Abstract P327: Associations Between Ectopic Cardiovascular Fat Depots and Aortic Calcification Vary by Race and Menopausal Status in Women at Midlife: The Study of Women’s Health Across the Nation (SWAN) Ectopic Cardiovascular Fat Ancillary Study

Objective: Mounting evidence demonstrates a role of ectopic cardiovascular fat (ECF), which surrounds the heart and vasculature, in the pathogenesis of cardiovascular disease (CVD). It is unknown whether ECF depots are related to atherosclerotic burden in women transitioning through menopause, a time of increasing CVD risk. We evaluated the cross-sectional associations between volumes of epicardial (EAT), pericardial (PAT), total heart (TAT; TAT=EAT+PAT) and perivascular (peri-aortic) (PVAT) adipose tissues and aortic calcification (AC) in a sample of white and black midlife women. Effect modifications by race and menopausal status were also examined. Design: Data were obtained from the SWAN ectopic cardiovascular fat ancillary study. AC and ECF depots were quantified by electron beam computed tomography. Outcomes were presence of AC among all women, and extent of AC among women with an Agatston score >0. Logistic and linear regression were used as appropriate. Final models were adjusted for age, race, study site, menopausal status, body mass index (BMI), systolic blood pressure, lipids and insulin resistance. Results: The study included 257 women (32.7% Black; 58.7% pre-/early peri-menopausal and 41.3% late peri-/postmenopausal) aged 46-58 years with data on any of the 4 ECF depots (EAT, PAT and TAT: n=227, PVAT: n=191). AC was found in 184 (71.6%) participants. Pre-/early peri menopausal women had less EAT (median (Q1, Q3): 35.0 (28.4, 51.7) cm 3 vs. 43.5 (32.9, 58.3) cm 3 , P = 0.02) and TAT (median (Q1, Q3): 42.5 (33.2, 64.5) cm 3 vs. 50.3 (38.9, 74.3) cm 3 , P = 0.05) than late peri-/postmenopausal women, respectively. In final models, only EAT (OR (95%CI): 3.29 (1.14, 9.54)) was associated with higher odds of presence of AC. Interactions with race or menopausal status were not significant. Relationships between ECF depots (EAT,PAT and TAT) and extent of AC varied by race (all P <0.05); in that higher volumes of EAT, PAT and TAT were associated with greater AC in black compared with white women in final models. Irrespective of race or menopausal status, higher volumes of PVAT (β (SE): 1.60 (0.63), P= 0.01, per 1 log-unit increase in PVAT) were associated with greater extent of AC in the fully adjusted model. In black women only, the associations of PAT and TAT with extent of AC varied by menopausal status (all P <0.05) independent of age, BMI and other CVD risk factors: late peri-/postmenopausal women had significantly more AC than pre-/early peri-menopausal women for each 1-log unit increase in PAT (β (SE): 1.57 (0.66), P=0.02) and TAT (β (SE): 2.29 (1.04), P=0.03). Conclusion: ECF depots are associated with aortic calcification in women at midlife and the associations vary by race and menopausal status. Perhaps ECF plays a role in the higher risk of CVD reported in women after menopause.

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Abstract 22: Cardiovascular Fat in Women at Midlife: Effects of Race, Overall Adiposity, and Central Adiposity. The SWAN Cardiovascular Fat Ancillary Study

Circulation ◽

10.1161/circ.133.suppl_1.22 ◽

2016 ◽

Vol 133 (suppl_1) ◽

Author(s):

Carrie L Hanley ◽

Karen Matthews ◽

Maria M Brooks ◽

Imke Janssen ◽

Matthew J Budoff ◽

...

Keyword(s):

Black Women ◽

Racial Differences ◽

Effect Size ◽

White Women ◽

Menopausal Status ◽

Effect Modification ◽

P Value ◽

Central Adiposity ◽

Ancillary Study ◽

Unit Increase

Background: Racial differences exist in overall (BMI) and central adiposity (abdominal visceral fat (VAT)) measures. Recently, it has been shown that white men have higher volumes of cardiovascular fat (CF) that were found to be greater per increment increase in BMI when compared to black men. It is unknown whether similar racial differences exist in women. We assessed whether CF volumes vary by race and tested the effect modification of race on the associations between adiposity measures and CF among women at midlife, a time period marked with increased cardiovascular risk. Methods: Volumes of CF depots (epicardial fat (EAT), paracardial fat (PAT), total heart fat (TAT), and aortic perivascular fat (PVAT)), BMI, and VAT were examined among participants from the Study of Women’s Health Across the Nation (SWAN) Cardiovascular Fat Ancillary study. Linear regression was used for statistical analyses. All adiposity measures were log-transformed to achieve normality. Results: A total of 543 women (mean age: 50.9 ± 2.9 years; 34% postmenopausal) were included. Women were either white (62%) or black (38%). Significant racial differences existed in volumes of all CF depots with white women having higher volumes compared to black women, after adjusting for age, menopausal status, hypertension, diabetes, and alcohol consumption (all P-values <0.05). These racial differences remained significant after further adjustment for BMI or VAT, with one exception of PAT after adjusting for VAT. Race significantly modified the associations between VAT and EAT (Interaction P-value=0.03) and between BMI and PAT (Interaction P-value=0.01), such that black women had more EAT than white women for every one-increment increase in VAT, while with every one-increment increase in BMI, white women had more PAT than black women. Race-stratified analyses confirmed the effect modification of race on the associations between VAT and EAT (effect size per 1 unit increase in VAT was higher in blacks (β (SE) = 0.62 (0.05) than in whites (β (SE) 0.51 (0.04)) and between BMI and PAT (effect size per 1 unit increase in BMI was higher in whites (β (SE) = 2.56 (0.18) than in blacks (β (SE) 1.92 (0.23)). Conclusions: Racial differences existed in CF volumes in midlife women similar to midlife men. Black women with greater central adiposity had higher EAT volumes than white women, while white women with greater overall adiposity had higher PAT volumes than black women. Future research should evaluate the impacts of these significant racial differences in explaining CVD risk disparity.

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Abstract MP008: Racial Differences in Total, Free, and Bioavailable 25(OH)D and PTH Levels and CVD Risk Among Postmenopausal Women

Circulation ◽

10.1161/circ.135.suppl_1.mp008 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Xi Zhang ◽

Wanzhu Tu ◽

Lesley Tinker ◽

JoAnn E Manson ◽

Simin Liu ◽

...

Keyword(s):

Vitamin D ◽

Cohort Study ◽

Black Women ◽

Postmenopausal Women ◽

Racial Differences ◽

White Women ◽

Sitting Time ◽

Cvd Risk ◽

Black And White ◽

Circulating Levels

Background: Recent evidence suggests that racial differences in circulating levels of free or bioavailable 25(OH)D rather than total 25(OH)D may explain the apparent racial disparities in cardiovascular disease(CVD).However, few prospective studies have directly tested this hypothesis. Objective: Our study prospectively examined black white differences in the associations of total, free, and bioavailable 25(OH)D, vitamin D binding protein (VDBP), and parathyroid hormone (PTH) levels at baseline with incident CVD in a large, multi-ethnic, geographically diverse cohort of postmenopausal women. Method: We conducted a case-cohort study among 79,705 black and non-Hispanic white postmenopausal women aged 50 to 79 years and free of CVD at baseline in the Women’s Health Initiative Observational Study (WHI-OS). We included a randomly chosen subcohort of 1,300 black and 1,500 white noncases at baseline and a total of 550 black and 1,500 white women who developed incident CVD during the follow up. We directly measured circulating levels of total 25(OH)D, VDBP (monoclonal antibody assay), albumin, and PTH and calculated free and bioavailable vitamin D levels. Weighted Cox proportional hazards models were used while adjusting for known CVD risk factors. Results: At baseline, white women had higher mean levels of total 25(OH)D and VDBP and lower mean levels of free and bioavailable 25(OH)D and PTH than black women (all P values < 0.0001). White cases had lower levels of total 25(OH)D and VDBP and higher levels of PTH than white noncases, while black cases had higher levels of PTH than black noncases (all P values < 0.05). There was a trend toward an increased CVD risk associated with low total 25(OH)D and VDBP levels or elevated PTH levels in both US black and white women. In the multivariable analyses, the total, free, and bioavailable 25(OH)D, and VDBP were not significantly associated with CVD risk in black or white women. A statistically significant association between higher PTH levels and increased CVD risk persisted in white women, however. The multivariate-adjusted hazard ratios [HRs] comparing the extreme quartiles of PTH were 1.37 (95% CI: 1.06-1.77; P-trend=0.02) for white women and 1.12 (95% CI: 0.79-1.58; P-trend=0.37) for black women. This positive association among white women was also independent of total, free, and bioavailable 25(OH)D or VDBP. There were no significant interactions with other pre-specified factors, including BMI, season of blood draw, sunlight exposure, recreational physical activity, sitting time, or renal function. Interpretation: Findings from a large multiethnic case-cohort study of US black and white postmenopausal women do not support the notion that circulating levels of vitamin D biomarkers may explain black-white disparities in CVD but indicate that PTH excess may be an independent risk factor for CVD in white women.

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Abstract 9509: Heart Fat, but Not Peri-Aortic Fat Depots Were Significantly Associated With Presence and Severity of Coronary Calcification in Women at Midlife: The Study of Women’s Health Across the Nation (SWAN) Ectopic Cardiovascular Fat Ancillary Study

Circulation ◽

10.1161/circ.130.suppl_2.9509 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Samar R El Khoudary ◽

Kelly Shields ◽

Matthew Budoff ◽

Emma Barinas-Mitchell ◽

Imke Janssen ◽

...

Keyword(s):

Regression Models ◽

Menopausal Status ◽

Resistance Index ◽

Coronary Calcification ◽

Midlife Women ◽

Agatston Score ◽

Model Assessment ◽

Tobit Regression ◽

Logistic Regression Models ◽

Fat Depots

Introduction: Increasing evidence demonstrates a role of cardiovascular fat in the pathogenesis of CAD. It is unknown whether heart and vascular fat depots are related to atherosclerotic burden in women transitioning through menopause, a time of increasing CAD risk. Hypothesis: We hypothesize that volumes of epicardial (EAT), pericardial (PAT), total heart (TAT=EAT+PAT) and peri-aortic (PVAT) adipose tissues are associated with presence and severity of coronary artery calcification (CAC) in a sample of white and black midlife women. Methods: CAC and cardiovascular fat depots were quantified by electron beam CT. Outcomes were presence of CAC (none vs. any: Agatston score >0), and severity of CAC (CAC Agatston score). Logistic and tobit regression were used. Final models were adjusted for age, race, study site, menopausal status, obesity (BMI ≥30 Kg/m 2 ), systolic blood pressure, lipids, homeostasis model assessment insulin resistance index, current smoking, physical activity, comorbidity (history of hypertension, stroke, angina, heart attack or diabetes) and medication use (cholesterol lowering, antihypertensive or antidiabetic medications). Results: The study included 509 women (37.9% black; 58.4% pre-/early perimenopausal, 41.6% late peri-/postmenopausal) aged 46-59 years with data on any of the 4 fat depots. CAC was found in 47.4% of the participants. Odds ratios (95% CI) from final logistic regression models showed that higher volumes of EAT (2.43 (1.22, 4.86), PAT (1.57 (1.04, 2.37), and TAT (2.43 (1.22, 4.87), were significantly associated with higher odds of presence of CAC. Similarly, tobit regression models showed that higher volumes per 1 log-unit increase of EAT (β (SE): 28.0 (10.7)), PAT (16.5 (6.6)), and TAT (30.0 (10.7)), were significantly associated with greater severity of CAC in final adjusted models. PVAT was not associated with either CAC presence or severity in final models. Conclusions: Heart fat (EAT, PAT and TAT), but not peri-aortic fat were independently associated with greater presence and severity of CAC in women at midlife, suggesting that local cardiovascular fat depots may contribute to CAD in midlife women. Future work is warranted to understand the underlying mechanistic pathways.

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Does methylation of NFATC1 and C-FOS genes are associated with post-menopausal osteoporosis?

10.1101/2020.02.19.955682 ◽

2020 ◽

Author(s):

Rasime Kalkan ◽

Özgür Tosun

Keyword(s):

Postmenopausal Women ◽

Epigenetic Regulation ◽

Methylation Status ◽

Menopausal Status ◽

Epigenetic Factors ◽

Post Menopausal Osteoporosis ◽

Menopausal Women ◽

Post Menopausal ◽

First Time ◽

Menopausal Osteoporosis

ABSTRACTGenetic and epigenetic factors have an important role during the development of osteoporosis. RANK/RANKL pathway is important for the bone remodeling and NFATC1 and c-FOS are the downtargets of this pathway. Here, we report methylation status of NFATC1 and C-FOS genes in post and premenopausal cases. In this study 30 pre-menopausal and 35 post-menopausal cases were included. MS-HRM was used for identification of NFATC1 and C-FOS metyhylation.NFATC1 were methylated in 11 of the 35 post-menopausal women and C-FOS were methylated in 6 of the postmenopausal women (p >0.005). Here, we found statistically significant association between unmethylation of NFATC1 and post-menopausal status. This result explains the epigenetic regulation of osteoclasts during the menopausal transition and our results can be used for epigenetic explanation of post-menopausal osteoporosis for the first time in the literature. Although the limited number of studies in this field makes our results crucial. Therefore, our results showed great value of epigenetic profile of post-menopausal women.

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Abstract P186: Quality of Total Heart Adipose Tissue May Contribute to the Presence and Extent of Coronary Artery Calcification in Women at Midlife: The Study of Women’s Health Across the Nation

Circulation ◽

10.1161/circ.131.suppl_1.p186 ◽

2015 ◽

Vol 131 (suppl_1) ◽

Author(s):

Carrie L Hanley ◽

Karen Matthews ◽

Maria M Brooks ◽

Imke Janssen ◽

Matthew J Budoff ◽

...

Keyword(s):

Adipose Tissue ◽

Coronary Artery ◽

Women’S Health ◽

Women's Health ◽

Coronary Artery Calcification ◽

Agatston Score ◽

Tobit Regression ◽

Cvd Risk ◽

Fat Depots

Background: The location and quantity of specific adipose tissue depots have been shown to be independent predictors of subclinical atherosclerosis. Most recently, attention has been focused on the quality of these fat depots as a novel marker of CVD risk. Adipose tissue attenuation, measured via radiodensity in computed tomography (CT) Hounsfield units (HU), is one such marker of fat quality. Our objective was to determine the cross-sectional association between total heart adipose tissue (TAT) radiodensity and coronary artery calcification (CAC) in women at midlife, a time period marked with an increase in CVD risk. Methods: Participants from the Study of Women’s Health Across the Nation (SWAN) Ectopic Cardiovascular Fat Ancillary Study were evaluated. CAC and TAT were measured using electron-beam CT. CAC was evaluated as 1) presence of CAC (CAC Agatston score >10), and 2) extent of CAC (continuous Agatston score). TAT radiodensity was evaluated as tertiles of HU (lowest tertile, -91 to -81 HU; middle tertile, -80 to -78 HU; highest tertile -77 to -67 HU). Logistic (for CAC presence) and Tobit regression (for CAC extent) were used for statistical analyses. Results: A total of 495 women with a mean age of 51 years were examined. This sample of women was 63% white, 37% black, 54% pre-/early peri-menopausal, 35% late peri-/postmenopausal, and 11% used hormones. In unadjusted logistic and Tobit regression models ( Table 1 ), the tertiles of TAT were significantly and inversely associated with the presence and extent of CAC. In fully adjusted models, the middle tertile remained significantly inversely associated with the presence and extent of CAC compared to the lowest tertile, but the adjusted estimates for the highest tertile were attenuated and non-significant ( Table 1 ). Conclusions: There appears to be an inverse relationship between TAT radiodensity and CAC which is more pronounced for those with mid-range radiodensity values. These results merit further investigation.

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Abstract MP41: Disentangling the Effects of Aging and Menopausal Status on Cardiovascular Risk Factors

Circulation ◽

10.1161/circ.133.suppl_1.mp41 ◽

2016 ◽

Vol 133 (suppl_1) ◽

Author(s):

Veerle Dam ◽

Annelien C de Kat ◽

N. C Onland-Moret ◽

Marinus J Eijkemans ◽

Frank J Broekmans ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Linear Regression ◽

Postmenopausal Women ◽

Menopausal Status ◽

Density Lipoprotein ◽

Premenopausal Women ◽

Lipoprotein Cholesterol ◽

Cvd Risk Factors ◽

Cvd Risk

Introduction: Menopause is thought to be associated with adverse cardiovascular disease (CVD) risk factors, in particular lipid levels, but risk factors also deteriorate because of natural aging. Hypothesis: We hypothesized that menopausal status has an effect on CVD risk factors independent of age. Methods: We used data from LifeLines, a population-based prospective cohort study in the Netherlands. Female participants aged 18-65 years old were divided into groups according to menopausal status: pre- (n=42,987), peri- (n=14,266), natural post- (n=11,175) and surgically postmenopausal (n=5,234). To assess the effect of menopausal status, we compared mean risk factor levels by menopausal status, within one-year age strata, using linear regression. We assessed the effect of age per year on mean CVD risk factor level, within each menopausal status, using linear regression and splines to check for non-linearity. Models were adjusted for oral contraceptive use, smoking status and body mass index (BMI). Results: As expected, systolic and diastolic blood pressure (SBP, DBP), and low-density lipoprotein cholesterol (LDL-c) levels increased with age for women in each menopausal status; but high-density lipoprotein cholesterol (HDL-c) also increased. The increase of SBP with age seemed more pronounced in premenopausal women (Figure 1). SBP levels were significantly higher in premenopausal women compared to peri-, natural post- and surgically postmenopausal women. Natural and surgically postmenopausal women had significantly higher LDL-c levels compared to premenopausal women. HDL-c levels were highest in natural postmenopausal women and lowest in surgically postmenopausal women. BMI increased slightly with age, and roughly stabilized from age 45. BMI was lowest in postmenopausal women, higher for pre- and perimenopausal women and highest for surgical postmenopausal women. Conclusions: This study provides evidence for an effect of menopausal status on CVD risk factors, independent of biological aging.

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Endogenous hormones and risk of invasive breast cancer in pre- and post-menopausal women: findings from the UK Biobank

British Journal of Cancer ◽

10.1038/s41416-021-01392-z ◽

2021 ◽

Author(s):

Sandar Tin Tin ◽

Gillian K. Reeves ◽

Timothy J. Key

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Invasive Breast Cancer ◽

Cox Regression ◽

Menopausal Status ◽

Endogenous Hormones ◽

Uk Biobank ◽

Menopausal Women ◽

Post Menopausal

Abstract Background Some endogenous hormones have been associated with breast cancer risk, but the nature of these relationships is not fully understood. Methods UK Biobank was used. Hormone concentrations were measured in serum collected in 2006–2010, and in a repeat subsample (N ~ 5000) in 2012–13. Incident cancers were identified through data linkage. Cox regression models were used, and hazard ratios (HRs) corrected for regression dilution bias. Results Among 30,565 pre-menopausal and 133,294 post-menopausal women, 527 and 2,997, respectively, were diagnosed with invasive breast cancer during a median follow-up of 7.1 years. Cancer risk was positively associated with testosterone in post-menopausal women (HR per 0.5 nmol/L increment: 1.18; 95% CI: 1.14, 1.23) but not in pre-menopausal women (pheterogeneity = 0.03), and with IGF-1 (insulin-like growth factor-1) (HR per 5 nmol/L increment: 1.18; 1.02, 1.35 (pre-menopausal) and 1.07; 1.01, 1.12 (post-menopausal); pheterogeneity = 0.2), and inversely associated with SHBG (sex hormone-binding globulin) (HR per 30 nmol/L increment: 0.96; 0.79, 1.15 (pre-menopausal) and 0.89; 0.84, 0.94 (post-menopausal); pheterogeneity = 0.4). Oestradiol, assessed only in pre-menopausal women, was not associated with risk, but there were study limitations for this hormone. Conclusions This study confirms associations of testosterone, IGF-1 and SHBG with breast cancer risk, with heterogeneity by menopausal status for testosterone.

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Association between Soy Food and Dietary Soy Isoflavone Intake and the Risk of Cardiovascular Disease in Women: A Prospective Cohort Study in Korea

Nutrients ◽

10.3390/nu13051407 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1407

Author(s):

Jihyun Im ◽

Kyong Park

Keyword(s):

Cardiovascular Disease ◽

Postmenopausal Women ◽

Premenopausal Women ◽

Soy Isoflavones ◽

Korean Women ◽

Cvd Risk ◽

Soy Isoflavone ◽

Soy Foods ◽

Cardiovascular Disease In Women

The association between soy food and soy isoflavone intake and cardiovascular disease (CVD) risk is uncertain, especially in women. We aimed to investigate this association in Korean women. We analyzed data from the Korean Genome and Epidemiology Study, including 4713 Korean women aged 40–69 years with no CVD or cancer at baseline. Dietary information was obtained using a validated semi-quantitative food frequency questionnaire, and the incidence of CVD was assessed using biennial self-reported questionnaires on medical history. The mean follow-up time was 7.4 years, during which 82 premenopausal and 200 postmenopausal women reported CVD incidence. The highest tofu, total soy foods, and dietary soy isoflavone intake groups were significantly associated with a decreased CVD risk in premenopausal women (tofu: hazard ratio (HR) 0.39; 95% confidence interval (CI), 0.19–0.80; total soy food: HR 0.36; 95% CI, 0.18–0.70; dietary soy isoflavones: HR 0.44; 95% CI, 0.22–0.89), whereas no association was observed in postmenopausal women. Other soy foods showed no association with CVD incidence. Dietary soy isoflavones and total soy foods are associated with a decreased CVD risk in premenopausal women. Among soy foods, only tofu showed significant health benefits.

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Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian Cancer Association Consortium

Endocrine Related Cancer ◽

10.1530/erc-12-0395 ◽

2013 ◽

Vol 20 (2) ◽

pp. 251-262 ◽

Cited By ~ 117

Author(s):

Catherine M Olsen ◽

Christina M Nagle ◽

David C Whiteman ◽

Roberta Ness ◽

Celeste Leigh Pearce ◽

...

Keyword(s):

Ovarian Cancer ◽

Menopausal Status ◽

Low Grade ◽

Ovarian Cancer Risk ◽

Histological Subtypes ◽

Increased Risk ◽

Modifiable Factors ◽

Menopausal Women ◽

Increase Risk ◽

Post Menopausal

Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We evaluated the association between BMI (recent, maximum and in young adulthood) and ovarian cancer risk using original data from 15 case–control studies (13 548 cases and 17 913 controls). We combined study-specific adjusted odds ratios (ORs) using a random-effects model. We further examined the associations by histological subtype, menopausal status and post-menopausal hormone use. High BMI (all time-points) was associated with increased risk. This was most pronounced for borderline serous (recent BMI: pooled OR=1.24 per 5 kg/m2; 95% CI 1.18–1.30), invasive endometrioid (1.17; 1.11–1.23) and invasive mucinous (1.19; 1.06–1.32) tumours. There was no association with serous invasive cancer overall (0.98; 0.94–1.02), but increased risks for low-grade serous invasive tumours (1.13, 1.03–1.25) and in pre-menopausal women (1.11; 1.04–1.18). Among post-menopausal women, the associations did not differ between hormone replacement therapy users and non-users. Whilst obesity appears to increase risk of the less common histological subtypes of ovarian cancer, it does not increase risk of high-grade invasive serous cancers, and reducing BMI is therefore unlikely to prevent the majority of ovarian cancer deaths. Other modifiable factors must be identified to control this disease.

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