Journal article
Inflammatory, lipid, thrombotic, and genetic markers of coronary heart disease risk in the women's health initiative trials of hormone therapy
Archives of internal medicine (1960), Vol.168(20), pp.2245-2253
11/10/2008
DOI: 10.1001/archinte.168.20.2245
PMCID: PMC2726792
PMID: 19001202
Abstract
Clinical trials of postmenopausal hormone therapy (HT) have shown increased risk of coronary heart disease (CHD) in the first few years after initiation of therapy and no overall benefit.
This nested case-control study evaluates a range of inflammatory, lipid, thrombotic, and genetic markers for their association with CHD in the 4 years after randomization and assesses whether any of these markers modified or mediated the initially increased risk associated with HT in postmenopausal women aged 50 to 79 years at baseline. Conjugated equine estrogens, 0.625 mg/d, or placebo was given to 10 739 hysterectomized women, and the same estrogen plus medroxyprogesterone acetate, 2.5 mg/d, was given to 16 608 women with an intact uterus.
In multivariate-adjusted analyses of 359 cases and 820 controls in the combined trials, baseline levels of 12 of the 23 biomarkers studied were associated with CHD events: interleukin 6, matrix metalloproteinase 9, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglycerides, D-dimer, factor VIII, von Willebrand factor, leukocyte count, homocysteine, and fasting insulin. Biomarkers tended to be more strongly associated with CHD in the initial 2 years after randomization. The genetic polymorphism glycoprotein IIIa leu33pro was significantly associated with CHD. Baseline low-density lipoprotein cholesterol interacted significantly with HT so that women with higher levels were at higher risk for CHD when given HT (P = .03 for interaction). The levels of several biomarkers were changed by HT, but these changes did not seem to be associated with future CHD events.
Several thrombotic, inflammatory, and lipid biomarkers were associated with CHD events in postmenopausal women, but only low-density lipoprotein cholesterol modified the effect of HT. Further research is needed to identify the mechanisms by which HT increases the risk of CHD.
clinicaltrials.gov Identifier: NCT00000611.
Details
- Title: Subtitle
- Inflammatory, lipid, thrombotic, and genetic markers of coronary heart disease risk in the women's health initiative trials of hormone therapy
- Creators
- Jacques E Rossouw - Women's Health Initiative Branch, Division of Prevention and Population Sciences, National Heart, Lung, and Blood Institute, 6701 Rockledge Dr, Rockledge 2 Bldg, Ste 10018, Bethesda, MD 20892, USA. rossouwj@nih.govMary CushmanPhilip GreenlandDonald M Lloyd-JonesPaul BrayCharles KooperbergMary PettingerJennifer RobinsonSusan HendrixJudith Hsia
- Resource Type
- Journal article
- Publication Details
- Archives of internal medicine (1960), Vol.168(20), pp.2245-2253
- DOI
- 10.1001/archinte.168.20.2245
- PMID
- 19001202
- PMCID
- PMC2726792
- NLM abbreviation
- Arch Intern Med
- ISSN
- 0003-9926
- eISSN
- 1538-3679
- Publisher
- American Medical Association; United States
- Grant note
- 24152 / PHS HHS 32108-9 / PHS HHS N01 WH022110-024 / WHI NIH HHS 32105-6 / PHS HHS 32122 / PHS HHS 32111-13 / PHS HHS 32115 / PHS HHS 42129-32 / PHS HHS 44221 / PHS HHS 32100-2 / PHS HHS 42107-26 / PHS HHS 32118-32119 / PHS HHS N01WH22110 / WHI NIH HHS
- Language
- English
- Date published
- 11/10/2008
- Academic Unit
- Epidemiology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9983995032202771
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