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.

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.

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 .

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.

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.

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.

Postmenopausal Women With Greater Paracardial Fat Have More Coronary Artery Calcification Than Premenopausal Women: The Study of Women's Health Across the Nation (SWAN) Cardiovascular Fat Ancillary Study.

BACKGROUND: Volumes of paracardial adipose tissue (PAT) and epicardial adipose tissue (EAT) are greater after menopause. Interestingly, PAT but not EAT is associated with estradiol decline, suggesting a potential role of menopause in PAT accumulation. We assessed whether volumes of heart fat depot (EAT and PAT) were associated with coronary artery calcification (CAC) in women at midlife and whether these associations were modified by menopausal status and estradiol levels. METHODS AND RESULTS: EAT and PAT volumes and CAC were measured using electron beam computed tomography scans. CAC was evaluated as (1) the presence of CAC (CAC Agatston score ≥10) and (2) the extent of any CAC (log CAC Agatston score >0). The study included 478 women aged 50.9 years (58% pre- or early perimenopausal, 10% late perimenopausal, and 32% postmenopausal). EAT was significantly associated with CAC measures, and these associations were not modified by menopausal status or estradiol. In contrast, associations between PAT and CAC measures were modified by menopausal status (interaction-P≤0.01). Independent of study covariates including other adiposity measures, each 1-SD unit increase in log PAT was associated with 102% higher risk of CAC presence (P=0.04) and an 80% increase in CAC extent (P=0.008) in postmenopausal women compared with pre- or early perimenopausal women. Additional adjustment for estradiol and hormone therapy attenuated these differences. Moreover, the association between PAT and CAC extent was stronger in women with lower estradiol levels (interaction P=0.004). CONCLUSIONS: The findings suggest that PAT is a potential menopause-specific coronary artery disease risk marker, supporting the need to monitor and target this fat depot for intervention in women at midlife.

Mexican American trial of community health workers: a randomized controlled trial of a community health worker intervention for Mexican Americans with type 2 diabetes mellitus.

OBJECTIVES: We assessed whether community health workers (CHWs) could improve glycemic control among Mexican Americans with diabetes. METHODS: We recruited 144 Mexican Americans with type 2 diabetes between January 2006 and September 2008 into the single-blinded, randomized controlled Mexican American Trial of Community Health Workers (MATCH) and followed them for 2 years. Participants were assigned to either a CHW intervention, delivering self-management training through 36 home visits over 2 years, or a bilingual control newsletter delivering the same information on the same schedule. RESULTS: Intervention participants showed significantly lower hemoglobin A1c levels than control participants at both year 1 Δ = -0.55; P = .021) and year 2 (Δ = -0.69; P = .005). We observed no effect on blood pressure control, glucose self-monitoring, or adherence to medications or diet. Intervention participants increased physical activity from a mean of 1.63 days per week at baseline to 2.64 days per week after 2 years. CONCLUSIONS: A self-management intervention delivered by CHWs resulted in sustained improvements in glycemic control over 2 years among Mexican Americans with diabetes. MATCH adds to the growing body of evidence supporting the use of CHWs to reduce diabetes-related health disparities.

The Mexican-American Trial of Community Health workers (MATCH): design and baseline characteristics of a randomized controlled trial testing a culturally tailored community diabetes self-management intervention.

OBJECTIVES: Community Health Workers (CHWs) have been recommended to reduce diabetes disparities, but few robust trials of this approach have been conducted. Limitations of prior studies include: unspecified a priori outcomes; lack of blinded outcome assessments; high participant attrition rates; and lack of attention to intervention fidelity. These limitations reflect challenges in balancing methodologic rigor with the needs of vulnerable populations. The Mexican-American Trial of Community Health workers (MATCH) was a blinded randomized controlled trial testing CHW efficacy in improving physiologic outcomes and self-management behaviors among Mexican-Americans with type 2 diabetes. This paper describes methods used to overcome limitations of prior studies. RESEARCH DESIGN AND METHODS: The primary aim was to determine if a CHW intervention would result in significant reductions in Hemoglobin A1c and rates of uncontrolled blood pressure. 144 Mexican-Americans with diabetes were randomized. The intervention consisted of self-management training delivered by CHWs over a 24-month period; the comparison population received identical information via bilingual newsletter. Blinded research assistants completed assessments at baseline, 12 months, and 24 months post-randomization. RESULTS: The MATCH cohort was characterized by low acculturation and socioeconomic status. Study participants had low rates of medication adherence and glucose monitoring. 70% had poor glycemic control with A1c levels over 7.0, and 57.3% had blood pressures worse than ADA target levels (<130/80). CONCLUSIONS: MATCH preserved community sensitivity and methodologic rigor. The study's attention to intervention fidelity, behavioral attention control, blinded outcomes assessment, and strategies to enhance participant retention can be replicated by researchers testing culturally-tailored CHW interventions.