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High-density lipoprotein (HDL) is commonly characterized by its cholesterol concentration (HDL-C) and inverse association with atherosclerotic cardiovascular disease.

Visceral and ectopic fat are key drivers of adverse cardiometabolic outcomes in obesity. We aimed to evaluate the effects of injectable liraglutide 3·0 mg daily on body fat distribution in adults with overweight or obesity without type 2 diabetes at high cardiovascular disease risk.

OBJECTIVE--To determine the association between circulating soluble receptor for advanced glycation end products (sRAGE) and coronary atherosclerosis. RESEARCH DESIGN AND METHODS--Using data from the Dallas Heart Study, a probability-based population [...]

IMPORTANCE: Higher coronary artery calcium (CAC) identifies individuals at increased atherosclerotic cardiovascular disease (ASCVD) risk. Whether it can also identify individuals likely to derive net benefit from aspirin therapy is unclear. OBJECTIVE: To examine the association between CAC, bleeding, and ASCVD and explore the net estimated effect of aspirin at different CAC thresholds. DESIGN, SETTING, AND PARTICIPANTS: Prospective population-based cohort study of Dallas Heart Study participants, free from ASCVD and not taking aspirin at baseline. Data were analyzed between February 1, 2020, and July 15, 2020. EXPOSURES: Coronary artery calcium score in the following categories: 0, 1-99, and 100 or higher. MAIN OUTCOMES AND MEASURES: Major bleeding and ASCVD events were identified from International Statistical Classification of Diseases and Related Health Problems, Ninth Revision codes. Meta-analysis–derived aspirin effect estimates were applied to observed ASCVD and bleeding rates to model the net effect of aspirin at different CAC thresholds. RESULTS: A total of 2191 participants (mean [SD], age 44 [9.1] years, 1247 women [57%], and 1039 black individuals [47%]) had 116 major bleeding and 123 ASCVD events over a median follow-up of 12.2 years. Higher CAC categories (CAC 1-99 and ≥100 vs CAC 0) were associated with both ASCVD and bleeding events (hazard ratio [HR], 1.6; 95% CI, 1.1-2.4; HR, 2.6; 95% CI, 1.5-4.3; HR, 4.8; 95% CI, 2.8-8.2; P < .001; HR, 5.3; 95% CI, 3.6-7.9; P < .001), but the association between CAC and bleeding was attenuated after multivariable adjustment. Applying meta-analysis estimates, irrespective of CAC, aspirin use was estimated to result in net harm in individuals at low (<5%) and intermediate (5%-20%) 10-year ASCVD risk and net benefit in those at high (≥20%) ASCVD risk. Among individuals at lower bleeding risk, a CAC score of at least 100 identified individuals who would experience net benefit, but only in those at borderline or higher (≥5%) 10-year ASCVD risk. In individuals at higher bleeding risk, there would be net harm from aspirin irrespective of CAC and ASCVD risk. CONCLUSIONS AND RELEVANCE: Higher CAC is associated with both ASCVD and bleeding events, with a stronger association with ASCVD. A high CAC score identifies individuals estimated to derive net benefit from primary prevention aspirin therapy from those who would not, but only in the setting of lower bleeding risk and estimated ASCVD risk that is not low.

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Supplemental Digital Content is available in the text.

IMPORTANCE: Familial hypercholesterolemia is an autosomal-dominant disorder that often causes premature coronary artery disease. Unfortunately, familial hypercholesterolemia remains largely undiagnosed. OBJECTIVE: To estimate the prevalence of familial hypercholesterolemia in a population of blood donors. DESIGN: This analysis of deidentified data from blood donors 16 years and older who donated to Carter BloodCare, one of the largest independent blood programs in the United States, between January 2002 and December 2016. Carter BloodCare, which serves a population of about 8 million in Texas, routinely measures total nonfasting serum cholesterol levels as part of a donor health screening program. Data analysis occurred from October 2017 to March 2019. EXPOSURE: Blood donation. MAIN OUTCOMES AND MEASURES: Familial hypercholesterolemia was defined using the Make Early Diagnosis to Prevent Early Death general population criteria, with total nonfasting serum cholesterol thresholds of 270, 290, 340, and 360 mg/dL for donors younger than 20 years, 20 to 29 years, 30 to 39 years, and 40 years or older, respectively (to convert cholesterol values to mmol/L, multiply by 0.0259). For repeated donors, the maximum observed total cholesterol level was used for analyses. RESULTS: The study included 1 178 102 individual donors with a total of 3 038 420 blood donations. Of all individual donors (median total cholesterol level, 183 [interquartile range (IQR), 157-212] mg/dL; median age, 32 [IQR, 19-47] years; 619 583 [52.6%] women), a total of 3473 individuals (or 1 in every 339) met criteria for familial hypercholesterolemia. This group had a median (IQR) total cholesterol of 332 (297-377) mg/dL. Estimated prevalence was higher at younger ages (<30 years: 1:257) compared with older ages (≥30 years: 1:469; P < .001) and in men (1:327) compared with women (1:351; P = .03). Among 2219 repeated donors who met familial hypercholesterolemia criteria at least once, 3116 of 10 833 total donations (28.8%) met FH criteria. CONCLUSIONS AND RELEVANCE: The prevalence of familial hypercholesterolemia using the Make Early Diagnosis to Prevent Early Death criteria in a large cohort of blood donors was similar to the estimated prevalence of this disorder in the general population. The blood donor screening program could be a novel strategy to detect and notify individuals with potential familial hypercholesterolemia, particularly younger individuals in whom early detection and treatment is especially helpful, as well as guide cascade screening.

Bloodstream infections (BSIs) are common in patients with continuous-flow left ventricular assist devices (CF-LVADs). Whether CF-LVADs modulate the febrile response to BSIs is unknown. We retrospectively compared the febrile response to BSIs in patients with heart failure (HF) with CF-LVADs versus a control population of patients with HF receiving inotropic infusions. BSIs were adjudicated using the Centers for Disease Control and Prevention and the National Healthcare Safety Network criteria. Febrile status (temperature =38°C, 100.4 °F), temperature at presentation with BSI, and the highest temperature within 72?hours (Tmax) were collected. We observed 59 BSIs in LVAD patients and 45 BSIs in controls. LVAD patients were more likely to be afebrile and to have a lower temperature at presentation than control (88% vs 58%, p=0.002,?and 37°C ±0.7 vs 37.7°C ±1.0, p=0.0009, respectively). By 72?hours, the difference in afebrile status diminished (53% vs 44%, p=0.42), and the Tmax was similar between the LVAD and control groups (37.9°C±0.9 vs 38.2°C±0.8, respectively, p=0.10). In conclusion, at presentation with a BSI, the vast majority of CF-LVAD patients were afebrile, an event which occurred at a higher frequency when compared with patients with advanced HF on chronic inotropes via an indwelling venous catheter. These data alert clinicians to have a very low threshold to obtain blood cultures in CF-LVAD patients even in the absence of fever. Further study is needed to determine whether a delayed or diminished febrile response represents another pathophysiological consequence of CF-LVADs.

Wearable mobile health (mHealth) technologies offer approaches for targeting physical activity (PA) in resource-limited, community-based interventions. We sought to explore user characteristics of PA tracking, wearable technology among a community-based population within a health and needs assessment. In 2014-2015, we conducted the Washington, D.C., Cardiovascular Health and Needs Assessment in predominantly African-American churches among communities with higher obesity rates and lower household incomes. Participants received a mHealth PA monitor and wirelessly uploaded PA data weekly to church data collection hubs. Participants (n = 99) were 59 ± 12 years, 79% female, and 99% African-American, with a mean body mass index of 33 ± 7 kg/m2. Eighty-one percent of participants uploaded PA data to the hub and were termed "PA device users." Though PA device users were more likely to report lower household incomes, no differences existed between device users and non-users for device ownership or technology fluency. Findings suggest that mHealth systems with a wearable device and data collection hub may feasibly target PA in resource-limited communities.

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Supplemental Digital Content is available in the text.

•GlycA more strongly predicted incident MI.•hsCRP more strongly predicted incident ischemic stroke.•GlycA may detect other inflammatory risk not captured by hsCRP

Aims Higher parity has been associated with increased maternal risk of cardiovascular disease, but the mechanism is not well delineated. Whether the number of live births is associated with coronary and aortic subclinical atherosclerosis has not been fully evaluated.Methods and results Women from the Dallas Heart Study, a multiethnic population-based cohort of subjects aged 30–65 years, were included if they had data on self-reported live births and coronary artery calcium (CAC) measured by computed tomography or aortic wall thickness (AWT) by MRI. Coronary artery calcium was positive if >10 Agatston units, and aortic wall thickness if greater than the 75thpercentile reference point for age and gender. Among the 1644 women included in the study, the mean age was 45 years and 55% were Black. Sequential multivariable models were done adjusting for age, race, traditional cardiovascular risk factors, body mass index, income, education, hormone replacement therapy, oral contraceptives, and physical activity. Using women with 2–3 live births as the reference, those with four or more live births had an increased prevalence of elevated coronary artery calcium (odds ratio (OR) 2.2, 95% confidence interval (CI) 1.28–3.65) and aortic wall thickness (OR 1.6, 95% CI 1.04–2.41). Women with 0–1 live births also had increased coronary artery calcium (OR 1.9, 95% CI 1.16–3.03) and aortic wall thickness (OR 1.5, 95% CI 1.05–2.09) after multivariable adjustment.Conclusion The number of live births is associated with subclinical coronary and aortic atherosclerosis, with an apparent U-shaped relationship. Further studies are needed to confirm this association and explore the biological underpinnings of these findings.

The purpose of this study was to assess whether N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels differ according to race/ethnicity.

IMPORTANCE: Understanding the relationships between age-related changes in brain structure and cognitive function has been limited by inconsistent methods for assessing brain imaging, small sample sizes, and racially/ethnically homogeneous cohorts with biased selection based on risk factors. These limitations have prevented the generalizability of results from brain morphology studies. OBJECTIVE: To determine the association of 3.0-T structural brain magnetic resonance (MR) imaging measurements with cognitive function in the multiracial/multiethnic, population-based Dallas Heart Study. DESIGN, SETTING, AND PARTICIPANTS: Whole-brain, 2-dimensional, fluid-attenuated inversion recovery and 3-dimensional, magnetization-prepared, rapid acquisition with gradient echo MR imaging at 3.0 T was performed in 1645 Dallas Heart Study participants (mean [SD] age, 49.9 [10.5] years; age range, 19-85 years) who received both brain MR imaging and cognitive screening with the Montreal Cognitive Assessment between September 18, 2007, and December 28, 2009. Measurements were obtained for white matter hyperintensity volume, total brain volume, gray matter volume, white matter volume, cerebrospinal fluid volume, and hippocampal volume. Linear regression and a best predictive model were developed to determine the association of MR imaging biomarkers with the Montreal Cognitive Assessment total score and domain-specific questions. MAIN OUTCOMES AND MEASURES: High-resolution anatomical MR imaging was used to quantify brain volumes. Scores on the screening Montreal Cognitive Assessment were used for cognitive assessment in participants. RESULTS: After adjustment for demographic variables, total brain volume (P < .0001, standardized estimate [SE] = .1069), gray matter volume (P < .0001, SE = .1156), white matter volume (P = .008, SE = .0687), cerebrospinal fluid volume (P = .012, SE = −.0667), and hippocampal volume (P < .0001) were significantly associated with cognitive performance. A best predictive model identified gray matter volume (P < .001, SE = .0021), cerebrospinal fluid volume (P = .01, SE = .0024), and hippocampal volume (P = .004, SE = .1017) as 3 brain MR imaging biomarkers significantly associated with the Montreal Cognitive Assessment total score. Questions specific to the visuospatial domain were associated with the most brain MR imaging biomarkers (total brain volume, gray matter volume, white matter volume, cerebrospinal fluid volume, and hippocampal volume), while questions specific to the orientation domain were associated with the least brain MR imaging biomarkers (only hippocampal volume). CONCLUSIONS AND RELEVANCE: Brain MR imaging volumes, including total brain volume, gray matter volume, cerebrospinal fluid volume, and hippocampal volume, were independently associated with cognitive function and may be important early biomarkers of risk for cognitive insult in a young multiracial/multiethnic population. A best predictive model indicated that a combination of multiple neuroimaging biomarkers may be more effective than a single brain MR imaging volume measurement.

To determine the association between cardiorespiratory fitness and sedentary behavior, independent of exercise activity.

Fitness and traditional risk factors have well-known associations with cardiovascular disease (CVD) death in both short-term (10 years) and across the remaining lifespan. However, currently available short-term and long-term risk prediction tools do not incorporate measured fitness.

This study sought to compare the cross-sectional associations between fitness and echocardiographic measures of cardiac structure and function.

A noninvasive biomarker that could accurately diagnose acute rejection (AR) in heart transplant recipients could obviate the need for surveillance endomyocardial biopsies. We assessed the performance metrics of a novel high-sensitivity cardiac troponin I (cTnI) assay for this purpose.

This study sought to examine the frequency and hemodynamic correlates of shortness of breath when bending forward, a symptom we have termed “bendopnea.”

The relation of body fat distribution to left ventricular (LV) structure and function is poorly defined.

Although right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) are correlated in heart failure, in a sizeable minority of patients, the RAP and PCWP are not tightly coupled. The basis of this variability in the RAPPCWP ratio, and whether it conveys prognostic value, is not known.

Family history of coronary heart disease (CHD) has been well studied as an independent risk factor for CHD events in the short term (<10 years). However, data are sparse on the association between family history and risk for CHD across long-term follow-up.

Objectives Electron beam computed tomography (EBCT) for coronary artery calcification can potentially evaluate liver fat, another marker of cardiovascular risk. We compared quantitative estimates of hepatic steatosis measured by EBCT with those obtained by a well-validated, accurate-measure, magnetic resonance spectroscopy (1H MRS).Methods EBCT and 1H MRS were performed in 2159 subjects from the Dallas Heart Study. Forty subjects were randomly selected from each of 5 subgroups of liver fat percent by 1H MRS (n = 200). EBCT average liver attenuation (HU) was determined in a 1- to 2-cm circular region of interest over the liver lobes. Pearson correlation coefficients were calculated. Using a previously defined 1H MRS hepatic steatosis cut point (>5.5%), an optimized EBCT liver attenuation cut point was determined by receiver operating characteristic analysis.Results 1H MRS liver fat content and EBCT average right lobe liver attenuation were moderately negatively correlated (r= -0.64, P< 0.0001) in all subjects and in those with 1H MRS hepatic steatosis (r= -0.71, P< 0.0001). This correlation did not improve with attenuation correction of the EBCT data using a standard calcium phantom or statistical transformation. Using an optimized receiver operating characteristic EBCT cut point (64.5 HU), sensitivity was 78% and specificity was 72% for detecting 1H MRS hepatic steatosis, with a high false negative rate. Risk factors for hepatic steatosis (obesity, diabetes mellitus, insulin resistance, metabolic syndrome) were more strongly correlated with 1H MRS than EBCT liver fat measures.Conclusions Liver attenuation on EBCT acquired for coronary artery calcification screening correlates modestly with 1H MRS measures of liver fat content, with a high false negative rate.

Left ventricular hypertrophy (LVH) is traditionally classified as concentric or eccentric, based on the ratio of LV wall thickness to chamber dimension. We propose a 4-tiered LVH classification based on LV concentricity0.67(mass/end-diastolic volume0.67) and indexed LV end-diastolic volume (EDV).

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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.

The natural history of white matter hyperintensity (WMH) progression resulting from normal aging versus comorbid vascular insults remains unclear. Therefore we investigated age-related differences in WMH volumes among a group with comorbid hypertension, abnormal body mass index, and diabetes mellitus to a normal aging group drawn from the same population lacking any of these comorbidities.

To evaluate the cardiometabolic outcomes associated with discordant visceral adipose tissue (VAT) and liver fat (LF) phenotypes in 2 cohorts.

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Introduction:The 2019 Primary Prevention Guideline suggests selective use of low-dose aspirin (ASA) for primary prevention of ASCVD given increased bleeding risk. Higher coronary calcium (CAC) may identify those more likely to benefit from ASA, but whether higher CAC also associates with more bleeding is unclear.Methods:Participants of the Dallas Heart Study, free from ASCVD and not on ASA at baseline were included. Fatal and non-fatal major bleeding events (gastrointestinal, intracranial, major other) were identified from ICD9 and 10 codes. Adjudicated ASCVD events (non-fatal MI, coronary heart disease death, non-fatal and fatal stroke) were identified using ICD codes and phone surveys. Multivariable Cox models were used to assess the independent association of CAC with incident bleeding and ASCVD events.Results:The cohort included 2184 participants (mean age 44y, 57% female, 33% black) with 109 major bleeding events and 123 ASCVD events over a median follow-up of 17 years. Older age, black race, diabetes, smoking, blood pressure, peptic ulcer disease, corticosteroid and antacid use were associated with bleeding. Higher CAC categories (0, 1-100, >100) were associated with both ASCVD and bleeding events (p<0.001 each; Figure). CAC better discriminated ASCVD risk (c-statistic 0.79, 95% CI 0.74 to 0.83) than bleeding risk (c-statistic 0.61, 95% CI 0.55 to 0.66), and CAC ?100 (vs. CAC=0) remained associated with ASCVD [HR, 95%CI 3.98 (2.07-7.64)], but not bleeding [HR-1.24 (0.68-2.27)] after multivariable adjustment . In exploratory analyses applying meta-analysis estimates of the effect of ASA, the absolute 10-year reduction of ASCVD would be 1.7% and absolute increased bleeding 2.2% in those with CAC ?100.Conclusions:Higher CAC is associated with both ASCVD and bleeding events, with a stronger association with ASCVD. Additional studies are warranted to determine if there are CAC thresholds with favorable net benefit of ASA for primary prevention of ASCVD.

Introduction:Impaired cholesterol efflux (CEC) from macrophages to apolipoprotein A-I is linked to coronary heart disease (CHD). Haptoglobin (Hp) binds to apolipoprotein A-I, and the Hp copy number variant designated by allele ?2? is linked to CEC and HDL dysfunction in diabetics. However, the direct effect of allele ?2? on CEC remains unknown. Given the effects of anacetrapib (ANA) on increased HDL-C, increased CEC, and reduced CHD, we hypothesized that allele ?2? would blunt the effect of ANA on CEC in diabetic patients.Objective:To determine how Hp CNV status impacts the effect of ANA on CEC in diabetics.Methods:This study included 332 participants with CHD and diabetes randomized to ANA 100mg vs. placebo in the DEFINE trial. BODIPY CEC from J774 macrophages to apo B-depleted plasma was measured at baseline and at 24 weeks. Hp CNV status was determined using a commercially available ELISA assay (Savyon Diagnostics, Ltd., St. Ashdod, Israel).Results:Among the 332 participants with diabetes, 51 had the 1-1, 162 had the 2-1, and 119 had the 2-2 Hp allele (194 Men and 138 Women). In unadjusted analyses, ANA was associated with a significant increase in CEC in those with the ?1? allele (18%; std beta = 0.42; p=0.0026) but not in those with the ?2? allele (11%; std beta = 0.08; p=0.16; p for interaction = 0.02; Figure). These findings remained significant adjusting for baseline risk factors and serial changes in lipids including apo AI and apo B (?1? allele: std beta = 0.55; p=0.05; ?2? allele: std beta = 0.19; p=0.18; p for interaction = 0.08). This effect modification by Hp genotype was consistent in both diabetic men and women but was not present in non-diabetics (p for interaction = 0.36).Conclusion:Among diabetic patients with CHD, the effect of ANA on raising CEC was blunted in those with a Hp CNV linked to dysfunctional HDL. These findings warrant validation and suggest a strategy to identify those most likely to benefit from interventions targeting reverse cholesterol transport.

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Introduction:Coronary artery calcium (CAC) is a well-established predictor of ASCVD events, which includes both CHD and stroke events. Given the gender and ethnic variation in CHD and stroke incidence rate, we sought to determine the predictive value of CAC for CHD and stroke risk across sex and race sub-groups of a population free of ASCVD.Hypothesis:CAC score is a better predictor of CHD risk than stroke risk and the strength of its association with ASCVD and CHD risk is stronger among men.Methods:Asymptomatic White, Black, and Hispanic participants of Multi-Ethnic Study of Atherosclerosis and Dallas Heart Study had CAC score measured at enrollment (2000-2002) and were followed for incident ASCVD events. ASCVD incidence rate and CHD-to-stroke incidence ratio across CAC score categories (0, 1-100, and >100) was assessed. Association of CAC with events was evaluated using multivariable-adjusted Cox models and multiplicative interactions between CAC and sex/race were tested.Results:Among 7,042 participants (57 years, 54% women, 36% Black, 23% Hispanic, 49% with CAC=0, and 19% with CAC >100) there were 574 ASCVD events (333 CHD, 241 strokes) over a 12-year median follow-up. The CHD-to-stroke incidence ratio increased from <1 with CAC=0 to ≥1.4 with CAC >100 in all participant groups. CAC >0 was independently associated with ASCVD and CHD risk in all groups, with a stronger association observed among men than women (p-interaction <0.05). There were no race-based interactions. CAC >0 was independently associated with stroke risk in the overall sample but not in sex/race groups, and the strength of this association was weaker than what was observed with CHD risk.Conclusions:In these multi-ethnic, population-based cohorts the CHD-to-stroke incidence ratio was higher with higher CAC score, CAC predicted CHD risk better than stroke, and CAC presence had a stronger association with ASCVD and CHD risk among men. These results may inform the utility of CAC testing for specific patient groups and event types where it is most predictive.

Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.