Menopause, complement, and hemostatic markers in women at midlife: the Study of Women's Health Across the Nation

Abstract

Objective: To evaluate whether higher circulating levels of complement proteins C3 and C4 are associated with menopausal status and with hemostatic/thrombus formation markers (circulating factor VII (factor VIIc), fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator antigen (tPA-ag)) in a sample of midlife women.

Methods and results: A total of 100 women (50 late peri-/postmenopausal and 50 pre-/early peri- menopausal women) from the Study of Women's Health Across the Nation (SWAN) Pittsburgh site were included in the present analysis. Factor VIIc and PAI-1 were log transformed. Linear regression was used for analysis. The mean age of the study participants was 50.5 ± 2.6 years with 73% were Caucasian and 27% were African American. C3 but not C4 was significantly higher in postmenopausal women compared to premenopausal women (P value = 0.03), adjusting for age, race and BMI. In final model (adjusting for age, race, BMI and menopausal status), C3 was associated with higher levels of log PAI-1 (P value = 0.0009) and tPA-ag (P value = 0.0003), while C4 was associated with higher levels of log factor VIIc (P value = 0.04) and fibrinogen (P value = 0.005).

Conclusions: These data suggest that C3 and C4 may be related to blood clots via their associations with hemostatic markers and that 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 and cardiovascular related events. It is important to replicate these findings in a larger sample size.

Keywords: Coagulation; Epidemiology; Fibrinolysis; Menopause; Risk factors.