Mortality Associated with Healthy Eating Index Components and an Empirical-Scores Healthy Eating Index in a Cohort of Postmenopausal Women.

BACKGROUND: Studies of diet and chronic disease include a recent important focus on dietary patterns. Patterns are typically defined by listing dietary variables and by totaling scores that reflect whether consumption is encouraged or discouraged for listed variables. However, precision may be improved by including total energy consumption among the dietary variables and by scoring dietary variables empirically. OBJECTIVES: To relate Healthy Eating Index (HEI)-2010 components and total energy intake to all-cause and cause-specific mortality in Women's Health Initiative (WHI) cohorts and to define and evaluate an associated Empirical-Scores Healthy Eating Index (E-HEI). METHODS: Analyses are conducted in WHI cohorts (n = 67,247) of healthy postmenopausal women, aged 50-79 y, when enrolled during 1993-1998 at 40 US clinical centers, with embedded nutrition biomarker studies. Replicate food-frequency assessments for HEI-2010 ratio variables and doubly labeled water total energy assessments, separated by ∼6 mo, are used as response variables to jointly calibrate baseline dietary data to reduce measurement error influences, using 2 nutrition biomarker studies (n = 199). Calibrated dietary variables are associated with mortality risk, and an E-HEI is defined, using cross-validated HR regression estimation. RESULTS: Of 15 dietary variables considered, all but empty calories calibrated well. Ten variables related significantly (P < 0.05) to total mortality, with favorable fruit, vegetable, whole grain, refined grain, and unsaturated fat associations and unfavorable sodium, saturated fat, and total energy associations. The E-HEI had cross-validated total mortality HRs (95% CIs) of 0.87 (0.82, 0.93), 0.80 (0.76, 0.86), 0.77 (0.72, 0.82), and 0.74 (0.69, 0.79) respectively, for quintiles 2 through 5 compared with quintile 1. These depart more strongly from the null than do HRs for HEI-2010 quintiles, primarily because of total energy. CONCLUSIONS: Mortality among US postmenopausal women depends strongly on diet, as evidenced by a new E-HEI that differs substantially from earlier dietary pattern score specifications.

Processed Meat, but Not Unprocessed Red Meat, Is Inversely Associated with Leukocyte Telomere Length in the Strong Heart Family Study.

BACKGROUND: Telomeres are repetitive nucleotide sequences (TTAGGG) and their associated proteins at the end of eukaryote chromosomes. Telomere length shortens throughout the lifespan with each cell division, and leukocyte telomere length (LTL) is often used as a biomarker of cellular aging. LTL is related to many chronic diseases, including cardiovascular disease and diabetes. However, to our knowledge, the relation between LTL and risk factors for cardiovascular disease and diabetes, such as dietary intake of processed meat and unprocessed red meat, is largely unknown. OBJECTIVE: We examined the associations of processed meat intake and unprocessed red meat intake with LTL. METHODS: This cross-sectional study comprised 2846 American Indians from the Strong Heart Family Study who participated in the 2001-2003 examination. Dietary factors, including past-year consumption of processed meat and unprocessed red meat, were assessed with the use of a 119-item Block Food-Frequency Questionnaire. LTL was measured with the use of quantitative polymerase chain reaction. Generalized estimating equations were used to examine the associations of intake of processed meat and unprocessed red meat with LTL. RESULTS: Consumption of processed meat was negatively associated with LTL after adjustment for age, sex, site, education, smoking, alcohol use, physical activity, and other dietary factors. For every additional daily serving of processed meat, LTL was 0.021 units (telomeric product-to-single-copy gene ratio) shorter (ß ± SE = -0.021 ± 0.008, P = 0.009). No association was observed between the intake of unprocessed red meat and LTL (ß ± SE = 0.008 ± 0.011, P = 0.46). CONCLUSIONS: In the Strong Heart Family Study, consumption of processed meat, but not unprocessed red meat, was associated with shorter LTL, a potential mediator for several age-related diseases. Further studies are needed to better understand the biological mechanism by which processed meat intake influences cellular aging.

Sex hormone associations with breast cancer risk and the mediation of randomized trial postmenopausal hormone therapy effects.

INTRODUCTION: Paradoxically, a breast cancer risk reduction with conjugated equine estrogens (CEE) and a risk elevation with CEE plus medroxyprogesterone acetate (CEE + MPA) were observed in the Women's Health Initiative (WHI) randomized controlled trials. The effects of hormone therapy on serum sex hormone levels, and on the association between baseline sex hormones and disease risk, may help explain these divergent breast cancer findings. METHODS: Serum sex hormone concentrations were measured for 348 breast cancer cases in the CEE + MPA trial and for 235 cases in the CEE trial along with corresponding pair-matched controls, nested within the WHI trials of healthy postmenopausal women. Association and mediation analyses, to examine the extent to which sex hormone levels and changes can explain the breast cancer findings, were conducted using logistic regression. RESULTS: Following CEE treatment, breast cancer risk was associated with higher concentrations of baseline serum estrogens, and with lower concentrations of sex hormone binding globulin. However, following CEE + MPA, there was no association of breast cancer risk with baseline sex hormone levels. The sex hormone changes from baseline to year 1 provided an explanation for much of the reduced breast cancer risk with CEE. Specifically, the treatment odds ratio (95% confidence interval) increased from 0.71 (0.43, 1.15) to 0.92 (0.41, 2.09) when the year 1 measures were included in the logistic regression analysis. In comparison, the CEE + MPA odds ratio was essentially unchanged when these year 1 measures were included. CONCLUSIONS: Breast cancer risk remains low following CEE use among women having favorable baseline sex hormone profiles, but CEE + MPA evidently produces a breast cancer risk for all women similar to that for women having an unfavorable baseline sex hormone profile. These patterns could reflect breast ductal epithelial cell stimulation by CEE + MPA that is substantially avoided with CEE, in conjunction with relatively more favorable effects of either regimen following a sustained period of estrogen deprivation. These findings may have implications for other hormone therapy formulations and routes of delivery. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00000611.

Development of an Assessment Tool to Measure Healthy Eating in Navajo Children and Their Families.

Background: To estimate the efficacy of interventions to improve healthy eating, valid measures are essential. Although simple dietary intake tools have been developed with other populations, few have been culturally tailored and assessed for validity and reliability among Navajo. Objectives: This study aimed to develop a simple dietary intake tool tailored to Navajo culture, derive healthy eating indices, and assess their validity and reliability in Navajo children and adults and to describe the process used to develop this tool. Methods: A picture-sort tool using typically consumed foods was developed. Elementary school children and family members provided qualitative feedback in focus groups, used to refine the tool. Next, school-aged children and adults completed assessments at baseline and follow-up. Baseline behavior measures including child self-efficacy for fruits and vegetables (F&V) were examined for internal consistency. Healthy eating indices were derived from intake frequencies from picture sorting. The convergent validity of the indices and behavior measures for children and adults were examined. The reliability of the indices at the 2 time points was derived using Bland-Altman plots. Results: The picture-sort was refined from feedback provided by the focus groups. Baseline measures from 25 children and 18 adults were obtained. In children, a modified Alternative Healthy Eating Index (AHEI) and 2 other indices from the picture-sort were correlated with self-efficacy for eating F&V and had good reliability. In adults, the modified AHEI and 3 other indices from the picture-sort had significant correlations with adult abbreviated food frequency of F&V or obesogenic dietary index and had good reliability. Conclusions: The Navajo foods picture-sort tool developed for Navajo children and adults is proven to be acceptable and feasible to implement. Indices derived from the tool has good convergent validity and repeatability, supporting use in evaluating dietary change interventions in Navajo, with the potential for broader use of the approach in other underserved populations.

Relationship of Socioeconomic Status Indicators to Obesity in Hispanic and Non-Hispanic White Middle-Aged Women: A Population Study.

BACKGROUND: Obesity rates differ between Hispanic and White (non-Hispanic) women in the United States, with higher rates among Hispanic women. Socioeconomic processes contribute to this disparity both at the individual and the environmental level. Understanding these complex relationships requires multilevel analyses within cohorts of women that have a shared environment. In population-based samples of Hispanic and White (non-Hispanic) women from the same neighborhoods, we evaluated within each ethnic group a) The association of individual-level socioeconomic status (SES) with body mass index (BMI); and b) The additional contribution of neighborhood-level measures of SES. METHODS: Using population-based multi-stage sampling methods, we oversampled low SES and Hispanic block groups. During household screening, we identified women aged 30 to 50 years. Among White women, we specifically oversampled women with low educational levels. 515 Hispanic and 503 White women completed baseline. Height and weight were measured. Baseline surveys, in Spanish and English, included four measures of SES. Three measures of area-level SES were examined. Analysis of loge BMI on each SES measure used linear mixed models, incorporating design effects. RESULTS: Among White women, low education, social status, and neighborhood SES were associated with higher BMI (p < 0.001, p < 0.0001, and p < 0.05, respectively), independent of other SES measures. Although the highest grouped category of education, income and subjective social status within the Hispanic cohort had the lowest mean estimated BMI, the point estimates across categories were not monotonic, and had wide confidence intervals. As a result, in contrast to the findings among White women, no statistically significant associations were found between BMI and measures of SES among Hispanic women. DISCUSSION: Neighborhood and individual measures of SES operate differently in Hispanic compared with White women. We had assumed the measures we included to be most salient and operate similarly for both groups of women. Rather the salient factors for Hispanic women have yet to be identified. Improved understanding may ultimately inform the design of culturally-relevant multilevel obesity prevention strategies.

Perceived neighborhood disorder, racial-ethnic discrimination and leading risk factors for chronic disease among women: California Behavioral Risk Factor Surveillance System, 2013.

Social environmental factors are theoretically identified as influential drivers of health behaviors - tobacco smoking, alcohol consumption, and physical activity - related to chronic disease disparities. Empirical studies investigating relationships involving social environmental factors have found that either greater interpersonal racial-ethnic discrimination or perceived neighborhood disorder were associated with adverse health behaviors, with potentially larger effects among women. We simultaneously tested whether measures of perceived racial-ethnic discrimination and perceived neighborhood disorder were associated with physical activity, alcohol consumption and tobacco smoking; lifestyle risk factors of major chronic disease among women. Data were from the 2013 California Behavioral Risk Factor Surveillance System. In addition to demographic and socioeconomic factors, women self-reported experiences with racial-ethnic discrimination and perception of neighborhood disorder (i.e., crime safety, traffic safety, and aesthetics/physical disorder). Survey-, and inverse probability of censoring-weighted regression models of each chronic disease risk factor were used to investigate associations involving racial-ethnic discrimination and neighborhood disorder, controlling for potential confounders. Perceiving racial-ethnic discrimination and greater neighborhood disorder were associated with a greater tobacco smoking prevalence. Experiences of racial-ethnic discrimination were associated with greater alcohol consumption among African American and Latino women, but not White women. Similarly, African American women reporting experiences with racial-ethnic discrimination report engaging in physical activity about half as much time as women reporting no racial-ethnic discrimination. Increases in perceived neighborhood disorder were associated with increases in alcohol consumption. All associations with social environmental factors were adjusted for potential confounders and each other. Neighborhood disorder and racial-ethnic discrimination may be important, independent contributors to chronic disease risk through relationships with tobacco smoking, alcohol consumption, and physical activity.

Associations between social capital and depression: A study of adult twins.

Social capital is associated with depression independently of individual-level risk factors. We used a sample of 1586 same-sex twin pairs to test the association between seven measures of social capital and two related measures of neighborhood characteristics with depressive symptoms accounting for uncontrolled selection factors (i.e., genetics and shared environment). All measures of cognitive social capital and neighborhood characteristics were associated with less depressive symptoms in between-twin analysis. However, only measures of cognitive social capital were significantly associated with less depressive symptoms within-pairs. These results demonstrate that cognitive social capital is associated with depressive symptoms free of confounding from genetic and environmental factors shared within twins.

Socioeconomic status differences in food consumption following a laboratory-induced stressor.

We examined food consumption in response to a laboratory-induced stressor (two challenging neuropsychological tasks) among non-Hispanic White women categorized as lower or higher in socioeconomic status based on education. The two socioeconomic status groups did not differ with respect to current hunger or baseline dietary habits. Perceived stress was measured pre- and post-challenge. Snacks were offered post-challenge; food consumption was measured by weighing snack bowls pre- and post-offering. Perceived stress increased pre- to post-challenge for both groups, but this effect was stronger for women lower in socioeconomic status. In addition, women lower versus higher in socioeconomic status consumed more food overall and more high-fat sweet food in particular (large effect sizes). These findings provide evidence of socioeconomic status differences in food consumption following an acute stressor.

Low-fat dietary pattern and cardiovascular disease: results from the Women's Health Initiative randomized controlled trial.

Background: The influence of a low-fat dietary pattern on the cardiovascular health of postmenopausal women continues to be of public health interest.Objective: This report evaluates low-fat dietary pattern influences on cardiovascular disease (CVD) incidence and mortality during the intervention and postintervention phases of the Women's Health Initiative Dietary Modification Trial.Design: Participants comprised 48,835 postmenopausal women aged 50-79 y; 40% were randomly assigned to a low-fat dietary pattern intervention (target of 20% of energy from fat), and 60% were randomly assigned to a usual diet comparison group. The 8.3-y intervention period ended in March 2005, after which >80% of surviving participants consented to additional active follow-up through September 2010; all participants were followed for mortality through 2013. Breast and colorectal cancer were the primary trial outcomes, and coronary heart disease (CHD) and overall CVD were additional designated outcomes.Results: Incidence rates for CHD and total CVD did not differ between the intervention and comparison groups in either the intervention or postintervention period. However, CHD HRs comparing these groups varied strongly with baseline CVD and hypertension status. Participants without prior CVD had an intervention period CHD HR of 0.70 (95% CI: 0.56, 0.87) or 1.04 (95% CI: 0.90, 1.19) if they were normotensive or hypertensive, respectively (P-interaction = 0.003). The CHD benefit among healthy normotensive women was partially offset by an increase in ischemic stroke risk. Corresponding HRs in the postintervention period were close to null. Participants with CVD at baseline (3.4%) had CHD HRs of 1.47 (95% CI: 1.12, 1.93) and 1.61 (95% CI: 1.02, 2.55) in the intervention and postintervention periods, respectively. However, various lines of evidence suggest that results in women with CVD or hypertension at baseline are confounded by postrandomization use of cholesterol-lowering medications.Conclusions: CVD risk in postmenopausal women appears to be sensitive to a change to a low-fat dietary pattern and, among healthy women, includes both CHD benefit and stroke risk. This trial was registered at clinicaltrials.gov as NCT00000611.

Dietary biomarker evaluation in a controlled feeding study in women from the Women's Health Initiative cohort.

BACKGROUND: Controlled human feeding studies are necessary for robust nutritional biomarker development and validation. Previous feeding studies have typically evaluated single nutrients and tested relatively few diets. OBJECTIVES: The objectives were 1) to simultaneously associate dietary intake with a range of potential nutritional biomarkers in postmenopausal women by using a controlled feeding study whereby each participant was provided a diet similar to her usual diet and 2) to evaluate serum concentrations of select nutrients as potential biomarkers with the use of established urinary recovery biomarkers of energy and protein as benchmarks for evaluation. DESIGN: Postmenopausal women from the Women's Health Initiative (n = 153) were provided with a 2-wk controlled diet in which each individual's menu approximated her habitual food intake as estimated from her 4-d food record and adjusted for estimated energy requirements. Serum biomarkers, including carotenoids, tocopherols, folate, vitamin B-12, and phospholipid fatty acids, were collected at the beginning and end of the feeding period. Doubly labeled water and urinary nitrogen biomarkers were used to derive estimates of energy and protein consumption, respectively. RESULTS: Linear regression of (ln-transformed) consumed nutrients on (ln-transformed) potential biomarkers and participant characteristics led to the following regression (R2) values for serum concentration biomarkers: folate, 0.49; vitamin B-12, 0.51; α-carotene, 0.53; ß-carotene, 0.39; lutein + zeaxanthin, 0.46; lycopene, 0.32; and α-tocopherol, 0.47. R2 values for percentage of energy from polyunsaturated fatty acids and urinary recovery biomarkers of energy and protein intakes were 0.27, 0.53, and 0.43, respectively. Phospholipid saturated fatty acids and monounsaturated fatty acids and serum γ-tocopherol were weakly associated with intake (R2 < 0.25). CONCLUSIONS: Serum concentration biomarkers of several vitamins and carotenoids performed similarly to established energy and protein urinary recovery biomarkers in representing nutrient intake variation in a feeding study, and thus are likely suitable for application in this population of postmenopausal women. Further work is needed to identify objective measures of categories of fatty acid intake. This trial was registered at clinicaltrials.gov as NCT00000611.

Effects of conjugated equine estrogen on risk of fractures and BMD in postmenopausal women with hysterectomy: results from the women's health initiative randomized trial.

UNLABELLED: Further analyses from the Women's Health Initiative estrogen trial shows that CEE reduced fracture risk. The fracture reduction at the hip did not differ appreciably among risk strata. These data do not support overall benefit over risk, even in women at highest risk for fracture. INTRODUCTION: The Women's Health Initiative provided evidence that conjugated equine estrogen (CEE) can significantly reduce fracture risk in postmenopausal women. Additional analysis of the effects of CEE on BMD and fracture are presented. MATERIALS AND METHODS: Postmenopausal women 50-79 years of age with hysterectomy were randomized to CEE 0.625 mg daily (n = 5310) or placebo (n = 5429) and followed for an average 7.1 years. Fracture incidence was assessed by semiannual questionnaire and verified by adjudication of radiology reports. BMD was measured in a subset of women (N = 938) at baseline and years 1, 3, and 6. A global index was used to examine whether the balance of risks and benefits differed by baseline fracture risk. RESULTS: CEE reduced the risk of hip (hazard ratio [HR], 0.65; 95% CI, 0.45-0.94), clinical vertebral (HR, 0.64; 95% CI, 0.44-0.93), wrist/lower arm (HR, 0.58; 95% CI, 0.47-0.72), and total fracture (HR, 0.71; 95% CI, 0.64-0.80). This effect did not differ among strata according to age, oophorectomy status, past hormone use, race/ethnicity, fall frequency, physical activity, or fracture history. Total fracture reduction was less in women at the lowest predicted fracture risk in both absolute and relative terms (HR, 0.86; 95% CI, 0.68-1.08). CEE also provided modest but consistent positive effects on BMD. The HRs of the global index for CEE were relatively balanced across tertiles of summary fracture risk (lowest risk: HR, 0.81; 95% CI, 0.62-1.05; mid risk: HR, 1.09; 95% CI, 0.92-1.30; highest risk: HR, 1.04; 95% CI, 0.88-1.23; interaction, p = 0.42). CONCLUSIONS: CEE reduces the risk of fracture and increases BMD in hysterectomized postmenopausal women. Even among the women with the highest risk for fractures, when considering the effects of estrogen on other important health outcomes, a summary of the burden of monitored effects does not indicate a significant net benefit.