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.

Increase HDL-C level over the menopausal transition is associated with greater atherosclerotic progression

“…One protein component that appears to be involved in the loss of anti-oxidative and anti-inflammatory activities of HDL is complement C3 protein, which was found to be enriched in HDL3 among CAD subjects (20). Interestingly, we reported higher levels of serum C3 in postmenopausal women compared to premenopausal women (21). …”

Inflammatory/hemostatic biomarkers and coronary artery calcification in midlife women of African-American and White race/ethnicity: the Study of Women's Health Across the Nation (SWAN) heart study

“…Post-menopausal women who reported taking hormones within the past month of the clinical visit were classified as hormone therapy users. For the current analyses, pre-menopausal and early perimenopausal women were combined into one group, as were late perimenopausal and post-menopausal women (19). …”

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

“…During this period, women are subjected to several biological alterations including adverse changes in sex hormones, lipid/lipoprotein profile and body fat composition (2, 3). Interestingly, women over 50 years of age significantly had higher level of circulating complement protein C3 (4), which was found to be associated with postmenopausal status (5). Several lines of evidence suggest a potential role of complement proteins in the atherosclerotic process.…”

“…C3, C4) and subclinical measures of atherosclerosis (6, 7) and demonstrated the activation of complement proteins within plaque in the arterial wall (8, 9). In light of the recent findings that complement protein C3 is higher in postmenopausal women (5), it is plausible to hypothesize that levels of complement proteins may play a potential role in explaining the higher risk of CVD after menopause (1). No previous study has assessed the association between complement proteins and subclinical measures of atherosclerosis in healthy midlife women.…”