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Complement proteins and arterial calcification in middle aged women: Cross-sectional effect of cardiovascular fat.
Nayana Nagaraj1, Karen A Matthews2, Kelly J Shields3
1University of Pittsburgh, Graduate School of Public Health, Department of Epidemiology, PA, USA.
Insights
Higher levels of complement protein C3 are linked to arterial calcification in midlife women. Cardiovascular fat may explain this association, suggesting C3 as a potential biomarker for early atherosclerosis detection.
Area of Science:
- Cardiovascular disease research
- Metabolic and endocrine studies
Background:
- Cardiovascular disease (CVD) risk escalates post-menopause.
- Elevated complement protein C3 and cardiovascular fat (CF) are observed in postmenopausal women.
- The relationship between complement proteins and early atherosclerosis markers in healthy midlife women, and the influence of local CF, remain unevaluated.
Purpose of the Study:
- To investigate the association between complement proteins (C3 and C4) and early atherosclerosis markers (arterial calcification) in healthy midlife women.
- To assess the impact of cardiovascular fat (CF) on these potential associations.
Main Methods:
- Utilized data from 100 participants (50% premenopausal) in the Study of Women's Health Across the Nation (SWAN).
- Quantified arterial calcification (aortic-AC, coronary-CAC) and cardiovascular fat (total heart-TAT, aortic perivascular adipose tissue-PVAT) using EBCT scans.
- Employed logistic and linear regression models to analyze the presence and extent of calcification.
Main Results:
- Complement protein C3 showed significant associations with both the presence and extent of arterial calcification (AC) and coronary calcification (CAC) (P<0.05).
- These associations were attenuated after adjusting for cardiovascular fat volumes (TAT and PVAT).
- A significant interaction indicated that the C3-AC association was more pronounced with higher volumes of heart perivascular adipose tissue (P=0.013). C4 showed no significant associations.
Conclusions:
- Higher C3 levels are significantly associated with the presence and extent of arterial calcification in midlife women.
- Cardiovascular fat volumes appear to mediate these associations, suggesting CF as a potential source of C3.
- C3 may serve as a non-invasive biomarker for the early diagnosis of atherosclerosis, warranting validation in larger studies.
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.
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