JoAnn E Manson

University of Arkansas at Little Rock, Little Rock, Arkansas, United States

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Publications (918)10807.81 Total impact

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    ABSTRACT: Aims: High body mass index (BMI) is a risk factor for atrial fibrillation (AF). The aim of this study was to determine whether lean body mass (LBM) predicts AF. Methods and results: The Women's Health Initiative is a study of post-menopausal women aged 50-79 enrolled at 40 US centres from 1994 to 1998. A subset of 11 393 participants at three centres underwent dual-energy X-ray absorptiometry. Baseline demographics and clinical histories were recorded. Incident AF was identified using hospitalization records and diagnostic codes from Medicare claims. A multivariable Cox hazard regression model adjusted for demographic and clinical risk factors was used to evaluate associations between components of body composition and AF risk. After exclusion for prevalent AF or incomplete data, 8832 participants with an average age of 63.3 years remained for analysis. Over the 11.6 years of average follow-up time, 1035 women developed incident AF. After covariate adjustment, all measures of LBM were independently associated with higher rates of AF: total LBM [hazard ratio (HR) 1.24 per 5 kg increase, 95% confidence intervals (CI) 1.14-1.34], central LBM (HR 1.51 per 5 kg increase, 95% CI 1.31-1.74), and peripheral LBM (HR 1.39 per 5 kg increase, 95% CI 1.19-1.63). The association between total LBM and AF remained significant after adjustment for total fat mass (HR 1.22 per 5 kg increase, 95% CI 1.13-1.31). Conclusion: Greater LBM is a strong independent risk factor for AF. After adjusting for obesity-related risk factors, the risk of AF conferred by higher BMI is primarily driven by the association between LBM and AF.
    European Heart Journal 09/2015; DOI:10.1093/eurheartj/ehv423 · 15.20 Impact Factor
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    ABSTRACT: Context: Wrist fractures are common among postmenopausal women. Associations of bone mineral density (BMD) and 10-year predicted risk of major osteoporotic fracture (MOF) with wrist fractures are poorly characterized. Objective: To examine associations between the Fracture Risk Assessment Tool (FRAX)-predicted risk of MOF, BMD, BMD change, and wrist fracture. Design: Prospective observational study; mean follow-up 8.5 years. Setting: Forty U.S. centers. Participants: 11,392 participants of the Women's Health Initiative BMD Cohort aged 50-79 years at baseline. Interventions: None. Main outcome: Incident wrist fracture Results: A FRAX-predicted MOF risk ≥ 9.3% identified 17% of the women aged < 65 years who subsequently experienced wrist fracture. Each one standard deviation lower BMD was associated with higher wrist fracture risk, with adjusted hazard ratio (aHR) (95% confidence interval [CI]) of 1.66 (1.42-1.93) for femoral neck (FN) BMD and 1.45 (1.28-1.64) for lumbar spine (LS) BMD. Compared with FN BMD T-score ≥-1.0, wrist fracture aHR (95% CI) were: 1.51 (1.06-2.16) for T-score between -1.01 and -1.49; 1.93 (1.36-2.72) for T-score between -1.50 and -1.99; 2.52 (1.77-3.60) for T-score between -2.00 and -2.49; and 2.65 (1.78-3.95) for T-score ≤-2.5. Decrease in FN BMD between baseline and year 3 was associated with increased risk of subsequent wrist fracture; however, change in LS BMD was not. Conclusions: Lumbar spine and femoral neck BMD were associated with incident wrist fracture, but the FRAX threshold recommended to identify screening candidates did not identify the majority of women who subsequently experienced wrist fracture. Improved understanding of determinants of wrist fractures is warranted.
    The Journal of Clinical Endocrinology and Metabolism 09/2015; DOI:10.1210/jc.2015-2568 · 6.21 Impact Factor
  • Andrew M Kaunitz · JoAnn E Manson
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    ABSTRACT: Most menopausal women experience vasomotor symptoms with bothersome symptoms often lasting longer than one decade. Hormone therapy (HT) represents the most effective treatment for these symptoms with oral and transdermal estrogen formulations having comparable efficacy. Findings from the Women's Health Initiative and other recent randomized clinical trials have helped to clarify the benefits and risks of combination estrogen-progestin and estrogen-alone therapy. Absolute risks observed with HT tended to be small, especially in younger women. Neither regimen increased all-cause mortality rates. Given the lower rates of adverse events on HT among women close to menopause onset and at lower baseline risk of cardiovascular disease, risk stratification and personalized risk assessment appear to represent a sound strategy for optimizing the benefit-risk profile and safety of HT. Systemic HT should not be arbitrarily stopped at age 65 years; instead treatment duration should be individualized based on patients' risk profiles and personal preferences. Genitourinary syndrome of menopause represents a common condition that adversely affects the quality of life of many menopausal women. Without treatment, symptoms worsen over time. Low-dose vaginal estrogen represents highly effective treatment for this condition. Because custom-compounded hormones have not been tested for efficacy or safety, U.S. Food and Drug Administration (FDA)-approved HT is preferred. A low-dose formulation of paroxetine mesylate currently represents the only nonhormonal medication FDA-approved to treat vasomotor symptoms. Gynecologists and other clinicians who remain abreast of data addressing the benefit-risk profile of hormonal and nonhormonal treatments can help menopausal women make sound choices regarding management of menopausal symptoms.
    Obstetrics and Gynecology 09/2015; DOI:10.1097/AOG.0000000000001058 · 5.18 Impact Factor
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    ABSTRACT: Objective: We developed and validated a hybrid risk classifier combining serum markers and epidemiologic risk factors to identify post-menopausal women at elevated risk for invasive fallopian tube, primary peritoneal, and ovarian epithelial carcinoma. Methods: To select epidemiologic risk factors for use in the classifier, Cox proportional hazards analyses were conducted using 74,786 Women's Health Initiative (WHI) Observational Study (OS) participants. To construct a combination classifier, 210 WHI OS cases and 536 matched controls with serum marker measurements were analyzed; validation employed 143 cases and 725 matched controls from the WHI Clinical Trial (CT) with similar data. Results: Analyses identified a combination risk classifier composed of two elevated-risk groups: 1) women with CA125 or HE4 exceeding a 98% specificity threshold; and 2) women with intact fallopian tubes, prior use of menopausal hormone therapy for at least two years, and either a first degree relative with breast or ovarian cancer or a personal history of breast cancer. In the WHI OS population, it classified 13% of women as elevated risk, identifying 30% of ovarian cancers diagnosed up to 7.8years post-enrollment (Hazard Ratio [HR]=2.6, p<0.001). In the WHI CT validation population, it classified 8% of women as elevated risk, identifying 31% of cancers diagnosed within 7years of enrollment (HR=4.6, p<0.001). Conclusion: CA125 and HE4 contributed significantly to a risk prediction classifier combining serum markers with epidemiologic risk factors. The hybrid risk classifier may be useful to identify post-menopausal women who would benefit from timely surgical intervention to prevent epithelial ovarian cancer.
    Gynecologic Oncology 09/2015; DOI:10.1016/j.ygyno.2015.08.024 · 3.77 Impact Factor
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    ABSTRACT: Adipokines and inflammation may provide a mechanistic link between obesity and postmenopausal breast cancer, yet epidemiologic data on their associations with breast cancer risk are limited. In a case-cohort analysis nested within the Women's Health Initiative Observational Study, a prospective cohort of postmenopausal women, baseline plasma samples from 875 incident breast cancer case patients and 839 subcohort participants were tested for levels of seven adipokines, namely leptin, adiponectin, resistin, interleukin-6, tumor necrosis factor-α, hepatocyte growth factor, and plasminogen activator inhibitor-1, and for C-reactive protein (CRP), an inflammatory marker. Data were analyzed by multivariable Cox modeling that included established breast cancer risk factors and previously measured estradiol and insulin levels. All statistical tests were two-sided. The association between plasma CRP levels and breast cancer risk was dependent on hormone therapy (HT) use at baseline (P interaction = .003). In a model that controlled for multiple breast cancer risk factors including body mass index (BMI), estradiol, and insulin, CRP level was positively associated with breast cancer risk among HT nonusers (hazard ratio for high vs low CRP levels = 1.67, 95% confidence interval = 1.04 to 2.68, P trend = .029). None of the other adipokines were statistically significantly associated with breast cancer risk. Following inclusion of CRP, insulin, and estradiol in a multivariable model, the association of BMI with breast cancer was attenuated by 115%. These data indicate that CRP is a risk factor for postmenopausal breast cancer among HT nonusers. Inflammatory mediators, together with insulin and estrogen, may play a role in the obesity-breast cancer relation. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:
    Journal of the National Cancer Institute 09/2015; 107(9). DOI:10.1093/jnci/djv169 · 12.58 Impact Factor
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    ABSTRACT: Living near major roadways has been associated with increased risk of cardiovascular morbidity and mortality, presumably from exposure to elevated levels of traffic-related air and/or noise pollution. This association may potentially be mediated through increased risk of incident hypertension, but results from prior studies are equivocal. Using Cox proportional hazards models we examined residential proximity to major roadways and incident hypertension among 38,360 participants of the Women's Health Initiative (WHI) Clinical Trial cohorts free of hypertension at enrollment and followed for a median of 7.9 years. Adjusting for participant demographics and lifestyle, trial participation, and markers of individual and neighborhood socioeconomic status, the hazard ratios for incident hypertension were 1.13 (95% CI: 1.00, 1.28), 1.03 (0.95, 1.11), 1.05 (0.99, 1.11), and 1.05 (1.00, 1.10) for participants living ≤50, >50-200, >200-400, and >400-1000m vs >1000m from the nearest major roadway, respectively (ptrend=0.013). This association varied substantially by WHI study region with hazard ratios for women living ≤50m from a major roadway of 1.61 (1.18, 2.20) in the West, 1.51 (1.22, 1.87) in the Northeast, 0.89 (0.70, 1.14) in the South, and 0.94 (0.75, 1.19) in the Midwest. In this large, national cohort of post-menopausal women, residential proximity to major roadways was associated with incident hypertension in selected regions of the U.S. If causal, these results suggest residential proximity to major roadways, as a marker for air, noise and other traffic-related pollution, may be a risk factor for hypertension. Copyright © 2015 Elsevier Inc. All rights reserved.
    Environmental Research 08/2015; 142:ER15803. DOI:10.1016/j.envres.2015.08.002 · 4.37 Impact Factor
  • JoAnn E Manson · Shari S Bassuk
    JAMA The Journal of the American Medical Association 08/2015; 314(6):627-628. DOI:10.1001/jama.2015.7558 · 35.29 Impact Factor
  • JoAnn E Manson
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    ABSTRACT: JoAnn E Manson is Professor of Medicine and the Michael and Lee Bell Professor of Women's Health at Harvard Medical School. She is also Chief of the Division of Preventive Medicine at Brigham and Women's Hospital. She is an endocrinologist, epidemiologist and Principal Investigator of several research studies, including the Women's Health Initiative Clinical Center, Boston site; the VITAL; the cardiovascular disease component of the Nurses' Health Study and the Boston site of the KEEPS trial. Her primary research interests include the role of endogenous and exogenous hormones as determinants of cardiovascular disease, diabetes and other chronic diseases, lifestyle and nutritional factors in prevention of these diseases, and biochemical and genetic factors in risk prediction. She has received numerous honors, including the Woman in Science Award from the American Medical Women's Association, the American Heart Association's Population Research Prize, the American Heart Association's Distinguished Scientist Award, election to the Institute of Medicine of the National Academies and the Bernadine Healy Award for Visionary Leadership in Women's Health. She is a past President of the North American Menopause Society. She has published more than 800 articles and is the author or editor of several books.
    Women s Health 08/2015; 11(4):1-4. DOI:10.2217/WHE.15.24
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    ABSTRACT: To describe the effects of six interventions for menopausal vasomotor symptoms relative to control in a pooled analysis, facilitating translation of the results for clinicians and symptomatic women. The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network tested these interventions in three randomized clinical trials. An analysis of pooled individual-level data from three randomized clinical trials is presented. Participants were 899 perimenopausal and postmenopausal women with at least 14 bothersome vasomotor symptoms per week. Interventions included 10-20 mg escitalopram per day, nonaerobic yoga, aerobic exercise, 1.8 g per day omega-3 fatty acid supplementation, 0.5 mg low-dose oral 17-beta-estradiol (E2) per day, and 75 mg low-dose venlafaxine XR per day. The main outcome measures were changes from baseline in mean daily vasomotor symptom frequency and bother during 8-12 weeks of treatment. Linear regression models estimated differences in outcomes between each intervention and corresponding control group adjusted for baseline characteristics. Models included trial-specific intercepts, effects of the baseline outcome measure, and time. The 8-week reduction in vasomotor symptom frequency from baseline relative to placebo was similar for escitalopram at -1.4 per day (95% confidence interval [CI] -2.7 to -0.2), low-dose E2 at -2.4 (95% CI -3.4 to -1.3), and venlafaxine at -1.8 (95% CI -2.8 to -0.8); vasomotor symptom bother reduction was minimal and did not vary across these three pharmacologic interventions (mean -0.2 to -0.3 relative to placebo). No effects on vasomotor symptom frequency or bother were seen with aerobic exercise, yoga, or omega-3 supplements. These analyses suggest that escitalopram, low-dose E2, and venlafaxine provide comparable, modest reductions in vasomotor symptom frequency and bother among women with moderate hot flushes.,, NCT00894543 (MsFLASH 01), NCT01178892 (MsFLASH 02), and NCT01418209 (MsFLASH 03).
    Obstetrics and Gynecology 08/2015; 126(2):413-422. DOI:10.1097/AOG.0000000000000927 · 5.18 Impact Factor
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    ABSTRACT: Dissatisfaction with one's body image is widespread and can have serious health consequences; however, research about its prevalence and correlates in older women is limited. We analyzed data from 75,256 women participating in the Women's Health Initiative Observational Study, a longitudinal study of post-menopausal women's health. Measures used in the study were collected at baseline and/or the third-year of follow-up between 1993 and 2002. The majority of participants (83%) in this study were dissatisfied with their bodies because they perceived themselves as heavier than their ideal. Overall, the multiple and significant correlates of body image dissatisfaction explained 36.2% of the variance in the body image dissatisfaction score, with body mass index (BMI) and change in BMI being the two most important contributors to explaining the variance. The results of this study suggest future research should focus on the utility of interventions to reduce dissatisfaction with body image in post-menopausal women that target either maintenance of a lower BMI through diet and exercise, and/or body acceptance. Further, future research should aim to identify factors in addition to body size that drive body image dissatisfaction.
    Women & Health 07/2015; DOI:10.1080/03630242.2015.1074636 · 1.05 Impact Factor
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    ABSTRACT: b>Context: The independent or interactive effects of vitamin D and calcium on adiposity remain inconclusive. Objective: The objective of this systematic review and meta-analysis was to assess whether vitamin D and calcium supplements cause changes in adiposity. Data Sources: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials databases were searched for literature published from 1966 to March 2014. Study Selection: A systematic search was conducted for randomized clinical trials with ≥50 participants aged ≥18 years at baseline who had received at least 12 weeks of treatment. Among the inclusion criteria were supplementation with vitamin D with or without calcium and measurement of adiposity (weight, body mass index [BMI], and/or fat mass). Data Extraction: The primary endpoints assessed were changes in weight, BMI, or fat mass. Data Synthesis: Of 953 trials identified, 26 randomized clinical trials (n = 12, vitamin D alone; n = 10, vitamin D plus calcium versus calcium control; n = 4, vitamin D plus calcium versus placebo) with a total of 42 430 participants (median duration, 12 months) met the inclusion criteria. When compared with placebo, vitamin D supplementation had no significant effect on BMI (weighted mean difference [WMD], −0.06 kg/m2; 95% confidence interval [95%CI], −0.14 to 0.03), weight (WMD, −0.05 kg; 95%CI, −0.32 to 0.23), or fat mass (WMD, −0.43 kg; 95%CI, −1.69 to 0.84). Likewise, no significant reduction in BMI (WMD, 0.02 kg/m2; 95%CI, −0.11 to 0.14), weight (WMD, 0.12 kg; 95%CI, −0.24 to 0.49), or fat mass (WMD, 0.12 kg; 95%CI, −0.22 to 0.45) was observed in participants who received vitamin D plus calcium compared with those who received calcium control. Conclusions: Supplementation with vitamin D showed no effect on adiposity measures in adults.
    Nutrition Reviews 07/2015; 73(9). DOI:10.1093/nutrit/nuv012 · 6.08 Impact Factor
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    ABSTRACT: To examine whether the effect of postmenopausal hormone therapy (HT) on brain volumes in women aged 65-79 years differs depending on type 2 diabetes status during postintervention follow-up of a randomized controlled clinical trial. The Women's Health Initiative randomized clinical trials assigned women to HT (0.625 mg/day conjugated equine estrogens with or without 2.5 mg/day medroxyprogesterone acetate) or placebo for an average of 5.6 years. A total of 1,402 trial participants underwent brain MRI 2.4 years after the trials; these were repeated in 699 women 4.7 years later. General linear models were used to assess the interaction between diabetes status and HT assignment on brain volumes. Women with diabetes at baseline or during follow-up who had been assigned to HT compared to placebo had mean decrement in total brain volume of -18.6 mL (95% confidence interval [CI] -29.6, -7.6). For women without diabetes, this mean decrement was -0.4 (95% CI -3.8, 3.0) (interaction p = 0.002). This interaction was evident for total gray matter (p < 0.001) and hippocampal (p = 0.006) volumes. It was not evident for changes in brain volumes over follow-up or for ischemic lesion volumes and was not influenced by diabetes duration or oral medications. For women aged 65 years or older who are at increased risk for brain atrophy due to type 2 diabetes, prescription of postmenopausal HT is associated with lower gray matter (total and hippocampal) volumes. Interactions with diabetes and insulin resistance may explain divergent findings on how estrogen influences brain volume among older women. © 2015 American Academy of Neurology.
    Neurology 07/2015; DOI:10.1212/WNL.0000000000001816 · 8.29 Impact Factor
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    ABSTRACT: The proportion of women entering pregnancy overweight or obese has been rising and, in turn, is associated with adverse maternal and fetal outcomes. Gestational weight gain (GWG) exceeding Institute of Medicine (IOM) guidelines further increases health risks and has been independently associated with postpartum weight retention. Hispanic women are disproportionately affected by overweight and obesity, but have had limited access to interventions that promote healthy lifestyles due to cultural, socioeconomic, and language barriers. Therefore, the overall goal of this randomized controlled trial is to test the efficacy of a culturally and linguistically modified, individually-tailored lifestyle intervention to reduce excess GWG, increase postpartum weight loss, and improve maternal metabolic status among overweight/obese Hispanic women. Overweight/obese Hispanic women are recruited in early pregnancy and randomly assigned to a Lifestyle Intervention (n = 150) or a Comparison Health and Wellness (control) intervention (n = 150). Multimodal contacts (i.e., in-person, telephone counseling, and mailed print-based materials) are used to deliver the intervention from early pregnancy (12 weeks gestation) to 6 months postpartum, with follow-up to 1 year postpartum. Targets of the intervention are to achieve IOM Guidelines for GWG and postpartum weight loss; American Congress of Obstetrician and Gynecologist guidelines for physical activity; and American Diabetes Association guidelines for diet. The intervention draws from Social Cognitive Theory and the Transtheoretical Model and includes strategies to address the specific social, cultural, and economic challenges faced by low-income Hispanic women. Assessments are conducted at baseline (~10 weeks gestation), mid pregnancy (24-28 weeks gestation), late pregnancy (32-34 weeks gestation) and postpartum at 6-weeks, 6-months, and 12-months by bicultural and bilingual personnel blinded to the intervention arm. Efficacy is assessed via GWG, postpartum weight loss, and biomarkers of glycemic control, insulin resistance, and cardiovascular disease risk factors. Changes in physical activity and diet are measured via 7-day accelerometer data and 24-h dietary recalls at each assessment time period. Hispanic women are the fastest growing minority group in the U.S. and are disproportionately affected by overweight and obesity. This randomised trial uses a high-reach, low-cost strategy that can readily be translated into clinical practice in underserved and minority populations. NCT01868230 May 29, 2013.
    BMC Pregnancy and Childbirth 07/2015; 15(1):157. DOI:10.1186/s12884-015-0575-3 · 2.19 Impact Factor
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    ABSTRACT: Objectives To prospectively assess the joint association of birth weight and established lifestyle risk factors in adulthood with incident type 2 diabetes and to quantitatively decompose the attributing effects to birth weight only, to adulthood lifestyle only, and to their interaction.Design Prospective cohort study.Setting Health Professionals Follow-up Study (1986-2010), Nurses’ Health Study (1980-2010), and Nurses’ Health Study II (1991-2011).Participants 149 794 men and women without diabetes, cardiovascular disease, or cancer at baseline.Main outcome measure Incident cases of type 2 diabetes, identified through self report and validated by a supplementary questionnaire. Unhealthy lifestyle was defined on the basis of body mass index, smoking, physical activity, alcohol consumption, and the alternate healthy eating index.Results During 20-30 years of follow-up, 11 709 new cases of type 2 diabetes were documented. The multivariate adjusted relative risk of type 2 diabetes was 1.45 (95% confidence interval 1.32 to 1.59) per kg lower birth weight and 2.10 (1.71 to 2.58) per unhealthy lifestyle factor. The relative risk of type 2 diabetes associated with a combination of per kg lower birth weight and per unhealthy lifestyle factor was 2.86 (2.26 to 3.63), which was more than the addition of the risk associated with each individual factor, indicating a significant interaction on an additive scale (P for interaction<0.001). The attributable proportions of joint effect were 22% (95% confidence interval 18.3% to 26.4%) to lower birth weight alone, 59% (57.1% to 61.5%) to unhealthy lifestyle alone, and 18% (13.9% to 21.3%) to their interaction.Conclusion Most cases of type 2 diabetes could be prevented by the adoption of a healthier lifestyle, but simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases.
    BMJ: British medical journal 07/2015; 351:h3672. DOI:10.1136/bmj.h3672 · 16.30 Impact Factor
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    ABSTRACT: To investigate the relationships of hypertension, antihypertensive treatment, and sodium intake on cognitive decline in older women. Prospective follow-up of 6,426 cognitively intact women aged 65-79 years enrolled in the Women's Health Initiative Memory Study (WHIMS) with a median follow-up of 9.1 years. Dietary sodium intake was determined by food frequency questionnaires. Hypertension was defined as self-report of current drug therapy for hypertension. Blood pressure (BP) control was assessed by treatment for hypertension and clinic measurement of systolic BP ≥ 140mm Hg or diastolic BP ≥ 90mm Hg at baseline. Cognitive functioning was assessed annually by global cognitive screening, neurocognitive, and neuropsychiatric evaluations. Cognitive decline was identified by the incidence of mild cognitive impairment (MCI) or probable dementia (PD). Cox proportional hazards analyses were used to calculate hazard ratios (HRs). Hypertension was associated with an increased risk for cognitive decline (HR 1.20; 95% confidence interval (CI) 1.04, 1.39; P = 0.02). Among women with antihypertensive medication, those with BP ≥140/90mm Hg (uncontrolled BP) were at highest risk for developing cognitive decline (HR 1.30; 95% CI 1.05, 1.60) compared to women without treatment and BP <140/90mm Hg (controlled BP). Sodium intake >1,500mg/day did not alter the risk for cognitive decline in hypertensive women or women with antihypertensive treatment (P for interaction = 0.96 or 0.97). Women with antihypertensive treatment and uncontrolled BP showed highest risk estimates for developing cognitive decline compared to non-hypertensive women. Sodium intake did not modify the risk for cognitive decline in women with hypertension or receiving antihypertensive medication. Unique identifier: NCT00685009 and NCT00745056. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email:
    American Journal of Hypertension 07/2015; DOI:10.1093/ajh/hpv081 · 2.85 Impact Factor
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    ABSTRACT: The repertoire of antigens associated with the development of an autoimmune response in breast cancer has relevance to detection and treatment strategies. We have investigated the occurrence of autoantibodies associated with the development of triple negative breast cancer (TNBC) in the prior to diagnosis setting and in samples collected at the time of diagnosis of TNBC. Lysate arrays containing protein fractions from the TNBC MDA-MB-231 cell line were hybridized with TNBC plasmas from the Women's Health Initiative cohort, collected prior to clinical diagnosis and with plasmas from matched controls. An immune response directed against spliceosome and glycolysis proteins was observed with case plasmas as previously reported in ER+ breast cancer. Importantly autoantibodies directed against networks involving BRCA1, TP53 and cytokeratin proteins associated with a mesenchymal/basal phenotype were distinct to TNBC prior to diagnosis samples. Concordant autoantibody findings were observed with mouse plasma samples collected prior to occurrence of palpable tumors from a C3(1)-T triple negative mouse model. Plasma samples collected at the time of diagnosis of stage II TNBC and from matched healthy controls were subjected to proteomic analysis by mass spectrometry to identify Ig bound proteins yielding a predominance of cytokeratins including several associated with a mesenchymal/basal phenotype among cases compared to controls. Our data provide evidence indicative of a dynamic repertoire of antigens associated with a humoral immune response reflecting disease pathogenesis in TNBC. Copyright © 2015, American Association for Cancer Research.
    Cancer Research 06/2015; 75(16). DOI:10.1158/0008-5472.CAN-15-0248 · 9.33 Impact Factor
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    ABSTRACT: To examine the putative adverse effects of ambient fine particulate matter (PM2.5 ) on brain volumes in older women. We conducted a prospective study of 1403 community-dwelling older women without dementia enrolled in the Women's Health Initiative Memory Study (WHIMS), 1996-8. Structural brain MRI scans were performed at age of 71-89 years in 2005-6 to obtain volumetric measures of gray matter (GM) and normal-appearing white matter (WM). Given residential histories and air monitoring data, we used a spatiotemporal model to estimate cumulative PM2.5 exposure in 1999-2006. Multiple linear regression was employed to evaluate the associations between PM2.5 and brain volumes, adjusting for intracranial volumes and potential confounders. Older women with greater PM2.5 exposures had significantly smaller WM, but not GM volumes, independent of geographic region, demographics, socioeconomic status, lifestyles, and clinical characteristics including cardiovascular risk factors. For each inter-quartile increment (3.49 µg/m(3) ) of cumulative PM2.5 exposure, the average WM volume (95% confidence interval) was 6.23 (3.72-8.74) cm(3) in the total brain and 4.47 (2.27-6.67) cm(3) lower in the association areas, equivalent to 1-2 years of brain aging. The adverse PM2.5 effects on smaller WM volumes were present in frontal and temporal lobes and corpus callosum (all p-values <0.01). Hippocampal volumes did not differ by PM2.5 exposure. PM2.5 exposure may contribute to WM loss in older women. Future studies are needed to determine whether exposures result in myelination disturbance, disruption of axonal integrity, damages to oligodendrocytes, or other WM neuropathologies. This article is protected by copyright. All rights reserved. © 2015 American Neurological Association.
    Annals of Neurology 06/2015; 78(3). DOI:10.1002/ana.24460 · 9.98 Impact Factor
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    ABSTRACT: Consistent evidence linking habitual sleep duration with risks of mild cognitive impairment (MCI) and dementia is lacking. 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. 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. In older women, habitual sleep duration predicts the future risk for cognitive impairments including dementia, independent of vascular risk factors. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 06/2015; DOI:10.1016/j.jalz.2015.03.004 · 12.41 Impact Factor
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    ABSTRACT: Although genome-wide association studies have separately identified many genetic susceptibility loci for ulcerative colitis (UC), Crohn's disease (CD), and colorectal cancer (CRC), there has been no large-scale examination for pleiotropy, or shared genetic susceptibility, for these conditions. We used logistic regression modeling to examine the associations of 181 UC and CD susceptibility variants previously identified by GWAS with risk of CRC using data from the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. We also examined associations of significant variants with clinical and molecular characteristics in a subset of the studies.Among 11,794 CRC cases and 14,190 controls, rs11676348, the susceptibility SNP for UC, was significantly associated with reduced risk of CRC (p = 7E-05). The multivariate-adjusted odds ratio of CRC with each copy of the T allele was 0.93 (95% CI, 0.89-0.96). The association of the SNP with risk of CRC differed according to mucinous histological features (Pheterogeneity=0.008). In addition, the (T) allele was associated with lower risk of tumors with Crohn's-like reaction but not tumors without such immune infiltrate (Pheterogeneity=0.02) and microsatellite instability-high (MSI-high) but not microsatellite stable or MSI-low tumors (Pheterogeneity = 0.03). The minor allele (T) in SNP rs11676348, located downstream from CXCR2 that has been implicated in CRC progression, is associated with a lower risk of CRC, particularly tumors with a mucinous component, Crohn's-like reaction, and MSI-high. Our findings offer the promise of risk stratification of inflammatory bowel disease patients for complications such as CRC. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email:
    Carcinogenesis 06/2015; 144(5). DOI:10.1093/carcin/bgv086 · 5.33 Impact Factor
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    ABSTRACT: More than two-thirds of US women are overweight or obese, placing them at increased risk for postmenopausal breast cancer. To investigate in this secondary analysis the associations of overweight and obesity with risk of postmenopausal invasive breast cancer after extended follow-up in the Women's Health Initiative (WHI) clinical trials. The WHI clinical trial protocol incorporated measured height and weight, baseline and annual or biennial mammography, and adjudicated breast cancer end points in 67 142 postmenopausal women ages 50 to 79 years at 40 US clinical centers. The women were enrolled from 1993 to 1998 with a median of 13 years of follow-up through 2010; 3388 invasive breast cancers were observed. Height and weight were measured at baseline, and weight was measured annually thereafter. Data were collected on demographic characteristics, personal and family medical history, and personal habits (smoking, physical activity). Women underwent annual or biennial mammograms. Breast cancers were verified by medical records reviewed by physician adjudicators. Women who were overweight and obese had an increased invasive breast cancer risk vs women of normal weight. Risk was greatest for obesity grade 2 plus 3 (body mass index [BMI], calculated as weight in kilograms divided by height in meters squared, >35.0) (hazard ratio [HR] for invasive breast cancer, 1.58; 95% CI, 1.40-1.79). A BMI of 35.0 or higher was strongly associated with risk for estrogen receptor-positive and progesterone receptor-positive breast cancers (HR, 1.86; 95% CI, 1.60-2.17) but was not associated with estrogen receptor-negative cancers. Obesity grade 2 plus 3 was also associated with advanced disease, including larger tumor size (HR, 2.12; 95% CI, 1.67-2.69; P = .02), positive lymph nodes (HR, 1.89; 95% CI, 1.46-2.45; P = .06), regional and/or distant stage (HR, 1.94; 95% CI, 1.52-2.47; P = .05), and deaths after breast cancer (HR, 2.11; 95% CI, 1.57-2.84; P < .001). Women with a baseline BMI of less than 25.0 who gained more than 5% of body weight over the follow-up period had an increased breast cancer risk (HR, 1.36; 95% CI, 1.1-1.65), but among women already overweight or obese we found no association of weight change (gain or loss) with breast cancer during follow-up. There was no effect modification of the BMI-breast cancer relationship by postmenopausal hormone therapy, and the direction of association across BMI categories was similar for never, past, and current hormone therapy use. Obesity is associated with increased invasive breast cancer risk in postmenopausal women. These clinically meaningful findings should motivate programs for obesity prevention. Identifier: NCT00000611.
    06/2015; 1(5). DOI:10.1001/jamaoncol.2015.1546

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82k Citations
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  • 2015
    • University of Arkansas at Little Rock
      Little Rock, Arkansas, United States
  • 1993–2015
    • Harvard University
      • Department of Nutrition
      Cambridge, Massachusetts, United States
  • 1991–2015
    • Brigham and Women's Hospital
      • • Division of Preventive Medicine
      • • Department of Medicine
      Boston, Massachusetts, United States
  • 1990–2015
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2014
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
  • 2013
    • University of Alabama at Birmingham
      • Department of Epidemiology
      Birmingham, AL, United States
    • McGill University
      • Department of Oncology
      Montréal, Quebec, Canada
    • University of Washington Seattle
      • Department of Medicine
      Seattle, Washington, United States
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      Torrance, California, United States
    • The Ohio State University
      Columbus, Ohio, United States
  • 2005–2013
    • University of Massachusetts Amherst
      • • Division of Biostatistics and Epidemiology
      • • Department of Public Health
      Amherst Center, Massachusetts, United States
    • University of California, San Diego
      • Department of Family and Preventive Medicine
      San Diego, CA, United States
    • Florida Atlantic University
      • Department of Biomedical Science
      Boca Raton, Florida, United States
    • University of Pittsburgh
      • Division of General Internal Medicine
      Pittsburgh, PA, United States
    • German Institute of Human Nutrition
      • Department of Epidemiology
      Potsdam, Brandenburg, Germany
  • 2012
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
  • 2011
    • University of California, San Francisco
      • Department of Obstetrics, Gynecology and Reproductive Sciences
      San Francisco, CA, United States
    • HealthPartners Institute for Education and Research
      Bloomington, Minnesota, United States
  • 2010
    • Medical University of South Carolina
      • Department of Medicine
      Charleston, South Carolina, United States
    • Kaiser Permanente
      Oakland, California, United States
  • 2009
    • Partners HealthCare
      Boston, Massachusetts, United States
    • John Wayne Cancer Institute
      Santa Monica, California, United States
  • 2004–2009
    • Fred Hutchinson Cancer Research Center
      • Division of Public Health Sciences
      Seattle, WA, United States
    • Wake Forest School of Medicine
      • Division of Public Health Sciences
      Winston-Salem, North Carolina, United States
  • 2003–2009
    • Massachusetts Department of Public Health
      Boston, Massachusetts, United States
    • Boston Children's Hospital
      • Department of Laboratory Medicine
      Boston, Massachusetts, United States
  • 2008
    • University of East Anglia
      • Norwich Medical School
      Norwich, England, United Kingdom
  • 2006–2008
    • Beth Israel Deaconess Medical Center
      • Division of Endocrinology, Diabetes and Metabolism
      Boston, Massachusetts, United States
    • VU University Amsterdam
      • Faculty of Earth and Life Sciences
      Amsterdamo, North Holland, Netherlands
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
    • University at Buffalo, The State University of New York
      • Department of Social and Preventive Medicine
      Buffalo, NY, United States
  • 2000–2008
    • Albert Einstein College of Medicine
      • Department of Epidemiology & Population Health
      New York City, NY, United States
    • University of Alaska Anchorage
      Anchorage, Alaska, United States
  • 2007
    • University of California, Los Angeles
      • Department of Epidemiology
      Los Angeles, CA, United States
  • 2006–2007
    • George Washington University
      • Department of Medicine
      Washington, Washington, D.C., United States
  • 2004–2006
    • Columbia University
      New York, New York, United States
  • 2004–2005
    • Simmons College
      • Program in Nutrition and Dietetics
      Boston, Massachusetts, United States
  • 2002
    • University of Zurich
      • Internal Medicine Unit
      Zürich, ZH, Switzerland
    • Duke University
      Durham, North Carolina, United States
    • Dana-Farber Cancer Institute
      • Department of Medical Oncology
      Boston, MA, United States
    • Boston University
      Boston, Massachusetts, United States
  • 1996
    • William Penn University
      Filadelfia, Pennsylvania, United States