Evaluation of FamMed essentials: a blended-learning program for capacity building of general practitioners in Pakistan.

BACKGROUND: To provide access to primary care and universal health coverage, Pakistan requires 60,000 trained family physicians by 2030. At present, most primary care is provided by general practitioners (GPs) who do not have any post-graduate training. Empowering GPs through competency-based programs, that strengthen their knowledge and skills, may be a cost-effective strategy for improving healthcare quality. We describe the development and evaluation of FamMed Essentials, a modular, blended-learning program to improve clinical knowledge and skills of GPs. METHODS: This is a mixed method study. We used the CIPP (content, input, process and product) framework for course development and evaluation. We describe the steps used in content development, strategies for teaching and assessments, and evaluation of strengths and weaknesses of the program. In depth focus group discussions were conducted to gather insight on participants' and faculty's perceptions regarding the program's effectiveness. RESULTS: Of the 137 participants who have completed the program, 72% were women and 49% had been practicing for more than five years. We saw a significant improvement in knowledge across all modules (p = < 0.001) and perceived confidence in clinical skills (p = < 0.001). An objective assessment showed participants' competence in patient management. Participants reported a high level of satisfaction (4.4 ± 0.83 on a 5-point Likert Scale). Focus group discussions revealed a positive impact on clinical practice. Flexibility and use of different teaching and learning strategies were additional strengths. In addition, participants reported an interest in further training. Power outages were highlighted as a major challenge. CONCLUSION: In resource-constrained health systems, a modular, blended-learning, competency-based program is helpful to upgrade GPs knowledge without impacting their busy schedules. Accreditation of such programs and provision of a career trajectory for the trained GPs are pivotal to expansion of such initiatives.

The Pandemic of Coronary Heart Disease in South Asia: What Clinicians Need to Know.

PURPOSE OF REVIEW: South Asia has around 1/6th of the current global population. Epidemiological studies suggest that South Asians living in South Asia and diaspora are at an increased risk of premature atherosclerotic cardiovascular diseases (ASCVDs). This is due to an interplay of genetic, acquired, and environmental risk factors. Due to its increasing share of the global population, clinicians need to know the reasons for this early predisposition, and strategies for early identification and mitigation. RECENT FINDINGS: South Asians have earlier onset of cardiometabolic risk factors such as insulin resistance, hypertension, and central adiposity. This increased risk is seen in both native South Asians and the diaspora. South Asians have earlier onset of ASCVD due to an earlier onset of cardiometabolic risk factors. Health promotion and early identification of these risk factors are essential to mitigate this ongoing crisis.

Needs assessment of general practitioners in Pakistan: A descriptive cross-sectional survey.

Background: With the growing and complex nature of medicine, it is imperative for physicians to update their knowledge and skills to reflect current standards of care. In Pakistan, 71% of primary care needs are met by general practitioners (GPs). GPs are not required to complete structured training and no regulatory mandates exist for continuing medical education. We conducted a needs assessment to evaluate the readiness for competency-based updating of knowledge and skills, and the use of technology by practicing GPs in Pakistan. Methods: A cross-sectional survey inviting registered GPs across Pakistan was administered online and in-person. Questions pertained to physician demographics, practice characteristics, confidence in knowledge and skills, and preferred modes of updating knowledge and barriers. Descriptive analyses were performed for GPs and patient-related characteristics and bivariate analyses to evaluate the relationship between parameters of interest. Results: Of the 459 GPs who responded, 35% were practicing for <5 years and 34% reported practicing for >10 years. Only 7% had a post-graduate qualification in family medicine. GPs reported needing practice in neonatal examination (52%), neurological exam (53%), depression screening (53%), growth charts (53%) and peak flow meter use (53%), interpretation of electrocardiograms (ECGs, 58%) and insulin dosing for diabetes (50%). High workload (44%) was the most common barrier to updating clinical knowledge. Sixty-two percent used the Internet on a regular basis. Conclusion: Most GPs have no structured training and encounter gaps in knowledge and skills in clinical practice. Flexible, hybrid, and competency-based continuing medical education programs can be used to update knowledge and skills.

Hypertension Pharmacological Treatment in Adults: A World Health Organization Guideline Executive Summary.

Hypertension is a major cause of cardiovascular disease and deaths worldwide especially in low- and middle-income countries. Despite the availability of safe, well-tolerated, and cost-effective blood pressure (BP)-lowering therapies, <14% of adults with hypertension have BP controlled to a systolic/diastolic BP <140/90 mm Hg. We report new hypertension treatment guidelines, developed in accordance with the World Health Organization Handbook for Guideline Development. Overviews of reviews of the evidence were conducted and summary tables were developed according to the Grading of Recommendations, Assessment, Development, and Evaluations approach. In these guidelines, the World Health Organization provides the most current and relevant evidence-based guidance for the pharmacological treatment of nonpregnant adults with hypertension. The recommendations pertain to adults with an accurate diagnosis of hypertension who have already received lifestyle modification counseling. The guidelines recommend BP threshold to initiate pharmacological therapy, BP treatment targets, intervals for follow-up visits, and best use of health care workers in the management of hypertension. The guidelines provide guidance for choice of monotherapy or dual therapy, treatment with single pill combination medications, and use of treatment algorithms for hypertension management. Strength of the recommendations was guided by the quality of the underlying evidence; the tradeoffs between desirable and undesirable effects; patient's values, resource considerations and cost-effectiveness; health equity; acceptability, and feasibility consideration of different treatment options. The goal of the guideline is to facilitate standard approaches to pharmacological treatment and management of hypertension which, if widely implemented, will increase the hypertension control rate world-wide.

Metabolic syndrome among children aged 6 to 11 years, Al Ain, United Arab Emirates: Role of obesity.

OBJECTIVES: To evaluate the association of metabolic syndrome with the varying degrees of obesity among children aged 6 to 11 years in Al Ain, United Arab Emirates (UAE). METHODS: As an ancillary to the primary study examining prevalence of MetS in a random sample of 1186 adolescents from 114 schools in Al Ain, parents and siblings aged 6 to 11 years were invited to participate in this study. After informed consent from parents and assent from children, trained nurses administered questionnaires to assess socio-demographic and lifestyle variables and conducted anthropometric measurements. Fasting blood samples were drawn to measure plasma lipids and glucose. We used Centers for Diseases Control and Prevention (CDC)-defined categories of body mass index (BMI = kg/m2 ) for normal weight (<85th percentile), overweight (≥85th to 94th percentile), and obese (≥95th percentiles). MetS was defined according to National Cholesterol Education Program's (NCEP)/Adult Treatment Panel III (ATP III) criteria. RESULTS: Of the total 234 siblings aged 6 to 11 years, 8.9% (95% Confidence Interval [CI]: 5.6-13.4) had MetS. The prevalence of MetS increased with the severity of obesity, 4.5% in normal, 16.7% in overweight, and 30.0% in obese subjects. The age, sex, and ethnicity adjusted odds (1.55, 95% CI: 1.23-1.96) of MetS increased significantly with per unit increase in BMI. CONCLUSIONS: The prevalence of MetS in study subjects increased with an increase in BMI. School-based interventions targeting metabolic risks in this population are urgently needed.

Meningococcal carriage among a university student population - United States, 2015.

OBJECTIVES: Several outbreaks of serogroup B meningococcal disease have occurred among university students in recent years. In the setting of high coverage of the quadrivalent meningococcal conjugate vaccine and prior to widespread use of serogroup B meningococcal vaccines among adolescents, we conducted surveys to characterize the prevalence and molecular characteristics of meningococcal carriage among university students. METHODS: Two cross-sectional oropharyngeal carriage surveys were conducted among undergraduates at a Rhode Island university. Isolates were characterized using slide agglutination, real-time polymerase chain reaction (rt-PCR), and whole genome sequencing. Adjusted prevalence ratios and 95% confidence intervals were calculated using Poisson regression to determine risk factors for carriage. RESULTS: A total of 1837 oropharyngeal specimens were obtained from 1478 unique participants. Overall carriage prevalence was 12.7-14.6% during the two survey rounds, with 1.8-2.6% for capsular genotype B, 0.9-1.0% for capsular genotypes C, W, or Y, and 9.9-10.8% for nongroupable strains by rt-PCR. Meningococcal carriage was associated with being male, smoking, party or club attendance, recent antibiotic use (inverse correlation), and recent respiratory infections. CONCLUSIONS: In this university setting, the majority of meningococcal carriage was due to nongroupable strains, followed by serogroup B. Further evaluation is needed to understand the dynamics of serogroup B carriage and disease among university students.

Isotemporal Analysis of the Association of Objectively Measured Physical Activity With Depressive Symptoms: Results From Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND: The burden of depression among Hispanics/Latinos indicates the need to identify factors related to depressive symptoms. This paper examines the relationship of physical activity (PA) and sedentary behavior (SB) with depressive symptoms in Hispanic/Latinos. METHODS: The Hispanic Community Health Study / Study of Latinos (HCHS/SOL) is a population-based, cohort study of Hispanic/Latinos in 4 United States metropolitan areas. Objectively measured PA was coded into: sedentary behavior (SB), light-intensity (LPA), moderate-intensity (MPA), and vigorous-intensity (VPA); and the Center for Epidemiological Studies Depression Scale-10 assessed depressive symptoms. Multiple regression analysis utilizing isotemporal substitution, adjusted for relevant covariates, examined PA as predictors of depressive symptoms. RESULTS: Substitution of 1 hour of SB with VPA resulted in a significant decrease in depressive symptoms (ß = -1.215, P = .021). Similar decreases were observed when VPA replaced LPA (ß = -1.212, P = .021) and MPA (ß = -1.50 P = .034). MPA and LPA were not associated with lower depressive symptoms. CONCLUSIONS: Previous research has focused on the relationship of MVPA on depressive symptoms. Our results suggest these constructs should be examined separately as they may have unique relationships with depressive symptoms. The association of SB with greater depressive symptoms confirms previous reports.

Predictors of Early Discontinuation of Effective Contraception by Teens at High Risk of Pregnancy.

STUDY OBJECTIVE: In the United States, teen pregnancy rates are declining. However, the United States still has the highest teen pregnancy rate among high-income countries. Understanding factors that predict discontinuation of effective contraception might help to further decrease teen pregnancy. We aimed to assess predictors of early discontinuation of effective contraception during typical use by high-risk teens. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We recruited 145 women aged 13-20 years (mean, 17.7 ± 1.8 years); 68% (99/145) Hispanic; 26% (38/145) black; 14% (20/145) ever pregnant; and 4% (6/145) high school dropouts who chose an effective contraceptive method during a health care visit and we prospectively assessed use of the method after 6 months. Contraceptive choices of the 130 participants who were reassessed at 6 months (90% retention) were: intrauterine device (IUD), 26% (34/130); depot medroxyprogesterone acetate (DMPA), 8% (10/130); combined oral contraceptives (COCs), 48% (62/130); transdermal patch (Patch), 13% (17/130); and intravaginal ring (Ring), 5% (7/130). RESULTS: After 6 months, only 49 of 130 (38%) continued their chosen method; 28 of 130 (22%) never initiated the method; and 53 of 130 (40%) discontinued. Users and nonusers at 6 months did not differ according to cultural and/or social characteristics (age, ethnicity, acculturation, education, health literacy) but differed according to contraceptive method type. For the 102 of 130 who initiated a method, 88% continued use of the IUD, 20% DMPA, 43% COC, 17% Patch and Ring (P < .001). Using Cox proportional hazards multivariable analysis, compared with IUDs, all other methods predicted discontinuation: DMPA (hazard ratio [HR], 5.6; 95% confidence interval [CI], 1.2-26.7; P < .05); COCs (HR, 6.6; 95% CI, 1.8-25; P < .01); Patch and Ring (HR, 12; 95% CI, 3.0-48; P < .001). Discontinuation was also predicted by past use of hormonal contraceptives (HR, 1.9; 95% CI, 1.0-3.6; P < .05) and high school dropout (HR, 8.2; 95% CI, 1.6-41; P < .01). CONCLUSION: Contraceptive method type is the strongest predictor of early discontinuation; compared with IUDs, all other methods are 6-12 times more likely to be discontinued. Cultural and/or social characteristics, with the exception of school dropout, are of little predictive value. Increasing the use of IUDs by high-risk teens could decrease discontinuation rates and possibly teen pregnancy rates.

Differences in Cardiometabolic Risk between Insulin-Sensitive and Insulin-Resistant Overweight and Obese Children.

BACKGROUND: It is known that 15-30% overweight/obese adults do not suffer cardiometabolic consequences. There is limited literature examining factors that can be used to assess cardiometabolic health in overweight/obese children. If such factors can be identified, they would aid in differentiating those most in need for aggressive management. METHODS: Baseline data from 7- to 12-year-old, overweight, and obese children enrolled in a weight management program at an urban hospital were analyzed. Homeostatic model assessment for insulin resistance (HOMA-IR) <2.6 was used to define insulin-sensitive and HOMA-IR ≥2.6 was used to defined insulin-resistant participants. Demographics, physical activity measures, and cardiometabolic risk factors were compared between the two phenotypes. Odds ratios (ORs) examining the association between intermediate endpoints (metabolic syndrome [MetS], nonalcoholic fatty liver disease [NAFLD], systemic inflammation, and microalbuminuria) and the two metabolic phenotypes were evaluated. RESULTS: Of the 362 overweight/obese participants, 157 (43.5%) were insulin sensitive and 204 (56.5%) were insulin resistant. Compared to the insulin-sensitive group, the insulin-resistant group was older (8.6±1.6 vs. 9.9±1.7; p<0.001) and had a higher BMI z-score (1.89±0.42 vs. 2.04±0.42; p=0.001). After multivariable adjustment, compared to the insulin-sensitive group, the insulin-resistant group had higher odds of having MetS (OR, 5.47; 95% confidence interval [CI]: 1.72, 17.35; p=0.004) and NAFLD (OR, 8.66; 95% CI, 2.48, 30.31; p=0.001), but not systemic inflammation (OR, 1.06; 95% CI: 0.56, 2.03; p=0.86) or microalbuminuria (OR, 1.71; 95% CI, 0.49, 6.04; p=0.403). CONCLUSIONS: Using a HOMA-IR value of ≥2.6, clinical providers can identify prepubertal and early pubertal children most at risk. Focusing limited resources on aggressive weight interventions may lead to improvement in cardiometabolic health.

Progression from metabolically benign to at-risk obesity in perimenopausal women: a longitudinal analysis of study of women across the nation (SWAN).

BACKGROUND: Little is known about the natural history of progression from a metabolically benign overweight/obese (MBO) to at-risk overweight/obese (ARO) phenotype. Improved understanding would help clinicians focus on controlling risk factors that predispose an obese individual to progression. METHODS: Using discrete-time proportional hazard modeling on data from the Study of Women's Health Across the Nation (SWAN), we examined the incident progression from MBO (less than two metabolic syndrome abnormalities) to ARO (two or more metabolic syndrome abnormalities) and factors associated with progression over a 7-year period. RESULTS: Of 866 MBO women at baseline, 43% progressed to the ARO phenotype. Compared with those who remained MBO, those who progressed had higher baseline BMI and a higher prevalence of cardiometabolic abnormalities (elevated glucose, triglycerides, blood pressure and low high-density lipoprotein cholesterol). In multivariable analyses, an increase in body mass index was associated with a modest increase in the risk of progression. Although all cardiometabolic abnormalities were associated with an increased risk, the baseline impaired fasting glucose showed the strongest association with the risk of progression [hazard ratio 3.24; 95% confidence interval 2.10, 4.92; P < .001]. Physical activity played a protective role in decreasing the risk of progression [hazard ratio 0.86; 95% confidence interval 0.80, 0.92; P < .001]. CONCLUSIONS: Increasing obesity and the presence of cardiometabolic abnormalities increase the risk of progression, whereas physical activity is the only lifestyle factor protective against progression from metabolically benign to the at-risk overweight/obese phenotype, a state that is unanimously associated with an elevated risk of cardiovascular morbidity and mortality.

The adipokine profile of metabolically benign obese and at-risk normal weight postmenopausal women: the Women's Health Initiative Observational Study.

OBJECTIVE: Nearly, a third of obese individuals, termed metabolically benign obese, have a low burden of adiposity-related cardiometabolic abnormalities, whereas a substantial proportion of normal-weight individuals possess risk factors. METHODS: In cross-sectional analyses of 699 normal weight and 1,294 overweight/obese postmenopausal women enrolled in a nested case-control stroke study ancillary to the Women's Health Initiative Observational Study, we compared levels of adiponectin, leptin, and resistin among metabolically benign normal weight, at-risk normal weight, metabolically benign obese, and at-risk obese women using components of the ATP III definition of the metabolic syndrome (metabolically benign: ≤1 of the four components; at-risk phenotype: ≥2 components or diabetes). RESULTS: Overall, 382/699 normal-weight women (54.6%) and 328/1,194 overweight/obese women (27.5%) were metabolically benign. Among normal-weight women, at-risk women had higher leptin and lower adiponectin levels compared to metabolically benign women; multivariate-adjusted odds ratios were significant for having leptin (OR: 2.51; 95% CI: 1.28-5.01) and resistin (1.46; 1.03-2.07) in the top tertile and adiponectin in the bottom tertile (2.64; 1.81-3.84). Compared to metabolically benign overweight/obese women, at-risk obese women had higher odds of having leptin in the top tertile (1.62; 1.24-2.12) and adiponectin in the bottom tertile (2.78; 2.04-3.77). CONCLUSIONS: Overall, metabolically benign overweight/obese women had an intermediate adipokine profile (between at-risk obese and metabolically benign normal-weight women), whereas at-risk normal-weight women had a less favorable profile compared to metabolically benign normal-weight women. As adiponectin was the only adipokine independent of BMI, it may be most likely to have a role in the etiological pathway of these phenotypes.

Evaluation of a community-based weight management program for predominantly severely obese, difficult-to-reach, inner-city minority adolescents.

BACKGROUND: Few interventions targeting severely obese minority youth have been implemented in community-based settings. We evaluate a 9-month multicomponent, community-based program for obese, inner-city adolescents. METHODS: Of 5250 estimated eligible adolescents, 349 were recruited; they had a mean age of 15 ± 2 years, mean BMI %ile 98.9 ± 1.5, and comprised 52% African American and 44% Hispanic. Longitudinal trends of anthropometric measures were compared 1 year before enrollment (T-12), at baseline (T0) and after program completion (T9). Dietary and physical activity behaviors were compared at T0 and T9. Anthropometric changes were compared at T9 and 18 months (T18) in completers and noncompleters. RESULTS: A majority of participants were severely obese (67%) and expressed low readiness to change behaviors (82%). For intervals T-12 to T0 versus T0 to T9, there were significant decreases in rates of gain in BMI (0.13 vs. 0.04, p < 0.01), BMI percentile (0.0002 vs. -0.0001, p < 0.01), percent overweight (0.001 vs. -0.001, p < 0.01), and BMI z-score (0.003 vs. -0.003, p < 0.01). Significant increases in vegetable and fruit consumption and in vigorous physical activity participation were observed. From T9 to T18, except for a significant increase in BMI (38.3 ± 7.4 vs. 39.0 ± 7.5, p < 0.01) in completers, all other anthropometric measures remained unchanged in completers and noncompleters. CONCLUSIONS: We demonstrate modest clinical improvements and increased healthy lifestyle behaviors in predominantly severely obese, difficult-to-reach, ethnic minority adolescents attending a community-based weight management program. The loss of clinical improvements 9 months after program completion implies that extending the duration of such a program may prevent long-term weight regain in severely obese adolescents.

Ectopic fat and adipokines in metabolically benign overweight/obese women: the Kronos Early Estrogen Prevention Study.

OBJECTIVE: It is unclear why despite a comparable cardiometabolic risk profile, "metabolically benign" overweight/obese individuals show an elevated risk of cardiovascular disease compared to normal weight individuals. DESIGN AND METHODS: In cross-sectional analyses, we compared levels of ectopic fat (epicardial, pericardial, and hepatic fat) and adipokines (leptin, soluble leptin receptor, and high molecular weight [HMW] adiponectin) among metabolically benign (MBO) and at-risk overweight/obese (ARO), and metabolically benign normal weight (MBNW) women, screened for the Kronos Early Estrogen Prevention Study. We defined "metabolically benign" with ≤ 1, and "at-risk" with ≥2 components of the metabolic syndrome. RESULTS: Compared to MBO women, ARO women had significantly elevated odds of being in the top tertile of epicardial fat (OR: 1.76, 95% CI: 1.04-2.99), hepatic fat (OR: 1.90, 95% CI:1.12-3.24) and leptin (OR: 2.15, 95% CI: 1.23-3.76), and the bottom tertile of HMW-adiponectin (OR: 2.90, 95% CI: 1.62-5.19). Compared to MBNW women, MBO women had significantly higher odds of being in the top tertile of epicardial fat (OR: 5.17, 95% CI: 3.22-8.29), pericardial fat (OR: 9.27, 95% CI: 5.52-15.56) and hepatic fat (OR: 2.72, 95% CI: 1.77-4.19) and the bottom tertile of HMW adiponectin levels (OR: 2.51, 95% CI: 1.60-3.94). CONCLUSIONS: Levels of ectopic fat and the adverse adipokine profile increase on a continuum of BMI, suggesting that the metabolically benign phenotype may be a transient state.

Independent and synergistic associations of asthma and obesity with systemic inflammation in adolescents.

INTRODUCTION: Both asthma and obesity often occur in the same individual. Each increases the risk of cardiovascular disease (CVD) with systemic inflammation likely playing a vital role. We examined the independent and synergistic associations of asthma and obesity with systemic inflammation using high-sensitivity C-reactive protein (hs-CRP) levels in adolescents. METHODS: This study involves the cross-sectional design carried out in the adolescent and respiratory medicine practices in a children's hospital. Out of 124 adolescents (mean age 16.1 ± 2.3 years), who were either of obese (N = 75) or of normal weight (N = 49). 51 had asthma (18 normal weight and 33 obese). RESULTS: hs-CRP levels were higher in obese versus normal weight groups (geometric mean ± SD: 2.38 ± 2.91 vs. 0.72 ± 3.54; p < .001), and in the asthmatic versus non-asthmatic groups (geometric mean ± SD: 1.21 ± 3.71 vs.1.96 ± 3.28; p = .039). We found a trend of increasing hs-CRP levels across the four groups (p < .001), with the obese asthmatic group having the highest level. In multivariate regression, we found a strong association between obesity and log-CRP (ß ± SE: 1.43 ± 0.23; p < .001) and a moderate association between asthma and log-CRP (ß ± SE: 0.48 ± 0.21; p < .028), with additive synergy between obesity and asthma. CONCLUSIONS: Both asthma and obesity are independently and synergistically associated with systemic inflammation. These findings underline the need of a multifaceted approach to address CVD risk in adolescence.

Associations between retinol-binding protein 4 and cardiometabolic risk factors and subclinical atherosclerosis in recently postmenopausal women: cross-sectional analyses from the KEEPS study.

BACKGROUND: The published literature regarding the relationships between retinol-binding protein 4 (RBP4) and cardiometabolic risk factors and subclinical atherosclerosis is conflicting, likely due, in part, to limitations of frequently used RBP4 assays. Prior large studies have not utilized the gold-standard western blot analysis of RBP4 levels. METHODS: Full-length serum RBP4 levels were measured by western blot in 709 postmenopausal women screened for the Kronos Early Estrogen Prevention Study. Cross-sectional analyses related RBP4 levels to cardiometabolic risk factors, carotid artery intima-media thickness (CIMT), and coronary artery calcification (CAC). RESULTS: The mean age of women was 52.9 (± 2.6) years, and the median RBP4 level was 49.0 (interquartile range 36.9-61.5) µg/mL. Higher RBP4 levels were weakly associated with higher triglycerides (age, race, and smoking-adjusted partial Spearman correlation coefficient = 0.10; P = 0.01), but were unrelated to blood pressure, cholesterol, C-reactive protein, glucose, insulin, and CIMT levels (all partial Spearman correlation coefficients ≤0.06, P > 0.05). Results suggested a curvilinear association between RBP4 levels and CAC, with women in the bottom and upper quartiles of RBP4 having higher odds of CAC (odds ratio [95% confidence interval] 2.10 [1.07-4.09], 2.00 [1.02-3.92], 1.64 [0.82-3.27] for the 1st, 3rd, and 4th RBP4 quartiles vs. the 2nd quartile). However, a squared RBP4 term in regression modeling was non-significant (P = 0.10). CONCLUSIONS: In these healthy, recently postmenopausal women, higher RBP4 levels were weakly associated with elevations in triglycerides and with CAC, but not with other risk factors or CIMT. These data using the gold standard of RBP4 methodology only weakly support the possibility that perturbations in RBP4 homeostasis may be an additional risk factor for subclinical coronary atherosclerosis. TRIAL REGISTRATION: ClinicalTrials.gov number NCT00154180.

Associations of obesity and asthma with functional exercise capacity in urban minority adolescents.

PURPOSE: To examine the independent association of asthma and obesity and of their co-existence with functional exercise capacity among urban adolescents. METHODS: One hundred eighteen Hispanic- and African-American adolescents including 33 obese asthmatics, 18 normal-weight asthmatics, 38 obese non-asthmatics, and 29 normal-weight non-asthmatics underwent anthropometric measures, 6-minute walk test (6MWT) as measure of functional exercise capacity and spirometry as measure of pulmonary function. The 6-minute walk distance (6MWD) was compared between the four study groups. The association of 6MWD with measures of lower airway obstruction, and measures of adiposity was assessed. RESULTS: The 6MWD was lower among the obese groups with the least distance covered by the obese asthmatic group (P = 0.02). In the obese asthmatic group, there was a negative correlation between 6MWD and body mass index (BMI) (r = -0.35, P = 0.03), but no association was noted with percent-predicted forced expiratory volume in the 1st second (FEV(1) ; r = 0.07, P = 0.70). Conversely, the 6MWD correlated with FEV(1) among normal-weight asthmatics (r = 0.45, P = 0.04) and normal-weight non-asthmatics (r = 0.4, P = 0.03), but was not associated with BMI in either of the two groups. After adjusting for age, height, gender, and ethnicity, BMI was noted to be a significant predictor (ß -2.76, 95% CI -4.77 to -0.76, P < 0.01) of the 6MWD among the obese while percent predicted FEV(1) (ß 1.87, 95% CI 0.28-3.45, P = 0.02) was a significant predictor among the normal-weight participants. CONCLUSIONS: Our findings suggest that among urban minority obese asthmatic adolescents, functional exercise capacity was associated with obesity, rather than pulmonary function.

Race-ethnic differences in adipokine levels: the Study of Women's Health Across the Nation (SWAN).

Differences in adipose tissue secretory profile, as measured by adipokine levels, may play a role in race-ethnic disparities in cardiovascular disease (CVD). We examined race-ethnic differences in adipokine levels in a group of mid-life Caucasian, African American (AA), Chinese and Japanese women, after accounting for adiposity. Data on 1876 women from the Study of Women's Health Across the Nation were analyzed. In multivariable adjustment, including total fat mass, differences in total and high molecular weight (HMW) adiponectin, leptin and soluble leptin receptor (sOB-R) levels were examined. Despite intermediate levels of adiposity, Caucasian women had higher levels of both total and HMW adiponectin, when compared to both AA and Chinese and Japanese women. After multivariable adjustment, compared to Caucasian women, AA women had significantly lower total (ß: -3.40; 95% CI: -4.29, -2.52; P<.001) and HMW adiponectin (ß: -0.53; 95% CI: -0.64, -0.43; P<.001) levels, higher leptin levels (ß: 3.26; 95% CI: 1.36, 5.16; P<.001) and lower sOB-R levels (ß: -0.07; 95% CI: -0.11, -0.03; P<.001). Compared to Caucasian women, both Chinese and Japanese women had lower total (Chinese: ß: -5.50; 95% CI: -7.07, -3.93; P<.001; Japanese: ß: -5.48; 95% CI: -6.95, -4.02; P<.001) and HMW adiponectin (Chinese: ß: -0.57; 95% CI: -0.75, -0.38; P<.001; Japanese: ß: -0.61; 95% CI: -0.78, -0.44; P<.001) levels and lower sOB-R levels (Chinese: ß: -0.13; 95% CI: -0.20, -0.06; P<.001; Japanese: ß: -0.09; 95% CI: -0.15, -0.02; P=.008). Significant race-ethnic differences exist in circulating adipokines, even after accounting for adiposity. Further research is needed to explicitly determine if such differences contribute to known racial differences in CVD risk.

Burden of subclinical cardiovascular disease in "metabolically benign" and "at-risk" overweight and obese women: the Study of Women's Health Across the Nation (SWAN).

BACKGROUND: Metabolically benign obese individuals have a 10-year cardiovascular disease (CVD) risk comparable to healthy normal weight individuals. However, the burden of subclinical CVD among metabolically benign obese is not well known. METHODS: In cross-sectional analyses of 475 mid-life women, we compared common carotid artery intima media thickness (CCA-IMT), aortic pulse wave velocity (aPWV) and coronary (CAC) and aortic calcification (AC) among three groups: healthy normal weight, metabolically benign overweight/obese (<3 metabolic syndrome components/elevated CRP), and at-risk overweight/obese (≥3 metabolic syndrome components/elevated CRP). RESULTS: The mean (SD) CCA-IMT and aPWV were lowest in the normal weight group (n=145), followed by the benign overweight/obese (n=260) and at-risk overweight/obese (n=70) groups [CCA-IMT: 0.64 (0.08) vs. 0.68 (0.09) vs. 0.73 (0.13) mm, p<0.001; aPWV: 731.0 (176.4) vs. 809.9 (182.3) vs. 875.7 (228.8) cm/s, p<0.001]. Similar results were found for the frequency (%) of women with increased CAC and AC [CAC: 13 (9%) vs. 53(20%) vs. 28(40%), p<0.001; AC: 47(32%) vs. 130 (50%) vs. 55(79%), p<0.001]. These differences remained significant after multivariable adjustment. Further adjustment for BMI attenuated the statistical significance of differences in aPWV and calcification between benign and at-risk overweight/obese women, but had little effect on the magnitude of these differences. CONCLUSIONS: Metabolically benign overweight/obese women have a significantly greater subclinical CVD burden than normal weight women, despite published data finding similar CVD event rates between the two groups. Prospective studies tracking the progression of subclinical atherosclerosis to clinical CVD in these women are needed.

Subcutaneous adipose tissue in relation to subclinical atherosclerosis and cardiometabolic risk factors in midlife women.

BACKGROUND: Limited data suggest that the effects of abdominal subcutaneous adipose tissue (SAT) on cardiovascular disease risk may depend on accompanying amounts of abdominal visceral adipose tissue (VAT). OBJECTIVE: The objective was to examine whether abdominal VAT area modifies the effects of abdominal SAT area on subclinical atherosclerosis and cardiometabolic risk factors in both whites and African Americans. DESIGN: Computed tomographic measures of abdominal SAT and VAT were examined in relation to carotid intima-media thickness (cIMT) and cardiometabolic risk factor levels in 500 African American and white women in midlife. A VAT × SAT interaction term was evaluated. RESULTS: The mean (±SD) age of the sample was 51.0 ± 2.9 y, and 37% were African American. Higher amounts of SAT and VAT were associated with higher cIMT, blood pressure, homeostasis model assessment insulin resistance index (HOMA-IR), and concentrations of glucose, triglycerides, and insulin and with lower concentrations of HDL cholesterol. However, in African Americans, but not in whites, higher amounts of VAT significantly attenuated associations between higher amounts of SAT and higher insulin concentrations (P for interaction = 0.032) and HOMA-IR (P for interaction = 0.011) and reversed associations with cIMT (P for interaction = 0.005) and glucose (P for interaction = 0.044). CONCLUSIONS: These results suggest that in midlife African American but not white women, adverse associations between abdominal SAT and cardiometabolic risk factors are attenuated and, in the case of subclinical atherosclerosis, are reversed as VAT amounts increase. Given that African American women suffer disproportionately from obesity and cardiovascular disease, further research into the role of this effect modification on obesity-associated vascular disease in African American women is warranted.

Upper airway structure and body fat composition in obese children with obstructive sleep apnea syndrome.

RATIONALE: Mechanisms leading to obstructive sleep apnea syndrome (OSAS) in obese children are not well understood. OBJECTIVES: The aim of the study was to determine anatomical risk factors associated with OSAS in obese children as compared with obese control subjects without OSAS. METHODS: Magnetic resonance imaging was used to determine the size of upper airway structure, and body fat composition. Paired analysis was used to compare between groups. Mixed effects regression models and conditional multiple logistic regression models were used to determine whether body mass index (BMI) Z-score was an effect modifier of each anatomic characteristic as it relates to OSAS. MEASUREMENTS AND MAIN RESULTS: We studied 22 obese subjects with OSAS (12.5 ± 2.8 yr; BMI Z-score, 2.4 ± 0.4) and 22 obese control subjects (12.3 ± 2.9 yr; BMI Z-score, 2.3 ± 0.3). As compared with control subjects, subjects with OSAS had a smaller oropharynx (P < 0.05) and larger adenoid (P < 0.01), tonsils (P < 0.05), and retropharyngeal nodes (P < 0.05). The size of lymphoid tissues correlated with severity of OSAS whereas BMI Z-score did not have a modifier effect on these tissues. Subjects with OSAS demonstrated increased size of parapharyngeal fat pads (P < 0.05) and abdominal visceral fat (P < 0.05). The size of these tissues did not correlate with severity of OSAS and BMI Z-score did not have a modifier effect on these tissues. CONCLUSIONS: Upper airway lymphoid hypertrophy is significant in obese children with OSAS. The lack of correlation of lymphoid tissue size with obesity suggests that this hypertrophy is caused by other mechanisms. Although the parapharyngeal fat pads and abdominal visceral fat are larger in obese children with OSAS we could not find a direct association with severity of OSAS or with obesity.