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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., Competing Interests: Funding Support and Author Disclosures The ARIC study has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under contracts HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I. The Dallas Heart Study was funded by a grant from the Donald W. Reynolds Foundation. The Multi-Ethnic Study of Atherosclerosis was supported by the National Heart, Lung, and Blood Institute (R01 HL071739 and contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, and N01-C-95169). The PREVEND cohort study was supported by The Dutch Kidney Foundation which supported the infrastructure of the PREVEND program from 1997 to 2003 (Grant E.033). The University Medical Center Groningen supported the infrastructure from 2003 to 2006. Dr Pandey is supported by the Texas Health Resources Clinical Scholarship, the Gilead Sciences Research Scholar Program, the National Institute of Aging GEMSSTAR Grant (1R03AG067960-01), and Applied Therapeutics; has served on the advisory board for Roche Diagnostics; and has received nonfinancial support from Pfizer and Merck. Dr Patel has served as a consultant to Novo Nordisk. Dr Segar has received speaker fees from Merck and is on the advisory board of descendantsDNA. Dr Shapiro has received grants from Amgen, Boehringer Ingelheim, 89Bio, Esperion, Novartis, Ionis, Merck, and New Amsterdam; has served on scientific advisory boards for Amgen, Agepha, Ionis, Novartis, Precision BioScience, New Amsterdam, and Merck; and has served as a consultant to Ionis, Novartis, Regeneron, Aidoc, Shanghai Pharma Biotherapeutics, Kaneka, and Novo Nordisk. Dr Connelly is an employee of Labcorp. Dr Rohatgi has received a research grant from CSL Behring; has served as a collaborator to Quest; has served as a consultant to HDL Diagnostics, JP Morgan, Johnson and Johnson, and Raydel. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: 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., Objectives: 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)., Methods: 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., Results: 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., Conclusion: 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., Competing Interests: Declaration of Competing Interest Anand Rohatgi: CSL, consultant, modest. Quest, academic collaboration, no salary. All other authors have no conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Background and Aims: Soluble Fms-like tyrosine kinase-1 (sFlt-1) plays a role in angiogenesis, atherogenesis, and preeclampsia. The relationship of sFlt-1 with markers of subclinical atherosclerosis and future atherosclerotic cardiovascular disease (ASCVD) events in a generally healthy population is unknown., Methods: Participants in the Dallas Heart Study with sFlt-1 measured were included (n = 3292). Abdominal aortic atherosclerosis was measured by MRI and coronary artery calcium (CAC) by CT. The cohort was also followed for subsequent ASCVD events (CV death, MI, stroke, unstable angina, revascularization). Multivariable linear and logistic regression analyses and Cox regression analyses were performed adjusting for demographics and traditional cardiac risk factors., Results: sFlt-1 levels were higher in older individuals, males, and African Americans, and tracked with most traditional risk factors. sFlt-1 was significantly associated with higher prevalence of aortic plaque [OR 1.33 (95% CI 1.02-1.73)], greater abdominal aortic wall thickness (p<0.01) and aortic plaque area (p<0.02) but no difference in coronary artery calcification. There were 322 ASCVD events over 12 years of follow-up. Higher sFlt-1 levels associated with increased ASCVD events in unadjusted (16.1% vs. 8.9%, p<0.001, quartile 4 vs. quartile 1) and adjusted analyses (HR 1.58 [1.14-2.18], p<0.01, quartile 4 vs. quartile 1). Findings were unchanged when analyzing sFlt-1 as a continuous variable or when excluding those with a history of ASCVD., Conclusions: In a population-based cohort, sFlt-1 is associated with measures of subclinical aortic atherosclerosis and clinical ASCVD events. Future studies are warranted on the therapeutic potential of targeting sFlt-1 for atherosclerotic disease., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Aims: Inflammatory biomarkers and adipocytokines (IBA) may contribute to atherosclerosis by promoting vascular inflammation. The association between IBA and coronary artery calcium (CAC), a marker of subclinical atherosclerosis, is not well defined in South Asians (SA). We hypothesized that IBA (high sensitivity C-reactive protein [hsCRP], tumor necrosis factor alpha [TNF-α], adiponectin, and leptin) were independently associated with and improved discrimination of CAC among SA., Methods: We analyzed IBA and CAC among participants in the prospective Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. We used logistic regression models to examine cross-sectional associations of IBA with CAC presence (CAC >0) and severity (CAC >100), and C-statistics to assess the incremental contribution of each IBA to traditional risk factors (TRF) from the AHA/ACC Pooled Cohort Equations (PCE) for discrimination of CAC., Results: Among 906 participants in the MASALA study, women (n = 420) had significantly higher levels of hsCRP, adiponectin, and leptin but lower levels of TNF-α than men (p < .01 for all). There was no significant association between any of the four IBA and either CAC category in multivariable-adjusted models, respectively. Lastly, none of the four IBA improved discrimination of CAC presence or severity when added to elements of the PCE., Conclusions: IBA were not associated with CAC presence or severity in the MASALA population. IBA did not help identify SA at risk of subclinical atherosclerosis, although associations with ASCVD events remain unclear. In SA, CAC may have a distinct pathophysiology independent of inflammation as measured by IBA., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (Copyright © 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Myeloperoxidase (MPO), a product of systemic inflammation, promotes oxidation of lipoproteins; whereas, high-density lipoprotein (HDL) exerts anti-oxidative effects in part via paraoxonase-1 (PON1). MPO induces dysfunctional HDL particles; however, the interaction of circulating levels of these measures in cardiovascular disease (CVD) has not been studied in humans. We tested whether serum levels of MPO indexed to HDL particle concentration (MPO/HDLp) are associated with increased CVD risk in a large multiethnic population sample, free of CVD at baseline., Methods: Levels of MPO, HDL-C, and HDL particle concentration (HDLp) by NMR were measured at baseline in 2924 adults free of CVD. The associations of MPO/HDLp with incident ASCVD (first non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or CVD death) and total CVD were assessed in Cox proportional-hazards models adjusted for traditional risk factors. The median follow-up period was 9.4 years., Results: Adjusted for sex and race/ethnicity, MPO/HDLp was associated directly with body mass index, smoking status, high-sensitivity C-reactive protein, and interleukin 18, and inversely with age, HDL-C levels, HDL size, and PON1 arylesterase activity, but not with cholesterol efflux. In fully adjusted models, the highest versus lowest quartile of MPO/HDLp was associated with a 74% increase in incident ASCVD (aHR, 1.74, 95% CI 1.12-2.70) and a 91% increase in total incident CVD (aHR, 1.91, 95% CI 1.27-2.85)., Conclusions: Increased MPO indexed to HDL particle concentration (MPO/HDLp) at baseline is associated with increased risk of incident CVD events in a population initially free of CVD over the 9.4 year period., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to assess whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels differ according to race/ethnicity., Background: Natriuretic peptides (NP) are hormones with natriuretic, diuretic, and vasodilatory effects. Experimental NP deficiency promotes salt-sensitive hypertension and cardiac hypertrophy, conditions that are more common among black individuals., Methods: We examined plasma NT-proBNP levels according to race/ethnicity in 3,148 individuals (51% black, 31% white, 18% Hispanic) free of prevalent cardiovascular disease in the Dallas Heart Study. NT-proBNP values in the bottom sex-specific quartile were defined as low. Multivariable linear and logistic regression analyses were performed adjusting for clinical covariates and magnetic resonance imaging measurements of cardiac structure and function., Results: Hypertension was present in 41%, 25%, and 16% of black, white, and Hispanic individuals, respectively. Unadjusted NT-proBNP levels were lowest in black (median: 24 pg/ml; interquartile range [IQR]: 10 to 52 pg/ml) as compared with Hispanic (30 pg/ml; IQR: 14 to 59 pg/ml) and white individuals (32 pg/ml; IQR: 16 to 62 pg/ml), p < 0.0001. In multivariable-adjusted models, black individuals still had significantly lower NT-proBNP levels (-39% [95% confidence interval: -46% to -31%]; p < 0.0001) and greater odds of having low NT-proBNP (odds ratio: 2.46 [95% confidence interval: 1.86 to 3.26]), compared with white individuals. In contrast, NT-proBNP levels did not significantly differ between Hispanic and white individuals (p = 0.28). The finding of lower NT-proBNP levels in black individuals was similar when analyses were restricted to healthy participants without cardiovascular risk factors., Conclusions: In this multiethnic cohort, NT-proBNP levels differ substantially according to race/ethnicity. Despite a higher prevalence of hypertension, black individuals had significantly lower NP levels than white and Hispanic individuals. A relative NP "deficiency" among black individuals may lead to greater susceptibility to salt retention and hypertension., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to compare the cross-sectional associations between fitness and echocardiographic measures of cardiac structure and function., Background: Cardiorespiratory fitness is inversely associated with heart failure risk. However, the mechanism through which fitness lowers heart failure risk is not fully understood., Methods: We included 1,678 men and 1,247 women from the Cooper Center Longitudinal Study who received an echocardiogram from 1999 to 2011. Fitness was estimated by Balke protocol (in metabolic equivalents) and also categorized into age-specific quartiles, with quartile 1 representing low fitness. Cross-sectional associations between fitness (in metabolic equivalents) and relative wall thickness, left ventricular end-diastolic diameter indexed to body surface area, left atrial volume indexed to body surface area, left ventricular systolic function, and E/e' ratio were determined using multivariable linear regression analysis., Results: Higher levels of mid-life fitness (metabolic equivalents) were associated with larger indexed left atrial volume (men: beta = 0.769, p < 0.0001; women: beta = 0.879, p value ≤0.0001) and indexed left ventricular end-diastolic diameter (men: beta = 0.231, p < 0.001; women: beta = 0.264, p < 0.0001). Similarly, a higher level of fitness was associated with a smaller relative wall thickness (men: beta = -0.002, p = 0.04; women: beta = -0.005, p < 0.0001) and E/e' ratio (men: beta = -0.11, p = 0.003; women: beta = -0.13, p = 0.01). However, there was no association between low fitness and left ventricular systolic function (p = NS)., Conclusions: Low fitness is associated with a higher prevalence of concentric remodeling and diastolic dysfunction, suggesting that exercise may lower heart failure risk through its effect on favorable cardiac remodeling and improved diastolic function., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to examine the frequency and hemodynamic correlates of shortness of breath when bending forward, a symptom we have termed "bendopnea.", Background: Many heart failure patients describe bendopnea such as when putting on their shoes. This symptom has not previously been characterized., Methods: We conducted a prospective study of 102 subjects with systolic heart failure referred for right-heart catheterization. Time to onset of bendopnea was measured prior to catheterization. Forty-six subjects also underwent hemodynamic assessment when sitting and bending. Hemodynamic profiles were assigned on the basis of whether pulmonary capillary wedge pressure (PCWP) was ≥ 22 mm Hg and cardiac index (CI) was ≤ 2.2 l/min/m(2)., Results: Bendopnea was present in 29 of 102 (28%) subjects with median (25th, 75th percentiles) time to onset of 8 (7, 11) seconds. Subjects with bendopnea had higher supine right atrial pressure (RAP) (p = 0.001) and PCWP (p = 0.0004) than those without bendopnea but similar CI (p = 0.2). RAP and PCWP increased comparably in subjects with and without bendopnea when bending, but CI did not change. In those with, versus without, bendopnea, there was more than a 3-fold higher frequency of a supine hemodynamic profile consisting of elevated PCWP with low CI (55% vs. 16%, respectively, p < 0.001) but no association with a profile of elevated PCWP with normal CI (p = 0.95)., Conclusions: Bendopnea is mediated via a further increase in filling pressures during bending when filling pressures are already high, particularly if CI is reduced. Awareness of bendopnea should improve noninvasive assessment of hemodynamics in subjects with heart failure., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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 © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Although risk factors for left ventricular (LV) hypertrophy in the native heart are well known, as is its association with increased risk of adverse outcomes, such information is poorly defined in heart transplant (HTx) recipients. We determined whether increased LV mass and concentricity (mass/volume) were associated with death in patients after HTx., Methods: Between May 2003 and May 2006, 140 HTx recipients underwent cardiac magnetic resonance imaging (MRI). Clinical characteristics associated with increased LV mass were determined. Cox proportional hazard models were constructed to assess the relationship of LV mass and concentricity with death., Results: MRIs were acquired a median of 6.0 years after transplant. The top quartile of indexed LV mass and concentricity were 35.8 g/m(2.7) or higher and 1.5 g/ml or higher, respectively. History of rejection (odds ratio [OR], 5.9; 95% confidence interval [CI], 2.1-16.4; p < 0.01), diabetes (OR, 3.3; 95% CI, 1.3-8.2; p = 0.01), and post-transplant year of MRI acquisition (OR, 1.2; 95% CI, 1.1-1.4; p < 0.01) were associated with the top quartile of LV mass in multivariable models. LV mass and concentricity were independently associated with cardiovascular death (hazard risk [HR], 1.11 per g/m;(2.7) HR, 10.1 per g/ml, p ≤ 0.01, respectively). LV concentricity was independently associated with all-cause mortality (HR, 4.4 per g/ml, p < 0.01)., Conclusion: A history of rejection and diabetes are associated with increased LV mass. Increased LV mass, particularly of a concentric phenotype, is an independent risk factor for cardiovascular and all-cause mortality after HTx., (Copyright © 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: Lymphotoxin β receptor (LTβR), a member of the tumor necrosis factor superfamily, binds ligands expressed by activated lymphocytes. Interruption of LTβR signaling improves autoimmune diseases and alters lipid homeostasis. We assayed circulating LTβR and examined its association with atherosclerosis phenotypes in a population-based sample., Methods and Results: Plasma LTβR was measured by ELISA in 3215 subjects enrolled in the Dallas Heart Study. Atherosclerosis was assessed using CT measurements of coronary calcium (CAC) and abdominal MRI measurements of aortic plaque (AP) (n=2252) and aortic wall thickness (AWT) (n=2265). We analyzed associations between LTβR and atherosclerosis using multivariable logistic and linear regression methods. Higher levels of LTβR associated with most traditional cardiovascular risk factors, multiple inflammatory markers, and markers of cardiac injury. Univariable analyses demonstrated significant associations of LTβR with CAC, AP, and AWT (p<0.0001 for each). In multivariable models adjusted for traditional risk factors, the 4th vs. the 1st quartile of LTβR remained associated with prevalent CAC, AP, and increased AWT (all p<0.05). Similar associations were observed when LTβR was modeled as a log-transformed continuous variable., Conclusion: LTβR levels are independently associated with atherosclerosis in multiple vascular beds. These findings support further investigation of the lymphotoxin/LTβR pathway in atherosclerosis., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

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 (> or =39%), and high short-term risk (> or =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/m(2) vs. 90 +/- 12 g/m(2) and women: 75 +/- 14 g/m(2) vs. 71 +/- 10 g/m(2), 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 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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.