Plasma homocysteine is weakly correlated with plasma endothelin and von Willebrand factor but not with endothelium-dependent vasodilatation in healthy postmenopausal women

Background: Hyperhomocysteinemia is an independent cardiovascular risk fact or, possibly through the induction of endothelial dysfunction. The postmeno pausal state is associated with increased plasma homocysteine. We examined whether increased homocysteine is associated; with impaired endothelial fun ction. Methods: Sixty-three hysterectomized but otherwise healthy postmenopausal w omen (54.8 +/- 3.5 years) participated in this study. Fasting total plasma homocysteine (tHcy) was measured as free plus protein-bound homocysteine, E ndothelial function was assessed by measuring plasma concentrations of the endothelium-derived proteins endothelin (ET), von Willebrand fatter (VWF), and plasminogen activator inhibitor type 1 (PAI-1) as well as brachial arte ry flow-mediated, endothelium-dependent vasodilatation (FMD). Results: Plasma tHcy was 9.8 +/- 2.5 mu mol/L. After adjustment for possibl e confounders, a 1 mu mol/L increase in tHcy was associated with an increas e 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 imp air some aspects of endothelial function. It is of clinical interest to stu dy whether homocysteine lowering can improve endothelial function and thus cardiovascular morbidity and mortality in postmenopausal women. (C) 1999 Am erican Association for Clinical Chemistry.