This revised application represents an ancillary study to the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a large cohort study supported by the NHLBI. Several studies have demonstrated cross-sectional associations of hyperandrogenism, the primary biochemical feature of clinically-diagnosed polycystic ovarian syndrome (PCOS), with coronary risk factors and atherosclerosis. We propose to examine whether serum androgens, measured earlier in life, and variation in genes related to androgen synthesis, metabolism, and signaling are associated with early-onset subclinical coronary atherosclerosis in young adult women from the community. Additionally, we will examine whether the clinical features of PCOS are associated with subclinical coronary atherosclerosis in young adult women, after taking into account serum androgens. CARDIA provides a unique platform to address these questions; and, the proposed ancillary study will add the laboratory and clinical measurements to CARDIA needed to examine these questions. In the prospective component of the proposed study, we will examine the associations of serum androgens and genetic polymorphisms and haplotypes in ten candidate genes with the presence of coronary artery calcium (CAC) by CT. Androgen and genotyping measures will be made using stored serum and DNA samples collected from 1550 women 5 and 13 years prior to the assessment of CAC at age 33 to 45 years. In the cross-sectional component, we will use information collected at a proposed ancillary study visit in Year 16 to examine the associations of the clinical features of PCOS, including the presence of polycystic ovaries detected using trans-vaginal ultrasound, menstrual irregularities, infertility, and hirsutism, with the presence of CAC at Year 15 (n= 1200). Secondarily, we will determine whether longitudinal changes in obesity, physical inactivity, and insulin levels influence the prospective associations of serum androgens and genetic variants in candidate genes with subclinical coronary atherosclerosis. In short, the proposed study addresses a potentially important and relatively unexplored area of investigation related to women's cardiovascular health.
| Wang, Erica T; Calderon-Margalit, Ronit; Cedars, Marcelle I et al. (2011) Polycystic ovary syndrome and risk for long-term diabetes and dyslipidemia. Obstet Gynecol 117:6-13 |
| Wellons, Melissa F; Lewis, Cora E; Schwartz, Stephen M et al. (2008) Racial differences in self-reported infertility and risk factors for infertility in a cohort of black and white women: the CARDIA Women's Study. Fertil Steril 90:1640-8 |
