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.

本项phs001334号子研究——《妇女健康倡议（Women's Health Initiative, WHI）中冠心病代谢组学研究》的核心目标，是采用嵌套病例对照设计（nested case-control design），分析女性群体的代谢物谱与新发冠心病（coronary heart disease, CHD）之间的关联。WHI队列研究参与者的汇总级表型数据可于顶级研究页面[phs000200](./study.cgi?study_id=phs000200) WHI队列中查阅。所有WHI顶级研究及子研究的个体级表型数据与分子数据，需通过申请WHI队列研究[phs000200](./study.cgi?study_id=phs000200)的授权访问权限方可获取。

研究团队在妇女健康倡议（WHI）的共计2306名女性参与者中完成了代谢组学特征检测。新发冠心病病例与匹配对照样本，选自妇女健康倡议观察性研究（WHI-Observational Study, WHI-OS）以及妇女健康倡议激素治疗试验（WHI-Hormone Therapy Trials, WHI-HT）的参与者群体；该队列在基线期（1994-1998年）纳入121073名50~79岁的绝经后女性，其中WHI-OS参与者93726名，WHI-HT参与者27347名。WHI-HT参与者被随机分配至单纯雌激素组（732名）或雌激素联合孕激素组（630名），每个治疗组均设有活性治疗亚组与安慰剂亚组：安慰剂亚组纳入647名参与者，活性治疗亚组纳入715名参与者。基线靶向代谢组学特征由博德研究所（Broad Institute）采用经过验证的液相色谱-质谱联用（liquid chromatography/mass spectroscopy, LC-MS）技术在标准化平台上完成检测，共报告376种代谢物。研究纳入10%的质量控制（blind duplicate，盲法重复）样本，其变异系数中位数为6.8%，四分位间距为2.9~14.7。

在激素治疗试验（HT）亚组中，共计681对病例-对照样本的基线代谢组学特征完成检测，而在WHI-OS亚组中则为472对病例-对照样本。WHI-HT亚组中，539名病例与532名对照参与者拥有1年随访的重复测量数据。本研究样本中女性参与者的平均年龄为66.7岁，病例组的中位CHD事件发生时间在WHI-OS亚组中为6.1年，在WHI-HT亚组中为3.5年。