Abstract P177: Associations Between Complement Proteins and Arterial Calcification in Midlife Women: Role of Cardiovascular Fat, The Study of Women’s Health Across the Nation (SWAN)

Abstract

Background: Risk of cardiovascular disease(CVD) in women increases after the fifth decade of life. We have previously shown that compared to premenopausal women, postmenopausal women have significantly higher levels of complement protein C3 and cardiovascular fat. We hypothesize that complement protein levels in women transitioning through menopause are positively associated with early markers of vascular disease, arterial calcification, and that this association will be explained by the higher volumes of cardiovascular fat in women at midlife. Methods: Pilot data from the Study of Women’s Health Across the Nation(SWAN) were used. Complement proteins C3 and C4 were measured using frozen serum specimens by immunoturbidimetric assay. Extent of Aortic(AC) and coronary calcification(CAC) were identified using EBCT scans and Agatston scoring method, and were used as continuous variables. Same CT scans were used to quantify volumes of cardiovascular fat around the heart (total heart adipose tissue: TAT) and the descending aorta(peri-vascular adipose tissue: PVAT). Tobit regression was used for statistical analyses. Results: A total of 100 women (50% late peri/postmenopausal; 73% Caucasian), mean age 50.48±2.63 were included. In univariate analyses, higher levels of C3 were significantly associated with greater CAC [β(SE)=0.87(0.23), P=0.0001] and AC [β(SE)=3.49(1.45), P=0.02], while higher levels of C4 were significantly associated with greater CAC only. Similar results were seen after adjusting for age, race and menopausal status. For CAC models, controlling for TAT did not change the significant associations with both C3 (P=0.008) and C4 (P=0.03). On the other hand, adjusting for PVAT partially explained the association between C3 and CAC (P=0.02), while the association between C4 and CAC disappeared (p=0.09). For AC models, associations of C3 and C4 with AC were more pronounced at greater volumes of TAT (Interactions p<0.001) but not of PVAT. Adjusting for PVAT eliminated the association between AC and C3 (p=0.2) Conclusion: Higher levels of complement proteins were significantly associated with greater CAC and AC in women at midlife. The associations with CAC were independent of TAT but not of PVAT, while the associations with AC largely explained by PVAT and modified by TAT. Our findings extend support for the potential inflammatory influence of small visceral adipose depots in the development of arterial calcification and possibly suggest PVAT as a local source for the complement proteins. Early recognition of the high complement protein levels and volumes of cardiovascular fat in women at midlife could be used in early diagnosis of subclinical CVD. These findings need to be replicated in larger samples.