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• Increasing alcohol consumption leads to increased HDL markers. • Moderate drinkers have higher HDL values compared to light drinkers. • Race and sex can modify the relationship between HDL and cholesterol efflux. • Unable to evaluate impact of HDL markers due to low number of cardiovascular events. Small studies have suggested that moderate alcohol consumption increases HDL cholesterol (HDL-C) levels and cholesterol efflux capacity (CEC), a main anti-atherosclerotic HDL function. This study aimed to understand the degree to which alcohol intake is associated with various HDL markers in a large, multiethnic population cohort, the Dallas Heart Study (DHS), and whether alcohol modifies the link between HDL markers and atherosclerotic cardiovascular disease (ASCVD). Participants of the DHS were included if they had self-reported alcohol intake and CEC measurements (N=2,919). Alcohol intake was analyzed continuously (grams/week) and as an ordered categorical variable (never, past, light, moderate, heavy, and binge drinkers). HDL-C, CEC, HDL particle number (HDL-P), HDL particle size (HDL-size), and ApoA-I were the primary HDL measures. After adjustment for confounding variables, increasing continuous measure of alcohol intake was associated with increased levels of all HDL markers. Moreover, as compared to moderate drinkers, light drinkers had decreased levels of the HDL markers. In a large, multiethnic cohort, increased alcohol intake was associated with increased levels of multiple markers of HDL metabolism. However, the association of HDL markers with ASCVD risk as modified by alcohol consumption is unable to be determined in this low-risk cohort. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Bendopnea, or dyspnea within 30 seconds of bending forward while not holding one's breath, is a recently described symptom of heart failure that has been associated with elevated pulmonary capillary wedge pressure (PCWP) and pulmonary artery pressures (PAP). Whether this symptom is due to elevation in PCWP or due to elevation in PAP has not previously been elucidated. The development of bendopnea is due to elevation in left-ventricular filling pressure, or PCWP, rather than elevation in PAP. We prospectively enrolled a cohort of 209 patients who were undergoing right heart catheterization for clinically indicated purposes either for evaluation of heart failure with reduced ejection fraction (HFrEF, n=156) or non-World Health Organization class II pulmonary hypertension (PH, n=53). In this study, we analyzed data from the 83 patients with HFrEF who had a PCWP ≥ 16mmHg and the 52 patients with PH who had a mean PAP ≥ 20mmHg. A detailed clinical examination, including assessment of bendopnea, was conducted prior to the invasive hemodynamic assessment, and the cardiologist performing the catheterization was blinded to the physical examination findings. Logistic regression analysis tested the association of bendopnea with PCWP, mean PAP, and systolic PAP. Informed consent was obtained, and the Institutional Review Board approved the study protocol. Bendopnea was present in 37/135 (27%) subjects. Those with HFrEF versus PH were more likely to have bendopnea as well as an elevated PCWP, while there was no difference in the mean PAP between the groups (Figure). In univariable regression analysis, PCWP was associated with bendopnea (OR 1.1 [1.05, 1.15], p<0.001) but PASP was not (p=0.75). In models in which both PASP and PCWP were entered as covariates, PCWP (OR 1.1 [1.04, 1.15], p<0.001) remained associated with bendopnea but PASP (p=0.99) was not. Likewise, in a similar analysis with PCWP and MPA, PCWP was associated with bendopnea (OR 1.1 [1.04, 1.15], p=0.001), but MPA (p=0.44) was not. Elevated left sided ventricular filling pressure, rather than pulmonary artery pressures, are the hemodynamic basis of bendopnea. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Development and change of coronary artery calcium (CAC) are associated with coronary heart disease. Interpretation of serial CAC measurements will require better understanding of changes in CAC beyond the variability in the test itself. Methods Dallas Heart Study participants (2888) with duplicate CAC scans obtained minutes apart were analyzed to determine interscan concordance and 95% confidence bounds (ie: repeatability limits) for each discrete CAC value. These data derived cutoffs were then used to define change above measurement variation and determine the frequency of CAC development and change among 1779 subjects with follow up CAC scans performed 6.9 years later. Results Binary concordance (0 vs. >0) was 91%. The value of CAC denoting true development of CAC by exceeding the 95% confidence bounds for a single score of 0 was 2.7 Agatston units (AU). Among those with scores >0, the 95% confidence bounds for CAC change were determined by the following formulas: for CAC≤100AU: 5.6√CAC + 0.3*CAC – 3.1; for CAC>100AU: 12.4√CAC – 67.7. Using these parameters, CAC development occurred in 15.0% and CAC change occurred in 48.9%. Although 225 individuals (24.9%) had a decrease in CAC over follow up, only 1 (0.1%) crossed the lower confidence bound. Compared with prior reported definition of CAC development (ie: >0), the novel threshold of 2.7AU resulted in better measures of model performance. In contrast, for CAC change, no consistent differences in performance metrics were observed compared with previously reported definitions. Conclusion There is significant interscan variability in CAC measurement, including around scores of 0. Incorporating repeatability estimates may help discern true differences from those due to measurement variability, an approach that may enhance determination of CAC development and change. [ABSTRACT FROM AUTHOR]

Objective To determine the feasibility of using oral 13 C labeled glycerol to assess effects of visceral adiposity on gluconeogenic pathways in obese humans. Research Design and Methods Obese (BMI ≥ 30 kg/m 2 ) participants without type 2 diabetes underwent visceral adipose tissue (VAT) assessment and stratification by median VAT into high VAT-fasting (n = 3), low VAT-fasting (n = 4), and high VAT-refed (n = 2) groups. Participants ingested [U- 13 C 3 ] glycerol and blood samples were subsequently analyzed at multiple time points over 3 h by NMR spectroscopy. The fractions of plasma glucose (enrichment) derived from [U- 13 C 3 ] glycerol via hepatic gluconeogenesis, pentose phosphate pathway (PPP), and tricarboxylic acid (TCA) cycle were assessed using 13 C NMR analysis of glucose. Mixed linear models were used to compare 13 C enrichment in glucose between groups. Results Mean age, BMI, and baseline glucose were 49 years, 40.1 kg/m 2 , and 98 mg/dl, respectively. Up to 20% of glycerol was metabolized in the TCA cycle prior to gluconeogenesis and PPP activity was minor (< 1% of total glucose) in all participants. There was a 21% decrease in 13 C enrichment in plasma glucose in the high VAT-fasting compared with low VAT-fasting group ( p = 0.03), suggesting dilution by endogenous glycerol. High VAT-refed participants had 37% less 13 C enrichment in glucose compared with high VAT-fasting ( p = 0.02). There was a trend toward lower [1,2- 13 C 2 ] (via PPP) and [5,6- 13 C 2 ]/[4,5,6- 13 C 3 ] (via TCA cycle) glucose in high VAT versus low VAT groups. Conclusions We applied a simple method to detect gluconeogenesis from glycerol in obese humans. Our findings provide preliminary evidence that excess visceral fat disrupts multiple pathways in hepatic gluconeogenesis from glycerol. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Adiponectin is a key component in multiple metabolic pathways. Studies evaluating associations of adiponectin with clinical outcomes in older adults have reported conflicting results. We investigated the association of adiponectin with mortality and cardiovascular disease (CVD) morbidity in a young, multiethnic adult population. We analyzed data from participants in the Dallas Heart Study without baseline CVD who underwent assessment of total adiponectin from 2000 to 2002. The primary outcome of all-cause mortality was assessed over median 10.4 years of follow-up using multivariable-adjusted Cox proportional hazards models. Secondary outcomes included CVD mortality, major adverse cardiovascular and cerebrovascular events (MACCE), and heart failure (HF). The study cohort included 3,263 participants, mean age 43.4 years, 44% women, and 50% black. There were 184 deaths (63 CVD), 207 MACCE, and 46 HF events. In multivariable models adjusted for age, gender, race, hypertension, diabetes, smoking, high-density lipoprotein cholesterol-C, hyperlipidemia, high-sensitivity C-reactive protein level, estimated glomerular filtration rate, and body mass index, increasing adiponectin quartiles were positively associated with all-cause mortality Q4 versus Q1 (hazard ratio [HR] = 2.27; 95% confidence interval [CI] 1.47, 3.50); CVD mortality Q4 versus Q1 (HR = 2.43; 95% CI 1.15, 5.15); MACCE Q4 versus Q1 (HR = 1.71; 95% CI 1.13, 2.60); and HF Q4 versus Q1 (HR = 2.95; 95% CI 1.14, 7.67). Findings were similar with adiponectin as a continuous variable and consistent across subgroups defined by age, gender, race, obesity, diabetes, metabolic syndrome, or elevated high-sensitivity C-reactive protein. In conclusion, higher adiponectin was associated with increased mortality and CVD morbidity in a young, multiethnic population. These findings may have implications for strategies aimed at lowering adiponectin to prevent adverse outcomes. [ABSTRACT FROM AUTHOR]

Objectives This study sought to assess the effect of coronary artery calcium (CAC) on coronary heart disease (CHD) risk prediction in a younger population. Background CAC measured by computed tomography improves CHD risk classification in older adults, but the effectiveness of CAC in younger populations has not been fully assessed. Methods In the DHS (Dallas Heart Study), a multiethnic probability-based population sample, traditional CHD risk factors and CAC were measured in participants without baseline cardiovascular disease or diabetes. Incident CHD—defined as CHD death, myocardial infarction, or coronary revascularization—was assessed over a median follow-up of 9.2 years. Predicted CHD risk was assessed with a Weibull model inclusive of traditional risk factors before and after the addition of CAC as ln(CAC + 1). Participants were divided into 3 10-year risk categories, <6%, 6% to <20%, and ≥20%, and the net reclassification improvement (NRI) was calculated. We also performed a random-effects meta-analysis of NRI from previous studies inclusive of older individuals. Results The analysis comprised 2,084 participants; mean age was 44.4 ± 9.0 years. CAC was independently associated with incident CHD (hazard ratio per SD: 1.90, 95% confidence interval [CI] 1.51 to 2.38; p < 0.001). The addition of CAC to the traditional risk factor model resulted in significant improvement in the C-statistic (delta = 0.03; p = 0.003). Among participants with CHD events, the addition of CAC resulted in net correct upward reclassification of 21%, and among those without CHD, a net correct downward reclassification of 0.5% (NRI: 0.216, p = 0.012). Results remained significant when the outcome was restricted to CHD death and myocardial infarction and when individuals with diabetes were included. The NRI observed in this study was similar to the pooled estimate from previous studies (0.200, 95% CI: 0.140 to 0.258) and the addition of our study to the meta-analysis did not result in significant heterogeneity (I 2 = 0%). Conclusions CAC scoring also improves CHD risk classification in younger adults. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Lifetime risk estimation for cardiovascular disease (CVD) has been proposed as a useful strategy to improve risk communication in the primary prevention setting. However, the perception of lifetime risk for CVD is unknown. We included 2,998 subjects from the Dallas Heart Study. Lifetime risk for developing CVD was classified as high (≥39%) versus low (<39%) according to risk factor burden as described in our previously published algorithm. Perception of lifetime risk for myocardial infarction was assessed by way of a 5-point scale. Baseline characteristics were compared across levels of perceived lifetime risk. Multivariable logistic regression analyses were performed to determine the association of participant characteristics with level of perceived lifetime risk for CVD and with correctness of perceptions. Of the 2,998 participants, 64.8% (n = 1,942) were classified as having high predicted lifetime risk for CVD. There was significant discordance between perceived and predicted lifetime risk. After multivariable adjustment, family history of premature myocardial infarction, high self-reported stress, and low perceived health were all strongly associated with high perceived lifetime risk (odds ratio [OR] 2.37, 95% confidence interval [CI] 1.72 to 3.27; OR 2.17, 95% CI 1.66 to 2.83; and OR 2.71, 95% CI 2.09 to 3.53; respectively). However, the association between traditional CVD risk factors and high perceived lifetime risk was more modest. In conclusion, misperception of lifetime risk for CVD is common and frequently reflects the influence of factors other than traditional risk factor levels. These findings highlight the importance of effectively communicating the significance of traditional risk factors in determining the lifetime risk for CVD. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to investigate the independent and joint associations between family history of myocardial infarction (FH) and coronary artery calcification (CAC) with incident coronary heart disease (CHD). Background FH and CAC are associated with each other and with incident CHD. It is not known whether FH retains its predictive value after CAC results are accounted for. Methods Among 2,390 participants without cardiovascular disease enrolled in the Dallas Heart Study, we assessed FH (myocardial infarction in a first-degree relative) and prevalent CAC by electron-beam computed tomography. The primary outcome, a composite of CHD-related death, myocardial infarction, and percutaneous or surgical coronary revascularization, was assessed over a mean follow-up of 8.0 ± 1.2 years. The individual and joint associations with the CHD composite outcome were determined for FH and CAC. Results The mean age of the population was 44 ± 9 years; 32% had FH and 47% had a CAC score of 0. In multivariate models adjusted for traditional risk factors, FH was independently associated with CHD (adjusted hazard ratio: 2.6; 95% confidence interval: 1.6 to 4.2; p < 0.001). Further adjustment for prevalent CAC did not diminish this association (adjusted hazard ratio: 2.6; 95% confidence interval: 1.6 to 4.2; p < 0.001). FH and CAC were additive: CHD event rates in those with both FH and CAC were 8.8% vs. 3.3% in those with prevalent CAC alone (p < 0.001). CHD rates were 1.9% in those with FH alone compared with 0.4% in those with neither FH nor CAC (p < 0.017). Among subjects without CAC, FH characterized a group with a more unfavorable cardiometabolic profile. Conclusions FH provided prognostic information that was independent of and additive to CAC. Among those with CAC, FH identified subjects at particularly high short-term risk, and, among those without it, selected a group with an adverse risk-factor profile. [ABSTRACT FROM AUTHOR]

Background: Although rosiglitazone favorably affects myriad intermediate markers of atherosclerosis, it appears to increase myocardial infarction (MI) risk. We analyzed the effects of rosiglitazone on a panel of 8 novel circulating biomarkers, 4 of which are independently associated with atherosclerosis: lymphotoxin β receptor, peptidoglycan recognition protein 1, chemokine ligand 23, and soluble receptor for advanced glycation end products (sRAGE) as well as on high-sensitivity C-reactive protein (hs-CRP). Methods: Blood samples were analyzed at baseline and after 6 months of study treatment from subjects with type 2 diabetes with or at high risk for coronary artery disease in a randomized trial comparing rosiglitazone versus placebo. Results: Data from 111 subjects (rosiglitazone 55, placebo 56) were analyzed. Mean age was 56 years, 41% were women, and 66% were nonwhite. Compared with baseline values, rosiglitazone adversely affected levels of lymphotoxin β receptor (1.7 vs 2.4 ng/mL, P = .002), peptidoglycan recognition protein 1 (29.0 vs 30.1 ng/mL, P = .01), and chemokine ligand 23 (0.76 vs 0.84 ng/mL, P = .02) and favorably affected levels of sRAGE (inversely associated with atherosclerosis, 1.1 vs 1.4 ng/mL, P = .003) and hs-CRP (0.42 vs 0.31 ng/mL, P = .02); no changes were observed with rosiglitazone in the other biomarkers. In the placebo group, change was observed only for sRAGE (1.0 vs 1.1 ng/mL, P = .046). Conclusion: Rosiglitazone adversely affected 3 novel biomarkers and favorably affected a fourth previously associated with atherosclerosis while improving hs-CRP, as has previously been shown. Whether these complex effects on circulating inflammatory biomarkers contribute to the signal of increased MI risk with rosiglitazone and whether pioglitazone has similar effects warrant further investigation. [Copyright &y& Elsevier]

Background: Guidelines recommend that patients with new-onset systolic heart failure (HF) receive a trial of medical therapy before an implantable cardiac defibrillator (ICD). This strategy allows for improvement of left ventricular ejection fraction (LVEF), thereby avoiding an ICD, but exposes patients to risk of potentially preventable sudden cardiac death during the trial of medical therapy. Methods: We reviewed a consecutive series of patients with HF of <6 months duration with a severely depressed LVEF (<30%) evaluated in a HF clinic (N = 224). The ICD implantation was delayed with plans to reassess LVEF approximately 6 months after optimization of β-blockers. Mortality was ascertained by the National Death Index. Results: Follow-up echocardiograms were performed in 115 of the 224 subjects. Of these, 50 (43%) had mildly depressed or normal LVEF at follow-up (“LVEF recovery”) such that an ICD was no longer indicated. In a conservative sensitivity analysis (using the entire study cohort, whether or not a follow-up echocardiogram was obtained, as the denominator), 22% of subjects had LVEF recovery. Mortality at 6, 12, and 18 months in the entire cohort was 2.3%, 4.5%, and 6.8%, respectively. Of 87 patients who tolerated target doses of β-blockers, only 1 (1.1%) died during the first 18 months. Conclusion: Patients with new-onset systolic HF have both a good chance of LVEF recovery and low 6-month mortality. Achievement of target β-blocker dose identifies a very low-risk population. These data support delaying ICD implantation for a trial of medical therapy. [ABSTRACT FROM AUTHOR]

Background: Physical activity (PA) participation differs by ethnicity, but contributing factors and cardiovascular (CV) outcomes related to these disparities are not well understood. We determined whether health beliefs regarding the benefit of PA contribute to ethnic differences in participation and assessed how these differences impact CV mortality. Methods: The Dallas Heart Study is a longitudinal study of CV health. We assessed PA participation and health perceptions by questionnaire among 3,018 African American, Hispanic, and white men and women at baseline visit (2000-2002). Participant mortality was obtained through 2008 using the National Death Index. Results: African Americans (odds ratio 0.65, 95% CI 0.53-0.80) and Hispanics (odds ratio 0.34, 95% CI 0.26-0.45) were less likely to be physically active compared with whites even after accounting for income, educational status, age, sex, body mass index, diabetes, hypertension, and hyperlipidemia. Beliefs regarding the benefits of PA did not contribute to this disparity, as >94% of individuals felt PA was effective in preventing a heart attack across ethnicity. Physical activity participation was associated with a lower risk of all-cause mortality (hazard ratio [HR] 0.66, 95% CI 0.46-0.93) and CV disease death (HR 0.56, 95% CI 0.32-0.97) in multivariable adjusted models. Similar results were seen when restricting to African Americans (CV disease death, HR 0.57, 95% CI 0.31-1.05). Conclusions: Ethnic minorities reported less PA participation, and lack of PA was associated with higher CV mortality overall and among African Americans. Health perception regarding the benefits of PA did not contribute to this difference, indicating there are other ethnic-specific factors contributing to physical inactivity that require future study. [Copyright &y& Elsevier]

Objectives: To examine whether individuals with low short-term risk of coronary heart disease but high lifetime predicted risk of cardiovascular disease (CVD) have greater prevalence of left ventricular (LV) hypertrophy and increased aortic wall thickness (AWT) than those with low short-term and low lifetime risk. Background: Lifetime risk prediction can be used for stratifying individuals younger than 50 years of age into 2 groups: low short-term/high lifetime and low short-term/low lifetime predicted risk of CVD. Individuals with low short-term/high lifetime risk have a greater burden of subclinical atherosclerosis as measured by coronary artery calcium and carotid intima-media thickness. However, >75% of individuals with low short-term/high lifetime risk do not have detectable coronary artery calcium, suggesting the presence of alternative subclinical abnormalities. Methods: We stratified 1,804 Dallas Heart Study subjects between the ages of 30 and 50 years who had cardiac magnetic resonance into 3 groups: low short-term (<10% 10-year risk of coronary heart disease)/low lifetime predicted risk (<39% lifetime risk of CVD), low short-term (<10%)/high lifetime risk (≥39%), and high short-term risk (≥10%, prevalent diabetes, or previous stroke, or myocardial infarction). In those with low short-term risk, we compared measures of LV hypertrophy and AWT between those with low versus high lifetime risk. Results: Subjects with low short-term/high lifetime risk compared with those with low short-term/low lifetime risk had increased LV mass (men: 95 ± 17 g/m2 vs. 90 ± 12 g/m2 and women: 75 ± 14 g/m2 vs. 71 ± 10 g/m2, respectively; p < 0.001 for both). LV concentricity (mass/volume), wall thickness, and AWT were also significantly greater in those with high lifetime risk in this comparison (p < 0.001 for all), but LV end-diastolic volume was not (p > 0.3). These associations persisted among participants without detectable coronary artery calcium. Conclusions: Among individuals 30 to 50 years of age with low short-term risk, a high lifetime predicted risk of CVD is associated with concentric LV hypertrophy and increased AWT. [Copyright &y& Elsevier]

Background: The Health ABC Heart Failure score has recently been shown to predict 5-year risk of incident heart failure in the elderly. We tested whether this risk score is associated with subclinical phenotypes of heart failure in a younger population. Methods: We stratified participants in the Dallas Heart Study aged 30 to 65 years who had a cardiac magnetic resonance imaging and no self-reported history of heart failure or cardiomyopathy into 4 previously defined Health ABC Heart Failure risk groups: low (<5%), average (5%-10%), high (10%-20%), and very high (>20% risk for heart failure within 5 years). We compared left ventricular (LV) structural and functional parameters and levels of B-type natriuretic peptide (BNP) and N-terminal proBNP among the 4 groups. Results: In the study cohort (N = 2,540), the percentage of subjects in the low-, average-, high-, and very high risk groups was 78%, 15%, 6%, and 1%, respectively. Indexed LV mass (80 ± 15 vs 90 ± 20 vs 95 ± 25 vs 116 ± 41 g/m2), concentricity (1.6 ± 0.3 vs 1.8 ± 0.4 vs 2.0 ± 0.5 vs 2.2 ± 0.7 g/mL), median BNP (2.8 vs 3.7 vs 4.9 vs 7.5 pg/mL) and N-terminal proBNP (26 vs 30 vs 40 vs 58 pg/mL), and prevalent LV systolic dysfunction and LV hypertrophy progressively increased across risk groups (P < .001 for all) independent of gender or method of indexing LV mass. Conclusions: The Health ABC Heart Failure score was associated with subclinical cardiac structural changes in the general population 30 to 65 years of age, suggesting that it may be a valid tool for identification of young individuals at increased risk for heart failure. [Copyright &y& Elsevier]

Abstract: Background: Peptidoglycan recognition protein-1 (PGLYRP-1) is part of the innate immune system and binds to peptidoglycan, a component of bacterial cell walls that has been found in human atherosclerotic lesions. Chronic exposure to bacterial antigens may cause or exacerbate the inflammatory response to lipid deposition within arterial walls. We hypothesized that PGLYRP-1 is associated with subclinical atherosclerosis as measured by computed tomography and magnetic resonance imaging. Methods and results: PGLYRP-1 was measured in 3222 subjects in the Dallas Heart Study, a probability-based population sample age 30–65 including 50% African-Americans and 56% women. Coronary artery calcium (CAC) was measured by electron beam computed tomography (n =2467), abdominal aortic wall thickness (AWT) by magnetic resonance imaging (MRI) (n =2270), and abdominal aortic plaque burden (APB) by MRI (n =2256). In univariable analyses, increasing levels of PGLYRP-1 were associated with all major cardiovascular risk factors, with inflammatory markers such as C-reactive protein, and with CAC, AWT, and APB (p <0.0001 for each). In multivariable models adjusted for traditional risk factors, logPGLYRP-1 remained significantly associated with CAC (OR 1.1, 95% CI 1.01–1.3 per S.D.; p =0.04) and AWT (p =0.009) but not APB (p =0.09). Further adjustment for novel biomarkers associated with PGLYRP-1 and atherosclerosis attenuated the association with CAC (p =0.18) but not with AWT (p =0.01) or APB (p =0.037). Conclusion: In this first reported clinical study of PGLYRP-1 in humans, PGLYRP-1 levels were independently associated with atherosclerosis phenotypes that represent different vascular beds and stages of atherosclerosis. [Copyright &y& Elsevier]

Background: Elevated lipoprotein(a) [Lp(a)] and coronary artery calcium (CAC) score are individually associated with increased atherosclerotic cardiovascular disease (ASCVD) risk but have not been studied in combination.Objectives: This study sought to investigate the independent and joint association of Lp(a) and CAC with ASCVD risk.Methods: Plasma Lp(a) and CAC were measured at enrollment among asymptomatic participants of the MESA (Multi-Ethnic Study of Atherosclerosis) (n = 4,512) and DHS (Dallas Heart Study) (n = 2,078) cohorts. Elevated Lp(a) was defined as the highest race-specific quintile, and 3 CAC score categories were studied (0, 1-99, and ≥100). Associations of Lp(a) and CAC with ASCVD risk were evaluated using risk factor-adjusted Cox regression models.Results: Among MESA participants (61.9 years of age, 52.5% women, 36.8% White, 29.3% Black, 22.2% Hispanic, and 11.7% Chinese), 476 incident ASCVD events were observed during 13.2 years of follow-up. Elevated Lp(a) and CAC score (1-99 and ≥100) were independently associated with ASCVD risk (HR: 1.29; 95% CI: 1.04-1.61; HR: 1.68; 95% CI: 1.30-2.16; and HR: 2.66; 95% CI: 2.07-3.43, respectively), and Lp(a)-by-CAC interaction was not noted. Compared with participants with nonelevated Lp(a) and CAC = 0, those with elevated Lp(a) and CAC ≥100 were at the highest risk (HR: 4.71; 95% CI: 3.01-7.40), and those with elevated Lp(a) and CAC = 0 were at a similar risk (HR: 1.31; 95% CI: 0.73-2.35). Similar findings were observed when guideline-recommended Lp(a) and CAC thresholds were considered, and findings were replicated in the DHS.Conclusions: Lp(a) and CAC are independently associated with ASCVD risk and may be useful concurrently for guiding primary prevention therapy decisions. [ABSTRACT FROM AUTHOR]

Aims Metabolic syndrome (MetS) increases atherosclerotic cardiovascular disease (ASCVD) risk. Low HDL cholesterol (HDL-C) is a diagnostic criterion of MetS and a major ASCVD risk factor. HDL particle concentration (HDL-P) associates with incident ASCVD independent of HDL-C, but its association with incident MetS has not been studied. We hypothesized that HDL-P would be inversely associated with incident metabolic syndrome independent of HDL-C and markers of adiposity and insulin resistance. Materials and methods HDL-P was measured by NMR and visceral fat by MRI in participants of the Dallas Heart Study, a probability-based population sample of adults age 30–65. Participants with prevalent MetS, DM, CVD, and any systemic illlness were excluded. Incident MetS as defined by NCEP ATPIII criteria was determined in all participants after median follow-up period of 7.0 years. Results Among 1120 participants without DM or MetS at baseline (57% women, 45% Black, mean age 43), 22.8% had incident MetS at follow-up. HDL-P and HDL-C were modestly correlated (r = 0.54, p < 0.0001). In models adjusted for traditional risk factors and MetS risk factors including visceral fat, HS-CRP, triglyceride to HDL-C ratio, and HOMA-IR, the lowest quartile of HDL-P was associated with a 2-fold increased risk of incident MetS (OR 2.1, 95%CI 1.4–3.1; p = 0.0003). Conclusions Low HDL-P is independently associated with incident MetS after adjustment for traditional risk factors, lipid parameters, adiposity, inflammation, and markers of insulin resistance. Further studies are warranted to validate these findings and elucidate the mechanisms underpinning this association. [ABSTRACT FROM AUTHOR]

Background: Elevated lipoprotein(a) (Lp[a]) and family history (FHx) of coronary heart disease (CHD) are individually associated with cardiovascular risk, and Lp(a) is commonly measured in those with FHx.Objectives: The aim of this study was to determine independent and joint associations of Lp(a) and FHx with atherosclerotic cardiovascular disease (ASCVD) and CHD among asymptomatic subjects.Methods: Plasma Lp(a) was measured and FHx was ascertained in 2 cohorts. Elevated Lp(a) was defined as the highest race-specific quintile. Independent and joint associations of Lp(a) and FHx with cardiovascular risk were determined using Cox regression models adjusted for cardiovascular risk factors.Results: Among 12,149 ARIC (Atherosclerosis Risk In Communities) participants (54 years, 56% women, 23% black, 44% with FHx), 3,114 ASCVD events were observed during 21 years of follow-up. FHx and elevated Lp(a) were independently associated with ASCVD (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.09 to 1.26, and HR: 1.25; 95% CI: 1.12 to 1.40, respectively), and no Lp(a)-by-FHx interaction was noted (p = 0.75). Compared with subjects without FHx and nonelevated Lp(a), those with either elevated Lp(a) or FHx were at a higher ASCVD risk, while those with both had the highest risk (HR: 1.43; 95% CI: 1.27 to 1.62). Similar findings were observed for CHD risk in ARIC, in analyses stratified by premature FHx, and in an independent cohort, the DHS (Dallas Heart Study). Presence of both elevated Lp(a) and FHx resulted in greater improvement in ASCVD and CHD risk reclassification and discrimination indexes than either marker alone.Conclusions: Elevated plasma Lp(a) and FHx have independent and additive joint associations with cardiovascular risk and may be useful concurrently for guiding primary prevention therapy decisions. [ABSTRACT FROM AUTHOR]

Background: Identifying asymptomatic individuals with American Heart Association/American College of Cardiology stage B heart failure (HF) in the population is an important step to prevent the development of symptomatic HF. The comparative utility of 2 screening strategies (biomarkers vs risk scores) in identifying prevalent stage B HF is unknown. Methods: Participants 30 to 65 years old without symptomatic HF in the Dallas Heart Study who had a cardiac magnetic resonance imaging were included (n = 2,277). Stage B HF (n = 284) was defined by left ventricular (LV) hypertrophy, reduced LV ejection fraction, or prior myocardial infarction. We compared the utility of 2 risk scores (Health Aging and Body Composition HF risk score and the Framingham Heart Failure risk score) with B-type natriuretic peptide (BNP) and N-terminal pro-BNP in identifying stage B HF using logistic regression. Results: Depending upon the method of indexing LV mass (body surface area, fat-free mass, or height2.7), the c-statistic for the Health Aging and Body Composition HF risk score (0.73, 0.75, and 0.64, respectively) was greater than that for BNP (0.62, 0.70, and 0.57, respectively) and N-terminal pro-BNP (0.62, 0.69, and 0.56, respectively) (P < .01 for all). These findings were similar for the Framingham Heart Failure risk score except when LV mass was indexed to fat-free mass. Addition of natriuretic peptide levels to the risk scores resulted in a modest but significant improvement in discrimination of stage B HF (Δ c-statistic, 0.01-0.03, P < .05 for all). Conclusions: Screening for stage B HF in the population is enhanced when natriuretic peptides are measured in addition to, rather than in place of, traditional risk scores. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study was to investigate the association between natriuretic peptides and body fat distribution in a multiethnic cohort. Background: Natriuretic peptides stimulate lipolysis, reduce weight gain, and promote adipocyte browning in animal models, but data are lacking in humans. Methods: A total of 2,619 participants without heart failure in the Dallas Heart Study underwent measurements of 1) B-type natriuretic peptide (BNP) and N-terminal pro–B-type natriuretic peptide (NT-proBNP); and 2) body fat distribution by dual energy x-ray absorptiometry and magnetic resonance imaging. Cross-sectional associations of natriuretic peptides with adiposity phenotypes were examined after adjustment for age, sex, race, comorbidities, and body mass index. Results: Median BNP and NT-proBNP levels in the study cohort (mean age 44 years; 56% women, 48% African Americans, 32% obese) were 3.0 and 28.1 pg/ml, respectively. Natriuretic peptide levels above the median were associated with a more favorable body fat profile and less insulin resistance, including lower visceral fat, liver fat, and homeostasis model assessment of insulin resistance index, and increased lower body fat and higher adiponectin (p < 0.05 for each). In multivariable analyses, NT-proBNP remained inversely associated with visceral fat (beta coefficient = −0.08; p < 0.0001) and liver fat (beta coefficient = −0.14; p < 0.0001) and positively associated with lower body fat (beta coefficient = 0.07; p < 0.0001) independent of age, sex, race, and obesity status; findings were similar with BNP. Adjustment for body composition, homeostasis model assessment of insulin resistance index, circulating androgens, and adipocytokines did not attenuate the associations. Conclusions: Higher natriuretic peptide levels were independently associated with a favorable adiposity profile, characterized by decreased visceral and liver fat and increased lower body fat, suggesting a link between the heart and adipose tissue distribution mediated through natriuretic peptides. [Copyright &y& Elsevier]

Objectives: This study sought to evaluate whether the relationship between C-reactive protein (CRP) and atherosclerosis is modified by body mass index (BMI). Background: CRP levels are affected by obesity, and it is unknown whether the associations between CRP and cardiovascular (CV) disease differ between obese and nonobese individuals. Methods: We measured CRP and multiple atherosclerosis phenotypes, including coronary artery calcification (CAC) (n = 2,685), aortic wall thickness (AWT) (n = 2,238), and aortic plaque burden (APB) (n = 2,224), in subjects ages 30 to 65 years from the Dallas Heart Study. The associations of CRP with CAC, AWT, and APB were compared across categories of BMI (normal, 18.5 to <25 kg/m2; overweight, 25 to <30 kg/m2; obese, ≥30 kg/m2) in sex-stratified analyses. Results: The overall prevalence of obesity was 38% in men and 53% in women. Increasing CRP levels (<1 mg/l, 1 to 3 mg/l, >3 mg/l) were associated with increased CAC prevalence in normal and overweight men and in normal weight women (p < 0.01), but not in obese subjects of either sex. Likewise, the correlations between CRP and AWT and APB diminished with increasing BMI and were nonsignificant in obese individuals (p < 0.05 in nonobese, p > 0.1 in obese). Interaction tests between CRP and obesity were significant for all atherosclerosis measures in men and for AWT and ABP in women (p interaction <0.05 each). In both sexes, the c-statistics of CRP for all 3 atherosclerosis measures were greater for normal weight than obese individuals. Conclusions: In a large, population-based study, the association between CRP and multiple measures of atherosclerosis is diminished in obese individuals. The role of CRP for predicting CV outcomes in obese subjects requires further evaluation. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Myeloperoxidase (MPO) is a leukocyte-derived enzyme that appears to be directly involved in atherosclerosis development. We evaluated the association of circulating MPO with coronary and aortic atherosclerosis in a large, multiethnic population. Methods and results: Plasma levels of MPO were measured in 3294 subjects participating in the Dallas Heart Study, a probability-based population sample. Coronary artery calcification (CAC) was measured by EBCT, and abdominal aorta plaque prevalence (AP) and burden (APB), as well as abdominal aorta wall thickness (AWT) were determined by MRI. Associations between MPO and atherosclerosis phenotypes were assessed in multivariable analyses adjusting for traditional atherosclerosis risk factors. MPO levels in the 4th compared with 1st quartile independently associated with prevalent AP (OR 1.41, 95% CI 1.08–1.84), APB (beta coefficient 0.23, p =0.02), and AWT (beta coefficient 0.04, p =0.03), but not with prevalent CAC (OR 0.84, 95% CI 0.61–1.17). MPO remained associated with aortic atherosclerosis phenotypes but not coronary calcification after adjustment for other inflammatory biomarkers. A significant interaction was observed between race/ethnicity, MPO and AP (p interaction =0.038), such that MPO levels in the 4th vs 1st quartile associated with prevalent AP in African Americans, (OR 1.81, 95% CI 1.23–2.65) but not in White or Hispanic participants (OR 0.99, 95% CI 0.68–1.44). Conclusion: Higher levels of MPO associated with aortic but not coronary atherosclerosis, with significant associations limited to African American participants. These findings suggest that MPO might be a novel risk factor contributing to racial disparities in peripheral vascular disease. [Copyright &y& Elsevier]

Whether concentric left ventricular (LV) hypertrophy (LVH) is a common precursor to depressed LV ejection fraction (EF) in humans is uncertain. From 1992 through 1994, 555 patients at our institution underwent echocardiography and had LVH (posterior or septal wall thickness ≥1.3 cm or concentric LVH noted) and normal LVEF. Of these, 220 (40%) had a follow-up assessment of LVEF by December 2008. The duration of follow-up was classified as short (≤7.5 years) or long (>7.5 years) term. The primary outcome was the development of a qualitatively depressed LVEF (mildly, moderately, or severely depressed). After a median follow-up of 7.5 years, 20% of the patients with concentric LVH developed a low LVEF. A low LVEF developed in 13% of subjects without interval myocardial infarction (MI) and 50% of subjects with interval MI during short-term follow-up (p <0.005). A low LVEF developed in 20% of subjects without interval MI and 44% of subjects with interval MI during long-term follow-up (p = 0.01). Of the subjects who developed a reduced LVEF, the relative wall thickness (median 0.5, 25th to 75th percentile 0.4 to 0.6) at follow-up was consistent with a concentric, rather than eccentric, phenotype. In conclusion, in patients with concentric LVH, the transition from a normal LVEF to a low LVEF was relatively infrequent (20%) after long-term follow-up in the absence of interval MI and usually did not result in a change in the LV geometry from a concentric to an eccentric phenotype. [Copyright &y& Elsevier]

Background: Cholesterol efflux capacity (CEC), which is a key step in the reverse cholesterol transport pathway, is independently associated with atherosclerotic cardiovascular disease (ASCVD). However, whether it predicts ASCVD beyond validated novel risk markers is unknown.Objectives: This study assessed if CEC improved ACSVD risk prediction beyond using coronary artery calcium (CAC), family history (FH), and high-sensitivity C-reactive protein (hs-CRP).Methods: CEC, CAC, self-reported FH, and hs-CRP were assessed among participants without baseline ASCVD who were enrolled in the Dallas Heart Study (DHS). ASCVD was defined as a first nonfatal myocardial infarction (MI) or stroke, coronary revascularization, or cardiovascular death, assessed over a median 9.4 years. Risk prediction was assessed using various modeling techniques and improvements in the c-statistic, the integrated discrimination index (IDI), and the net reclassification index (NRI).Results: The mean age of the population (N = 1,972) was 45 years, 52% had CAC (>0), 31% had FH, and 58% had elevated hs-CRP (≥2 mg/l). CEC greater than the median was associated with a 50% reduced incidence of ASCVD in those with CAC (5.4% vs. 10.5%; p = 0.003), FH (5.8% vs. 10%; p = 0.05), and elevated hs-CRP (3.8% vs. 7.9%; p = 0.004). CEC improved all metrics of discrimination and reclassification when added to CAC (c-statistic, p = 0.004; IDI, p = 0.02; NRI: 0.38; 95% confidence interval [CI]: 0.13 to 0.53), FH (c-statistic, p = 0.006; IDI, p = 0.008; NRI: 0.38; 95% CI: 0.13 to 0.55), or elevated hs-CRP (c-statistic p = 0.008; IDI p = 0.02; NRI: 0.36; 95% CI 0.12 to 0.52).Conclusions: CEC improves ASCVD risk prediction beyond using CAC, FH, and hs-CRP and warrants consideration as a novel ASCVD risk marker. [ABSTRACT FROM AUTHOR]

Therapies targeting high-density lipoprotein cholesterol content (HDL-C) have not improved coronary heart disease (CHD) outcomes. High-density lipoprotein particle concentration (HDL-P) may better predict CHD. However, the impact of race/ethnicity on the relations between HDL-P and subclinical atherosclerosis and incident CHD events has not been described. Participants from the Dallas Heart Study (DHS), a multiethnic, probabilitybased, population cohort of Dallas County adults, underwent the following baseline measurements: HDL-C, HDL-P by nuclear magnetic resonance imaging, and coronary artery calcium by electron-beam computed tomography. Participants were followed for a median of 9.3 years for incident CHD events (composite of first myocardial infarction, stroke, coronary revascularization, or cardiovascular death). The study comprised 1,977 participants free of CHD (51% women, 46% black). In adjusted models, HDL-C was not associated with prevalent coronary artery calcium (p = 0.13) or incident CHD overall (hazard ratio [HR] per 1 SD 0.89, 95% confidence interval [CI] 0.76 to 1.05). However, HDL-C was inversely associated with incident CHD among nonblack (adjusted HR per 1 SD 0.67, 95% CI 0.46 to 0.97) but not black participants (HR 0.94,95% CI 0.78 to 1.13, Pinteraction = 0.05). Conversely, HDL-P, adjusted for risk factors and HDL-C, was inversely associated with prevalent coronary artery calcium (p = 0.009) and with incident CHD overall (adjusted HR per 1 SD 0.73, 95% CI 0.62 to 0.86), with no interaction by black race/ethnicity (Pinteraction = 0.57). In conclusion, in contrast to HDL-C, the inverse relation between HDL-P and incident CHD events is consistent across ethnicities. These findings suggest that HDL-P is superior to HDL-C in predicting prevalent atherosclerosis as well as incident CHD events across a diverse population and should be considered as a therapeutic target. [ABSTRACT FROM AUTHOR]

Background Obesity has been linked to the development of hypertension, but whether total adiposity or site-specific fat accumulation underpins this relationship is unclear. Objectives This study sought to determine the relationship between adipose tissue distribution and incident hypertension. Methods Normotensive participants enrolled in the Dallas Heart Study were followed for a median of 7 years for the development of hypertension (systolic blood pressure [SBP] ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or initiation of blood pressure medications). Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) was quantified by magnetic resonance imaging and proton-spectroscopic imaging, and lower body fat (LBF) was imaged by dual-energy x-ray absorptiometry. Multivariable relative risk regression was performed to test the association between individual fat depots and incident hypertension, adjusting for age, sex, race/ethnicity, diabetes, smoking, SBP, and body mass index (BMI). Results Among 903 participants (median age, 40 years; 57% women; 60% nonwhite; median BMI 27.5 kg/m 2 ), 230 (25%) developed incident hypertension. In multivariable analyses, higher BMI was significantly associated with incident hypertension (relative risk: 1.24; 95% confidence interval: 1.12 to 1.36, per 1-SD increase). However, when VAT, SAT, and LBF were added to the model, only VAT remained independently associated with incident hypertension (relative risk: 1.22; 95% confidence interval: 1.06 to 1.39, per 1-SD increase). Conclusions Increased visceral adiposity, but not total or subcutaneous adiposity, was robustly associated with incident hypertension. Additional studies will be needed to elucidate the mechanisms behind this association. [ABSTRACT FROM AUTHOR]

Objectives: The study sought to determine the 99th percentile upper reference limit for the high-sensitivity cardiac troponin T assay (hs-cTnT) in 3 large independent cohorts. Background: The presently recommended 14 ng/l cut point for the diagnosis of myocardial infarction using the hs-cTnT assay was derived from small studies of presumably healthy individuals, with relatively little phenotypic characterization. Methods: Data were included from 3 well-characterized population-based studies: the Dallas Heart Study (DHS), the Atherosclerosis Risk in Communities (ARIC) Study, and the Cardiovascular Health Study (CHS). Within each cohort, reference subcohorts were defined excluding individuals with recent hospitalization, overt cardiovascular disease, and kidney disease (subcohort 1), and further excluding those with subclinical structural heart disease (subcohort 2). Data were analyzed stratified by age, sex, and race. Results: The 99th percentile values for the hs-cTnT assay in DHS, ARIC, and CHS were 18, 22, and 36 ng/l (subcohort 1) and 14, 21, and 28 ng/l (subcohort 2), respectively. These differences in 99th percentile values paralleled age differences across cohorts. Analyses within sex/age strata yielded similar results between cohorts. Within each cohort, 99th percentile values increased with age and were higher in men. More than 10% of men 65 to 74 years of age with no cardiovascular disease in our study had cardiac troponin T values above the current myocardial infarction threshold. Conclusions: Use of a uniform 14 ng/l cutoff for the hs-cTnT assay may lead to over-diagnosis of myocardial infarction, particularly in men and the elderly. Clinical validation is needed of new age- and sex-specific cutoff values for this assay. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study was to determine if biomarkers of subclinical myocardial injury and hemodynamic stress identify asymptomatic individuals with left ventricular hypertrophy (LVH) at higher risk for heart failure (HF) and death. Background: The interaction between LVH, low but detectable cardiac troponin T (cTnT), and elevated N-terminal pro–B-type natriuretic peptide (NT-proBNP) on cardiovascular (CV) outcomes in the general population is unknown. Methods: Participants in the Dallas Heart Study without clinical HF, LV dysfunction, or chronic kidney disease underwent measurement of LV mass by magnetic resonance imaging (MRI), cTnT by highly sensitive assay, and NT-proBNP analysis (n = 2,413). Subjects were stratified according to LVH and by detectable cTnT (≥3 pg/ml) and increased NT-proBNP (>75th age- and sex-specific percentile) levels. For each analysis, participants were categorized into groups based on the presence (+) or absence (–) of LVH and biomarker levels above (+) or below (–) the predefined threshold. Results: Nine percent of participants were LVH+, 25% cTnT+, and 24% NT-proBNP+. Those LVH+ and cTnT+ and/or NT-proBNP+ (n = 144) were older and more likely to be male, with a greater risk factor burden and more severe LVH compared with those who were LVH+ biomarker– (p < 0.01 for each). The cumulative incidence of HF or CV death over 8 years among LVH+ cTnT+ was 21% versus 1% (LVH– cTnT–), 4% (LVH– cTnT+), and 6% (LVH+ cTnT–) (p < 0.0001). The interactions between LVH and cTnT (pinteraction = 0.0005) and LVH and NT-proBNP (pinteraction = 0.014) were highly significant. Individuals who were LVH+ and either cTnT+ or NT-proBNP+ remained at >4-fold higher risk for HF or CV death after multivariable adjustment for CV risk factors, renal function, and LV mass compared with those who were LVH– biomarker–. Conclusions: Minimal elevations in biomarkers of subclinical cardiac injury and hemodynamic stress modify the association of LVH with adverse outcomes, identifying a malignant subphenotype of LVH with high risk for progression to HF and CV death. [Copyright &y& Elsevier]

Objectives: The aim of this study was to determine the relative contribution of the muscle and ventilatory pumps to stroke volume in patients without a subpulmonic ventricle. Background: In patients with Fontan circulation, it is unclear how venous return is augmented to increase stroke volume and cardiac output during exercise. Methods: Cardiac output (acetylene rebreathing), heart rate (electrocardiography), oxygen uptake (Douglas bag technique), and ventilation were measured in 9 patients age 15.8 ± 6 years at 6.1 ± 1.8 years after Fontan operation and 8 matched controls. Data were obtained at rest, after 3 min of steady-state exercise (Ex) on a cycle ergometer at 50% of individual working capacity, during unloaded cycling at 0 W (muscle pump alone), during unloaded cycling with isocapnic hyperpnea (muscle and ventilatory pump), during Ex plus an inspiratory load of 12.8 ± 1.5 cm water, and during Ex plus an expiratory load of 12.8 ± 1.6 cm water. Results: In Fontan patients, the largest increases in stroke volume and stroke volume index were during zero-resistance cycling. An additional increase with submaximal exercise occurred in controls only. During Ex plus expiratory load, stroke volume indexes were reduced to baseline, non-exercise levels in Fontan patients, without significant changes in controls. Conclusions: With Fontan circulation increases in cardiac output and stroke volume during Ex were due to the muscle pump, with a small additional contribution by the ventilatory pump. An increase in intrathoracic pressure played a deleterious role in Fontan circulation by decreasing systemic venous return and stroke volume. [Copyright &y& Elsevier]