Subclinical atherosclerosis will be evaluated in 728 women (305 African American, 423 Caucasian) enrolled in the Pittsburgh and Chicago sites of the Study of Women's Health Across the Nation (SWAN), a multicenter study characterizing the biological and psychosocial antecedents and sequellae of menopause. The extent to which diminishing ovarian function affects vascular function and accelerates the development of atherosclerosis in the coronary arteries, aorta and carotid arteries will be evaluated. Serial measures of coronary and aortic calcification (by EBCT), carotid atherosclerosis, endothelial function and aortic stiffening will be performed two years apart. The prevalence and progression of subclinical atherosclerosis will be evaluated in relation to serial measures of ovarian function, psychosocial and behavioral factors, markers of clotting and inflammation as well as traditional cardiovascular risk factors, all collected in SWAN. Decreased ovarian function and premenopausal obesity are likely the primary determinants of early coronary atherosclerosis as measured by calcification on EBCT. Aortic calcification occurs earlier than coronary calcification, may predict coronary calcification, and is expected to be the best marker of risk associated with traditional factors in these younger women. Preliminary data indicate that changes in coronary and aortic calcification can be observed over short periods of time in these women. A period of diminishing estrogen levels is the optimum time to observe changes in endothelial function which likely precede measurable atherosclerosis and thus may be the earliest markers for disease potential. Vascular stiffness, a marker for the biologic aging of the vascular system, is highly correlated with measures of insulin sensitivity which is altered in women at mid-life in conjunction with increases in central adiposity. Racial differences in disease prevalence and the relative importance of certain risk factors are likely. The investigators state that in summary, this application will allow a detailed elucidation of how diminishing ovarian function affects cardiovascular disease, which can only be done within the context of a careful prospective study of the menopausal transition such as SWAN.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL065591-02
Application #
6390870
Study Section
Special Emphasis Panel (ZRG1-EDC-1 (03))
Program Officer
Nelson, Cheryl R
Project Start
2000-09-18
Project End
2004-07-31
Budget Start
2001-08-01
Budget End
2002-07-31
Support Year
2
Fiscal Year
2001
Total Cost
$618,099
Indirect Cost
Name
University of Pittsburgh
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Hanley, Carrie; Shields, Kelly J; Matthews, Karen A et al. (2018) Associations of cardiovascular fat radiodensity and vascular calcification in midlife women: The SWAN cardiovascular fat ancillary study. Atherosclerosis 279:114-121
Hanley, Carrie; Matthews, Karen A; Brooks, Maria M et al. (2018) Cardiovascular fat in women at midlife: effects of race, overall adiposity, and central adiposity. The SWAN Cardiovascular Fat Study. Menopause 25:38-45
Wang, Norman C; Matthews, Karen A; Barinas-Mitchell, Emma J M et al. (2016) 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. Menopause 23:653-61
Wang, Norman C; Matthews, Karen A; Barinas-Mitchell, Emma J M et al. (2016) Inflammatory/Hemostatic Biomarkers and Coronary Artery Calcium Progression in Women at Midlife (from the Study of Women's Health Across the Nation, Heart Study). Am J Cardiol 118:311-8
Shahabi, Leila; Karavolos, Kelly; Everson-Rose, Susan A et al. (2016) Associations of Psychological Well-Being With Carotid Intima Media Thickness in African American and White Middle-Aged Women. Psychosom Med 78:511-9
Janssen, Imke; Powell, Lynda H; Matthews, Karen A et al. (2016) Relation of Persistent Depressive Symptoms to Coronary Artery Calcification in Women Aged 46 to 59 Years. Am J Cardiol 117:1884-9
El Khoudary, Samar R; Shields, Kelly J; Janssen, Imke et al. (2015) Cardiovascular Fat, Menopause, and Sex Hormones in Women: The SWAN Cardiovascular Fat Ancillary Study. J Clin Endocrinol Metab 100:3304-12
Nagaraj, Nayana; Matthews, Karen A; Shields, Kelly J et al. (2015) Complement proteins and arterial calcification in middle aged women: Cross-sectional effect of cardiovascular fat. The SWAN Cardiovascular Fat Ancillary Study. Atherosclerosis 243:533-9
El Khoudary, Samar R; Brooks, Maria M; Thurston, Rebecca C et al. (2014) Lipoprotein subclasses and endogenous sex hormones in women at midlife. J Lipid Res 55:1498-504
El Khoudary, Samar R; Wildman, Rachel P; Matthews, Karen et al. (2013) Progression rates of carotid intima-media thickness and adventitial diameter during the menopausal transition. Menopause 20:8-14

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