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Associations between complement proteins and arterial calcification in mid-life women: Role of cardiovascular fat, the Study of Women’s Health Across the Nation (SWAN)

Nagaraj, Nayana (2015) Associations between complement proteins and arterial calcification in mid-life women: Role of cardiovascular fat, the Study of Women’s Health Across the Nation (SWAN). Master Essay, University of Pittsburgh.

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Abstract

The risk of cardiovascular disease (CVD) increases in women after menopause along with levels of complement protein C3. Recent data has shown higher cardiovascular fat in postmenopausal women. Increasing evidence suggest this fat depots are a source of cytokines and various inflammatory markers. Both complement protein C3 and cardiovascular fat are associated with increased risk of CVD. The association between these factors needs to be evaluated in women at midlife. Hypothesis: Circulating complement protein levels in women at midlife are positively associated with arterial calcification, and this association can be explained by higher volumes of cardiovascular fat. Methods: Pilot data from the SWAN were used. C3 and C4 were measured by immunoturbidimetric assay. EBCT scans were used to measure the arterial calcification (aortic-AC and coronary-CAC) using Agatston scores and the volumes of fat around the heart (total heart adipose tissue-TAT) and the descending thoracic aorta (perivascular adipose tissue-PVAT). Arterial calcification and fat volumes were log transformed. Tobit regression was used for statistical analyses. Results: A total of 100 women (50% late peri/postmenopausal; 73% Caucasian) were included. In models adjusted for age, race, menopausal status, and LDL-C, C3 was significantly associated with both CAC (β(SE)=0.43(0.17),p=0.012) and AC (0.59(0.28),p=0.036) per 1 standard deviation increase of C3 (SD=33.28 mg/dl). Additional adjustment for either TAT or PVAT nullified the association of C3 with both CAC and AC. Association between C3 and AC was more pronounced at higher volumes of TAT, independent of potential covariates (p=0.036). C4 was not associated with any of the calcification measures. Conclusions: Higher levels of C3 were significantly associated with greater CAC and AC scores in women at midlife. These associations were explained by volumes of TAT and PVAT. Our findings extend support to the outside-in theory of atherosclerosis and suggest TAT as a potential source of circulating C3. Similar results are reported in unhealthy populations. The public health significance lies in the fact that by extending these findings to the general population, we have potentially found a non-invasive biomarker that could be useful in early diagnosis of subclinical atherosclerosis. These findings need to be replicated in larger samples.


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Details

Item Type: Other Thesis, Dissertation, or Long Paper (Master Essay)
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Nagaraj, Nayananan45@pitt.eduNAN45
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
Committee ChairEl Khoudary, Samar Relkhoudarys@edc.pitt.eduSAE25UNSPECIFIED
Committee MemberMatthews, Karen Amatthewska@upmc.eduXYOOUNSPECIFIED
Committee MemberShields, Kellykshield1@wpahs.orgUNSPECIFIEDUNSPECIFIED
Date: April 2015
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Publisher: University of Pittsburgh
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: MPH - Master of Public Health
Thesis Type: Master Essay
Refereed: Yes
Date Deposited: 03 Nov 2015 17:29
Last Modified: 04 Feb 2019 14:58
URI: http://d-scholarship.pitt.edu/id/eprint/25023

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