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Abstract Objective White matter hyperintensities (WMH) on brain MRI images are the most common feature of cerebral small vessel disease (CSVD). Studies have yielded divergent findings on the modifiable risk factors for WMH and WMH’s impact on cognitive decline. Mounting evidence suggests sex differences in WMH burden and subsequent effects on cognition. Thus, we aimed to identify sex-specific modifiable risk factors for WMH. We then explored whether there were sex-specific associations of WMH to longitudinal clinical dementia outcomes. Methods Participants aged 49–89 years were recruited at memory clinics and underwent a T2-weighted fluid-attenuated inversion recovery (FLAIR) 3T MRI scan to measure WMH volume. Participants were then recruited for two additional follow-up visits, 1–2 years apart, where clinical dementia rating sum of boxes (CDR-SB) scores were measured. We first explored which known modifiable risk factors for WMH were significant when tested for a sex-interaction effect. We additionally tested which risk factors were significant when stratified by sex. We then tested to see whether WMH is longitudinally associated with clinical dementia that is sex-specific. Results The study utilized data from 713 participants (241 males, 472 females) with a mean age of 72.3 years and 72.8 years for males and females, respectively. 57.3% and 59.5% of participants were diagnosed with mild cognitive impairment (MCI) for males and females, respectively. 40.7% and 39.4% were diagnosed with dementia for males and females, respectively. Of the 713 participants, 181 participants had CDR-SB scores available for three longitudinal time points. Compared to males, females showed stronger association of age to WMH volume. Type 2 Diabetes was associated with greater WMH burden in females but not males. Finally, baseline WMH burden was associated with worse clinical dementia outcomes longitudinally in females but not in males. Discussion Older females have an accelerated increase in cerebrovascular burden as they age, and subsequently are more vulnerable to clinical dementia decline due to CSVD. Additionally, females are more susceptible to the cerebrovascular consequences of diabetes. These findings emphasize the importance of considering sex when examining the consequences of CSVD. Future research should explore the underlying mechanisms driving these sex differences and personalized prevention and treatment strategies. Clinical trial registration The BICWALZS is registered in the Korean National Clinical Trial Registry (Clinical Research Information Service; identifier, KCT0003391). Registration Date 2018/12/14.

Objective: High-density lipoprotein cholesterol (HDL-C) is one of 5 components [high blood pressure, glucose, triglycerides, waist circumference, low HDL-C], 3 of which, needed to diagnose metabolic syndrome (MetS). Evolving research shows that higher HDL-C is not necessarily cardioprotective in midlife women, supporting a need to re-evaluate HDL-C's contribution to risks related to MetS. We tested whether risk of future diabetes and higher carotid intima-media thickness (cIMT) differ by HDL-C status in midlife women diagnosed with MetS based on the other 4 components. Methods: Midlife women were classified into 3 groups: 1) no MetS, 2) MetS with HDL-C ≥ 50 mg/dL (MetS hiHDL), and 3) MetS with HDL-C < 50 mg/dL (MetS loHDL). cIMT was measured 13.8 ± 0.6 years post baseline. Incident diabetes was assessed yearly. Results: Among 2773 women (1350 (48 %) of them had cIMT), 2383 (86 %) had no MetS, 117 (4 %) had MetS hiHDL, 273 (10 %) had MetS loHDL. Compared with no MetS, both MetS- hiHDL and loHDL groups had higher cIMT and diabetes risk. Risk of having high cIMT did not differ between MetS loHDL vs. hiHDL groups. Adjusting for levels of MetS criteria other than HDL-C at baseline explained the associations of each of the two MetS groups with cIMT. Conversely, after adjustment, associations of MetS hiHDL and MetS loHDL with incident diabetes persisted. Conclusions: In midlife women, HDL-C status matters for predicting risk of incident diabetes but not higher cIMT beyond other MetS components.

BackgroundWomen carrying the APOE4 allele are at greater risk of developing Alzheimer’s disease (AD) from ages 65–75 years compared to men. To better understand the elevated risk conferred by APOE4 carrier status among midlife women, we investigated the separate and interactive associations of endogenous estrogens, plasma AD biomarkers, and APOE4 carrier status on regional brain volumes in a sample of late midlife postmenopausal women.MethodsParticipants were enrolled in MsBrain, a cohort study of postmenopausal women (n = 171, mean age = 59.4 years, mean MoCA score = 26.9; race = 83.2% white, APOE4 carriers = 40). Serum estrone (E1) and estradiol (E2) levels were assessed using liquid chromatography–tandem mass spectrometry. APOE genotype was determined using TaqMan SNP genotyping assays. Plasma AD biomarkers were measured using single molecule array technology. Cortical volume was measured and segmented by FreeSurfer software using individual T1w MPRAGE images. Multiple linear regression models were conducted to determine whether separate and interactive associations between endogenous estrogen levels, plasma AD biomarkers (Aβ42/Aβ40, Aβ42/p-tau181), and APOE4 carrier status predict regional brain volume (21 regions per hemisphere, selected a priori); and, whether significant interactive associations between estrogens and AD biomarkers on brain volume differed by APOE4 carrier status.ResultsThere was no main effect of APOE4 carrier status on regional brain volumes, endogenous estrogen levels, or plasma AD biomarkers. Estrogens did not associate with regional brain volumes, except for positive associations with left caudal middle frontal gyrus and fusiform volumes. The interactive association of estrogens and APOE4 carrier status on brain volume was not significant for any region. The interactive association of estrogens and plasma AD biomarkers predicted brain volume of several regions. Higher E1 and E2 were more strongly associated with greater regional brain volumes among women with a poorer AD biomarker profile (lower Aβ42/40, lower Aβ42/p-tau181 ratios). In APOE4-stratified analyses, these interactions were driven by non-APOE4 carriers.ConclusionWe demonstrate that the brain volumes of postmenopausal women with poorer AD biomarker profiles benefit most from higher endogenous estrogen levels. These findings are driven by non-APOE4 carriers, suggesting that APOE4 carriers may be insensitive to the favorable effects of estrogens on brain volume in the postmenopause.

Background. Spinal cord injuries typically result in a range of negative health outcomes and health states, which impacts overall functioning, health and well-being. It remains important to establish the prevalence (burden) of health outcomes to help with the development of optimal treatment strategies. Objectives. To determine the prevalence and treatment rates of secondary health conditions (SHCs) and mental health states in persons with long-term spinal cord injury (SCI) receiving public compared with private healthcare services in South Africa. Methods. A cross-sectional survey included 200 community-dwelling persons with long-term SCI, 60% with paraplegia, 53% with complete injuries and 156 from the public and 44 from private healthcare sectors. The following modules of the International Spinal Cord Injury (InSCI) community survey were used: (i) demographic and injury characteristics; (ii) SHCs and treatment rates; and (iii) vitality and emotional well-being. All statistical analyses were stratified according to healthcare sector. Results. Pain (47% v. 57), sexual dysfunction (59% v. 41%) and muscle spasms (54% v. 43%) were the most common SHCs in both cohorts, and the period prevalence was significantly higher for sleeping problems (41% v. 25%), sexual dysfunction (59% v. 41%) and contractures (42% v. 20%) in the public compared with the private cohort. Persons with SCI in the private cohort received treatment more often for sleeping problems (100% v. 45%), autonomic dysreflexia (75% v. 27%) and pain (56% v. 33%) than their counterparts with public insurance. Negative mental health states were prevalent in both groups. Conclusion. SHCs and negative mental health were common in persons with SCI in South Africa, while those with public insurance reporter a higher occurrence of sleep problems and contractures, as well as lower treatment rates. Overall, a need exists to better support persons with SCI in the long-term context to facilitate improved functioning and wellbeing.

Background Childhood maltreatment has been associated with arterial stiffness. This relationship has not been examined specifically among women at midlife, a time of increased arterial stiffness in women. This study tested whether childhood maltreatment is associated with arterial stiffness among a cohort of midlife women. Methods and Results A total of 162 nonsmoking perimenopausal and postmenopausal women free of clinical cardiovascular disease (mean age, 54 years; 72% White race, 23% Black race, and 5% Asian/Pacific Islander or Mixed race) completed the Child Trauma Questionnaire at baseline. At a follow‐up visit 5 years later, blood pressure and carotid‐femoral pulse wave velocity (a measure of arterial stiffness) were assessed. Relationships between childhood maltreatment and carotid‐femoral pulse wave velocity were tested in linear regression models, adjusting for time between visits, age, race and ethnicity, education, body mass index, heart rate, hypertension medication, and diastolic blood pressure. Seventy‐one women (44% of the sample) met criteria for a history of childhood maltreatment. Women with a history of childhood maltreatment had higher carotid‐femoral pulse wave velocity (B [SE]=0.47 [0.21]; P=0.03) than women without this history, controlling for time between visits, age, race and ethnicity, education, body mass index, heart rate, hypertension medication, and diastolic blood pressure. Conclusions Among these midlife women, childhood maltreatment was associated with arterial stiffness, highlighting the potential long‐term cardiovascular implications of childhood maltreatment.

The objective of this study was to determine the diagnostic ability of serum amyloid A (SAA) and fibrinogen for early detection of surgical site infection (SSI) after equine internal fixation. Horses undergoing internal fixation for fracture, arthrodesis, or osteotomy with internal fixation for limb deformity were included in the study. SAA and fibrinogen were measured on blood samples preoperatively and on days 1, 3, 5, 7, 10, and 14 postoperatively. Statistical analysis included use of Spearman's rank correlation, logistic regression, and calculating the area under the receiver operating characteristic (ROC) curve. SAA and fibrinogen measurements were both associated with SSI, with SAA being considered an excellent marker (area under the ROC curve 0.8) and fibrinogen being considered acceptable (

Background Traumatic experiences have been linked to risk for cardiovascular disease (CVD). Interpersonal violence is a trauma that is prevalent in women. Among midlife women followed up for 2 decades, we examined whether interpersonal violence (childhood abuse, adulthood abuse, or intimate partner violence [IPV]) was related to increased risk of subsequent clinical CVD events. Methods and Results A total of 2201 women, aged 42 to 52 years at baseline, underwent up to 16 in‐person visits over 22 years. Measures included questionnaires (including of childhood physical/sexual abuse, adult physical/sexual abuse, and IPV), physical measures, phlebotomy, and reported CVD events (myocardial infarction, stroke, heart failure, and revascularization). Death certificates were collected. Relationships between childhood abuse, adult abuse, and IPV with incident fatal/nonfatal CVD were tested in Cox proportional hazards models. Women with a childhood abuse history had increased risk for incident CVD (versus no abuse; hazard ratio [HR] [95% CI], 1.65 [1.12–2.44]; P=0.01; adjusted for demographics and CVD risk factors); associations were strongest for childhood sexual abuse. Adult abuse was not significantly associated with CVD. Women with IPV had a doubling of risk for incident CVD in demographic‐adjusted models (versus no IPV; IPV: HR [95% CI], 2.06 [1.01–4.23]; P=0.04; no partner: HR [95% CI], 1.79 [0.91–3.53]; P=0.09); systolic blood pressure partially mediated relationships between IPV and CVD. Conclusions Childhood abuse, particularly sexual abuse, was associated with increased risk of CVD in women. IPV was associated with risk for CVD, with the higher systolic blood pressure among IPV‐exposed women important in these associations. Interpersonal violence prevention may contribute to CVD risk reduction in women.

Background Hypertension is a prevalent condition in women and an important modifiable risk factor for cardiovascular disease. Despite women’s experiences of sexual violence being common, no prospective studies have examined lifetime sexual assault and workplace sexual harassment in relationship to hypertension in large civilian samples with extended follow‐up. Here, we examined whether these experiences were prospectively associated with greater risk of developing hypertension over 7 years. Methods and Results Data are from a substudy of the Nurses’ Health Study II and include women free of hypertension at the time of sexual assault and workplace sexual harassment assessment in 2008 (n=33 127). Hypertension was defined as self‐reported doctor diagnosis or initiating antihypertensive medication use, assessed biennially through 2015. We performed Cox proportional hazards regression models to predict time to developing hypertension associated with sexual violence exposure, adjusting for relevant covariates. Over follow‐up, 7096 women developed hypertension. Sexual assault and workplace sexual harassment were prevalent (23% and 12%, respectively; 6% of women experienced both). Compared with women with no exposure, women who experienced both sexual assault and workplace sexual harassment had the highest risk of developing hypertension (hazard ratio [HR], 1.21; 95% CI, 1.09–1.35), followed by women who experienced workplace sexual harassment (HR, 1.15; 95% CI, 1.05–1.25) and then by women who experienced sexual assault (HR, 1.11; 95% CI, 1.03–1.19), after adjusting for relevant covariates. Conclusions Sexual assault and workplace sexual harassment are prospectively associated with greater risk of hypertension. Reducing such violence is important in its own right and may also improve women’s cardiovascular health.

Background Direct-acting oral anticoagulants (DOACs) do not require monitoring. Measurement of DOAC effect would be useful in the event of bleeding, trauma, and thromboembolism while on anticoagulation. We evaluated the effectiveness of the investigational DOAC assays on the TEG®6s Hemostasis Analyzer to assess the anticoagulant effect of DOACs in patients treated for atrial fibrillation or deep vein thrombosis (DVT). Methods Patients on treatment for a minimum of 7 days with standard doses of dabigatran, rivaroxaban, and apixaban were included. DOAC plasma concentrations and TEG®6s Reaction (R)-time were measured and correlated. The sensitivity, specificity, and negative predictive value (NPV) of R-time to detect DOAC concentrations of ≥30, ≥50, and ≥100 ng/mL were calculated. Results A total of 189 patients were included, (n = 50) on apixaban, (n = 62) on rivaroxaban, (n = 53) on dabigatran, and (n = 24) on no DOAC were studied. Using the direct thrombin inhibitor (DTI) channel, R-time demonstrated strong linear correlation with dabigatran levels (r = 0.93, p

Background Younger age at final menstrual period (FMP) is associated with increased risk for cardiovascular disease events. This paper evaluated whether older age at FMP is associated with more favorable patterns of lipid changes during the menopause transition and whether these changes are associated with less subclinical carotid disease in the postmenopausal years. Methods and Results Lipids and lipoproteins were measured repeatedly among 1554 premenopausal women who had a natural menopause during follow‐up years (median=18.8 years); a subset of 890 women also had measures of carotid intima media thickness, adventitial diameter, and plaque. Women who had an older FMP age had less adverse changes in cholesterol from 1 to 3 years after FMP, and in triglycerides from FMP to 3 years after FMP, but they had more adverse changes in ApoB and Apo A1 from 3 years before to 1 year after the FMP. Increasing cholesterol and ApoB from 1 to 3 years after FMP were associated with greater intima media thickness and adventitial diameter, and the greater likelihood of a plaque score >2 the older the age at FMP. Conclusions Despite the epidemiological literature showing early age at FMP is associated with elevated risk for cardiovascular disease events, older age at FMP had inconsistent associations with less adverse lipid changes in midlife, which did not translate into less risk for subclinical carotid disease and in some cases more risk. These findings are restricted to women who experience FMP in the normative age range for the menopausal transition.

Abstract New 3D multi‐azimuthal receiver function analysis identified four regional seismic discontinuities dipping at 7–13° within the mantle of the Superior craton of North America; most are discordant to known major upper crustal structures. Widely observed crustal‐scale structures with near‐vertical axial planes striking east‐west indicate that the most recent and dominant phase of folding and horizontal shortening strain occurred during the Kenoran (D2) crustal deformation concurrent with Au‐mineralization and peak metamorphism at 2.72–2.66 Ga. Two mantle discontinuities strike 065° and 249°, dipping to the southeast and northwest, respectively. These strikes roughly parallel the northern margin of the Superior craton and some intra‐cratonic features such as the axis of the Quetico Basin. Two discontinuities strike 355° and 187°, dipping to the east and west, respectively, and parallel to the western margin of the craton. Our new observations reveal neither moderately dipping, east‐west striking discontinuities nor coherent eclogitic layers characteristic of modern plate tectonic subduction zones. Prominent east‐ and west‐dipping mantle structures relate best to a Paleoproterozoic (Trans‐Hudson) deformation, which is rarely observed in the crust. A new analysis of mantle xenoliths and xenocrysts indicates that carbonatitic metasomatism predominates above some discontinuities where strongly localized conductivity occurs whereas kimberlitic metasomatism predominates below the discontinuities in the broadly conductive mantle.

Background The menopausal transition is characterized by increased cardiovascular risk, weight gain, and increased adiposity for many women. The adipose‐derived secretory proteins adiponectin and leptin are associated with insulin resistance, metabolic syndrome, and cardiovascular disease but their role in subclinical atherosclerotic disease is unclear. This cross‐sectional study evaluated the associations of adiponectin and leptin with carotid artery intima‐media thickness, adventitial diameter, presence of carotid plaques, and brachial‐ankle pulse wave velocity (baPWV) in women aged 54 to 65 years. Methods and Results Participants were 1399 women from SWAN (Study of Women's Health Across the Nation), a community‐based study of women transitioning through menopause. Carotid ultrasound and baPWV measures were obtained at SWAN follow‐up visits 12 or 13, when 97% of participants were post‐menopausal. Adipokines were assayed from serum specimens obtained concurrently at these visits. Linear and logistic regression models were used to evaluate adiponectin or leptin, both log‐transformed attributable to skewness, in relationship to carotid artery intima‐media thickness, adventitial diameter, baPWV, and presence of carotid plaque. Covariates included age, race, study site, smoking, alcohol use, obesity, cardiovascular disease risk factors, and menopausal status. Lower levels of adiponectin were related to greater carotid artery intima‐media thickness, wider adventitial diameter, and faster baPWV; associations were attenuated after adjusting for cardiovascular disease risk factors. Higher levels of leptin were associated with greater carotid artery intima‐media thickness and wider adventitial diameter in minimally and fully adjusted models, and contrary to expectation, with slower baPWV, particularly among women with diabetes mellitus or obesity. Conclusions Adiponectin and leptin are 2 important inflammatory pathways that may contribute to adverse subclinical cardiovascular disease risk profiles in women at midlife.

Background Sexual assault is a risk factor for poor mental health, yet its relationship to cardiovascular disease risk is not understood. We tested whether women with a sexual assault history had greater carotid atherosclerosis levels and progression over midlife. Methods and Results A total of 169 non‐smoking, cardiovascular disease‐free women aged 40 to 60 years were assessed twice over 5 years. At each point, women completed questionnaires, physical measures, phlebotomy, and carotid ultrasounds. Associations between sexual assault and carotid plaque level (score 0, 1, ≥2) and progression (score change) were assessed in multinomial logistic and linear regression models, adjusted for age, race/ethnicity, education, body mass index, blood pressure, lipids, insulin resistance, and additionally depression/post‐traumatic stress symptoms; 28% of the women reported a sexual assault history. Relative to non‐exposed women, women with a sexual assault history had an over 4‐fold odds of a plaque score of ≥2 at baseline (≥2, odds ratio [OR] [95% CI]=4.35 [1.48–12.79], P=0.008; 1, OR [95% CI]=0.49 [0.12–1.97], P=0.32, versus no plaque; multivariable); and an over 3‐fold odds of plaque ≥2 at follow‐up (≥2, OR [95% CI]=3.65 [1.40–9.51], P=0.008; 1, OR [95% CI]=1.52 [0.46–4.99], P=0.49, versus no plaque; multivariable). Women with a sexual assault history also had an over 3‐folds greater odds of a plaque score progression of ≥2 (OR [95% CI]=3.48[1.11–10.93], P=0.033, multivariable). Neither depression nor post‐traumatic symptoms were related to plaque. Conclusions Sexual assault is associated with greater carotid atherosclerosis level and progression over midlife. Associations were not explained by standard cardiovascular disease risk factors. Future work should consider whether sexual assault prevention reduces women's cardiovascular disease risk.

Background Cardiovascular disease (CVD) in women has unique features, including associations with reproductive factors that are incompletely understood. Vasomotor symptoms (VMS), the classic menopausal symptom, are linked to CVD risk factors and subclinical CVD. Evidence linking VMS to CVD events is limited. We tested whether frequent and/or persistent VMS were associated with increased risk for fatal and nonfatal CVD events in SWAN (Study of Women’s Health Across the Nation). Methods and Results A total of 3083 women, aged 42 to 52 years at baseline, underwent up to 16 in‐person visits over 22 years. Assessments included questionnaires on VMS frequency (0, 1–5, or ≥6 days/2 weeks), physical measures, phlebotomy, and reported CVD events (myocardial infarction, stroke, heart failure, and revascularization). A subset of events was adjudicated via medical record. Death certificates were obtained. Relationships between baseline VMS or persistent VMS over the follow‐up (proportion of visits with frequent VMS) with combined incident nonfatal and fatal CVD were tested in Cox proportional hazards models adjusted for demographics, medication use, and CVD risk factors. Participants experienced 231 CVD events over the follow‐up. Women with frequent baseline VMS had an elevated risk of subsequent CVD events (relative to no VMS; ≥6 days: hazard ratio [HR] [95% CI], 1.51 [1.05–2.17], P=0.03; 1–5 days: HR [95% CI], 1.02 [0.75–1.39], P=0.89, multivariable). Women with frequent VMS that persisted over time also had an increased CVD event risk (>33% versus ≤33% of visits: HR [95% CI], 1.77 [1.33–2.35], P

Most studies of menopause and brain aging have focused on the role of the sex steroid hormone, estradiol, as a key mechanisms contributing to cognitive and brain aging in women. An emerging literature demonstrates that beyond endogenous estradiol levels, menopausal symptoms, particularly vasomotor symptoms (VMS), are also key determinants of menopause-related changes in cognition and brain function. Critically, that literature shows the importance of using objective techniques to identify associations of VMS with memory performance, brain structure, and brain function. While self-report measures are important patient-centered outcomes in women's health research, objective measures of VMS typically relate more strongly to indices of cognitive and brain health. Currently, it is premature to make a causal claim about VMS and memory dysfunction, but initial findings raise the possibility that women with VMS might experience an improvement in cognition with VMS treatment. More generally, these findings underscore the utility of investigating female-specific risk factors for cognitive decline.

Background The extent to which cardiovascular disease (CVD) risk factors across the menopause explain racial/ethnic differences in subclinical vascular disease in late midlife women is not well documented and was explored in a multi‐ethnic cohort. Methods and Results Participants (n=1357; mean age 60 years) free of clinical CVD from the Study of Women's Health Across the Nation had common carotid artery intima‐media thickness, interadventitial diameter, and carotid plaque presence assessed by ultrasonography on average 13.7 years after baseline visit. Early to late midlife time‐averaged cumulative burden of traditional CVD risk factors calculated using serial measures from baseline to the ultrasound visit were generally less favorable in black and Hispanic women compared with white and Chinese women, including education and smoking status and time‐averaged cumulative blood pressure, high‐density lipoprotein cholesterol, and fasting insulin. Independent of these risk factors, BMI, and medications, common carotid artery intima‐media thickness was thicker in black women, interadventitial diameter was wider in Chinese women, yet plaque presence was lower in black and Hispanic women compared with white women. CVD risk factor associations with subclinical vascular measures did not vary by race/ethnicity except for high‐density lipoprotein cholesterol on common carotid artery intima‐media thickness; an inverse association between high‐density lipoprotein cholesterol and common carotid artery intima‐media thickness was observed in Chinese and Hispanic but not in white or black women. Conclusions Race/ethnicity did not particularly moderate the association between traditional CVD risk factors measured across the menopause transition and late midlife subclinical vascular disease. Unmeasured socioeconomic, cultural, and nontraditional biological risk factors likely play a role in racial/ethnic differences in vascular health and merit further exploration.

BackgroundAdverse pregnancy outcomes, such as preterm birth (PTB), have been associated with elevated risk of maternal cardiovascular disease, but their effect on late midlife blood pressure (BP) and subclinical vascular measures remains understudied. Methods and ResultsWe conducted a cross‐sectional analysis with 1220 multiethnic parous women enrolled in SWAN (Study of Women's Health Across the Nation) to evaluate the impact of self‐reported history of adverse pregnancy outcomes (PTB, small‐for‐gestational‐age, stillbirth), on maternal BP, mean arterial pressure, and subclinical vascular measures (carotid intima‐media thickness, plaque, and pulse wave velocity) in late midlife. We also examined whether these associations were modified by race/ethnicity. Associations were tested in linear and logistic regression models adjusting for sociodemographics, reproductive factors, cardiovascular risk factors, and medications. Women were on average aged 60 years and 255 women reported a history of an adverse pregnancy outcome. In fully adjusted models, history of PTB was associated with higher BP (systolic: β=6.40; SE, 1.62 [P

The objective of this work was to evaluate the associations between levels of endogenous sex hormones in women at midlife and lipoprotein subclasses. One hundred and twenty women (68 late peri-/postmenopausal and 52 pre-/early perimenopausal) from the Study of Women's Health Across the Nation (Pittsburgh site) were included. Lipoprotein subclasses were quantified using NMR spectroscopy. Participants (57.5#x0025; White and 42.5#x0025; Black) were 50.4 ± 1.9 years old. Adjusting for age, race, cycle day of blood draw, BMI, physical activity, and alcohol consumption, a negative correlation was found between estradiol (E2) and medium-small LDL particle (LDL-P) concentration (ρ = −0.19, P = 0.04). Further, E2 was positively correlated with HDL particle (HDL-P) size (ρ = 0.22, P = 0.02). For sex hormone binding globulin (SHBG), independent negative correlation was found with total small LDL-P concentration. SHBG was also positively correlated with LDL-P and HDL-P sizes (P < 0.05 for all). For free androgen index (FAI), positive correlations were found with concentrations of total VLDL particles, total LDL-Ps, and total small LDL-Ps. Additionally, FAI was negatively correlated with large HDL-P concentration, and HDL-P and LDL-P sizes (P < 0.05 for all). Lower levels of E2 and SHBG, and higher levels of FAI were associated with a more atherogenic profile of lipoprotein subclasses. Sex hormone levels at midlife may increase women's risk of coronary heart disease.