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Background: Visceral and ectopic fat are key drivers of adverse cardiometabolic outcomes in obesity. We aimed to evaluate the effects of injectable liraglutide 3·0 mg daily on body fat distribution in adults with overweight or obesity without type 2 diabetes at high cardiovascular disease risk., Methods: In this randomised, double-blind, placebo-controlled, phase 4, single centre trial, we enrolled community-dwelling adults, recruited from the University of Texas Southwestern Medical Center, with BMI of at least 30 kg/m 2 or BMI of at least 27 kg/m 2 with metabolic syndrome but without diabetes and randomly assigned them, in a 1:1 ratio, to 40 weeks of treatment with once-daily subcutaneous liraglutide 3·0 mg or placebo, in addition to a 500 kcal deficient diet and guideline-recommended physical activity counselling. The primary endpoint was percentage reduction in visceral adipose tissue (VAT) measured with MRI. All randomly assigned participants with a follow-up imaging assessment were included in efficacy analyses and all participants who received at least one dose of study drug were included in the safety analyses. The trial is registered on ClinicalTrials.gov: NCT03038620., Findings: Between July 20, 2017 and Feb 21, 2020 from 235 participants assessed for eligibility, 185 participants were randomly assigned (n=92 liraglutide, n=93 placebo) and 128 (n=73 liraglutide, n=55 placebo) were included in the final analysis (92% female participants, 37% Black participants, 24% Hispanic participants, mean age 50·2 years (SD 9·4), mean BMI 37·7 kg/m 2 ). Mean change in VAT over median 36·2 weeks was -12·49% (SD 9·3%) with liraglutide compared with -1·63% (SD 12·3%) with placebo, estimated treatment difference -10·86% (95% CI -6·97 to -14·75, p<0·0001). Effects seemed consistent across subgroups of age, sex, race-ethnicity, BMI, and baseline prediabetes. The most frequently reported adverse events were gastrointestinal-related (43 [47%] of 92 with liraglutide and 12 [13%] of 93 with placebo) and upper respiratory tract infections (10 [11%] of 92 with liraglutide and 14 [15%] of 93 with placebo)., Interpretation: In adults with overweight or obesity at high cardiovascular disease risk, once-daily liraglutide 3·0 mg plus lifestyle intervention significantly lowered visceral adipose tissue over 40 weeks of treatment. Visceral fat reduction may be one mechanism to explain the benefits seen on cardiovascular outcomes in previous trials with liraglutide among patients with type 2 diabetes., Funding: NovoNordisk., Competing Interests: Declaration of interests IJN has previously received consulting income from Merck, honoraria, consulting, speaking fees, and travel support from Boehringer-Ingelheim–Lilly Alliance, a research grant from Novo Nordisk, and has been a member of the scientific advisory board of AMRA Medical. PHJ has received consulting income from Regeneron and Bayer, reports equity in G3 Therapeutics, and grant support from AHA, NASA, Novo Nordisk, Amgen, GlaxoSmithKline, Sanofi, AstraZeneca, and Novartis. SPM has received consulting income from Novo Nordisk, Boston Scientific, Asahi Intec, and Abbott Vascular. All other authors have no potential competing interests to report. AP has served on the advisory board of Roche Diagnostics, has received non-financial support from Pfizer and Merck, has received research support from the Texas Health Resources Clinical Scholarship, the Gilead Sciences Research Scholar Program, the National Institute of Aging GEMSSTAR Grant (1R03AG067960-01), and Applied Therapeutics., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to determine the effects of empagliflozin on glycerol-derived hepatic gluconeogenesis in adults with obesity without type 2 diabetes mellitus (T2DM) using oral carbon 13 ( 13 C)-labeled glycerol., Methods: A randomized, double-blind, placebo-controlled trial was performed in participants with magnetic resonance imaging assessment of body fat and measurement of glycerol-derived 13 C enrichment in plasma glucose by nuclear magnetic resonance spectroscopy following ingestion of [U- 13 C 3 ]glycerol. Participants were randomized to oral empagliflozin 10 mg once daily or placebo for 3 months. Glycerol-derived 13 C enrichment studies were repeated, and treatment differences in the mean percentage of 13 C glycerol enrichment in glucose were compared using mixed linear models., Results: Thirty-five participants completed the study. Empagliflozin increased glycerol-derived 13 C enrichment between baseline and follow-up by 6.5% (P = 0.005), consistent with less glycerol from visceral adipose tissue (VAT). No difference was found with placebo. Glycerol-derived 13 C enrichment was lower in participants with high VAT compared with low VAT by 12.6% (P = 0.04), but there was no heterogeneity of the treatment effect by baseline VAT. Glycerol-derived 13 C enrichment was inversely correlated with VAT but was not correlated with weight loss., Conclusions: VAT is associated with endogenous glycerol-derived hepatic gluconeogenesis, and empagliflozin reduces endogenous glycerol gluconeogenesis in adults with obesity without T2DM. These findings suggest a mechanism by which sodium-glucose cotransporter 2 inhibitors may prevent T2DM in obesity., (© 2020 The Obesity Society.)

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 ≥30kg/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 3h 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 49years, 40.1kg/m 2 , and 98mg/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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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

Objective: Visceral (VAT) and abdominal subcutaneous (SAT) adipose tissues contribute to obesity but may have different metabolic and atherosclerosis risk profiles. We sought to determine the associations of abdominal VAT and SAT mass with markers of cardiac and metabolic risk in a large, multiethnic, population-based cohort of obese adults., Design and Methods: Among obese participants in the Dallas Heart Study, we examined the cross-sectional associations of abdominal VAT and SAT mass, assessed by magnetic resonance imaging (MRI) and indexed to body surface area (BSA), with circulating biomarkers of insulin resistance, dyslipidemia, and inflammation (n = 942); and with aortic plaque and liver fat by MRI and coronary calcium by computed tomography (n = 1200). Associations of VAT/BSA and SAT/BSA were examined after adjustment for age, sex, race, menopause, and body mass index., Results: In multivariable models, VAT significantly associated with the homeostasis model assessment of insulin resistance (HOMA-IR), lower adiponectin, smaller LDL and HDL particle size, larger VLDL size, and increased LDL and VLDL particle number (p < 0.001 for each). VAT also associated with prevalent diabetes, metabolic syndrome, hepatic steatosis, and aortic plaque (p < 0.001 for each). VAT independently associated with C-reactive protein but not with any other inflammatory biomarkers tested. In contrast, SAT associated with leptin and inflammatory biomarkers, but not with dyslipidemia or atherosclerosis. Associations between SAT and HOMA-IR were significant in univariable analyses but attenuated after multivariable adjustment., Conclusion: VAT associated with an adverse metabolic, dyslipidemic, and atherogenic obesity phenotype. In contrast, SAT demonstrated a more benign phenotype, characterized by modest associations with inflammatory biomarkers and leptin, but no independent association with dyslipidemia, insulin resistance, or atherosclerosis in obese individuals. These findings suggest that abdominal fat distribution defines distinct obesity sub-phenotypes with heterogeneous metabolic and atherosclerosis risk., (Copyright © 2012 The Obesity Society.)

Background: The relation of body fat distribution to left ventricular (LV) structure and function is poorly defined., Methods and Results: A total of 2710 participants without heart failure or LV dysfunction in the Dallas Heart Study underwent dual energy x-ray absorptiometry and MRI assessment of fat distribution, LV morphology, and hemodynamics. Cross-sectional associations of fat distribution with LV structure and function were examined after adjustment for age, sex, race, comorbidities, and lean mass. Mean age was 44 years with 55% women; 48% blacks; and 44% obese. After multivariable adjustment, visceral adipose tissue was associated with concentric remodeling characterized by lower LV end-diastolic volume (β=-0.21), higher concentricity (β=0.20), and wall thickness (β=0.09; P<0.0001 for all). In contrast, lower body subcutaneous fat was associated with higher LV end-diastolic volume (β=0.48), reduced concentricity (β=-0.50), and wall thickness (β=-0.28, P<0.0001 for all). Visceral adipose tissue was also associated with lower cardiac output (β=-0.10, P<0.05) and higher systemic vascular resistance (β=0.08, P<0.05), whereas lower body subcutaneous fat associated with higher cardiac output (β=0.20, P<0.0001) and lower systemic vascular resistance (β=-0.18, P<0.0001). Abdominal subcutaneous fat showed weaker associations with concentric remodeling and was not associated with hemodynamics. Among the subset of obese participants, visceral adipose tissue, but not abdominal subcutaneous fat, was significantly associated with concentric remodeling., Conclusions: Visceral adipose tissue, a marker of central adiposity, was independently associated with concentric LV remodeling and adverse hemodynamics. In contrast, lower body subcutaneous fat was associated with eccentric remodeling. The impact of body fat distribution on heart failure risk requires prospective study.

Objectives: Although psychosocial stress can result in adverse health outcomes, little is known about how perceptions of neighborhood conditions, a measure of environment-derived stress, may impact obesity. The association between perceptions of neighborhood environment and obesity (defined as body mass index [BMI] ≥ 30 kg/m(2) ) among 5,907 participants in the Dallas Heart Study, a multi-ethnic, probability-based sample of Dallas County residents was examined., Design and Methods: Participants were asked to respond to 18 questions about perceptions of their neighborhood. Factor analysis was used to identify three factors associated with neighborhood perceptions: neighborhood violence, physical environment, and social cohesion. Logistic regression analyses were performed to determine the relationship between each factor (higher quintile = more unfavorable perceptions) and the odds of obesity., Results: Decreasing age, income, and education associated with unfavorable overall neighborhood perceptions and unfavorable perceptions about specific neighborhood factors (P trend <0.05 for all). Increasing BMI was associated with unfavorable perceptions about physical environment (P trend <0.05) but not violence or social cohesion. After adjustment for race, age, sex, income, education, and length of residence, physical environment perception score in the highest quintile remained associated with a 25% greater odds of obesity (OR 1.25, [95% CI 1.03-1.50]). Predictors of obesity related to environmental perceptions included heavy traffic (OR 1.39, [1.17-1.64]), trash/litter in neighborhood (OR 1.27, [1.01-1.46]), lack of recreational areas (OR 1.21, [1.01-1.46]), and lack of sidewalks (OR 1.25, [95% CI 1.04-1.51])., Conclusions: Thus, unfavorable perceptions of environmental physical conditions are related to increased obesity. Efforts to improve the physical characteristics of neighborhoods, or the perceptions of those characteristics, may assist in the prevention of obesity in this community., (Copyright © 2012 The Obesity Society.)

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/m(2); overweight, 25 to <30 kg/m(2); obese, ≥30 kg/m(2)) 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., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Context: The risk of type 2 diabetes mellitus is heterogeneous among obese individuals. Factors that discriminate prediabetes or diabetes risk within this population have not been well characterized. A dysfunctional adiposity phenotype, characterized by excess visceral fat and insulin resistance, may contribute to diabetes development in those with obesity., Objective: To investigate associations between adiposity phenotypes and risk for incident prediabetes and diabetes in a multiethnic, population-based cohort of obese adults., Design, Setting, and Participants: Among 732 obese participants (body mass index ≥30) aged 30 to 65 years without diabetes or cardiovascular disease enrolled between 2000 and 2002 in the Dallas Heart Study, we measured body composition by dual energy x-ray absorptiometry and magnetic resonance imaging (MRI); circulating adipokines and biomarkers of insulin resistance, dyslipidemia, and inflammation; and subclinical atherosclerosis and cardiac structure and function by computed tomography and MRI., Main Outcome Measures: Incidence of diabetes through a median 7.0 years (interquartile range, 6.6-7.6) of follow-up. In a subgroup of 512 participants with normal fasting glucose values at baseline, incidence of the composite of prediabetes or diabetes was determined., Results: Of the 732 participants (mean age, 43 years; 65% women; 71% nonwhite), 84 (11.5%) developed diabetes. In multivariable analysis, higher baseline visceral fat mass (odds ratio [OR] per 1 SD [1.4 kg], 2.4; 95% CI, 1.6-3.7), fructosamine level (OR per 1 SD [1.1 μmol/L], 2.0; 95% CI, 1.4-2.7), fasting glucose level (OR per 1 SD [1.1 μmol/L], 1.9; 95% CI, 1.4-2.6), family history of diabetes (OR, 2.3; 95% CI, 1.3-4.3), systolic blood pressure (OR per 10 mm Hg, 1.3; 95% CI, 1.1-1.5), and weight gain over follow-up (OR per 1 kg, 1.06; 95% CI, 1.02-1.10) were independently associated with diabetes, with no associations observed for body mass index, total body fat, or abdominal subcutaneous fat. Among the 512 participants with normal baseline glucose values, the composite outcome of prediabetes or diabetes occurred in 39.1% and was independently associated with baseline measurements of visceral fat mass; levels of fasting glucose, insulin, and fructosamine; older age; nonwhite race; family history of diabetes; and weight gain over follow-up (P < .05 for each) but not with measurements of general adiposity., Conclusion: Excess visceral fat and insulin resistance, but not general adiposity, were independently associated with incident prediabetes and type 2 diabetes mellitus in obese adults.

Clinician counseling is a catalyst for lifestyle modification in obesity. Unfortunately, clinicians do not appropriately counsel all obese patients about lifestyle modification. The extent of disparities in clinician counseling is not well understood. Obese participants (BMI ≥30 kg/m(2), N = 2097) in the Dallas Heart Study (DHS), a probability-based sample of Dallas County residents ages 18-65, were surveyed regarding health-care utilization and lifestyle counseling over the year prior to DHS enrollment. Health-care utilization and counseling were compared between obese participants across three categories based on the presence of 0, 1, or 2+ of the following cardiovascular (CV) risk factors: hypertension, hypercholesterolemia, or diabetes. Logistic regression modeling was used to determine likelihood of counseling in those with 0 vs. 1+ CV risk factors, stratified by race, adjusting for age, sex, insurance status, and education. Among obese subjects who sought medical care, those with 0 CV risk factors, compared to those with 1 or 2+ CV risk factors, were less likely to report counseling about losing weight (41% vs. 67% vs. 87%, P trend <0.001), dietary changes (44% vs. 71% vs. 85%, P trend <0.001), and physical activity (46% vs. 71% vs. 86%, P trend <0.001). Blacks and Hispanics without CV risk factors had a lower odds of receiving counseling than whites without risk factors on weight loss (adjusted odds ratio (OR), 95% confidence interval (CI) for nonwhites 0.19, [0.13-0.28], whites 0.48, [0.26-0.87]); dietary changes (nonwhites 0.19, [0.13-0.27], whites 0.37, [0.21-0.64]); and physical activity (nonwhites 0.22, [0.16-0.32], whites 0.32, [0.18-0.57]). Lifestyle counseling rates by clinicians are suboptimal among obese patients without CV risk factors, especially blacks and Hispanics. Systematic education about and application of lifestyle interventions could capitalize on opportunities for primary CV risk prevention.

Background--Although contributors to remodeling of the left ventricle (LV) have been well studied in general population cohorts, few data are available describing factors influencing changes in left atrial (LA) structure. Methods and Results--Maximum LA volume was determined by cardiac magnetic resonance imaging among 748 participants in the Dallas Heart Study at 2 visits a mean of 8 years apart. Associations of changes in LA volume (ΔLAV) with traditional risk factors, biomarkers, LV geometry, and remodeling by cardiac magnetic resonance imaging and detailed measurements of global and regional adiposity (by magnetic resonance imaging and dual-energy x ray absorptiometry) were assessed using multivariable linear regression. Greater ΔLAV was independently associated with black and Hispanic race/ethnicity, change in systolic blood pressure, LV mass and ΔLV mass, N-terminal probrain natriuretic peptide and change in N-terminal probrain natriuretic peptide, and body mass index (P<0.05 for each). In subanalyses, the associations of ΔLAV with LV mass parameters were driven by associations with baseline and ΔLV end diastolic volume (P<0.0001 for each) and not wall thickness (P=0.21). Associations of ΔLAV with body mass index were explained exclusively by associations with visceral fat mass (P=0.002), with no association seen between ΔLAV and subcutaneous abdominal fat (P=0.47) or lower body fat (P=0.30). Conclusions--Left atrial dilatation in the population is more common in black and Hispanic than in white individuals and is associated with parallel changes in the LV. LA dilatation may be mediated by blood pressure control and the development of visceral adiposity. [ABSTRACT FROM AUTHOR]

Background We compared cardiovascular (CV) risk factors (CVRFs) of community-based participatory research (CBPR) participants with the community population to better understand how CBPR participants relate to the population as a whole. Methods GoodNEWS participants in 20 African-American churches in Dallas, Texas were compared with age/sex-matched African-Americans in the Dallas Heart Study (DHS), a probability-based sample of Dallas County residents. DHS characteristics were sample-weight adjusted to represent the Dallas County population. Results Despite having more education (college education: 75 versus 51%, P< 0.0001), GoodNEWS participants were more obese (mean body mass index: 34 versus 31 kg/m2, P< 0.001) and had more diabetes (23 versus 12%, P< 0.001) and hyperlipidemia (53 versus 14%, P< 0.001) compared with African-Americans in Dallas County. GoodNEWS participants had higher rates of treatment and control of most CVRFs (treated hyperlipidemia: 95 versus 64%, P< 0.001; controlled diabetes: 95 versus 21%, P< 0.001; controlled hypertension: 70 versus 52%, P= 0.003), were more physically active (233 versus 177 metabolic equivalent units-min/week, P< 0.0001) and less likely to smoke (10 versus 30%, P< 0.001). Conclusions Compared with African-Americans in Dallas County, CBPR participants in church congregations were more educated, physically active and had more treatment and control of most CVRFs. Surprisingly, this motivated population had a greater obesity burden, identifying them as a prime target for CBPR-focused obesity treatment. [ABSTRACT FROM PUBLISHER]

Obesity and decreased cardiorespiratory fitness (CRF) are independent risk factors for mortality, but higher CRF may minimize the adverse impacts of obesity. Using deep phenotyping, we explored what blood-based and imaging biomarkers were associated with higher CRF among both non-obese and obese individuals in a large multiethnic epidemiological cohort to better understand the biology of the fat but fit phenotype. We performed a cross-sectional analysis of participants enrolled in the Dallas Heart Study between 2007 to 2009 without cardiovascular disease, HIV, cancer, or end-stage renal disease. A total of 2351 individuals were divided into four groups by obesity status (BMI < or ≥30 kg/m2) and CRF (unfit or fit defined as >25th percentile by age and sex, measured using a submaximal treadmill test). Multivariate logistic regression analyses were used to compare circulating biomarkers of cardiometabolic risk, cardiac structure by cardiac magnetic resonance, and adipose depots by dual-energy X-ray absorptiometry between these groups. There were 1052 non-obese and fit, 227 non-obese and unfit, 716 obese and fit, and 356 obese and unfit persons. After adjustment for sex, race, and BMI, factors that were independently associated with fitness in the obese group (versus obese and unfit group) were lower pulse rate (OR, 0.56; 95% CI 0.44-0.71), higher end-diastolic volume indexed to body-surface-area (OR, 1.37; 95% CI 1.06-1.77), and lower subcutaneous fat indexed to body-surface-area (OR, 0.57; 95% CI 0.34-0.96). Lower pulse rate and subcutaneous fat were also associated with being more fit in the non-obese; but contrary to the obese, no cardiac structural measures were statistically significant. These findings suggest that the fat but fit phenotype is characterized by a lower resting pulse, less subcutaneous fat, and a higher left ventricular end-diastolic volume. Being fit is linked to beneficial physiological and cardiovascular changes, irrespective of BMI. [ABSTRACT FROM AUTHOR]

The Fick principle (cardiac output [Qc] = oxygen uptake [Vo 2]/arteriovenous oxygen difference) can be used to calculate Qc, with VO2 frequently estimated by derived equations. To compare the accuracy of measured versus estimated VO2, data were analyzed from 2 studies in which VO2 at rest was measured using the Douglas bag technique. One study comprised adults with diabetes, and the other was an exercise study of healthy adults. VO2 at rest was estimated as VO2 (ml/min) = 125 ml/min/m2 × body surface area (m2), with sensitivity analyses evaluating 2 other commonly used equations. Mean absolute difference (milliliters per minute) and ordinary least products regression were used to assess agreement between measured and estimated VO2. Overall, mean measured versus estimated VO2 differed significantly (307.2 ± 75.2 vs 259.9 ± 36.7 ml/min, p <0.0001), with a mean absolute difference of 52.9 ± 43.2 ml/min (p <0.0001); 20% of the estimates differed by >25% from the measured VO2. Mean absolute difference increased from 36.7 ml/min in the lowest body mass index group (<25 kg/m2) to 91.7 ml/min in the highest group (≥40 kg/m2) (p for trend = 0.001) and was significantly higher in men than in women (65.6 vs 33.9 ml/min, p = 0.001); error was similar by median-split age (p = 0.65) and race (p = 0.34). Similar results were obtained when evaluating each of the other 2 estimating equations. Estimation of VO2 at rest is inaccurate, especially in men and with increasing adiposity. In conclusion, when clinical hemodynamic assessment is performed, VO2 should be measured, not estimated. [ABSTRACT FROM AUTHOR]

Background: GlycA, an integrated glycosylation protein of five acute phase reactants, is a novel inflammatory biomarker associated with both obesity and cardiovascular disease (CVD). We assessed the hypothesis that visceral adipose tissue (VAT) associates with GlycA and this association may partially explain the pathophysiological link between VAT and CVD. Methods: Baseline measurements of risk factors, body mass index (BMI), waist circumference (WC), and VAT were obtained from 2352 adults in the Dallas Heart Study, a multi-ethnic population-based cohort. GlycA was derived from NMR spectral features. Linear regression was used to assess associations between adiposity variables and GlycA. Cox proportional hazards models were used to assess the associations of VAT and GlycA with first or subsequent CVD event over a median of 11.4 years among those with obesity (BMI >=30). Results: Median age was 43, 56% women and 47% blacks. VAT, BMI and WC were each associated with GlycA in separate models adjusted for traditional risk factors (standardized beta estimates of 0.26, 0.27, and 0.27, respectively; all p < 0.0001). VAT remained directly associated with GlycA when additionally adjusting for BMI or WC. In adjusted models for first and recurrent CV events, the significant direct association between VAT and CV events (HR 1.22, 95% CI 1.04 to 1.44; p=0.01) was partially attenuated when adjusted for GlycA (HR 1.19, 95% CI 1.00 to 1.40; p=0.05). In contrast, VAT remained associated with CV events when adjusted for high sensitivity C-reactive protein. GlycA remained strongly associated with CV events despite adjustment for VAT (HR 1.30, 95% CI 1.13 to 1.49; p=0.0002; Table). Conclusions: Direct imaging assessment of VAT is associated with GlycA, a novel marker of inflammation. The link between VAT and CVD may be partly explained by inflammation reflected by GlycA. These findings suggest that GlycA may be a potentially useful surrogate marker for the adverse CVD risk associated with VAT. [ABSTRACT FROM AUTHOR]