Abstract P287: Complement Proteins C3 and C4 are Associated with Higher Levels of Hemostatic Markers in Women at Midlife: The Study of Women’s Health Across the Nation
Objective: Complement proteins have been associated with atherosclerosis and cardiovascular risk factors. Recent data suggest a potential role of complement protein C3 in clot stability with hypofibrinolytic and prothrombotic features. Women after menopause are at greater risk of cardiovascular disease and have significantly higher levels of C3 compared with younger women. To better understand the association between complement proteins and atherosclerosis we evaluated the cross-sectional associations between complement proteins C3 and C4 and hemostatic markers (factor VIIc, fibrinogen, plasminogen activator inhibitor-1 (PAI-1) antigen and tissue plasminogen activator (tPA) antigen) in a sample of midlife women.
Design: Pilot data from the Study of Women’s Health Across the Nation (SWAN) Pittsburgh site were used. Both C3 and C4 were measured using frozen serum specimens by immunoturbidimetric assay. Data for hemostatic markers were available in SWAN Core data (factor VIIc and fibrinogen were available for 44% of the study participants). Factor VIIc and PAI-1were log transformed. Linear regression was used for analysis.
Results: A total of 100 women (50% late peri/postmenopausal, 50% pre/early peri-menopausal; 73% Caucasian, 27% African American), mean age 50.48±2.63 were included. C3 but not C4 was significantly higher in late peri/postmenopausal women compared to pre/early peri-menopausal women (β(SE)=14.97(6.62), P value=0.03) adjusting for age, race and BMI. In models adjusted for age, race, menopausal status and BMI, C3 was independently associated with higher levels of log PAI-1 (β(SE)=0.01(0.003), P value=0.001) and tPA (β(SE)=0.04(0.01), P value=0.0003) while C4 was independently associated with higher levels of log factor VIIc (β(SE)=0.01(0.005), P value=0.04) and fibrinogen (β(SE)=2.80(0.95), P value=0.005).
Conclusions: Complement protein C3 is independently associated with two important hemostatic markers, PAI-1 and tPA antigens, that have significant roles in thrombus development, stabilization and destabilization in lesion areas. These data suggest that C3 may be related to blood clots via its association with hemostatic markers. The current data also suggest a possible novel association between C4 and thrombus development factors: factor VIIc and fibrinogen. C3 is related to menopausal status. Complement proteins C3 and C4 could be possible pathways by which postmenopausal women are at higher risk of atherosclerosis. It is important to replicate these findings in a larger sample size.
- © 2013 by American Heart Association, Inc.