Hyperhomocysteinaemia is a prothrombotic condition that may cause oxidative endothelial injury and impair endogenous fibrinolysis. Vitamin supplementation enhances endothelial function in hyperhomocysteinaemic patients, but responses in patients with co-existing coronary artery disease have been variable. It is also unknown whether hyperhomocysteinaemia is associated with reduced fibrinolytic responses in patients with coronary artery disease. The study aims were to test the hypothesis that patients with recent myocardial infarction and hyperhomocysteinaemia have impaired endothelium-dependent vasomotion and fibrinolysis that is rectified by vitamin supplementation. From a cohort of 120 patients admitted with acute myocardial infarction, 18 patients were recruited from the upper (n=9) and lower (n=9) plasma homocysteine quartiles into a randomized double-blind placebo-controlled crossover trial. Following a 4-week course of placebo or folate/cyanocobalamin/pyridoxine supplements, FBF (forearm blood flow) was measured using venous occlusion plethysmography during intra-arterial substance P (4–16 pmol/min), acetylcholine (5–20 μg/min) and sodium nitroprusside (2–8 μg/min) infusions. All vasodilators caused dose-dependent increases in infused FBF (P<0.05). Patients in the upper homocysteine quartile (16.8±2.9 compared with 7.9±0.7 μmol/l; P=0.003) had reduced vasodilatation to acetylcholine (P=0.01) and substance P (P<0.05), but not sodium nitroprusside. There were no differences in substance P-induced tissue plasminogen activator release. Vitamin supplementation increased serum folate and vitamin B12 concentrations (P<0.05), but did not significantly lower homocysteine, or affect FBF or fibrinolytic responses. In patients with recent myocardial infarction, hyperhomocysteinaemia is associated with impaired endothelium-dependent vasodilatation, but no alteration in the acute fibrinolytic capacity. This endothelial vasomotor dysfunction is unaltered by vitamin supplementation.
Endothelial dysfunction in patients with recent myocardial infarction and hyperhomocysteinaemia: effects of vitamin supplementation
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Stanley CHIA, Robert WILSON, Christopher A. LUDLAM, David J. WEBB, Andrew D. FLAPAN, David E. NEWBY; Endothelial dysfunction in patients with recent myocardial infarction and hyperhomocysteinaemia: effects of vitamin supplementation. Clin Sci (Lond) 1 January 2005; 108 (1): 65–72. doi: https://doi.org/10.1042/CS20040150
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