Restrictive Versus Liberal Transfusion in Patients with Type 1 or Type 2 Myocardial Infarction: A Prespecified Analysis of the Myocardial Ischemia and Transfusion (MINT) Trial.

BACKGROUND: The MINT trial raised concern for harm from a restrictive versus liberal transfusion strategy in patients with acute myocardial infarction (MI) and anemia. Type 1 and type 2 MI are distinct pathophysiological entities that may respond differently to blood transfusion. This analysis sought to determine if the effects of transfusion varied among patients with a type 1 or a type 2 MI and anemia. We hypothesized that the liberal transfusion strategy would be of greater benefit in type 2 than in type 1 MI. METHODS: We compared rates of death or MI at 30 days in patients with type 1 (n=1460) and type 2 (n=1955) MI and anemia who were randomly allocated to a restrictive (threshold of 7 to 8 g/dL) or a liberal (threshold of 10 g/dL) transfusion strategy. RESULTS: The primary outcome of death or MI was observed in 16% of type 1 MI and 15.4% of type 2 MI patients. The rate of death or MI was higher in patients with type 1 MI randomized to a restrictive (18.2%) versus liberal (13.2%) transfusion strategy (RR 1.32, 95% CI 1.04 - 1.67) with no difference observed between the restrictive (15.8% ) and liberal (15.1% ) transfusion strategies in patients with type 2 MI (RR 1.05 95% CI 0.85-1.29). The test for a differential effect of transfusion strategy by MI type was not statistically significant (P-interaction = 0.16). CONCLUSIONS: The concern for harm with a restrictive transfusion strategy in patients with acute MI and anemia raised in the MINT primary outcome manuscript may be more apparent in patients with type 1 than type 2 MI. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT02981407.

HDL-C criterion of the metabolic syndrome and future diabetes and atherosclerosis in midlife women: The SWAN Study.

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.

Longitudinal Exposure to Neighborhood Concentrated Poverty Contributes to Differences in Adiposity in Midlife Women.

Background: Neighborhood poverty is associated with adiposity in women, though longitudinal designs, annually collected residential histories, objectively collected anthropometric measures, and geographically diverse samples of midlife women remain limited. Objective: To investigate whether longitudinal exposure to neighborhood concentrated poverty is associated with differences in body mass index (BMI) and waist circumference (WC) among 2,328 midlife women (age 42-52 years at baseline) from 6 U.S. cities enrolled in the Study of Women's Health Across the Nation (SWAN) from 1996 to 2007. Methods: Residential addresses and adiposity measures were collected at approximately annual intervals from the baseline visit through a 10-year follow-up. We used census poverty data and local spatial statistics to identify hot-spots of high concentrated poverty areas and cold-spots of low concentrated poverty located within each SWAN site region, and used linear mixed-effect models to estimate percentage differences (95% confidence interval [CI]) in average BMI and WC levels between neighborhood concentrated poverty categories. Results: After adjusting for individual-level sociodemographics, health-related factors, and residential mobility, compared to residents of moderate concentrated poverty communities, women living in site-specific hot-spots of high concentrated poverty had 1.5% higher (95% CI: 0.6, 2.3) BMI and 1.3% higher (95% CI: 0.5, 2.0) WC levels, whereas women living in cold-spots of low concentrated poverty had 0.7% lower (95% CI: -1.2, -0.1) BMI and 0.3% lower (95% CI: -0.8, 0.2) WC. Site-stratified results remained in largely similar directions to overall estimates, despite wide CIs and small sample sizes. Conclusions: Longitudinal exposure to neighborhood concentrated poverty is associated with slightly higher BMI and WC among women across midlife.

High-density lipoprotein metrics during midlife and future subclinical atherosclerosis in women: the SWAN HDL study.

OBJECTIVE: The clinical utility of high-density lipoprotein cholesterol (HDL-C) in risk classification is limited, especially in midlife women. Novel metrics of HDL may better reflect this risk. We clustered a comprehensive profile of HDL metrics into favorable and unfavorable clusters and assessed how these two clusters are related to future subclinical atherosclerosis (carotid intima media thickness [cIMT], interadventitial diameter [IAD], and carotid plaque presence) in midlife women. METHODS: Four hundred sixty-one women (baseline age: 50.4 [2.7] years; 272 White, 137 Black, 52 Chinese) from the Study of Women's Health Across the Nation HDL ancillary study who had baseline measures of HDL cholesterol efflux capacity (HDL-CEC), lipid contents (HDL-phospholipids [HDL-PL] and HDL triglycerides [HDL-Tg]), and HDL particle (HDL-P) distribution and size, followed by carotid ultrasound (average 12.9 [SD: 2.6] years later), were included. Using latent cluster analysis, women were clustered into a favorable (high HDL-CEC, HDL-PL, large and medium HDL-P, less HDL-Tg and small HDL-P, larger size) or an unfavorable HDL cluster (low HDL-CEC, HDL-PL, large and medium HDL-P, more HDL-Tg, and small HDL-P, smaller size) and then linked to future subclinical atherosclerosis using linear or logistic regression. RESULTS: The favorable HDL cluster was associated with lower cIMT, IAD, and odds of carotid plaque presence. These associations were attenuated by body mass index, except in Chinese women where the association with cIMT persisted (0.72 [0.63, 0.83]). CONCLUSIONS: The association between favorable HDL clusters and a better postmenopausal subclinical atherosclerosis profile is largely explained by body mass index; however, racial/ethnic differences may exist.

Relationships between the vaginal microbiota and genitourinary syndrome of menopause symptoms in postmenopausal women: the Study of Women's Health Across the Nation.

OBJECTIVE: To describe vaginal microbiota classified by community state types (CST) in a diverse cohort of postmenopausal women and evaluate relationships among genitourinary syndrome of menopause (GSM) symptoms (vaginal dryness, vulvovaginal irritation, sexual pain, dysuria, urinary urgency), CSTs, estrogen, vaginal maturation index (VMI), and vaginal pH. METHODS: In the Study of Women's Health Across the Nation, 1,320 women aged 60.4 to 72.5 years self-collected (2015-2017) vaginal samples analyzed for microbiota composition and structure (CSTs) using 16S rRNA gene amplicon sequencing, VMI, and pH. GSM symptoms were collected with self-administered questionnaires; interviewers elicited estrogen use and measured body mass index. Serum E2 and E1 were measured using high-performance liquid chromatography. We analyzed data using Pearson χ2 tests, analysis of variance, Kruskal-Wallis tests, and binomial logistic regression. RESULTS: The most frequently occurring CST was low Lactobacillus species IV-C (49.8%); 36.4% of women had CSTs dominated by Lactobacillus species. More than half of the women with vaginal atrophy biomarkers (VMI <50 and pH >5) had CST IV-C0, whereas women using estrogen or with higher E1 and E2 levels had a higher prevalence of Lactobacillus crispatus -dominated CST I ( P values < 0.001). Sexual pain was associated with atrophy biomarkers and independently associated with Streptococcus species-dominated CST IV-C1 (odds ratio, 2.26; 95% confidence intervals, 1.20-4.23). For all other GSM symptoms, we found no consistent associations with E1 or E2 levels, atrophy biomarkers, or any CST. CONCLUSIONS: Although close relationships exist among estrogen, CSTs, VMI, and pH, sexual pain was the only GSM symptom associated with the structure of vaginal microbiota and atrophy biomarkers.

Low-density lipoprotein subclasses over the menopausal transition and risk of coronary calcification and carotid atherosclerosis: the SWAN Heart and HDL ancillary studies.

OBJECTIVE: Perimenopausal women experience a steep increase in low-density lipoprotein cholesterol (LDL-C) that is related to a higher risk of carotid plaque later in life. Low-density lipoprotein subclasses have been linked to cardiovascular diseases beyond LDL-C, promising a better risk stratification. We aim to characterize changes in LDL subclasses and assess their associations with presence of coronary artery calcium (CAC score ≥10) and carotid intima-media thickness (cIMT) over the menopausal transition (MT) and by menopause stage. METHODS: Nuclear magnetic resonance spectroscopy LDL subclasses were measured for a maximum of five time points. Coronary artery calcification and cIMT were measured for a maximum of two time points. LOESS (locally weighted regression with scatter smoothing) plots, linear mixed-effects models, and generalized estimating equations were used for analyses. RESULTS: The study included 471 women (baseline: age, 50.2 ± 2.7 years; 79.0% premenopausal/early perimenopausal), of whom 221 had data on CAC or cIMT. Low-density lipoprotein subclasses increased over the MT, whereas intermediate density-lipoprotein particles declined. In adjusted models, higher total LDL particles (LDL-P) and apolipoprotein B were associated with greater CAC prevalence and greater cIMT. Although none of the associations were modified by menopause stage, higher LDL-C, apolipoprotein B, and total LDL-P were associated with greater cIMT during the perimenopause or postmenopause stages, whereas higher LDL-C and small LDL-P were associated with greater CAC prevalence, mainly during perimenopause. CONCLUSIONS: During the MT, women experience significant increases in LDL subclasses found to be related to greater cIMT levels and CAC prevalence. Whether these changes could better predict future risk of hard cardiovascular disease events beyond LDL-C remains a research question to address.

Respiratory Fungal Communities are Associated with Systemic Inflammation and Predict Survival in Patients with Acute Respiratory Failure.

Rationale: Disruption of respiratory bacterial communities predicts poor clinical outcomes in critical illness; however, the role of respiratory fungal communities (mycobiome) is poorly understood. Objectives: We investigated whether mycobiota variation in the respiratory tract is associated with host-response and clinical outcomes in critically ill patients. Methods: To characterize the upper and lower respiratory tract mycobiota, we performed rRNA gene sequencing (internal transcribed spacer) of oral swabs and endotracheal aspirates (ETA) from 316 mechanically-ventilated patients. We examined associations of mycobiome profiles (diversity and composition) with clinical variables, host-response biomarkers, and outcomes. Measurements and Main Results: ETA samples with >50% relative abundance for C. albicans (51%) were associated with elevated plasma IL-8 and pentraxin-3 (p=0.05), longer time-to-liberation from mechanical ventilation (p=0.04) and worse 30-day survival (adjusted hazards ratio (adjHR): 1.96 [1.04-3.81], p=0.05). Using unsupervised clustering, we derived two clusters in ETA samples, with Cluster 2 (39%) showing lower alpha diversity (p<0.001) and higher abundance of C. albicans (p<0.001). Cluster 2 was significantly associated with the prognostically adverse hyperinflammatory subphenotype (odds ratio 2.07 [1.03-4.18], p=0.04) and predicted worse survival (adjHR: 1.81 [1.03-3.19], p=0.03). C. albicans abundance in oral swabs was also associated with the hyperinflammatory subphenotype and mortality. Conclusions: Variation in respiratory mycobiota was significantly associated with systemic inflammation and clinical outcomes. C. albicans abundance emerged as a negative predictor in both the upper and lower respiratory tract. The lung mycobiome may play an important role in the biological and clinical heterogeneity among critically ill patients and represent a potential therapeutic target for lung injury in critical illness.

Longitudinal profiles of neighborhood socioeconomic vulnerability influence blood pressure changes across the female midlife period.

PURPOSE: To examine whether longitudinal exposure to neighborhood socioeconomic vulnerability influences blood pressure changes throughout midlife in a racially, ethnically, and geographically-diverse cohort of women transitioning through menopause. METHODS: We used longitudinal data on 2738 women (age 42-52 at baseline) living in six United States cities from The Study of Women's Health Across the Nation. Residential histories, systolic blood pressures (SBP), and diastolic blood pressures (DBP) were collected annually for ten years. We used longitudinal latent profile analysis to identify patterns of neighborhood socioeconomic vulnerability occurring from 1996 to 2007 in participant neighborhoods. We used linear mixed-effect models to determine if a woman's neighborhood profile throughout midlife was associated with blood pressure changes. RESULTS: We identified four unique profiles of neighborhood socioeconomic vulnerability - differentiated by residential socioeconomic status, population density, and vacant housing conditions - which remained stable across time. Women residing in the most socioeconomically vulnerable neighborhoods experienced the steepest increase in annual SBP growth by 0.93 mmHg/year (95% CI: 0.65-1.21) across ten-year follow-up. CONCLUSIONS: Neighborhood socioeconomic vulnerability was significantly associated with accelerated SBP increases throughout midlife among women.

The quantity and quality of cardiovascular fat at mid-life and future cognitive performance among women: The SWAN cardiovascular fat ancillary study.

INTRODUCTION: Cardiovascular fat is a novel risk factor that may link to dementia. Fat volume and radiodensity are measurements of fat quantity and quality, respectively. Importantly, high fat radiodensity could indicate healthy or adverse metabolic processes. METHODS: The associations of cardiovascular fat (including epicardial, paracardial, and thoracic perivascular adipose tissue [PVAT]) quantity and quality assessed at mean age of 51 with subsequent cognitive performance measured repeatedly over 16 years of follow-up were examined using mixed models among 531 women. RESULTS: Higher thoracic PVAT volume was associated with a higher future episodic memory (ß[standard error (SE)] = 0.08 [0.04], P = 0.033), while higher thoracic PVAT radiodensity with lower future episodic (ß[SE] = -0.06 [0.03], P = 0.045) and working (ß[SE] = -0.24 [0.08], P = 0.003) memories. The latter association is prominent at higher volume of thoracic PVAT. DISCUSSION: Mid-life thoracic PVAT may have a distinct contribution to future cognition possibly due to its distinct adipose tissue type (brown fat) and anatomical proximity to the brain circulation. HIGHLIGHTS: Higher mid-life thoracic perivascular adipose tissue (thoracic PVAT) volume is related to a better future episodic memory in women. Higher mid-life thoracic PVAT radiodensity is related to worse future working and episodic memories. Negative association of high thoracic PVAT radiodensity with working memory is prominent at higher thoracic PVAT volume. Mid-life thoracic PVAT is linked to future memory loss, an early sign of Alzheimer's disease. Mid-life women's epicardial and paracardial fat are not related to future cognition.

Identifying Predictors of Adherence to the Physical Activity Goal: A Secondary Analysis of the SMARTER Weight Loss Trial.

INTRODUCTION/PURPOSE: Research is needed to inform tailoring supportive strategies for promoting physical activity (PA) in the context of behavioral treatment of obesity. We aimed to identify baseline participant characteristics and short-term intervention response predictors associated with adherence to the study-defined PA goal in a mobile health (mHealth) weight loss trial. METHODS: A secondary analysis was conducted of a 12-month weight loss trial (SMARTER) that randomized 502 adults with overweight or obesity to either self-monitoring of diet, PA, and weight with tailored feedback messages ( n = 251) or self-monitoring alone ( n = 251). The primary outcome was average adherence to the PA goal of ≥150 min·wk -1 of moderate- and vigorous-intensity aerobic activities (MVPA) from Fitbit Charge 2™ trackers over 52 wk. Twenty-five explanatory variables were considered. Machine learning methods and linear regression were used to identify predictors of adherence to the PA goal. RESULTS: The sample ( N = 502) was mostly female (80%), White (82%) with the average age of 45 ± 14.4 yr and body mass index of 33.7 ± 4.0 kg·m -2 . Machine learning methods identified PA goal adherence for the first week as the most important predictor of long-term PA goal adherence. In the parsimonious linear regression model, higher PA goal adherence for the first week, greater PA FB messages opened, older age, being male, higher education, being single and not having obstructive sleep apnea were associated with higher long-term PA goal adherence. CONCLUSIONS: To our knowledge, this is the first study using machine learning approaches to identify predictors of long-term PA goal adherence in a mHealth weight loss trial. Future studies focusing on facilitators or barriers to PA among young and middle-age adults and women with low PA goal adherence are warranted.

The independent associations of anti-Müllerian hormone and estradiol levels over the menopause transition with lipids/lipoproteins: The Study of Women's health Across the Nation.

BACKGROUND: The menopause transition (MT) is linked to adverse changes in lipids/lipoproteins. However, the related contributions of anti-Müllerian hormone (AMH) and estradiol (E2) are not clear. OBJECTIVE: To evaluate the independent associations of premenopausal AMH and E2 levels and their changes with lipids/lipoproteins levels [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1)] over the MT. METHODS: SWAN participants who transitioned to menopause without exogenous hormone use, hysterectomy, or bilateral oophorectomy with data available on both exposure and outcomes when they were premenopausal until the 1st visit postmenopausal were studied. RESULTS: The study included 1,440 women (baseline-age:mean±SD=47.4±2.6) with data available from up to 9 visits (1997-2013). Lower premenopausal levels and greater declines in AMH were independently associated with greater TC and HDL-C, whereas lower premenopausal levels and greater declines in E2 were independently associated with greater TG and apo B and lower HDL-C. Greater declines in AMH were independently associated with greater apoA-1, and greater declines in E2 were independently associated with greater TC and LDL-C. CONCLUSIONS: AMH and E2 and their changes over the MT relate differently to lipids/lipoproteins profile in women during midlife. Lower premenopausal and/or greater declines in E2 over the MT were associated with an atherogenic lipid/lipoprotein profile. On the other hand, lower premenopausal AMH and/or greater declines in AMH over the MT were linked to higher apo A-1 and HDL-C; the later found previously to be related to a greater atherosclerotic risk after menopause.

Association of Driving Distance to Maternity Hospitals and Maternal and Perinatal Outcomes.

OBJECTIVE: To assess whether there are associations between driving distance from the patient residence to the delivery hospital and adverse maternal and perinatal health outcomes. METHODS: We performed a retrospective cohort study using 2011-2015 Pennsylvania birth records of live births at 20 weeks of gestation or more, excluding inpatient hospital transfers or implausible distances. The shortest driving distance from patient residence to the delivery hospital was calculated in ArcGIS and was evaluated in association with a composite of adverse maternal outcomes (blood transfusion, unplanned operation, ruptured uterus, unplanned hysterectomy, or intensive care unit admission) and neonatal intensive care unit (NICU) admission. Multivariable-adjusted Poisson models were used to estimate relative risks with 95% CIs with a referent difference of 1 km distance to the delivery hospital. RESULTS: A total 662,245 birth records were included, and the median driving distance to the hospital was 11.3 km (interquartile range 5.4-21.6 km). The overall rate of the composite maternal outcome was 0.6% and of NICU admission was 8.4%. Compared with the referent distance, increasing driving distance was significantly associated with increased adjusted risks of the maternal composite outcome (adjusted relative risk [aRR] 1.22, 95% CI 1.07-1.36 for 60 km; aRR 1.36, 95% CI 1.19-1.53 for 70 km; and 1.53, 95% CI 1.31-1.75 for 80 km) and NICU admission (aRR 1.70, 95% CI 1.65-1.76 for 60 km; aRR 1.96, 95% CI 1.90-2.02 for 70 km; and aRR 2.25, 95% CI 2.18-2.33 for 80 km). CONCLUSION: Longer distances to the delivery hospital were associated with greater risk of adverse maternal outcomes and NICU admission. Whether these findings reflect health care delivery deficits or simply serve as a marker of social deprivation requires further study.

Early Midlife Cardiovascular Health Influences Future HDL Metrics in Women: The SWAN HDL Study.

Background Utility of high-density lipoprotein cholesterol (HDL-C) in assessing the antiatherogenic properties of HDL may be limited in midlife women. Novel metrics of HDL function, lipid contents, and subclasses may better reflect the atheroprotective capacities of HDL, supporting the need to evaluate how cardiovascular health affects these metrics in women. We assessed the relationship of early midlife Life's Simple 7 (LS7) score and its health behavior components with future HDL function (HDL-cholesterol efflux capacity), HDL-phospholipid, HDL-triglyceride, HDL particles (HDL-P) and size, and the relationship between LS7 score and changes in HDL metrics over time. Methods and Results We analyzed 529 women (baseline age: 46.4 [2.6] years, 57% White) from the SWAN HDL (Study of Women's Health Across the Nation HDL) study who had baseline LS7 followed by future repeated HDL metrics. Multivariable linear mixed models were used. Higher LS7 score was associated with favorable future HDL profile (higher HDL-phospholipid, total HDL-P and large HDL-P, lower HDL-triglyceride, and larger overall HDL size). Ideal body mass index was associated with higher HDL-cholesterol efflux capacity, HDL-phospholipid, and large HDL-P, lower HDL-triglyceride and small HDL-P, and larger overall HDL size. Ideal physical activity was associated with higher HDL-phospholipid, and total, large, and medium HDL-P. Ideal smoking was associated with less HDL-triglycerides. Diet was not related to HDL metrics. Higher LS7 score and ideal body mass index were associated with slower progression of HDL size over time. Conclusions Novel HDL metrics may better reflect the clinical utility of HDL. Improving lifestyle at midlife, particularly maintaining ideal body mass index, is associated with better future HDL phenotype.

Associations of HDL subclasses and lipid content with complement proteins over the menopause transition: The SWAN HDL ancillary study: HDL and complement proteins in women.

BACKGROUND: The menopause transition (MT) could trigger low-grade chronic inflammation which may modify high-density lipoproteins (HDL) and lead to additional inflammatory responses contributing to atherosclerosis development. OBJECTIVE: To test whether complement proteins C3 and C4 increase around the final menstrual period (FMP), and whether changes in HDL subclasses and lipid content associate with C3 and C4 levels over time in midlife women. METHODS: The study included 471 women (at baseline: age 50.2(2.7) years; 87.3% pre or peri-menopausal) who had nuclear magnetic resonance spectroscopy HDL subclasses, lipid content, and C3 and C4 measured up to 5 times over the MT. RESULTS: Adjusted annual changes in C3 and C4 varied by time segments relative to FMP with significant increases, steeper for C3, only observed within 1 year before to 2 years after the FMP. Greater decreases in large HDL particles (HDL-P), HDL size, and HDL-phospholipids, and greater increases in small HDL-P and HDL-Triglycerides were associated with higher C3 and C4 over time, although associations with C4 were weaker than those with C3. CONCLUSION: Complement proteins C3 and C4 significantly rise around menopause with C3 showing the steepest rise. Changes in HDL subclasses, overall size, and lipid content, over the MT may play a role in modulating inflammation responses known to be related to atherosclerosis. These results raise the possibility that novel therapeutic agents focusing on HDL might contribute to CVD protection by modulating inflammation.

Lipoprotein subfractions and subclinical vascular health in middle aged women: does menopause status matter?

OBJECTIVE: During midlife, women experience changes in lipoprotein profiles and deterioration in vascular health measures. We analyzed the associations of groups of lipoprotein subfractions as determined by principal component analysis (PCA) with subclinical vascular health measures in midlife women and tested if these associations were modified by menopause status. METHODS: PCA was used to generate principal components (PCs) from 12 lipoprotein subfractions quantified among 545 midlife women. The associations of the identified PCs and concurrent vascular health measures were assessed using linear or logistic regressions among participants with carotid intima-media thickness (cIMT; n = 259), coronary artery calcium (n = 249), or aortic calcium (n = 248) scores. RESULTS: PCA generated four PCs representing groups of (1) small, medium, and large very low-density lipoproteins subclasses-very low-density lipoprotein PC; (2) very small, small, and medium low-density lipoprotein (LDL) subclasses-small-medium LDL-PC; (3) large and small high-density lipoproteins subclasses and midzone particles-high-density lipoprotein PC; and (4) large LDL and small intermediate-density lipoproteins-large LDL-PC. Small-medium LDL-PC was positively associated with cIMT, coronary artery calcium, and aortic calcium in unadjusted but not in adjusted models. Menopause status modified the positive association of the small-medium LDL-PC with cIMT (interaction P = 0.02) such that this association was stronger after versus before menopause ( P = 0.01). CONCLUSIONS: Carotid intimal medial thickening is positively and independently associated with small- and medium-sized LDL particles after menopause. Monitoring levels of specific lipoprotein fractions may have value in identifying midlife women at risk for developing atherosclerotic vascular disease.

Design and rationale of the mobile health intervention for rural atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a highly morbid condition which requires long-term adherence to oral anticoagulation and may be associated with adverse quality of life and health care utilization. We developed a relational agent-an interactive smartphone-based intervention accessible regardless of digital or health literacy-to assist individuals residing in rural, Western Pennsylvania, with AF with chronic disease self-management. METHODS: The "Mobile health intervention for rural atrial fibrillation" is a single center, parallel-arm randomized clinical trial for adults with AF funded by the National Institute of Health's National Heart, Lung, and Blood Institute to enroll 264 participants. All participants receive a smartphone with data plan: The intervention is a 4 month relational agent coupled with the AliveCor Kardia for heart rate and rhythm monitoring provided by smartphone, and the control a pre-installed, smartphone-based application for health-related information (WebMD). The study uses remote recruitment and engagement to enroll individuals who would otherwise be unlikely to participate in clinical research due to rurality. The primary outcome of the trial is adherence to oral anticoagulation, determined by proportion of days covered, as measured at 12 months. The secondary outcomes are quality of life, both AF-specific and general, and health care utilization. The study entails a baseline visit, a 4 month intervention phase, and 8 and 12 month follow-up visits. CONCLUSIONS: This mobile health trial tests the effectiveness of a smartphone-based relational agent to improve clinical and patient-reported outcomes in rural-dwelling individuals.

Excessive Gestational Weight Gain and Long-Term Maternal Cardiovascular Risk Profile: The Study of Women's Health Across the Nation.

Background: Excessive gestational weight gain (GWG) is consistently linked with maternal risk of obesity. However, the literature on its long-term cardiovascular risk is minimal and conflicting. We evaluated whether excessive GWG is associated with a high-risk cardiovascular profile among parous women in midlife. Materials and Methods: Participants were women in the multiethnic cohort Study of Women's Health Across the Nation with a history of live birth(s). Excessive GWG was defined according to Institute of Medicine guidelines and collected by self-recall. Outcomes were the atherosclerotic cardiovascular disease (ASCVD) risk score and C-reactive protein (CRP), measured at the study baseline when mean age was 47 years, and at 10 follow-up visits (1996-2017). We estimated the association of excessive GWG with outcomes through linear mixed model regression. Results: The analytic sample included 1318 women with 3049 singleton births. Over 40% (536) reported one or more pregnancies with excessive GWG. Longitudinal models estimated that at a mean age of 67, women with a history of excessive GWG had a 9.8% (9.2, 10.5) 10-year ASCVD risk, compared to 9.5% (8.9, 10.1) for those without, and mean CRP of 2.20 mg/L (1.89, 2.57) versus 1.85 mg/L (1.61, 2.14), respectively, adjusted for participant characteristics. Conclusions: In this multiethnic cohort of parous women, a history of excessive GWG was associated with a small, but statistically significant difference in ASCVD risk, and a moderate, statistically significant difference in CRP across midlife. More research is necessary to understand the mechanistic pathway between excessive GWG and long-term maternal cardiovascular health.

Associations of Abdominal and Cardiovascular Adipose Tissue Depots With HDL Metrics in Midlife Women: the SWAN Study.

CONTEXT: The menopause transition is accompanied by declines in the atheroprotective features of high-density lipoprotein (HDL), which are linked to deleterious cardiovascular (CV) outcomes. OBJECTIVE: This work aimed to assess the relationship between abdominal and CV visceral adipose tissues (VAT) with future HDL metrics in midlife women, and the role of insulin resistance (IR) on these associations. METHODS: Temporal associations compared abdominal and CV fat with later measures of HDL metrics. This community-based cohort comprised 299 women, baseline mean age 51.1 years (SD: 2.8 years), 67% White, 33% Black, from the Study of Women's Health Across the Nation (SWAN) HDL ancillary study. Exposures included volumes of abdominal VAT, epicardial AT (EAT), paracardial AT (PAT), or perivascular AT (PVAT). Main outcomes included HDL cholesterol efflux capacity (HDL-CEC); HDL phospholipids (HDL-PL), triglycerides (HDL-Tgs), and cholesterol (HDL-C); apolipoprotein A-I (ApoA-I), and HDL particles (HDL-P) and size. RESULTS: In multivariable models, higher abdominal VAT was associated with lower HDL-CEC, HDL-PL, HDL-C, and large HDL-P and smaller HDL size. Higher PAT was associated with lower HDL-PL, HDL-C, and large HDL-P and smaller HDL size. Higher EAT was associated with higher small HDL-P. Higher PVAT volume was associated with lower HDL-CEC. The Homeostatic Model Assessment of Insulin Resistance partially mediated the associations between abdominal AT depots with HDL-CEC, HDL-C, large HDL-P, and HDL size; between PVAT with HDL-CEC; and PAT with HDL-C, large HDL-P, and HDL size. CONCLUSION: In midlife women, higher VAT volumes predict HDL metrics 2 years later in life, possibly linking them to future CV disease. Managing IR may preclude the unfavorable effect of visceral fat on HDL metrics.