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Plasma Homocysteine Is Weakly Correlated with Plasma Endothelin and von Willebrand Factor but not with Endothelium-dependent Vasodilatation in Healthy Postmenopausal Women

¹ Department of Endocrinology, Research Institute for Endocrinology, Reproduction and Metabolism; Departments of
² Internal Medicine and
³ Obstetrics and Gynaecology, Institute for Cardiovascular Research-Vrije Universiteit; and
⁴ Department of Clinical Chemistry, University Hospital Vrije Universiteit Amsterdam, De Boelelaan 1117, Postbus 7057, 1007 MB Amsterdam, The Netherlands.

⁵ The Gaubius Laboratory, TNO-PG, Postbus 2215, 2301 CE Leiden, The Netherlands.
^a Author for correspondence. Fax 31-20-4440502; e-mail C.Netelen{at}azvu.nl

Background: Hyperhomocysteinemia is an independent cardiovascular risk factor, possibly through the induction of endothelial dysfunction. The postmenopausal state is associated with increased plasma homocysteine. We examined whether increased homocysteine is associated with impaired endothelial function.

Methods: Sixty-three hysterectomized but otherwise healthy postmenopausal women (54.8 ± 3.5 years) participated in this study. Fasting total plasma homocysteine (tHcy) was measured as free plus protein-bound homocysteine. Endothelial function was assessed by measuring plasma concentrations of the endothelium-derived proteins endothelin (ET), von Willebrand factor (vWF), and plasminogen activator inhibitor type 1 (PAI-1) as well as brachial artery flow-mediated, endothelium-dependent vasodilatation (FMD).

Results: Plasma tHcy was 9.6 ± 2.5 µmol/L. After adjustment for possible confounders, a 1 µmol/L increase in tHcy was associated with an increase in ET of 0.08 ng/L (P = 0.045) and an increase in vWF of 4.2% (P = 0.05). No statistically significant association was present between tHcy and PAI-1 or FMD.

Conclusions: Increased fasting homocysteine in postmenopausal women may impair some aspects of endothelial function. It is of clinical interest to study whether homocysteine lowering can improve endothelial function and thus cardiovascular morbidity and mortality in postmenopausal women.© 1999 American Association for Clinical Chemistry

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