Metabolomics of Coronary Heart Disease (CHD) in the WHI

The primary goal of this substudy phs001334 Metabolomics of CHD in WHI study was to analyze the relationship between metabolite profiles and incident coronary heart disease (CHD) in women using a nested case-control design. Summary level phenotypes for the WHI Cohort study participants can be viewed at the top-level study page [phs000200](./study.cgi?study_id=phs000200) WHI Cohort. Individual level phenotype data and molecular data for all WHI top-level study and substudies are available by requesting Authorized Access to the WHI Cohort study [phs000200](./study.cgi?study_id=phs000200).

Metabolomic profiles were measured on a total of 2306 women in the Women's Health Initiative (WHI). Incident CHD cases and matched controls were selected from participants in the Women's Health Initiative Observational Study (WHI-OS), and the WHI Hormone Therapy Trials (WHI-HT), a cohort of 121,073 (93,726 WHI-OS and 27,347 WHI-HT) postmenopausal women age 50-79 years at baseline (1994-1998). Women in the WHI-HT included women randomized to the estrogen alone (732 women) or estrogen plus progestin arms (630 women). Each HT arm had active and placebo arms; 647 in placebo arms, 715 in active arms. Baseline targeted metabolomic profiles were measured by liquid chromatography/mass spectroscopy at the Broad Institute on a validated, platform. A total of 376 metabolites were reported. Ten percent quality control (blind duplicate) samples were included, with a median coefficient of variation of 6.8%, interquartile range 2.9-14.7.

Baseline metabolomic profiles were measured on a total of 681 case/control pairs in the hormone trials (HT) and 472 case/control pairs in the WHI-OS. Repeated measured at one year were available among 539 cases and 532 controls in the WHI-HT. Mean age of the women in our sample was 66.7 years, and median time to CHD event for cases was 6.1 years in the WHI-OS and 3.5 years in the WHI-HT.