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 Samar R. El Khoudary, PhD, MPH, BPharm; Kelly J. Shields, PhD; Imke Janssen, PhD; Matthew J. Budoff, MD; Susan A. Everson-Rose, PhD; Lynda H. Powell, PhD; Karen A. Matthews, PhD 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. ( J Am Heart Assoc. 2017;6:e004545. DOI: 10. 1161/JAHA.116.004545.) Key Words: calcification • epicardial fat • menopause • paracardial fat T he incidence of coronary artery disease (CAD), which is the leading cause of death in women, increases after menopause. 1,2 As women transition though menopause, they are undergo adverse alterations in body fat composition, 3–7 lipids, and lipoproteins 8 and vascular remodeling 9 that could increase their CAD risk. The menopausal transition, indepen- dent of aging, is believed to be associated with changes in body fat deposition rather than increases in weight. 3–7,10,11 The fat surrounding the heart (heart fat) is hypothesized to be more detrimental for cardiovascular risk than other fat depots because of its close anatomic location. 12 Increasing evidence supports a role of heart fat in the pathogenesis of CAD, 13,14 cardiovascular disease (CVD) events, 15–17 and all-cause mortality. 18 Based on fat location in the pericardium, 2 distinct heart fat depots can be quantified: (1) epicardial adipose tissue (EAT), which is the fat that directly covers the From the Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA (S.R.E., K.A.M.); Lupus Center of Excellence, Autoimmunity Institute, Department of Medicine, Allegheny Health Network, PA, USA (K.J.S.); Department of Preventive Medicine, Rush University Medical Center, Chicago, IL (I.J., L.H.P.); Division of Cardiology, Los Angeles Biomedical Research Institute, Torrance, CA (M.J.B.); Department of Medicine and Program in Health Disparities Research, University of Minnesota Medical School, Minneapolis, MN (S.A.E.-R.); Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA (K.A.M.). Correspondence to: Samar R. El Khoudary, PhD, MPH, BPharm, FAHA, University of Pittsburgh, 4420 Bayard Street, Suite 600, Pittsburgh, PA 15260. E-mail: elkhoudarys@edc.pitt.edu Received August 23, 2016; accepted December 28, 2016. ª 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. DOI: 10.1161/JAHA.116.004545 Journal of the American Heart Association 1 ORIGINAL RESEARCH