Statin therapy for primary prevention in men: What is the role for coronary artery calcium?

Current cholesterol guidelines for primary prevention of atherosclerotic cardiovascular disease (ASCVD) base statin treatment decisions on multiple risk factor algorithms (e.g., Pooled Cohort Equations [PCEs]). By available PCEs, most older middle-aged men are statin eligible. But several studies cast doubt on predictive accuracy of available PCEs for ASCVD risk assessment. Recent studies suggest that accuracy can be improved by measurement of coronary artery calcium (CAC). This method has the advantage of identifying men at low risk in whom statin therapy can be delayed for several years, provided they are monitored periodically for progression of CAC. Thus, there are two approaches to statin therapy in men ≥ 55 years: first all men could be treated routinely, or second, treatment can be based on the extent of coronary calcium. The latter could allow a sizable fraction of men to avoid treatment for several years or indefinitely. Whether with initial CAC scan or with periodic rescanning, a CAC score ≥ 100 Agatston units is high enough to warrant statin therapy. In otherwise high-risk men (e.g., diabetes, severe hypercholesterolemia, 10-year risk by PCE ≥ 20%), a statin is generally indicated without the need for CAC; but in special cases, CAC measurement may aid in treatment decisions.

Is There a Role for Coronary Calcium in Patients With Diabetes?

In the primary prevention of atherosclerotic cardiovascular disease (ASCVD), a significant portion of high-risk patients have diabetes. Two decades ago, patients with or without cardiovascular disease were identified as having coronary heart disease (CHD) risk equivalents because prospective studies showed that they were at risk for future CHD events equivalent to that of patients with established CHD. Thus, for patients with CHD, cholesterol guidelines recommended that patients with diabetes should be treated routinely with statins. However, recently, the treatment of diabetes has been greatly improved, and the risk for ASCVD has decreased. For this reason, it may be appropriate to re-evaluate the recommendations for routine use of statins in patients with diabetes. One of the major advances in the risk assessment for ASCVD is the introduction of coronary artery calcium measurement. This report will examine the role of coronary artery calcium scanning for the decision to initiate statin therapy in the primary prevention for patients with diabetes.

Prevalence and significance of risk enhancing biomarkers in the United States population at intermediate risk for atherosclerotic disease.

BACKGROUND: Pooled cohort equations (PCEs) estimate 10-year risk for atherosclerotic cardiovascular disease (ASCVD) in US adults. One use is to guide statin eligibility. However, PCEs risk estimate is inaccurate in some US subpopulations. OBJECTIVE: Recent cholesterol guidelines proposed addition of risk enhancing factors to improve risk assessment for selection of statin therapy. This study examines frequencies of several risk enhancing biomarkers in NHANES subjects at intermediate risk (7.5 -<20% 10-year risk for ASCVD) and considers how they may be used to better assess risk for individuals. METHODS: Prevalence of the following biomarkers were determined; elevations in apolipoprotein B-containing lipoproteins, i.e., LDL cholesterol (LDL-C) (160-189 mg/dL), non-HDL-cholesterol (non-HDL-C) (190-219 mg/dL), or total apolipoprotein B (apoB) (≥ 130 mg/dL), serum triglyceride (≥175 mg/dL), hemoglobin A1c (5.7-6.4%), high sensitivity C-reactive protein (2-10 mg/L), and waist circumference ≥ 102 cm, and abnormal estimated glomerular filtration rate (15 - ≤ 60 mg/min/1.73 m2). RESULTS: 25% of NHANES population had intermediate risk. In this subpopulation, 85% had ≥ 1 biomarkers-similarly in women and men-with a third having ≥3 abnormal markers. Frequencies were not age-related, except in those 40-49 years, in whom > 40% had ≥3 abnormal biomarkers. It made little difference whether LDL-C, non-HDL-C or apoB was used as the atherogenic lipoprotein. CONCLUSION: Three or more enhancing risk factors in intermediate risk subjects can complement PCE-estimated 10-year risk and guide the patient-provider discussion toward use of lipid-lowering medication. Future research is needed to integrate risk estimates by PCE and multiple risk enhancers.

Why is elevation of serum cholesterol associated with exposure to perfluoroalkyl substances (PFAS) in humans? A workshop report on potential mechanisms.

Serum concentrations of cholesterol are positively correlated with exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) in humans. The associated change in cholesterol is small across a broad range of exposure to PFOA and PFOS. Animal studies generally have not indicated a mechanism that would account for the association in humans. The extent to which the relationship is causal is an open question. Nonetheless, the association is of particular importance because increased serum cholesterol has been considered as an endpoint to derive a point of departure in at least one recent risk assessment. To gain insight into potential mechanisms for the association, both causal and non-causal, an expert workshop was held Oct 31 and Nov 1, 2019 to discuss relevant data and propose new studies. In this report, we summarize the relevant background data, the discussion among the attendees, and their recommendations for further research.

The association of cardiorespiratory fitness, body mass index, and age with testosterone levels at screening of healthy men undergoing preventive medical examinations: The Cooper Center Longitudinal Study.

BACKGROUND: Currently, exogenous hormone replacement is used in many men with hypogonadism without clear organic cause. This study examines the contribution of modifiable health behaviors, i.e., physical activity and weight control, to the maintenance of testosterone levels with aging. METHODS: In a cross-sectional study of 2994 healthy men aged 50-79 years examined at a preventive medicine clinic from January 2012 to March 2016, screening morning total testosterone levels were measured and categorized as low (<250 ng/dL), low normal (250-399 ng/dL), and normal (>400 ng/dL). Cardiorespiratory fitness (fitness) was estimated from a maximal exercise treadmill test. Multiple logistic regression models were used to test the associations between low testosterone levels and age, body mass index (BMI), and fitness. FINDINGS: Mean testosterone levels were in the normal range for each age group (50-59, 60-69, and 70-79). There was a similar prevalence of low testosterone in each age group (11·3%, 10%, and 10·5%, respectively). The prevalence of low testosterone was positively associated with BMI and negatively associated with fitness but was not associated with age. INTERPRETATION: This study found no evidence that low testosterone is an inevitable consequence of aging. Maintenance of healthy weight and fitness may help maintain normal testosterone levels.

Relation of plasma ceramides to visceral adiposity, insulin resistance and the development of type 2 diabetes mellitus: the Dallas Heart Study.

AIMS/HYPOTHESIS: Ceramides are sphingolipids that contribute to insulin resistance in preclinical studies. We hypothesised that plasma ceramides would be associated with body fat distribution, insulin resistance and incident type 2 diabetes in a multi-ethnic cohort. METHODS: A total of 1557 participants in the Dallas Heart Study without type 2 diabetes underwent measurements of metabolic biomarkers, fat depots by MRI and plasma ceramides by liquid chromatography-mass spectrometry. Diabetes outcomes were assessed after 7 years. Associations of body fat and insulin resistance with ceramides at baseline and of ceramides with incident diabetes outcomes were analysed. RESULTS: The cohort had a mean age of 43 years, with 58% women, 45% black participants and a mean BMI of 28 kg/m2. Total cholesterol levels were associated with all ceramides, but higher triacylglycerols and lower HDL-cholesterol and adiponectin were associated only with saturated fatty acid chain ceramides (p < 0.0003). After adjusting for clinical characteristics and total body fat, visceral adipose tissue was positively associated with saturated fatty acid ceramides (per SD, ß = 0.16 to 0.18) and inversely associated with polyunsaturated fatty acid ceramides (ß = -0.14 to -0.16, p < 0.001 for all). Lower-body subcutaneous fat showed an opposite pattern to that for visceral fat. HOMA-IR was positively associated with saturated (ß = 0.08 to 0.09, p < 0.001) and inversely with polyunsaturated ceramides (ß = -0.06 to -0.07, p < 0.05). Ceramides were not associated with incident type 2 diabetes after adjustment for clinical factors. CONCLUSIONS/INTERPRETATION: Plasma ceramides demonstrate a biologically complex relationship with metabolic and imaging indicators of dysfunctional adiposity. The role of ceramides in a shared pathway of metabolic dysfunction linking visceral adiposity and insulin resistance requires further investigation.

Upper body fat predicts metabolic syndrome similarly in men and women.

BACKGROUND: The metabolic syndrome is a constellation of risk factors including dyslipidemia, dysglycemia, hypertension, a pro-inflammatory state, and a prothrombotic state. All of these factors are accentuated by obesity. However, obesity can be defined by body mass index (BMI), percent body fat, or by body fat distribution. The latter consists of upper body fat (subcutaneous and visceral fat) and lower body fat (gluteofemoral fat). Waist circumference is a common surrogate marker for upper body fat. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) for the years 1999-2006 was examined for associations of metabolic risk factors with percent body fat, waist circumference, and BMI. RESULTS: Associations between absolute measures of waist circumference and risk factors were similiar for men and women. The similarities of associations between waist circumference and risk factors suggests that greater visceral fat in men does not accentuate the influence of upper body fat on risk factors. CONCLUSIONS: Different waist concumference values should not be used to define abdominal obesity in men and women.

Moderate to High Levels of Cardiorespiratory Fitness Attenuate the Effects of Triglyceride to High-Density Lipoprotein Cholesterol Ratio on Coronary Heart Disease Mortality in Men.

OBJECTIVE: To examine the prospective relationships among cardiorespiratory fitness (CRF), fasting blood triglyceride to high density lipoprotein cholesterol ratio (TG:HDL-C), and coronary heart disease (CHD) mortality in men. METHODS: A total of 40,269 men received a comprehensive baseline clinical examination between January 1, 1978, and December 31, 2010. Their CRF was determined from a maximal treadmill exercise test. Participants were divided into CRF categories of low, moderate, and high fit by age group and by TG:HDL-C quartiles. Hazard ratios for CHD mortality were computed using Cox regression analysis. RESULTS: A total of 556 deaths due to CHD occurred during a mean ± SD of 16.6±9.7 years (669,678 man-years) of follow-up. A significant positive trend in adjusted CHD mortality was shown across decreasing CRF categories (P for trend<.01). Adjusted hazard ratios were significantly higher across increasing TG:HDL-C quartiles as well (P for trend<.01). When grouped by CRF category and TG:HDL-C quartile, there was a significant positive trend (P=.04) in CHD mortality across decreasing CRF categories in each TG:HDL-C quartile. CONCLUSION: Both CRF and TG:HDL-C are significantly associated with CHD mortality in men. The risk of CHD mortality in each TG:HDL-C quartile was significantly attenuated in men with moderate to high CRF compared with men with low CRF. These results suggest that assessment of CRF and TG:HDL-C should be included for routine CHD mortality risk assessment and risk management.

Orthorexia Nervosa and Eating Disorder Symptoms in Registered Dietitian Nutritionists in the United States.

BACKGROUND: Registered dietitian nutritionists are trained to identify optimal food choices for clients based on medical state and lifestyle. Orthorexia nervosa (ON) is a proposed disorder related to obsessions about eating healthfully. Eating disorders (EDs) are serious mental illnesses with symptoms related to eating, body image, and self-esteem. Both ON and EDs are more common among RDNs than the general population. OBJECTIVE: This study examined the prevalence of ON and EDs in RDNs in the United States and, among this sample, assessed whether the presence of ON symptoms related to symptoms of EDs, including weight, shape, eating, and restraint. DESIGN: A cross-sectional design compared responses for participants after dividing into three groups: those scoring at-risk for ON, those with a current or past ED, and a comparison group. PARTICIPANTS: A sample of 2,500 RDNs were invited to complete surveys electronically; 636 responses were received. MAIN OUTCOME MEASURES: Scores on the Orthorexia Nervosa Questionnaire (ORTO-15) and Eating Disorder Examination Questionnaire (EDE-Q) determined prevalence of ON and EDs. Differences in these measures, and body mass index were compared among the three groups. STATISTICAL ANALYSES: Analysis of variance and χ2 analyses were used to compare the groups. RESULTS: For the entire sample, scores on the ORTO-15 suggested 49.5% were at risk for ON, and scores on the EDE-Q suggested 12.9% were at risk for an ED, with 8.2% of RDNs self-disclosing treatment for an ED. Both the group disclosing ED treatment and the group at risk for ON had a lower mean body mass index, lower scores on the ORTO-15, and higher scores on the EDE-Q and all its subscales than the comparison group. CONCLUSIONS: Clarifying the relationship between ON and EDs is warranted because ON symptoms appear to be associated not only with disturbances in eating, but also with elevated shape and weight concerns.

An Analysis of Individual Body Fat Depots and Risk of Developing Cancer: Insights From the Dallas Heart Study.

OBJECTIVE: To examine the association between specific adipose tissue depots and the risk of incident cancer in the Dallas Heart Study. PATIENTS AND METHODS: Individuals without prevalent cancer in the Dallas Heart Study underwent quantification of adipose depots: visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue, and liver fat by magnetic resonance imaging, and subcutaneous lower-body fat (LBF) by dual-energy X-ray absorptiometry from January 1, 2000, through December 31, 2002, and were observed for the development of cancer for up to 12 years. Multivariable Cox proportional hazards modeling was performed to examine the association between fat depots and cancer. RESULTS: Of 2627 participants (median age, 43 years; 69% nonwhite race), 167 (6.4%) developed cancer. The most common primary sites of cancer were the breast (in women) and the prostate (in men). In multivariable models adjusted for age, sex, race, smoking, alcohol use, family history of malignancy, and body mass index, a 1-SD increase in VAT was not associated with increased risk of cancer (hazard ratio [HR], 0.94; 95% CI, 0.77-1.14). In contrast, each 1-SD increase in LBF was associated with a reduced incidence of cancer (HR, 0.69; 95% CI, 0.52-0.92) in the fully adjusted model. CONCLUSIONS: In this study, adiposity-associated cancer risk was heterogeneous and varied by fat depot: VAT was not independently associated with incident cancer, and LBF seemed to protect against cancer development. Further studies of the adiposity-cancer relationship, including serial assessments, are needed to better elucidate this relationship.

Effect of losartan and spironolactone on triglyceride-rich lipoproteins in diabetic nephropathy.

UNLABELLED: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) can improve dyslipidemia in patients with diabetes and albuminuria. Whether combined ACEi+ARB or ACEi+mineralocorticoid receptor blockade improves dyslipidemia is not known. We hypothesized long-term administration of either losartan 100 mg or spironolactone 25 mg once daily added onto lisinopril 80 mg once daily would improve dyslipidemia in diabetic nephropathy (DN). We measured lipid levels, very-low-density (V), intermediate-density (I), low-density (LDL), high-density (HDL) lipoprotein, LDL particle size with their respective cholesterol (C) and apolipoprotein B levels (ApoB), and urine albumin/creatinine ratio (UACR) at 12-week interval during a 48-week randomized, double-blind placebo-controlled trial in 81 patients with DN. Plasma lipids and lipoprotein C were analyzed enzymatically and Apo B was determined chemically. Data were analyzed by mixed model repeated measures. ΔUACR differed among treatment arms (placebo -24.6%, los -38.2%, spiro -51.6%, p=0.02). No correlation existed between ΔUACR and ΔTG or any of the lipid or lipoprotein measurements. Compared with placebo losartan, but not spironolactone, decreased TG (-20.9% vs +34.3%, p<0.01), V+I C(-18.8% vs +21.3%, p<0.01), and V+I-ApoB (-13.2% vs +21%, p<0.01). There were no significant changes in body weight, HbA1c or other lipoprotein variables. We conclude losartan improves dyslipidemia in patients with DN. We speculate the mechanism improved clearance of VLDL and remnant lipoproteins. TRIAL REGISTRATION NUMBER: NCT00381134; Results.

Association of multiple adiposity exposures and cardiorespiratory fitness with all-cause mortality in men: the Cooper Center Longitudinal Study.

OBJECTIVE: To examine the additive effects of an increased number of positive adiposity exposures on all-cause mortality in men before and after stratification by cardiorespiratory fitness (CRF) level. PATIENTS AND METHODS: A total of 36,836 men underwent a physical examination at the Cooper Clinic from January 1, 1971, through December 31, 2006. Exposures included body mass index, waist circumference, percentage of body fat, and CRF as determined by duration of a maximal exercise test. Participants were identified as being either obese (positive) or nonobese (negative) for each adiposity exposure and then grouped into 4 categories: group 1, negative for all adiposity exposures; group 2, positive for any 1 exposure; group 3, positive for any 2 exposures; and group 4, positive for all exposures. Then CRF was grouped as fit or unfit on the basis of the upper 80% and lower 20% of the age-standardized CRF distribution as previously reported in the Cooper Center Longitudinal Study. Hazard ratios were computed with Cox regression analysis. RESULTS: A total of 2294 deaths occurred during a mean ± SD of 15.5 ± 8.1 years of follow-up. Adjusted hazard ratios across adiposity groups were 1.0 (referent), 1.05, 1.37, and 1.87 for groups 1 through 4, respectively (P for trend <.001). Mortality rates were significantly lower within each of the first 3 adiposity groups in fit compared with unfit men (P<.009 for all comparisons). CONCLUSION: An increasing number of positive adiposity exposures were associated with increased mortality in men. Because moderate to high CRF attenuated mortality rates in all adiposity groups, measurement of CRF should be included for identifying men at increased risk for all-cause mortality.

Association of urinary sodium-to-potassium ratio with obesity in a multiethnic cohort.

BACKGROUND: Previous studies that reported an association of dietary Na(+) intake with metabolic syndrome were limited by the use of imprecise measures of obesity, Na(+) intake, or exclusion of multiethnic populations. The effect of dietary K(+) intake on obesity is less well described. OBJECTIVE: We hypothesized that high dietary Na(+) and low K(+), based on the ratio of urinary Na(+) to K(+) (U[Na(+)]/[K(+)]) in a first-void morning urinary sample, is independently associated with total body fat. DESIGN: In a prospective population-based cohort, 2782 participants in the community-dwelling, probability-sampled, multiethnic Dallas Heart Study were analyzed. The primary outcome established a priori was total-body percentage fat (TBPF) measured by dual-energy X-ray absorptiometry. The main predictor was U[Na(+)]/[K(+)]. Robust linear regression was used to explore an independent association between U[Na(+)]/[K(+)] and TBPF. The analyses were stratified by sex and race after their effect modifications were analyzed. RESULTS: Of the cohort, 55.4% were female, 49.8% African American, 30.8% white, 17.2% Hispanic, and 2.2% other races. The mean (±SD) age was 44 ± 10 y, BMI (in kg/m(2)) was 30 ± 7, TBPF was 32 ± 10%, and U[Na(+)]/[K(+)] was 4.2 ± 2.6; 12% had diabetes. In the unadjusted and adjusted models, TBPF increased by 0.75 (95% CI: 0.25, 1.25) and 0.43 (0.15, 0.72), respectively (P = 0.003 for both), for every 3-unit increase in U[Na(+)]/[K(+)]. A statistically significant interaction was found between race and U[Na(+)] /[K(+)], so that the non-African American races had a higher TBPF than did the African Americans per unit increase in U[Na(+)]/[K(+)] (P-interaction < 0.0001 for both). No interaction was found between sex and U[Na(+)]/[K(+)]. CONCLUSIONS: The ratio of dietary Na(+) to K(+) intake may be independently associated with TBPF, and this association may be more pronounced in non-African Americans. Future studies should explore whether easily measured spot U[Na(+)]/[K(+)] can be used to monitor dietary patterns and guide strategies for obesity management.

Relation of regional fat distribution to left ventricular structure and function.

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 (ß=-0.21), higher concentricity (ß=0.20), and wall thickness (ß=0.09; P<0.0001 for all). In contrast, lower body subcutaneous fat was associated with higher LV end-diastolic volume (ß=0.48), reduced concentricity (ß=-0.50), and wall thickness (ß=-0.28, P<0.0001 for all). Visceral adipose tissue was also associated with lower cardiac output (ß=-0.10, P<0.05) and higher systemic vascular resistance (ß=0.08, P<0.05), whereas lower body subcutaneous fat associated with higher cardiac output (ß=0.20, P<0.0001) and lower systemic vascular resistance (ß=-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.

Associations of visceral and abdominal subcutaneous adipose tissue with markers of cardiac and metabolic risk in obese adults.

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.

Higher natriuretic peptide levels associate with a favorable adipose tissue distribution profile.

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.

Relationship between perceptions about neighborhood environment and prevalent obesity: data from the Dallas Heart 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.

Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes in obese adults.

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.