Late peri-/postmenopausal women have greater volumes of heart fat compared with pre-/early perimenopausal women independent of age, obesity, and other covariates. Endogenous sex hormones are associated with CF. Perhaps CF plays a role in the higher risk of coronary heart disease reported in women after menopause.

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.

Lower TAT radiodensity was associated with a less favorable cardiometabolic profile. Women with mid-range TAT radiodensity values had a lower odds of CAC presence, independent of CVD risk factors and BMI. More research is necessary to understand radiodensity as a surrogate marker of fat quality in midlife women.

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.

Background: Ectopic fat may be a better indicator of CVD risk than conventional measures of obesity such as BMI. Data are lacking in how changes in ectopic fat relate to changes in arterial stiffness, and whether there are differences by sex. Our objectives were to determine: (1) how ectopic fat changes after a behavioral weight loss intervention and whether changes differ by sex; and (2) if the changes in ectopic fat are associated with changes in arterial stiffness independently of BMI change. Methods: Longitudinal analyses were conducted on 203 participants with complete ectopic fat and vascular stiffness data in the Slow Adverse Vascular Effects study, a randomized trial of a behavioral weight loss intervention in 349 men and women aged 20-45 years and BMI 25-40 kg/m 2 . CT scans measured total abdominal adipose tissue (TAAT), visceral AT (VAT), total thigh AT (TTAT), and intramuscular thigh AT(IMAT). Carotid-femoral (cf) and brachial-ankle (ba) pulse-wave velocity (PWV) were measures of central and mixed central/peripheral arterial stiffness, respectively. T-tests evaluated how ectopic fat and PWV measures differed between men and women at and between baseline and 12-months. Sex-stratified linear regression analyses evaluated associations between changes in regional adiposity and arterial stiffness from baseline to 12 months. Results: Mean age of participants at baseline was 38.2 ± 5.9 years; mean BMI was 32.2 ± 3.9 kg/m 2 ; 150 (73.9%) were women; and 166 (81.8%) were white. Men were significantly (all p<0.05) different from women at baseline with more VAT (159.1 vs. 100.0 cm 2 ), less TTAT (96.1 vs. 147.8 cm 2 ), higher BMI (33.5 vs. 31.8 kg/m 2 ), higher baPWV (1257.3 vs. 1193.5 cm/s), and higher cfPWV (968.6 vs. 850.9 cm/s). At 12 months, men lost significantly more VAT (-29.2 vs. -13.7 cm 2 ) and had a greater decrease in cfPWV (-103.2 vs. -24.7 cm/s) compared to women (both p<0.05). After adjusting for age, baseline PWV, and change in SBP, decreases in TAAT and TTAT were significantly associated with improved vascular stiffness as measured by baPWV among men, and a decrease in VAT was significantly associated with improved cfPWV among women (all p<0.05). These relationships lost significance after adjusting for change in BMI. Change in BMI was itself not a significant predictor for the change in the arterial stiffness measures in either men or women in final models. Conclusions: We found several novel associations between changes in ectopic fat and PWV in young adults in a weight loss intervention; these associations differed by sex and dissipated after controlling for change in BMI. Change in BMI itself was not a significant predictor of change in either arterial stiffness measure in men or women. Further research with a larger sample and more diverse population may be warranted to better understand these associations.