OBJECTIVES: Mild hyperhomocysteinaemia, fasting as well as after a methionine load, occurs in families and is associated with premature atherosclerosis. We hypothesised that endothelial dysfunction plays a role in the relation between hyperhomocysteinaemia and clinical vascular disease. METHODS: In this study flow-mediated, endothelium-dependent vasodilatation of the brachial artery and, as a marker of biophysical changes of the vessel wall such as increased smooth muscle cell tone or collagen formation, arterial distensibility of the common carotid artery were investigated in 123 healthy first-degree relatives of patients with mild hyperhomocysteinaemia and coronary, cerebral or peripheral artery disease. RESULTS: In multiple linear regression analyses, the increase in the homocysteine concentration after a standard methionine load was a significant determinant of an impaired flow-mediated vasodilatation of the brachial artery (measured on a separate day). The only other predictors were the baseline vessel diameter and age. Fasting homocysteine level was not associated with flow-mediated vasodilatation in the brachial artery. There was no relationship between homocysteine levels and nitroglycerine-induced, endothelium-independent vasodilatation of the brachial artery. Arterial distensibility of the carotid artery was also not related to homocysteine levels. CONCLUSIONS: In healthy first-degree relatives of patients with mild hyperhomocysteinaemia, the increase in homocysteine level after a methionine load is an independent predictor of endothelial dysfunction. The results also suggest that fasting and post-methionine homocysteine levels may reflect distinct disturbances in methionine metabolism, which may be linked to vascular dysfunction through distinct mechanisms.
OBJECTIVES: Mild hyperhomocysteinaemia, fasting as well as after a methionine load, occurs in families and is associated with premature atherosclerosis. We hypothesised that endothelial dysfunction plays a role in the relation between hyperhomocysteinaemia and clinical vascular disease. METHODS: In this study flow-mediated, endothelium-dependent vasodilatation of the brachial artery and, as a marker of biophysical changes of the vessel wall such as increased smooth muscle cell tone or collagen formation, arterial distensibility of the common carotid artery were investigated in 123 healthy first-degree relatives of patients with mild hyperhomocysteinaemia and coronary, cerebral or peripheral artery disease. RESULTS: In multiple linear regression analyses, the increase in the homocysteine concentration after a standard methionine load was a significant determinant of an impaired flow-mediated vasodilatation of the brachial artery (measured on a separate day). The only other predictors were the baseline vessel diameter and age. Fasting homocysteine level was not associated with flow-mediated vasodilatation in the brachial artery. There was no relationship between homocysteine levels and nitroglycerine-induced, endothelium-independent vasodilatation of the brachial artery. Arterial distensibility of the carotid artery was also not related to homocysteine levels. CONCLUSIONS: In healthy first-degree relatives of patients with mild hyperhomocysteinaemia, the increase in homocysteine level after a methionine load is an independent predictor of endothelial dysfunction. The results also suggest that fasting and post-methionine homocysteine levels may reflect distinct disturbances in methionine metabolism, which may be linked to vascular dysfunction through distinct mechanisms.