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Objective: Aspirin has been used for primary prevention of atherosclerotic cardiovascular disease (ASCVD) for decades, but this indication has become controversial with recent trial data. The 2022 US Preventive Services Task Force (USPSTF) provided a recommendation to consider aspirin use for primary prevention in adults 40–59 years with a 10-year ASCVD risk ≥10 % and not at increased risk of bleeding, yet population estimates for the impact of this recommendation are unknown. The objective of this study is to determine the prevalence and demographics of the US population who meet eligibility criteria for aspirin under the new 2022 USPSTF guidelines. Methods: This is a serial cross-sectional study using data from the 2011-March 2020 National Health and Nutrition Examination Survey (NHANES) database. Individuals aged 40–59 years without a self-reported history of ASCVD were included. 10-year estimated ASCVD risk ≥10 % as calculated by the Pooled Cohort Equations (PCE) and increased bleeding risk determined using variables adapted from USPSTF guidelines were further applied as inclusion and exclusion criteria, respectively. The weighted frequencies of US adults aged 40–59 years qualifying for primary prevention aspirin, subgrouped by gender, age, and race/ethnicity, were calculated. Results: Among 72,840,734 US individuals aged 40–59 years, 7.2 million (10 %) are eligible for consideration of primary prevention aspirin by PCE criteria. Of these, approximately 30 % would be potentially excluded based on increased bleeding risks, resulting in a net eligible cohort of 5 million. This represents 7 % of US adults aged 40–59 years and only 2.6 % of adults ≥18 years. Men, age 50–59 years, and Black race have higher proportions meeting aspirin use eligibility. Conclusions: The overall prevalence of US individuals who qualify for aspirin for primary prevention under the 2022 USPSTF guidelines is modest, with larger proportional eligibility among men, older age, and Black individuals.

Background High‐density lipoprotein (HDL) particle concentration likely outperforms HDL cholesterol in predicting atherosclerotic cardiovascular events. Whether size‐based HDL subspecies explain the atheroprotective associations of HDL particle concentration remains unknown. Our objective was to assess whether levels of specific size‐based HDL subspecies associate with atherosclerotic cardiovascular disease in a multiethnic pooled cohort and improve risk prediction beyond traditional atherosclerotic cardiovascular disease risk factors. Methods and Results Seven HDL size‐based subspecies were quantified by nuclear magnetic resonance (LP4 algorithm; H1=smallest; H7=largest) among participants without prior atherosclerotic cardiovascular disease in ARIC (Atherosclerosis Risk in Communities), MESA (Multi‐Ethnic Study of Atherosclerosis), PREVEND (Prevention of Renal and Vascular Endstage Disease), and DHS (Dallas Heart Study) cohorts (n=15 371 people). Multivariable Cox proportional hazards models were used to evaluate the association between HDL subspecies and incident myocardial infarction (MI) or ischemic stroke at follow‐up (average 8–10 years) adjusting for HDL cholesterol and risk factors. Improvement in risk prediction was assessed via discrimination and reclassification analysis. Within the pooled cohort (median age 57 years; female 54%; Black 22%) higher H1 (small) and H4 (medium) concentrations were inversely associated with incident MI (hazard ratio [HR]/SD, H1 0.88 [95% CI, 0.81–0.94]; H4 0.89 [95% CI, 0.82–0.97]). H4 but not H1 improved risk prediction indices for incident MI. Increasing H2 and H4 were inversely associated with improved risk prediction indices for composite end point of stroke, MI, and cardiovascular death (HR/SD, H2 0.94 [95% CI, 0.88–0.99]; H4 0.91 [95% CI, 0.85–0.98]). Levels of the large subspecies (H6 and H7) were not associated with any vascular end point. Conclusions Two of 7 HDL size‐based subspecies modestly improved risk prediction for MI and composite vascular end points in a large multiethnic pooled cohort. These findings support assessment of precise HDL subspecies for future studies regarding clinical utility.

Therapeutic Area: ASCVD/CVD Risk Assessment Background: Low socioeconomic status (SES) is associated with atherosclerotic cardiovascular disease (ASCVD) and possible underestimation of risk by pooled cohort equations (PCE). Whether coronary artery calcium (CAC) scores can improve risk discrimination in low SES populations is unknown. Methods: Multi-Ethnic Study of Atherosclerosis (MESA) and Dallas Heart Study (DHS) participants free of ASCVD and with CAC scans were evaluated. Low SES was defined as annual household income $30,000) or educational attainment HS). The relationships between SES, CAC scores (0, 1-99, ≥100), and ASCVD events (fatal/non-fatal MI or stroke) were assessed before/after ASCVD risk factor adjustment (Table). The incremental predictive value of CAC across SES groups was assessed using c-statistics and categorical net reclassification improvement (NRI) ($30K comprised 19.1%, 18.4%, and 62.5%, and 18.2%, 22.4%, and 59.4% of the study populations, respectively. Individuals with low SES by income ($30K) [HRadj 1.38 (95% CI 1.14-1.54) MESA; HRadj 2.52 (1.65-3.85) DHS]. Higher CAC scores were associated with greater 10-year ASCVD risk in each SES category, but the low SES group had the greatest ASCVD risk with CAC=0 (4.9% MESA; 4.3% DHS). CAC scores were independently associated with ASCVD risk among low SES individuals in MESA but not in DHS [CAC>0 vs. 0 HRadj 2.38 (1.64-3.45) MESA; HRadj 1.09 (0.43-2.76) DHS]. Overall, the discriminative ability of CAC for ASCVD was smallest in low SES individuals (c-statistics 0.643 vs. 0.685, 0.711 MESA; 0.680 vs. 0.790, 0.806 DHS) (Table). The addition of CAC to PCE for low SES individuals yielded the smallest incremental improvement in c-statistic and NRI. Defining SES by education yielded similar results. Conclusions: Individuals with low SES have significantly higher ASCVD risk. CAC scores may predict this risk, but have lower ASCVD risk discrimination in this group, and CAC=0 provides less reassurance compared to those at higher SES. These results can assist in determining applications of CAC scanning in those with low SES.

Therapeutic Area: CVD Prevention – Primary and Secondary Background: Aspirin for the primary prevention of cardiovascular disease (CVD) remains controversial. The 2022 US Preventive Services Task Force (USPSTF) guidelines give a grade C recommendation to consider aspirin use for primary prevention in adults aged 40-59 years with a 10-year ASCVD risk ≥10% and not at increased risk of bleeding. We sought to determine the prevalence and demographics of the US adult population who meet eligibility criteria under these guidelines. Methods: Adults from the 2011-2018 National Health and Nutrition Examination Survey (NHANES) database aged ≥18 years without a self-reported history of CVD and with a 10-year ASCVD risk ≥10% calculated by the Pooled Cohort Equations were included. Increased bleeding risk variables were selected per the USPSTF modeling criteria and adapted to available NHANES variables, including congestive heart failure, atrial fibrillation, chronic or diabetic kidney disease, peptic ulcer disease, bleeding history, thrombocytopenia, and use of anticoagulation, corticosteroids, selective serotonin reuptake inhibitors, NSAID drugs, or other antiplatelet agents. The weighted frequencies of US adults aged 40-59 and ≥18 years who qualify for primary prevention aspirin were calculated. Results: The study sample included 6730 individuals aged 40-59 years, representing 80 million people in the US population. A total of 7.8 million individuals in this age group are eligible for consideration of aspirin use for primary prevention, with approximately 30% meeting criteria for increased bleeding risk. This results in a net eligible cohort of 5.4 million individuals, representing 6.8% of adults aged 40-59 years. Male sex, age 50-59 years, and Black race have higher proportions meeting aspirin use eligibility and increased bleeding risk. Notably, only 2.1% of women in this age group are aspirin eligible. Among the entire US adult population ≥18 years, 2.5% are eligible under these guidelines. Conclusions: The prevalence of US individuals who qualify for aspirin use for the primary prevention of CVD under the 2022 USPSTF guidelines is small, with larger proportional eligibility among men, older age, and Black individuals. These findings suggest that the clinical application of aspirin for primary prevention in the modern era using traditional eligibility criteria under USPSTF recommendations remains limited.

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10–25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease.The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.

Objective: Inflammatory markers are associated with cardiovascular disease (CVD); however, the ability to specifically predict myocardial infarction (MI) as well as ischemic stroke remains unknown. There has not been a direct comparison of the associations between GlycA and hsCRP and MI and ischemic stroke in a multi-ethnic pooled cohort. Methods: Multi-center, multi-ethnic, population-based community prospective pooled cohort of the Dallas Heart Study (DHS) and Multi-Ethnic Study of Atherosclerosis (MESA). 9,785 participants without baseline CVD enrolled with median follow-up of 13.4 years. Fatal/nonfatal MI and fatal/nonfatal ischemic stroke were assessed separately and then combined. Results: GlycA was moderately associated with hsCRP (R=0.58 in DHS and R=0.55 in MESA). In adjusted Cox proportional hazards models with competing risk adjusted for both inflammatory markers, GlycA was directly associated with MI (HR Q4 vs. Q1 1.90, 95% CI 1.39 to 2.58), whereas hsCRP was not (HR Q4 vs. Q1 0.92, 95% CI 0.70 to 1.21). Conversely, hsCRP was directly associated with ischemic stroke (HR Q4 vs. Q1 1.73, 95% CI 1.15 to 2.59), but GlycA was not (HR Q4 vs. Q1 1.21, 95% CI 0.77 to 1.90). GlycA improved net reclassification for MI and hsCRP did so for ischemic stroke. Conclusions: Although both GlycA and hsCRP were associated with incident CVD, GlycA more strongly predicted incident MI, and hsCRP more strongly predicted ischemic stroke.

Background Pregnancy is a major life event unique to women and leads to significant hemodynamic, hormonal, and metabolic changes. The purpose of this study was to use the DHS (Dallas Heart Study), a multiethnic population‐based cohort study of Dallas county adults, to evaluate the association between number of live births and cardiac magnetic resonance imaging and ECG parameters later in life. Methods and Results Women were included if they had data on self‐reported live births and ECG or cardiac magnetic resonance imaging measurements. The 3014 women were stratified by number of live births: 0, 1, 2, 3, 4, and ≥5. Higher number of live births was associated with larger left ventricular (LV) end‐diastolic volume (β, 1.31±0.41; P

Background The value of coronary artery calcium (CAC) in the allocation of PCSK9i (proprotein convertase subtilisin/kexin type 9 inhibitors) among individuals without clinically evident atherosclerotic cardiovascular disease (ASCVD) is unknown for indications that do not require confirmed familial hypercholesterolemia. We aimed to assess the ability of CAC to stratify ASCVD risk under 3 non–familial hypercholesterolemia PCSK9i allocation paradigms. Methods and Results We included participants without clinically evident ASCVD from MESA (Multi‐Ethnic Study of Atherosclerosis), CARDIA (Coronary Artery Risk Development in Young Adults) study, DHS (Dallas Heart Study), and HNR (Heinz Nixdorf Recall) study. Three PCSK9i eligibility scenarios were defined: a broad scenario informed only by high low‐density lipoprotein cholesterol levels (N=567), a restrictive one combining higher low‐density lipoprotein cholesterol levels and presence of ≥2 additional risk factors (N=127), and a high‐risk scenario where individuals with subclinical organ damage or high estimated risk would be treated to achieve low‐density lipoprotein cholesterol

This review examines key studies published in 2021 that are related to primary prevention of atherosclerotic cardiovascular disease (ASCVD). Major randomized clinical trials (RCTs) concerning traditional risk factors or ASCVD events, meta‐analyses, and key observational studies related to primary prevention of ASCVD were considered. The review includes interventions for weight loss, cardiometabolic and renal disease, blood pressure control, diet, and the occurrence of cardiovascular disease events. A few studies considered both primary and secondary prevention populations. The review is not exhaustive. We did not include studies that focused on heart failure or clinical presentations that may be difficult to classify, such as acute or chronic ischemic cardiovascular disease without myocardial infarction. Our purpose was to highlight recent research that will help the reader stay abreast of the changing field of cardiovascular prevention.

NASA has recently completed several long-duration missions to the International Space Station and is solidifying plans to return to the Moon, with an eye toward Mars and beyond. As NASA pushes the boundaries of human space exploration, the hazards of spaceflight, including space radiation, levy an increasing burden on astronaut health and performance. The cardiovascular system may be especially vulnerable due to the combined impacts of space radiation exposure, lack of gravity, and other spaceflight hazards. On Earth, the risk for cardiovascular disease (CVD) following moderate to high radiation doses is well-established from clinical, environmental, and occupational exposures (largely from gamma- and x-rays). Less is known about CVD risks associated with high-energy charged ions found in space and increasingly used in radiotherapy applications on Earth, making this a critical area of investigation for occupational radiation protection. Assessing CVD risk is complicated by its multifactorial nature, where an individual's risk is strongly influenced by factors such as family history, blood pressure, and lipid profiles. These known risk factors provide the basis for development of a variety of clinical risk prediction models (CPMs) that inform the likelihood of medical outcomes over a defined period. These tools improve clinical decision-making, personalize care, and support primary prevention of CVD. They may also be useful for individualizing risk estimates for CVD following radiation exposure both in the clinic and in space. In this review, we summarize unique aspects of radiation risk assessment for astronauts, and we evaluate the most widely used CVD CPMs for their use in NASA radiation risk assessment applications. We describe a comprehensive dual-use risk assessment framework that supports both clinical care and operational management of space radiation health risks using quantitative metrics. This approach is a first step in using personalized medicine for radiation risk assessment to support safe and productive spaceflight and long-term quality of life for NASA astronauts.

Background: The U.S. Centers for Disease Control and Prevention (CDC) recognizes that older adults and individuals with certain medical conditions are at increased risk of severe COVID-19 infection. Understanding the proportion of the population at risk of severe infection, including among those with heart disease, could assist current vaccine strategy efforts. Methods: Using data from the 2015-2018 National Health and Nutrition Examination Survey (NHANES), we estimated the weighted prevalence of any of eight of eleven increased-risk conditions (including age ≥65) in U.S. adults aged ≥18 (N = 10,581) and extrapolated these results to a population of 233.8 million U.S. adults ≥18, and subgroups from the overall population defined by race/ethnicity, education, income and history of heart disease. Results: An estimated 176.1 million individuals representing 75.4% of U.S. adults had at least one increased-risk condition, 40.3% ≥2 and, 18.5% ≥3 conditions. Approximately 129 million adults aged 0.05) and Hispanics in the younger population (70.8 vs 68.4%) were estimated to be at increased-risk. Conversely, a greater proportion of individuals with lower education and income levels were estimated to be at increased-risk both in the overall and younger population. In addition, an estimated 6.2 million individuals (14.5%) had heart disease. Among these, virtually all had at least one additional CDC risk factor (97.9%) and most had ≥2 or ≥3 risk factors (83.8% and 58.5%, respectively). Conclusions: As vaccination strategies are being explored, these results demonstrate that >75% of adults in the U.S. would be considered at increased-risk for severe COVID-19 infection by CDC criteria. Risk factor prevalence alone may not adequately capture the totality of risk, particularly among Black and Hispanic racial/ethnic groups and those with heart disease.

Background: The Dutch cascade screening model for FH was the most successful of such programs in the world. It remains unclear whether aspects of the Dutch model (i.e. direct engagement with FH probands and relatives outside usual healthcare settings) are feasible in the US. This is especially important since prior attempts at cascade screening in the US have had very low screening rates (

Knowing the patient's current cardiovascular disease (CVD) status, as well as the patient's current and future CVD risk, helps the clinician make more informed patient-centered management recommendations towards the goal of preventing future CVD events. Imaging tests that can assist the clinician with the diagnosis and prognosis of CVD include imaging studies of the heart and vascular system, as well as imaging studies of other body organs applicable to CVD risk. The American Society for Preventive Cardiology (ASPC) has published “Ten Things to Know About Ten Cardiovascular Disease Risk Factors.” Similarly, this “ASPC Top Ten Imaging” summarizes ten things to know about ten imaging studies related to assessing CVD and CVD risk, listed in tabular form. The ten imaging studies herein include: (1) coronary artery calcium imaging (CAC), (2) coronary computed tomography angiography (CCTA), (3) cardiac ultrasound (echocardiography), (4) nuclear myocardial perfusion imaging (MPI), (5) cardiac magnetic resonance (CMR), (6) cardiac catheterization [with or without intravascular ultrasound (IVUS) or coronary optical coherence tomography (OCT)], (7) dual x-ray absorptiometry (DXA) body composition, (8) hepatic imaging [ultrasound of liver, vibration-controlled transient elastography (VCTE), CT, MRI proton density fat fraction (PDFF), magnetic resonance spectroscopy (MRS)], (9) peripheral artery / endothelial function imaging (e.g., carotid ultrasound, peripheral doppler imaging, ultrasound flow-mediated dilation, other tests of endothelial function and peripheral vascular imaging) and (10) images of other body organs applicable to preventive cardiology (brain, kidney, ovary). Many cardiologists perform cardiovascular-related imaging. Many non-cardiologists perform applicable non-cardiovascular imaging. Cardiologists and non-cardiologists alike may benefit from a working knowledge of imaging studies applicable to the diagnosis and prognosis of CVD and CVD risk – both important in preventive cardiology.

Abstract Background Though the proportion of female Internal Medicine (IM) residents and faculty has increased, there is minimal large scale modern data comparing resident performance by gender. This study sought to examine the effects of resident and faculty gender on resident evaluations. Methods Retrospective observational study over 5 years in a single IM program. IM certifying examination pass rates were obtained from the American Board of IM. Results Four hundred eighty-eight residents (195 women, 293 men), evaluated by 430 attending physicians (163 women, 270 men) were included. Twelve thousand six hundred eighty-one evaluations between 2007 and 2012 were analyzed. Female residents scored higher in two domains (Medical Interviewing, and Interpersonal and Communication Skills) (p

Introduction: Significant heterogeneity in cardiovascular disease (CVD) risk and healthcare resource allocation has been demonstrated in the United States, but optimal methods to capture heterogeneity in county-level characteristics that contribute to CVD mortality differences are unclear. We evaluated the feasibility of unsupervised machine learning (ML)-based phenomapping in identifying subgroups of county-level social and demographic risk factors with differential CVD outcomes. Methods: We performed a cross-sectional study using county-level data from 2008 to 2018 from the Centers for Disease Control (CDC) WONDER platform and the 2020 Robert Wood Johnson County Health Rankings program. Unsupervised clustering was performed on 46 facets of population characteristics spanning the demographic, health behaviors, socioeconomic, and healthcare access domains. Spatial autocorrelation was assessed using the Moran’s I test, and temporal trends in age-adjusted CVD outcomes were evaluated using linear mixed effect models and least square means. Results: Among 2676 counties, 4 county-level phenogroups were identified (Moran’s I p-value

Background Current strategies for cardiovascular disease (CVD) risk assessment focus on 10‐year or longer timeframes. Shorter‐term CVD risk is also clinically relevant, particularly for high‐risk occupations, but is under‐investigated. Methods and Results We pooled data from participants in the ARIC (Atherosclerosis Risk in Communities study), MESA (Multi‐Ethnic Study of Atherosclerosis), and DHS (Dallas Heart Study), free from CVD at baseline (N=16 581). Measurements included N‐terminal pro‐B‐type natriuretic peptide (>100 pg/mL prospectively defined as abnormal); high‐sensitivity cardiac troponin T (abnormal >5 ng/L); high‐sensitivity C‐reactive protein (abnormal >3 mg/L); left ventricular hypertrophy by ECG (abnormal if present); carotid intima‐media thickness, and plaque (abnormal >75th percentile for age and sex or presence of plaque); and coronary artery calcium (abnormal >10 Agatston U). Each abnormal test result except left ventricular hypertrophy by ECG was independently associated with increased 3‐year risk of global CVD (myocardial infarction, stroke, coronary revascularization, incident heart failure, or atrial fibrillation), even after adjustment for traditional CVD risk factors and the other test results. When a simple integer score counting the number of abnormal tests was used, 3‐year multivariable‐adjusted global CVD risk was increased among participants with integer scores of 1, 2, 3, and 4, by ≈2‐, 3‐, 4.5‐ and 8‐fold, respectively, when compared with those with a score of 0. Qualitatively similar results were obtained for atherosclerotic CVD (fatal or non‐fatal myocardial infarction or stroke). Conclusions A strategy incorporating multiple biomarkers and atherosclerosis imaging improved assessment of 3‐year global and atherosclerotic CVD risk compared with a standard approach using traditional risk factors.

The coronavirus disease 2019 (COVID-19) pandemic has consumed our healthcare system, with immediate resource focus on the management of high numbers of critically ill patients. Those that fare poorly with COVID-19 infection more commonly have cardiovascular disease (CVD), hypertension and diabetes. There are also several other conditions that raise concern for the welfare of patients with and at high risk for CVD during this pandemic. Traditional ambulatory care is disrupted and many patients are delaying or deferring necessary care, including preventive care. New impediments to medication access and adherence have arisen. Social distancing measures can increase social isolation and alter physical activity and nutrition patterns. Virtually all facility based cardiac rehabilitation programs have temporarily closed. If not promptly addressed, these changes may result in delayed waves of vulnerable patients presenting for urgent and preventable CVD events.Here, we provide several recommendations to mitigate the adverse effects of these disruptions in outpatient care. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers should be continued in patients already taking these medications. Where possible, it is strongly preferred to continue visits via telehealth, and patients should be counselled about promptly reporting new symptoms. Barriers to medication access should be reviewed with patients at every contact, with implementation of strategies to ensure ongoing provision of medications. Team-based care should be leveraged to enhance the continuity of care and adherence to lifestyle recommendations. Patient encounters should include discussion of safe physical activity options and access to healthy food choices. Implementation of adaptive strategies for cardiac rehabilitation is recommended, including home based cardiac rehab, to ensure continuity of this essential service. While the practical implementation of these strategies will vary by local situation, there are a broad range of strategies available to ensure ongoing continuity of care and health preservation for those at higher risk of CVD during the COVID-19 pandemic.

Objectives: Patients with severe hyperlipidemia (low-density lipoprotein-cholesterol (LDL-C) ≥190 ​mg/dL) have a significantly increased risk of cardiovascular disease (CVD) and are more likely to have familial hypercholesterolemia (FH). We sought to determine how often health care providers recognize the implications of and adjust therapy for an LDL-C ≥190 ​mg/dL. Methods: We conducted a retrospective review of patients with an LDL-C measurement in the medical record of a large health care system between November 2015 and June 2016. Patients were restricted to those with LDL-C ≥190 ​mg/dL and without secondary causes of dyslipidemia, with sensitivity analyses for those with LDL-C ≥220 ​mg/dL. Results: Of 27,963 patients, 227 had LDL-C ≥190 ​mg/dL. Only 21% were on a statin at the time of LDL-C measurement. More than 90% had a follow-up clinic visit, but 41% had no change in treatment. FH was only included in the differential for 14%. The presence/absence of a family history of dyslipidemia, myocardial infarction, and premature CVD were documented in 26%, 29%, and 31%. Only 20.7% and 22.1% had documentation of the presence or absence of tendinous xanthomas or corneal arcus, respectively. Among those without prior specialist care (cardiologist or endocrinologist), only 13% were referred. These measures were only slightly better for those with LDL-C ≥220 ​mg/dL. Conclusion: In a large health care system, the possibility of FH was rarely acknowledged in those with residual LDL-C ≥190 ​mg/dL, few were referred to specialists, and therapeutic adjustments were suboptimal. Additional efforts are required to understand barriers to improving the evaluation and management of patients with LDL-C ≥190 ​mg/dL.

Background The incidence and clinical manifestations of cardiovascular disease (CVD) differ between blacks and whites. Biomarkers that reflect important pathophysiological pathways may provide a window to allow deeper understanding of racial differences in CVD. Methods and Results The study included 2635 white and black participants from the Dallas Heart Study who were free from existing CVD. Cross‐sectional associations between race and 32 biomarkers were evaluated using multivariable linear regression adjusting for age, traditional CVD risk factors, imaging measures of body composition, renal function, insulin resistance, left ventricular mass, and socioeconomic factors. In fully adjusted models, black women had higher lipoprotein(a), leptin, d‐dimer, osteoprotegerin, antinuclear antibody, homoarginine, suppression of tumorigenicity‐2, and urinary microalbumin, and lower adiponectin, soluble receptor for advanced glycation end products and N‐terminal pro‐B‐type natriuretic peptide versus white women. Black men had higher lipoprotein(a), leptin, d‐dimer, high‐sensitivity C‐reactive protein, antinuclear antibody, symmetrical dimethylarginine, homoarginine, high‐sensitivity cardiac troponin T, suppression of tumorigenicity‐2, and lower adiponectin, soluble receptor for advanced glycation end products, and N‐terminal pro‐B‐type natriuretic peptide versus white men. Adjustment for biomarkers that were associated with higher CVD risk, and that differed between blacks and whites, attenuated the risk for CVD events in black women (unadjusted hazard ratio 2.05, 95% CI 1.32, 3.17 and adjusted hazard ratio 1.15, 95% CI 0.69, 1.92) and black men (unadjusted hazard ratio 2.39, 95% CI 1.64, 3.46, and adjusted hazard ratio 1.21, 95% CI 0.76, 1.95). Conclusions Significant racial differences were seen in biomarkers reflecting lipids, adipokines, and biomarkers of endothelial function, inflammation, myocyte injury, and neurohormonal stress, which may contribute to racial differences in the development and complications of CVD.

BackgroundEvidence supporting nonstatin lipid‐lowering therapy in atherosclerotic cardiovascular disease risk reduction is variable. We aim to examine nonstatin utilization and expenditures in the United States between 2002 and 2013. Methods and ResultsWe used the Medical Expenditure Panel Survey database to estimate national trends in nonstatin use and cost (total and out‐of‐pocket, adjusted to 2013 US dollars using a gross domestic product deflator) among adults 40 years or older. Nonstatin users increased from 3 million (2.5%) in 2002‐2003 (20.1 million prescriptions) to 8 million (5.6%) in 2012‐2013 (45.8 million prescriptions). Among adults with atherosclerotic cardiovascular disease, nonstatin use increased from 7.5% in 2002‐2003 to 13.9% in 2012‐2013 after peaking at 20.3% in 2006‐2007. In 2012‐2013, 15.9% of high‐intensity statin users also used nonstatins, versus 9.7% of low/moderate‐intensity users and 3.6% of statin nonusers. Nonstatin use was significantly lower among women (odds ratio 0.80; 95% confidence interval 0.75‐0.86), racial/ethnic minorities (odds ratio 0.41; 95% confidence interval 0.36‐0.47), and the uninsured (odds ratio 0.47; 95% confidence interval 0.40‐0.56). Total nonstatin expenditures increased from $1.7 billion (out‐of‐pocket cost, $0.7 billion) in 2002‐2003 to $7.9 billion (out‐of‐pocket cost $1.6 billion) in 2012‐2013, as per‐user nonstatin expenditure increased from $550 to $992. Nonstatin expenditure as a proportion of all lipid‐lowering therapy expenditure increased 4‐fold from 8% to 32%. ConclusionsBetween 2002 and 2013, nonstatin use increased by 124%, resulting in a 364% increase in nonstatin‐associated expenditures.

Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples of European ancestry, rs16847548, was the most strongly associated in White (P = 0.005) and Black (P = 3.6 x 10(-5)) participants, with the same direction of effect in Hispanics (P = 0.17), and further showed a significant SNP x sex-interaction (P = 0.03). A second SNP, rs16856785, uncorrelated with rs16847548, was also associated with QT interval in Blacks (P = 0.01), with qualitatively similar results in Whites and Hispanics. In a previously genotyped cohort of 14,107 White individuals drawn from the combined Atherosclerotic Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) cohorts, we validated both the second locus at rs16856785 (P = 7.63 x 10(-8)), as well as the sex-interaction with rs16847548 (P = 8.68 x 10(-6)). These data extend the association of genetic variants in NOS1AP with QT interval to a Black population, with similar trends, though not statistically significant at P