W14 - Additional Assays on W6 CVD Biomarkers

This page provides study documentation for Core Study W14. 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
 
Core study approved by WHI Steering Committee

Introduction/Intent

W6 - HT CVD Biomarkers Case-Control Study of CHD, Stroke, and VTE was conducted in several stages: Phase I: cases within 2 years of randomization; and Phase II: > 2 years after randomization. See also
- W14-Additional Assays on W6 CVD Biomarkers described below.
 
The purpose of this proposal is to include additional CVD analytes to the initial W6 - HT CVD Biomarkers Study to help elucidate the E+P intervention effect on early increases in cardiovascular events (as defined by coronary heart disease, cerebrovascular accidents and venous thromboembolic events).
Initial and secondary tiers of analytes to explore the CVD outcomes from the E+P are complete or in progress. However, there have been scientific advances in the field of explanatory analytes that might be valuable addition or substitutions to the analytes already approved that would help WHI contribute to a greater understanding of this early CVD risk. Specific analytes proposed for consideration of incorporation are listed below. The proposed analytes and a brief description is:
 
1. NMR lipoprofiles (www.liposcience.com) for CHD/stroke baseline & year 1– Assay quantifies 10 lipoprotein subfractions, as well as LDL particle size and LDL particle concentration, which predict coronary risk and are modulated by hormone therapy (JAMA 2003;290:2030).
 
2. Progesterone receptor polymorphisms – Very few previously reported. David Herrington has identified 75 SNPs, but doesn’t know which (if any) are clinically relevant.
 
3. Substitute panel of cytokines for TGF-beta and IL-1beta (Vermont), which were on original list, but not yet run. IL-6 was associated with stroke risk in our study (OR ~10, p for interaction with E+P = 0.02). In unpublished paper from EPIC-Norfolk study, adjusted OR 1.98 (1.09, 3.61) for CHD by IL-8 quartile.
 
4. Change activated protein C resistance (Vermont) in CHD/stroke/VTE cases/control to better assay, APC – ETP (endogenous thrombin potential), currently performed in Dr. Rosendaal’s lab. The new APC-ETP has been shown in recent studies to be associated with hormone-induced changes that would make it very interesting to examine in the E+P and E-alone CT for all CVD outcomes. Dr. Rosendaal provided unpublished paper showing OR 4.7 (95% CI 1.4, 15.6) for venous thrombosis cases in postmenopausal women.
 
5. Substitute free and total TFPI (tissue factor pathway inhibitor) antigen + TFPI activity instead of factor VII antigen (Vermont) in CHD/stroke/VTE cases/controls. TFPI falls 20% with hormones (J Thromb Haemost 2003;1:1208); OR 1.6 for VTE (Blood 2003;101:4387). Some suggestion of role in CHD (Circ 2003;108:2864).
 
 
 
W14 - new tests on W6 cases
W11-New strokes
Assays
Study
CHD
Stroke1
VTE
Controls5
Stroke
Con-trols2
B
Y1
B
Y1
B
Y1
B
Y1
B
Y1
B
Y1
Insulin,
Glucose*
E+P
220
150
145
100
150
85
515
335
123
123
123
123
E-Alone
170
115
125
80
70
50
365
245
193
193
193
193
CRP, IL-6, E-selectin
E+P
 
 
0
0
 
 
0
0
123
123
123
123
E-Alone
 
 
 
 
193
193
193
193
APC-ETP
E+P
220
150
145
100
150
85
515
335
123
123
123
123
E-Alone
 
 
125
80
70
50
195
130
193
193
193
193
Free and Total TFPI;
TFPI activity
E+P
220
150
145
100
150
85
515
335
123
123
123
123
E-Alone
 
 
125
80
70
50
195
130
193
193
193
193
Progesterone receptor polymorphisms
E+P
220
145
150
515
123
123
E-Alone
170
125
70
365
193
193
 
W6-Previously identified cases and controls
10 lipopro-tein subfrac-tions, LDL particle size, and LDL particle conc
 
lipo-
proteins
E+P
220
150
 
 
 
 
220
150
-
-
-
-
E-Alone
170
115
 
 
 
 
170
115
-
-
-
-
1 - Includes early stroke cases (before Feb 2001)
2 - Tests done only on corresponding controls, not all controls.
 
Results/Findings (for W6, W11, and W14)
 
See Publications: 204, 210, 222, 273, 345, 347, 350, 429, 445, 462, 526, 854, 866, 972, 1114. WHI publications by study lists published WHI papers that have been generated by ancillary studies. A complete list of WHI papers is available in the Bibliography section of this website