUND: Healthy diet and exercise can improve quality of life and prognosis among men with prostate cancer. Understanding the perceived barriers to lifestyle change and patient preferences in a diverse cohort of men with prostate cancer is necessary to inform mobile health (mHealth) lifestyle interventions and increase health equity. OBJECTIVE: We conducted a multisite study to understand the preferences, attitudes, and health behaviors related to diet and lifestyle in this patient population. This report focuses on the qualitative findings from 4 web-based focus groups comprising a racially and ethnically diverse group of patients with advanced prostate cancer who are on androgen deprivation therapy. METHODS: We used grounded theory analyses including open, axial, and selective coding to generate codes. Qualitative data were analyzed as a whole rather than by focus group to optimize data saturation and the transferability of results. We present codes and themes that emerged for lifestyle intervention design and provide recommendations and considerations for future mHealth intervention studies. RESULTS: Overall, 14 men participated in 4 racially and ethnically concordant focus groups (African American or Black: 3/14, 21%; Asian American: 3/14, 21%; Hispanic or Latino: 3/14, 21%; and White: 5/14, 36%). Analyses converged on 7 interwoven categories: context (home environment, access, competing priorities, and lifestyle programs), motivation (accountability, discordance, feeling supported, fear, and temptation), preparedness (health literacy, technological literacy, technological preferences, trust, readiness to change, identity, adaptability, and clinical characteristics), data-driven design (education, psychosocial factors, and quality of life), program mechanics (communication, materials, customization, and being holistic), habits (eg, dietary habits), and intervention impressions. These results suggest actionable pathways to increase program intuitiveness. Recommendations for future mHealth intervention design and implementation include but are not limited to assessment at the individual, household, and neighborhood levels to support a tailored intervention; prioritization of information to disseminate based on individuals' major concerns and the delivery of information based on health and technological literacy and communication preferences; prescribing a personalized intervention based on individuals' baseline responses, home and neighborhood environment, and support network; and incorporating strategies to foster engagement (eg, responsive and relevant feedback systems) to aid participant decision-making and behavior change. CONCLUSIONS: Assessing a patient's social context, motivation, and preparedness is necessary when tailoring a program to each patient's needs in all racial and ethnic groups. Addressing the patients' contexts and motivation and preparedness related to diet and exercise including the household, access (to food and exercise), competing priorities, health and technological literacy, readiness to change, and clinical characteristics will help to customize the intervention to the participant. These data support a tailored approach leveraging the identified components and their interrelationships to ensure that mHealth lifestyle interventions will engage and be effective in racially and ethnically diverse patients with cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT05324098; https://clinicaltrials.gov/ct2/show/NCT05324098.

Diagnostic yield of repeat evaluation for asymptomatic microscopic hematuria after negative initial workup.

PURPOSE: The American Urological Association guideline for asymptomatic microhematuria recommends in patients with a negative initial workup, repeat workup should be considered for those with persistent/recurrent microhematuria. However, there is little data on the yield of repeat evaluation. Our hypothesis was that repeat workup yields a low detection rate of urologic malignancy. MATERIALS AND METHODS: We retrospectively reviewed all patients at our institution who underwent microhematuria workup with cystoscopy and upper tract imaging from May 2010 to June 2016. Microhematuria was defined as ≥3 RBCs/HPF on a properly collected specimen in the absence of a benign cause. Demographics, age, smoking history, history of radiation, and findings on repeat cystoscopy and imaging were collected. Our primary endpoint was a new diagnosis of urologic malignancy. RESULTS: Our initial cohort included 1,332 patients, of whom 21 were diagnosed with urothelial carcinoma and 7 with suspicious renal masses on initial workup. A total of 637 patients with negative initial workup had persistent/recurrent microhematuria. Repeat cystoscopy was performed in 161 (25%) patients at a median of 39 months, and repeat upper tract imaging was performed in 317 (50%) patients at a median of 39 months. Overall, repeat cystoscopy revealed new bladder cancer in 2 (1.2%) patients and repeat imaging revealed new suspicious renal mass in 4 (1.3%) patients. CONCLUSIONS: We observed a low number of newly diagnosed malignancies among patients with persistent/recurrent asymptomatic microhematuria who had a prior negative workup. Additional research is required to determine the utility of a repeat AMH workup.

Tracking Lower Urinary Tract Symptoms and Tamsulosin Side Effects Among Older Men Using a Mobile App (PERSONAL): Feasibility and Usability Study.

BACKGROUND: Continuous α1a-blockade is the first-line treatment for lower urinary tract symptoms (LUTS) among older men with suspected benign prostatic hyperplasia. Variable efficacy and safety for individual men necessitate a more personalized, data-driven approach to prescribing and deprescribing tamsulosin for LUTS in older men. OBJECTIVE: We aim to evaluate the feasibility and usability of the PERSONAL (Placebo-Controlled, Randomized, Patient-Selected Outcomes, N-of-1 Trials) mobile app for tracking daily LUTS severity and medication side effects among older men receiving chronic tamsulosin therapy. METHODS: We recruited patients from the University of California, San Francisco health care system to participate in a 2-week pilot study. The primary objectives were to assess recruitment feasibility, study completion rates, frequency of symptom tracking, duration of tracking sessions, and app usability rankings measured using a follow-up survey. As secondary outcomes, we evaluated whether daily symptom tracking led to changes in LUTS severity, perceptions of tamsulosin, overall quality of life, medication adherence between baseline and follow-up surveys, and perceived app utility. RESULTS: We enrolled 19 men within 23 days, and 100% (19/19) of the participants completed the study. Each participant selected a unique combination of symptoms to track and recorded data in the PERSONAL app, with a median daily completion rate of 79% (11/14 days). The median duration of the app session was 44 (IQR 33) seconds. On a scale of 1 (strongly disagree) to 5 (strongly agree), the participants reported that the PERSONAL app was easy to use (mean 4.3, SD 1.0), that others could learn to use it quickly (mean 4.2, SD 0.9), and that they felt confident using the app (mean 4.4, SD 0.8). LUTS severity, quality of life, and medication adherence remained unchanged after the 2-week study period. Fewer men were satisfied with tamsulosin after using the app (14/19, 74% vs 17/19, 89% at baseline), although the perceived benefit from tamsulosin remained unchanged (18/19, 95% at baseline and at follow-up). In total, 58% (11/19) of the participants agreed that the PERSONAL app could help people like them manage their urinary symptoms. CONCLUSIONS: This pilot study demonstrated the high feasibility and usability of the PERSONAL mobile app to track patient-selected urinary symptoms and medication side effects among older men taking tamsulosin to manage LUTS. We observed that daily symptom monitoring had no adverse effects on the secondary outcomes. This proof-of-concept study establishes a framework for future mobile app studies, such as digital n-of-1 trials, to collect comprehensive individual-level data for personalized LUTS management in older men.

Perceptions of Older Men Using a Mobile Health App to Monitor Lower Urinary Tract Symptoms and Tamsulosin Side Effects: Mixed Methods Study.

BACKGROUND: Mobile health (mHealth) apps may provide an efficient way for patients with lower urinary tract symptoms (LUTS) to log and communicate symptoms and medication side effects with their clinicians. OBJECTIVE: The aim of this study was to explore the perceptions of older men with LUTS after using an mHealth app to track their symptoms and tamsulosin side effects. METHODS: Structured phone interviews were conducted after a 2-week study piloting the daily use of a mobile app to track the severity of patient-selected LUTS and tamsulosin side effects. Quantitative and qualitative data were considered. RESULTS: All 19 (100%) pilot study participants completed the poststudy interviews. Most of the men (n=13, 68%) reported that the daily questionnaires were the right length, with 32% (n=6) reporting that the questionnaires were too short. Men with more severe symptoms were less likely to report changes in perception of health or changes in self-management; 47% (n=9) of the men reported improved awareness of symptoms and 5% (n=1) adjusted fluid intake based on the questionnaire. All of the men were willing to share app data with their clinicians. Thematic analysis of qualitative data yielded eight themes: (1) orientation (setting up app, format, symptom selection, and side-effect selection), (2) triggers (routine or habit and symptom timing), (3) daily questionnaire (reporting symptoms, reporting side effects, and tailoring), (4) technology literacy, (5) perceptions (awareness, causation or relevance, data quality, convenience, usefulness, and other apps), (6) self-management, (7) clinician engagement (communication and efficiency), and (8) improvement (reference materials, flexibility, language, management recommendations, and optimize clinician engagement). CONCLUSIONS: We assessed the perceptions of men using an mHealth app to monitor and improve management of LUTS and medication side effects. LUTS management may be further optimized by tailoring the mobile app experience to meet patients' individual needs, such as tracking a greater number of symptoms and integrating the app with clinicians' visits. mHealth apps are likely a scalable modality to monitor symptoms and improve care of older men with LUTS. Further study is required to determine the best ways to tailor the mobile app and to communicate data to clinicians or incorporate data into the electronical medical record meaningfully.

Web-Based Lifestyle Interventions for Prostate Cancer Survivors: Qualitative Study.

BACKGROUND: Exercise and a healthy diet can improve the quality of life and prognosis of prostate cancer survivors, but there have been limited studies on the feasibility of web-based lifestyle interventions in this population. OBJECTIVE: This study aims to develop a data-driven grounded theory of web-based engagement by prostate cancer survivors based on their experience in the Community of Wellness, a 12-week randomized clinical trial designed to support healthy diet and exercise habits. METHODS: TrueNTH's Community of Wellness was a four-arm pilot study of men with prostate cancer (N=202) who received progressive levels of behavioral support (level 1: website; level 2: website with individualized diet and exercise recommendations; level 3: website with individualized diet and exercise recommendations, Fitbit, and text messages; and level 4: website with individualized diet and exercise recommendations, Fitbit and text messages, and separate phone calls with an exercise trainer and a registered dietitian). The primary aim of the study is to determine the feasibility and estimate the effects on behaviors (results reported in a separate paper). Following the 12-week intervention, we invited participants to participate in 4 focus groups, one for each intervention level. In this report, we used grounded theory analyses including open, axial, and selective coding to generate codes and themes from the focus group transcripts. Categories were refined across levels using embodied categorization and constant comparative methods. RESULTS: In total, 20 men with prostate cancer participated in the focus groups: 5, 4, 5, and 6 men in levels 1, 2, 3, and 4, respectively. Participants converged on 5 common factors influencing engagement with the intervention: environment (home environment, competing priorities, and other lifestyle programs), motivation (accountability and discordance experienced within the health care system), preparedness (technology literacy, health literacy, trust, and readiness to change), program design (communication, materials, and customization), and program support (education, ally, and community). Each of these factors influenced the survivors' long-term impressions and habits. We proposed a grounded theory associating these constructs to describe the components contributing to the intuitiveness of a web-based lifestyle intervention. CONCLUSIONS: These analyses suggest that web-based lifestyle interventions are more intuitive when we optimize participants' technology and health literacy; tailor interface design, content, and feedback; and leverage key motivators (ie, health care providers, family members, web-based coach) and environmental factors (ie, familiarity with other lifestyle programs). Together, these grounded theory-based efforts may improve engagement with web-based interventions designed to support prostate cancer survivorship.

Bladder Preservation for Patients With Bladder Paragangliomas: Case Series and Review of the Literature.

Bladder paragangliomas are rare tumors, with no prospective studies or guidelines on the management of this disease. We present a case series of 6 patients managed with bladder preservation over a median follow-up period of 124 months. We also present a review of the recent literature on bladder paragangliomas. We aim to provide a timely synthesis of the recent evidence on bladder paragangliomas as changing paradigms necessitate individualized treatment.

Initial Precipitants and Recurrence of Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) may occur after an acute precipitant and subsequently resolve. Management guidelines for AF in these settings are unclear as the risk of recurrent AF and related morbidity is poorly understood. We examined the relations between acute precipitants of AF and long-term recurrence of AF in a clinical setting. METHODS: From a multi-institutional longitudinal electronic medical record database, we identified patients with newly diagnosed AF between 2000 and 2014. We developed algorithms to identify acute AF precipitants (surgery, sepsis, pneumonia, pneumothorax, respiratory failure, myocardial infarction, thyrotoxicosis, alcohol, pericarditis, pulmonary embolism, and myocarditis). We assessed risks of AF recurrence in individuals with and without a precipitant and the relations between AF recurrence and heart failure, stroke, and mortality. RESULTS: Among 10 723 patients with newly diagnosed AF (67.9±9.9 years, 41% women), 19% had an acute AF precipitant, the most common of which were cardiac surgery (22%), pneumonia (20%), and noncardiothoracic surgery (15%). The cumulative incidence of AF recurrence at 5 years was 41% among individuals with a precipitant compared with 52% in those without a precipitant (adjusted hazard ratio [HR], 0.75 [95% CI, 0.69-0.81]; P<0.001). The lowest risk of recurrence among those with precipitants occurred with postoperative AF (5-year incidence 32% in cardiac surgery and 39% in noncardiothoracic surgery). Regardless of the presence of an initial precipitant, recurrent AF was associated with increased adjusted risks of heart failure (hazard ratio, 2.74 [95% CI, 2.39-3.15]; P<0.001), stroke (hazard ratio, 1.57 [95% CI, 1.30-1.90]; P<0.001), and mortality (hazard ratio, 2.96 [95% CI, 2.70-3.24]; P<0.001). CONCLUSIONS: AF after an acute precipitant frequently recurs, although the risk of recurrence is lower than among individuals without an acute precipitant. Recurrence is associated with substantial long-term morbidity and mortality. Future studies should address surveillance and management after newly diagnosed AF in the setting of an acute precipitant.

Indications for and Findings on Transthoracic Echocardiography in COVID-19.

BACKGROUND: Despite growing evidence of cardiovascular complications associated with coronavirus disease 2019 (COVID-19), there are few data regarding the performance of transthoracic echocardiography (TTE) and the spectrum of echocardiographic findings in this disease. METHODS: A retrospective analysis was performed among adult patients admitted to a quaternary care center in New York City between March 1 and April 3, 2020. Patients were included if they underwent TTE during the hospitalization after a known positive diagnosis for COVID-19. Demographic and clinical data were obtained using chart abstraction from the electronic medical record. RESULTS: Of 749 patients, 72 (9.6%) underwent TTE following positive results on severe acute respiratory syndrome coronavirus-2 polymerase chain reaction testing. The most common clinical indications for TTE were concern for a major acute cardiovascular event (45.8%) and hemodynamic instability (29.2%). Although most patients had preserved biventricular function, 34.7% were found to have left ventricular ejection fractions ≤ 50%, and 13.9% had at least moderately reduced right ventricular function. Four patients had wall motion abnormalities suggestive of stress-induced cardiomyopathy. Using Spearman rank correlation, there was an inverse relationship between high-sensitivity troponin T and left ventricular ejection fraction (ρ = -0.34, P = .006). Among 20 patients with prior echocardiograms, only two (10%) had new reductions in LVEF of >10%. Clinical management was changed in eight individuals (24.2%) in whom TTE was ordered for concern for acute major cardiovascular events and three (14.3%) in whom TTE was ordered for hemodynamic evaluation. CONCLUSIONS: This study describes the clinical indications for use and diagnostic performance of TTE, as well as findings seen on TTE, in hospitalized patients with COVID-19. In appropriately selected patients, TTE can be an invaluable tool for guiding COVID-19 clinical management.

COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review.

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.

Development and Validation of a Prediction Model for Atrial Fibrillation Using Electronic Health Records.

OBJECTIVES: This study sought to determine whether the risk of atrial fibrillation AF can be estimated accurately by using routinely ascertained features in the electronic health record (EHR) and whether AF risk is associated with stroke. BACKGROUND: Early diagnosis of AF and treatment with anticoagulation may prevent strokes. METHODS: Using a multi-institutional EHR, this study identified 412,085 individuals 45 to 95 years of age without prevalent AF between 2000 and 2014. A prediction model was derived and validated for 5-year AF risk by using split-sample validation and model performance was compared with other methods of AF risk assessment. RESULTS: Within 5 years, 14,334 individuals developed AF. In the derivation sample (7,216 AF events of 206,042 total), the optimal risk model included sex, age, race, smoking, height, weight, diastolic blood pressure, hypertension, hyperlipidemia, heart failure, coronary heart disease, valvular disease, prior stroke, peripheral arterial disease, chronic kidney disease, hypothyroidism, and quadratic terms for height, weight, and age. In the validation sample (7,118 AF events of 206,043 total) the AF risk model demonstrated good discrimination (C-statistic: 0.777; 95% confidence interval [CI:] 0.771 to 0.783) and calibration (0.99; 95% CI: 0.96 to 1.01). Model discrimination and calibration were superior to CHARGE-AF (Cohorts for Heart and Aging Research in Genomic Epidemiology AF) (C-statistic: 0.753; 95% CI: 0.747 to 0.759; calibration slope: 0.72; 95% CI: 0.71 to 0.74), C2HEST (Coronary artery disease / chronic obstructive pulmonary disease; Hypertension; Elderly [age ≥75 years]; Systolic heart failure; Thyroid disease [hyperthyroidism]) (C-statistic: 0.754; 95% CI: 0.747 to 0.762; calibration slope: 0.44; 95% CI: 0.43 to 0.45), and CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Prior stroke, transient ischemic attack [TIA], or thromboembolism, Vascular disease, Age 65-74 years, Sex category [female]) scores (C-statistic: 0.702; 95% CI: 0.693 to 0.710; calibration slope: 0.37; 95% CI: 0.36 to 0.38). AF risk discriminated incident stroke (n = 4,814; C-statistic: 0.684; 95% CI: 0.677 to 0.692) and stroke within 90 days of incident AF (n = 327; C-statistic: 0.789; 95% CI: 0.764 to 0.814). CONCLUSIONS: A model developed from a real-world EHR database predicted AF accurately and stratified stroke risk. Incorporating AF prediction into EHRs may enable risk-guided screening for AF.

Frequency of Cardiac Rhythm Abnormalities in a Half Million Adults.

BACKGROUND: The frequency of cardiac rhythm abnormalities and their risk factors in community-dwelling adults are not well characterized. METHODS: We determined the frequency of rhythm abnormalities in the UK Biobank, a national prospective cohort. We tested associations between risk factors and incident rhythm abnormalities using multivariable proportional hazards regression. RESULTS: Of 502 627 adults (median age, 58 years [interquartile range, 13]; 54.4% women), 2.35% had a baseline rhythm abnormality. The prevalence increased with age with 4.84% of individuals aged 65 to 73 years affected. During 3 368 332 person-years of follow-up, 15 906 new rhythm abnormalities were detected (4.72 per 1000 person-years; 95% confidence interval [CI]: 4.65-4.80). Atrial fibrillation (3.11 per 1000 person-years; 95% CI: 3.05-3.17), bradyarrhythmias (0.89 per 1000 person-years; 95% CI: 0.86-0.92), and conduction system diseases (1.06 per 1000 person-years; 95% CI: 1.02-1.09) were more common than supraventricular (0.51 per 1000 person-years; 95% CI: 0.48-0.53) and ventricular arrhythmias (0.57 per 1000 person-years; 95% CI: 0.55-0.60). Older age (hazard ratio [HR]: 2.35 per 10-year increase; 95% CI: 2.29-2.41; P<0.01), male sex (HR: 1.83; 95% CI: 1.76-1.89; P<0.01), hypertension (HR: 1.49; 95% CI: 1.44-1.54; P<0.01), chronic kidney disease (HR: 1.95; 95% CI: 1.67-2.27; P<0.01), and heart failure (HR: 1.99; 95% CI: 1.76-2.26; P<0.01) were associated with new rhythm abnormalities. CONCLUSIONS: The frequency of rhythm abnormalities in middle-aged to older community-dwelling adults is substantial. Atrial fibrillation, bradyarrhythmias, and conduction system diseases account for most rhythm conditions.

Causes and Predictors of Death in Patients With Coronary Heart Disease (from the Heart and Soul Study).

Although the prevalence of coronary heart disease (CHD) in the United States has increased during the past 25 years, cardiovascular mortality has decreased due to advances in CHD therapy and prevention. We sought to determine the proportion of patients with CHD who die from cardiovascular versus noncardiovascular causes and the causes and predictors of death, in a cohort of patients with CHD. The Heart and Soul Study enrolled 1,024 participants with stable CHD from 2000 to 2002 and followed them for 10 years. Causes of mortality were assigned based on detailed review of medical records, death certificates, and coroner reports by blinded adjudicators. During 7,680 person-years of follow-up, 401 participants died. Of these deaths, 42.4% were cardiovascular and 54.4% were noncardiovascular. Myocardial infarction, stroke, and sudden death accounted for 72% of cardiovascular deaths. Cancer, pneumonia, and sepsis accounted for 67% of noncardiovascular deaths. Independent predictors of cardiac mortality were older age, inducible ischemia on stress echocardiography, higher heart rate at rest, smoking, lower hemoglobin, and higher N-terminal pro-brain natriuretic peptide (all p values <0.05); independent predictors of noncardiac mortality included older age, inducible ischemia, higher heart rate, lower exercise capacity, and nonuse of statins (all p values <0.05). In conclusion, mortality in this cohort was more frequently due to noncardiovascular causes, and predictors of noncardiovascular mortality included factors traditionally associated with cardiovascular mortality.