AS137 - Postmenopause CHD Risk: Platelet Genes and Hormone Therapy

This page provides study documentation for AS137.  For description of the specimen results, see Specimen Results Description (open to public). Data sets of the specimen results are included in the existing WHI datasets located on the WHI Data on this site (sign in and a completed Data Distribution Agreement are required; see details on the Data site).

Investigator Names and Contact Information

Paul Bray, MD

Introduction/Intent

The effect of hormone replacement therapy (HRT) on coronary heart disease (CHD) is still controversial and may be due to inter-individual differences in the response to this therapy.  It would not be surprising that there is variability in the platelet phenotype after HRT, but an interaction between inherited effects and response to HRT has never been studied, either with respect to platelet function or CHD events.  The goal of these studies is to test for associations between relevant platelet polymorphisms and clinical outcomes in the Observational Study (OS) arm of the Women’s Health Initiative (WHI).  These data would provide crucial information toward predicting who might derive benefit from HRT and who might be at risk for adverse CHD outcomes.

Aim 1: Test for associations between platelet polymorphisms and ischemic coronary events in the OS arm of WHI.

  • Hypothesis:  Inherited variations (polymorphisms) in platelets are risk factors for ischemic coronary events in women.
  • Rationale: Inherited variations in platelets, such as the PlA2 polymorphism of the GPIIb-IIIa receptor, induce a prothrombotic state and have been associated with ischemic coronary events.  Women were not included or were underrepresented in many studies, but in three of these studies the risk appeared greater in women than men.

Aim 2: Test for interactions between platelet polymorphisms and HRT as a risk for ischemic coronary events in the OS arm of WHI.

  • Hypothesis:  Inherited variations (polymorphisms) in platelets interact with HRT to enhance the risk for ischemic coronary events.
  • Rationale:  HRT produced no benefit in the HERS despite a beneficial effect on lipids, suggesting a malevolent effect on another component of the pathogenesis of ischemic coronary events.  Estrogen induces a prothrombotic platelet phenotype, perhaps mediated through platelet estrogen receptor (ER) beta.  The PlA2 risk appears greater in women than men and PlA2 interacts with estrogen’s effects on in vitro platelet function.
 

Results/Findings

Some of the publications related to this ancillary study are:  

Ms482 - Schernhammer E, Wolpin B, Rifai N, Cochrane B, Manson JA, Ma J, Giovannucci E, Thomson C, Stampfer MJ, Fuchs C. Plasma folate, vitamin B6, vitamin B12, and homocysteine and pancreatic cancer risk in four large cohorts. Cancer Res. 2007 Jun 1;67(11):5553-60.

Ms483 - Michaud DS, Wolpin B, Giovannucci E, Liu S, Cochrane B, Manson JE, Pollak MN, Ma J, Fuchs CS. Prediagnostic plasma C-peptide and pancreatic cancer risk in men and women. Cancer Epidemiol Biomarkers Prev. 2007 Oct;16(10):2101-9. Epub 2007 Sep 28.

Ms484 - Wolpin BM, Michaud DS, Giovannucci EL, Schernhammer ES, Stampfer MJ, Manson JE, Cochrane BB, Rohan TE, Ma J, Pollak MN, Fuchs CS. Circulating insulin-like growth factor axis and the risk of pancreatic cancer in four prospective cohorts. Br J Cancer. 2007 Jul 2;97(1):98-104. Epub 2007 May 29.

Ms576 - Wolpin BM, Michaud DS, Giovannucci EL, Schernhammer ES, Stampfer MJ, Manson JE, Cochrane BB, Rohan TE, Ma J, Pollak MN, Fuchs CS. Circulating insulin-like growth factor binding protein-1 and the risk of pancreatic cancer. Cancer Res. 2007 Aug 15;67(16):7923-8.

For a complete, up-to-date list of WHI papers related to this ancillary study, please use the searchable Bibliography section of this website. To search for papers by study number, access the Simple Search, and enter the study number in the “Related Studies” field.