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Importance: Obesity is a global health challenge and a risk factor for atherosclerotic cardiovascular disease (ASVCD). Performance of the pooled cohort equations (PCE) for ASCVD risk by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is unknown., Objective: To assess performance of the PCE across clinical BMI categories., Design, Setting, and Participants: This cohort study used pooled individual-level data from 8 community-based, prospective, longitudinal cohort studies with 10-year ASCVD event follow-up from 1996 to 2016. We included all adults ages 40 to 79 years without baseline ASCVD or statin use, resulting in a sample size of 37 311 participants. Data were analyzed from August 2017 to July 2020., Exposures: Participant BMI category: underweight (<18.5), normal weight (18.5 to <25), overweight (25 to <30), mild obesity (30 to <35), and moderate to severe obesity (≥35)., Main Outcomes and Measures: Discrimination (Harrell C statistic) and calibration (Nam-D'Agostino χ2 goodness-of-fit test) of the PCE across BMI categories. Improvement in discrimination and net reclassification with addition of BMI, waist circumference, and high-sensitivity C-reactive protein (hsCRP) to the PCE., Results: Among 37 311 participants (mean [SD] age, 58.6 [11.8] years; 21 897 [58.7%] women), 380 604 person-years of follow-up were conducted. Mean (SD) baseline BMI was 29.0 (6.2), and 360 individuals (1.0%) were in the underweight category, 9937 individuals (26.6%) were in the normal weight category, 13 601 individuals (36.4%) were in the overweight category, 7783 individuals (20.9%) were in the mild obesity category, and 5630 individuals (15.1%) were in the moderate to severe obesity category. Median (interquartile range [IQR]) 10-year estimated ASCVD risk was 7.1% (2.5%-15.4%), and 3709 individuals (9.9%) developed ASCVD over a median (IQR) 10.8 [8.5-12.6] years. The PCE overestimated ASCVD risk in the overall cohort (estimated/observed [E/O] risk ratio, 1.22; 95% CI, 1.18-1.26) and across all BMI categories except the underweight category. Calibration was better near the clinical decision threshold in all BMI groups but worse among individuals with moderate or severe obesity (E/O risk ratio, 1.36; 95% CI, 1.25-1.47) and among those with the highest estimated ASCVD risk ≥20%. The PCE C statistic overall was 0.760 (95% CI, 0.753-0.767), with lower discrimination in the moderate or severe obesity group (C statistic, 0.742; 95% CI, 0.721-0.763) compared with the normal-range BMI group (C statistic, 0.785; 95% CI, 0.772-0.798). Waist circumference (hazard ratio, 1.07 per 1-SD increase; 95% CI, 1.03-1.11) and hsCRP (hazard ratio, 1.07 per 1-SD increase; 95% CI, 1.05-1.09), but not BMI, were associated with increased ASCVD risk when added to the PCE. However, these factors did not improve model performance (C statistic, 0.760; 95% CI, 0.753-0.767) with or without added metrics., Conclusions and Relevance: These findings suggest that the PCE had acceptable model discrimination and were well calibrated at clinical decision thresholds but overestimated risk of ASCVD for individuals in overweight and obese categories, particularly individuals with high estimated risk. Incorporation of the usual clinical measures of obesity did not improve risk estimation of the PCE. Future research is needed to determine whether incorporation of alternative high-risk obesity markers (eg, weight trajectory or measures of visceral or ectopic fat) into the PCE may improve risk prediction.

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.)

Background and Purpose: The natural history of white matter hyperintensity (WMH) progression resulting from normal aging versus comorbid vascular insults remains unclear. Therefore we investigated age-related differences in WMH volumes among a group with comorbid hypertension, abnormal body mass index, and diabetes mellitus to a normal aging group drawn from the same population lacking any of these comorbidities., Methods: WMH volumes were acquired using 3T MRI for 2011 Dallas Heart Study participants. The slope of the WMH versus age regression was compared between normal and comorbidity groups<50 and ≥50 years of age where a change in slope was demonstrated., Results: Aging was linearly associated with greater log WMH volume for both normal (P=0.02) and comorbidity (P<0.0001) groups. Beyond 50 years of age, more rapid increases in WMH volumes for age were seen in the group with comorbidities (P<0.0001) but not in the normal group (P=0.173). The between-group difference in slope of expected WMH for age was significantly greater in the comorbidity groups≥50 years of age (P=0.0008) but not <50 years of age (P=0.752)., Conclusions: After 50 years of age, but not before, comorbid hypertension, obesity, and diabetes mellitus were associated with significantly larger WMH volumes for age compared with a normal aging group lacking these conditions. These results support the assertion that age-related differences in WMH volumes are significantly increased in the presence of comorbidities, but the effect is only detectable after 50 years of age.

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

Sirolimus is an immunosuppressive agent increasingly used in cardiac transplant recipients in the setting of allograft vasculopathy or worsening renal function. Recently, sirolimus has been associated with increased risk of venous thromboembolism ( VTE) in lung transplant recipients. To investigate whether this association is also present in cardiac transplant recipients, we retrospectively reviewed the charts of 67 cardiac transplant recipients whose immunosuppressive regimen included sirolimus and 134 matched cardiac transplant recipients whose regimen did not include sirolimus. Rates of VTE were compared. Multivariable Cox proportional hazards models tested the association of sirolimus use with VTE. A higher incidence of VTE was seen in patients treated with vs. without sirolimus (8/67 [12%] vs. 9/134 [7%], log-rank statistic: 4.66, p = 0.03). Lower body mass index ( BMI) and total cholesterol levels were also associated with VTE (p < 0.05). The association of sirolimus with VTE persisted when adjusting for BMI (hazard ratio [95% confidence interval]: 2.96 [1.13, 7.75], p = 0.03) but not when adjusting for total cholesterol (p = 0.08). These data suggest that sirolimus is associated with an increased risk of VTE in cardiac transplant recipients, a risk possibly mediated through comorbid conditions. Larger, more conclusive studies are needed. Until such studies are completed, a heightened level of awareness for VTE in cardiac transplant recipients treated with sirolimus appears warranted. [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]

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]