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BACKGROUND: Although gestational diabetes mellitus and delivering high-birthweight infants are known to predict a higher risk of future type 2 diabetes mellitus, the association of hypertensive disorders of pregnancy and other adverse pregnancy outcomes with type 2 diabetes mellitus is not well established. OBJECTIVE: This study aimed to examine the associations between different types of adverse pregnancy outcomes and incident type 2 diabetes mellitus among postmenopausal women. STUDY DESIGN: The Womens Health Initiative, a nationwide cohort of postmenopausal women, collected self-reported history of adverse pregnancy outcomes, including gestational diabetes mellitus, hypertensive disorders of pregnancy, preterm birth, and delivering low- birthweight (4500 g) infants. Participants were followed up annually for self-reported incident type 2 diabetes mellitus treated with medication from baseline (1993-1998) to March 2021. This study used logistic regression to examine the associations of any and individual adverse pregnancy outcomes with diabetes mellitus. Stratified analyses were performed to assess effect modification by body mass index, race and ethnicity, education, parity, breastfeeding, and age at first birth. RESULTS: This analysis included 49,717 women without a history of diabetes mellitus at enrollment who had a least 1 pregnancy and responded to the questionnaire about adverse pregnancy outcomes. After adjusting for body mass index, demographic, lifestyle, and reproductive factors, gestational diabetes mellitus (odds ratio, 2.26; 95% confidence interval, 1.94-2.63), high birthweight (odds ratio, 1.30; 95% confidence interval, 1.18-1.44), and hypertensive disorders of pregnancy (odds ratio, 1.18; 95% confidence interval, 1.08-1.30) were independently associated with higher odds of type 2 diabetes mellitus, whereas preterm birth and low birthweight were not associated with diabetes mellitus risk. A history of ≥2 adverse pregnancy outcomes was associated with higher odds of type 2 diabetes mellitus (odds ratio, 1.55; 95% confidence interval, 1.28-1.88). This study further observed higher odds of type 2 diabetes mellitus (odds ratio, 3.69; 95% confidence interval, 2.38-5.70) among women with a history of both gestational diabetes mellitus and hypertensive disorders of pregnancy than those without any adverse pregnancy outcomes. CONCLUSION: Postmenopausal women with a history of gestational diabetes mellitus, those delivering high-birthweight infants, or those with hypertensive disorders of pregnancy are at risk of future type 2 diabetes mellitus. In addition, women with ≥2 conditions had an augmented risk and might be prioritized for screening and prevention efforts for type 2 diabetes mellitus.

The WHI (Womens Health Initiative) enrolled 161,808 racially and ethnically diverse postmenopausal women, ages 50-79 years, from 1993 to 1998 at 40 clinical centers across the United States. In its clinical trial component, WHI evaluated 3 randomized interventions (menopausal hormone therapy; diet modification; and calcium/vitamin D supplementation) for the primary prevention of major chronic diseases, including cardiovascular disease, in older women. In the WHI observational study, numerous clinical, behavioral, and social factors have been evaluated as predictors of incident chronic disease and mortality. Although the original interventions have been completed, the WHI data and biomarker resources continue to be leveraged and expanded through ancillary studies to yield novel insights regarding cardiovascular disease prevention and healthy aging in women.

BackgroundColor groups of fruits and vegetables (FV) are part of a healthy diet, but evidence for an association with cardiometabolic outcomes is inconsistent.ObjectiveTo examine the association between intake of FV of different colors with incident diabetes and cardiometabolic risk biomarkers among U.S. Hispanics/Latinos.Subjects/methodsWe used data from 9206 adults ages 18-74 years who were free of diabetes at baseline (2008-2011) and had follow-up data at visit 2 (2014-2017) in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a multicenter, prospective cohort study of self-identified Hispanics/Latinos. Dietary intake was assessed using two 24 h recalls at baseline. FV were categorized into five color groups: green, white, yellow/orange, red/purple, and uncategorized. Diabetes was defined based on laboratory measures and self-reported antihyperglycemic medication. We used survey logistic regression models to evaluate the association between FV color groups and incident diabetes and survey linear regression models to evaluate the association of FV color groups with cardiometabolic risk biomarkers at visit 2.ResultsDuring ~6 years of follow-up, 970 incident cases of diabetes were documented. The red/purple FV color group was the least consumed (0.21 servings/day), whereas white FV were the most consumed (0.92 servings/day). For each serving of total FV intake, body mass index (BMI) was lower by 0.24% (p = 0.03) and insulin by 0.69% (p = 0.03). For each serving of red/purple FV intake, HDL was 1.59% higher (p = 0.04). For each serving of white FV intake (with potato), post-OGTT was 0.83% lower (p = 0.04) and triglycerides 1.43% lower (p = 0.04). There was no association between FV intake and incident diabetes.ConclusionsSpecific FV colors were associated with cardiometabolic benefits though the associations were of relatively small magnitudes. Dietary recommendations could consider varying colors of FV intake, especially white and red/purple color groups, for a healthy diet.

ImportanceSome prior evidence suggests that adverse pregnancy outcomes (APOs) may be associated with heart failure (HF). Identifying unique factors associated with the risk of HF and studying HF subtypes are important next steps.ObjectiveTo investigate the association of APOs with incident HF overall and stratified by HF subtype (preserved vs reduced ejection fraction) among postmenopausal women in the Women's Health Initiative (WHI).Design, setting, and participantsIn 2017, an APO history survey was administered in the WHI study, a large multiethnic cohort of postmenopausal women. The associations of 5 APOs (gestational diabetes, hypertensive disorders of pregnancy [HDP], low birth weight, high birth weight, and preterm delivery) with incident adjudicated HF were analyzed. In this cohort study, the association of each APO with HF was assessed using logistic regression models and with HF subtypes using multinomial regression, adjusting for age, sociodemographic characteristics, smoking, randomization status, reproductive history, and other APOs. Data analysis was performed from January 2020 to September 2021.ExposuresAPOs (gestational diabetes, HDP, low birth weight, high birth weight, and preterm delivery).Main outcomes and measuresAll confirmed cases of women hospitalized with HF and HF subtype were adjudicated by trained physicians using standardized methods.ResultsOf 10 292 women (median [IQR] age, 60 [55-64] years), 3185 (31.0%) reported 1 or more APO and 336 (3.3%) had a diagnosis of HF. Women with a history of any APO had a higher prevalence of hypertension, diabetes, coronary heart disease, or smoking. Of the APOs studied, only HDP was significantly associated with HF with a fully adjusted odds ratio (OR) of 1.75 (95% CI, 1.22-2.50), and with HF with preserved ejection fraction in fully adjusted models (OR, 2.06; 95% CI, 1.29-3.27). In mediation analyses, hypertension explained 24% (95% CI, 12%-73%), coronary heart disease 23% (95% CI, 11%-68%), and body mass index 20% (95% CI, 10%-64%) of the association between HDP and HF.Conclusions and relevanceIn this large cohort of postmenopausal women, HDP was independently associated with incident HF, particularly HF with preserved ejection fraction, and this association was mediated by subsequent hypertension, coronary heart disease, and obesity. These findings suggest that monitoring and modifying these factors early in women presenting with HDP may be associated with reduced long-term risk of HF.

The potential role of nutritional factors in the development of peripheral arterial disease (PAD) remains poorlyunderstood. We evaluated multiple recommended eating patterns as reflected by predefined diet quality indices in relation tolong-term risk of PAD. We included 138 506 US postmenopausal women in the Women’s Health Initiative who had no knownPAD at baseline (1993–1998). Four diet quality indices, including alternate Mediterranean diet index, alternate HealthyEating Index-2010, Dietary Approaches to Stop Hypertension diet index, and Healthy Eating Index-2015, were derivedusing dietary information collected by a validated food frequency questionnaire at baseline. Incident cases of symptomaticPAD in the lower extremities were ascertained and adjudicated through March 2019 via medical record review. During amedian 18.6 years of follow-up, 1036 incident PAD cases were identified. After multivariable adjustment, all diet qualityscores were significantly and inversely associated with 21% (for alternate Healthy Eating Index 2010) to 34% (for DietaryApproaches to Stop Hypertension index) lower risk of PAD when comparing the highest with the lowest quartiles (all P-fortrend values ≤0.010). Among contributing food groups and nutrients, intakes of legumes, dietary fiber, and vegetable proteinwere associated lower risk of PAD, while intakes of unprocessed red meat, processed meat, and regular soft drinks wereassociated with higher risk. In a broad sample of US postmenopausal women, adhering to different recommended eatingpatterns is associated with lower risk of PAD. Our findings suggest that current clinical and public health strategies thatrecommend healthful eating patterns may also be applicable to PAD prevention. (

BackgroundThe potential cardiovascular impact of dietary cholesterol intake has been actively debated for decades.ObjectivesWe aimed to evaluate associations of dietary cholesterol and egg intakes with incident cardiovascular disease (CVD) and all-cause and cause-specific mortality.MethodsWe included 96,831 US postmenopausal women aged 50-79 y without known CVD or cancer during baseline enrollment (1993-1998) of the Women's Health Initiative. Dietary information was collected using a validated FFQ. Incident CVD [i.e., ischemic heart disease (IHD) and stroke] and all-cause and cause-specific mortality were ascertained and adjudicated through February 2018.ResultsA total of 9808 incident CVD cases and 19,508 all-cause deaths occurred during a median follow-up of 17.8 y and 18.9 y, respectively. After multivariable adjustment for traditional risk factors and key dietary nutrients including dietary saturated fat, there were modest associations of dietary cholesterol intake with incident CVD (HRQ5versusQ1: 1.12; 95% CI: 1.03, 1.21; P-trend  0.05). Higher egg consumption was also associated with modestly higher risk of incident CVD (P-trend = 0.004) and all-cause mortality (P-trend

BackgroundWomen without cardiovascular disease (CVD) or hypertension at baseline assigned to intervention in the Women's Health Initiative Dietary Modification (DM) trial experienced 30% lower risk of coronary heart disease (CHD), whereas results in women with hypertension or prior CVD could have been confounded by postrandomization use of statins.ObjectivesIntervention participants reported various self-selected changes to achieve the 20% total fat goals. Reviewed are intervention compared with comparison group HRs for CHD, stroke, and total CVD in relation to specific dietary changes in normotensive participants.MethodsDietary change was assessed by comparing baseline with year 1 FFQ data in women (n = 10,371) without hypertension or CVD at baseline with intake of total fat above the median to minimize biases due to use of the FFQ in trial eligibility screening.ResultsIntervention participants self-reported compensating reduced energy intake from total fat by increasing carbohydrate and protein. Specifically they increased plant protein, with those in the upper quartile (increased total protein by ≥3.3% of energy) having a CHD HR of 0.39 (95% CI: 0.22, 0.71), compared with 0.92 (95% CI: 0.57, 1.48) for those in the lower quartile of change (decreased total protein ≥0.6% of energy), with P-trend of 0.04. CHD HR did not vary significantly with change in percentage energy from carbohydrate, and stroke HR did not vary significantly with any macronutrient changes. Scores reflecting adherence to recommended dietary patterns including the Dietary Approaches to Stop Hypertension Trial and the Healthy Eating Index showed favorable changes in the intervention group.ConclusionsIntervention group total fat reduction replaced with increased carbohydrate and some protein, especially plant-based protein, was related to lower CHD risk in normotensive women without CVD who reported high baseline total fat intake. This trial was registered at clinicaltrials.gov as NCT00000611. Link to the WHI trial protocol: https://www.whi.org/about/SitePages/Dietary%20Trial.aspx.

RationaleCocoa and its major flavanol component, epicatechin, have therapeutic properties that may improve limb perfusion and increase calf muscle mitochondrial activity in people with lower extremity peripheral artery disease (PAD).ObjectiveIn a phase II randomized clinical trial, to assess whether 6 months of cocoa improved walking performance in people with PAD, compared with placebo.Methods and resultsSix-month double-blind, randomized clinical trial in which participants with PAD were randomized to either cocoa beverage versus placebo beverage. The cocoa beverage contained 15 g of cocoa and 75 mg of epicatechin daily. The identical appearing placebo contained neither cocoa nor epicatechin. The 2 primary outcomes were 6-month change in 6-minute walk distance measured 2.5 hours after a study beverage at 6-month follow-up and 24 hours after a study beverage at 6-month follow-up, respectively. A 1-sided P

Background: Postmenopausal women represent the highest population-based burden of cardiovascular disease, including sudden cardiac death (SCD). Our understanding of the etiology and risk factors contributing to fatal coronary heart disease (CHD) and SCD, particularly among women, is limited. This study examines the association between dietary magnesium intake and fatal CHD and SCD. Materials and Methods: We examined 153,569 postmenopausal women who participated in the Women's Health Initiative recruited between 1993 and 1998. Magnesium intake at baseline was assessed using a validated food frequency questionnaire, adjusting for energy via the residual method. Fatal CHD and SCD were identified over an average follow-up of 10.5 years. Results: For every standard deviation increase in magnesium intake, there was statistically significant risk reduction, after adjustment for confounders, of 7% for fatal CHD (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.89-0.97), and 18% risk reduction for SCD (HR 0.82, 95% CI 0.58-1.15) the latter of which did not reach statistical significance. In age-adjusted quartile analysis, women with the lowest magnesium intake (189 mg/day) had the greatest risk for fatal CHD (HR 1.54, 95% CI 1.40-1.69) and SCD (HR 1.70, 95% CI 0.94-3.07). This association was attenuated in the fully adjusted model, with HRs of 1.19 (95% CI 1.06-1.34) for CHD and 1.24 (95% CI 0.58-2.65) for SCD for the lowest quartile of magnesium intake. Conclusions: This study provides evidence of a potential inverse association between dietary magnesium and fatal CHD and a trend of magnesium with SCD in postmenopausal women. Future studies should confirm this association and consider clinical trials to test whether magnesium supplementation could reduce fatal CHD in high-risk individuals.

BACKGROUND:Earlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are associated with adult breast density, which could mediate the increased risk. METHODS:From 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006-2008, 182 participants then aged 25-29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV. RESULTS:The mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2-86.1. Age at thelarche was negatively associated with %DBV (p trend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (p trend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2-26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9-17.5%)). CONCLUSIONS:Our results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk.

Background and aimsThe association of fatty acids with coronary heart disease (CHD) has been examined, mainly through dietary measurements, and has generated inconsistent results due to measurement error. Large observational studies and randomized controlled trials have shown that plasma phospholipid fatty acids (PL-FA), especially those less likely to be endogenously synthesized, are good biomarkers of dietary fatty acids. Thus, PL-FA profiles may better predict CHD risk with less measurement error.MethodsWe performed a matched case-control study of 2428 postmenopausal women nested in the Women's Health Initiative Observational Study. Plasma PL-FA were measured using gas chromatography and expressed as molar percentage (moL %). Multivariable conditional logistic regression was used to calculate odds ratios (95% CIs) for CHD associated with 1 moL % change in PL-FA.ResultsHigher plasma PL long-chain saturated fatty acids (SFA) were associated with increased CHD risk, while higher n-3 polyunsaturated fatty acids (PUFA) were associated with decreased risk. No significant associations were observed for very-long-chain SFA, monounsaturated fatty acids (MUFA), PUFA n-6 or trans fatty acids (TFA). Substituting 1 moL % PUFA n-6 or TFA with an equivalent proportion of PUFA n-3 were associated with lower CHD risk.ConclusionsHigher plasma PL long-chain SFA and lower PUFA n-3 were associated with increased CHD risk. A change in diet by limiting foods that are associated with plasma PL long-chain SFA and TFA while enhancing foods high in PUFA n-3 may be beneficial in CHD among postmenopausal women.

Women with history of pregnancy loss (PL) have higher burden of cardiovascular disease (CVD) later in life, yet it is unclear whether this is attributable to an association with established CVD risk factors (RFs). We examined whether PL is associated with CVD RFs and biomarkers in parous postmenopausal women in the Women's Health Initiative, and whether the association between PL and CVD RFs accounted for the association between PL and incident CVD. Linear and logistic regressions were used to estimate associations between baseline history of PL and CVD RFs. Cox proportional hazards regression models were used to estimate the associations between baseline history of PL and incident CVD after adjustment for baseline RFs. Of 79,121 women, 27,272 (35%) had experienced PL. History of PL was associated with higher body mass index (p < 0.0001), hypertension (p < 0.0001), diabetes (p = 0.003), depression (p < 0.0001), and lower income (p < 0.0001), physical activity (p = 0.01), poorer diet (p < 0.0001), smoking (p < 0.0001), and alcohol use (p < 0.0001). After adjustment for CVD RFs, PL was significantly associated with incident CVD over mean follow up of 16 years (hazard ratio 1.11, 95% confidence interval 1.06 to 1.16). In conclusion, several CVD RFs are associated with PL, but they do not entirely account for the association between PL and incident CVD.

BackgroundUnderstanding the social lives of South Asian immigrants in the United States (U.S) and their influence on health can inform interpersonal and community-level health interventions for this growing community. This paper describe the rationale, survey design, measurement, and network properties of 700 South Asian individuals in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) social networks ancillary study.MethodsMASALA is a community-based cohort, established in 2010, to understand risk factors for cardiovascular disease among South Asians living in the U.S. Survey data collection on personal social networks occurred between 2014 and 2017. Network measurements included size, composition, density, and organizational affiliations. Data on participants' self-rated health and social support functions and health-related discussions among network members were also collected.ResultsParticipants' age ranged from 44 to 84 (average 59 years), and 57% were men. South Asians had large (size=5.6, SD=2.6), kin-centered (proportion kin=0.71, SD=0.28), and dense networks. Affiliation with religious and spiritual organizations was perceived as beneficial to health. Emotional closeness with network members was positively associated with participants' self-rated health (p-value

PurposeCarbohydrate intake increases postprandial insulin secretion and may affect breast density, a strong risk factor for breast cancer, early in life. We examined associations of adolescent and early adulthood intakes of total carbohydrates, glycemic index/load, fiber, and simple sugars with breast density among 182 young women.MethodsDiet was assessed using three 24-h recalls at each of five Dietary Intervention Study in Children (DISC) clinic visits when participants were age 10-19 years and at the DISC06 Follow-Up Study clinic visit when participants were age 25-29 years. Associations between energy-adjusted carbohydrates and MRI-measured percent dense breast volume (%DBV) and absolute dense breast volume (ADBV) at 25-29 years were quantified using multivariable-adjusted mixed-effects linear models.ResultsAdolescent sucrose intakes and premenarcheal total carbohydrates intakes were modestly associated with higher %DBV (mean %DBVQ1 vs Q4, 16.6 vs 23.5% for sucrose; and 17.2 vs 22.3% for premenarcheal total carbohydrates, all Ptrend ≤ 0.02), but not with ADBV. However, adolescent intakes of fiber and fructose were not associated with %DBV and ADBV. Early adulthood intakes of total carbohydrates, glycemic index/load, fiber, and simple sugars were not associated with %DBV and ADBV.ConclusionsInsulinemic carbohydrate diet during puberty may be associated with adulthood breast density, but our findings need replication in larger studies. Clinical Trials Registration ClinicalTrials.gov Identifier, NCT00458588 April 9, 2007; NCT00000459 October 27, 1999.

Studies of the associations of sodium and potassium intakes with cardiovascular disease incidence often rely on self-reported dietary data. In the present study, self-reported intakes from postmenopausal women at 40 participating US clinical centers are calibrated using 24-hour urinary excretion measures in cohorts from the Women's Health Initiative, with follow-up from 1993 to 2010. The incidence of hypertension was positively related to (calibrated) sodium intake and to the ratio of sodium to potassium. The sodium-to-potassium ratio was associated with cardiovascular disease incidence during an average follow-up period of 12 years. The estimated hazard ratio for a 20% increase in the sodium-to-potassium ratio was 1.13 (95% confidence interval (CI): 1.04, 1.22) for coronary heart disease, 1.20 (95% CI: 1.01, 1.42) for heart failure, and 1.11 (95% CI: 1.04, 1.19) for a composite cardiovascular disease outcome. The association with total stroke was not significant, but it was positive for ischemic stroke and inverse for hemorrhagic stroke. Aside from hemorrhagic stroke, corresponding associations of cardiovascular disease with sodium and potassium jointly were positive for sodium and inverse for potassium, although some were not statistically significant. Specifically, for coronary heart disease, the hazard ratios for 20% increases were 1.11 (95% CI: 0.95, 1.30) for sodium and 0.85 (95% CI: 0.73, 0.99) for potassium; and corresponding values for heart failure were 1.36 (95% CI: 1.02, 1.82) for sodium and 0.90 (95% CI: 0.69, 1.18) for potassium.