title: Complement proteins and arterial calcification in middle aged women: Cross-sectional effect of cardiovascular fat. The SWAN Cardiovascular Fat Ancillary Study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Pittsburgh, Graduate School of Public Health, Department of Epidemiology, PA, USA. Electronic address: nayana.nagaraj@pitt.edu.
authors.forename: Nayana
authors.initials: N
authors.lastname: Nagaraj
authors.affiliation: University of Pittsburgh, Graduate School of Public Health, Department of Epidemiology, PA, USA; University of Pittsburgh, School of Medicine, Department of Psychiatry, PA, USA. Electronic address: matthewska@upmc.edu.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Matthews
authors.affiliation: Lupus Center of Excellence, Autoimmunity Institute, Department of Medicine, Allegheny Health Network, PA, USA. Electronic address: kshield1@wpahs.org.
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Shields
authors.affiliation: University of Pittsburgh, Graduate School of Public Health, Department of Epidemiology, PA, USA. Electronic address: barinas@edc.pitt.edu.
authors.forename: Emma
authors.initials: E
authors.lastname: Barinas-Mitchell
authors.affiliation: Department of Medicine, Los Angeles Biomedical Research Institute, Torrance, CA, USA. Electronic address: mbudoff@labiomed.org.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Budoff
authors.affiliation: University of Pittsburgh, Graduate School of Public Health, Department of Epidemiology, PA, USA. Electronic address: elkhoudarys@edc.pitt.edu.
authors.forename: Samar R
authors.initials: SR
authors.lastname: El Khoudary
mesh_terms: D000273:Adipose Tissue / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D050154:Adiposity; D000367:Age Factors; D001018:Aortic Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology; D001027:Aortography / Q000379:methods; D050197:Atherosclerosis / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D003176:Complement C3 / Q000032:analysis*; D003181:Complement C4 / Q000032:analysis; D017023:Coronary Angiography / Q000379:methods; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008875:Middle Aged; D010865:Pilot Projects; D011379:Prognosis; D012307:Risk Factors; D012737:Sex Factors; D014057:Tomography, X-Ray Computed; D014481:United States; D015854:Up-Regulation; D061205:Vascular Calcification / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; C038245:C3 protein, human; D003176:Complement C3; D003181:Complement C4
keywords: Cardiovascular fat; Complement proteins; Midlife; Subclinical atherosclerosis; Women