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.

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.

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.

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.

North to south gradient and local waves of influenza in Chile.

Influenza seasonality is caused by complex interactions between environmental factors, viral mutations, population crowding, and human travel. To date, no studies have estimated the seasonality and latitudinal patterns of seasonal influenza in Chile. We obtained influenza-like illness (ILI) surveillance data from 29 Chilean public health networks to evaluate seasonality using wavelet analysis. We assessed the relationship between the start, peak, and latitude of the ILI epidemics using linear and piecewise regression. To estimate the presence of incoming and outgoing traveling waves (timing vs distance) between networks and to assess the association with population size, we used linear and logistic regression. We found a north to south gradient of influenza and traveling waves that were present in the central, densely populated region of Chile. Our findings suggest that larger populations in central Chile drive seasonal influenza epidemics.

Rurality and atrial fibrillation: a pathway to virtual engagement and clinical trial recruitment in response to COVID-19.

Study Objective: To summarize trial adaptation from in-clinic to virtual design in response to the SARS-2 coronavirus-2 (COVID-19). Design: A clinical trial of a mobile health intervention to improve chronic disease self-management for rural individuals with atrial fibrillation (AF). The trial has a 4-month intervention - accessible regardless of health or digital literacy - to enhance AF medication adherence and patient experience with 8- and 12-month assessments of sustainability. Setting: Rural, western Pennsylvania. Participants: Rural individuals with AF receiving oral anticoagulation for stroke prevention. Interventions: Enrolled participants underwent a telephone-based orientation, provided verbal consent, and were randomized using a digital platform. They received a smartphone with intervention or control applications and a curriculum on usage tailored for study arm. Participants received study assessments by mail with telephone-based administration and contact for the 12-month trial. Main Outcome Measures: Successful adaptation to virtual engagement and recruitment. Results: The study enrolled 18 participants during in-clinic recruitment (January-March 2020). From 5/1/2020 to 5/6/2021 the study team enrolled 130 individuals (median age 72.4 years, range 40.8-92.2; 49.2% women, 63.1% without college degree, and 45.4% with limited health literacy. Retention of participants enrolled using virtual methods during the 4-month intervention phase is 92%. Conclusions: We report a virtual trial of a mobile health intervention for rural individuals with AF. Our successful implementation suggests promise for engaging geographically isolated rural individuals, potential to enhance digital health access, and advance rural health equity.

Abdominal visceral adipose tissue over the menopause transition and carotid atherosclerosis: the SWAN heart study.

OBJECTIVES: To characterize abdominal visceral adipose tissue (VAT) trajectory relative to the final menstrual period (FMP), and to test whether menopause-related VAT accumulation is associated with greater average, common carotid artery intima-media thickness (cIMT) and/or internal carotid artery intima-media thickness (ICA-IMT). METHODS: Participants were 362 women (at baseline: age was (mean ±â€ŠSD) 51.1 ±â€Š2.8 y; 61% White, 39% Black) with no cardiovascular disease from the Study of Women's Health Across the Nation Heart study. Women had up to two measurements of VAT and cIMT over time. Splines revealed a nonlinear trajectory of VAT with two inflection points demarcating three time segments: segment 1: >2 years before FMP; segment 2: 2 years before FMP to FMP; and segment 3: after FMP. Piecewise-linear random-effects models estimated changes in VAT. Random-effects models tested associations of menopause-related VAT with each cIMT measure separately. Estimates were adjusted for age at FMP, body mass index, and sociodemographic, lifestyle, and cardiovascular disease risk factors. RESULTS: VAT increased significantly by 8.2% (95% CI: 4.1%-12.5%) and 5.8% (3.7%-7.9%) per year in segments 2 and 3, respectively, with no significant change in VAT within segment 1. VAT predicted greater ICA-IMT in segment 2, such that a 20% greater VAT was associated with a 2.0% (0.8%-3.1%) greater ICA-IMT. VAT was not an independent predictor of ICA-IMT in the other segments or of the other cIMT measures after adjusting for covariates. CONCLUSIONS: Women experience an accelerated increase in VAT starting 2 years before menopause. This menopause-related increase in VAT is associated with greater risk of subclinical atherosclerosis in the internal carotid artery.

Video Summary:http://links.lww.com/MENO/A722 .

Gestational Weight Gain and Long-term Maternal Obesity Risk: A Multiple-Bias Analysis.

BACKGROUND: Lifecourse research provides an important framework for chronic disease epidemiology. However, data collection to observe health characteristics over long periods is vulnerable to systematic error and statistical bias. We present a multiple-bias analysis using real-world data to estimate associations between excessive gestational weight gain and mid-life obesity, accounting for confounding, selection, and misclassification biases. METHODS: Participants were from the multiethnic Study of Women's Health Across the Nation. Obesity was defined by waist circumference measured in 1996-1997 when women were age 42-53. Gestational weight gain was measured retrospectively by self-recall and was missing for over 40% of participants. We estimated relative risk (RR) and 95% confidence intervals (CI) of obesity at mid-life for presence versus absence of excessive gestational weight gain in any pregnancy. We imputed missing data via multiple imputation and used weighted regression to account for misclassification. RESULTS: Among the 2,339 women in this analysis, 937 (40%) experienced obesity in mid-life. In complete case analysis, women with excessive gestational weight gain had an estimated 39% greater risk of obesity (RR = 1.4, CI = 1.1, 1.7), covariate-adjusted. Imputing data, then weighting estimates at the guidepost values of sensitivity = 80% and specificity = 75%, increased the RR (95% CI) for obesity to 2.3 (2.0, 2.6). Only models assuming a 20-point difference in specificity between those with and without obesity decreased the RR. CONCLUSIONS: The inference of a positive association between excessive gestational weight gain and mid-life obesity is robust to methods accounting for selection and misclassification bias.

Identifying women who share patterns of reproductive hormones, vasomotor symptoms, and sleep maintenance problems across the menopause transition: group-based multi-trajectory modeling in the Study of Women's Health Across the Nation.

OBJECTIVE: To identify groups of women who share levels and patterns of change in follicle-stimulating hormone (FSH), self-reported sleep maintenance problems, and frequent vasomotor symptoms (VMS) up to 10 years before and after their final menstrual period and to evaluate their premenopausal characteristics. METHOD: Group-based multi-trajectory modeling grouped 1,407 women from the Study of Women's Health Across the Nation who had an observed natural menopause and did not use hormone therapy, based on repeated measures of FSH, sleep maintenance problems, and frequent VMS relative to final menstrual period. Multivariable analyses assessed race/ethnicity, body mass index, smoking, and depressive symptoms as predictors of group membership. RESULTS: Women formed five distinct groups: (1) low symptoms (low VMS/sleep problems)/high FSH rise (N = 552; 39.2%); (2) moderate VMS and sleep problems/low FSH rise (N = 169; 12.0%); (3) dominant sleep problems (lower VMS/high sleep problems)/high FSH rise (N = 203; 14.4%); (4) dominant VMS (high VMS/lower sleep problems)/high FSH rise (N = 297; 21.1%)); and (5) high symptoms (high VMS/high sleep problems)/intermediate FSH rise (N = 186; 13.2%)). Multivariate analyses showed that race/ethnicity, premenopausal body mass index and depressive symptoms, and increasing depressive symptoms during the early phase of the transition predicted group membership. CONCLUSIONS: Women can be classified based on shared levels and patterns of FSH, sleep maintenance problems, and frequent VMS across the menopause transition. Either VMS or sleep maintenance problems can be dominant in the face of high FSH. Experiencing one menopause-related symptom or hormone profile does not automatically imply that another is also being experienced.

Excessive gestational weight gain is associated with severe maternal morbidity.

PURPOSE: We determined the association between gestational weight gain and severe maternal morbidity. METHODS: We used data on 84,241 delivery hospitalizations at Magee-Womens Hospital, Pittsburgh, PA (2003-2012). Total gestational weight gain (kilogram) was converted to gestational age-standardized z-scores. We defined severe maternal morbidity as having ≥1 of the 21 Centers for Disease Control diagnosis or procedure codes for severe maternal morbidity identification, intensive care unit admission, or extended postpartum stay. We used multivariable logistic regression to determine the association between weight gain and severe maternal morbidity after confounder adjustment. RESULTS: High gestational weight gain z-scores were associated with an increased risk of severe maternal morbidity. Compared with z-score 0 SD (equivalent to 16 kg at 40 weeks in a normal-weight woman), risk differences (95% confidence intervals) for z-scores -2 SD (7 kg), -1 SD (11 kg), +1 SD (23 kg), and +2 SD (31 kg) were 1.5 (-0.71, 3.7), 0.056 (-0.81, 0.93), 3.4 (1.7, 5.0), and 8.6 (4.0, 13) per 1000 deliveries. The results did not vary by gestational age at delivery or prepregnancy body mass index. CONCLUSIONS: The increased risk of severe maternal morbidity with high pregnancy weight gain may allow scientists to understand and prevent this serious condition.

Heart fat and carotid artery atherosclerosis progression in recently menopausal women: impact of menopausal hormone therapy: The KEEPS trial.

OBJECTIVE: Heart fat deposition has been linked to atherosclerosis, and both accelerate after menopause. Hormone therapy (HT) may differentially slow heart fat deposition and progression of atherosclerosis, depending on the specific HT agent or its route of administration. Our objective was to evaluate the effects of different HT agents, oral and transdermal, on associations between heart fat accumulation and atherosclerosis progression, measured by carotid intima-media thickness (CIMT), in recently menopausal women from the Kronos Early Estrogen Prevention Study (KEEPS) trial. METHODS: KEEPS was a randomized, placebo-controlled trial of the effects of 0.45 mg/d oral conjugated equine estrogens (o-CEE) or 50 mcg/d transdermal 17ß-estradiol (t-E2), compared with placebo, on 48 months progression of CIMT. Epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT) volumes were quantified by computed tomography. RESULTS: In all, 467 women (mean age [SD] 52.7 [2.5]; 78.2% White; 30% on o-CEE, 30.8% t-E2, 39.2% placebo) with heart fat volumes and CIMT at baseline and 48 months were included. EAT and PAT changes were not associated with CIMT progression; however, the assigned treatment significantly modified the association between PAT (but not EAT) change and CIMT progression. In the o-CEE group, adjusted CIMT progression was 12.66 µm (95% confidence interval [CI] 1.80, 23.52) lower than in t-E2 group (P = 0.02), and 10.09 µm (95% CI 0.79, 19.39) lower than in placebo group (P = 0.03), as per 1-SD increase in PAT. CONCLUSION: Compared with t-E2, o-CEE appears to slow down the adverse effect of increasing PAT on progression of atherosclerosis. Whether this beneficial association is specific to CEE or to the oral route of CEE administration is unclear and should be assessed further.

Arterial Stiffness Accelerates Within 1 Year of the Final Menstrual Period: The SWAN Heart Study.

OBJECTIVE: Menopause may augment age-dependent increases in arterial stiffness, with black women having greater progression in midlife compared with white women. We sought to determine whether and when women experience changes in arterial stiffness relative to the final menstrual period (FMP) and whether these changes differ between black and white midlife women. Approach and Results: We evaluated 339 participants from the SWAN (Study of Women's Health Across the Nation) Heart Ancillary study (Study of Women's Health Across the Nation). Women had ≤2 carotid-femoral pulse-wave velocity (cfPWV) exams over a mean±SD of 2.3±0.5 years of follow-up. Annual percentage changes in cfPWV were estimated in 3 time segments relative to FMP and compared using piecewise linear mixed-effects models. At baseline, women were 51.1±2.8 years of age and 36% black. Annual percentage change (95% CI) in cfPWV varied by time segments: 0.9% (-0.6% to 2.3%) for >1 year before FMP, 7.5% (4.1% to 11.1%) within 1 year of FMP, and -1.0% (-2.8% to 0.8%) for >1 year after FMP. Annual percentage change in cfPWV within 1 year of FMP was significantly greater than the other 2 time segments; P<0.05 for both comparisons. Adjusting for concurrent cardiovascular disease risk factors explained part of the change estimates but did not eliminate the difference. Black women had greater increase in cfPWV compared with white women in the first segment; P for interaction, 0.04. CONCLUSIONS: The interval within 1 year of FMP is a critical period for women when vascular functional alterations occur. These findings underscore the importance of more intensive lifestyle modifications in women transitioning through menopause.

The menopause transition and women's health at midlife: a progress report from the Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: Our initial understanding of the menopause transition (MT) has been framed by clinical samples of women seeking treatment rather than by population-based studies. The Study of Women's Health Across the Nation (SWAN) initiated in 1996 with an overall goal to define the MT, to characterize its biological and psychosocial antecedents and sequelae in an ethnically and racially diverse sample of midlife women. METHODS: This review summarizes the central findings of SWAN to date that can inform women and their healthcare providers about the impact of the MT and midlife aging on overall health and well-being. RESULTS: SWAN characterized changes in reproductive axis and menstrual cycle patterns that informed the development of the reproductive aging staging system Staging of Reproductive Aging Workshop+10; MT-related symptoms and mental health (vasomotor symptoms, sleep complaints, psychological symptoms, cognitive performance, and urogenital and sexual health); and physiological systems and functions (cardiovascular and cardiometabolic health, bone health, physical function performance) that are influenced by the MT. SWAN demonstrated substantial interrelations among these changes and significant racial/ethnic differences in the rate and magnitude of change in multiple health indictors in midlife women. The findings point to midlife as a critical stage for adopting healthy behavior and preventive strategies. CONCLUSIONS: Over the past 23 years, SWAN has advanced our understanding of the impact of the MT and midlife aging on health and well-being in women. SWAN will be instrumental to determine whether MT-related changes during midlife are related to unfavorable health and well-being in early old age.

Optimal Blood Pressure Thresholds for Minimal Coronary Artery Disease Risk in Type 1 Diabetes.

OBJECTIVE: We aimed to determine optimal blood pressure (BP) thresholds for minimizing coronary artery disease (CAD) risk in people with childhood-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: The Pittsburgh Epidemiology of Diabetes Complications (EDC) Study participants without known CAD at baseline (n = 605) were included and followed for 25 years. The associations of time-weighted BP measures (systolic BP [SBP], diastolic BP [DBP], and mean arterial pressure) with incident CAD were examined by using Cox models. Areas under the receiver operating characteristic curve (AUC) were summarized by different cut points of time-weighted BPs. Risk stratification analyses were then performed on the basis of BP (<120/80 vs. ≥120/80 mmHg) and HbA1c (<8% vs. ≥8%). RESULTS: Baseline mean age was 27 years. Half of the cohort were women and 98% were white. A dose-gradient association was observed for categorized time-weighted BPs and CAD. According to AUC, the optimal cut point for SBP was 120 mmHg and for DBP was 80 mmHg. BP ≥120/80 mmHg was associated with a 1.9 times (95% CI 1.4, 2.6) greater risk of developing CAD than that for BP <120/80 mmHg. Participants with good control of both BP and HbA1c had BP <120/80 mmHg and HbA1c <8%. Those with only high BP (hazard ratio [HR] 2.0 [95% CI 1.1, 3.9]) carried a similar risk of developing CAD as those with only high HbA1c (HR 1.6 [95% CI 0.97, 2.8]). CONCLUSIONS: The optimal BP threshold associated with minimal CAD risk is 120/80 mmHg in young adults with childhood-onset type 1 diabetes.

Cardiovascular fat in women at midlife: effects of race, overall adiposity, and central adiposity. The SWAN Cardiovascular Fat Study.

OBJECTIVES: Cardiovascular fat (CF) is associated with greater coronary heart disease (CHD) risk. Postmenopausal women have greater CF volumes than premenopausal women, and the association between specific CF depot volumes and CHD risk is more pronounced after menopause. Race, central adiposity, and visceral adiposity are important factors that could impact CF volumes. Whether racial differences in CF volumes and in their associations with central (visceral fat [VAT]) and general adiposity (body mass index [BMI]) exist in midlife women have not been addressed before. METHODS: In all, 524 participants from the Study of Women's Health Across the Nation (mean age: 50.9 ±â€Š2.9 years; 62% White and 38% Black) who had data on CF volumes (epicardial fat [EAT], paracardial fat [PAT], total heart fat, and aortic perivascular fat), VAT, and BMI were studied. RESULTS: In models adjusted for age, study site, menopausal status, comorbid conditions, alcohol consumption, and physical activity, Black women had 19.8% less EAT, 24.5% less PAT, 20.4% less total heart fat, and 13.2% less perivascular fat than White women (all P < 0.001). These racial differences remained significant after additional adjustment for BMI or VAT. Race significantly modified associations between adiposity measures and CF volumes. Every 1-SD higher BMI was associated with 66.7% greater PAT volume in White compared with 42.4% greater PAT volume in Black women (P = 0.004), whereas every 1-SD higher VAT was associated with 32.3% greater EAT volume in Black compared with 25.3% greater EAT volume in White women (P = 0.039). CONCLUSIONS: Racial differences were found in CF volumes and in their associations with adiposity measures among midlife women. Future research should determine how race-specific changes in CF volumes impact CHD risk in women.

SRS-22r Scores in Nonoperated Adolescent Idiopathic Scoliosis Patients With Curves Greater Than Forty Degrees.

STUDY DESIGN: Case control comparative series. OBJECTIVE: Describe surgical range adolescent idiopathic scoliosis (AIS) patients electing to forgo surgery and compare health-related quality-of-life outcomes to a similar cohort of operated AIS patients by the same single surgeon. SUMMARY OF BACKGROUND DATA: No data have been published either documenting SRS-22r scores of nonoperated patients with curves ≥40° or comparing these scores to a demographically similar operated cohort. METHODS: Individuals with curves ≥40°, age ≥18 years, and electing to forgo surgery were identified. All patients completed an SRS-22r questionnaire. This nonoperated cohort's SRS-22r scores were compared to those of a large demographically similar cohort operated by the same surgeon. Group differences between the SRS-22r scores were evaluated by comparing these to published Minimal Clinically Important Differences (MCID) for the SRS-22r. RESULTS: One hundred ninety subjects with nonoperated curves were compared to 166 individuals who underwent surgery. The nonoperated cohort averaged 23.5 years of age, averaged 7.7 years since curve reached 40°, and had an average 50° Cobb angle at last follow-up. No statistical significant differences were found between the groups on the Pain, Function, or Mental Health domains of the SRS-22r. Statistically significant differences in favor of the operative cohort were found for self-image, satisfaction, and total score. The observed group differences did not meet the established thresholds for minimal clinically important differences in any of the domain scores, the average total score, or raw scores. CONCLUSION: There are no meaningful clinically significant differences in SRS-22r scores at average 8-year follow-up between AIS patients with curves ≥40° treated with or without surgery. These data in conjunction with an absence of long-term evidence of serious medical consequences with nonsurgical management of curves ≥40° should encourage surgeons to reevaluate the benefits of routine surgical care. LEVEL OF EVIDENCE: 3.

Lipoprotein subclasses and endogenous sex hormones in women at midlife.

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% White and 42.5% 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.