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Complement proteins and arterial calcification in middle aged women: Cross-sectional effect of cardiovascular fat. The SWAN Cardiovascular Fat Ancillary Study.

  • Author(s): Nagaraj, Nayana;
  • Matthews, Karen A;
  • Shields, Kelly J;
  • Barinas-Mitchell, Emma;
  • Budoff, Matthew J;
  • El Khoudary, Samar R
  • et al.


CVD risk increases in women after menopause. Recent data suggest higher levels of complement protein C3 and cardiovascular fat (CF) in postmenopausal women. Whether complement proteins are associated with early markers of atherosclerosis in healthy midlife women has never been evaluated. Additionally, the potential impact of the local CF on these associations has never been assessed.


Participants (n = 100, age (mean(SD)):50.48(2.63), 50% premenopausal) were from the Study of Women's Health Across the Nation (SWAN). Arterial calcification (aortic-AC and coronary-CAC) and CF volumes around the heart and aorta (total heart-TAT and aortic perivascular adipose tissue-PVAT) were quantified using EBCT scans. AC and CAC were each evaluated as presence (Agatston scores >0) and extent of calcification (log (Agatston scores+1)). Logistic and linear regression models were used for statistical analysis.


Adjusting for age, race, menopausal status and lipids, C3 was significantly associated with both presence and extent of AC and CAC, all P values <0.05. Associations between C3 and presence and extent of AC and CAC were explained by additional adjustment for log TAT and log PVAT, respectively. Association between C3 and log(AC+1) was more pronounced at higher volumes of log TAT (interaction-P = 0.013) adjusting for study variables. No associations were found with C4.


Higher C3 was significantly associated with presence and greater extent of arterial calcification in midlife women. These associations were explained by higher volumes of CF, suggesting CF as a potential source of C3. C3 could be a potential non-invasive biomarker of early diagnosis of atherosclerosis. These findings need to be replicated in larger studies.

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