Publications by authors named "JoAnn E Manson"

1,174 Publications

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Host and gut microbial tryptophan metabolism and type 2 diabetes: an integrative analysis of host genetics, diet, gut microbiome and circulating metabolites in cohort studies.

Gut 2021 Jun 14. Epub 2021 Jun 14.

Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.

Objective: Tryptophan can be catabolised to various metabolites through host kynurenine and microbial indole pathways. We aimed to examine relationships of host and microbial tryptophan metabolites with incident type 2 diabetes (T2D), host genetics, diet and gut microbiota.

Method: We analysed associations between circulating levels of 11 tryptophan metabolites and incident T2D in 9180 participants of diverse racial/ethnic backgrounds from five cohorts. We examined host genome-wide variants, dietary intake and gut microbiome associated with these metabolites.

Results: Tryptophan, four kynurenine-pathway metabolites (kynurenine, kynurenate, xanthurenate and quinolinate) and indolelactate were positively associated with T2D risk, while indolepropionate was inversely associated with T2D risk. We identified multiple host genetic variants, dietary factors, gut bacteria and their potential interplay associated with these T2D-relaetd metabolites. Intakes of fibre-rich foods, but not protein/tryptophan-rich foods, were the dietary factors most strongly associated with tryptophan metabolites. The fibre-indolepropionate association was partially explained by indolepropionate-associated gut bacteria, mostly fibre-using . We identified a novel association between a host functional variant (determining lactase persistence) and serum indolepropionate, which might be related to a host gene-diet interaction on gut , a probiotic bacterium significantly associated with indolepropionate independent of other fibre-related bacteria. Higher milk intake was associated with higher levels of gut and serum indolepropionate only among genetically lactase non-persistent individuals.

Conclusion: Higher milk intake among lactase non-persistent individuals, and higher fibre intake were associated with a favourable profile of circulating tryptophan metabolites for T2D, potentially through the host-microbial cross-talk shifting tryptophan metabolism toward gut microbial indolepropionate production.
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http://dx.doi.org/10.1136/gutjnl-2021-324053DOI Listing
June 2021

Women's Health - Traversing Medicine and Public Policy.

N Engl J Med 2021 Jun 29;384(22):2073-2076. Epub 2021 May 29.

From the Department of Medicine, University of California, San Diego, School of Medicine, La Jolla (C.A.S.); and the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School - both in Boston (J.E.M.).

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http://dx.doi.org/10.1056/NEJMp2105292DOI Listing
June 2021

Response to the letter to the editor: "The link between Vitamin D and COVID-19".

Contemp Clin Trials 2021 06 29;105:106418. Epub 2021 May 29.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

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http://dx.doi.org/10.1016/j.cct.2021.106418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163558PMC
June 2021

Omega-3 supplementation and heart failure: A meta-analysis of 12 trials including 81,364 participants.

Contemp Clin Trials 2021 May 28;107:106458. Epub 2021 May 28.

Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Heart failure (HF) remains a leading cause of hospitalization and mortality. Marine omega-3 fatty acid supplements (omega-3 s) have shown efficacy in decreasing sudden cardiac death and improving the left ventricle ejection fraction percent (LVEF%). In this review, we evaluated the effect of marine omega-3 fatty acid supplements (omega-3 s) on HF hospitalization, recurrent HF hospitalization, and cardiovascular mortality in patients with heart failure. We found that omega-3 supplementation did not reduce first HF hospitalization or cardiovascular mortality but did significantly reduce recurrent HF hospitalizations, as compared with placebo.
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http://dx.doi.org/10.1016/j.cct.2021.106458DOI Listing
May 2021

Clonal hematopoiesis associated with epigenetic aging and clinical outcomes.

Aging Cell 2021 06 29;20(6):e13366. Epub 2021 May 29.

Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.

Clonal hematopoiesis of indeterminate potential (CHIP) is a common precursor state for blood cancers that most frequently occurs due to mutations in the DNA-methylation modifying enzymes DNMT3A or TET2. We used DNA-methylation array and whole-genome sequencing data from four cohorts together comprising 5522 persons to study the association between CHIP, epigenetic clocks, and health outcomes. CHIP was strongly associated with epigenetic age acceleration, defined as the residual after regressing epigenetic clock age on chronological age, in several clocks, ranging from 1.31 years (GrimAge, p < 8.6 × 10 ) to 3.08 years (EEAA, p < 3.7 × 10 ). Mutations in most CHIP genes except DNA-damage response genes were associated with increases in several measures of age acceleration. CHIP carriers with mutations in multiple genes had the largest increases in age acceleration and decrease in estimated telomere length. Finally, we found that ~40% of CHIP carriers had acceleration >0 in both Hannum and GrimAge (referred to as AgeAccelHG+). This group was at high risk of all-cause mortality (hazard ratio 2.90, p < 4.1 × 10 ) and coronary heart disease (CHD) (hazard ratio 3.24, p < 9.3 × 10 ) compared to those who were CHIP-/AgeAccelHG-. In contrast, the other ~60% of CHIP carriers who were AgeAccelHG- were not at increased risk of these outcomes. In summary, CHIP is strongly linked to age acceleration in multiple clocks, and the combination of CHIP and epigenetic aging may be used to identify a population at high risk for adverse outcomes and who may be a target for clinical interventions.
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http://dx.doi.org/10.1111/acel.13366DOI Listing
June 2021

Sex and Race Differences in the Risk of Ischemic Stroke Associated With Fasting Blood Glucose in REGARDS.

Neurology 2021 May 27. Epub 2021 May 27.

Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL.

Background: To investigate sex and race differences in the association between fasting blood glucose (FBG) and risk of ischemic stroke (IS).

Methods: This prospective longitudinal cohort study included adults age ≥45 years at baseline in the Reasons for Geographic And Racial Differences in Stroke Study, followed for a median of 11.4 years. The exposure was baseline FBG (mg/dL); suspected IS events were ascertained by phone every 6 months and were physician-adjudicated. Cox proportional hazards were used to assess the adjusted sex/race-specific associations between FBG (by category and as a restricted cubic spline) and incident IS.

Results: Of 20,338 participants, mean age was 64.5(SD 9.3) years, 38.7% were Black, 55.4% were women, 16.2% were using diabetes medications, and 954 IS events occurred. Compared to FBG <100, FBG ≥150 was associated with 59% higher hazards of IS (95%CI 1.21-2.08) and 61% higher hazards of IS among those on diabetes medications (95%CI 1.12-2.31). The association between FBG and IS varied by race/sex (HR, FBG ≥ 150 vs. FBG <100: White women 2.05 (95% CI 1.23-3.42), Black women 1.71 (95%CI 1.10-2.66), Black men 1.24 (95%CI 0.75-2.06), White men 1.46 (95%CI 0.93-2.28), p=0.004). Analyses using FBG splines suggest that sex was the major contributor to differences by race/sex subgroups.

Conclusions: Sex differences in the strength and shape of the association between FBG and IS are likely driving the significant differences in the association between FBG and IS across race/sex subgroups. These findings should be explored further and may inform tailored stroke prevention guidelines.
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http://dx.doi.org/10.1212/WNL.0000000000012296DOI Listing
May 2021

Estimating the effect of nutritional interventions using observational data: the American Heart Association's 2020 Dietary Goals and mortality.

Am J Clin Nutr 2021 May 27. Epub 2021 May 27.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: Because randomized trials of sustained dietary changes are sometimes impractical for long-term outcomes, the explicit emulation of a (hypothetical) target trial using observational data may be an important tool for nutritional epidemiology.

Objectives: We describe a methodological approach that aims to emulate a target trial of dietary interventions sustained over many years using data from observational cohort studies.

Methods: We estimated the 20-y risk of all-cause mortality under the sustained implementation of the food-based goals of the American Heart Association (AHA) 2020 using data from 3 prospective observational studies of US men [Health Professionals Follow-up Study (HPFS)] and women [Nurses' Health Study (NHS) and Nurses' Health Study II (NHS II)]. We applied the parametric g-formula to estimate the 20-y mortality risk under a dietary intervention and under no dietary intervention.

Results: There were 165,411 participants who met the eligibility criteria. The mean age at baseline was 57.4 y (range, 43-82 y) in the HPFS, 52.4 y (range, 39-66 y) in the NHS, and 40.2 y (range, 30-50 y) in the NHS II. During 20 y of follow-up, 13,241 participants died. The estimated 20-y mortality risks under a dietary intervention versus no intervention were 21.9% compared with 25.8%, respectively, in the HPFS (risk difference, -3.9%; 95% CI: -4.9% to -3.2%); 10.0% compared with 12.6%, respectively, in the NHS (risk difference, -2.6%; 95% CI: -3.1% to -1.8%); and 2.1% compared with 2.5%, respectively, in the NHS II (risk difference, -0.35%; 95% CI: -0.56% to -0.09%). The corresponding risk ratios were 0.85 (95% CI: 0.81-0.88) in the HPFS, 0.79 (95% CI: 0.75-0.85) in the NHS, and 0.86 (95% CI: 0.78-0.96) in the NHS II.

Conclusions: We estimated that adherence to the food-based AHA 2020 Dietary Goals starting in midlife may reduce the 20-y risk of mortality.
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http://dx.doi.org/10.1093/ajcn/nqab100DOI Listing
May 2021

Homocysteine Is Associated With Future Venous Thromboembolism in 2 Prospective Cohorts of Women.

Arterioscler Thromb Vasc Biol 2021 May 27:ATVBAHA121316397. Epub 2021 May 27.

Division of Preventive Medicine (A.W.A., E.K.D., M.V.D., E.K., W.G.C., J.E.M., P.M.R., A.D.P.).

Objective: Case-control studies have identified plasma homocysteine as a risk marker for venous thromboembolism (VTE). Prospective data, particularly among women, are sparse. We examined whether plasma homocysteine associates with incident VTE in 2 large prospective cohorts of women. Approach and Results: In the WHS (Women's Health Study), a prospective cohort study of 27 555 women ≥45 years old and free of cardiovascular disease and VTE, we assessed baseline homocysteine concentration along with other thrombotic biomarkers for association with future VTE (n=743), pulmonary embolism (n=363), and deep vein thrombosis (n=545). We used a second cohort of 2672 women (n=102 VTE events) in the WAFACS (Women's Antioxidant and Folic Acid Cardiovascular Study) to corroborate our findings. In age-adjusted analyses, elevated homocysteine, hsCRP (high-sensitivity C-reactive protein), fibrinogen, and sICAM-1 (soluble intercellular adhesion molecule 1) were associated with incident VTE ( for extreme quartile comparisons and -trend <0.05). In multivariable models adjusting for body mass index and other traditional VTE risk factors, only the association for homocysteine persisted (HR, 1.31 [95% CI, 1.06-1.63]). Elevated homocysteine levels were associated with unprovoked pulmonary embolism (HR, 2.13 [95% CI, 1.30-3.51]) and deep vein thrombosis (HR, 1.59 [95% CI, 1.05-2.40]) but not provoked events. In WAFACS, elevated homocysteine levels were also associated with VTE events (-trend 0.023).

Conclusions: Higher plasma homocysteine levels associate with VTE events in 2 cohorts of middle-aged and older women. Among VTE subtypes, homocysteine was associated with unprovoked, but not provoked, events. These data suggest a plausible biological role for homocysteine in the development of VTE.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00000479, NCT00000541.
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http://dx.doi.org/10.1161/ATVBAHA.121.316397DOI Listing
May 2021

Low-fat dietary pattern and breast cancer mortality by metabolic syndrome components: a secondary analysis of the Women's Health Initiative (WHI) randomised trial.

Br J Cancer 2021 May 18. Epub 2021 May 18.

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.

Background: In the Women's Health Initiative (WHI) dietary modification (DM) randomised trial, the low-fat dietary intervention reduced deaths from breast cancer (P = 0.02). Extending these findings, secondary analysis examined dietary intervention influence on breast cancer mortality by metabolic syndrome (MS) components.

Methods: In total, 48,835 postmenopausal women with no prior breast cancer were randomised to a low-fat dietary intervention or comparison groups. Four MS components were determined at entry in 45,833 participants: (1) high waist circumference, (2) high blood pressure, (3) high cholesterol and (4) diabetes history. Forest plots of hazard ratios (HRs) were generated with P-values for interaction between randomisation groups and MS component score. Primary outcome was death from breast cancer by metabolic syndrome score.

Results: HRs and 95% confidence intervals (CI) for dietary intervention influence on death from breast cancer were with no MS components (n = 10,639), HR 1.09, 95% CI 0.63-1.87; with 1-2 MS components (n = 30,948), HR 0.80, 95% CI 0.62-1.02; with 3-4 MS components (n = 4,246), HR 0.31, 95% CI 0.14-0.69 (interaction P = 0.01).

Conclusions: While postmenopausal women with 3-4 MS components were at higher risk of death from breast cancer, those randomised to a low-fat dietary intervention more likely had reduction in this risk.

Registry: ClinicalTrials.gov (NCT00000611).
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http://dx.doi.org/10.1038/s41416-021-01379-wDOI Listing
May 2021

The Impact of a Lifestyle Intervention on Postpartum Weight Retention Among At-Risk Hispanic Women.

Am J Prev Med 2021 Jul 13;61(1):44-54. Epub 2021 May 13.

Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, Massachusetts. Electronic address:

Introduction: This study assesses the impact of a culturally modified, motivationally targeted, individually tailored intervention on postpartum weight retention among Hispanic women with abnormal glucose tolerance during pregnancy.

Methods: Estudio Parto (Project Aiming to Reduce Type twO diabetes) was an RCT conducted in Western Massachusetts (collected 2013‒2017, analyzed 2018-2020). Hispanic women with blood glucose ≥140 mg/dL (7.77 mmol/L) on routine nonfasting oral glucose challenge test were randomized to a Lifestyle Intervention (n=100) focusing on healthy exercise and diet or to a comparison Health and Wellness Intervention (n=104) with no mention of exercise or diet behavior changes. The primary outcome was change in weight, calculated as the difference between prepregnancy weight and 6-week, 6-month, and 12-month postpartum weight. The secondary outcome was achievement of weight reduction to prepregnancy weight if prepregnancy BMI was normal, or a 5% reduction if prepregnancy BMI was overweight/obese.

Results: In intent-to-treat analyses, there were no significant differences in weight change pattern between the intervention arms across all follow-up timepoints (β=0.03, 95% CI= -3.38, 3.45). However, at 12 months postpartum, women in the Lifestyle Intervention arm had a statistically significant 2.5-fold higher odds of meeting the secondary weight reduction outcome (OR=2.52, 95% CI=1.09, 5.82) than women in the Health and Wellness arm. Regardless of intervention arm, women who reported higher levels of postpartum sports/exercise had a greater decrease in weight (β= -2.39, 95% CI= -4.66, -0.13, p=0.04) than women reporting lower levels.

Conclusions: In this randomized trial among Hispanic women, no significant overall differences in weight change pattern between intervention arms were observed. Higher levels of self-reported physical activity were associated with greater weight loss in both arms.
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http://dx.doi.org/10.1016/j.amepre.2021.02.005DOI Listing
July 2021

Does publication bias explain the divergent findings on menopausal hormone therapy and cardioprotection in the literature?

Res Pract Thromb Haemost 2021 May 4;5(4):e12515. Epub 2021 May 4.

Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston MA USA.

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http://dx.doi.org/10.1002/rth2.12515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105155PMC
May 2021

Cardiovascular disease (CVD) risk scores, age, or years since menopause to predict cardiovascular disease in the Women's Health Initiative.

Menopause 2021 05 3;28(6):610-618. Epub 2021 May 3.

Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA.

Objective: To assess the utility of cardiovascular disease (CVD) risk scores compared to age or years since menopause for prediction of CVD events in the WHI clinical trials.

Methods: Briefly, in the randomized clinical trial 27,347 postmenopausal women age 50 to 79 years entered from 1993 to 1998. Women with a uterus (16,608) were randomized to receive daily oral conjugated equine estrogen (CEE) (0.625 mg) plus medroxyprogesterone acetate (2.5 mg) (5.7 years or placebo), while women with a hysterectomy (10,739) were randomized to receive daily oral CEE (0.625 mg) alone or placebo (7.2 y). CVD risk scores were assessed at baseline and CVD events were adjudicated throughout the follow-up period to the end of the main study phase and to the end of cumulative follow-up. The median follow-up time after the start of the randomized clinical trial to the end of the main study phase was 8.2 years. The median follow-up time to the end of cumulative follow-up was 17.6 years. We compared The American Heart Association/American College of Cardiology (AHA/ACC) and Framingham Heart Study risk scores to age or years since menopause all obtained at baseline to predict subsequent CVD events. The absolute event rates, hazard ratios, and C-statistics (Uno Concordance from Cox proportional models) were compared.

Results: Overall, the hazard ratios for CVD events were highest with calculated CVD scores calculated at trial onset both at the end of the main study (ranging from 2.02 to 10.8 for Q2-Q5, compared to Q1) and at cumulative follow-up (ranging from 1.76 to 8.86 for Q2-Q5, compared to Q1). While older age and years since menopause at baseline were also associated with higher CVD event rates, better risk prediction was accomplished by using CVD risk scores. The Framingham Heart Study BMI score had the highest C-statistic at the end of the main study (0.711) and after 17.6 years through the end of follow-up (0.689).

Conclusions: CVD risk scores can help identify postmenopausal women at higher risk for CVD beyond age or time since menopause. Risk scoring that better estimates vascular aging may facilitate CVD risk prevention. When performed prior to initiation of menopausal hormone therapy, scores can better inform HT risk/benefit discussions.
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http://dx.doi.org/10.1097/GME.0000000000001753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141005PMC
May 2021

Egg consumption, overall diet quality, and risk of type 2 diabetes and coronary heart disease: A pooling project of US prospective cohorts.

Clin Nutr 2021 May 11;40(5):2475-2482. Epub 2021 Mar 11.

Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.

Background And Aims: Data on the relation of egg consumption with risk of type 2 diabetes (T2D) and coronary heart disease (CHD) are limited and inconsistent. Few studies have controlled for overall dietary patterns in egg-T2D or egg-CHD analyses, and it is unclear whether any observed elevated risks of T2D and CHD with frequent egg consumption is real or due to confounding by dietary habits. We tested the hypothesis that frequent egg consumption is associated with a higher risk of T2D and CHD risk after adjustment for overall dietary patterns among adults.

Design: We used prospective cohort design to complete time-to-event analyses.

Methods: We pooled de novo, harmonized, individual-level analyses from nine US cohorts (n = 103,811). Cox regression was used to estimate hazard ratios separately in each cohort adjusting for age, ethnicity, body mass index (BMI), exercise, smoking, alcohol intake, and dietary patterns. We pooled cohort-specific results using an inverse-variance weighted method to estimate summary relative risks.

Results: Median age ranged from 25 to 72 years. Median egg consumption was 1 egg per week in most of the cohorts. While egg consumption up to one per week was not associated with T2D risk, consumption of ≥2 eggs per week was associated with elevated risk [27% elevated risk of T2D comparing 7+ eggs/week with none (95% CI: 16%-37%)]. There was little evidence for heterogeneity across cohorts and we observed similar conclusions when stratified by BMI. Overall, egg consumption was not associated with the risk of CHD. However, in a sensitivity analysis, there was a 30% higher risk of CHD (95% CI: 3%-56%) restricted to older adults consuming 5-6 eggs/week.

Conclusions: Our data showed an elevated risk of T2D with egg consumption of ≥2 eggs per week but not with <2 eggs/week. While there was no overall association of egg consumption with CHD risk, the elevated CHD observed with consumption of 5-6 eggs/week in older cohorts merits further investigation.
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http://dx.doi.org/10.1016/j.clnu.2021.03.003DOI Listing
May 2021

Dose-Response Models May Explain Age-Related Macular Degeneration and Vitamin Treatments-Reply.

JAMA Ophthalmol 2021 Jun;139(6):677

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jamaophthalmol.2021.1040DOI Listing
June 2021

Biomarker-Calibrated Macronutrient Intake and Chronic Disease Risk among Postmenopausal Women.

J Nutr 2021 Apr 20. Epub 2021 Apr 20.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Background: Knowledge about macronutrient intake and chronic disease risk has been limited by the absence of objective macronutrient measures. Recently, we proposed novel biomarkers for protein, protein density, carbohydrate, and carbohydrate density, using established biomarkers and serum and urine metabolomics profiles in a human feeding study.

Objectives: We aimed to use these biomarkers to develop calibration equations for macronutrient variables using dietary self-reports and personal characteristics and to study the association between biomarker-calibrated intake estimates and cardiovascular disease, cancer, and diabetes risk in Women's Health Initiative (WHI) cohorts.

Methods: Prospective disease association analyses are based on WHI cohorts of postmenopausal US women aged 50-79 y when enrolled at 40 US clinical centers (n = 81,954). We used biomarker intake values in a WHI nutritional biomarker study (n = 436) to develop calibration equations for each macronutrient variable, leading to calibrated macronutrient intake estimates throughout WHI cohorts. We then examined the association of these intakes with chronic disease incidence over a 20-y (median) follow-up period using HR regression methods.

Results: In analyses that included doubly labeled water-calibrated total energy, HRs for cardiovascular diseases and cancers were mostly unrelated to calibrated protein density. However, many were inversely related to carbohydrate density, with HRs (95% CIs) for a 20% increment in carbohydrate density of 0.81 (0.69, 0.95) and 0.83 (0.74, 0.93), respectively, for primary outcomes of coronary heart disease and breast cancer, as well as 0.74 (0.60, 0.91) and 0.87 (0.81, 0.93) for secondary outcomes of heart failure and total invasive cancer. Corresponding HRs (95% CIs) for type 2 diabetes incidence in relation to protein density and carbohydrate density were 1.17 (1.09, 1.75) and 0.73 (0.66, 0.80), respectively.

Conclusions: At specific energy intake, a diet high in carbohydrate density is associated with substantially reduced risk of major chronic diseases in a population of US postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00000611.
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http://dx.doi.org/10.1093/jn/nxab091DOI Listing
April 2021

Nutritional epidemiology and the Women's Health Initiative: a review.

Am J Clin Nutr 2021 05;113(5):1083-1092

Lundquist Institute for Innovative Biomedical Research at Harbor-UCLA Medical Center, Torrance, CA, USA.

The dietary modification (DM) clinical trial, within the Women's Health Initiative (WHI), studied a low-fat dietary pattern intervention that included guidance to increase vegetables, fruit, and grains. This study was motivated in part from uncertainty about the reliability of observational studies examining the association between dietary fat and chronic disease risk by using self-reported dietary data. In addition to this large trial, which had breast and colorectal cancer as its primary outcomes, a substantial biomarker research effort was initiated midway in the WHI program to contribute to nutritional epidemiology research more broadly. Here we review and update findings from the DM trial and from the WHI nutritional biomarker studies and examine implications for future nutritional epidemiology research. The WHI included the randomized controlled DM trial (n = 48,835) and a prospective cohort observational (OS) study (n = 93,676), both among postmenopausal US women, aged 50-79 y when enrolled during 1993-1998. Also reviewed is a nutrition and physical activity assessment study in a subset of 450 OS participants (2007-2009) and a related controlled feeding study among 153 WHI participants (2010-2014). Long-term follow-up in the DM trial provides evidence for intervention-related reductions in breast cancer mortality, diabetes requiring insulin, and coronary artery disease in the subset of normotensive healthy women, without observed adverse effects or changes in all-cause mortality. Studies of intake biomarkers, and of biomarker-calibrated intake, suggest important associations of total energy intake and macronutrient dietary composition with the risk for major chronic diseases among postmenopausal women. Collectively these studies argue for a nutrition epidemiology research agenda that includes major efforts in nutritional biomarker development, and in the application of biomarkers combined with self-reported dietary data in disease association analyses. We expect such efforts to yield novel disease association findings and to inform disease prevention approaches for potential testing in dietary intervention trials. This trial was registered at clinicaltrials.gov as NCT00000611.
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http://dx.doi.org/10.1093/ajcn/nqab091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120331PMC
May 2021

Associations of Dairy Intake with Circulating Biomarkers of Inflammation, Insulin Response, and Dyslipidemia among Postmenopausal Women.

J Acad Nutr Diet 2021 Apr 13. Epub 2021 Apr 13.

Background: Cardiometabolic diseases are prevalent in aging Americans. Although some studies have implicated greater intake of dairy products, it is not clear how dairy intake is related to biomarkers of cardiometabolic health.

Objective: Our aim was to test the hypothesis that associations of dairy foods with biomarkers of lipid metabolism, insulin-like growth factor signaling, and chronic inflammation may provide clues to understanding how dairy can influence cardiometabolic health.

Design: This was a cross-sectional study in the Women's Health Initiative using baseline food frequency questionnaire data to calculate dairy intake.

Participants/setting: Participants were 35,352 postmenopausal women aged 50 to 79 years at 40 clinical centers in the United States.

Main Outcome Measures: Baseline (1993-1998) concentrations of 20 circulating biomarkers were measured.

Statistical Analyses: Multivariable-adjusted linear regression was used to estimate percent difference in biomarker concentrations per serving of total dairy and individual foods (milk, cheese, yogurt, butter, and low-fat varieties).

Results: Lower triglyceride concentrations were associated with greater intake of total dairy (-0.8% [95% CI -1.2% to -0.3%]), mainly driven by full-fat varieties. Individual dairy foods had specific associations with circulating lipid components. For example, greater total milk intake was associated with lower concentrations of total cholesterol (-0.4% [95% CI -0.7% to -0.2%]) and high-density lipoprotein cholesterol (-0.5% [95% CI -0.9% to -0.1%]), whereas greater butter intake was associated with higher total cholesterol (0.6% [95% CI 0.2% to 1.0%]) and high-density lipoprotein cholesterol (1.6% [95% CI 1.1% to 2.0%]) concentrations. In contrast, higher total yogurt intake was associated with lower total cholesterol (-1.1% [95% CI -2.0% to -0.2%]) and higher high-density lipoprotein cholesterol (1.8% [95% CI 0.5% to 3.1%]). Greater total dairy intake (regardless of fat content), total cheese, full-fat cheese, and yogurt were consistently associated with lower concentrations of glucose, insulin, and C-reactive protein. However, milk and butter were not associated with these biomarkers.

Conclusions: Higher dairy intake, except butter, was associated with a favorable profile of lipids, insulin response, and inflammatory biomarkers, regardless of fat content. Yet, specific dairy foods might influence these markers uniquely. Findings do not support a putative role of dairy in cardiometabolic diseases observed in some previous studies.
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http://dx.doi.org/10.1016/j.jand.2021.02.029DOI Listing
April 2021

Recommended Hormone Therapy in Menopause: Concepts, Controversies and Approach to Treatment.

Endocr Rev 2021 Apr 15. Epub 2021 Apr 15.

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, Massachusetts USA.

Hormone therapy (HT) is an effective treatment for menopausal symptoms, including vasomotor symptoms and genitourinary syndrome of menopause. Randomized trials also demonstrate positive effects on bone health, and age-stratified analyses indicate more favorable effects on coronary heart disease and all-cause mortality in younger women (close proximity to menopause) than in women more than a decade past menopause. In the absence of contraindications or other major comorbidities, recently menopausal women with moderate or severe symptoms are appropriate candidates for HT. The WHI hormone therapy trials- estrogen and progestin (E+P) trial and the estrogen-alone (E-alone) trial- clarified the benefits and risks of HT, including how the results differed by age. A key lesson from the WHI trials, which was unfortunately lost in the post-trial cacophony, was that the risk:benefit ratio and safety profile of HT differed markedly by clinical characteristics of the participants, especially age, time since menopause, and comorbidity status. In the present review of the WHI and other recent HT trials, we aim to provide readers with an improved understanding of the importance of the timing of HT initiation, type and route of administration, and of patient-specific considerations that should be weighed when prescribing HT.
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http://dx.doi.org/10.1210/endrev/bnab011DOI Listing
April 2021

Risks, Benefits, and Treatment Modalities of Menopausal Hormone Therapy: Current Concepts.

Front Endocrinol (Lausanne) 2021 26;12:564781. Epub 2021 Mar 26.

Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.

Menopausal hormone therapy (HT) prescribing practices have evolved over the last few decades guided by the changing understanding of the treatment's risks and benefits. Since the Women's Health Initiative (WHI) trial results in 2002, including post-intervention analysis and cumulative 18-year follow up, it has become clear that the risks of HT are low for healthy women less than age 60 or within ten years from menopause. For those who are experiencing bothersome vasomotor symptoms, the benefits are likely to outweigh the risks in view of HT's efficacy for symptom management. HT also has a role in preventing osteoporosis in appropriate candidates for treatment. A comprehensive overview of the types, routes, and formulations of currently available HT, as well as HT's benefits and risks by outcomes of interest are provided to facilitate clinical decision making.
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http://dx.doi.org/10.3389/fendo.2021.564781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034540PMC
March 2021

Biomarkers of phthalates and inflammation: Findings from a subgroup of Women's Health Initiative participants.

Int J Hyg Environ Health 2021 May 1;234:113743. Epub 2021 Apr 1.

Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, MA, USA. Electronic address:

Background: Recent experimental work has shown that phthalates may increase inflammation. Prior research has not examined the role of exposure to phthalates in relation to inflammatory status among postmenopausal women who are at higher risk of developing inflammation-related chronic disorders.

Objectives: We aimed to examine the associations of urinary phthalate biomarker concentrations with circulating levels of c-reactive protein [CRP] and interleukin-6 [IL-6] among 443 postmenopausal women selected into a breast cancer case-control study nested within the Women's Health Initiative (WHI).

Methods: A total of 13 phthalate metabolites were measured in urine samples provided at WHI enrollment from 1993 to 1998. We also measured baseline levels of CRP and IL-6 in these women's serum or plasma samples. Multivariable linear models were used to investigate the role of each phthalate biomarker in relation to CRP and IL-6, adjusting for potential confounding factors and specifically evaluating the role of BMI.

Results: In adjusted models we observed positive associations of monocarboxynonyl phthalate (MCNP) with CRP (β = 0.092; 95% CI 0.026, 0.158) and IL-6 (β = 0.108; 95% CI 0.013, 0.204). These positive associations were attenuated and non-significant, however, after further adjustment for body mass index (BMI). In contrast, we observed inverse associations of monoethyl phthalate (MEP) (β = -0.019; 95% CI -0.036, -0.001) and monobenzyl phthalate (MBzP) (β = -0.034; 95% CI -0.058, -0.010) with CRP levels only after adjustment for BMI. Other phthalate biomarkers examined were not significantly associated with either CRP or IL-6 levels.

Conclusions: Overall, these results do not suggest an important role for phthalates in promoting an inflammatory response. Future prospective studies are warranted to improve understanding of these associations, particularly in clarifying the role of BMI.
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http://dx.doi.org/10.1016/j.ijheh.2021.113743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096686PMC
May 2021

Metabolically Healthy/Unhealthy Overweight/Obesity Associations With Incident Heart Failure in Postmenopausal Women: The Women's Health Initiative.

Circ Heart Fail 2021 Apr 29;14(4):e007297. Epub 2021 Mar 29.

Heart Disease Prevention Program, Division of Cardiology, Department of Medicine (A.R.C.H., N.D.W.), UC Irvine School of Medicine, University of California.

Background: Obesity is associated with an increased risk of heart failure (HF); however, how metabolic weight groups relate to HF risk, especially in postmenopausal women, has not been demonstrated.

Methods: We included 19 412 postmenopausal women ages 50 to 79 without cardiovascular disease from the Women's Health Initiative. Normal weight was defined as a body mass index ≥18.5 and <25 kg/m and waist circumference <88 cm and overweight/obesity as a body mass index ≥25 kg/m or waist circumference ≥88 cm. Metabolically healthy was based on <2 and unhealthy ≥2 cardiometabolic traits: triglycerides ≥150 mg/dL, systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥85 mm Hg or blood pressure medication, fasting glucose ≥100 mg/dL or diabetes medication, and HDL-C (high-density lipoprotein cholesterol) <50 mg/dL. Risk factor-adjusted Cox regression examined the hazard ratios (HRs) for incident hospitalized HF among metabolically healthy normal weight (reference), metabolically unhealthy normal weight, metabolically healthy overweight/obese, and metabolically unhealthy overweight/obese.

Results: Among our sample, 455 (2.34%) participants experienced HF hospitalizations over a mean follow-up time of 11.3±1.1 years. Compared with metabolically healthy normal weight individuals, HF risk was greater in metabolically unhealthy normal weight (HR, 1.66 [95% CI, 1.01-2.72], =0.045) and metabolically unhealthy overweight/obese individuals (HR, 1.95 [95% CI, 1.35-2.80], =0.0004), but not metabolically healthy overweight/obese individuals (HR, 1.15 [95% CI, 0.78-1.71], =0.48). Subdividing the overweight/obese into separate groups showed HRs for metabolically unhealthy obese of 2.62 (95% CI, 1.80-3.83; <0.0001) and metabolically healthy obese of 1.52 (95% CI, 0.98-2.35; =0.06).

Conclusions: Metabolically unhealthy overweight/obese and metabolically unhealthy normal weight are associated with an increased risk of HF in postmenopausal women.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007297DOI Listing
April 2021

Association of spontaneous abortion with all cause and cause specific premature mortality: prospective cohort study.

BMJ 2021 03 24;372:n530. Epub 2021 Mar 24.

Department of Nutrition, Harvard T H Chan School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA

Objective: To investigate the association of spontaneous abortion with the risk of all cause and cause specific premature mortality (death before the age of 70).

Design: Prospective cohort study.

Setting: The Nurses' Health Study II (1993-2017), United States.

Participants: 101 681 ever gravid female nurses participating in the Nurses' Health Study II.

Main Outcomes Measures: Lifetime occurrence of spontaneous abortion in pregnancies lasting less than 6 months, determined by biennial questionnaires. Hazard ratios and 95% confidence intervals for all cause and cause specific premature death according to the occurrence of spontaneous abortion, estimated with time dependent Cox proportional hazards models.

Results: During 24 years of follow-up, 2936 premature deaths were recorded, including 1346 deaths from cancer and 269 from cardiovascular disease. Crude all cause mortality rates were comparable for women with and without a history of spontaneous abortion (1.24 per 1000 person years in both groups) but were higher for women experiencing three or more spontaneous abortions (1.47 per 1000 person years) and for women reporting their first spontaneous abortion before the age of 24 (1.69 per 1000 person years). The corresponding age adjusted hazard ratios for all cause premature death during follow-up were 1.02 (95% confidence interval 0.94 to 1.11), 1.39 (1.03 to 1.86), and 1.27 (1.11 to 1.46), respectively. After adjusting for confounding factors and updated dietary and lifestyle factors, the occurrence of spontaneous abortion was associated with a hazard ratio of 1.19 (95% confidence interval 1.08 to 1.30) for premature mortality during follow-up. The association was stronger for recurrent spontaneous abortions (hazard ratio 1.59, 95% confidence interval 1.17 to 2.15 for three or more spontaneous abortions; 1.23, 1.00 to 1.50 for two; and 1.16, 1.05 to 1.28 for one compared with none), and for spontaneous abortions occurring early in a woman's reproductive life (1.32, 1.14 to 1.53 for age ≤23; 1.16, 1.01 to 1.33 for ages 24-29; and 1.12, 0.98 to 1.28 for age ≥30 compared with none). When cause specific mortality was evaluated, the association of spontaneous abortion with premature death was strongest for deaths from cardiovascular disease (1.48, 1.09 to 1.99). Spontaneous abortion was not related to premature death from cancer (1.08, 0.94 to 1.24).

Conclusions: Spontaneous abortion was associated with an increased risk of premature mortality, particularly death from cardiovascular disease.
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http://dx.doi.org/10.1136/bmj.n530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988453PMC
March 2021

Urinary Phthalate Biomarkers and Bone Mineral Density in Postmenopausal Women.

J Clin Endocrinol Metab 2021 Jun;106(7):e2567-e2579

Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA.

Context: Phthalates are endocrine-disrupting chemicals that could disrupt normal physiologic function, triggering detrimental impacts on bone.

Objective: We evaluated associations between urinary phthalate biomarkers and BMD in postmenopausal women participating in the prospective Women's Health Initiative (WHI).

Methods: We included WHI participants enrolled in the BMD substudy and selected for a nested case-control study of phthalates and breast cancer (N = 1255). We measured 13 phthalate biomarkers and creatinine in 2 to 3 urine samples per participant collected over 3 years, when all participants were cancer free. Total hip and femoral neck BMD were measured at baseline and year 3, concurrent with urine collection, via dual-energy x-ray absorptiometry. We fit multivariable generalized estimating equation models and linear mixed-effects models to estimate cross-sectional and longitudinal associations, respectively, with stratification on postmenopausal hormone therapy (HT) use.

Results: In cross-sectional analyses, mono-3-carboxypropyl phthalate and the sum of di-isobutyl phthalate metabolites were inversely associated with total hip BMD among HT nonusers, but not among HT users. Longitudinal analyses showed greater declines in total hip BMD among HT nonusers and with highest concentrations of mono-3-carboxyoctyl phthalate (-1.80%; 95% CI, -2.81% to -0.78%) or monocarboxynonyl phthalate (-1.84%; 95% CI, -2.80% to -0.89%); similar associations were observed with femoral neck BMD. Among HT users, phthalate biomarkers were not associated with total hip or femoral neck BMD change.

Conclusion: Certain phthalate biomarkers are associated with greater percentage decreases in total hip and femoral neck BMD. These findings suggest that phthalate exposure may have clinically important effects on BMD, and potentially fracture risk.
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http://dx.doi.org/10.1210/clinem/dgab189DOI Listing
June 2021

Prediagnostic Inflammation and Pancreatic Cancer Survival.

J Natl Cancer Inst 2021 Mar 19. Epub 2021 Mar 19.

Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.

Background: Chronic inflammation may promote initiation and progression of pancreatic cancer, but no studies have examined the association between inflammation in the period before diagnosis and pancreatic cancer survival.

Methods: We prospectively examined the association of prediagnostic plasma levels of C-reactive protein, interleukin-6, and tumor necrosis factor-α receptor 2 with survival among 492 participants from 5 large US prospective cohort studies who developed pancreatic cancer. Using an empirical dietary inflammatory pattern (EDIP) score, we evaluated whether long-term proinflammatory diets were associated with survival among 1153 patients from 2 of the 5 cohorts. Cox proportional hazards regression was used to estimate hazard ratios for death with adjustment for potential confounders.

Results: Higher prediagnostic levels of C-reactive protein, interleukin-6, and tumor necrosis factor-α receptor 2 were individually associated with reduced survival (Ptrend = .03, .01, and .04, respectively). Compared to patients with a combined inflammatory biomarker score of 0 (all 3 markers levels below medians), those with a score of 3 (all 3 markers levels above medians) had a hazard ratio for death of 1.57 (95% confidence interval = 1.16 to 2.12; Ptrend = .003), corresponding to median overall survival times of 8 versus 5 months. Patients consuming the most proinflammatory diets (EDIP quartile 4) in the prediagnostic period had a hazard ratio for death of 1.34 (95% confidence interval = 1.13 to 1.59; Ptrend = .01), compared to those consuming the least proinflammatory diets (EDIP quartile 1).

Conclusion: Prediagnostic levels of inflammatory biomarkers and long-term proinflammatory diets were inversely associated with pancreatic cancer survival.
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http://dx.doi.org/10.1093/jnci/djab040DOI Listing
March 2021

Effect of Marine Omega-3 Fatty Acid and Vitamin D Supplementation on Incident Atrial Fibrillation: A Randomized Clinical Trial.

JAMA 2021 03;325(11):1061-1073

Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Importance: Atrial fibrillation (AF) is the most common heart rhythm disturbance, continues to increase in incidence, and results in significant morbidity and mortality. The marine omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamin D have been reported to have both benefits and risks with respect to incident AF, but large-scale, long-term randomized trial data are lacking.

Objective: To test the effects of long-term administration of marine omega-3 fatty acids and vitamin D on incident AF.

Design, Setting, And Participants: An ancillary study of a 2 × 2 factorial randomized clinical trial involving 25 119 women and men aged 50 years or older without prior cardiovascular disease, cancer, or AF. Participants were recruited directly by mail between November 2011 and March 2014 from all 50 US states and were followed up until December 31, 2017.

Interventions: Participants were randomized to receive EPA-DHA (460 mg/d of EPA and 380 mg/d of DHA) and vitamin D3 (2000 IU/d) (n = 6272 analyzed); EPA-DHA and placebo (n = 6270 analyzed); vitamin D3 and placebo (n = 6281 analyzed); or 2 placebos (n = 6296 analyzed).

Main Outcomes And Measures: The primary outcome was incident AF confirmed by medical record review.

Results: Among the 25 119 participants who were randomized and included in the analysis (mean age, 66.7 years; 50.8% women), 24 127 (96.1%) completed the trial. Over a median 5.3 years of treatment and follow-up, the primary end point of incident AF occurred in 900 participants (3.6% of study population). For the EPA-DHA vs placebo comparison, incident AF events occurred in 469 (3.7%) vs 431 (3.4%) participants, respectively (hazard ratio, 1.09; 95% CI, 0.96-1.24; P = .19). For the vitamin D3 vs placebo comparison, incident AF events occurred in 469 (3.7%) vs 431 (3.4%) participants, respectively (hazard ratio, 1.09; 95% CI, 0.96-1.25; P = .19). There was no evidence for interaction between the 2 study agents (P = .39).

Conclusions And Relevance: Among adults aged 50 years or older, treatment with EPA-DHA or vitamin D3, compared with placebo, resulted in no significant difference in the risk of incident AF over a median follow-up of more than 5 years. The findings do not support the use of either agent for the primary prevention of incident AF.

Trial Registration: ClinicalTrials.gov Identifiers: NCT02178410; NCT01169259.
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http://dx.doi.org/10.1001/jama.2021.1489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967086PMC
March 2021

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.

Am J Hum Genet 2021 04 12;108(4):564-582. Epub 2021 Mar 12.

The Charles R. Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.
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http://dx.doi.org/10.1016/j.ajhg.2021.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059339PMC
April 2021

Effects of menopausal hormone therapy on erythrocyte n-3 and n-6 PUFA concentrations in the Women's Health Initiative randomized trial.

Am J Clin Nutr 2021 06;113(6):1700-1706

Department of Epidemiology, College of Public Health, Iowa City, IA, USA.

Background: The factors other than dietary intake that determine tissue concentrations of EPA and DHA remain obscure. Prior studies suggested that, in women, endogenous estrogen may accelerate synthesis of DHA from ɑ-linolenic acid (ALA), but the effects of exogenous estrogen on RBC n-3 (ɷ-3) PUFA concentrations are unknown.

Objective: We tested the hypothesis that menopausal hormone therapy (HT) would increase RBC n-3 PUFA concentrations.

Methods: Postmenopausal women (ages 50-79 y) were assigned to HT or placebo in the Women's Health Initiative (WHI) randomized trial. The present analyses included a subset of 1170 women (ages 65-79 y) who had RBC PUFA concentrations measured at baseline and at 1 y as participants in the WHI Memory Study. HT included conjugated equine estrogens (E) alone for women without a uterus (n = 560) and E plus medroxyprogesterone acetate (P) for those with an intact uterus (n = 610). RBC n-3 and n-6 (ɷ-6) PUFAs were quantified.

Results: Effects of E alone and E+P on PUFA profiles were similar and were thus combined in the analyses. Relative to the changes in the placebo group after 1 y of HT, docosapentaenoic acid (DPA; n-3) concentrations decreased by 10% (95% CI: 7.3%, 12.5%), whereas DHA increased by 11% (95% CI: 7.4%, 13.9%) in the HT group. Like DHA, DPA n-6 increased by 13% from baseline (95% CI: 10.0%, 20.3%), whereas linoleic acid decreased by 2.0% (95% CI: 1.0%, 4.1%; P values at least <0.01 for all). EPA and arachidonic acid concentrations were unchanged.

Conclusions: HT increased RBC concentrations of the terminal n-3 and n-6 PUFAs (DHA and DPA n-6). These findings are consistent with an estrogen-induced increase in DHA and DPA n-6 synthesis, which is consistent with an upregulation of fatty acid elongases and/or desaturases in the PUFA synthetic pathway. The clinical implications of these changes require further study. The Women's Health Initiative Memory Study is registered at clinicaltrials.gov as NCT00685009. Note that the data presented here were not planned as part of the original trial, and therefore are to be considered exploratory.
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http://dx.doi.org/10.1093/ajcn/nqaa443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168349PMC
June 2021

Weight and mortality: why body composition matters.

Am J Clin Nutr 2021 03;113(3):493-494

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

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http://dx.doi.org/10.1093/ajcn/nqaa409DOI Listing
March 2021

Quality of Plant-Based Diet and Risk of Total, Ischemic, and Hemorrhagic Stroke.

Neurology 2021 04 10;96(15):e1940-e1953. Epub 2021 Mar 10.

From the Department of Nutrition (M.Y.B., Z.S., F.W., Y.L., E.B.R., W.C.W., F.B.H.), Department of Epidemiology (J.E.M., E.B.R., W.C.W., F.B.H.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Metabolic Medicine (M.Y.B.), Osaka University Graduate School of Medicine, Japan; Channing Division of Network Medicine (J.E.M., W.C.W., F.B.H.), Department of Medicine, Division of Preventive Medicine (J.E.M.), Department of Medicine, and Division of Women's Health (K.M.R.), Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.

Objective: To determine whether a healthful plant-based diet is related to lower stroke risk, we examined the associations of plant-based diet quality with risk of total, ischemic, and hemorrhagic stroke.

Methods: The participants were 73,890 women in Nurses' Health Study (NHS; 1984-2016), 92,352 women in NHSII (1991-2017), and 43,266 men in Health Professionals Follow-Up Study (1986-2012) without cardiovascular disease and cancer at baseline. Plant-based diet quality was evaluated by the overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI). Participants who reported that their meat and/or fish intakes were 0 or <1 serving per month were categorized as vegetarians, and others were classified as nonvegetarians. Strokes with available medical records were subtyped as ischemic or hemorrhagic.

Results: During the follow-up, 6,241 total stroke cases (including 3,015 ischemic and 853 hemorrhagic strokes) were documented. Compared to participants with the lowest PDIs, among participants with the highest PDIs, the hazard ratios (HRs) for total stroke were 0.94 (95% confidence interval 0.86-1.03) for PDI, 0.90 (0.83-0.98) for hPDI, and 1.05 (0.96-1.15) for uPDI. Participants in the highest hPDI showed marginally lower HR for ischemic stroke (0.92 [0.82-1.04]) and no consistent associations for hemorrhagic stroke. We observed no association between a vegetarian diet and total stroke (1.00 [0.76-1.32]), although the number of cases was small.

Conclusion: Lower risk of total stroke was observed by those who adhered to a healthful plant-based diet.
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http://dx.doi.org/10.1212/WNL.0000000000011713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166423PMC
April 2021