Abstract

Introduction: Women with systemic lupus erythematosus (SLE) are at greater risk of developing cardiovascular disease (CVD), which is not explained by traditional CVD and SLE-related risk factors. Mounting evidence implicates small visceral adipose depots surrounding the heart and vasculature in the pathogenesis of CVD. Previously, we found that women with SLE had a greater volume of aortic perivascular adipose tissue (aPVAT) compared to healthy controls (HC). Here we quantify epicardial (EPI), paracardial (PARA), and total heart (TOT = EPI+PARA) adipose and evaluate their associations with aPVAT, CVD risk factors and coronary artery (CAC) and aortic (AC) calcification. Design: Data included clinically CVD-free SLE women never (SLEc-) or ever (SLEc+) on corticosteroids, and healthy controls (HC) (HEARTS cohort). Electron beam CT scans were used to quantify adipose depots and AC/CAC. Logistic and linear regressions were used and final models were adjusted for waist-to-hip ratio. Results: In this study, age- and race-matched women participated: 15 SLEc-, 15 SLEc+, and 15 HC. More SLE women had hypertension (p=0.04), elevated circulating eSelectin (p=0.04), albumin (p=0.01), and homocysteine (p=0.02) compared to HC. SLEc+ women had decreased circulating C3 (p=0.04) and C4 (p<0.01) compared to SLEc- women. TOT tended to be greater in SLE (mean(std): 108(92)cm3, p=0.07) vs. HC (85.2(30) cm3) and in SLEc+ (122(45) cm3,p=0.06) vs. vs SLEc- (93.5(32) cm3). There were no differences in EPI (p=0.2) or aPVAT (p=0.3), but PARA was greater in SLEc+ (54.2(27) cm3) vs. SLEc-(36.9(19) cm3) (p=0.05). TOT was correlated with aPVAT in SLE (rho,p: 0.47, 0.01) and HC (0.69, <0.01) with PARA volume (SLE(0.43, 0.02) and HC (0.57, 0.03)) driving this association. In HC, EPI and PARA were correlated with insulin (p<0.03) and HOMA-IR (p<0.04) while PARA was correlated with CRP (p=0.04). Glucose levels were correlated with EPI in SLEc+ (0.53, 0.04) and with PARA in SLEc- (-0.55, 0.03). AC was detected in 21/28 SLE women and 11/15 HC while CAC was detected in 13/28 SLE and 4/15 HC. Only aPVAT was associated with increasing AC (OR(95%CI),p): 1.09 (1.0-1.2), 0.04) and CAC (1.11 (1.0-1.2), 0.03) in SLEc+. In adjusted models, only aPVAT(log) remained associated with greater extent of AC in SLE(β(SE),p: 2.90(1.3), 0.04), which was driven by SLEc+ (5.13(1.8), 0.02) women. Conclusion: Adipose depots surrounding the heart and vasculature are greater in clinically CVD-free women with SLE and specifically SLEc+, with significant associations among CVD risk factors and calcification dependent on their location. Corticosteroid treatment may suppress circulating inflammatory markers, but is associated with greater adipose volumes surrounding the heart and increased calcification. Just as AC generally precedes CAC development, aPVAT may be a precursor to extensive PARA and EPI development, with PARA more strongly associated.

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