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BACKGROUND: Few studies have examined accelerometer-measured physical activity and incident breast cancer (BC). Thus, this study examined associations between accelerometer-measured vector magnitude counts per 15 seconds (VM/15s) and average daily minutes of light physical activity (LPA), moderate-to-vigorous PA (MVPA), and total PA (TPA) and BC risk among women in the Women’s Health Accelerometry Collaboration (WHAC). METHODS: The WHAC comprised 21,089 postmenopausal women (15,375 from the Women’s Health Study [WHS]; 5714 from the Women’s Health Initiative Objective Physical Activity and Cardiovascular Health Study [OPACH]). Women wore an ActiGraph GT3X+ on the hip for ≥4 days and were followed for 7.4 average years to identify physician-adjudicated in situ (n = 94) or invasive (n = 546) BCs. Multivariable stratified Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for tertiles of physical activity measures in association with incident BC overall and by cohort. Effect measure modification was examined by age, race/ethnicity, and body mass index (BMI). RESULTS: In covariate-adjusted models, the highest (vs. lowest) tertiles of VM/15s, TPA, LPA, and MVPA were associated with BC HRs of 0.80 (95% CI, 0.64–0.99), 0.84 (95% CI, 0.69–1.02), 0.89 (95% CI, 0.73–1.08), and 0.81 (95% CI, 0.64–1.01), respectively. Further adjustment for BMI or physical function attenuated these associations. Associations were more pronounced among OPACH than WHS women for VM/15s, MVPA, and TPA; younger than older women for MVPA; and women with BMI ≥30 than

Dietary supplements are touted for cognitive protection, but supporting evidence is mixed. COSMOS-Mind tested whether daily administration of cocoa extract (containing 500 mg/day flavanols) versus placebo and a commercial multivitamin-mineral (MVM) versus placebo improved cognition in older women and men.COSMOS-Mind, a large randomized two-by-two factorial 3-year trial, assessed cognition by telephone at baseline and annually. The primary outcome was a global cognition composite formed from mean standardized (z) scores (relative to baseline) from individual tests, including the Telephone Interview of Cognitive Status, Word List and Story Recall, Oral Trail-Making, Verbal Fluency, Number Span, and Digit Ordering. Using intention-to-treat, the primary endpoint was change in this composite with 3 years of cocoa extract use. The pre-specified secondary endpoint was change in the composite with 3 years of MVM supplementation. Treatment effects were also examined for executive function and memory composite scores, and in pre-specified subgroups at higher risk for cognitive decline.A total of 2262 participants were enrolled (mean age = 73y; 60% women; 89% non-Hispanic White), and 92% completed the baseline and at least one annual assessment. Cocoa extract had no effect on global cognition (mean z-score = 0.03, 95% CI: -0.02 to 0.08; P = .28). Daily MVM supplementation, relative to placebo, resulted in a statistically significant benefit on global cognition (mean z = 0.07, 95% CI 0.02 to 0.12; P = .007), and this effect was most pronounced in participants with a history of cardiovascular disease (no history: 0.06, 95% CI 0.01 to 0.11; history: 0.14, 95% CI -0.02 to 0.31; interaction, nominal P = .01). Multivitamin-mineral benefits were also observed for memory and executive function. The cocoa extract by MVM group interaction was not significant for any of the cognitive composites.Cocoa extract did not benefit cognition. However, COSMOS-Mind provides the first evidence from a large, long-term, pragmatic trial to support the potential efficacy of a MVM to improve cognition in older adults. Additional work is needed to confirm these findings in a more diverse cohort and to identify mechanisms to account for MVM effects.COSMOS-Mind was a large simple pragmatic randomized clinical trial in older adults conducted by mail and telephone. The trial used a two-by-two factorial design to assess treatment effects of two different interventions within a single large study. We found no cognitive benefit of daily cocoa extract administration (containing 500 mg flavanols) for 3 years. Daily multivitamin-mineral (MVM) supplementation for 3 years improved global cognition, episodic memory, and executive function in older adults. The MVM benefit appeared to be greater for adults with cardiovascular disease.

BACKGROUND The IBIS/Tyrer-Cuzick model is used clinically to guide breast cancer screening and prevention, but was developed primarily in non-Hispanic White women. Little is known about its long-term performance in a racially/ethnically diverse population. METHODS The Women's Health Initiative study enrolled postmenopausal women from 1993-1998. Women were included who were aged

Background Cardiometabolic abnormalities are a leading cause of death among women, including women with cancer. Methods This study examined the association between prediagnosis cardiovascular health and total and cause-specific mortality among 12,076 postmenopausal women who developed local- or regional-stage invasive cancer in the Women's Health Initiative (WHI). Cardiovascular risk factors included waist circumference, hypertension, high cholesterol, and type 2 diabetes. Obesity-related cancers included breast cancer, colorectal cancer, endometrial cancer, kidney cancer, pancreatic cancer, ovarian cancer, stomach cancer, liver cancer, and non-Hodgkin lymphoma. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for important predictors of survival. Results After a median follow-up of 10.0 years from the date of the cancer diagnosis, there were 3607 total deaths, with 1546 (43%) due to cancer. Most participants (62.9%) had 1 or 2 cardiometabolic risk factors, and 8.1% had 3 or 4. In adjusted models, women with 3 to 4 risk factors (vs none) had a higher risk of all-cause mortality (HR, 1.99; 95% CI, 1.73-2.30), death due to cardiovascular disease (CVD) (HR, 4.01; 95% CI, 2.88-5.57), cancer-specific mortality (HR, 1.37; 95% CI, 1.1-1.72), and other-cause mortality (HR, 2.14; 95% CI, 1.70-2.69). A higher waist circumference was associated with greater all-cause mortality (HR, 1.17; 95% CI, 1.06-1.30) and cancer-specific mortality (HR, 1.22; 95% CI, 1.04-1.42). Conclusions Among postmenopausal women diagnosed with cancer in the WHI, cardiometabolic risk factors before the cancer diagnosis were associated with greater all-cause, CVD, cancer-specific, and other-cause mortality. These results raise hypotheses regarding potential clinical intervention strategies targeting cardiometabolic abnormalities that require future prospective studies for confirmation. Lay summary This study uses information from the Women's Health Initiative (WHI) to find out whether cardiac risk factors are related to a greater risk of dying among older women with cancer. The WHI is the largest study of medical problems faced by older women in this country. The results show that women who have 3 or 4 risk factors are more likely to die of any cause, heart disease, or cancer in comparison with women with no risk factors. It is concluded that interventions to help to lower the burden of cardiac risk factors can have an important impact on survivorship among women with cancer.

Objective While a number of single nucleotide polymorphisms (SNPs) associated with Alzheimer's disease (AD) or cognitive impairment have been identified, independent replications remain the only way to validate proposed signals. We investigated SNPs in candidate genes associated with either cognitive impairment or AD pathogenesis and their relationships with probable dementia (PD) in the Women's Health Initiative Memory Study (WHIMS). Methods We analyzed 96 SNPs across five genes (APOE/TOMM40, BDNF, COMT, SORL1, and KIBRA) in 2857 women (ages ≥65) from the WHIMS randomized trials of hormone therapy using a custom Illumina GoldenGate assay; 19% of the sample were MCI (N = 165) or PD (N = 387), and the remaining 81% were free of cognitive impairment. SNP associations were evaluated for PD in non-Hispanic whites adjusting for age and HT using logistic regression under an additive genetic model. Results One SNP (rs157582), located in the TOMM40 gene nearby APOE, was associated with the PD phenotype based on a P value accounting for multiple comparisons. An additional 12 SNPs were associated with the PD phenotype at P ≤ 0.05 (APOE: rs405509, rs439401; TOMM40: rs8106922, and KIBRA: rs4320284, rs11740112, rs10040267, rs13171394, rs6555802, rs2241368, rs244904, rs6555805, and rs10475878). Results of the sensitivity analyes excluding MCI were similar, with addition of COMT rs737865 and BDNF rs1491850 (P ≤ 0.05). Conclusions Our results in older women provide supporting evidence that the APOE/TOMM40 genes confer dementia risk and extend these findings to COMT, BDNF, and KIBRA. Our findings may lead to a better understanding of the role these genes play in cognition and cognitive impairment.

The WHI found an unexpected reduced breast cancer risk in women using CEE alone. We hypothesized CEE alone induces estrogen hydroxylation along the 2-pathway rather than the competing 16-pathway, a pattern linked to reduced postmenopausal breast cancer risk. One thousand eight hundred and sixty-four women in a WHIOS case-control study of estrogen metabolism and ovarian and endometrial cancer were studied of whom 609 were current E + P users (351 used CEE + MPA), while 272 used E alone (162 used CEE). Fifteen EM were measured, and analyses were conducted for each metabolite, hydroxylation pathway (2-, 4-, or 16-pathway) and ratios of pathway concentrations using inverse probability weighted linear regression. Compared to E + P users, all EM were higher in E alone users (significant for unconjugated estrone, total/conjugated estradiol, total/unconjugated 2-methoxyestrone, 4-methoxyestrone and unconjugated estriol). The relative concentrations of 2- and 4-pathway EM did not differ between the MHT users (2-pathway EM comprised 15% and 4-pathway EM

BACKGROUND AND AIM Gallstone disease has been related to a higher prevalence and incidence of chronic conditions, such as dyslipidemia, obesity, and cardiovascular disease (CVD). However, limited data are available regarding whether gallstone disease is related to mortality. METHODS We examined the relationship of a history of gallstone disease and risk of death, using Cox proportional hazards regression analysis, among 86 030 women from the Nurses' Health Study and 43 949 men from the Health Professionals Follow-up Study. RESULTS During the up-to 32 years of follow-up, 34 011 all-cause deaths were confirmed, of which 8138 were CVD deaths and 12 173 were cancer deaths. For the participants with a history of gallstone disease compared with those without, the hazard ratio of total mortality was 1.16 (95% confidence interval 1.13, 1.20), of CVD mortality 1.11 (1.05, 1.17), of cancer mortality 1.15 (1.09, 1.20), and of other mortality 1.19 (1.14, 1.25) from a pooled-analysis of women and men (all P

Statins have been shown to induce a phosphoprotein signature that modifies MYC (myelocytomatosis viral oncogene) activation and to have anti‐inflammatory activity that may impact the risk of Non‐Hodgkin's lymphoma (NHL). We analyzed the relationship between statins and risk of NHL using data from the Women's Health Initiative (WHI). The study population included 161,563 postmenopausal women ages 50–79 years from which 712 cases of NHL were diagnosed after 10.8 years of follow‐up. Information on statin use and other risk factors was collected by self‐ and interviewer‐administered questionnaires. Multivariable‐adjusted HR and 95% CI evaluating the relationship between statin use at baseline, as well as in a time‐dependent manner and risk of NHL, were computed from Cox proportional hazards analyses. A separate analysis was performed for individual NHL subtypes: diffuse large B‐Cell lymphoma (DLBCL) (n = 228), follicular lymphoma (n = 169), and small lymphocytic lymphoma (n = 74). All statistical tests were two‐sided. There was no significant association between use of statins at baseline and risk of NHL (HR 0.85, 95% C.I. 0.67–1.08). However, in the multivariable‐adjusted time‐dependent models, statin use was associated with a borderline lower risk of NHL (HR 0.81, 95% C.I. 0.66–1.00). Considering subtypes of NHL, statin use was associated with a lower risk of DLBCL (HR 0.62, 95% C.I. 0.42–0.91). This effect was driven by lipophilic statins (HR 0.62, 95% C.I. 0.40–0.96). In the WHI, statins were associated with a lower overall risk of DLBCL, particularly attributable to lipophilic statins. These results may have impact on primary or secondary prevention of NHL, particularly DLBCL.

Epidemiologic studies have demonstrated an association of elevated plasma homocysteine levels with greater bone resorption and fracture risk. Vitamins B12 , B6 , and folic acid are cofactors in homocysteine metabolism, and supplementation with B vitamins is effective in lowering homocysteine levels in humans. However, randomized trials of supplemental B vitamins for reduction of fracture risk have been limited. Therefore, we performed an ancillary study to the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a large randomized trial of women with preexisting cardiovascular disease or three or more coronary risk factors, to test whether a daily B vitamin intervention including folic acid (2.5 mg/day), vitamin B6 (50 mg/day), and vitamin B12 (1 mg/day) reduces nonspine fracture risk over 7.3 years of treatment and follow-up. Among 4810 women, we confirmed 349 nonspine fracture cases by centralized review of medical records. In a substudy of 300 women (150 in treatment group and 150 controls) with paired plasma samples at randomization and follow-up (7.3 years later), we measured two bone turnover markers, including C-terminal cross-linking telopeptide of type I collagen (CTX) and intact type I procollagen N-propeptide (P1NP). In Cox proportional hazards models based on intention-to-treat, we found no significant effects of B vitamin supplementation on nonspine fracture risk (relative hazard = 1.08; 95% confidence interval, 0.88 to 1.34). In a nested case-cohort analysis, there were no significant effects of B vitamins on fracture risk among women with elevated plasma homocysteine levels, or low levels of vitamins B12 or B6 , or folate at baseline. Furthermore, treatment with B vitamins had no effect on change in markers of bone turnover. We found no evidence that daily supplementation with B vitamins reduces fracture risk or rates of bone metabolism in middle-aged and older women at high risk of cardiovascular disease. © 2017 American Society for Bone and Mineral Research.

Background Sex hormones may play important roles in sex-specific biological aging. We specifically examined the associations between circulating concentrations of sex hormones and leukocyte telomere length (TL). Methods We conducted a cross-sectional study of 1124 black, 444 Hispanic, and 289 Asian/Pacific Islander women in the Women's Health Initiative Observational Cohort. Concentrations of estradiol and testosterone were measured using electrochemiluminescence immunoassays. TL was measured using quantitative PCR. Results Women included in the study were 50 to 79 years of age. Levels of estradiol were not significantly associated with TL in this sample of women. The associations between total and free testosterone and TL differed by race/ethnicity (P for interaction = 0.03 for total testosterone and 0.05 for free testosterone). Total and free testosterone concentrations were not associated with TL in black and Hispanic women, whereas in Asian/Pacific Islanders, their concentrations were inversely associated with TL (P-trend = 0.003 for both). These associations appeared robust in multiple subgroup analysis and multivariable models adjusted for potential confounding factors. In Asian/Pacific Islanders, doubling of serum free testosterone concentration was associated with 202 bp shorter TL (95% CI, 51 to 353 bp), and doubling of total testosterone concentration was associated with 203 bp shorter TL (95% CI, 50 to 355 bp). Conclusions Serum concentration of estradiol was not associated with leukocyte TL in this large sample of postmenopausal women. Total and free testosterone levels were inversely associated with TL in Asian/Pacific Islander women but not in black and Hispanic women, although future studies to replicate our observations are warranted particularly to address potential ethnicity-specific relations. The significant findings of the study This study elucidates the potential roles of sex hormones in biological aging, and identified that total and free testosterone levels were inversely associated with telomere length in Asian/Pacific Islander women but not in black and Hispanic women. The study adds The findings of this study suggest that Asian/Pacific Islander women may be susceptible to the potential detrimental effects of high testosterone level on biologic aging.

Fatty acids (FAs) are essential components of cell membranes and play an integral role in membrane fluidity. The lipophilic index [LI, defined as the sum of the products between FA levels and melting points (°C), divided by the total amount of FA: $${\text{LI}} = \frac{{\mathop \sum \nolimits_{k} [{\text{fatty acid}} \times {\text{melting point}}]}}{{\mathop \sum \nolimits_{k} {\text{fatty acid}} }}$$ ] is thought to reflect membrane and lipoprotein fluidity and may be associated with the risk of coronary heart disease (CHD). Therefore, we examined the associations of dietary and plasma phospholipid (PL) LI with CHD risk among postmenopausal women. We determined dietary LI for the cohort with completed baseline food frequency questionnaires and free of prevalent cardiovascular diseases in the Women’s Health Initiative (WHI) observational study (N = 85,563). We additionally determined plasma PL LI in a matched case-control study (N = 2428) nested within the WHI observational cohort study. Cox proportional hazard regression and multivariable conditional logistic regression were used to calculate HRs/ORs for CHD risk between quartiles of LI after adjusting for potential sources of confounding and selection bias. Higher dietary LI in the cohort study and plasma PL LI in the case-control study were significantly associated with increased risk of CHD: HR = 1.18 (95% CI 1.07–1.31, P for trend

Introduction The Mediterranean and Dietary Approaches to Stop Hypertension diets have been associated with lower dementia risk. We evaluated dietary inflammatory potential in relation to mild cognitive impairment (MCI)/dementia risk. Methods Baseline food frequency questionnaires from n = 7085 women (aged 65–79 years) were used to calculate Dietary Inflammatory Index (DII) scores that were categorized into four groups. Cognitive function was evaluated annually, and MCI and all-cause dementia cases were adjudicated centrally. Mixed effect models evaluated cognitive decline on over time; Cox models evaluated the risk of MCI or dementia across DII groups. Results Over an average of 9.7 years, there were 1081 incident cases of cognitive impairment. Higher DII scores were associated with greater cognitive decline and earlier onset of cognitive impairment. Adjusted hazard ratios (HRs) comparing lower (anti-inflammatory; group 1 referent) DII scores to the higher scores were group 2-HR: 1.01 (0.86–1.20); group 3-HR: 0.99 (0.82–1.18); and group 4-HR: 1.27 (1.06–1.52). Conclusions Diets with the highest pro-inflammatory potential were associated with higher risk of MCI or dementia.

Aim To examine the association of cutaneous nevi with Type 2 diabetes risk. Methods We prospectivly examined the associations between nevus count and risk of Type 2 diabetes among 26 240 men (1988–2010) from the Health Professionals Follow-up Study and 67 050 women (1986–2010) from the Nurses’ Health Study. Information on the numbers of cutaneous nevi on arms at baseline and incident cases of Type 2 diabetes was collected using validated questionnaires. Results During 1 879 287 person-years of follow-up, we documented 9040 incident cases of Type 2 diabetes. After adjustment for age, BMI and other diabetes risk factors, greater number of nevi was associated with higher risk of Type 2 diabetes. Multivariable-adjusted hazard ratios for

Objective To examine whether changes in diet quality predict changes in central adiposity among postmenopausal women. Methods At baseline and 3-year follow-up, Women's Health Initiative Observational Study participants completed food frequency questionnaires, and waist circumference was measured (WC, n = 67,175). In a subset, trunk fat was measured via dual-energy X-ray absorptiometry (DXA, n = 4,254). Using multivariable linear regression, 3-year changes in dietary patterns (Healthy Eating Index-2010, Alternate Healthy Eating Index-2010, Alternate Mediterranean Diet, and Dietary Approaches to Stop Hypertension) were examined as predictors of concurrent changes in WC and, secondarily, DXA. Results Mean (SD) age and 3-year changes in weight and WC were 63 (7) years, 0.52 (4.26) kg, and 0.94 (6.65) cm. A 10% increase in any dietary pattern score, representing improved diet quality, was associated with 0.07 to 0.43 cm smaller increase in WC over 3 years (all P < 0.05). After adjusting for weight change, associations attenuated to 0.02 to 0.10 cm but remained statistically significant for all patterns except Alternate Mediterranean Diet. Results were similar for DXA trunk fat. Conclusions Three-year improvements in diet quality are modestly protective against gain in WC and partially explained by lesser weight gain. Achieving and maintaining a healthful diet after menopause may protect against gains in central adiposity.

Findings from studies of metformin use with risk of cancer incidence and outcome provide mixed results; with few studies examined associations by recency of diabetes diagnosis or duration of medication use. Thus, in the Women's Health Initiative, we examined these associations and further explored whether associations differ by recency of diabetes and duration of metformin use. Cox regression models were used to estimate hazard ratios (HR) and their 95% confidence intervals. Diabetes was associated with higher risk of total invasive cancer (HR, 1.13; p < 0.001) and of several site-specific cancers (HR, 1.2-1.4, and up to over twofold). Diabetes was also associated with higher risk of death from cancer (HR, 1.46; p < 0.001). There was no overall difference in cancer incidence by diabetes therapy (p = 0.66). However, there was a lower risk of death from cancer for metformin users, compared to users of other medications, relative to women without diabetes, overall (HRs, 1.08 vs. 1.45; p = 0.007) and for breast cancer (HRs, 0.50 vs. 1.29; p = 0.05). Results also suggested that lower cancer risk associated with metformin may be evident only for a longer duration of use in certain cancer sites or subgroup populations. We provide further evidence that postmenopausal women with diabetes are at higher risk of invasive cancer and cancer death. Metformin users, particularly long-term users, may be at lower risk of developing certain cancers and dying from cancer, compared to users of other anti-diabetes medications. Future studies are needed to determine the long-term effect of metformin in cancer risk and survival from cancer.

Introduction Consistent evidence linking habitual sleep duration with risks of mild cognitive impairment (MCI) and dementia is lacking. Methods We conducted a prospective study on 7444 community-dwelling women (aged 65–80 y) with self-reported sleep duration, within the Women's Health Initiative Memory Study in 1995–2008. Incident MCI/dementia cases were ascertained by validated protocols. Cox models were used to adjust for multiple sociodemographic and lifestyle factors, depression, cardiovascular disease (CVD), and other clinical characteristics. Results We found a statistically significant ( P = .03) V-shaped association with a higher MCI/dementia risk in women with either short (≤6 hours/night) or long (≥8 hours/night) sleep duration (vs. 7 hours/night). The multicovariate-adjusted hazard for MCI/dementia was increased by 36% in short sleepers irrespective of CVD, and by 35% in long sleepers without CVD. A similar V-shaped association was found with cognitive decline. Discussion In older women, habitual sleep duration predicts the future risk for cognitive impairments including dementia, independent of vascular risk factors.

OBJECTIVE To test the hypothesis that greater chocolate-candy intake is associated with more weight gain in postmenopausal women.

The use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced risks of cancers at several sites in some studies; however, we recently reported no association between their use and total cancer risk in women in a prospective study. Here we examine the association between NSAIDs and total and site-specific cancer incidence in the large, prospective Women's Health Initiative (WHI). Women (129,013) were recruited to participate in the WHI at 40 US clinical centers from 1993 to 1998 and followed prospectively. After 9.7 years of follow-up, 12,998 incident, first primary, invasive cancers were diagnosed. NSAID use was systematically collected at study visits. We used Cox proportional hazards regression models to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations between NSAIDs use and total and site-specific cancer risk. Relative to non-use, consistent use (i.e., use at baseline and year 3 of follow-up) of any NSAID was not associated with total cancer risk (HR 1.00, 95% CI: 0.94-1.06). Results for individual NSAIDs were similar to the aggregate measure. In site-specific analyses, NSAIDs were associated with reduced risks of colorectal cancer, ovarian cancer, and melanoma. Our study confirms a chemopreventive benefit for colorectal cancer in women and gives preliminary evidence for a reduction of the risk of some rarer cancers. NSAIDs' benefit on cancer risk was therefore limited to specific sites and not evident when total cancer risk was examined. This information may be of importance when NSAIDs are considered as chemopreventive agents.

Objective We sought to determine the relationship between the omega-3 fatty acid content of red blood cell membranes (RBC), in particular docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and baseline and new-onset depressive symptoms in postmenopausal women. We secondarily sought to characterize the association between dietary omega-3 fatty acid intake and depressive symptomatology.

Objective To evaluate the association between self-reported daily sitting time and the incidence of type 2 diabetes in a cohort of postmenopausal women. Methods Women (N=88,829) without diagnosed diabetes reported the number of hours spent sitting over a typical day. Incident cases of diabetes were identified annually by self-reported initiation of using oral medications or insulin for diabetes > 14.4 years follow-up. Results Each hour of sitting time was positively associated with increased risk of diabetes [risk ratio (RR): 1.05; 95% confidence interval (CI): 1.02–1.08]. However, sitting time was only positively associated with incident diabetes in obese women. Obese women reporting sitting 8–11 (RR: 1.08; 95% CI 1.0–1.1), 12–15 (OR: 1.13; 95% CI 1.0–1.2), and ≥16 hours (OR: 1.25; 95% CI 1.0–1.5) hours per day had an increased risk of diabetes compared to women sitting ≤7 hours per day. These associations were adjusted for demographics, health conditions, behaviors (smoking, diet, and alcohol intake), and family history of diabetes. Time performing moderate to vigorous intensity physical activity did not modify these associations. Conclusions Time spent sitting was independently associated with increased risk of diabetes diagnosis among obese women—a population already at high risk of the disease.

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.

Objective: Several genome–wide association studies (GWAS) have demonstrated that common genetic variants contribute to obesity. However, studies of this complex trait have focused on ancestrally European populations, despite the high prevalence of obesity in some minority groups. Design and Methods: As part of the “Population Architecture using Genomics and Epidemiology (PAGE)” Consortium, we investigated the association between 13 GWAS-identified single-nucleotide polymorphisms (SNPs) and BMI and obesity in 69,775 subjects, including 6,149 American Indians, 15,415 African-Americans, 2,438 East Asians, 7,346 Hispanics, 604 Pacific Islanders, and 37,823 European Americans. For the BMI-increasing allele of each SNP, we calculated β coefficients using linear regression (for BMI) and risk estimates using logistic regression (for obesity defined as BMI ≥ 30) followed by fixed-effects meta-analysis to combine results across PAGE sites. Analyses stratified by racial/ethnic group assumed an additive genetic model and were adjusted for age, sex, and current smoking. We defined “replicating SNPs” (in European Americans) and “generalizing SNPs” (in other racial/ethnic groups) as those associated with an allele frequency-specific increase in BMI. Results: By this definition, we replicated 9/13 SNP associations (5 out of 8 loci) in European Americans. We also generalized 8/13 SNP associations (5/8 loci) in East Asians, 7/13 (5/8 loci) in African Americans, 6/13 (4/8 loci) in Hispanics, 5/8 in Pacific Islanders (5/8 loci), and 5/9 (4/8 loci) in American Indians. Conclusion: Linkage disequilibrium patterns suggest that tagSNPs selected for European Americans may not adequately tag causal variants in other ancestry groups. Accordingly, fine-mapping in large samples is needed to comprehensively explore these loci in diverse populations.

Objectives: To examine the effects of vitamin D and calcium on cognitive outcomes in elderly women. Design: Post hoc analysis of a randomized double-blind placebo-controlled trial. Setting: Forty Women's Health Initiative (WHI) clinical centers across the United States. Participants: Four thousand one hundred forty-three women aged 65 and older without probable dementia at baseline who participated in the WHI Calcium and Vitamin D Trial and the WHI Memory Study. Intervention: Two thousand thirty-four women were randomized to receive 1,000 mg of calcium carbonate combined with 400 IU of vitamin D3 (treatment) and 2,109 to placebo. Measurements: Primary: classifications of probable dementia or mild cognitive impairment (MCI) based on a four-phase protocol that included central adjudication. Secondary: global cognitive function and individual cognitive subtests. Results: Mean age of participants was 71. During a mean follow-up of 7.8 years, 39 participants in the treatment group and 37 in the placebo group developed incident dementia (hazard ratio (HR) = 1.11, 95% confidence interval (CI) = 0.71�1.74, P = .64). Likewise, 98 treatment participants and 108 placebo participants developed incident MCI (HR = 0.95, 95% CI = 0.72�1.25, P = .72). There were no significant differences in incident dementia or MCI or in global or domain-specific cognitive function between groups. Conclusion: There was no association between treatment assignment and incident cognitive impairment. Further studies are needed to investigate the effects of vitamin D and calcium separately, on men, in other age and ethnic groups, and with other doses.

A study was undertaken to relate dietary fat types to cognitive change in healthy community-based elders.Among 6,183 older participants in the Women's Health Study, we related intake of major fatty acids (saturated [SFA], monounsaturated [MUFA], total polyunsaturated [PUFA], trans-unsaturated) to late-life cognitive trajectory. Serial cognitive testing, conducted over 4 years, began 5 years after dietary assessment. Primary outcomes were global cognition (averaging tests of general cognition, verbal memory, and semantic fluency) and verbal memory (averaging tests of recall). We used analyses of response profiles and logistic regression to estimate multivariate-adjusted differences in cognitive trajectory and risk of worst cognitive change (worst 10%) by fat intake.Higher SFA intake was associated with worse global cognitive (p for linear trend = 0.008) and verbal memory (p for linear trend = 0.01) trajectories. There was a higher risk of worst cognitive change, comparing highest versus lowest SFA quintiles; the multivariate-adjusted odds ratio (OR) with 95% confidence interval (CI) was 1.64 (1.04-2.58) for global cognition and 1.65 (1.04-2.61) for verbal memory. By contrast, higher MUFA intake was related to better global cognitive (p for linear trend0.001) and verbal memory (p for linear trend = 0.009) trajectories, and lower OR (95% CI) of worst cognitive change in global cognition (0.52 [0.31-0.88]) and verbal memory (0.56 [0.34-0.94]). Total fat, PUFA, and trans-fat intakes were not associated with cognitive trajectory.Higher SFA intake was associated with worse global cognitive and verbal memory trajectories, whereas higher MUFA intake was related to better trajectories. Thus, different consumption levels of the major specific fat types, rather than total fat intake itself, appeared to influence cognitive aging.

Using data (n=60,775 women) from the Women’s Health Initiative Clinical Trial (WHI CT)— a national study of postmenopausal women aged 50 to 79 years — we analyzed cross-sectional associations between the availability of different types of food outlets in the 1.5 miles surrounding a woman’s residence, census tract neighborhood socioeconomic status (NSES), body mass index (BMI) and blood pressure (BP). We simultaneously modeled NSES and food outlets using linear and logistic regression models, adjusting for multiple socio-demographic factors, population density and random effects at the tract and metropolitan statistical area (MSA) level. We found significant associations between NSES, availability of food outlets and individual-level measurements of BMI and BP. As grocery store/supermarket availability increased from the 10th to the 90th percentile of its distribution, controlling for confounders, BMI was lower by 0.30 kg/m2. Conversely, as fast-food outlet availability increased from the 10th to the 90th percentile, BMI was higher by 0.28 kg/m2. When NSES increased from the 10th to the 90th percentile of its distribution, BMI was lower by 1.26 kg/m2. As NSES increased from the 10th to the 90th percentile, systolic and diastolic BP were lower by 1.11 mm and 0.40 mm Hg, respectively. As grocery store/supermarket outlet availability increased from the 10th and 90th percentiles diastolic BP was lower by 0.31 mm Hg. In this national sample of post-menopausal women, we found important independent associations between the food and socioeconomic environments and BMI and BP. These findings suggest that changes in the neighborhood environment may contribute to efforts to control obesity and hypertension.