INTRODUCTION:Understanding the risk factors that associate with early cognitive decline in Alzheimer's disease (AD) is important to identify high-risk individuals and initiate early intervention. Existing studies show that APOEε4, systemic inflammation, and diabetes may play roles in cognitive decline, but the extent to which these factors interact with each other remains unclear. Our objective was to examine the main effects and higher-order interactions between APOEε4, high sensitivity-C-reactive protein (hs-CRP) as a measure of systemic inflammation, and diabetes on domain-specific measures of cognitive function in two ancillary studies of post-menopausal women from the Women's Health Initiative (WHI). METHOD:We identified 2979 cognitively unimpaired women from the WHI Epidemiology of Cognitive Health Outcomes and the WHI Memory Study of Younger Women with cognitive follow-up of up to 13 years. Linear mixed-effects models examined the main and interactive effects of APOEε4, hs-CRP, and diabetes on longitudinal changes in the personal communication for Cognitive Status-modified Test (TICS-m), East Boston Memory Test (immediate and delayed; EBMT), Oral Trail Making Test (OTMT), Verbal Fluency Test (VF-A), Digit Span Test Backwards (DST-backward), and the California Verbal Learning Test (CVLT). All models were adjusted for baseline age, education, body mass index, the WHI randomization arm, and the cohort. RESULTS:APOEε4 carriers had steeper cognitive decline in TICS-m, EBMT (immediate and delayed), VF-A, and CVLT scores relative to non-carriers. Higher levels of hs-CRP were associated with steeper cognitive decline in the DST-backwards scores. There was no association of diabetes or any evidence of interactive effects on cognitive decline in our study. CONCLUSIONS:In this large longitudinal study of post-menopausal women, our findings support the hypothesis that genetic risk and systemic inflammation independently influence cognitive decline, but there was no evidence of synergistic effects in postmenopausal women. Further research is needed to elucidate the mechanistic pathways underlying these associations with cognitive decline.

OBJECTIVE:To evaluate whether effects of oral hormone therapy (HT) on risks of venous and arterial vascular events differ by baseline statin or aspirin use. METHODS:We performed time-to-event analysis using data from the Women's Health Initiative menopausal HT randomized trials to assess risk of thrombotic events. Women were randomized to oral conjugated equine estrogens (CEEs) alone or placebo among women with prior hysterectomy (n = 10,739), and CEE with medroxyprogesterone acetate (MPA) or placebo among women with an intact uterus (n = 16,608), stratified by baseline personal use of statins and aspirin. We evaluated risk of prespecified, adjudicated thrombotic events, including coronary heart disease, stroke, venous thromboembolism, and/or composite major adverse cardiovascular events, at 2 and 5 years. RESULTS:Baseline statin use (n = 827 in CEE-alone trial; n = 1,115 in CEE+MPA trial) or aspirin use (n = 2,212; n = 3,431) was limited. At 5-year follow-up, coronary heart disease risk for CEE-alone versus placebo was hazard ratio (HR) = 0.81 (95% CI: 0.44-1.49) in statin users, similar to nonusers, HR = 1.07 (95% CI: 0.82-1.40). For CEE+MPA, there was also no difference by statin use, HR = 1.02 (95% CI: 0.55-1.89) and HR = 1.47 (95% CI: 1.13-1.90), respectively. Neither statin nor aspirin exposure significantly modified effects of HT on any arterial or venous thrombotic outcome at 2 or 5 years. CONCLUSIONS:In this secondary randomized clinical trial analysis, neither statins nor aspirin significantly modified effects of oral HT on key arterial or venous thrombotic outcomes at 2 or 5 years. Results, however, may be underpowered given low baseline exposure prevalence for both statins and aspirin.

INTRODUCTION:The brains of female mammals evolved to undergo structural and functional changes during pregnancy and lactation, equipping them for motherhood. However, long-term cognitive health implications of these adaptations in women are poorly understood. METHODS:In the Women's Health Initiative (WHI) Memory Study (WHIMS; n = 7427) and WHI Study of Cognitive Aging (WHISCA; n = 2304), postmenopausal women completed reproductive history interviews, annual global cognitive assessment from mean age 70 for up to 13 years, and multi-domain cognitive testing for up to 8 years. RESULTS:Each additional month pregnant was associated with higher scores of global cognition. Each additional month of breastfeeding corresponded to higher scores of global cognition, verbal memory, and visual memory. We observed equivalent results for binary formulations of gravidity and breastfeeding. DISCUSSION:Low rates of fertility and breastfeeding may have implications for postmenopausal cognitive health at the population level. Next steps include examining mechanisms linking women's reproductive history with postmenopausal cognitive health. HIGHLIGHTS:Motherhood may leave an enduring mark on women's brains, shaping cognitive health. Over 7000 women were assessed annually from approximately age 70 for up to 13 years. Ever being pregnant and cumulative time pregnant were linked with better cognition. Ever having breastfed and more time breastfeeding were linked with better cognition. These results imply that declining fertility may affect cognitive aging in future generations.

BACKGROUND AND OBJECTIVES:Migraine is a known risk factor for stroke in women of reproductive age, although its relationship with stroke among postmenopausal women remains unclear. We assessed the association between migraine history and incident stroke in a sample of postmenopausal women. METHODS:We included women enrolled in the Women's Health Initiative, a large US longitudinal cohort study of postmenopausal women, and excluded those with previous stroke or those with missing data on key variables. The primary exposure was self-reported, physician-diagnosed migraine at baseline, and the primary outcome was incident stroke (total, ischemic, or hemorrhagic). Multivariable Cox proportional hazards models were used to test the cause-specific hazard ratios (HRs) between migraine history and total, ischemic (overall and by subtype), and hemorrhagic stroke, sequentially adjusted for age, traditional cardiovascular risk factors, and female-specific risk factors (age at menopause, age at menarche, menstrual irregularity, presence of vasomotor symptoms, parity, breastfeeding, and use of menopausal hormone therapy). We then quantified the association between a history of migraine and total stroke by age at baseline (in 5-year age groups) using multivariable models. Data on the presence of aura and migraine frequency were not available. RESULTS:Participants (N = 130,277) had a median age of 63 years (interquartile range [IQR] 57-69). A total of 5,743 incident stroke events occurred over a median follow-up period of 19.9 years (IQR 9.1-25). In multivariable models, there was no significant association between migraine history and total stroke (HR 1.07, 95% CI 0.99-1.17), but there was a significant association between migraine history and ischemic stroke (HR 1.12, 95% CI 1.02-1.23). In planned secondary analysis of ischemic subtypes, the associations were most pronounced in the cardioembolic (HR 1.17, 95% CI 0.98-1.39) and undetermined (HR 1.14, 95% CI 0.98-1.33) categories. Migraine was not associated with hemorrhagic stroke (HR 0.85, 95% CI 0.67-1.09). Risk did not differ significantly by age group. DISCUSSION:Over 20 years of follow-up, postmenopausal women with a history of migraine had a higher risk of ischemic stroke, but not total or hemorrhagic stroke. Along with other factors, a history of migraine should be considered a risk marker when assessing ischemic stroke risk after menopause.

Racial disparities in all-cause mortality after breast cancer (BC) have been documented. While elevated risk of BC mortality experienced by Black women is clear, it is unclear the relative contribution of cardiovascular disease (CVD) mortality to the survival disparity in Black women. This analysis from the Women’s Health Initiative (WHI) included 8,410 women diagnosed with invasive BC during follow-up. Cardiovascular (CV) events were defined as adjudicated myocardial infarction, heart failure, or stroke. Cause of death was determined through adjudication by medical chart review, ICD codes, death certificate, and/or autopsy report. 10-year cumulative incidence rates were calculated for CV events, CVD mortality, and BC mortality, stratified by race. Sub-distribution hazards ratios (sHR) were calculated using Fine and Gray models to account for competing risks. In BC survivors (mean age = 70.9 years, median follow-up = 15.1 years), 8.5

Supplementary Table 1 shows population characteristics among current MHT users; Supplementary Table 2 shows relative proportions of adrenal androgens and estrogens; Supplementary Table 3-6 show the associations with adjustment for waist-to-hip ratio; Supplementary Table 7-10 show the associations stratified by current BMI

Objective:To assess atherogenic apolipoprotein lipids and markers of vascular function in pregnancy after prepregnancy weight loss. Design:Retrospective cohort study. Subjects:The weight loss cohort included pregnant women who achieved prepregnancy weight loss, and the weight gain cohort consisted of those who gained weight before pregnancy. All patients became pregnant after enrolling in the randomized clinical trial "Improving Reproductive Fitness Through Pretreatment with Lifestyle Modification in Obese Women with Unexplained Infertility" and delivered a single live birth at ≥36 weeks of gestation. Exposure:Prepregnancy weight loss. Main Outcome Measures:Apolipoprotein lipid levels. Results:Prepregnancy weight loss was associated with lower atherogenic apolipoprotein lipid levels during pregnancy and better indicators of vascular function. Conclusion:Our findings suggest that encouraging prepregnancy weight loss in obese women leads to improved vascular function during pregnancy. Prepregnancy weight loss has significant implications for healthcare professionals because it underscores the potential benefits of weight loss interventions in reducing the risk of cardiovascular disease for women who become pregnant.

OBJECTIVE: To assess the long-term changes in cardiovascular biomarkers during the WHI (Women's Health Initiative) hormone therapy (HT) clinical trials of conjugated equine estrogens (CEE) alone and CEE plus medroxyprogesterone acetate (MPA). METHODS: HT trial participants from the CEE alone (n=1,188, 0.625 mg/d CEE or placebo) and the CEE+MPA (n=1,508, 0.625 mg/d CEE plus continuous 2.5 mg/d MPA or placebo) trials provided blood samples at baseline and after 1, 3, and 6 years. Low-density lipoprotein cholesterol (LDL-C; primary endpoint), high-density lipoprotein cholesterol (HDL-C), triglycerides, total cholesterol, lipoprotein(a), glucose, insulin, and homeostatic model assessment for insulin resistance were measured. Repeated-measures regression models estimated the geometric means of each log-transformed biomarker by restricted maximum likelihood. A constant treatment effect across visits was used to estimate the overall effect, expressed as a ratio of geometric means, and was complemented with geometric means (95% CIs) by randomization group and corresponding ratios of geometric means (95% CI; HT vs placebo) at each visit. RESULTS: During the intervention phase of the CEE-alone trial, randomization to CEE reduced LDL-C by 11% over 6 years (ratio of geometric means 0.89, 95% CI, 0.88-0.91, P<.001). The overall reduction in LDL-C was similar for CEE+MPA relative to placebo (ratio of geometric means 0.88, 95% CI, 0.86-0.89, P<.001). Relative to placebo, HDL-C and triglycerides were 13.0% and 7.0% higher with CEE and CEE+MPA, respectively. The homeostatic model assessment for insulin resistance decreased by 14.0% and 8.0% for CEE-alone and CEE+MPA trial participants, respectively. Relative to placebo, lipoprotein(a) decreased by 15.0% and 20.0% for participants randomized to CEE alone and CEE+MPA, respectively. CONCLUSION: Lipoprotein(a), LDL-C, and homeostatic model assessment for insulin resistance were lower and HDL-C levels were higher for HT compared with placebo. Triglycerides increased in both the CEE and CEE+MPA trials, however. Future research should assess whether other progestogens attenuate the effect of estrogen on HDL-C. These results may be used to counsel younger menopausal women with bothersome symptoms who are deciding whether to initiate oral HT within the context of published effects of oral HT on rates of cardiovascular events. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00000611.

Older women have a higher prevalence of Alzheimer’s disease relative to comparably aged men. Although the biological mechanisms driving this sex difference remain elusive, emerging data suggest that longevity, APOEε 4, inflammation, and blood glucose levels may play roles. Our objective was to examine the associations of APOEε 4, high sensitivity-C-reactive protein (hs-CRP), and fasting blood glucose levels with cognitive changes over time among women enrolled in two ancillary studies of the Women’s Health Initiative (WHI). We identified 2,534 women from WHIMS-ECHO (Enrollment age mean(SD) = 70(4) years) and 400 women from WHIMS-Y (Enrollment age mean(SD) = 52(1) years) with baseline data available for APOEε 4 carriage, plasma hs-CRP, and serum-measured fasting blood glucose, and longitudinal cognitive measures, including the TICSm, EBMT, EBMT-recall, verbal fluency, Digit Span Backwards, and CVLT scores. A series of linear mixed-effects models were used to examine these three predictors’ main and interactive effects on longitudinal cognition changes, adjusting for age, education level, body mass index, diabetes status, WHI randomization arm, and cohort (including random intercepts and slopes). Hs-CRP levels were log transformed and glucose levels were inverse transformed. All data were z-scored. APOEε 4 carriage was associated with steeper cognitive decline on the TICSm, EMBT, EBMT-recall, verbal fluency, Digit Span Backwards, and CVLT-correct scores compared to non-carriers (Table 1). APOEε 4 carriers with lower blood glucose levels showed steeper cognitive decline on TICSm and EBMT-recall scores but less intrusions on the CVLT compared to APOEε 4 carriers with higher glucose levels. Additionally, APOEε 4 carriers with higher levels of hs-CRP demonstrated a steeper decline on CVLT-correct scores relative to APOEε 4 carriers with lower hs-CRP levels. Women with higher levels of hs-CRP alone exhibited steeper cognitive decline on the EBMT and Digit Span Backwards test compared to women with lower hs-CRP. Women with higher levels of both hs-CRP and blood glucose also showed significantly faster rates of decline on TICSm and verbal fluency scores relative to women with higher hs-CRP who had lower blood glucose levels. Three-way interaction tests ( APOEε 4*CRP*glucose) did not yield significant results. These findings underscore the complex interplay between genetic risk, metabolic and inflammatory health, and their associations with cognitive decline among older women.

Objective: We examined if thyroid autoimmunity is relevant to the relationship between maternal thyroid stimulating hormone (TSH) levels and pregnancy outcomes. Design: Retrospective cohort analysis of data from 2 randomized controlled trials (RCTs). Subjects: Participants of the Pregnancy in Polycystic Ovary Syndrome (PPCOS II, n = 746) and the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS, n = 832 with unexplained infertility) RCTs. Exposure: Pre-RCT intervention levels of TSH at threshold of >= 2.0 mU/L and thyroid peroxidase antibody (TPO-Ab) at titer threshold of >= 30 U/mL. model (GLM) analyses examined the relationship between exposure to TSH and TPO-Ab at specified thresholds with the specified (vs. unexplained infertility), and randomized intervention arm in the respective RCTs. Results: On adjusted analyses, live birth was significantly reduced in the exposed population (those with TSH >= 2.0 mU/L and TPO-Ab >= 30 U/mL, n = 117/1,578, 7.4%, adjusted risk ratio [ARR]: 0.55; 95% CI: 0.35-0.87) compared with the unexposed (those with TSH <2.0 mU/L and TPO-Ab <30 U/mL, n = 865/1,578, 54.8%). Furthermore, the risk of pregnancy loss and of early preterm birth (<32 weeks) was significantly higher in the exposed compared with the unexposed (ARR for pregnancy loss was 1.66; 95% CI: Conclusion: In women with TPO-Ab titers >= 30 U/mL, pregnancy outcomes may be compromised at TSH threshold of >= 2 mU/L. These findings of an interaction between TSH and TPO for pregnancy outcomes merit further investigation in prospective studies. Trial Registration Number: NCT00719186 and NCT01044862. (Fertil Steril (R) 2025;123:873-82. (c) 2024 by American Society for Repro-ductive Medicine.) El resumen est & aacute; disponible en Espa & ntilde;ol al final del art & iacute;culo.

To evaluate longitudinal transitions in sedentary behavior and physical activity for the associations with all-cause and cause-specific mortality (i.e., cardiovascular disease [CVD], cancer, respiratory, and Alzheimer's disease/dementia mortality) among postmenopausal women. This prospective cohort study included 58,168 multiethnic US postmenopausal women from the Women’s Health Initiative Observational Study, who had self-reported data on various sedentary behaviors and recreational physical activity at baseline (Y0: 1993–1998; age range: 50–79 years) and after 6 years (Y6). According to sedentary time (≥ 8 h/day or not) or physical activity (≥ 8.5 MET-h/week or not) at Y0 and Y6 assessments, participants were grouped by transition in sedentary behavior (consistently non-sedentary, sedentary to non-sedentary, non-sedentary to sedentary, and consistently sedentary) or physical activity levels (consistently low, high to low, low to high, and consistently high). Over a median follow-up of 15.0 years (from Y6 to March 2019), 17,354 all-cause deaths occurred, ranging from 1336 respiratory to 5111 CVD deaths. Compared to the consistently non-sedentary group, the two groups with unfavorable transitions in sedentary behavior (i.e., from non-sedentary to sedentary or being consistently sedentary) both had a higher risk of all-cause mortality and mortality from CVD, cancer, and respiratory disease. Conversely, the two groups with favorable transitions in physical activity (i.e., transitioning to or maintaining high activity), as compared with the consistently-low activity group, both had a lower risk mortality from all causes and several specific causes. Significant interactions were observed between transitions in sedentary behavior and physical activity on the risk of all-cause and CVD mortality (P-interaction < 0.01). Specifically, unfavorable sedentary transitions were associated with an elevated risk only among women with unfavorable transitions in physical activity. Among US postmenopausal women, maintaining or transiting to a sedentary lifestyle over 6 years was associated with a higher risk of mortality, predominantly among those not achieving regular physical activity over the years.

Background: Although calcium and vitamin D (CaD) supplementation may affect chronic disease in older women, evidence of long-term effects on health outcomes is limited. Objective: To evaluate long-term health outcomes among postmenopausal women in the Women's Health Initiative CaD trial. Design: Post hoc analysis of long-term postintervention follow-up of the 7-year randomized intervention trial of CaD. (ClinicalTrials.gov: NCT00000611) Setting: A multicenter (n = 40) trial across the United States. Participants: 36 282 postmenopausal women with no history of breast or colorectal cancer. Intervention: Random 1:1 assignment to 1000 mg of calcium carbonate (400 mg of elemental calcium) with 400 IU of vitamin D3 daily or placebo. Measurements: Incidence of colorectal, invasive breast, and total cancer; disease-specific and all-cause mortality; total cardiovascular disease (CVD); and hip fracture by randomization assignment (through December 2020). Analyses were stratified on personal supplement use. Results: For women randomly assigned to CaD versus placebo, a 7% reduction in cancer mortality was observed after a median cumulative follow-up of 22.3 years (1817 vs. 1943 deaths; hazard ratio [HR], 0.93 [95% CI, 0.87 to 0.99]), along with a 6% increase in CVD mortality (2621 vs. 2420 deaths; HR, 1.06 [CI, 1.01 to 1.12]). There was no overall effect on other measures, including all-cause mortality (7834 vs. 7748 deaths; HR, 1.00 [CI, 0.97 to 1.03]). Estimates for cancer incidence varied widely when stratified by whether participants reported supplement use before randomization, whereas estimates on mortality did not vary, except for CVD mortality. Limitation: Hip fracture and CVD outcomes were available on only a subset of participants, and effects of calcium versus vitamin D versus joint supplementation could not be disentangled. Conclusion: Calcium and vitamin D supplements seemed to reduce cancer mortality and increase CVD mortality after more than 20 years of follow-up among postmenopausal women, with no effect on all-cause mortality. Primary Funding Source: National Heart, Lung, and Blood Institute of the National Institutes of Health.

Cardiovascular disease (CVD) is the leading cause of death among women and its incidence has been increasing recently, particularly among younger women. Across major professional society guidelines, dyslipidemia management remains a central tenet for atherosclerotic CVD prevention for both women and men. Despite this, women, particularly young women, who are candidates for statin therapy are less likely to be treated and less likely to achieve their recommended therapeutic objectives for low-density lipoprotein cholesterol (LDL-C) levels. Elevated LDL-C and triglycerides are the two most common dyslipidemias that should be addressed during pregnancy due to the increased risk for adverse pregnancy outcomes, such as preeclampsia, gestational diabetes mellitus, and pre-term delivery, as well as pancreatitis in the presence of severe hypertriglyceridemia. In this National Lipid Association Expert Clinical Consensus, we review the roles of nutrition, physical activity, and pharmacotherapy as strategies to address elevated levels of LDL-C and/or triglycerides among women of reproductive age. We include a special focus on points to consider during the shared decision-making discussion regarding pharmacotherapy for dyslipidemia during preconception planning, pregnancy, and lactation.

INTRODUCTION:Apolipoprotein E4 (APOE4) carriers' tendency toward hypercholesterolemia may contribute to Alzheimer's disease (AD) risk through oxysterols, which traverse the blood-brain barrier. METHODS:Relationships between baseline plasma oxysterols, APOE status, serum lipids, and cognitive impairment risk were examined in 328 postmenopausal women from the Women's Health Initiative Memory Study. Women were followed for 25 years or until incident dementia or cognitive impairment. RESULTS:Levels of 24(S)-hydroxycholesterol (24-OHC), 27-hydroxycholesterol (27-OHC), and 24-OHC/27-OHC ratio did not differ by APOE status (p's > 0.05). Higher 24-OHC and 27-OHC were associated with higher total, low density lipoprotein (LDL), non-high density lipoprotein (HDL), remnant, LDL/HDL, and total/HDL cholesterol and triglycerides (p's < 0.05). Higher 24-OHC/27-OHC was associated with greater dementia risk (hazard ratio = 1.51, 95% confidence interval:1.02-2.22), which interaction analyses revealed as significant for APOE3 and APOE4+, but not APOE2+ carriers. DISCUSSION:Less favorable lipid profiles were associated with higher oxysterol levels. A higher ratio of 24-OHC/27-OHC may contribute to dementia risk in APOE3 and APOE4+ carriers.

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 Women's 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 (<2500 g) or high-birthweight (>4500 g) infants. Participants were fol-lowed 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.

Background: In the Women's Health Initiative (WHI) randomized trial, dietary intervention significantly reduced breast cancer mortality, especially in women with more metabolic syndrome (MetS) components. Therefore, this study investigated the associations of MetS and obesity with postmenopausal breast cancer after long-term follow-up in the WHI clinical trials. Methods: A total of 68,132 postmenopausal women, without prior breast cancer and with normal mammogram, were entered into WHI randomized clinical trials; 63,330 women with an entry MetS score comprised the study population. At entry, body mass index (BMI) was determined; MetS score (0, 1-2, and 3-4) included the following: (1) high waist circumference (>= 88 cm), (2) high blood pressure (systolic >= 130 mm Hg and/or diastolic >= 85 mm Hg, or hypertension history), (3) high-cholesterol history, and (4) diabetes history. Study outcomes included breast cancer incidence, breast cancer mortality, deaths after breast cancer, and results by hormone receptor status. Results: After a >20-year mortality follow-up, a higher MetS score (3-4), adjusted for BMI, was significantly associated with more poor prognosis, estrogen receptor (ER)-positive, progesterone receptor (PR)-negative cancers (p = .03), 53% more deaths after breast cancer (p < .001), and 44% higher breast cancer mortality (p = .03). Obesity status, adjusted for MetS score, was significantly associated with more good prognosis, ER-positive, PR-positive cancers (p < .001), more total breast cancers (p < .001), and more deaths after breast cancer (p < .001), with higher breast cancer mortality only in women with severe obesity (BMI, >= 35 kg/m(2); p < .001). Conclusions: MetS and obesity status have independent, but differential, adverse associations with breast cancer receptor subtypes and breast cancer mortality risk. Both represent separate targets for breast cancer prediction and prevention strategies.

Background/Synopsis Preeclampsia poses a cardiovascular disease risk. Abnormal lipid metabolism is important in the pathogenesis of preeclampsia. Dyslipidemia is strongly associated with atherosclerotic cardiovascular disease (ASCVD) and has a direct effect on endothelial function. Elevated serum or plasma low density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C) and lipoprotein (a) [Lp(a)] levels are known independent risk factors for ASCVD, however, extensive lipid changes in preeclampsia are incompletely characterized. Objective/Purpose This study sought to characterize serum and plasma lipoproteins in preeclampsia and control subjects. Methods Frozen serum and plasma from pregnant patients enrolled in the Child Health Advances from Research with Mothers (CHARM) study. Visit 1, 30 cases, 89 controls, gestational age 89 days (36d-247d) and Visit 2, 22 cases, 64 controls, gestational age 189 days (136d-256d), were shipped to Boston Heart Diagnostics for blinded analysis. Patients with gestational diabetes were excluded. Standard serum lipids, direct LDL-C, sdLDL-C, and apolipoprotein (apo) A-I, A-II, and B, and Lp(a) levels were measured by standard chemical methods, and plasma apolipoproteins and particle numbers were assessed using nuclear magnetic resonance (NMR) methodology. Results were adjusted for gestational age, and smoking, and obtained for preeclampsia compared to normal controls - using general linear models for fixed factor analysis. Log transformations were carried out for non-normally distributed parameters. Results In the serum chemistries, significant (p<.05) elevations were found in preeclampsia cases versus controls for direct LDL-C (+10%), small dense LDL-C (+18%), apoB (+10%), and Lp(a) (+50%). Similar alterations were noted in lipoprotein and apolipoprotein analyses by NMR. Results apply in aggregate to all gestational ages. Conclusions There are significant serum and plasma lipoprotein and apolipoprotein alterations seen in preeclampsia cases versus control subjects. Increases in atherogenic small dense LDL particles and their constituents have also been associated with increased ASCVD risk in the general population.