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ImportanceSelf-measured blood pressure (SMBP) with commercially available connected smartphone applications may help patients effectively use SMBP measurements.ObjectiveTo determine if enhanced SMBP paired with a connected smartphone application was superior to standard SMBP for blood pressure (BP) reduction or patient satisfaction.Design, Setting, and ParticipantsThis randomized clinical trial was conducted among 23 health systems participating in PCORnet, the National Patient-Centered Clinical Research Network, and included patients who reported having uncontrolled BP at their last clinic visit, a desire to lower their BP, and a smartphone. Enrollment and randomization occurred from August 3, 2019, to December 31, 2020, which was followed by 6 months of follow-up for each patient. Analysis commenced shortly thereafter.InterventionsEligible participants were randomly assigned to enhanced SMBP using a device that paired with a connected smartphone application (enhanced) or a standard device (standard). Participants received their device in the mail, along with web-based educational materials and phone-based support as needed. No clinician engagement was undertaken, and the study provided no special mechanisms for delivering measurements to clinicians for use in BP management.Main Outcomes and MeasuresReduction in systolic BP, defined as the difference between clinic BP at baseline and the most recent clinic BP extracted from electronic health records at 6 months.ResultsEnrolled participants (1051 enhanced [50.0%] vs 1050 standard [50.0%]; 1191 women [56.7%]) were mostly middle-aged or older (mean [SD] age, 58 [13] years), nearly a third were Black or Hispanic (645 [31%]), and most were relatively comfortable using technology (mean [SD], 4.1 [1.1] of 5). The mean (SD) change in systolic BP from baseline to 6 months was −10.8 (18) mm Hg vs −10.6 (18) mm Hg (enhanced vs standard: adjusted difference, −0.19 mm Hg; 95% CI, −1.83 to 1.44; P = .81). Secondary outcomes were mostly null, except for documented attainment of BP control to lower than 140/Conclusions and RelevanceThis randomized clinical trial found that enhanced SMBP paired with a smartphone application is not superior to standard SMBP for BP reduction or patient satisfaction.Trial RegistrationClinicalTrials.gov Identifier: NCT03796689

INTRODUCTION AND OBJECTIVES Data are scarce on outcomes of transvenous lead removal (TLR) in adult congenital heart disease (CHD). We evaluated the safety of the TLR procedure in adult CHD patients from a 10-year national database. METHODS We used the Healthcare Cost and Utilization Project Nationwide Inpatient Sample to identify TLR procedures in adult patients with and without CHD from 2005 to 2014. Outcomes included in-hospital mortality and complications. RESULTS Of 132 068 adult patients undergoing TLR, 1939 had simple CHD, 657 had complex CHD, and 626 had unclassified CHD. The number of TLR procedures in adult CHD slightly increased from 236 in 2005 to 445 in 2014, with fluctuations over the study period. The overall rate of any complications in the TLR procedure was 16.6% in patients with CHD vs 10.1% in patients without CHD (P

IMPORTANCE: Sleep has major consequences for physical and emotional well-being. Hospitalized patients experience frequent iatrogenic sleep interruptions and there is evidence that such interruptions can be safely reduced. OBJECTIVE: To determine whether a clinical decision support tool, powered by real-time patient data and a trained prediction algorithm, can help physicians identify clinically stable patients and safely discontinue their overnight vital sign checks. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial, with inpatient encounters randomized 1:1 to intervention vs usual care, was conducted from March 11 to November 24, 2019. Participants included physicians serving on the primary team of 1699 patients on the general medical service (not in the intensive care unit) of a tertiary care academic medical center. INTERVENTIONS: A clinical decision support notification informed the physician if the patient had a high likelihood of nighttime vital signs within the reference ranges based on a logistic regression model that used real-time patient data as input. The notification provided the physician an opportunity to discontinue measure of nighttime vital signs, dismiss the notification for 1 hour, or dismiss the notification for that day. MAIN OUTCOMES AND MEASURES: The primary outcome was delirium, as determined by bedside nurse assessment of Nursing Delirium Screening Scale scores, a standardized delirium screening tool (delirium diagnosed with score ≥2). Secondary outcomes included mean nighttime vital sign checks. Potential harms included intensive care unit transfers and code blue alarms. All analyses were conducted on the basis of intention-to-treat. RESULTS: A total of 1930 inpatient encounters in 1699 patients (intervention encounters: 566 of 966 [59%] men; mean [SD] age, 53 [15] years) were randomized. In the intervention vs control arm, there was a significant decrease in the mean (SD) number of nighttime vital sign checks (0.97 [0.95] vs 1.41 [0.86]; P

The global burden of diabetes is rapidly increasing, from 451 million people in 2019 to 693 million by 20451. The insidious onset of type 2 diabetes delays diagnosis and increases morbidity2. Given the multifactorial vascular effects of diabetes, we hypothesized that smartphone-based photoplethysmography could provide a widely accessible digital biomarker for diabetes. Here we developed a deep neural network (DNN) to detect prevalent diabetes using smartphone-based photoplethysmography from an initial cohort of 53,870 individuals (the ‘primary cohort’), which we then validated in a separate cohort of 7,806 individuals (the ‘contemporary cohort’) and a cohort of 181 prospectively enrolled individuals from three clinics (the ‘clinic cohort’). The DNN achieved an area under the curve for prevalent diabetes of 0.766 in the primary cohort (95% confidence interval: 0.750–0.782; sensitivity 75%, specificity 65%) and 0.740 in the contemporary cohort (95% confidence interval: 0.723–0.758; sensitivity 81%, specificity 54%). When the output of the DNN, called the DNN score, was included in a regression analysis alongside age, gender, race/ethnicity and body mass index, the area under the curve was 0.830 and the DNN score remained independently predictive of diabetes. The performance of the DNN in the clinic cohort was similar to that in other validation datasets. There was a significant and positive association between the continuous DNN score and hemoglobin A1c (P ≤ 0.001) among those with hemoglobin A1c data. These findings demonstrate that smartphone-based photoplethysmography provides a readily attainable, non-invasive digital biomarker of prevalent diabetes. A deep neural network applied to smartphone-based vascular imaging can detect diabetes, opening new possibilities for non-invasive diagnosis.

Background: Prolonged heart rate-corrected QT (QTc) interval has been associated with incident cardiovascular diseases (CVD) in general Western populations. However, this association is unclear in Asian population. We aim to estimate the association between QTc interval and incident CVD in a general Chinese population.Methods: We analyzed 8,867 participants age ≥35 years and free of CVD at baseline in the Northeast China Rural Cardiovascular Health Study. A resting 12-lead electrocardiogram was performed on all participants, and QTc interval computed using the Framingham formula. Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for associations between QTc interval and incident stroke, coronary heart disease, and combined CVD events.Results: Over a median follow-up of 4.66 years, a total of 439 CVD events occurred (298 stroke cases and 152 CHD cases). After full adjustment, prolonged QTc defined by a sex-specific cutoff was associated with increased risk of developing stroke (HR: 1.82, 95% CI 1.20–2.75, P = 0.004) and combined CVD (HR: 1.52, 95% CI 1.05–2.19, P = 0.026). Spline analyses demonstrated no clear thresholds; when modeled as a linear relationship, each 10 ms increase of QTc interval was associated with an HR of 1.12 (95% CI 1.06–1.19, P < 0.001) for stroke and an HR of 1.10 (95% CI 1.05–1.15, P < 0.001) for combined CVD. Baseline QTc interval was not associated with incident CHD with either modeling strategy.Conclusions: Baseline QTc interval is associated with incident stroke and CVD in adults without prior CVD from a general Chinese population.

This retrospective study examined changes in medication orders as a risk factor for future acute hypoglycemic events. The investigators identified factors associated with acute hypoglycemic events resulting in emergency department visits or inpatient admissions. Non-Hispanic Black race, chronic kidney disease, insulin at baseline, and non-private insurance were associated with higher risk of an acute hypoglycemic event, whereas age, sex, and A1C were not. After adjustment for other risk factors, changes in insulin orders after A1C measurement were associated with a 1.5 times higher risk of an acute hypoglycemia (adjusted hazard ratio 1.48, 95% CI 1.08–2.03). These results further understanding of risk factors and clinical processes relevant to predicting and preventing acute hypoglycemia.

Background and AimsIn patients with chronic liver diseases (CLD) with or without cirrhosis, existing data on the risk of adverse outcomes with SARS-CoV-2 infection have been mixed or have limited generalizability. We used the National COVID Cohort Collaborative (N3C) Data Enclave, a harmonized electronic health record (EHR) dataset of 5.9 million nationally-representative, diverse, and gender-balanced patients, to describe outcomes in patients with CLD and cirrhosis with SARS-CoV-2.MethodsWe identified all chronic liver diseases patients with and without cirrhosis who had SARS-CoV-2 testing documented in the N3C Data Enclave as of data release date 5/15/2021. The primary outcome was 30-day all-cause mortality. Survival analysis methods were used to estimate cumulative incidences of death, hospitalization, and mechanical ventilation, and to calculate the associations of SARS-CoV-2 infection, presence of cirrhosis, and demographic and clinical factors to 30-day mortality.ResultsWe isolated 217,143 patients with CLD: 129,097 (59%) without cirrhosis and SARS-CoV-2 negative, 25,844 (12%) without cirrhosis and SARS-CoV-2 positive, 54,065 (25%) with cirrhosis and SARS-CoV-2 negative, and 8,137 (4%) with cirrhosis and SARS-CoV-2 positive. Among CLD patients without cirrhosis, 30-day all-cause mortality rates were 0.4% in SARS-CoV-2 negative patients and 1.8% in positive patients. Among CLD patients with cirrhosis, 30-day all-cause mortality rates were 4.0% in SARS-CoV-2 negative patients and 9.7% in positive patients.Compared to those who tested SARS-CoV-2 negative, SARS-CoV-2 positivity was associated with more than two-fold (aHR 2.43, 95% CI 2.23-2.64) hazard of death at 30 days among patients with cirrhosis. Compared to patients without cirrhosis, the presence of cirrhosis was associated with a three-fold (aHR 3.39, 95% CI 2.96-3.89) hazard of death at 30 days among patients who tested SARS-CoV-2 positive. Age (aHR 1.03 per year, 95% CI 1.03-1.04) was associated with death at 30 days among patients with cirrhosis who were SARS-CoV-2 positive.ConclusionsIn this study of nearly 220,000 CLD patients, we found SARS-CoV-2 infection in patients with cirrhosis was associated with 2.43-times mortality hazard, and the presence of cirrhosis among CLD patients infected with SARS-CoV-2 were associated with 3.39-times mortality hazard. Compared to previous studies, our use of a nationally-representative, diverse, and gender-balanced dataset enables wide generalizability of these findings.

Background Independent associations between cardiovascular risk factor exposures during midlife and later life development of heart failure (HF) with preserved ejection fraction (HFpEF) versus reduced EF (HFrEF) have not been previously studied. Methods We pooled data from 4 US cohort studies (Atherosclerosis Risk in Communities, Cardiovascular Health, Health , Aging and Body Composition, and Multi-Ethnic Study of Atherosclerosis) and imputed annual risk factor trajectories for body mass index, systolic and diastolic blood pressure, low-density lipoprotein and high-density lipoprotein cholesterol, and glucose starting from age 40 years. Time-weighted average exposures to each risk factor during midlife and later life were calculated and analyzed for associations with the development of HFpEF or HFrEF. Results A total of 23,861 participants were included (mean age at first in-person visit, 61.8 ±1 0.2 years; 56.6% female). During a median follow-up of 12 years, there were 3666 incident HF events, of which 51% had EF measured, including 934 with HFpEF and 739 with HFrEF. A high midlife systolic blood pressure and low midlife high-density lipoprotein cholesterol were associated with HFrEF, and a high midlife body mass index, systolic blood pressure, pulse pressure, and glucose were associated with HFpEF. After adjusting for later life exposures, only midlife pulse pressure remained independently associated with HFpEF. Conclusions Midlife exposure to cardiovascular risk factors are differentially associated with HFrEF and HFpEF later in life. Having a higher pulse pressure during midlife is associated with a greater risk for HFpEF but not HFrEF, independent of later life exposures.

Context The independent contribution of young adult exposure to overweight and obesity to later-life incident diabetes is not well studied. Objective To assess the associations of exposures to elevated body mass index (BMI) and waist circumference (WC) in young adulthood (ages 18-39 years) with incident diabetes later in life (≥40 years). Design Pooled data from 6 US prospective cohorts (Atherosclerosis Risk in Communities Study, Cardiovascular Risk Development in Young Adults Study, Cardiovascular Health Study, (4) Framingham Heart Study Offspring Cohort, (5) Health, Aging and Body Composition Study, and (6) Multi-Ethnic Study of Atherosclerosis. Setting Population-based cohort studies. Participants 30 780 participants (56.1% female, 69.8% non-Hispanic white) without a diagnosis of diabetes by age 40. Interventions We imputed BMI and WC trajectories from age 18 for every participant and estimated time-weighted average exposures to BMI or WC during young adulthood and later life. Main Outcome Measure(s) Incident diabetes defined as fasting glucose ≥126 mg/dL, nonfasting glucose ≥200 mg/dL, or use of diabetes medications. Results During a 9-year median follow-up, 4323 participants developed incident diabetes. Young adult BMI and WC were associated with later-life incident diabetes after controlling for later-life exposures [hazard ratios (HR) 1.99 for BMI ≥ 30 kg/m2 and 2.13 for WC > 88cm (women)/>102cm (men) compared to normal ranges]. Young adult homeostatic model of insulin resistance mediated 49% and 44% of the association between BMI and WC with later-life incident diabetes. High-density lipoproteins and triglycerides mediated a smaller proportion of these associations. Conclusions Elevated BMI and WC during young adulthood were independently associated with later-life incident diabetes. Insulin resistance may be a key mediator.

Highlights • Patients strongly wanted to pursue alternative treatments before starting a statin. • Attitudes about taking statins based on risk differ from scientific recommendations. • 52% of patients did not tell their prescriber that they might not take the statin. • The existing literature likely underestimates rates of primary nonadherence., Statin medications reduce cardiovascular events, but many patients never start taking their prescribed statin (primary nonadherence). Limited knowledge exists about the attitudes and beliefs of those with primary nonadherence. In this study, patients with primary nonadherence to statin medications (n = 173) completed a self-administered cross-sectional survey that assessed their attitudes and beliefs related to primary nonadherence and to potential motivators for statin use. Patients were recruited in 2019 from two academic health systems and nationwide internet advertisements. Only 49 of 173 (28.3%) patients with primary nonadherence reported having cardiovascular disease (CVD). Ninety-nine patients (57.2%) never filled their prescription, and 74 (42.8%) filled but never took any statin. Over half failed to initially inform their prescriber they might not take the statin. Patients strongly or somewhat agreed that they desired alternate treatment plans such as diet and/or exercise (n = 134; 77.4%) or natural remedies/dietary supplements (n = 125; 72.3%). Ninety-eight (56.6%) stronglyor somewhat worried about the possibility of statin dependence or addiction. Twenty-seven (15.6%) patients noted that they would not take a statin based solely on CVD risk estimates; 50 (28.9%) selected a CVD risk threshold of >20%; and 23 (13.3%) a threshold of >50% as motivating factors to take statins. Patients with primary nonadherence have attitudes about taking statins based on CVD risk that differ from scientific recommendations, may not tell providers about their hesitation to take statins, and likely prefer alternative initial approaches to cholesterol lowering. Early shared decision-making and assessment of patient attitudes about statins could potentially better align initial approaches for CVD risk reduction.

BackgroundIn the absence of universal testing, effective therapies, or vaccines, identifying risk factors for viral infection, particularly readily modifiable exposures and behaviors, is required to identify effective strategies against viral infection and transmission.MethodsWe conducted a world-wide mobile application-based prospective cohort study available to English speaking adults with a smartphone. We collected self-reported characteristics, exposures, and behaviors, as well as smartphone-based geolocation data. Our main outcome was incident symptoms of viral infection, defined as fevers and chills plus one other symptom previously shown to occur with SARS-CoV-2 infection, determined by daily surveys.FindingsAmong 14, 335 participants residing in all 50 US states and 93 different countries followed for a median 21 days (IQR 10-26 days), 424 (3%) developed incident viral symptoms. In pooled multivariable logistic regression models, female biological sex (odds ration [OR] 1.75, 95% CI 1.39-2.20, pInterpretationWhile several immutable characteristics were associated with the risk of developing viral symptoms, multiple immediately modifiable exposures and habits that influence risk were also observed, potentially identifying readily accessible strategies to mitigate risk in the Covid-19 era.FundingThis study was funded by IU2CEB021881-01 and 3U2CEB021881-05S1 from the NIH/ NIBIB to Drs. Marcus, Olgin, and Pletcher.Research in contextEvidence before this studyPredictors of incident viral infection have been determined largely from cross-sectional studies prone to recall bias among individuals representing geographically constrained regions, and most were conducted before the era of the current Covid-19 pandemic.Added value of this studyWe conducted a world-wide, mobile application-based, longitudinal cohort study utilizing time-updated predictors and outcomes, providing novel and current information regarding risk-factors for incident viral symptoms based on real-time information in the era of Covid-19.Implications of all the available evidenceThese data suggest that certain immutable characteristics influence the risk for incident viral symptoms, while smoking cessation, physical distancing to avoid contact with individuals outside the household, regular exercise, and sanitizing one’s phone may each help mitigate the risk of viral infection.

Author(s): Tison, Geoffrey H; Avram, Robert; Kuhar, Peter; Abreau, Sean; Marcus, Greg M; Pletcher, Mark J; Olgin, Jeffrey E

Background Long-term cardiovascular health effects of marijuana are understudied. Future cardiovascular disease is often indicated by subclinical atherosclerosis for which carotid intima-media thickness is an established parameter. Methods Using the data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort of 5115 Black and white women and men at Year 20 visit, we studied the association between carotid intima-media thickness in midlife and lifetime exposure to marijuana (1 marijuana year = 365 days of use) and tobacco smoking (1 pack-year = 20 cigarettes/day for 365 days). We measured carotid intima-media thickness by ultrasound and defined high carotid intima-media thickness at the threshold of the 75th percentile of all examined participants. We fit logistic regression models stratified by tobacco smoking exposure, adjusting for demographics, cardiovascular risk factors, and other drug exposures. Results Data was complete for 3257 participants; 2722 (84%) reported ever marijuana use; 374 (11%) were current users; 1539 (47%) reported ever tobacco smoking; 610 (19%) were current smokers. Multivariable adjusted models showed no association between cumulative marijuana exposure and high carotid intima-media thickness in never or ever tobacco smokers, odds ratio (OR) 0.87 (95% confidence interval [CI]: 0.63-1.21) at 1 marijuana-year among never smokers and OR 1.11 (95% CI: 0.85-1.45) among ever tobacco smokers. Cumulative exposure to tobacco was strongly associated with high carotid intima-media thickness, OR 1.88 (95%CI: 1.20-2.94) for 20 pack-years of exposure. Conclusions This study adds to the growing body of evidence that there might be no association between the average population level of marijuana use and subclinical atherosclerosis.

Electronic health record (EHR) systems can be configured to deliver novel EHR interventions that influence clinical decision making and to support efficient randomized controlled trials (RCTs) designed to evaluate the effectiveness, safety, and costs of those interventions. In designing RCTs of EHR interventions, one should carefully consider the unit of randomization (for example, patient, encounter, clinician, or clinical unit), balancing concerns about contamination of an intervention across randomization units within clusters (for example, patients within clinical units) against the superior control of measured and unmeasured confounders that comes with randomizing a larger number of units. One should also consider whether the key computational assessment components of the EHR intervention, such as a predictive algorithm used to target a subgroup for decision support, should occur before randomization (so that only 1 subgroup is randomized) or after randomization (including all subgroups). When these components are applied after randomization, one must consider expected heterogeneity in the effect of the differential decision support across subgroups, which has implications for overall impact potential, analytic approach, and sample size planning. Trials of EHR interventions should be reviewed by an institutional review board, but may not require patient-level informed consent when the interventions being tested can be considered minimal risk or quality improvement, and when clinical decision making is supported, rather than controlled, by an EHR intervention. Data and safety monitoring for RCTs of EHR interventions should be conducted to guide institutional pragmatic decision making about implementation and ensure that continuing randomization remains justified. Reporting should follow the CONSORT (Consolidated Standards of Reporting Trials) Statement, with extensions for pragmatic trials and cluster RCTs when applicable, and should include detailed materials to enhance reproducibility.

Background Regular physical activity is an important determinant of cardiovascular health and quality of life. Previous investigations examining the association between exercise and atrial fibrillation (AF) have been limited by self-reported, retrospectively collected activity data. Objective The purpose of this study was to objectively quantify differences in daily physical activity among individuals with and those without AF using electronic wearable activity trackers. Methods Daily exercise data were directly obtained from wrist-worn activity trackers (Fitbit, San Francisco, CA) among participants in the Health eHeart (HeH) study. Average daily step count was compared between individuals with and those without AF both before and after adjusting for comorbidities. AF severity was quantified using the Atrial Fibrillation Effect on QualiTy of Life (AFEQT) survey. Results Among 171,284 HeH study participants, 3333 individuals (234 with AF [7%]) submitted activity data. In unadjusted analysis, AF participants ambulated an average of 723 fewer steps per day (95% confidence interval [CI] 292–1154; P = .001) compared to individuals without AF. After adjustment for demographics and comorbid diseases, participants with AF demonstrated 591 fewer steps per day (95% CI 149–1033; P = .009). Among AF patients, AF severity was associated with less physical activity. For each single point decrease in AFEQT score (corresponding to more symptomatic AF), physical activity decreased by a mean 24 steps per day (95% CI 1–46; P = .04). Conclusion Objective, automatically collected step count data demonstrate that individuals with AF engage in significantly less average daily physical activity. In addition, worsening AF symptom severity is associated with reduced daily exercise.

Importance Determining blood pressure (BP) patterns in young adulthood that are associated with cardiovascular disease (CVD) events in later life may help to identify young adults who have an increased risk for CVD. Objective To determine whether the long-term variability of BP across clinical visits and the rate of change in BP from young adulthood to midlife are associated with CVD and all-cause mortality by middle age, independently of mean BP during young adulthood and a single BP in midlife. Design, Setting, and Participants This prospective cohort study included a community-based sample of 3394 African American and white participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, enrolled from March 1985 through June 1986. Patterns of systolic BP (SBP) were evaluated with measurements at year 0 (baseline) and 2, 5, 7, and 10 years after baseline. Visit-to-visit SBP variability was estimated as BP variability independent of the mean (VIM). Data were collected from March 1985 through August 2015 and analyzed from June through October 2019. Main Outcomes and Measures Cardiovascular disease and all-cause mortality experienced through August 2015 were adjudicated. The associations of each SBP pattern with CVD events and all-cause mortality were determined using Cox proportional hazards regression models. Results At year 10, the mean (SD) age of the 3394 participants was 35.1 (3.6) years; 1557 (45.9%) were African American; 1892 (55.7%) were women; and 103 (3.0%) were taking antihypertensive medication. During a median follow-up of 20.0 (interquartile range, 19.4-20.2) years, 162 CVD events and 181 deaths occurred. When all BP pattern measurements were entered into the same model including a single SBP measurement at the year 10 examination, the hazard ratios for CVD events for each 1-SD increase in SBP measures were 1.25 (95% CI, 0.90-1.74) for mean SBP, 1.23 (95% CI, 1.07-1.43) for VIM SBP, and 0.99 (95% CI, 0.81-1.26) for annual change of SBP. The VIM for SBP was the only BP pattern associated with all-cause mortality (hazard ratio, 1.24; 95% CI, 1.09-1.41). Conclusions and Relevance The results of this study suggest that the assessment of visit-to-visit SBP variability may help identify young adults at increased risk for CVD and all-cause mortality later in life.

IMPORTANCE: Atrial fibrillation (AF) is the most common arrhythmia. Although patients have reported that various exposures determine when and if an AF event will occur, a prospective evaluation of patient-selected triggers has not been conducted, and the utility of characterizing presumed AF-related triggers for individual patients remains unknown. OBJECTIVE: To test the hypothesis that n-of-1 trials of self-selected AF triggers would enhance AF-related quality of life. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial lasting a minimum of 10 weeks tested a smartphone mobile application used by symptomatic patients with paroxysmal AF who owned a smartphone and were interested in testing a presumed AF trigger. Participants were screened between December 22, 2018, and March 29, 2020. INTERVENTIONS: n-of-1 Participants received instructions to expose or avoid self-selected triggers in random 1-week blocks for 6 weeks, and the probability their trigger influenced AF risk was then communicated. Controls monitored their AF over the same time period. MAIN OUTCOMES AND MEASURES: AF was assessed daily by self-report and using a smartphone-based electrocardiogram recording device. The primary outcome comparing n-of-1 and control groups was the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) score at 10 weeks. All participants could subsequently opt for additional trigger testing. RESULTS: Of 446 participants who initiated (mean [SD] age, 58 [14] years; 289 men [58%]; 461 White [92%]), 320 (72%) completed all study activities. Self-selected triggers included caffeine (n = 53), alcohol (n = 43), reduced sleep (n = 31), exercise (n = 30), lying on left side (n = 17), dehydration (n = 10), large meals (n = 7), cold food or drink (n = 5), specific diets (n = 6), and other customized triggers (n = 4). No significant differences in AFEQT scores were observed between the n-of-1 vs AF monitoring-only groups. In the 4-week postintervention follow-up period, significantly fewer daily AF episodes were reported after trigger testing compared with controls over the same time period (adjusted relative risk, 0.60; 95% CI, 0.43- 0.83; P

Despite the high rate of sudden death after myocardial infarction among patients with a low ejection fraction, implantable cardioverter-defibrillators are contraindicated until 40 to 90 days after myocardial infarction. Whether a wearable cardioverter-defibrillator would reduce the incidence of sudden death during this high-risk period is unclear.We randomly assigned (in a 2:1 ratio) patients with acute myocardial infarction and an ejection fraction of 35% or less to receive a wearable cardioverter-defibrillator plus guideline-directed therapy (the device group) or to receive only guideline-directed therapy (the control group). The primary outcome was the composite of sudden death or death from ventricular tachyarrhythmia at 90 days (arrhythmic death). Secondary outcomes included death from any cause and nonarrhythmic death.Of 2302 participants, 1524 were randomly assigned to the device group and 778 to the control group. Participants in the device group wore the device for a median of 18.0 hours per day (interquartile range, 3.8 to 22.7). Arrhythmic death occurred in 1.6% of the participants in the device group and in 2.4% of those in the control group (relative risk, 0.67; 95% confidence interval [CI], 0.37 to 1.21; P=0.18). Death from any cause occurred in 3.1% of the participants in the device group and in 4.9% of those in the control group (relative risk, 0.64; 95% CI, 0.43 to 0.98; uncorrected P=0.04), and nonarrhythmic death in 1.4% and 2.2%, respectively (relative risk, 0.63; 95% CI, 0.33 to 1.19; uncorrected P=0.15). Of the 48 participants in the device group who died, 12 were wearing the device at the time of death. A total of 20 participants in the device group (1.3%) received an appropriate shock, and 9 (0.6%) received an inappropriate shock.Among patients with a recent myocardial infarction and an ejection fraction of 35% or less, the wearable cardioverter-defibrillator did not lead to a significantly lower rate of the primary outcome of arrhythmic death than control. (Funded by the National Institutes of Health and Zoll Medical; VEST ClinicalTrials.gov number, NCT01446965 .).

Cardiac devices are increasingly an element of treatment for the elderly, leading to more frequent transvenous lead removal (TLR) procedures in this population. Data on TLR in very elderly patients, especially nonagenarians, is scarce. We used Healthcare Cost and Utilization Project Nationwide Inpatient Sample to identify a total of 36,099 patients ≥70 years who underwent TLR from 2005 to 2012, with outcomes including in-hospital mortality and complications. The in-hospital mortality rate was significantly higher in nonagenarians without device infection (0.9% in age 70 to 79 vs 0.7% in age 80 to 89 vs 2.6% in age ≥90, p = 0.012), but overall complication rates were not different in age groups regardless of infection status and co-morbidity index (all p >0.05). Among patients with device infection, octogenarians, and nonagenarians were not associated with increased risk of in-hospital mortality relative to septuagenarians after controlling for all other confounders. However, in patients without device infection, logistic regression showed significantly higher mortality in patients age ≥90 years (odd ratio 4.22, 95% confidence interval 1.66 to 10.75, p = 0.003), but not in patients age 80 to 89 years (odd ratio 1.05, 95% confidence interval 0.48 to 2.30, p = 0.907), compared with patients age 70 to 79 years. In conclusion, in nonagenarians with infection, mortality is driven more by the patient's other conditions than by age. For patients without infection, however, nonagenarians experienced higher mortality than younger patients.

The relationship between sleep disruption, independent of obstructive sleep apnea (OSA), and atrial fibrillation (AF) is unknown.The purpose of this study was to determine whether poor sleep itself is a risk factor for AF.We first performed an analysis of participants in the Health eHeart Study and validated those findings in the longitudinal Cardiovascular Health Study, including a subset of patients undergoing polysomnography. To determine whether the observed relationships readily translated to medical practice, we examined 2005-2009 data from the California Healthcare Cost and Utilization Project.Among 4553 Health eHeart participants, the 526 with AF exhibited more frequent nighttime awakening (odd ratio [OR] 1.47; 95% confidence interval [CI] 1.14-1.89; P = .003). In 5703 Cardiovascular Health Study participants followed for a median 11.6 years, frequent nighttime awakening predicted a 33% greater risk of AF (hazard ratio [HR] 1.33; 95% CI 1.17-1.51; P.001). In patients with polysomnography (N = 1127), every standard deviation percentage decrease in rapid eye movement (REM) sleep was associated with a 18% higher risk of developing AF (HR 1.18; 95% CI 1.00-1.38; P = .047). Among 14,330,651 California residents followed for a median 3.9 years, an insomnia diagnosis predicted a 36% increased risk of new AF (HR 1.36; 95% CI 1.30-1.42; P.001).Sleep disruption consistently predicted AF before and after adjustment for OSA and other potential confounders across several different populations. Sleep quality itself may be important in the pathogenesis of AF, potentially representing a novel target for prevention.

OBJECTIVE Individuals with type 1 diabetes have experienced an increase in life expectancy, yet it is unknown what level of glycemic control is ideal for maintaining late-life brain health. We investigated the association of long-term glycemic control with dementia in older individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS We followed 3,433 members of a health care system with type 1 diabetes, aged ≥50 years, from 1996 to 2015. Repeated measurements of hemoglobin A1c (HbA1c), dementia diagnoses, and comorbidities were ascertained from health records. Cox proportional hazards models were fit to evaluate the association of time-varying glycemic exposure with dementia, with adjustment for age, sex, race/ethnicity, baseline health conditions, and frequency of HbA1c measurement. RESULTS Over a mean follow-up of 6.3 years, 155 individuals (4.5%) were diagnosed with dementia. Patients with ≥50% of HbA1c measurements at 8–8.9% (64–74 mmol/mol) and ≥9% (≥75 mmol/mol) had 65% and 79% higher risk of dementia, respectively, compared with those with CONCLUSIONS Among older patients with type 1 diabetes, those with majority exposure to HbA1c 8–8.9% and ≥9% had increased dementia risk, while those with majority exposure to HbA1c 6–6.9% and 7–7.9% had reduced risk. Currently recommended glycemic targets for older patients with type 1 diabetes are consistent with healthy brain aging.

BACKGROUND AND AIMS Unlike tobacco, the effect of marijuana smoke on subclinical atherosclerosis, a surrogate measure for cardiovascular disease, is not known. This study aimed to determine the association between lifetime exposure to marijuana and measures of subclinical atherosclerosis in mid-life. DESIGN, SETTING AND PARTICIPANTS We used data from the US-based Coronary Artery Risk Development in Young Adults (CARDIA) Study, a cohort of black and white men and women aged 18-30 years at baseline in 1985-86, with up to 7 follow-up exams over 25 years. The number of CARDIA participants included in this study was 3,498. MEASUREMENTS Cumulative years of exposure to marijuana (expressed in 'marijuana-years', with 1 marijuana-year equivalent to 365 days of use) using repeated assessments every 2-5 years, over 25 years. Abdominal artery calcium (AAC) and coronary artery calcium (CAC) scores measured by computed tomography at Year 25 exam. RESULTS Among 3,117 participants with AAC and CAC measurements, 2,627 (84%) reported past marijuana use and 1,536 (49%) past daily tobacco smoking. Compared with tobacco smokers, of which 46% reported 10 or more pack-years of use, only 12% of marijuana users reported 5 or more marijuana-years of use and only 6% reported having used marijuana daily. We found a significant interaction between never- and ever- tobacco users on the association between cumulative marijuana use and AAC (p=0.05). Among those who never smoked tobacco, cumulative marijuana-years were not associated with AAC or CAC in models adjusted for demographics, cardiovascular risk factors, licit and illicit drug exposure and depression symptoms. However, among ever tobacco smokers, marijuana exposure was associated with AAC and CAC. At 5 marijuana-years of exposure, using AAC=0 and CAC=0 as a reference group, the odds ratio (OR) was 1.97 (95%CI:1.21-3.21,p=0.007) for AAC>0/CAC=0 and 1.83 (95%CI:1.02-3.31,p=0.04) for CAC>0, regardless of AAC. Tobacco smoking was strongly associated with both AAC and CAC. CONCLUSION Marijuana use appears to be associated with subclinical atherosclerosis, but only among ever tobacco users.

Background & Aims In patients with chronic liver disease (CLD) with or without cirrhosis, existing studies on the outcomes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have limited generalizability. We used the National COVID Cohort Collaborative (N3C), a harmonized electronic health record dataset of 6.4 million, to describe SARS-CoV-2 outcomes in patients with CLD and cirrhosis. Methods We identified all patients with CLD with or without cirrhosis who had SARS-CoV-2 testing in the N3C Data Enclave as of July 1, 2021. We used survival analyses to associate SARS-CoV-2 infection, presence of cirrhosis, and clinical factors with the primary outcome of 30-day mortality. Results We isolated 220,727 patients with CLD and SARS-CoV-2 test status: 128,864 (58%) were noncirrhosis/negative, 29,446 (13%) were noncirrhosis/positive, 53,476 (24%) were cirrhosis/negative, and 8941 (4%) were cirrhosis/positive patients. Thirty-day all-cause mortality rates were 3.9% in cirrhosis/negative and 8.9% in cirrhosis/positive patients. Compared to cirrhosis/negative patients, cirrhosis/positive patients had 2.38 times adjusted hazard of death at 30 days. Compared to noncirrhosis/positive patients, cirrhosis/positive patients had 3.31 times adjusted hazard of death at 30 days. In stratified analyses among patients with cirrhosis with increased age, obesity, and comorbid conditions (ie, diabetes, heart failure, and pulmonary disease), SARS-CoV-2 infection was associated with increased adjusted hazard of death. Conclusions In this study of approximately 221,000 nationally representative, diverse, and sex-balanced patients with CLD; we found SARS-CoV-2 infection in patients with cirrhosis was associated with 2.38 times mortality hazard, and the presence of cirrhosis among patients with CLD infected with SARS-CoV-2 was associated with 3.31 times mortality hazard. These results provide an additional impetus for increasing vaccination uptake and further research regarding immune responses to vaccines in patients with severe liver disease.

The aims of this study are to assess the relationships of visit-to-visit blood pressure (BP) variability in young adulthood to hippocampal volume and integrity at middle age. We used data over 8 examinations spanning 25 years collected in the CARDIA study (Coronary Artery Risk Development in Young Adults) of black and white adults (age, 18–30 years) started in 1985 to 1986. Visit-to-visit BP variability was defined as by SD BP and average real variability (ARV BP , defined as the absolute differences of BP between successive BP measurements). Hippocampal tissue volume standardized by intracranial volume (%) and integrity assessed by fractional anisotropy were measured by 3-Tesla magnetic resonance imaging at the year-25 examination (n=545; mean age, 51 years; 54% women and 34% African Americans). Mean systolic BP (SBP)/diastolic BP levels were 110/69 mm Hg at year 0 (baseline), 117/73 mm Hg at year 25, and ARV SBP and SD SBP were 7.7 and 7.9 mm Hg, respectively. In multivariable-adjusted linear models, higher ARV SBP was associated with lower hippocampal volume (unstandardized regression coefficient [standard error] with 1-SD higher ARV SBP : −0.006 [0.003]), and higher SD SBP with lower hippocampal fractional anisotropy (−0.02 [0.01]; all P SBP or SD SBP with hippocampal volume or integrity. In conclusion, visit-to-visit BP variability during young adulthood may be useful in assessing the potential risk for reductions in hippocampal volume and integrity in midlife.

Background: Vest Prevention of Early Sudden Death Trial did not demonstrate a significant reduction in arrhythmic death with the wearable cardioverter‐defibrillator (WCD), but compliance with the device may have substantially affected the results. ThePletcher influence of WCD compliance on outcomes has not yet been fully evaluated. Methods: Using linear and pooled logistic models, we performed as‐treated analyses omitting person‐time in the hospital and adjusted for correlates of WCD compliance. To assess the impact of early stopping of WCD, we performed a per‐protocol Kaplan‐Meier analysis, censoring after the last day the WCD was worn. Interactions of potential effect modifiers with treatment assignment and WCD compliance on outcomes were investigated. Finally, we used linear models to identify predictors of WCD compliance. Results: A per‐protocol analysis demonstrated a significant reduction in total (P

Aims To evaluate the prevalence of electrocardiogram (ECG) abnormalities in marijuana users as an indirect measure of subclinical cardiovascular disease (CVD). Design Longitudinal and cross-sectional secondary data analysis from the CARDIA (Coronary Artery Risk Development in Young Adults) study. Setting Four communities in the United States. Participants A total of 2585 participants from the 5115 black and white men and women recruited at age 18-30 years in 1985 to 1986 in CARDIA. Measurements ECG abnormalities coded as minor and major abnormalities with the Minnesota code of electrocardiographic findings at year 20. Self-reported current (past 30 days) and computed cumulative life-time marijuana use (one 'marijuana-year' corresponds to 365 days of use) through assessments every 2-5 years. We fitted logistic regression models adjusting for sex, race, center, education, age, tobacco smoking, physical activity, alcohol use and body mass index. Findings Among the 2585 participants with an ECG at year 20, mean age was 46, 57% were women, 45% were black; 83% had past exposure to marijuana and 11% were using marijuana currently. One hundred and seventy-three participants (7%) had major abnormalities and 944 (37%) had minor abnormalities. Comparing current with never use in multivariable-adjusted models, the odds ratio (OR) for major ECG abnormalities was 0.60 [95% confidence interval (CI) = 0.32-1.15] and for minor ECG abnormalities 1.21 (95% CI = 0.87-1.68). Results did not change after stratifying by sex and race. Cumulative marijuana use was not associated with ECG abnormalities. Conclusion In a middle-aged US population, life-time cumulative and occasional current marijuana use were not associated with increases in electrocardiogram abnormalities. This adds to the growing body of evidence that occasional marijuana use and cardiovascular disease events and markers of subclinical atherosclerosis are not associated.

Background: New technology and healthcare delivery approaches may help improve blood pressure (BP) control. Randomized controlled trials (RCTs) can demonstrate effectiveness of these emerging approaches, both overall and especially within underserved populations, but RCTs are expensive. Our objective is to establish a national platform to support BP control surveillance and efficient RCTs. Methods: The PCORnet BP Control Laboratory, designed and launched in partnership with the American Heart Association (AHA) and the American Medical Association (AMA), leverages electronic health record (EHR) systems throughout the US, the National Patient-Centered Outcomes Research Network (PCORnet), and the NIH-funded Eureka Research Platform, which enables direct-to-participant research including collection of patient-reported outcomes and mHealth data from wearable devices and smartphones. We will use these resources to 1) Conduct national surveillance through quarterly EHR data queries to calculate and track institution- and clinic-level BP control metrics across 23 PCORnet institutions, overall and within key subgroups, and support participation in the AHA/AMA’s Target:BP recognition program (BP Track); 2) Compare effectiveness of a Full Support versus Self-Guided version of the AMA’s Measure Accurately, Act Rapidly, and Partner with Patients (MAP) program at improving BP control in a cluster randomized trial of 24 safety net clinics (BP MAP); and 3) Compare effectiveness of Smartphone-linked versus standard home BP monitoring at reducing systolic BP in an individual-level, direct-to-participant RCT of 2000 patients with uncontrolled BP (BP Home). Results: Preliminary BP Track queries demonstrate an overall BP control rate of 56%, lower control in Black patients (51%), substantial heterogeneity in clinic-level metrics (e.g., 33% vs. 64% BP control), and low rates of medication intensification (9% prescribed a new medication class when BP was high). BP Track will launch PCORnet-wide queries in June; BP MAP in May; and BP Home in August 2019. Conclusions: Feasibility testing is underway to determine if the PCORnet BP Control Laboratory will be useful for investigators interested in conducting efficient RCTs of BP control interventions.

IMPORTANCE: American College of Cardiology/American Heart Association cholesterol guidelines prioritize primary prevention statin therapy based on 10-year absolute risk (AR(10)) of atherosclerotic cardiovascular disease (ASCVD). However, given the same AR(10), patients with higher levels of low-density lipoprotein cholesterol (LDL-C) experience greater absolute risk reduction from statin therapy. OBJECTIVES: To estimate the cost-effectiveness of expanding preventive statin treatment eligibility from standard care to patients at borderline risk (AR(10), 5.0%-7.4%) for ASCVD and with high levels of LDL-C and to estimate cost-effectiveness of statin treatment across ranges of age, sex, AR(10), and LDL-C levels. DESIGN, SETTING, AND PARTICIPANTS: This study evaluated 100 simulated cohorts, each including 1 million ASCVD-free survey respondents (50% men and 50% women) aged 40 years at baseline. Cohorts were created by probabilistic sampling of the 1999-2014 US National Health and Nutrition Examination Surveys from the perspective of the US health care sector. The CVD Policy Model microsimulation version projected lifetime health and cost outcomes. Probability of first-ever coronary heart disease or stroke event was estimated by analysis of 6 pooled US cohort studies and recalibrated to match contemporary event rates. Other model variables were derived from national surveys, meta-analyses, and published literature. Data were analyzed from May 15, 2018, through June 10, 2019. EXPOSURES: Four statin treatment strategies were compared: (1) treat all patients with AR(10) of at least 7.5%, diabetes, or LDL-C of at least 190 mg/dL (standard care); (2) add treatment for borderline risk and LDL-C levels of 160 to 189 mg/dL; (3) add treatment for borderline risk and LDL-C levels of 130 to 159 mg/dL; and (4) add treatment for remainder of patients with AR(10) of at least 5.0%. Statin treatment was also compared with no statin treatment in age, sex, AR(10), and LDL-C strata. MAIN OUTCOMES AND MEASURES: Lifetime quality-adjusted life-years (QALYs) and costs (2019 US dollars) were projected and discounted 3.0% annually. The primary outcome was the incremental cost-effectiveness ratio. RESULTS: In these 100 simulated cohorts, each with 1 million patients aged 40 years at baseline (50% women and 50% men), adding preventive statins to individuals with borderline AR(10) and LDL-C levels of 160 to 189 mg/dL would be cost-saving; further treating borderline AR(10) and LDL-C levels of 130 to 159 mg/dL would also be cost-saving; and treating all individuals with AR(10) of at least 5.0% would be highly cost-effective ($33 558/QALY) and would prevent the most ASCVD events. Within age, AR(10), and sex categories, individuals with higher baseline LDL-C levels gained more QALYs from statin therapy. Cost-effectiveness increased with LDL-C level and AR(10). CONCLUSIONS AND RELEVANCE: In this study, lifetime statin treatment of patients in a hypothetical cohort with borderline ASCVD risk and LDL-C levels of 160 to 189 mg/dL was found to be cost-saving. Results suggest that treating all patients at borderline risk regardless of LDL-C level would likely be highly cost-effective.

BACKGROUND: Family history has been shown to be associated with increased risk of atrial fibrillation (AF). However, the specific AF characteristics that travel with a family history have not yet been elucidated. The purpose of this study was to determine whether a family history of AF is associated with specific patient characteristics in a worldwide, remote cohort. METHODS: From the Health eHeart Study, an internet-based prospective cohort, we performed a cross-sectional analysis of AF participants who reported their family history and completed questionnaires regarding their medical conditions and AF symptoms. We assessed demographics, cardiovascular comorbidities, and AF symptom characteristics in AF participants with and without a family history of AF. RESULTS: In multivariable analysis of 5,884 participants with AF (mean age 59.9 ± 14.5, 59% male, 92% white), female sex (odds ratio [OR]=1.35, 95% CI, 1.17-1.54, p

Background Persistent severe left ventricular (LV) systolic dysfunction after myocardial infarction (MI) is associated with increased mortality and is a class I indication for implantation of a cardioverter-defibrillator. Objectives This study developed models and assessed independent predictors of LV recovery to >35% and ≥50% after 90-day follow-up in patients presenting with acute MI and severe LV dysfunction. Methods Our multicenter prospective observational study enrolled participants with ejection fraction (EF) of ≤35% at the time of MI (n = 231). Predictors for EF recovery to >35% and ≥50% were identified after multivariate modeling and validated in a separate cohort (n = 236). Results In the PREDICTS (PREDiction of ICd Treatment Study) study, 43% of patients had persistent EF ≤35%, 31% had an EF of 36% to 49%, and 26% had an EF ≥50%. The model that best predicted recovery of EF to >35% included EF at presentation, length of stay, prior MI, lateral wall motion abnormality at presentation, and peak troponin. The model that best predicted recovery of EF to ≥50% included EF at presentation, peak troponin, prior MI, and presentation with ventricular fibrillation or cardiac arrest. After predictors were transformed into point scores, the lowest point scores predicted a 9% and 4% probability of EF recovery to >35% and ≥50%, respectively, whereas profiles with the highest point scores predicted an 87% and 49% probability of EF recovery to >35% and ≥50%, respectively. Conclusions In patients with severe systolic dysfunction following acute MI with an EF ≤35%, 57% had EF recovery to >35%. A model using clinical variables present at the time of MI can help predict EF recovery.

Introduction: Prehypertension defined as blood pressure (BP) 120-139/80-89 mmHg, has a prevalence of 23% in U.S. young adults (age 20-39 years). Young adult high diastolic blood pressure (DBP) has been associated with later life coronary heart disease (CHD), but it is unclear if lifelong benefits of early blood pressure control outweigh costs and side-effect risks. Objective: We estimated CHD events and life-long cost-effectiveness of U.S. Preventive Service Task Force recommended lifestyle modification (LM) or pharmacotherapy in young adults with DBP ≥80mmHg, incremental to later life hypertension treatment. Methods: A microsimulation model simulated CHD events from age 20 until death for 20-year olds selected from 1999-2014 NHANES. Individual risk factor trajectories were assigned, and risk functions predicted CHD based on Framingham Offspring Study data, accounting for both age 20-39 time-weighted average DBP and later life systolic blood pressure (SBP). Simulated interventions lowered DBP ≥80mmHg for age 20-39 years, and SBP ≥140mmHg for age ≥40 years. Cost-effectiveness was measured as incremental cost-effectiveness ratios (ICERs) and net health benefit (NHB) at willingness to pay (WTP) threshold $50,000/quality adjusted life year (QALY). Results: In 40,000 young adults with DBP ≥80 mmHg (50% women), pharmacologic BP control in young adulthood and later life prevented the most CHD events (Table). The strategy that yielded highest NHB in women was pharmacologic control after age 40 (ICER $26,536/QALY). In men, lifestyle modification to control DBP in young adulthood plus pharmacotherapy for later life hypertension (ICER $42,481/QALY) yielded highest NHB. Conclusion: Early DBP control in young adults could achieve substantial health benefits over the life course but standard interventions to achieve this goal are costly. Innovative strategies to reduce pharmacotherapy costs and improve sustainability of lifestyle modification could make early BP control a higher-value prevention strategy in young adults.

E-cigarettes are promoted as healthier alternatives to conventional cigarettes. Many cigarette smokers use both products. It is unknown whether the additional use of e-cigarettes among cigarette smokers (dual users) is associated with reduced exposure to tobacco-related health risks. Cross-sectional analysis was performed using baseline data from the Health eHeart Study, among English-speaking adults, mostly from the United States. Cigarette use (# cigarettes/day) and/or e-cigarette use (# days, # cartridges, and # puffs) were compared between cigarette only users vs. dual users. Additionally, we examined cardiopulmonary symptoms/ conditions across product use: no product (neither), e-cigarettes only, cigarettes only, and dual use. Among 39,747 participants, 573 (1.4%) reported e-cigarette only use, 1,693 (4.3%) reported cigarette only use, and 514 (1.3%) dual use. Dual users, compared to cigarette only users, reported a greater median (IQR) number of cigarettes per day, 10.0 (4.0-20.0) vs. 9.0 (3.0-15.0) (p < .0001), a lower (worse) median (IQR) SF-12 general health score, 3.3 (2.8-3.8) vs. 3.5 (2.8-3.9) (p = .0014), and a higher (worse) median (IQR) breathing difficulty score in the past month, 2.0 (1.0-2.0) vs. 1.0 (1.0-2.0) (p = .001). Of the 19 cardiopulmonary symptoms/ conditions, having a history of arrhythmia was significantly different between cigarette only users (14.2%) and dual users (17.8%) (p = .02). In this sample, dual use was not associated with reduced exposure to either (i) cigarettes, compared to cigarette only users or (ii) e-cigarettes, compared to e-cigarette only users. E-cigarette only use, compared to no product use, was associated with lower general health scores, higher breathing difficulty scores (typically and past month), and greater proportions of those who responded 'yes' to having chest pain, palpitations, coronary heart disease, arrhythmia, COPD, and asthma. These data suggest the added use of e-cigarettes alone may have contributed to cardiopulmonary health risks particularly respiratory health risks.

Aims/hypothesisThe impact of marijuana use on metabolic health is largely unknown. This study sought to clarify the cross-sectional and longitudinal associations between self-reported marijuana use, and prediabetes (defined as fasting glucose 5.6-6.9 mmol/l, 2 h glucose post OGTT 7.8-11.0 mmol/l or HbA1c 5.7-6.4% [39-47 mmol/mol]) and diabetes.MethodsData from the community-based Coronary Artery Risk Development in Young Adults (CARDIA) study were used to determine marijuana use and the presence of prediabetes and diabetes among participants. The association between marijuana use and the prevalence of prediabetes and diabetes was examined in 3,034 participants at CARDIA examination year 25 (2010-2011), while the incidence of prediabetes and diabetes according to previous marijuana use was assessed in 3,151 individuals who were free from prediabetes/diabetes at year 7 (1992-1993) and who returned for at least one of the four subsequent follow-up examinations over 18 years.ResultsThe percentage of individuals who self-reported current use of marijuana declined over the course of the study's follow-up. After multivariable adjustment, higher odds of prediabetes were found for individuals who reported current use of marijuana (OR 1.65 [95% CI 1.15, 2.38]) and a lifetime use of 100 times or more (OR 1.49 [95% CI 1.06, 2.11]), compared with individuals who reported never using marijuana. There was no association between marijuana use and diabetes at CARDIA examination year 25. Over 18 years of follow-up, a greater risk of prediabetes (but not diabetes) was found for individuals who reported a lifetime use of marijuana of 100 times or more (HR 1.39 [95% CI 1.13, 1.71]), compared with individuals who had never used marijuana.Conclusions/interpretationMarijuana use in young adulthood is associated with an increased risk of prediabetes by middle adulthood, but not with the development of diabetes by this age.

Despite the equipoise regarding alcohol’s cardiovascular effects and absence of relevant rigorous controlled trials, the lay press frequently portrays alcohol as “heart healthy.” The public perception of alcohol’s heart effects, the sources of those perceptions, and how they may affect behavior are unknown. We performed a cross-sectional analysis of data obtained between March, 2013 and September, 2014 from consecutive participants enrolled in the Health eHeart Study. Of 5,582 participants, 1,707 (30%) viewed alcohol as heart healthy, 2,157 (39%) viewed it as unhealthy, and 1,718 (31%) were unsure. Of those reporting alcohol as heart healthy, 80% cited lay press as a source of their knowledge. After adjustment, older age (odds ratio 1.11), higher education (odds ratio, 1.37), higher income (odds ratio 1.07), US residence (odds ratio 1.63) and coronary artery disease (CAD) (odds ratio 1.51) were associated with perception of alcohol as heart healthy (all p < 0.003). Ever smokers (odds ratio 0.76, p = 0.004) and those with heart failure (HF) (odds ratio 0.5, p = 0.01) were less likely to cite alcohol as heart healthy. Those perceiving alcohol as heart healthy consumed on average 47% more alcohol on a regular basis (95% confidence interval 27–66%, p < 0.001). In conclusion, among more than 5,000 consecutive Health eHeart participants, approximately one third believed alcohol to be heart healthy, and the majority cited the lay press as the origin of that perception. Those with a perception of alcohol as heart healthy drink substantially more alcohol.

BackgroundOnly half of hypertensive adults achieve blood pressure (BP) control in the United States, and it is unclear how BP control rates may be improved most effectively and efficiently at the population level.ObjectiveWe sought to compare the potential effects of system-wide isolated improvements in medication adherence, visit frequency, and higher physician prescription rate on achieving BP control at 52 weeks.DesignWe developed a Markov microsimulation model of patient-level, physician-level, and system-level processes involved in controlling hypertension with medications. The model is informed by data from national surveys, cohort studies and trials, and was validated against two multicenter clinical trials (ALLHAT and VALUE).SubjectsWe studied a simulated, nationally representative cohort of patients with diagnosed but uncontrolled hypertension with a usual source of care.InterventionsWe simulated a base case and improvements of 10 and 50%, and an ideal scenario for three modifiable parameters: visit frequency, treatment intensification, and medication adherence. Ideal scenarios were defined as 100% for treatment intensification and adherence, and return visits occurring within 4 weeks of an elevated office systolic BP.Main outcomeBP control at 52 weeks of follow-up was examined.ResultsAmong 25,000 hypothetical adult patients with uncontrolled hypertension (systolic BP ≥ 140 mmHg), only 18% achieved BP control after 52 weeks using base-case assumptions. With 10/50%/idealized enhancements in each isolated parameter, enhanced treatment intensification achieved the greatest BP control (19/23/71%), compared with enhanced visit frequency (19/21/35%) and medication adherence (19/23/26%). When all three processes were idealized, the model predicted a BP control rate of 95% at 52 weeks.ConclusionSubstantial improvements in BP control can only be achieved through major improvements in processes of care. Healthcare systems may achieve greater success by increasing the frequency of clinical encounters and improving physicians' prescribing behavior than by attempting to improve patient adherence to medications.

Background Cardiac sarcoidosis (CS) is a life-threatening disease that is frequently under-diagnosed.Methods and Results:We used a nationwide inpatient sample to identify CS patients from 2005 to 2011 in the USA. The annual admissions of CS increased from 1,108 in 2005 to 2,182 in 2011, representing a 2-fold rise over a short time. The proportions of CS patients with severe comorbidities, ventricular tachycardia, ventricular fibrillation and heart failure all increased from 2005 to 2011. However, the in-hospital mortality rate declined. Conclusions An increasing trend of CS was observed. Cardiologists should notice that CS is not as rare as thought.

This randomized clinical trial assessed the feasibility of a home-based trial of melatonin vs placebo for adolescent migraine prevention.

IMPORTANCE: Many published randomized clinical trials (RCTs) make claims for subgroup differences. OBJECTIVE: To evaluate how often subgroup claims reported in the abstracts of RCTs are actually supported by statistical evidence (P < .05 from an interaction test) and corroborated by subsequent RCTs and meta-analyses. DATA SOURCES: This meta-epidemiological survey examines data sets of trials with at least 1 subgroup claim, including Subgroup Analysis of Trials Is Rarely Easy (SATIRE) articles and Discontinuation of Randomized Trials (DISCO) articles. We used Scopus (updated July 2016) to search for English-language articles citing each of the eligible index articles with at least 1 subgroup finding in the abstract. STUDY SELECTION: Articles with a subgroup claim in the abstract with or without evidence of statistical heterogeneity (P < .05 from an interaction test) in the text and articles attempting to corroborate the subgroup findings. DATA EXTRACTION AND SYNTHESIS: Study characteristics of trials with at least 1 subgroup claim in the abstract were recorded. Two reviewers extracted the data necessary to calculate subgroup-level effect sizes, standard errors, and the P values for interaction. For individual RCTs and meta-analyses that attempted to corroborate the subgroup findings from the index articles, trial characteristics were extracted. Cochran Q test was used to reevaluate heterogeneity with the data from all available trials. MAIN OUTCOMES AND MEASURES: The number of subgroup claims in the abstracts of RCTs, the number of subgroup claims in the abstracts of RCTs with statistical support (subgroup findings), and the number of subgroup findings corroborated by subsequent RCTs and meta-analyses. RESULTS: Sixty-four eligible RCTs made a total of 117 subgroup claims in their abstracts. Of these 117 claims, only 46 (39.3%) in 33 articles had evidence of statistically significant heterogeneity from a test for interaction. In addition, out of these 46 subgroup findings, only 16 (34.8%) ensured balance between randomization groups within the subgroups (eg, through stratified randomization), 13 (28.3%) entailed a prespecified subgroup analysis, and 1 (2.2%) was adjusted for multiple testing. Only 5 (10.9%) of the 46 subgroup findings had at least 1 subsequent pure corroboration attempt by a meta-analysis or an RCT. In all 5 cases, the corroboration attempts found no evidence of a statistically significant subgroup effect. In addition, all effect sizes from meta-analyses were attenuated toward the null. CONCLUSIONS AND RELEVANCE: A minority of subgroup claims made in the abstracts of RCTs are supported by their own data (ie, a significant interaction effect). For those that have statistical support (P < .05 from an interaction test), most fail to meet other best practices for subgroup tests, including prespecification, stratified randomization, and adjustment for multiple testing. Attempts to corroborate statistically significant subgroup differences are rare; when done, the initially observed subgroup differences are not reproduced.

Background Benefit‐targeted statin prescribing may be superior to risk‐targeted statin prescribing (the current standard), but the impact and efficiency of this approach are unclear. Methods and Results We analyzed the National Health and Nutrition Examination Survey ( NHANES ) using an open‐source model (the Prevention Impact and Efficiency Model) to compare targeting of statin therapy according to expected benefit (benefit‐targeted) versus baseline risk (risk‐targeted) in terms of projected population‐level impact and efficiency. Impact was defined as relative % reduction in atherosclerotic cardiovascular disease in the US population for the given strategy compared to current statin treatment patterns; and efficiency as the number needed to treat over 10 years ( NNT 10 , average and maximum) to prevent each atherosclerotic cardiovascular disease event. Benefit‐targeted moderate‐intensity statin therapy at a treatment threshold of 2.3% expected 10‐year absolute risk reduction could produce a 5.7% impact (95% confidence interval, 4.8–6.7). This is approximately equivalent to the potential impact of risk‐targeted therapy at a treatment threshold of 5% 10‐year atherosclerotic cardiovascular disease risk (5.6% impact [4.7–6.6]). Whereas the estimated maximum NNT 10 is much improved for benefit‐targeted versus risk‐targeted therapy at these equivalent‐impact thresholds (43.5 vs 180), the average NNT 10 is nearly equivalent (24.2 vs 24.6). Reaching 10% impact (half the Healthy People 2020 impact objective, loosely defined) is theoretically possible with benefit‐targeted moderate‐intensity statins of persons with expected absolute risk reduction >2.3% if we expand age eligibility and account for treatment of all persons with diabetes mellitus or with low‐density lipoprotein >190 mg/dL (impact=12.4%; average NNT 10 =23.0). Conclusions Benefit‐based targeting of statin therapy provides modest gains in efficiency over risk‐based prescribing and could theoretically help attain approximately half of the Healthy People 2020 impact goal with reasonable efficiency.

Background— The coronary artery calcium (CAC) score predicts coronary heart disease (CHD) events, but methods for interpreting the score in combination with conventional CHD risk factors have not been established. Methods and Results— We analyzed CAC scores and CHD risk factor measurements from 6757 black, Chinese, Hispanic, and white men and women aged 45 to 84 years in the Multi-Ethnic Study of Atherosclerosis (MESA). CAC was associated with age, sex, race/ethnicity, and all conventional CHD risk factors. Multivariable models using these factors predicted the presence of CAC (C statistic=0.789) and degree of elevation (16% of variation explained) and can be used to update a “pretest” CHD risk estimate, such as the 10-year Framingham Risk Score, that is based on an individual’s conventional risk factors. In scenarios in which a high CAC score is expected, a moderately elevated CAC score of 50 is reassuring (eg, reducing risk from 10% to 6% in a healthy older white man), but when a low/zero CAC score is expected, even with identical pretest CHD risk, the same CAC score of 50 may be alarmingly high (eg, increasing risk from 10% to 20% in a middle-aged black woman with multiple risk factors). Both the magnitude and direction of the shift in risk varied markedly with pretest CHD risk and with the pattern of risk factors. Conclusions— Knowledge of what CAC score to expect for an individual patient, based on their conventional risk factors, may help clinicians decide when to order a CAC test and how to interpret the results.

Although obesity and the metabolic syndrome (MS) often co-occur, many obese (OB) subjects have a favorable metabolic profile. It is unclear whether these factors independently influence cardiac electrophysiology including prolongation of the QT interval. We examined associations among obesity, MS, and prolonged corrected QT (QTc) interval in a large sample of Chinese research participants aged ≥35 years recruited from rural areas of Liaoning Province during 2012 to 2013. Of the 11,209 participants, 6,364 (56.8%) were nonobese and metabolically healthy (OB-/MS-), 2,853 (25.5%) were OB-/MS+, 493 (4.4%) were OB+/MS-, and 1,499 (13.4%) were OB+/MS+. Mean (±SD) QTc intervals were higher in OB-/MS+ (436.3 ± 24.3) and OB+/MS+ (436.6 ± 25.9) participants but not OB+/MS- participants (425.4 ± 24.0) than in OB-/MS- participants (426.8 ± 21.5, p0.001), and the prevalence of QTc prolongation was higher in OB-/MS+ and OB+/MS+ participants (adjusted odds ratios [aOR] 1.68, 95% confidence interval [CI] 1.52 to 1.85; aOR 1.92, 95% CI 1.69 to 2.17, respectively) compared with OB-/MS- group but not in OB+/MS- participants (aOR 0.92, 95% CI 0.73 to 1.15). Prevalence increased with each MS component (aOR 1.27, 95% CI 1.22 to 1.32) but not with body mass index (aOR 1.01, 95% CI 0.99 to 1.02). In conclusion, prolonged QTc interval is associated with the MS and not independently associated with obesity.

Higher blood pressure during young adulthood may increase cardiovascular and kidney disease risk later in life. This study examined the association of cumulative systolic blood pressure (SBP) exposure during young adulthood through midlife with urine albumin-to-creatinine ratios (ACR) measured during midlife.We used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a biracial cohort recruited in 4 urban areas during years 1985-1986. Cumulative SBP was calculated as the average SBP between 2 exams multiplied by years between exams over 20 year years. ACR was measured 20 years after baseline when participants were age 43-50 years (midlife). A generalized additive model was used to examine the association of log ACR as a function of cumulative SBP with adjustment for covariates including SBP measured concurrently with ACR.Cumulative SBP ranged from a low of 1,671 to a high of 3,260 mm Hg. Participants in the highest cumulative SBP quartile were more likely to be male (61.4% vs. 20.7%; P0.001), Black (61.5% vs. 25.6%; P0.001) and have elevated ACR (18.7% vs. 4.8%; P0.001) vs. lowest quartile. Spline regression curves of ACR vs. cumulative SBP demonstrated an inflection point in ACR with cumulative SBP levels2,350 mm Hg with linear increases in ACR above this threshold. Adjusted geometric mean ACR values were significantly higher with cumulative SBP ≥2,500 vs.2500 (9.18 [1.06] vs. 6.92 [1.02]; P0.0001).Higher SBP during young adulthood through midlife is associated with higher ACR during midlife.

BackgroundIt is unclear whether coronary heart disease (CHD) risk factor exposure during early adulthood contributes to CHD risk later in life. Our objective was to analyze whether extent of early adult exposures to systolic and diastolic blood pressure (SBP, DBP) and low-and high-density lipoprotein cholesterol (LDL, HDL) are independent predictors of CHD events later in life.Methods and findingsWe used all available measurements of SBP, DBP, LDL, and HDL collected over 40 years in the Framingham Offspring Study to estimate risk factor trajectories, starting at age 20 years, for all participants. Average early adult (age 20-39) exposure to each risk factor was then estimated, and used to predict CHD events (myocardial infarction or CHD death) after age 40, with adjustment for risk factor exposures later in life (age 40+). 4860 participants contributed an average of 6.3 risk factor measurements from in-person examinations and 24.5 years of follow-up after age 40, and 510 had a first CHD event. Early adult exposures to high SBP, DBP, LDL or low HDL were associated with 8- to 30-fold increases in later life CHD event rates, but were also strongly correlated with risk factor levels later in life. After adjustment for later life levels and other risk factors, early adult DBP and LDL remained strongly associated with later life risk. Compared with DBP≤70 mmHg, adjusted hazard ratios (HRs) were 2.1 (95% confidence interval: 0.8-5.7) for DBP = 71-80, 2.6 (0.9-7.2) for DBP = 81-90, and 3.6 (1.2-11) for DBP>90 (p-trend = 0.019). Compared with LDL≤100 mg/dl, adjusted HRs were 1.5 (0.9-2.6) for LDL = 101-130, 2.2 (1.2-4.0) for LDL = 131-160, and 2.4 (1.2-4.7) for LDL>160 (p-trend = 0.009). While current levels of SBP and HDL were also associated with CHD events, we did not detect an independent association with early adult exposure to either of these risk factors.ConclusionsUsing a mixed modeling approach to estimation of young adult exposures with trajectory analysis, we detected independent associations between estimated early adult exposures to non-optimal DBP and LDL and CHD events later in life.

OBJECTIVES Obesity and hypertension are associated with an adverse metabolic profile and systemic low-grade inflammation. Metformin reduces weight and inflammation in patients with diabetes, but it is unclear whether it has beneficial effects in patients without diabetes. The objective was to explore whether metformin-based treatment could benefit obesity-related hypertension without diabetes. METHODS A randomized, double-blind, placebo-controlled factorial trial was conducted in 360 obese hypertensive patients without diabetes in Chongqing, China. After a 1-2-week run-in period, patients were randomly assigned to metformin (500 mg once per day) or placebo, as well as to an antihypertensive medication. Change in blood pressure, obesity measurements and metabolic profile were assessed at 24 weeks. RESULTS The 180 participants randomized to metformin and 180 randomized to placebo were similar at baseline. At 24 weeks, metformin compared with placebo did not have significant effects on blood pressure, blood glucose, high-density or low-density lipoprotein cholesterol, but it did reduce total serum cholesterol (0.2 mmol/l, P = 0.038). Metformin also significantly reduced weight (-0.7 kg, P = 0.006), BMI (-0.2 kg/m, P = 0.024), waist circumference (-0.9 cm, P = 0.008), and both subcutaneous (-6.1 cm, P = 0.043) and visceral adiposity (-5.4 cm, P = 0.028) as measured by computed tomography, and lowered serum high-sensitivity C-reactive protein levels (-0.6 mg/dl, P < 0.001). There was no significant difference in adverse events (P = 0.785). CONCLUSIONS Metformin has no effect on blood pressure and blood glucose levels, but it does reduce total cholesterol, abdominal obesity and C-reactive protein levels in obese hypertensive patients without diabetes.

Nighttime blood pressure (BP) dipping can be quantified as the ratio of mean nighttime (sleep) BP to mean daytime (awake) BP. People whose dipping ratio is ≥0.90 have been referred to as nondippers, and nondipping is associated with cardiovascular disease events. We examined the relationship between systolic nighttime BP dipping in young adults and the presence of coronary artery calcium (CAC) 10 to 15 years later using data from the ambulatory BP monitoring substudy of the Coronary Artery Risk Development in Young Adults Study. Among 239 participants with adequate measures of both nighttime and daytime readings and coronary artery calcium, the systolic BP dipping ratio ranged from 0.72 to 1.24 (mean, 0.88; SD, 0.06), and CAC was present 10 to 15 years later in 54 participants (22.6%). Compared with those whose systolic BP dipping ratio ranged from 0.88 to 0.92 (quartile 3), the 57 participants (23.9%) with less pronounced or absent dipping (ratio, 0.92–1.24; quartile 4) had an unadjusted odds ratio of 4.08 (95% CI, 1.48–11.2) for the presence of CAC. The 60 participants (25.1%) with a more pronounced dipping (ratio, 0.72–0.85; quartile 1) also had greater odds for presence of CAC (odds ratio, 4.76 [95% CI, 1.76–12.9]). When modeled as a continuous predictor, a U-shaped relationship between systolic BP dipping ratio and future CAC was apparent and persisted after adjustment for multiple potential confounders ( P

Objective To evaluate whether telomerase activity, measured in circulating blood leukocytes, might be associated with prevalent atherosclerosis, or predict future coronary artery disease risk. Methods and results We examined associations of telomerase activity levels measured at year 15 in the Coronary Artery Risk Development in Young Adults (CARDIA) Study with prevalent coronary artery calcium (CAC), progressive CAC at year 20, and incident CAC between years 15 and 20, in 440 black and white men aged 33–45 years. Telomere length was also measured in a subset of participants ( N =129). In multivariate-adjusted analysis, higher quartiles of telomerase were cross-sectionally associated with greater odds of prevalent CAC at year 15 (quartile 2: OR=1.32, 95% CI: 0.54–3.23; quartile 3: OR=1.40, 95% CI: 0.60–3.30; quartile 4: OR=3.27, 95% CI: 1.39–7.71 compared with quartile 1, p -continuous=0.012) and progressive CAC at year 20, but telomerase was not significantly associated with incidence of newly detectable CAC. Higher telomerase activity levels predicted greater CAC progression at year 20 among persons with short telomere length; low telomerase and short TL predicted less CAC progression. Conclusion Telomerase activity in leukocytes was associated with calcified atherosclerotic plaque, and was also a predictor of advancing plaque among persons with short telomeres.

Purpose: Recent reports suggest that nephrolithiasis and atherosclerosis share a number of risk factors. To our knowledge there has been no previous examination of the relationship between kidney stones and subclinical atherosclerotic disease. We studied the relationship between nephrolithiasis, and carotid wall thickness and carotid stenosis assessed by B-mode ultrasound in the general community using data from the CARDIA study.Materials and Methods: The CARDIA study is a United States, population based, observational study of 5,115 white and African-American men and women between the ages of 18 and 30 years at recruitment in 1985 to 1986.Results: By the year 20 examination 200 (3.9%) CARDIA participants had reported ever having kidney stones. Symptomatic kidney stones were associated with greater carotid wall thickness measured at the year 20 examination, particularly of the internal carotid/bulb region. Using a composite dichotomous end point of carotid stenosis and/or the upper quartile of internal ca...

OBJECTIVE To evaluate the public health impact of statin prescribing strategies based on the Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin Study (JUPITER). METHODS We studied 2268 adults aged 35 75 without cardiovascular disease in a population based study in Switzerland in 2003 2006. We assessed the eligibility for statins according to the Adult Treatment Panel III (ATPIII) guidelines and by adding "strict" (hs CRP=2.0 mg/L and LDL cholesterol