Familial hyperhomocysteinaemia and endothelium-dependent vasodilatation and arterial distensibility of large arteries

Objectives: Mild hyperhomocysteinaemia, fasting as well as after a methioni ne load, occurs in families and is associated with premature atherosclerosi s. We hypothesised that endothelial dysfunction plays a role in the relatio n between hyperhomocysteinaemia and clinical vascular disease. Methods: In this study flow-mediated, endothelium-dependent vasodilatation of the brach ial artery and, as a marker of biophysical changes of the vessel wall such as increased smooth muscle cell tone or collagen formation, arterial disten sibility of the common carotid artery were investigated in 123 healthy firs t-degree relatives of patients with mild hyperhomocysteinaemia and coronary , cerebral or peripheral artery disease. Results: In multiple linear regres sion analyses, the increase in the homocysteine concentration after a stand ard methionine load was a significant determinant of an impaired flow-media ted vasodilatation of the brachial artery (measured on a separate day). The only other predictors were the baseline vessel diameter and age. Fasting h omocysteine level was not associated with flow-mediated vasodilatation in t he brachial artery. There was no relationship between homocysteine levels a nd nitroglycerine-induced, endothelium-independent vasodilatation of the br achial artery. Arterial distensibility of the carotid artery was also not r elated to homocysteine levels. Conclusions: In healthy first-degree relativ es of patients with mild hyperhomocysteinaemia, the increase in homocystein e level after a methionine load is an independent predictor of endothelial dysfunction. The results also suggest that fasting and post-methionine homo cysteine levels may reflect distinct disturbances in methionine metabolism which may be linked to vascular dysfunction through distinct mechanisms. (C ) 1999 Elsevier Science B.V. All rights reserved.