Ghada N. Farhat

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.

Volumetric BMD and vascular calcification in middle-aged women : The study of women's health across the nation

The association of spine vBMD with AC and CAC was studied in a biracial cohort of 490 middle‐aged women in the Study of Womens Health Across the Nation. Lower vBMD was related to high AC, but not to CAC, independent of age and shared risk factors between osteoporosis and cardiovascular disease.

Relationship Between Mammographic Density and Breast Cancer Death in the Breast Cancer Surveillance Consortium

BACKGROUND Women with elevated mammographic density have an increased risk of developing breast cancer. However, among women diagnosed with breast cancer, it is unclear whether higher density portends reduced survival, independent of other factors. METHODS We evaluated relationships between mammographic density and risk of death from breast cancer and all causes within the US Breast Cancer Surveillance Consortium. We studied 9232 women diagnosed with primary invasive breast carcinoma during 1996-2005, with a mean follow-up of 6.6 years. Mammographic density was assessed using the Breast Imaging Reporting and Data System (BI-RADS) density classification. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression; women with scattered fibroglandular densities (BI-RADS 2) were the referent group. All statistical tests were two-sided. RESULTS A total of 1795 women died, of whom 889 died of breast cancer. In multivariable analyses (adjusted for site, age at and year of diagnosis, American Joint Committee on Cancer stage, body mass index, mode of detection, treatment, and income), high density (BI-RADS 4) was not related to risk of death from breast cancer (HR = 0.92, 95% CI = 0.71 to 1.19) or death from all causes (HR = 0.83, 95% CI = 0.68 to 1.02). Analyses stratified by stage and other prognostic factors yielded similar results, except for an increased risk of breast cancer death among women with low density (BI-RADS 1) who were either obese (HR = 2.02, 95% CI = 1.37 to 2.97) or had tumors of at least 2.0 cm (HR = 1.55, 95% CI = 1.14 to 2.09). CONCLUSIONS High mammographic breast density was not associated with risk of death from breast cancer or death from any cause after accounting for other patient and tumor characteristics. Thus, risk factors for the development of breast cancer may not necessarily be the same as factors influencing the risk of death after breast cancer has developed.

Volumetric and Areal Bone Mineral Density Measures Are Associated with Cardiovascular Disease in Older Men and Women: The Health, Aging, and Body Composition Study

The associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with prevalent cardiovascular disease (CVD) and subclinical peripheral arterial disease (PAD) were investigated in a cohort of older men and women enrolled in the Health, Aging, and Body Composition Study. Participants were 3,075 well-functioning white and black men and women (42% black, 51% women), aged 68–80 years. Total hip, femoral neck, and trochanter aBMD were measured using dual-energy X-ray absorptiometry. Quantitative computed tomography was used to evaluate spine trabecular, integral, and cortical vBMD measures in a subgroup (n = 1,489). Logistic regression was performed to examine associations of BMD measures with CVD and PAD. The prevalence of CVD (defined by coronary heart disease, PAD, cerebrovascular disease, or congestive heart failure) was 29.8%. Among participants without CVD, 10% had subclinical PAD (defined as ankle-arm index <0.9). Spine vBMD measures were inversely associated with CVD in men (odds ratio of integral [ORintegral] = 1.34, 95% confidence interval [CI] 1.10–1.63; ORtrabecular = 1.25, 95% CI 1.02–1.53; ORcortical = 1.36, 95% CI 1.11–1.65). In women, for each standard deviation decrease in integral vBMD, cortical vBMD, or trochanter aBMD, the odds of CVD were significantly increased by 28%, 27%, and 22%, respectively. Total hip aBMD was associated with subclinical PAD in men (OR = 1.39, 95% CI 1.03–1.84) but not in women. All associations were independent of age and shared risk factors between BMD and CVD and were not influenced by inflammatory cytokines (interleukin-6 and tumor necrosis factors-α). In conclusion, our results provide further evidence for an inverse association between BMD and CVD in men and women. Future research should investigate common pathophysiological links for osteoporosis and CVD.

Sex Hormone Levels and Risks of Estrogen Receptor–Negative and Estrogen Receptor–Positive Breast Cancers

BACKGROUND Endogenous sex hormone levels are associated with risks of breast cancer overall and estrogen receptor (ER)-positive breast tumors; however, their associations with ER-negative tumors remain unclear. METHODS In a case-cohort study within the Womens Health Initiative Observational Study among postmenopausal women aged 50-79 years, we examined associations between endogenous testosterone and estradiol levels and the risks of ER-negative and ER-positive breast cancers. Serum levels of bioavailable testosterone and estradiol were assessed at the baseline visit in 317 invasive breast cancer case subjects and in a subcohort of 594 women. Bioavailable sex hormone levels were calculated using the total hormone level and the sex hormone-binding globulin concentration (measured by radioimmunoassays and a chemiluminescent immunoassay, respectively). Cox proportional hazards regression was used for statistical analysis. All statistical tests were two-sided. RESULT The unadjusted absolute rates of ER-negative breast cancer for testosterone quartiles 1-4 were 0.34, 0.20, 0.23, and 0.21 per 10,000 person-years, respectively. Compared with women in the lowest quartile of testosterone level, those in quartile 2 had a 56% lower risk of ER-negative cancer (hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.23 to 0.85), those in quartile 3 had a 45% lower risk (HR = 0.55, 95% CI = 0.30 to 1.01), and those in quartile 4 had a 49% lower risk (HR = 0.51, 95% CI = 0.28 to 0.94), independent of other risk factors. Estradiol level was not associated with ER-negative breast cancer. ER-positive breast cancer risk increased with higher testosterone levels (P(trend) = .04), but this trend was not statistically significant after adjustment for estradiol (P(trend) = .15). ER-positive cancer risk was approximately twofold higher in women with estradiol levels in quartiles 2-4 compared with women in quartile 1, independent of risk factors. CONCLUSION Higher serum levels of bioavailable testosterone are associated with lower risks of ER-negative breast cancer in postmenopausal women.

The development and deployment of Common Data Elements for tissue banks for translational research in cancer – An emerging standard based approach for the Mesothelioma Virtual Tissue Bank

BackgroundRecent advances in genomics, proteomics, and the increasing demands for biomarker validation studies have catalyzed changes in the landscape of cancer research, fueling the development of tissue banks for translational research. A result of this transformation is the need for sufficient quantities of clinically annotated and well-characterized biospecimens to support the growing needs of the cancer research community. Clinical annotation allows samples to be better matched to the research question at hand and ensures that experimental results are better understood and can be verified. To facilitate and standardize such annotation in bio-repositories, we have combined three accepted and complementary sets of data standards: the College of American Pathologists (CAP) Cancer Checklists, the protocols recommended by the Association of Directors of Anatomic and Surgical Pathology (ADASP) for pathology data, and the North American Association of Central Cancer Registry (NAACCR) elements for epidemiology, therapy and follow-up data. Combining these approaches creates a set of International Standards Organization (ISO) – compliant Common Data Elements (CDEs) for the mesothelioma tissue banking initiative supported by the National Institute for Occupational Safety and Health (NIOSH) of the Center for Disease Control and Prevention (CDC).MethodsThe purpose of the project is to develop a core set of data elements for annotating mesothelioma specimens, following standards established by the CAP checklist, ADASP cancer protocols, and the NAACCR elements. We have associated these elements with modeling architecture to enhance both syntactic and semantic interoperability. The system has a Java-based multi-tiered architecture based on Unified Modeling Language (UML).ResultsCommon Data Elements were developed using controlled vocabulary, ontology and semantic modeling methodology. The CDEs for each case are of different types: demographic, epidemiologic data, clinical history, pathology data including block level annotation, and follow-up data including treatment, recurrence and vital status. The end result of such an effort would eventually provide an increased sample set to the researchers, and makes the system interoperable between institutions.ConclusionThe CAP, ADASP and the NAACCR elements represent widely established data elements that are utilized in many cancer centers. Herein, we have shown these representations can be combined and formalized to create a core set of annotations for banked mesothelioma specimens. Because these data elements are collected as part of the normal workflow of a medical center, data sets developed on the basis of these elements can be easily implemented and maintained.

Quantifying mediating effects of endogenous estrogen and insulin in the relation between obesity, alcohol consumption and breast cancer

Background: Increased exposure to endogenous estrogen and/or insulin may partly explain the relationship of obesity, physical inactivity, and alcohol consumption and postmenopausal breast cancer. However, these potential mediating effects have not been formally quantified in a survival analysis setting. Methods: We combined data from two case–cohort studies based in the Womens Health Initiative-Observational Study with serum estradiol levels, one of which also had insulin levels. A total of 1,601 women (601 cases) aged 50 to 79 years who were not using hormone therapy at enrollment were included. Mediating effects were estimated by applying a new method based on the additive hazard model. Results: A five-unit increase in body mass index (BMI) was associated with 50.0 [95% confidence interval (CI), 23.2–76.6] extra cases per 100,000 women at-risk per year. Of these, 23.8% (95% CI, 2.9–68.4) could be attributed to estradiol and 65.8% (95% CI, 13.6–273.3) through insulin pathways. The mediating effect of estradiol was greater (48.8%; 95% CI, 18.8–161.1) for BMI when restricted to estrogen receptor positive (ER+) cases. Consuming 7+ drinks/wk compared with abstinence was associated with 164.9 (95% CI, 45.8–284.9) breast cancer cases per 100,000, but no significant contribution from estradiol was found. The effect of alcohol on breast cancer was restricted to ER+ breast cancers. Conclusions: The relation of BMI with breast cancer was partly mediated through estradiol and, to a greater extent, through insulin. Impact: The findings provide support for evaluation of interventions to lower insulin and estrogen levels in overweight and obese postmenopausal women to reduce breast cancer risk. Cancer Epidemiol Biomarkers Prev; 21(7); 1203–12. ©2012 AACR.

The association of menopause status with physical function: the Study of Women's Health Across the Nation.

ObjectiveThe aim of this study was to determine whether postmenopause status is associated with self-reported limitations in physical function. MethodsThe Study of Women’s Health Across the Nation is a multisite, multiethnic, longitudinal study of midlife women. Women aged 45 to 57 years (N = 2,566) completed the physical function scale of the Medical Outcomes Study Short-Form 36 on visit 4 (2000-2001). Scores created a three-category variable of physical function limitations: none (86-100), moderate (51-85), and substantial (0-50). In the Study of Women’s Health Across the Nation, menopause status is a five-category list variable based on menstrual bleeding patterns and gynecological surgery. Premenopausal and perimenopausal women using hormones (n = 284) or missing physical function scores (n = 46) were excluded. Multinomial logistic regression was used to relate physical function and menopause status after adjustment for age, ethnicity, site, education, body mass index (BMI), and self-reported diabetes, hypertension, arthritis, depressive symptoms, smoking, and hormone use among postmenopausal women. ResultsOf 2,236 women, 8% were premenopausal, 51% were early perimenopausal, 12% were late perimenopausal, 24% were naturally postmenopausal, and 5% were surgically postmenopausal. In the full model, substantial limitations in physical function were higher in postmenopausal women, whether naturally postmenopausal (odds ratio, 3.82; 95% CI, 1.46-10.0) or surgically postmenopausal (odds ratio, 3.54; 95% CI, 1.15-10.84), than in premenopausal women. These associations were attenuated by higher BMI and depressive symptoms but remained significant. Moderate limitations in physical function were not significantly related to menopause status. ConclusionsWomen experiencing surgical or naturally occurring postmenopause report greater limitations in physical function compared with premenopausal women, independent of age and only partly explained by higher BMI and depressive symptoms. This suggests that physiological changes in menopause could contribute directly to limitations in physical function.

Sex Hormone Levels and Risk of Breast Cancer With Estrogen Plus Progestin

BACKGROUND Although high endogenous sex hormone levels and estrogen plus progestin (E+P) therapy are associated with increased breast cancer risk, it is unknown whether pretreatment levels of sex hormones modify E+P effect on breast cancer. METHODS We conducted a nested case-control study within the Womens Health Initiative randomized clinical trial of E+P. The trial enrolled 16608 postmenopausal women aged 50 to 79 years with intact uterus and no breast cancer history. During a mean of 5.6 years of follow-up, 348 incident breast cancer case subjects were identified and matched with 348 control subjects. Case and control subjects had their sex hormone levels measured at baseline (estrogens, testosterone, progesterone, and sex hormone-binding globulin [SHBG]) and year 1 (estrogens and SHBG) using sensitive assays. All statistical tests were two-sided. RESULTS Statistically significant elevations in breast cancer risk were seen with greater pretreatment levels of total estradiol (P trend = .04), bioavailable estradiol (P trend = .03), estrone (P trend = .007), and estrone sulfate (P trend = .007). E+P increased all measured estrogens and SHGB at year 1 (all P < .001). The effect of E+P on breast cancer risk was strongest in women whose pretreatment levels of total estradiol, bioavailable estradiol, and estrone were in the lowest quartiles. For example, the odds ratio for E+P relative to placebo was 2.47 (95% confidence interval [CI] = 1.28 to 4.79) in the lowest total estradiol quartile, compared with 0.96 (95% CI = 0.44 to 2.09) in the highest total estradiol quartile; P interaction = .04). CONCLUSIONS Women with lower pr-treatment endogenous estrogen levels were at greater risk of breast cancer during E+P therapy compared with those with higher levels. Further studies are warranted to confirm these findings.

Assessment of Dietary Intake Patterns and Their Correlates among University Students in Lebanon

Introduction: Unhealthy dietary habits are major risk factors for chronic diseases, particularly if adopted during early years of adulthood. Limited studies have explored the food consumption patterns among young adults in Lebanon. Our study aimed to examine common dietary patterns and their correlates among a large sample of university student population in Lebanon, focusing on correlation with gender and body mass index (BMI). Methods: A cross-sectional study was carried out on 3384 students, using a proportionate cluster sample of Lebanese students from both public and private universities. A self-administered food frequency questionnaire was used to assess dietary intake of university students. Factor analysis of food items and groups, cluster analysis of dietary patterns, and multivariate regressions were carried out. Results: Three dietary patterns were identified among university youth namely a vegetarian/low calorie dietary pattern (characterized mainly by consumption of plant-based food while avoiding “western” food, composite dishes, and bread); a mixed dietary pattern (characterized by high consumption of plant-based food, followed by composite dishes, bread, and a low consumption of western type food); and finally, a westernized dietary pattern (characterized by high consumption of white bread and western food, and a strong avoidance of plant food and composite dishes). We observed significant differences between males and females in terms of their reported food intake and dietary patterns. Females were particularly more prone to adopt the vegetarian/low calorie diet than males (ORa = 1.69; p < 0.001), while males were more likely to adopt a westernized diet (ORa = 1.51; p < 0.001), seemingly in private universities (p = 0.053). Students with high income and obese students (BMI ≥ 30 kg/m2) were more likely to consume vegetarian/low calorie diets (p < 0.05). Conclusion: Male university students reported a higher consumption of the westernized dietary pattern as compared to female university students in Lebanon, while the latter reported a higher adoption of a vegetarian diet. Health promotion programs are needed to address the dietary intakes and lifestyle behaviors of young adults in Lebanon to help prevent obesity and other associated comorbidities.