Subclinical Myocardial Injury and the Phenotype of Clinical Congestion in Patients With Heart Failure and Reduced Left Ventricular Ejection Fraction.

BACKGROUND: Clinical congestion is associated with adverse outcomes in patients with heart failure. The pathophysiological mediators of this association remain uncertain. METHODS AND RESULTS: We prospectively enrolled a cohort of patients with heart failure and reduced left ventricular ejection fraction and performed a detailed clinical examination followed on the same day by an invasive right heart catheterization and blood sampling for biomarkers. High-sensitivity troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured. A clinical congestion score was calculated based on jugular venous pressure (cm H20 <10 = 0, 10-14 = 1, >14 = 2 points), bendopnea (0 vs 1), a third heart sound (0 vs 1), or peripheral edema (0-2). Congestion was categorized into tiers as absent (0 points), mild (1 point), or moderate to severe (≥ 2 points). We tested for associations of high-sensitivity troponin T, NT-proBNP, and elevated ventricular filling pressures with clinical congestion in both univariate and multivariable analyses. Of 153 participants, 65 (42%) had absent, 35 mild (23%), and 53 (35%) had moderate to severe clinical congestion. Congestion tier was associated with higher NT-proBNP and hs-troponin levels, and the right atrial pressure and pulmonary capillary wedge pressure (P < .001 for each). Increased congestion tier was also associated with the coexistent presence of elevated troponin T (≥52 ng/L), NT-proBNP (≥1000 pg/mL), and pulmonary capillary wedge pressure (≥22 mm Hg). Specifically, 78% of those with absent clinical congestion had 0 to 1 of these findings, whereas 75% of those with moderate-severe congestion had 2 or all 3 of these abnormalities (P < .001). An elevated hs-troponin was associated with mild or greater clinical congestion (odds ratio 3, 95% confidence interval 1.2-7.5, P = .02) in multivariable analysis adjusting for potential confounders including the right atrial pressure, pulmonary capillary wedge pressure, and NT-proBNP levels. CONCLUSIONS: Clinical congestion is a phenotype in which there is a high coexistent presence of elevated ventricular filling pressures, elevated natriuretic peptide levels, and subclinical myocardial injury. An elevated troponin was associated with clinical congestion in multivariable models that adjusted for ventricular filling pressures and natriuretic peptide levels. These data strengthen the evidence base for an association of elevated troponin with clinical congestion, suggesting that subclinical myocardial injury may be an important contributor to the pathophysiology of the congested state.

Racial Differences in Malignant Left Ventricular Hypertrophy and Incidence of Heart Failure: A Multicohort Study.

BACKGROUND: A malignant subphenotype of left ventricular hypertrophy (LVH) has been described, in which minimal elevations in cardiac biomarkers identify individuals with LVH at high risk for developing heart failure (HF). We tested the hypothesis that a higher prevalence of malignant LVH among blacks may contribute to racial disparities in HF risk. METHODS: Participants (n=15 710) without prevalent cardiovascular disease were pooled from 3 population-based cohort studies, the ARIC Study (Atherosclerosis Risk in Communities), the DHS (Dallas Heart Study), and the MESA (Multi-Ethnic Study of Atherosclerosis). Participants were classified into 3 groups: those without ECG-LVH, those with ECG-LVH and normal biomarkers (hs-cTnT (high sensitivity cardiac troponin-T) <6 ng/L and NT-proBNP (N-terminal pro-B-type natriuretic peptide) <100 pg/mL), and those with ECG-LVH and abnormal levels of either biomarker (malignant LVH). The outcome was incident HF. RESULTS: Over the 10-year follow-up period, HF occurred in 512 (3.3%) participants, with 5.2% in black men, 3.8% in white men, 3.2% in black women, and 2.2% in white women. The prevalence of malignant LVH was 3-fold higher among black men and women versus white men and women. Compared with participants without LVH, the adjusted hazard ratio for HF was 2.8 (95% CI, 2.1-3.5) in those with malignant LVH and 0.9 (95% CI, 0.6-1.5) in those with LVH and normal biomarkers, with similar findings in each race/sex subgroup. Mediation analyses indicated that 33% of excess hazard for HF among black men and 11% of the excess hazard among black women was explained by the higher prevalence of malignant LVH in blacks. Of black men who developed HF, 30.8% had malignant LVH at baseline, with a corresponding population attributable fraction of 0.21. The proportion of HF cases occurring among those with malignant LVH, and the corresponding population attributable fraction, were intermediate and similar among black women and white men and lowest among white women. CONCLUSIONS: A higher prevalence of malignant LVH may in part explain the higher risk of HF among blacks versus whites. Strategies to prevent development or attenuate risk associated with malignant LVH should be investigated as a strategy to lower HF risk and mitigate racial disparities.

Associations Between High-Density Lipoprotein Particles and Ischemic Events by Vascular Domain, Sex, and Ethnicity: A Pooled Cohort Analysis.

BACKGROUND: High-density lipoprotein (HDL) cholesterol concentration (HDL-C) is an established atheroprotective marker, in particular for coronary artery disease; however, HDL particle concentration (HDL-P) may better predict risk. The associations of HDL-C and HDL-P with ischemic stroke and myocardial infarction (MI) among women and Blacks have not been well studied. We hypothesized that HDL-P would consistently be associated with MI and stroke among women and Blacks compared with HDL-C. METHODS: We analyzed individual-level participant data in a pooled cohort of 4 large population studies without baseline atherosclerotic cardiovascular disease: DHS (Dallas Heart Study; n=2535), ARIC (Atherosclerosis Risk in Communities; n=1595), MESA (Multi-Ethnic Study of Atherosclerosis; n=6632), and PREVEND (Prevention of Renal and Vascular Endstage Disease; n=5022). HDL markers were analyzed in adjusted Cox proportional hazard models for MI and ischemic stroke. RESULTS: In the overall population (n=15 784), HDL-P was inversely associated with the combined outcome of MI and ischemic stroke, adjusted for cardiometabolic risk factors (hazard ratio [HR] for quartile 4 [Q4] versus quartile 1 [Q1], 0.64 [95% CI, 0.52-0.78]), as was HDL-C (HR for Q4 versus Q1, 0.76 [95% CI, 0.61-0.94]). Adjustment for HDL-C did not attenuate the inverse relationship between HDL-P and atherosclerotic cardiovascular disease, whereas adjustment for HDL-P attenuated all associations between HDL-C and events. HDL-P was inversely associated with the individual end points of MI and ischemic stroke in the overall population, including in women. HDL-P was inversely associated with MI among White participants but not among Black participants (HR for Q4 versus Q1 for Whites, 0.49 [95% CI, 0.35-0.69]; for Blacks, 1.22 [95% CI, 0.76-1.98]; Pinteraction=0.001). Similarly, HDL-C was inversely associated with MI among White participants (HR for Q4 versus Q1, 0.53 [95% CI, 0.36-0.78]) but had a weak direct association with MI among Black participants (HR for Q4 versus Q1, 1.75 [95% CI, 1.08-2.83]; Pinteraction<0.0001). CONCLUSIONS: Compared with HDL-C, HDL-P was consistently associated with MI and ischemic stroke in the overall population. Differential associations of both HDL-C and HDL-P for MI by Black ethnicity suggest that atherosclerotic cardiovascular disease risk may differ by vascular domain and ethnicity. Future studies should examine individual outcomes separately.

Effects of gender in resident evaluations and certifying examination pass rates.

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 < 0.01 for each), with no significant difference between genders for the other domains (Medical Knowledge, Overall Patient Care, Physical Examination, Procedural Skills, Professionalism, Practice Based Learning and Improvement, System Based Practices and Overall score). There were no differences in scoring between female and male attending physicians. There were no differences in certifying examination scores between women and men among graduating residents. National pass rates for women were not statistically different to pass rates for men from 1987 to 2015. CONCLUSIONS: Data from one large academic medical center demonstrate higher ratings for female residents on performance domains reflecting bedside care and interpersonal skills, with similar scores for medical knowledge and remaining domains. No significant difference was seen locally in certifying examination scores, nor in recent national pass rates, an objective measure of medical knowledge. Despite imbalanced female representation in areas of medicine, our data suggest that gender-based disparities in Internal Medicine resident medical knowledge and physician competency are no longer present.

Sex-Based Differences in Cardiometabolic Biomarkers.

BACKGROUND: Few data are available comparing cardiovascular disease (CVD) biomarker profiles between women and men in the general population. We analyzed sex-based differences in multiple biomarkers reflecting distinct pathophysiological pathways, accounting for differences between women and men in CVD risk factors, body composition, and cardiac morphology. METHODS: A cross-sectional analysis was performed using data from the Dallas Heart Study, a multiethnic population-based study. Associations between sex and 30 distinct biomarkers representative of 6 pathophysiological categories were evaluated using multivariable linear regression adjusting for age, race, traditional CVD risk factors, kidney function, insulin resistance, MRI and dual-energy x-ray absorptiometry measures of body composition and fat distribution, and left ventricular mass. RESULTS: After excluding participants with CVD, the study population included 3439 individuals, mean age 43 years, 56% women, and 52% black. Significant sex-based differences were seen in multiple categories of biomarkers, including lipids, adipokines, and biomarkers of inflammation, endothelial dysfunction, myocyte injury and stress, and kidney function. In fully adjusted models, women had higher levels of high-density lipoprotein cholesterol and high-density lipoprotein particle concentration, leptin, d-dimer, homoarginine, and N-terminal pro B-type natriuretic peptide, and lower levels of low-density lipoprotein cholesterol, adiponectin, lipoprotein-associated phospholipase A2 mass and activity, monocyte chemoattractant protein-1, soluble endothelial cell adhesion molecule, symmetrical dimethylarginine, asymmetrical dimethylarginine, high-sensitivity troponin T, and cystatin C. CONCLUSIONS: Biomarker profiles differ significantly between women and men in the general population. Sex differences were most apparent for biomarkers of adiposity, endothelial dysfunction, inflammatory cell recruitment, and cardiac stress and injury. Future studies are needed to characterize whether pathophysiological processes delineated by these biomarkers contribute to sex-based differences in the development and complications of CVD.

Multimodality Strategy for Cardiovascular Risk Assessment: Performance in 2 Population-Based Cohorts.

BACKGROUND: Current strategies for cardiovascular disease (CVD) risk assessment among adults without known CVD are limited by suboptimal performance and a narrow focus on only atherosclerotic CVD (ASCVD). We hypothesized that a strategy combining promising biomarkers across multiple different testing modalities would improve global and atherosclerotic CVD risk assessment among individuals without known CVD. METHODS: We included participants from MESA (Multi-Ethnic Study of Atherosclerosis) (n=6621) and the Dallas Heart Study (n=2202) who were free from CVD and underwent measurement of left ventricular hypertrophy by ECG, coronary artery calcium, N-terminal pro B-type natriuretic peptide, high-sensitivity cardiac troponin T, and high-sensitivity C-reactive protein. Associations of test results with the global composite CVD outcome (CVD death, myocardial infarction, stroke, coronary or peripheral revascularization, incident heart failure, or atrial fibrillation) and ASCVD (fatal or nonfatal myocardial infarction or stroke) were assessed over >10 years of follow-up. Multivariable analyses for the primary global CVD end point adjusted for traditional risk factors plus statin use and creatinine (base model). RESULTS: Each test result was independently associated with global composite CVD events in MESA after adjustment for the components of the base model and the other test results (P<0.05 for each). When the 5 tests were added to the base model, the c-statistic improved from 0.74 to 0.79 (P=0.001), significant integrated discrimination improvement (0.07, 95% confidence interval [CI] 0.06-0.08, P<0.001) and category free net reclassification improvement (0.47; 95% CI, 0.38-0.56; P=0.003) were observed, and the model was well calibrated (χ2=12.2, P=0.20). Using a simple integer score counting the number of abnormal tests, compared with those with a score of 0, global CVD risk was increased among participants with a score of 1 (adjusted hazard ratio, 1.9; 95% CI, 1.4-2.6), 2 (hazard ratio, 3.2; 95% CI, 2.3-4.4), 3 (hazard ratio, 4.7; 95% CI, 3.4-6.5), and ≥4 (hazard ratio, 7.5; 95% CI, 5.2-10.6). Findings replicated in the Dallas Health Study were similar for the ASCVD outcome. CONCLUSIONS: Among adults without known CVD, a novel multimodality testing strategy using left ventricular hypertrophy by ECG, coronary artery calcium, N-terminal pro B-type natriuretic peptide, high-sensitivity cardiac troponin T, and high-sensitivity C-reactive protein significantly improved global CVD and ASCVD risk assessment.

HDL cholesterol efflux capacity and incident cardiovascular events.

BACKGROUND: It is unclear whether high-density lipoprotein (HDL) cholesterol concentration plays a causal role in atherosclerosis. A more important factor may be HDL cholesterol efflux capacity, the ability of HDL to accept cholesterol from macrophages, which is a key step in reverse cholesterol transport. We investigated the epidemiology of cholesterol efflux capacity and its association with incident atherosclerotic cardiovascular disease outcomes in a large, multiethnic population cohort. METHODS: We measured HDL cholesterol level, HDL particle concentration, and cholesterol efflux capacity at baseline in 2924 adults free from cardiovascular disease who were participants in the Dallas Heart Study, a probability-based population sample. The primary end point was atherosclerotic cardiovascular disease, defined as a first nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization or death from cardiovascular causes. The median follow-up period was 9.4 years. RESULTS: In contrast to HDL cholesterol level, which was associated with multiple traditional risk factors and metabolic variables, cholesterol efflux capacity had minimal association with these factors. Baseline HDL cholesterol level was not associated with cardiovascular events in an adjusted analysis (hazard ratio, 1.08; 95% confidence interval [CI], 0.59 to 1.99). In a fully adjusted model that included traditional risk factors, HDL cholesterol level, and HDL particle concentration, there was a 67% reduction in cardiovascular risk in the highest quartile of cholesterol efflux capacity versus the lowest quartile (hazard ratio, 0.33; 95% CI, 0.19 to 0.55). Adding cholesterol efflux capacity to traditional risk factors was associated with improvement in discrimination and reclassification indexes. CONCLUSIONS: Cholesterol efflux capacity, a new biomarker that characterizes a key step in reverse cholesterol transport, was inversely associated with the incidence of cardiovascular events in a population-based cohort. (Funded by the Donald W. Reynolds Foundation and others.).

Soluble endothelial cell-selective adhesion molecule and incident cardiovascular events in a multiethnic population.

BACKGROUND: Cell adhesion molecules are key regulators of atherosclerotic plaque development, but circulating levels of soluble fragments, such as intercellular adhesion molecule (sICAM-1) and vascular cell adhesion molecule (sVCAM-1), have yielded conflicting associations with atherosclerotic cardiovascular disease (ASCVD). Endothelial cell-selective adhesion molecule (ESAM) is expressed exclusively in platelets and endothelial cells, and soluble ESAM (sESAM) levels have been associated with prevalent subclinical atherosclerosis. We therefore hypothesized that sESAM would be associated with incident ASCVD. METHODS: sESAM, sICAM-1, and sVCAM-1 were measured in 2,442 participants without CVD in the Dallas Heart Study, a probability-based population sample aged 30-65 years enrolled between 2000 and 2002. ASCVD was defined as first myocardial infarction, stroke, coronary revascularization, or CV death. A total of 162 ASCVD events were analyzed over 10.4 years. RESULTS: Increasing sESAM was associated with ASCVD, independent of risk factors (HR Q4 vs Q1: 2.7, 95% CI 1.6-4.6). Serial adjustment for renal function, sICAM-1, VCAM-1, and prevalent coronary calcium did not attenuate these associations. Continuous ESAM demonstrated similar findings (HR 1.31, 95% CI 1.2-1.4). Addition of sESAM to traditional risk factors improved discrimination and reclassification (delta c-index: P = .009; integrated-discrimination-improvement index P = .001; net reclassification index = 0.42, 95% CI 0.15-0.68). Neither sICAM-1 nor sVCAM-1 was independently associated with ASCVD. CONCLUSIONS: sESAM but not sICAM-1 or sVCAM-1 levels are associated with incident ASCVD. Further studies are warranted to investigate the role of sESAM in ASCVD.

Bendopnea and risk of adverse clinical outcomes in ambulatory patients with systolic heart failure.

BACKGROUND: Recently, the symptom of bendopnea, that is, shortness of breath when bending forwards such as when putting on shoes, has been described in heart failure patients and found to be associated with higher ventricular filling pressures, particularly in the setting of low cardiac index. However, it is not known whether bendopnea is associated with clinical outcomes. METHODS: In a prospective convenience sample of 179 patients followed in our heart failure disease management clinic, we determined the presence of bendopnea at the time of enrollment and ascertained clinical outcomes through 1 year of follow-up. We performed univariate and stepwise multivariable modeling to test the association of bendopnea with clinical outcomes. RESULTS: Bendopnea was present in 32 of 179 (18%) subjects. At 1 year, those with versus without bendopnea were at increased risk of the composite endpoint of death, heart failure admission, inotrope initiation, left ventricular assist device implantation, or cardiac transplantation in univariate (hazard ratio [HR] 1.9, P < .05) but not multivariable (HR 1.9, P = .11) analysis. Bendopnea was more strongly associated with short-term outcomes including heart failure admission at 3 months in both univariate (HR 3.1, P < .004) and multivariable (HR 2.5, P = .04) analysis. CONCLUSIONS: Bendopnea was associated with an increased risk of adverse outcomes in ambulatory patients with heart failure, particularly heart failure admission at 3 months.

Longitudinal changes in serum 25-hydroxyvitamin D in the Dallas Heart Study.

CONTEXT: While the prevalence of vitamin D deficiency is well described in various populations, limited data are available regarding longitudinal variation in serum 25-hydroxyvitamin D concentrations. OBJECTIVES: To evaluate the temporal trends in serum 25(OH)D, prevalence of vitamin D deficiency and factors influencing these trends. PARTICIPANTS, DESIGN AND SETTING: Adults enrolled in the Dallas Heart Study, a longitudinal, probability-based, multiethnic, population study in Dallas, Texas, USA. MAIN OUTCOME MEASURES: Prevalence of vitamin D deficiency and predictors of change in serum 25(OH)D. RESULTS: A total of 2045 participants had serum 25(OH)D measured on two occasions (2000-2002 and 2007-2009) at a median interval of 7 years. Serum 25(OH)D decreased (42.7-39.4 nmol/L, P<.001) and the prevalence of vitamin D deficiency [25(OH)D <50 nmol/L] increased significantly (60.6%-66.4%, P<.0001) despite vitamin D supplementation increasing over the interval (7.2%-23.0%; P<.0001). In a multivariable model adjusting for sex, race, BMI, age, season of blood draw, smoking and exercise, a greater decline in serum 25(OH)D was noted in men compared with women (-8.0 vs -3.5 nmol/L, P<.0001), in participants of Hispanic ethnicity vs White and Black ethnicity (P<.0001), in nonobese vs obese participants (-7.2 vs -4.0 nmol/L, P=.005) and in nonusers vs users of vitamin D supplements (-5.7 vs -1.7 nmol/L, P=.032). CONCLUSIONS: Despite increased vitamin D supplementation, serum 25(OH)D decreased in an ethnically diverse cohort of Dallas County residents between 2000-2002 and 2007-2009. Features most predictive of a decline in serum 25(OH)D include male sex, Hispanic ethnicity and weight gain.

Procedural outcomes with use of the flash ostial system in aorto-coronary ostial lesions.

BACKGROUND: The Flash Ostial system (Ostial Corporation, Sunnyvale, CA) was designed to optimize implantation of aorto-ostial coronary stents by flaring the proximal stent struts against the aortic wall. METHODS: We retrospectively reviewed the medical record, angiograms, and intravascular ultrasound images of 22 aorto-ostial percutaneous coronary interventions performed at our institution between March and September 2015. The Flash Ostial system was used in 13 cases (59%). RESULTS: Mean age was 67 ± 8 years and all patients were men. The target vessel was the right coronary artery (59%), left main (27%), or a saphenous vein graft (14%); 59% of the lesions had moderate/severe calcification. The mean number of predilation balloons was 1.8 ± 1.6, mean Flash ostial balloon diameter was 3.3 ± 0.5 mm and mean inflation pressure was 13.1 ± 4.0 atmospheres. Intravascular ultrasonography (available for 19 patients) revealed mean ostial minimum lumen cross-sectional area (MLA) of 9.2 ± 3.0 mm2 and reference MLA of 8.5 ± 2.7 mm2 . The percent difference between ostial and reference MLA was higher in cases in which the Flash Ostial system was used versus those where it was not (9.6 ± 5.5% vs. 4.0 ± 2.8%, P = 0.03). All stent struts were well apposed. Technical success was 100%. One patient developed a left groin pseudoaneurysm treated with thrombin injection and one patient had a periprocedural myocardial infarction. Median contrast, fluoroscopy time, and procedure time were 235 mL, 33 min, and 118 min, respectively. CONCLUSIONS: The Flash Ostial system can be successfully used in aorto-ostial stenting, resulting in large ostial vessel MLA. © 2016 Wiley Periodicals, Inc.

Inaccuracy of estimated resting oxygen uptake in the clinical setting.

BACKGROUND: The Fick principle (cardiac output = oxygen uptake ( O2)/systemic arterio-venous oxygen difference) is used to determine cardiac output in numerous clinical situations. However, estimated rather than measured O2 is commonly used because of complexities of the measurement, though the accuracy of estimation remains uncertain in contemporary clinical practice. METHODS AND RESULTS: From 1996 to 2005, resting O2 was measured via the Douglas bag technique in adult patients undergoing right heart catheterization. Resting O2 was estimated by each of 3 published formulae. Agreement between measured and estimated O2 was assessed overall, and across strata of body mass index, sex, and age. The study included 535 patients, with mean age 55 yrs, mean body mass index 28.4 kg/m2; 53% women; 64% non-white. Mean (±standard deviation) measured O2 was 241 ± 57 ml/min. Measured O2 differed significantly from values derived from all 3 formulae, with median (interquartile range) absolute differences of 28.4 (13.1, 50.2) ml/min, 37.7 (19.4, 63.3) ml/min, and 31.7 (14.4, 54.5) ml/min, for the formulae of Dehmer, LaFarge, and Bergstra, respectively (P<0.0001 for each). The measured and estimated values differed by >25% in 17% to 25% of patients depending on the formula used. Median absolute differences were greater in severely obese patients (body mass index > 40 kg/m2), but were not affected by sex or age. CONCLUSIONS: Estimates of resting O2 derived from conventional formulae are inaccurate, especially in severely obese individuals. When accurate hemodynamic assessment is important for clinical decision-making, O2 should be directly measured.

Homoarginine and cardiovascular outcome in the population-based Dallas Heart Study.

OBJECTIVE: The nonproteinogenic amino acid homoarginine has been postulated to have antiatherosclerotic effects as a weak substrate of nitric oxide synthase. This investigation in the population-based Dallas Heart Study (DHS) aimed to evaluate the association of homoarginine with clinical and subclinical cardiovascular outcomes. APPROACH AND RESULTS: Plasma homoarginine was measured in 3514 participants of the DHS using liquid chromatography-tandem mass spectrometry. Associations between homoarginine and major adverse cardiovascular events and all-cause mortality were analyzed using Cox proportional hazard models adjusting for cardiovascular risk factors. Linear regression was used to assess cross-sectional associations between homoarginine and subclinical cardiovascular disease, including coronary artery calcium measured by electron beam-computed tomography, and aortic plaque burden and aortic wall thickness by MRI. Median age was 43 (interquartile range, 36-52) years, with 56% women and 52% black participants. Median follow-up was 9.4 (9.0-9.8) years. Median plasma homoarginine was 2.80 (2.14-3.54) µmol/L. In multivariable models, higher homoarginine was associated with lower rate of major adverse cardiovascular events (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98) and lower all-cause mortality (hazard ratio, 0.82; 0.73-0.92; per 1 log SD increase in homoarginine). Homoarginine was inversely and independently associated with aortic wall thickness (ß-estimate, -0.04; P<0.01) but not with aortic plaque burden and coronary artery calcium. CONCLUSIONS: Homoarginine is inversely associated with subclinical vascular disease and with risk for cardiovascular disease events. Additional studies are needed to evaluate whether the regulation of plasma homoarginine could emerge as a novel therapeutic option to improve outcomes in cardiovascular disease.

Association between low ankle-brachial index and accelerometer-derived sedentary and exercise time in the asymptomatic general population.

Sedentary behavior is an adverse health risk factor that is independent of physical activity. The relationship between sedentary behavior, exercise activity and the ankle-brachial index (ABI) is not well understood. We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004. Accelerometer data were used to quantify exercise and sedentary time for each participant. A low ABI was defined as a value <1.0 (including borderline values). Multi-variable adjusted logistic regression analyses were performed with sedentary and exercise times as independent variables, adjusting for important confounders. There were 1443 asymptomatic participants (mean age 61 years, 49% female, 55% current/prior smokers) with mean daily sedentary and exercise times of 454 ± 144 and 18 ± 20 minutes, respectively. Of the participants, 23% had an ABI <1.0 (8.7% with ABI <0.9). Sedentary time was positively associated with a low ABI (odds ratio [OR] 1.22 per 1 standard deviation [SD], [95% confidence interval (CI), 1.03-1.43]; p=0.02) while exercise time was inversely associated with a low ABI (OR 0.71 per 1 SD, [95% CI, 0.57-0.89]; p=0.003). Sedentary time is associated with low ABI values in the asymptomatic population. This association appears to be independent of exercise time and warrants further investigation.

Effect of normal aging versus hypertension, abnormal body mass index, and diabetes mellitus on white matter hyperintensity volume.

BACKGROUND AND PURPOSE: 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. METHODS: WMH volumes were acquired using 3T MRI for 2011 Dallas Heart Study participants. The slope of the WMH versus age regression was compared between normal and comorbidity groups<50 and ≥50 years of age where a change in slope was demonstrated. RESULTS: Aging was linearly associated with greater log WMH volume for both normal (P=0.02) and comorbidity (P<0.0001) groups. Beyond 50 years of age, more rapid increases in WMH volumes for age were seen in the group with comorbidities (P<0.0001) but not in the normal group (P=0.173). The between-group difference in slope of expected WMH for age was significantly greater in the comorbidity groups≥50 years of age (P=0.0008) but not <50 years of age (P=0.752). CONCLUSIONS: After 50 years of age, but not before, comorbid hypertension, obesity, and diabetes mellitus were associated with significantly larger WMH volumes for age compared with a normal aging group lacking these conditions. These results support the assertion that age-related differences in WMH volumes are significantly increased in the presence of comorbidities, but the effect is only detectable after 50 years of age.

In-hospital cardiopulmonary arrests in patients with left ventricular assist devices.

UNLABELLED: Background: Basic and advanced cardiac life support guidelines do not address resuscitation of patients with continuous-flow (CF) left ventricular assist devices (LVADs). As the population of LVAD patients increases, it becomes important to understand how to provide emergency care to such patients. METHODS AND RESULTS: We retrospectively reviewed a consecutive series of patients with an implanted CF-LVAD who had an in-hospital cardiopulmonary arrest at our medical center from January 2011 to October 2013. We compared them with a matched cohort of patients without LVADs who had an inhospital cardiopulmonary arrest during the same time period. Code documentation was used to determine arrest characteristics, perfusion assessment techniques, and time to cardiopulmonary resuscitation (CPR) initiation. There were 415 in-hospital arrests during the study period, and 4% (n 5 16) occurred in patients with CF-LVADs. Response teams used various approaches to assess arterial perfusion, including palpation or Doppler of the arterial pulse and measurement of blood pressure by Doppler or arterial line. Nine of the 16 patients required CPR, but only 5 (56%) received CPR in !2 minutes. In the control group (n 5 32) of patients without an LVAD, 22 received CPR, which was initiated within 2 minutes in all (100%) of the patients. CONCLUSIONS: Cardiopulmonary arrests in LVAD patients accounted for 4% of all arrests in our center. We identified important time delays in CPR initiation, highlighting the need to develop resuscitation guidelines for this patient population.

Variation of heart transplant rates in the United States during holidays.

BACKGROUND: Some cardiac transplant programs may upgrade listed patients to United Network for Organ Sharing (UNOS) 1A-status during the holidays. Whether more transplants actually occur during holidays is unknown. METHODS: We assessed rates of single-organ heart transplantation from 2001 to 2010 for recipients age ≥18 yr using the UNOS database. Patients were stratified by transplantation during holiday (±3 d, n = 2375) and non-holiday periods (n = 16 112). Holidays included Easter/Spring break, Memorial Day, July 4th, Labor Day, Thanksgiving, and Christmas/New Years (winter holidays). Secondary analysis assessing transplant rates across seasons was also completed. RESULTS: Donor and recipient characteristics were similar between groups. Compared with non-holidays, July 4th had higher transplant rates (5.69 vs. 5.09 transplants/d, p = 0.03) while the winter holiday had lower transplant rates (4.50 vs. 5.09 transplants/d, p < 0.01). There was a trend toward lower transplant rates for all holidays compared with non-holidays (p = 0.06). Transplant rates were significantly different across seasons with greater rates in spring and summer (p < 0.01). CONCLUSION: Heart transplant rates were higher during the July 4th and lower during the winter holidays. Although there was a higher likelihood of transplantation during the spring and summer seasons, upgrading patients to 1A status during most holidays may not improve their chances for transplantation.

Symmetrical dimethylarginine predicts mortality in the general population: observations from the Dallas heart study.

OBJECTIVE: Increased asymmetrical dimethylarginine (ADMA), a NO synthase inhibitor, and its congener symmetrical dimethylarginine (SDMA), predict cardiovascular and all-cause mortality in at-risk populations. Their prognostic value in the general population remains uncertain. We investigated the correlations of SDMA and ADMA with atherosclerosis and cardiovascular/all-cause mortality in the Dallas Heart Study, a multiethnic probability-based cohort aged 30 to 65 years. APPROACH AND RESULTS: SDMA and ADMA were measured by liquid chromatography-tandem mass-spectrometry (n=3523), coronary artery calcium by electron-beam computed tomography, and abdominal aortic wall thickness by MRI. In unadjusted analyses, categories of increasing SDMA and ADMA were associated with higher prevalence of cardiovascular risk factors, increased risk markers, and all-cause and cardiovascular mortality (median follow-up, 7.4 years). After adjustment for age, sex, and race, traditional cardiovascular risk factors, and renal function, SDMA and ADMA analyzed as continuous variables were associated with coronary artery calcium >10, but only SDMA was associated with abdominal aortic wall thickness. SDMA, but not ADMA, was associated with cardiovascular mortality (hazard ratio per log unit change, 3.36 [95% confidence interval, 1.49-7.59]; P=0.004). SDMA and ADMA were both associated with all-cause mortality, but after further adjustment for N-terminal pro-brain-type natriuretic peptide, high-sensitivity C-reactive protein, and high-sensitivity cardiac troponin T, only SDMA was associated with all-cause mortality (hazard ratio per log unit change, 1.86 [95% confidence interval, 1.04-3.30]; P=0.01). CONCLUSIONS: SDMA, but not ADMA, was an independent predictor of all-cause and cardiovascular mortality in a large multiethnic population-based cohort.

Left atrial structure and function and clinical outcomes in the general population.

AIMS: Left atrial (LA) structural and functional abnormalities may be subclinical phenotypes, which identify individuals at increased risk of adverse outcomes. METHODS AND RESULTS: Maximum LA volume (LAmax) and LA emptying fraction (LAEF) were measured via cardiac magnetic resonance imaging in 1802 participants in the Dallas Heart Study. The associations of LAEF and LAmax indexed to body surface area (LAmax/BSA) with traditional risk factors, natriuretic peptide levels, and left ventricular (LV) structure [end-diastolic volume (EDV) and concentricity(0.67) (mass/EDV(0.67))] and function (ejection fraction) were assessed using linear regression analysis. The incremental prognostic value of LAmax/BSA and LAEF beyond traditional risk factors, LV ejection fraction, and LV mass was assessed using the Cox proportional-hazards model. Both increasing LAmax/BSA and decreasing LAEF were associated with hypertension and natriuretic peptide levels (P < 0.05 for all). In multivariable analysis, LAmax/BSA was most strongly associated with LV end-diastolic volume/BSA, while LAEF was strongly associated with LV ejection fraction and concentricity(0.67). During a median follow-up period of 8.1 years, there were 81 total deaths. Decreasing LAEF [hazard ratio (HR) per 1 standard deviation (SD) (8.0%): 1.56 (1.32-1.87)] but not increasing LAmax/BSA [HR per 1 SD (8.6 mL/m(2)): 1.14 (0.97-1.34)] was independently associated with mortality. Furthermore, the addition of LAEF to a model adjusting Framingham risk score, diabetes, race, LV mass, and ejection fraction improved the c-statistic (c-statistics: 0.78 vs. 0.77; P < 0.05, respectively), whereas the addition of LAmax/BSA did not (c-statistics: 0.76, P = 0.20). CONCLUSION: In the general population, both LAmax/BSA and LAEF are important subclinical phenotypes but LAEF is superior and incremental to LAmax/BSA.

Association of High-Density Lipoprotein Parameters and Risk of Heart Failure: A Multicohort Analysis.

BACKGROUND: High-density lipoprotein (HDL) is commonly characterized by its cholesterol concentration (HDL-C) and inverse association with atherosclerotic cardiovascular disease. OBJECTIVES: The authors sought to evaluate the association of HDL particle concentration (HDL-P), HDL particle size (HDL-size), HDL-C, and cholesterol content per particle (HDL-C/HDL-P) with risk of overall heart failure (HF) and subtypes. METHODS: Participants from the Atherosclerosis Risk In Communities Study, Dallas Heart Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-stage Disease studies without HF history were included. Associations of HDL-P, HDL-size, HDL-C, and HDL-C/HDL-P with risk of overall HF, HF with reduced and preserved ejection fraction were assessed using adjusted Cox models. RESULTS: Among 16,925 participants (53.5% women; 21.8% Black), there were 612 incident HF events (3.6%) (HF with reduced ejection fraction, 309 [50.5%]; HF preserved ejection fraction, 303 [49.5%]) over median follow-up of 11.4 years. In adjusted models, higher HDL-P was significantly associated with lower HF risk (HR of highest vs lowest tertile of HDL-P: 0.76 [95% CI: 0.62-0.93]). Larger HDL-size was significantly associated with higher overall HF risk (HR of largest vs smallest tertile of HDL-size: 1.27 [95% CI: 1.03-1.58]). HF risk associated with HDL-P and HDL-size was similar for HF subtypes. In adjusted analyses, there was no significant association between HDL-C and HF risk. Higher HDL-C/HDL-P was significantly associated with higher overall HF risk (HR of highest vs lowest tertile of HDL-C/HDL-P: 1.29 [95% CI: 1.04-1.60]). CONCLUSIONS: Higher HDL-P was associated with a lower risk of HF. In contrast, larger HDL-size was associated with higher risk of HF and there was no significant association observed between HDL-C and HF risk after accounting for cardiovascular risk factors.