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Introduction: Extended periods of exposure to elevated blood pressure (BP) in early adult life contribute independently to later life coronary heart disease (CHD) risk. Currently, there are significant gaps in hypertension awareness, treatment, and control in young adults. The long-term health benefits of controlling high BP in young adults have not previously been quantified. Objective: This study aimed to project CHD prevention benefits from controlling raised blood pressure starting in early adulthood compared with control at age 40 or older. Method: A state-transition microsimulation model estimated individual-level CHD outcomes, dependent on risk factors exposures and accounting for competing risk of stroke or non-cardiovascular death. Risk for first CHD event after age 40 was conditioned both on time-weighted average of early adult (ages 20-39) diastolic blood pressure (DBP), and raised DBP or systolic blood pressure (SBP) at age ≥ 40. We simulated CHD outcomes in a cohort of US adults with DBP ≥ 85 mmHg any time in young adulthood in 3 scenarios: no treatment, later life SBP control alone, or early DBP control plus later life BP control. Results: By age 39, 2.2% of the CVD-free young adult U.S. population was estimated to have early elevated DBP and was eligible for treatment. With follow up until age 69 years, early BP control prevented twice the number of primary CHD events (Table). Conclusion: This study quantifies the opportunity cost of failing to control hypertension identified in young adulthood. It is unclear whether early blood pressure control should be achieved by lifestyle or pharmacological intervention.

Introduction: Intensive blood pressure (BP) goals are considered for high cardiovascular disease (CVD) risk adults ≥50 years old; the long-term value of intensive BP goals in younger high CVD risk patients has not been studied. Objectives: We used individual patient computer simulations to assess the incremental value of intensive BP goals in high CVD risk patients as young as 40 years. Methods: Six age/sex cohorts of 100,000 individuals were assembled by sampling NHANES surveys 1999-2010. BP and other risk factor trajectories were projected from ages 60 to 69, 50 to 69, and 40 to 69 years based on Framingham Offspring Cohort analyses. One BP treatment scenario simulated treating BP Results: Intensive goals were generally cost-effective in high-risk CVD risk patients (Table). Treating 40-year old cohorts was the highest value strategy. This was because of large life-year gains when events are prevented early in life and because hypertensive 40 year-olds “age into” much higher BPs and CVD risk over time. To illustrate the latter, mean untreated systolic BPs at age 60 were 152, 148, and 146 mmHg, and mean 10-year CVD risk scores were 17%, 15% and 13% for 40-, 50- and 60-year-old male cohorts, respectively. Conclusion: Intensive BP goals were projected to be cost-effective over a 30-year time horizon in high-risk hypertensive patients as young as 40 years old.

Background— Ascertainment of hospitalizations is critical to assess quality of care and the effectiveness and adverse effects of various therapies. Smartphones, mobile geolocators that are ubiquitous, have not been leveraged to ascertain hospitalizations. Therefore, we evaluated the use of smartphone-based geofencing to track hospitalizations. Methods and Results— Participants aged ≥18 years installed a mobile application programmed to geofence all hospitals using global positioning systems and cell phone tower triangulation and to trigger a smartphone-based questionnaire when located in a hospital for ≥4 hours. An in-person study included consecutive consenting patients scheduled for electrophysiology and cardiac catheterization procedures. A remote arm invited Health eHeart Study participants who consented and engaged with the study via the internet only. The accuracy of application-detected hospitalizations was confirmed by medical record review as the reference standard. Of 22 eligible in-person patients, 17 hospitalizations were detected (sensitivity 77%; 95% confidence interval, 55%–92%). The length of stay according to the application was positively correlated with the length of stay ascertained via the electronic medical record ( r =0.53; P =0.03). In the remote arm, the application was downloaded by 3443 participants residing in all 50 US states; 243 hospital visits at 119 different hospitals were detected through the application. The positive predictive value for an application-reported hospitalization was 65% (95% confidence interval, 57%–72%). Conclusions— Mobile application–based ascertainment of hospitalizations can be achieved with modest accuracy. This first proof of concept may ultimately be applicable to geofencing other types of prespecified locations to facilitate healthcare research and patient care.

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.

AIMS To estimate physical activity trajectories for people who quit smoking, and compare them to what would have been expected had smoking continued. DESIGN, SETTING AND PARTICIPANTS A total of 5115 participants in the Coronary Artery Risk Development in Young Adults Study (CARDIA) study, a population-based study of African American and European American people recruited at age 18-30 years in 1985/6 and followed over 25 years. MEASUREMENTS Physical activity was self-reported during clinical examinations at baseline (1985/6) and at years 2, 5, 7, 10, 15, 20 and 25 (2010/11); smoking status was reported each year (at examinations or by telephone, and imputed where missing). We used mixed linear models to estimate trajectories of physical activity under varying smoking conditions, with adjustment for participant characteristics and secular trends. FINDINGS We found significant interactions by race/sex (P = 0.02 for the interaction with cumulative years of smoking), hence we investigated the subgroups separately. Increasing years of smoking were associated with a decline in physical activity in black and white women and black men [e.g. coefficient for 10 years of smoking: -0.14; 95% confidence interval (CI) = -0.20 to -0.07, P

Internet and mobile based research are powerful tools in the creation of large, cohort studies (eCohort). However, recent analysis indicates that an underrepresentation of minority and low income groups in these studies might exceed that found in traditional research [1–5]. In this report, we present findings from an experiment in research engagement using the Eureka Research Platform developed to enroll diverse populations in support of biomedical clinical research. This experiment involved the recruitment of African American and Latino participants in a smartphone based survey at a temporary, charitable, dental event sponsored, in part, by the research team, in order to explore the impact of setting and approach on recruitment outcomes. 211 participants enrolled including a significant representation of African Americans (51%) and Latinos (31%) and those with education levels at high school or less (37%). Interviews conducted after the study confirmed that our recruitment efforts within the context of a service event affected the decision to participate. While further research is necessary, this experiment holds promise for the engagement of underrepresented groups in research. Keywords: eCohort studies, Recruitment, Minority populations, Community engagement, Clinical trials

Background New electronic cohort (e-Cohort) study designs provide resource-effective methods for collecting participant data. It is unclear if implementing an e-Cohort study without direct, in-person participant contact can achieve successful participation rates. Objective The objective of this study was to compare 2 distinct enrollment methods for setting up mobile health (mHealth) devices and to assess the ongoing adherence to device use in an e-Cohort pilot study. Methods We coenrolled participants from the Framingham Heart Study (FHS) into the FHS–Health eHeart (HeH) pilot study, a digital cohort with infrastructure for collecting mHealth data. FHS participants who had an email address and smartphone were randomized to our FHS-HeH pilot study into 1 of 2 study arms: remote versus on-site support. We oversampled older adults (age ≥65 years), with a target of enrolling 20% of our sample as older adults. In the remote arm, participants received an email containing a link to enrollment website and, upon enrollment, were sent 4 smartphone-connectable sensor devices. Participants in the on-site arm were invited to visit an in-person FHS facility and were provided in-person support for enrollment and connecting the devices. Device data were tracked for at least 5 months. Results Compared with the individuals who declined, individuals who consented to our pilot study (on-site, n=101; remote, n=93) were more likely to be women, highly educated, and younger. In the on-site arm, the connection and initial use of devices was ≥20% higher than the remote arm (mean percent difference was 25% [95% CI 17-35] for activity monitor, 22% [95% CI 12-32] for blood pressure cuff, 20% [95% CI 10-30] for scale, and 43% [95% CI 30-55] for electrocardiogram), with device connection rates in the on-site arm of 99%, 95%, 95%, and 84%. Once connected, continued device use over the 5-month study period was similar between the study arms. Conclusions Our pilot study demonstrated that the deployment of mobile devices among middle-aged and older adults in the context of an on-site clinic visit was associated with higher initial rates of device use as compared with offering only remote support. Once connected, the device use was similar in both groups.

Importance Disability measures in multiple sclerosis (MS) fail to capture potentially important variability in walking behavior. More sensitive and ecologically valid outcome measures are needed to advance MS research. Objectives To assess continuous step count activity remotely among individuals with MS for 1 year and determine how average daily step count is associated with other measures of MS disability. Design, Setting, and Participants In a prospective longitudinal observational cohort study, 95 adults with relapsing or progressive MS who were able to walk more than 2 minutes with or without an assistive device were recruited between June 15, 2015, and August 8, 2016, and remotely monitored in their natural environment for 1 year. Patients were excluded if they had a clinical relapse within 30 days or comorbidity contributing to ambulatory impairment. Longitudinal analysis was performed from October 2017 to March 2018. Revised analysis was performed in December 2018. Intervention Activity monitoring of step count using a wrist-worn accelerometer. Main Outcomes and Measures Average daily step count compared with in-clinic assessments and patient-reported outcomes. Results Of the 95 participants recruited (59 women and 36 men; mean [SD] age, 49.6 [13.6] years [range, 22.0-74.0 years]), 35 (37%) had progressive MS, and the median baseline Expanded Disability Status Scale score was 4.0 (range, 0-6.5). At 1 year, 79 participants completed follow-up (83% retention). There was a modest reduction in accelerometer use during the 1 year of the study. A decreasing average daily step count during the study was associated with worsening of clinic-based outcomes (Timed 25-Foot Walk, β = −13.09; P, This longitudinal cohort study assesses how remote monitoring of continuous step count activity for 1 year among individuals with multiple sclerosis is associated with other measures of multiple sclerosis disability., Key Points Question Is remote monitoring of continuous activity for 1 year among individuals with multiple sclerosis associated with other measures of ambulatory disability? Findings In this longitudinal cohort study, 95 individuals with multiple sclerosis were asked to wear accelerometers for 1 year; at baseline, a low step count was associated with increased risk of clinical worsening at 1 year. Step count reduction during the study was associated with worsening of clinic-based and patient-reported outcomes and occurred even when conventional disability measures remained stable. Meaning Remote step count monitoring might represent a sensitive longitudinal outcome measure with direct implications for multiple sclerosis clinical trials and care.

Up to a third of patients with diabetes are undiagnosed, and therefore go untreated. Widely available consumer technologies could detect diabetes at an early stage. Since diabetes is associated with vascular changes, we examined whether diabetes could be detected using only the photoplethysmography

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.

Large randomized clinical trials in cardiovascular disease have proliferated over the past 3 decades, with results that have influenced every aspect of cardiology practice. Despite these advances, there remains a substantial need for more high-quality evidence to inform cardiovascular clinical practice, given the increasing prevalence of cardiovascular disease around the world. Traditional clinical trials are increasingly challenging due to rising costs, increasing complexity and length, and burdensome institutional and regulatory requirements. This review will examine the current landscape of cardiovascular clinical trials in the United States, highlight recently conducted registry-based clinical trials, and discuss the potential attributes of the recently launched pragmatic clinical trial by the Patient-Centered Outcomes Research Institute's National Patient-Centered Clinical Research Network, called the ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing the Benefits and Long-term Effectiveness) trial.

Introduction: Stroke death rates have declined nationally, but less in men and non-Hispanic Blacks. We quantified case-fatality and risk factor trend contributions to non-Hispanic Black and non-Hispanic White 1999-2012 stroke mortality trends. Methods: The CVD Policy Model is a computer simulation of heart disease and stroke incidence, prevalence, and mortality in US adults ≥ 35 years old. We modeled mean systolic blood pressure (SBP), low-density lipoprotein (LDL), and body mass index (BMI), prevalence of diabetes and smoking, and case fatality for 1999-2002, 2003-06, and 2007-12 by sex and race (NHANES; NHDS) to predict stroke mortality trends and these predictions were compared with observed data (CDC Wonder; ICD-10 I60-69). We then simulated the effects of isolated risk factors on stroke mortality in younger (age 35-64 years) and older (age 65-84 years) men and women. Results: Model predictions mirrored observed trends for stroke mortality in Whites (men: predicted -27.0% v. observed -29.2%; women: -34.8% v. -33.3%) and Blacks (men: -23.8% v. -22.2%; women: -31.0% v. -30.0%). Case fatality was the main contributor to the observed decrease in stroke mortality (approximately -25%) but did not explain differences between race groups. Combined risk factor trends contributed to decreased mortality in women (-12.8% in Whites; -8.7% in Blacks), but not men. Decreased mean SBP contributed in all women (-10.7% to -12.6%, depending on age/race) and older men (-4.0%), but not young men. Increased diabetes prevalence offset improvements in stroke mortality in older White men (+2.5%), younger Blacks (men: +4.0, women: +1.5%) and, to a larger degree, older Blacks (men: +9.9%, women: +5.6% ). Conclusions: Reduced case fatality was the strongest driver of decreased stroke mortality from 1999-2012 overall, while risk factor trends explained gender and race differences. Targeting high blood pressure in young adult men and preventing diabetes at all ages could further decrease stroke mortality and reduce racial differences. Blacks would benefit most from more aggressive stroke risk factor control.

The American College of Medical Genetics and Genomics (ACMG) recommends that mutations in 56 genes for 24 conditions are clinically actionable and should be reported as secondary findings after whole-genome sequencing (WGS). Our aim was to identify published economic evaluations of detecting mutations in these genes among the general population or among targeted/high-risk populations and conditions and identify gaps in knowledge. A targeted PubMed search from 1994 through November 2014 was performed, and we included original, English-language articles reporting cost-effectiveness or a cost-to-utility ratio or net benefits/benefit-cost focused on screening (not treatment) for conditions and genes listed by the ACMG. Articles were screened, classified as targeting a high-risk or general population, and abstracted by two reviewers. General population studies were evaluated for actual cost-effectiveness measures (e.g., incremental cost-effectiveness ratios (ICER)), whereas studies of targeted populations were evaluated for whether at least one scenario proposed was cost-effective (e.g., ICER of ≤$100,000 per life-year or quality-adjusted life-year gained). A total of 607 studies were identified, and 32 relevant studies were included. Identified studies addressed fewer than one-third (7 of 24; 29%) of the ACMG conditions. The cost-effectiveness of screening in the general population was examined for only 2 of 24 conditions (8%). The cost-effectiveness of most genetic findings that the ACMG recommends for return has not been evaluated in economic studies or in the context of screening in the general population. The individual studies do not directly address the cost-effectiveness of WGS.

Background Cigarette smoking is a risk factor for atrial fibrillation (AF), but whether secondhand smoke (SHS) impacts the risk of AF remains unknown. Objective To determine if SHS exposure is associated with an increased risk of AF. Methods We performed a cross-sectional analysis of data from participants enrolled in the Health eHeart Study, an internet-based, longitudinal cardiovascular cohort study, who completed baseline SHS exposure and medical conditions questionnaires. SHS was assessed through a validated 22-question survey, and prevalent AF was assessed by self-report, with validation of a subset (n = 42) by review of electronic medical records. Results Of 4976 participants, 593 (11.9%) reported having AF. In unadjusted analyses, patients with AF were more likely to have been exposed to SHS in utero, as a child, as an adult, at home, and at work. After multivariable adjustment for potential confounders, having had a smoking parent during gestational development (OR 1.37, 95% CI 1.08–1.73, P = .009) and residing with a smoker during childhood (OR 1.40, 95% CI 1.10–1.79, P = .007) were each significantly associated with AF. Both positive associations were more pronounced among patients without risk factors for AF ( P values for interaction Conclusions SHS exposure during gestational development and during childhood was associated with having AF later in life. This association was even stronger in the absence of established risk factors for AF. Our findings indicate that SHS in early life may be an important, potentially modifiable risk factor for the development of AF.

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.

Background— Noninvasive stress testing might guide the use of aspirin and statins for primary prevention of coronary heart disease, but it is unclear if such a strategy would be cost effective. Methods and Results— We compared the status quo, in which the current national use of aspirin and statins was simulated, with 3 other strategies: (1) full implementation of Adult Treatment Panel III guidelines, (2) a treat-all strategy in which all intermediate-risk persons received statins (men and women) and aspirin (men only), and (3) a test-and-treat strategy in which all persons with an intermediate risk of coronary heart disease underwent stress testing and those with a positive test were treated with high-intensity statins (men and women) and aspirin (men only). Healthcare costs, coronary heart disease events, and quality-adjusted life years from 2011 to 2040 were projected. Under a variety of assumptions, the treat-all strategy was the most effective and least expensive strategy. Stress electrocardiography was more effective and less expensive than other test-and-treat strategies, but it was less expensive than treat all only if statin cost exceeded $3.16/pill or if testing increased adherence from 75%. However, stress electrocardiography could be cost effective in persons initially nonadherent to the treat-all strategy if it raised their adherence to 5% and cost saving if it raised their adherence to 13%. Conclusions— When generic high-potency statins are available, noninvasive cardiac stress testing to target preventive medications is not cost effective unless it substantially improves adherence.

To date, most genetic association studies of tobacco use have been conducted in European American subjects using the phenotype of smoking quantity (cigarettes per day). However, smoking quantity is a very imprecise measure of exposure to tobacco smoke constituents. Analyses of alternate phenotypes and populations may improve our understanding of tobacco addiction genetics. Cotinine is the major metabolite of nicotine, and measuring serum cotinine levels in smokers provides a more objective measure of nicotine dose than smoking quantity. Previous genetic association studies of serum cotinine have focused on individual genes. We conducted a genetic association study of the biomarker in African American (N=365) and European American (N=315) subjects from the Coronary Artery Risk Development in Young Adults study using a chip containing densely-spaced tag SNPs in ∼2100 genes. We found that rs11187065, located in the non-coding region (intron 1) of insulin-degrading enzyme (IDE), was the most strongly associated SNP (p=8.91 × 10(-6)) in the African American cohort, whereas rs11763963, located on chromosome 7 outside of a gene transcript, was the most strongly associated SNP in European Americans (p=1.53 × 10(-6)). We then evaluated how the top variant association in each population performed in the other group. We found that the association of rs11187065 in IDE was also associated with the phenotype in European Americans (p=0.044). Our top SNP association in European Americans, rs11763963 was non-polymorphic in our African American sample. It has been previously shown that psychostimulant self-administration is reduced in animals with lower insulin because of interference with dopamine transmission in the brain reward centers. Our finding provides a platform for further investigation of this, or additional mechanisms, involving the relationship between insulin and self-administered nicotine dose.

background: Fertility potential and reproductive fitness may reflect a man’s future health, given that over one-third of the male human genome is involved in reproduction. We sought to determine if offspring number predicts cardiovascular death in the US men. methods: Using data from the NIH-AARP Diet and Health Study, 137 903 men (aged 50 –71) without prior cardiovascular disease were followed-up for an average of 10.2 years. International Classification of Diseases, ninth edition, codes were used to establish the cause of death, and multivariable Cox proportional hazards modeling was used to estimate the association between offspring number and cardiovascular death while accounting for sociodemographic and lifestyle characteristics. results: Almost all (92%) participants had fathered at least one child and 50% had three or more offspring. A total of 3082 men died of cardiovascular causes during follow-up for an age-adjusted incidence rate of 2.70 per 1000 person-years. Compared with fathers, after adjusting for sociodemographic and lifestyle factors, childless men had a 17% [hazard ratio (HR): 1.17; 95% confidence interval (CI): 1.03– 1.32] increased risk of death from cardiovascular disease contracted in the study period, and this elevated risk appeared to extend also to men with only one child. In comparison with fathers of five or more children, adjusted relative hazards for cardiovascular mortality of this sort were 1.06 (95% CI: 0.92 –1.22) for four children, 1.02 (0.90–1.16) for three children, 1.02 (0.90–1.16) for two children, 1.11 (0.95–1.30) for one child and 1.21 (1.03–1.41) for no children. conclusions: Married men who have no children have a higher risk of dying from cardiovascular disease contracted after the age of 50 than men with two or more children.

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...

Background The goal of this investigation is to discover whether or not patients with psychiatric diagnoses are less likely to be prescribed opioids for pain in emergency departments compared with other patients. Methods Pain-related visits to US emergency departments were identified using reason-for-visit and physician diagnosis codes for 13 years (1993–2005) of the National Hospital Ambulatory Medical Care Survey. The outcome measure was the prescription or administration of an opioid analgesic. Results Roughly 10 million pain-related visits were made by persons with psychiatric diagnoses in the USA between 1993 and 2005. Across all years, only 18% (95% CI 16 to 20) of pain-related visits by patients with psychiatric diagnoses resulted in an opioid prescription, whereas 33% (95% CI 32 to 34) of visits by other patients did. Lower prescription rates for patients with psychiatric diagnoses were seen for every year of the survey and this difference occurred at every level of pain severity. Controlling for confounding factors did not attenuate this difference. In a multivariate model, patients with psychiatric diagnoses were about half as likely as other patients to be prescribed opiates (adjusted OR 0.49; 95% CI 0.44 to 0.56). Major limitations of the study include the uncertain precision of psychiatric and drug/alcohol diagnoses and the lack of detail about each patient visit. Conclusion Having a psychiatric diagnosis was associated with a lower likelihood of receiving an opioid among persons presenting with pain to the ED.

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

Introduction: Menthol cigarette smokers may find it harder to quit smoking than smokers of nonmenthol cigarettes. Methods: We conducted a systematic review of published studies examining the association between menthol cigarette smoking and cessation. Electronic databases and reference lists were searched to identify studies published through May 2010, and results were tabulated. Results: Ten studies were located that reported cessation outcomes for menthol and nonmenthol smokers. Half of the studies found evidence that menthol smoking is associated with lower odds of cessation, while the other half found no such effects. The pattern of results in these studies suggest that the association between smoking menthol cigarettes and difficulty quitting is stronger in (a) racial/ethnic minority populations, (b) younger smokers, and (c) studies carried out after1999. This pattern is consistent with an effect that relies on menthol to facilitate increased nicotine intake from fewer cigarettes where economic pressure restricts the number of cigarettes smokers can afford to purchase. Conclusions: There is growing evidence that certain subgroups of smokers find it harder to quit menthol versus non menthol cigarettes. There is a need for additional research, and particularly for studies including adequately powered and diverse samples of menthol and nonmenthol smokers, with reliable measurement of cigarette brands, socioeconomic status, and biomarkers of nicotine intake.

Summary Appetite regulatory neural network and adipocyte homeostasis molecular pathways are critical to long-term weight maintenance. Associations between obesity-related phenotypes and four genes in these pathways – leptin (LEP), leptin receptor (LEPR), neuropeptide Y2 receptor (NPY2R) and peptide YY (PYY) were examined in CARDIA Study participants (aged 18–30 at recruitment in 1985–6). Weight, BMI and waist circumference were measured at baseline and at years 2, 5, 7, 10, 15, and 20. Genotyping was conducted using tag SNPs characterising common genetic variations in these genes. Generalized estimating equation (GEE) models estimated associations between SNPs and repeated anthropometric measurements, controlling for sex and age. False discovery rate was used to adjust for multiple testing. In African-Americans, SNPs across the LEP gene demonstrated significant overall associations with all obesity-related phenotypes. The associations between LEP rs17151919 with weight tended to strengthen with time – the difference in weight associated with each additional minor allele increased from 2.6 kg at baseline to 4.8 kg at year 20 (SNP*time interaction p = 0.0193). NPY2R gene SNPs were associated with waist circumference among African-American men (p = 0.0462). In Caucasians, LEP SNPs also tended to be associated with weight (p = 0.0471), and PYY rs11684664 was associated with obesity-related phenotypes in women only (p = 0.010–0.026). Several LEP, and NPY2R and PYY SNPs were associated with obesity-related phenotypes in young adults, particularly among African-Americans.

Young adults below 35 years of age who do not have an exceedingly rare genetic disorder such as familial hypercholesterolemia are at very low short-term (5- to 10-year) risk for coronary heart disease (CHD), and lipid-lowering treatment at this stage in life is unlikely to provide any short-term

Introduction:The objective of this study was to identify the factors that lead to increased use of emergency medical services (EMS) by patients ≥65 years of age in an urban EMS system.Methods:Retrospective, case-control study of frequent EMS use among elderly patients transported during one year in an urban EMS system. Three distinct groups were examined for transports that took place in 1999: (1) 1–3 transports per year (low use); (2) 4–9 times per year (high use); and (3) those transported 10+ times (very high use). This frequency-use indicator variable is the primary outcome measurement. Predictors included age, gender, preexisting medical diseases, ethnicity, number of medications, number of medical problems, primary physician, psychiatric diagnosis, and homelessness. Analysis of predictors was done using ordinal logistic regression model, and a global test of interaction terms.Results:Male gender, black ethnicity, homelessness, and a variety of types of medical problems were associated with increased use of EMS resources. The strongest single predictor of case status remained homelessness, which was nearly eight times as commonly associated with frequent EMS use than for the controls. The number of medical problems and medications also were significantly associated with EMS use in this patient population. There was a lack of association of alcohol, substance abuse, and psychiatric disorders with EMS use. Patients with asthma who did not have a primary care physician were more likely to use EMS services than were those who had a physician.Conclusions:This analysis highlights homelessness as being strongly associated with frequent EMS use among the elderly and downplays other associated factors, such as psychiatric disease and substance use. Medical illness severity, particularly asthma when no primary care physician is available, also appears to drive frequent EMS use. Both findings have implications in terms of targeting of public resources; providing housing to medically ill elderly and primary care to asthmatics in particular, may provide dividends not only in terms of social welfare and medical care, but in preventing frequent EMS use by the elderly.

Atrial fibrillation (AF) affects 34 million people worldwide and is a leading cause of stroke. A readily accessible means to continuously monitor for AF could prevent large numbers of strokes and death.To develop and validate a deep neural network to detect AF using smartwatch data.In this multinational cardiovascular remote cohort study coordinated at the University of California, San Francisco, smartwatches were used to obtain heart rate and step count data for algorithm development. A total of 9750 participants enrolled in the Health eHeart Study and 51 patients undergoing cardioversion at the University of California, San Francisco, were enrolled between February 2016 and March 2017. A deep neural network was trained using a method called heuristic pretraining in which the network approximated representations of the R-R interval (ie, time between heartbeats) without manual labeling of training data. Validation was performed against the reference standard 12-lead electrocardiography (ECG) in a separate cohort of patients undergoing cardioversion. A second exploratory validation was performed using smartwatch data from ambulatory individuals against the reference standard of self-reported history of persistent AF. Data were analyzed from March 2017 to September 2017.The sensitivity, specificity, and receiver operating characteristic C statistic for the algorithm to detect AF were generated based on the reference standard of 12-lead ECG-diagnosed AF.Of the 9750 participants enrolled in the remote cohort, including 347 participants with AF, 6143 (63.0%) were male, and the mean (SD) age was 42 (12) years. There were more than 139 million heart rate measurements on which the deep neural network was trained. The deep neural network exhibited a C statistic of 0.97 (95% CI, 0.94-1.00; P .001) to detect AF against the reference standard 12-lead ECG-diagnosed AF in the external validation cohort of 51 patients undergoing cardioversion; sensitivity was 98.0% and specificity was 90.2%. In an exploratory analysis relying on self-report of persistent AF in ambulatory participants, the C statistic was 0.72 (95% CI, 0.64-0.78); sensitivity was 67.7% and specificity was 67.6%.This proof-of-concept study found that smartwatch photoplethysmography coupled with a deep neural network can passively detect AF but with some loss of sensitivity and specificity against a criterion-standard ECG. Further studies will help identify the optimal role for smartwatch-guided rhythm assessment.

The relation between alcohol consumption and incident hypertension is unclear, and most observational studies have not accounted for socioeconomic factors. This study examined the association between alcohol consumption in a diverse group of young adults and incident hypertension over 20 years. Participants (n ¼ 4,711) were from the Coronary Artery Risk Development in Young Adults Study cohort, recruited in 1985 (aged 18–30 years) from Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California. The 20-year incidence of hypertension for never, former, light, moderate, and at-risk drinkers was 25.1%, 31.8%, 20.9%, 22.2%, and 18.8%, respectively (P < 0.001). Race, gender, age, family history of hypertension, body mass index, income, education, and difficulty paying for basics and medical care were associated with hypertension. Adjustment using Cox proportional hazard models revealed no association between baseline alcohol consumption and incident hypertension, except among European-American women in whom any current alcohol consumption was associated with lower risk of incident hypertension. The lack of association between alcohol and hypertension in the majority of this socioeconomically diverse cohort is not definitive. Future studies should include social factors, such as income and education, and consider additional characteristics that may modify or confound associations between alcohol and blood pressure. African continental ancestry group; alcohol drinking; cohort studies; European continental ancestry group; hypertension; incidence

Telomere length (TL) has been proposed as a marker of mitotic cell age and as a general index of human organismic aging. Short absolute leukocyte telomere length has been linked to cardiovascular-related morbidity and mortality. Our aim was to test whether the rate of change in leukocyte TL is related to mortality in a healthy elderly cohort. We examined a subsample of 236 randomly selected Caucasian participants from the MacArthur Health Aging Study (aged 70 to 79 years). DNA samples from baseline and 2.5 years later were assayed for mean TL of leukocytes. Percent change in TL was calculated as a measure of TL change (TLC). Associations between TL and TLC with 12-year overall and cardiovascular mortality were assessed. Over the 2.5 year period, 46% of the study participants showed maintenance of mean bulk TL, whereas 30% showed telomere shortening, and, unexpectedly, 24% showed telomere lengthening. For women, short baseline TL was related to greater mortality from cardiovascular disease (OR = 2.3; 95% CI: 1.0 - 5.3). For men, TLC (specifically shortening), but not baseline TL, was related to greater cardiovascular mortality, OR = 3.0 (95% CI: 1.1 - 8.2). This is the first demonstration that rate of telomere length change (TLC) predicts mortality and thus may be a useful prognostic factor for longevity.

Dependence on and abuse of prescription opioid drugs is now a major health problem, with initiation of prescription opioid abuse exceeding cocaine in young people. Coincident with the emergence of abuse and dependence on prescription opioids, there has been an increased emphasis on the treatment of pain. Pain is now the "5th vital sign" and physicians face disciplinary action for failure to adequately relieve pain. Thus, physicians are whipsawed between the imperative to treat pain with opioids and the fear of producing addiction in some patients. In this article, the authors characterize the emerging epidemic of prescription opioid abuse, discuss the utility of buprenorphine in the treatment of addiction to prescription opioids, and present illustrative case histories of successful treatment with buprenorphine.

Research with college populations suggests that elevated levels of heavy drinking do not generally persist into later adulthood for most individuals. The aims of this study were to determine whether this pattern applies to the population as a whole and to identify those for whom heavy drinking in early adulthood does lead to continued high levels of consumption throughout the life course.Patterns of heavy drinking were assessed, and a mixture model was used to evaluate relationships between psychological profiles and trajectories of heavy drinking in early to middle adulthood for race-gender groups. Subjects (N = 5,115; 55% women) were drawn from the longitudinal study of Coronary Artery Risk Development in Young Adults (CARDIA) conducted in four major U.S. cities from 1985 to 1995.Patterns of heavy drinking differed by race and gender, with higher rates observed among whites and men. Heavy drinking was generally most common in the early 20s and dropped sharply thereafter. For a subset with psychological profiles characterized by elevated levels of hostility, anxiety, and depressive symptoms, high rates of heavy drinking persisted into later adulthood; 20% of whites and 50% of blacks in the overall sample were in this subset. Rates of heavy drinking in this group were similar for blacks and whites.At a population level, heavy drinking in early adulthood tends not to continue into later life. For a subset of psychologically vulnerable individuals, however, early adult heavy drinking persists into the middle adulthood years.

The authors investigated whether substance use and self-reported racial discrimination were associated in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Smoking status, alcohol consumption, and lifetime use of marijuana, amphetamines, and opiates were ascertained in 2000–2001, 15 years after baseline(1985–1986). Most of the 1,507 African Americans reported having experienced racial discrimination, 79.5% at year 7 and 74.6% at year 15, compared with 29.7% and 23.7% among the 1,813 Whites. Compared with African Americans experiencing no discrimination, African Americans reporting any discrimination had more education and income, while the opposite was true for Whites (all p < 0.001). African Americans experiencing racial discrimination in at least three of seven domains in both years had 1.87 (95% confidence interval (CI): 1.18, 2.96) and 2.12 (95% CI: 1.42, 3.17) higher odds of reporting current tobacco use and having any alcohol in the past year than did their counterparts experiencing no discrimination. With control for income and education, African Americans reporting discrimination in three or more domains in both years had 3.31 (95% CI: 1.90, 5.74) higher odds of using marijuana 100 or more times in their lifetime, relative to African Americans reporting no discrimination. These associations were similarly positive in Whites but not significant. Substance use may be an unhealthy coping response to perceived unfair treatment for some individuals, regardless of their race/ethnicity.

Background: Alcohol may have important effects on heart disease, but studies have generally relied on self-reported alcohol consumption and have yielded conflicting results. We utilized differences in county-level alcohol sales laws as a natural experiment to investigate the relationship between alcohol consumption and heart disease. Hypothesis: Wet counties residents have higher rates of atrial fibrillation (AF) and lower rates of myocardial infarction (MI) and congestive heart failure (CHF) related admissions. Methods: All counties in Texas with no restriction (“wet”) or complete prohibition (“dry”) of alcohol sales or a change in such laws between 2005 and 2010 were identified. Data from the Texas Inpatient Research Data File was used to characterize the hospitalizations of adult residents of those counties. Differences in alcohol use rates were validated using alcohol abuse and alcoholic liver disease outcomes. Adjustment covariates included age, race, ethnicity, sex, diabetes, hypertension, obesity, CHF, CAD, lung disease, and valvular disease. Results: Among 1,106,968 patients; wet county residents had a greater incidence of alcohol abuse (HR 1.36, 95% CI 1.23-1.50, p Conclusions: Greater access to alcohol is associated with more alcohol abuse, alcoholic liver disease and AF, and less MI and CHF, though there is an increased risk of CHF shortly after alcohol sales are liberalized.

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.This study developed models and assessed independent predictors of LV recovery to35% and ≥50% after 90-day follow-up in patients presenting with acute MI and severe LV dysfunction.Our multicenter prospective observational study enrolled participants with ejection fraction (EF) of ≤35% at the time of MI (n = 231). Predictors for EF recovery to35% and ≥50% were identified after multivariate modeling and validated in a separate cohort (n = 236).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 to35% 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 to35% and ≥50%, respectively, whereas profiles with the highest point scores predicted an 87% and 49% probability of EF recovery to35% and ≥50%, respectively.In patients with severe systolic dysfunction following acute MI with an EF ≤35%, 57% had EF recovery to35%. A model using clinical variables present at the time of MI can help predict EF recovery.

Pragmatic research that compares interventions to improve the organization and delivery of health care may overlap, in both goals and methods, with quality improvement activities. When activities have attributes of both research and quality improvement, confusion often arises about what ethical oversight is, or should be, required. For routine quality improvement, in which the delivery of health care is modified in minor ways that create only minimal risks, oversight by local clinical or administrative leaders utilizing institutional policies may be sufficient. However, additional consideration should be given to activities that go beyond routine, local quality improvement to first determine whether such non-routine activities constitute research or quality improvement and, in either case, to ensure that independent oversight will occur. This should promote rigor, transparency, and protection of patients’ and clinicians’ rights, well-being, and privacy in all such activities. Specifically, we recommend that (1) health care organizations should have systematic policies and processes for designating activities as routine quality improvement, non-routine quality improvement, or quality improvement research and determining what oversight each will receive. (2) Health care organizations should have formal and explicit oversight processes for non-routine quality improvement activities that may include input from institutional quality improvement experts, health services researchers, administrators, clinicians, patient representatives, and those experienced in the ethics review of health care activities. (3) Quality improvement research requires review by an institutional review board; for such review to be effective, institutional review boards should develop particular expertise in assessing quality improvement research. (4) Stakeholders should be included in the review of non-routine quality improvement and quality improvement–related research proposals. Only by doing so will we optimally leverage both pragmatic research on health care delivery and local implementation through quality improvement as complementary activities for improving health.

There are situations in which the requirement to obtain conventional written informed consent can impose significant or even insurmountable barriers to conducting pragmatic clinical research, including some comparative effectiveness studies and cluster-randomized trials. Although certain federal regulations governing research in the United States (45 CFR 46) define circumstances in which any of the required elements may be waived, the same standards apply regardless of whether any single element is to be waived or whether consent is to be waived in its entirety. Using the same threshold for a partial or complete waiver limits the options available to institutional review boards as they seek to optimize a consent process. In this article, we argue that new standards are necessary in order to enable important pragmatic clinical research while at the same time protecting patients’ rights and interests.

Background It is unclear whether antihypertensive treatment can restore cardiovascular disease risk to the risk level of persons with ideal blood pressure ( BP ) levels. Methods and Results Data from the Multi‐Ethnic Study of Atherosclerosis ( MESA ) and the Coronary Artery Risk Development in Young Adults ( CARDIA ) study were analyzed. Outcomes were compared among participants without or with antihypertensive treatment at 3 BP levels: BP 120 to 139 mm Hg or diastolic BP 80 to 89 mm Hg (120 to 129/≤80 mm Hg for participants with diabetes), and systolic BP ≥140 or diastolic BP ≥90 mm Hg (systolic BP ≥130 or diastolic BP ≥80 mm Hg for participants with diabetes). Among MESA participants aged ≥50 years at baseline, those with BP 2 , prevalence of coronary calcium score >100, and twice the incident cardiovascular disease rate over 9.5 years of follow‐up than those with BP CARDIA at year 25, persons with BP BP and higher risk of end‐organ damage and subclinical atherosclerosis than those with BP 3000 mm Hg–years in 25 years), the increase in left ventricular mass index accelerated. Conclusions The data suggest that based on the current approach, antihypertensive treatment cannot restore cardiovascular disease risk to ideal levels. Emphasis should be placed on primordial prevention of BP increases to further reduce cardiovascular disease morbidity and mortality.

Background— Hemoglobin A1C (HbA1C) is associated with increased risk of cardiovascular events, but its use for prediction of cardiovascular disease (CVD) events in combination with conventional risk factors has not been well defined. Methods and Results— To understand the effect of HbA1C on CVD risk in the context of other CVD risk factors, we analyzed HbA1C and other CVD risk factor measurements in 2000 individuals aged 40 to 79 years without pre-existing diabetes mellitus or CVD from the 2011 to 2012 National Health and Nutrition Examination Surveys survey. The resulting regression model was used to predict the HbA1C distribution based on individual patient characteristics. We then calculated post-test 10-year atherosclerotic CVD risk incorporating the actual versus predicted HbA1C, according to established methods, for a set of example scenarios. Age, sex, race/ethnicity, and traditional cardiovascular risk factors were significant predictors of HbA1C in our model, with the expected HbA1C distribution being significantly higher in non-Hispanic black, non-Hispanic Asian, and Hispanic individuals than that in non-Hispanic white/other individuals. Incorporating the expected HbA1C distribution into pretest atherosclerotic CVD risk has a modest effect on post-test atherosclerotic CVD risk. In the patient examples, we assessed that having an HbA1C of Conclusions— HbA1C has modest effects on predicted atherosclerotic CVD risk when considered in the context of conventional risk factors.

OBJECTIVE To evaluate lactation duration in relation to subsequent atherosclerosis in women during midlife. METHODS The Coronary Artery Risk Development in Young Adults study is a multicenter prospective cohort that enrolled 2,787 women in 1985-1986 (ages 18-30 years, 52% black, 48% white), of whom 2,014 (72%) attended the 20-year follow-up examination in 2005-2006. We selected 846 women (46% black) without heart disease or diabetes at baseline who delivered one or more times after the baseline evaluation, had cardiometabolic risk factors measured at baseline, and had maximum common carotid intima-media thickness (mm) measured at the 20-year follow-up examination in 2005-2006. Lactation duration was summed across all postbaseline births for each woman and (n, women) categorized as: 0 to less than 1 month (n=262), 1 to less than 6 months (n=210), 6 to less than 10 months (n=169), and 10 months or greater (n=205). Multiple linear regression models estimated mean common carotid intima-media thickness (95% confidence interval) and mean differences among lactation duration groups compared with the 0 to less than 1-month group adjusted for prepregnancy obesity, cardiometabolic status, parity, and other risk factors. RESULTS Lactation duration had a graded inverse association with common carotid intima-media thickness; mean differences between 10 months or greater compared with 0 to less than 1 month ranged from -0.062 mm for unadjusted models (P trend

BackgroundEvidence to guide primary prevention in adults aged 75 years or older is limited.ObjectiveTo project the population impact and cost-effectiveness of statin therapy in adults aged 75 years or older.DesignForecasting study using the Cardiovascular Disease Policy Model, a Markov model.Data sourcesTrial, cohort, and nationally representative data sources.Target populationU.S. adults aged 75 to 94 years.Time horizon10 years.PerspectiveHealth care system.InterventionStatins for primary prevention based on low-density lipoprotein cholesterol threshold of 4.91 mmol/L (190 mg/dL), 4.14 mmol/L (160 mg/dL), or 3.36 mmol/L (130 mg/dL); presence of diabetes; or 10-year risk score of at least 7.5%.Outcome measuresMyocardial infarction (MI), coronary heart disease (CHD) death, disability-adjusted life-years, and costs.Results of base-case analysisAll adults aged 75 years or older in the National Health and Nutrition Examination Survey have a 10-year risk score greater than 7.5%. If statins had no effect on functional limitation or cognitive impairment, all primary prevention strategies would prevent MIs and CHD deaths and be cost-effective. Treatment of all adults aged 75 to 94 years would result in 8 million additional users and prevent 105000 (4.3%) incident MIs and 68000 (2.3%) CHD deaths at an incremental cost per disability-adjusted life-year of $25200.Results of sensitivity analysisAn increased relative risk for functional limitation or mild cognitive impairment of 1.10 to 1.29 could offset the cardiovascular benefits.LimitationLimited trial evidence targeting primary prevention in adults aged 75 years or older.ConclusionAt effectiveness similar to that in trials, statins are projected to be cost-effective for primary prevention; however, even a small increase in geriatric-specific adverse effects could offset the cardiovascular benefit. Improved data on the potential benefits and harms of statins are needed to inform decision making.Primary funding sourceAmerican Heart Association Western States Affiliate, National Institute on Aging, and the National Institute for Diabetes on Digestive and Kidney Diseases.

Author(s): Phillips, Kathryn A; Ladabaum, Uri; Pletcher, Mark J; Marshall, Deborah A; Douglas, Michael P

Background: Moderate consumption of alcohol may provide protection against myocardial infarction and mortality, but also likely increases blood pressure and incidence of atrial fibrillation. Despite the absence of rigorous controlled trials on the actual cardiovascular benefits of alcohol, the lay press frequently portrays alcohol as “heart healthy” (HH). No study to date has described individuals’ perceptions regarding the health effects of alcohol, how they gained this perception, nor how that perception may influence behavior. Methods: We performed a cross-sectional analysis of data obtained between March 8, 2013 to September 29, 2014 from consecutive participants enrolled in the Health eHeart Study, a prospective, internet-based cohort study. The characteristics of participants that reported alcohol as HH were determined. Results: A total of 5,417 participants answered questions regarding their perception of alcohol. Thirty percent (n=1,707) viewed alcohol as HH, 39% (n=2,157) viewed it as bad for the heart, and 31% (n=1,718) were unsure. Of those reporting alcohol as HH, 78% cited lay press as a source of their knowledge, 14% cited their doctor, and 92% reported that red wine exclusively was HH. In adjusted analyses, older age, higher education, higher income, and United States residence were associated with a perception of alcohol as HH (Figure). Those with a history of heart failure (HF) were significantly less likely to cite alcohol as HH. Compared to those who did not report alcohol as HH, those who perceived alcohol as HH consumed more alcohol (median 5 drinks per week, IQR 2-8 vs. median 3 drinks, IQR 1-7, p=0.001; adjusted: 10% more alcohol per week, 95% CI 1-20% more, p=0.02). Conclusions: Among more than 5,000 consecutive Health eHeart participants, approximately one third believe alcohol is HH and one third believes it is not. Those who believe alcohol is HH were of higher socioeconomic status, more likely to be American, less likely to have HF, and reported drinking more alcohol.

Background— The 6-minute walk test (6MWT) independently predicts congestive heart failure severity, death, and heart failure hospitalizations, but must be administered in clinic by qualified staff on a premeasured course. As part of the Health eHeart Study, we sought to develop and validate a self-administered 6MWT mobile application (SA-6MWTapp) for independent use at home by patients. Methods and Results— We performed a validation study of an SA-6MWTapp in 103 participants. In phase 1 (n=52), we developed a distance-estimation algorithm for the SA-6MWTapp by comparing step counts from an Actigraph and measured distance on a premeasured 6MWT course with step counts and estimated distance obtained simultaneously from our SA-6MWTapp (best estimation algorithm, r=0.89 [95% confidence interval 0.78–0.99]). In phase 2, 32 participants (including those with congestive heart failure and pulmonary hypertension) used the SA-6MWTapp independently in clinic, and the distance estimated by the SA-6MWTapp was compared with the measured distance (r=0.83 [95% confidence interval 0.79–0.92]). In phase 3, 19 patients with congestive heart failure and pulmonary hypertension consecutively enrolled from clinic performed 3.2±1 SA-6MWTapp tests per week at home over 2 weeks. Distances estimated from the SA-6MWTapp during home 6MWTs were highly repeatable (coefficient of variation =4.6%) and correlated with in-clinic–measured distance (r=0.88 [95% confidence interval 0.87–0.89]). Usability surveys performed during the second (in-clinic) and third (at-home) phases demonstrated that the SA-6MWTapp was simple and easy to use independently. Conclusions— An SA-6MWTapp is easy to use and yields accurate repeatable measurements in the clinic and at home.

New health technologies are often portrayed in the media as being low-cost innovations that will save health care costs. In the case of genomic sequencing – high-speed analysis of multiple genes in parallel fashion – there has been a great deal of media attention about the falling cost of sequencing, referred to as the “$1000 Genome” – with the implication that the full cost of testing is actually $1000. Genomic sequencing (herein called “sequencing”) – is entering clinical care even though there are ongoing challenges of accuracy and reporting.(1, 2) We examine how the full benefits and costs of sequencing will vary widely depending on how the technology is used – emphasizing that the net cost of sequencing will never simply be the cost of testing itself, even though sequencing may provide benefits in many scenarios. As providers and decisionmakers consider when sequencing might be useful clinically, we suggest a framework for evaluating sequencing’s full benefits and costs so that the focus on the “$1000 price tag” for the sequencing technology per se does not obscure the complex decisions to be made about its effective and efficient use.(3) We also provide simulations of the possible economic impact of sequencing using a case study. (Note: We use the term “sequencing” throughout as a simplifying term but discuss how the term has various definitions depending on the context and use.)