Hormone replacement therapy does not affect plasma homocysteine in postmenopausal women with coronary artery disease. Free tissue factor pathway inhibitor antigen, a circulating anticoagulant, is related to plasma homocysteine.
OBJECTIVE
The objective was to evaluate the effect of hormone replacement therapy (HRT) on plasma homocysteine levels in postmenopausal women with coronary artery disease (CAD) and to investigate associations of homocysteine to other cardiovascular risk factors.


METHODS
The women in this single-center, controlled, and randomized study were examined at baseline, and after 3 and 12 months, after they had been recruited consecutively from patients referred for investigational coronary angiography. All analyses were performed examiner blind. They were randomized to HRT consisting of transdermal application of continuous 17beta-estradiol with cyclic medroxyprogesterone acetate (MPA) tablets for 14 days every 3rd month, or to a control group.


RESULTS
After 3 months of unopposed 17beta-estradiol, no significant effect on homocysteine was observed compared to the control group. The absolute decrease of 5% in median plasma homocysteine levels after 12-month HRT did not reach statistical significance. Plasma homocysteine seemed slightly higher in women with three- or four-vessel disease, but the difference was not significant. With increasing homocysteine levels, free tissue factor pathway inhibitor (TFPI) antigen increased, whereas E-selectin decreased. In women with diabetes or elevated blood glucose >6.0 mmol/l, plasma homocysteine was correlated to body mass index, C-peptide and insulin as well as age.


CONCLUSIONS
Transdermal application of 17beta-estradiol and sequential MPA do not affect plasma homocysteine in women with established CAD. Plasma homocysteine is stable in women with CAD over time, and unless special intervention is undertaken, repetitive measurements are not necessary in this particular group of high-risk individuals. The circulating anticoagulant TEPI is related to plasma homocysteine.
Os
Ingrid
I
Department of Internal Medicine, Ullevål University Hospital, Oslo, Norway. ingrid.os@ioks.uio.no
Os
Audun
A
Sandset
Per Morten
PM
Bølling
Silje
S
Seljeflot
Ingebjorg
I
Djurovic
Srdjan
S
Westheim
Arne
A
D000279:Administration, Cutaneous; D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood / Q000187:drug effects; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy*; D019040:E-Selectin / Q000097:blood / Q000187:drug effects; D004958:Estradiol / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D005260:Female; D006710:Homocysteine / Q000097:blood* / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000187:drug effects; D017270:Lipoprotein(a) / Q000097:blood / Q000187:drug effects; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood* / Q000187:drug effects*; D045167:Progesterone Congeners / Q000627:therapeutic use; D012720:Severity of Illness Index; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000097:blood / Q000187:drug effects; D053773:Transforming Growth Factor beta1; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000187:drug effects; D016387:Women's Health
D015415:Biomarkers; D002096:C-Peptide; D019040:E-Selectin; D017270:Lipoprotein(a); D045167:Progesterone Congeners; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1; D006710:Homocysteine; D018799:Intercellular Adhesion Molecule-1; D004958:Estradiol; D017258:Medroxyprogesterone Acetate