Unab I. Khan

Incident Cardiovascular Disease Events in Metabolically Benign Obese Individuals

Nearly one‐third of obese individuals are classified as metabolically benign; however whether this subgroup is at a lower risk of cardiovascular disease (CVD) is unclear. Using pooled data from the Atherosclerosis Risk in Communities and Cardiovascular Health Studies, we assessed incident CVD (coronary heart disease and stroke) using three definitions of the metabolically benign phenotype: (i) the ATP‐III metabolic syndrome definition (≤2 of the ATP‐III components, excluding abdominal obesity (ii) the expanded ATP‐III definition (≤1 of: any ATP‐III components, insulin resistance (IR), or systemic inflammation), and (iii) the IR‐based definition (sex‐specific lowest quartile of the HOMAIR distribution). The sample included 6,106 normal weight, 7,115 overweight, and 4,323 obese participants. Among obese, 27.0%, 18.1%, and 20.4% were metabolically benign by the three definitions, respectively. The CVD incidence rates (mean follow‐up 11.8 years) were 7.1, 5.8, and 8.4 per 1,000 person‐years in metabolically benign obese via the three definitions, respectively, compared to 14.3, 13.8, and 13.3 in at‐risk obese, and 7.5, 6.7, and 8.2 in metabolically benign normal weight participants. Multivariable‐adjusted hazard ratios of incident CVD in metabolically benign obese compared to their at‐risk obese counterparts were 0.59 (95% CI 0.47–0.73), 0.52 (0.39–0.68), and 0.71 (0.57–0.90), respectively; and 1.24 (0.99–1.57), 1.16 (0.86–1.56), and 1.28 (1.01–1.62) compared to metabolically benign normal weight individuals. Only 28.7% of obese participants classified as metabolically benign by at least one definition were “metabolically benign” by all three definitions. Despite similar CVD risk estimates, the three definitions identified different subgroups of the obese population, perhaps suggesting distinct etiologies.

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.

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.

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 Womens 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 (β: -3.40; 95% CI: -4.29, -2.52; P<.001) and HMW adiponectin (β: -0.53; 95% CI: -0.64, -0.43; P<.001) levels, higher leptin levels (β: 3.26; 95% CI: 1.36, 5.16; P<.001) and lower sOB-R levels (β: -0.07; 95% CI: -0.11, -0.03; P<.001). Compared to Caucasian women, both Chinese and Japanese women had lower total (Chinese: β: -5.50; 95% CI: -7.07, -3.93; P<.001; Japanese: β: -5.48; 95% CI: -6.95, -4.02; P<.001) and HMW adiponectin (Chinese: β: -0.57; 95% CI: -0.75, -0.38; P<.001; Japanese: β: -0.61; 95% CI: -0.78, -0.44; P<.001) levels and lower sOB-R levels (Chinese: β: -0.13; 95% CI: -0.20, -0.06; P<.001; Japanese: β: -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.

A qualitative assessment of barriers and facilitators to achieving behavior goals among obese inner-city adolescents in a weight management program

Purpose The purpose of this study was (1) to examine the reasons for managing weight, (2) to investigate the barriers and facilitators to achieving behavior goals, and (3) to assess how a behavior coach affects the goalsetting process of obese innercity adolescents in a weight management program. Methods Obese adolescents participating in a pilot study assessing the role of a behavior coach on successful weight management (n = 18) were interviewed to identify barriers and facilitators to reaching behavior goals. Data were analyzed using descriptive statistics and the constant comparative method of qualitative analysis. Results In the rationale for weight control, adolescent girls and boys reported a desire to improve physical appearance and physical conditioning, respectively. Barriers to reaching physical activity goals among girls included unsafe neighborhoods and a negative body image. Maintaining unrealistic behavior and weight goals hindered satisfaction with behavior change and weight loss in both genders. Overall, coaching provided support that helped the obese teens feel more successful in the goalsetting process and address issues related to their disruptive environments. Conclusions Diabetes educators can include a behavior coach as part of a weight management program to help teens set behavior goals and overcome barriers to reaching behavior goals.

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.

The adipokine profile of metabolically benign obese and at-risk normal weight postmenopausal women: the women’s health initiative observational study

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.

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

To examine the independent association of asthma and obesity and of their co‐existence with functional exercise capacity among urban adolescents.

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

BackgroundThe 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.MethodsFull-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).ResultsThe 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).ConclusionsIn 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 registrationClinicalTrials.gov number NCT00154180

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 Womens 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.