Rachel P. Wildman

The Obese Without Cardiometabolic Risk Factor Clustering and the Normal Weight With Cardiometabolic Risk Factor Clustering Prevalence and Correlates of 2 Phenotypes Among the US Population (NHANES 1999-2004)

BACKGROUND The prevalence and correlates of obese individuals who are resistant to the development of the adiposity-associated cardiometabolic abnormalities and normal-weight individuals who display cardiometabolic risk factor clustering are not well known. METHODS The prevalence and correlates of combined body mass index (normal weight, < 25.0; overweight, 25.0-29.9; and obese, > or = 30.0 [calculated as weight in kilograms divided by height in meters squared]) and cardiometabolic groups (metabolically healthy, 0 or 1 cardiometabolic abnormalities; and metabolically abnormal, > or = 2 cardiometabolic abnormalities) were assessed in a cross-sectional sample of 5440 participants of the National Health and Nutrition Examination Surveys 1999-2004. Cardiometabolic abnormalities included elevated blood pressure; elevated levels of triglycerides, fasting plasma glucose, and C-reactive protein; elevated homeostasis model assessment of insulin resistance value; and low high-density lipoprotein cholesterol level. RESULTS Among US adults 20 years and older, 23.5% (approximately 16.3 million adults) of normal-weight adults were metabolically abnormal, whereas 51.3% (approximately 35.9 million adults) of overweight adults and 31.7% (approximately 19.5 million adults) of obese adults were metabolically healthy. The independent correlates of clustering of cardiometabolic abnormalities among normal-weight individuals were older age, lower physical activity levels, and larger waist circumference. The independent correlates of 0 or 1 cardiometabolic abnormalities among overweight and obese individuals were younger age, non-Hispanic black race/ethnicity, higher physical activity levels, and smaller waist circumference. CONCLUSIONS Among US adults, there is a high prevalence of clustering of cardiometabolic abnormalities among normal-weight individuals and a high prevalence of overweight and obese individuals who are metabolically healthy. Further study into the physiologic mechanisms underlying these different phenotypes and their impact on health is needed.

Indices of abdominal obesity are better discriminators of cardiovascular risk factors than BMI: a meta-analysis

OBJECTIVE To determine which simple index of overweight and obesity is the best discriminator of cardiovascular risk factors. STUDY DESIGN AND SETTING This is a meta-analysis of published literature. MEDLINE was searched. Studies that used receiver-operating characteristics (ROC) curve analysis and published area under the ROC curves (AUC) for overweight and obesity indices with hypertension, type-2 diabetes, and/or dyslipidemia were included. The AUC for each of the four indices, with each risk factor, was pooled using a random-effects model; male and female data were analyzed separately. RESULTS Ten studies met the inclusion criteria. Body mass index (BMI) was the poorest discriminator for cardiovascular risk factors. Waist-to-height ratio (WHtR) was the best discriminator for hypertension, diabetes, and dyslipidemia in both sexes; its pooled AUC (95% confidence intervals) ranged from 0.67 (0.64, 0.69) to 0.73 (0.70, 0.75) and from 0.68 (0.63, 0.72) to 0.76 (0.70, 0.81) in males and females, respectively. CONCLUSION Statistical evidence supports the superiority of measures of centralized obesity, especially WHtR, over BMI, for detecting cardiovascular risk factors in both men and women.

Measures of Obesity Are Associated With Vascular Stiffness in Young and Older Adults

Abstract—Obesity has reached epidemic levels and carries a risk for cardiovascular disease. Obesity’s effects on the vascular systems of young adults and African Americans have not been well characterized. The aim of this study was to assess the association between measures of obesity and aortic stiffness in 186 young adults (20 to 40 years, 50% African American) and 177 older adults (41 to 70 years, 33% African American). Aortic stiffness was measured by aortic pulse-wave velocity. The median pulse-wave velocity value was 468 cm/s for young adults and 627 cm/s for older adults (P <0.001). Higher body weight, body mass index, waist and hip circumferences, and waist-hip ratio were strongly correlated with higher pulse-wave velocity, independent of age, systolic blood pressure, race, and sex overall and among both age groups (P <0.01 for all). Even among the 20- to 30-year-olds, obese individuals (body mass index>30) had a mean pulse-wave velocity value 47 cm/s higher than did nonobese individuals (P <0.001). Obesity measures were among the strongest independent predictors of pulse-wave velocity overall and for both age groups. Results were consistent by race. In conclusion, excess body weight is associated with higher aortic stiffness in whites and African Americans as young as 20 to 30 years. The strength of the association, the early age at which it appears, and the prevalence of obesity among the young warn of substantially increased cardiovascular disease incidence as this cohort ages.

Sex Hormone–Binding Globulin and the Free Androgen Index Are Related to Cardiovascular Risk Factors in Multiethnic Premenopausal and Perimenopausal Women Enrolled in the Study of Women Across the Nation (SWAN)

Background—Recent clinical trials have shifted attention away from estrogens and toward androgens and sex hormone–binding globulin (SHBG) as potential mediators of increasing cardiovascular (CV) risk in women at midlife. Methods and Results—The correlation between reproductive hormones and CV risk factors was evaluated in a multiethnic (white, black, Hispanic, Chinese, and Japanese) sample of 3297 premenopausal and perimenopausal women. Testosterone and estradiol (E2) were evaluated along with SHBG and the free androgen index (FAI), the amount of testosterone not bound by SHBG. Low SHBG and high FAI were strongly and consistently related to elevated CV risk factors (higher insulin, glucose, and hemostatic and inflammatory markers and adverse lipids) even after controlling for body mass index (P<0.001 for all). Low levels of E2 were associated with elevated CV risk factors to a lesser degree. These observations were consistent across the 5 ethnic groups. Compared with whites, blacks had higher levels of SHBG and lower levels of FAI, and Chinese had lower levels of SHBG and higher levels of FAI. Conclusions—Low SHBG and high FAI are strongly associated with CV risk factors in racially diverse women, and thus, androgens likely play a role in the CV risk profile of perimenopausal women.

Weight Change Is Associated With Change in Arterial Stiffness Among Healthy Young Adults

Risk factors for arterial stiffness progression have not been well characterized. We examined the relationship between arterial stiffness progression and body weight and weight gain in a group of healthy young adults. Aortic pulse-wave velocity was assessed at 2 time points approximately 2 years apart in 152 white and black adults aged 20 to 40 years, and was standardized by the time between visits to obtain annualized pulse-wave velocity changes. Blacks had 15.5 cm/s per year larger annual pulse-wave velocity increases compared with whites (P=0.02), even after multivariable adjustment for weight and blood pressure changes. Larger annual pulse-wave velocity increases were also associated with larger baseline body weight (P=0.02), waist girth (P=0.003), and body mass index (P<0.001), and greater annual weight gain (P=0.02), after adjustment for baseline pulse-wave velocity. After multivariable adjustment that included blood pressure changes, larger baseline waist girth (P=0.009), baseline body mass index (P=0.001), body mass index increase (P=0.037), and weight gain (P=0.017) remained significantly associated with larger annual pulse-wave velocity progression. Weight change showed a direct relationship with pulse-wave velocity change; mean annual pulse-wave velocity changes were −29.9 cm/s per year (regression) for those with ≥4.5 kg annual weight loss and 18.2 cm/s per year (progression) for those with ≥4.5 kg annual weight gain. These data show strong associations between weight gain and arterial stiffness progression, as well as between weight loss and arterial stiffness regression. These data greatly underscore the vascular benefit of weight loss. Successful weight loss programs in young adults, particularly blacks, are needed.

Prevalence of Physical Activity Among Chinese Adults: Results From the International Collaborative Study of Cardiovascular Disease in Asia

OBJECTIVES Determining physical activity levels in the community provides a context for the development and implementation of programs aimed at increasing these activity levels. Therefore, we assessed overall, work-related, and leisure-time physical activity in a representative sample of Chinese adults, aged 35 to 74 years, using data from the International Collaborative Study of Cardiovascular Disease in Asia. METHODS Being physically active was defined as participating in 30 or more minutes of moderate or vigorous activity daily. Work-related and leisure-time physical activities were defined as being physically active and participating in any moderate or vigorous activity at work or during leisure time, respectively. RESULTS In rural and urban China, 78.1% and 21.8% of residents, respectively, were physically active; 75.8% and 16.5%, respectively, participated in work-related activity; and 28.9% and 7.9%, respectively, participated in leisure-time physical activity. In both rural and urban settings, younger adults, men, and southern residents were more likely to be physically active and to participate in work-related and leisure-time physical activity than older adults, women, and northern residents. CONCLUSIONS Intervention strategies to promote leisure-time physical activity, especially among urban residents, should be considered a major health priority in China.

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.

Measures of adiposity and cardiovascular disease risk factors.

Objective: To determine which of five measures of adiposity maintains the strongest association with cardiovascular disease risk factors.

Associations of Endogenous Sex Hormones with the Vasculature in Menopausal Women: The Study of Women's Health Across the Nation (SWAN)

Objective: As associations between endogenous sex hormones and the vasculature are not well characterized, the objective was to examine the cross-sectional associations of menopausal status and endogenous sex hormones with vascular characteristics. Design: Common carotid artery adventitial diameter and intima-media thickness were determined using B-mode ultrasonography among 483 middle-aged women enrolled in the Pittsburgh and Chicago sites of the Study of Womens Health Across the Nation. Results: Sixty-two percent of women were pre- or early perimenopausal (<3 mo amenorrhea), 12% were late perimenopausal (3-12 mo amenhorrhea), and 27% were postmenopausal (≥12 mo amenorrhea). After adjustment for age, compared with pre-/early perimenopause, late perimenopause was associated with a 0.28-mm larger adventitial diameter (P = 0.001), whereas postmenopause was associated with a 0.15-mm larger adventitial diameter (P = 0.040). Adjustment for traditional cardiovascular risk factors slightly attenuated these associations, but the association with late perimenopause remained statistically significant (P = 0.001). Each SD lower log estradiol value was associated with a 0.07-mm larger adventitial diameter after adjustment for traditional cardiovascular risk factors (P = 0.023), whereas other endogenous hormones showed no associations. Intima-media thickness values were not significantly associated with menopausal status or endogenous sex hormones after adjustment for age. Conclusions: The menopausal transition and declining estrogen levels are associated with alterations of the peripheral vasculature, which may help to explain the increased risk of cardiovascular disease with postmenopause.

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.