Experimental hyperhomocysteinemia impairs coronary flow velocity reserve

Background Hyperhomocysteinemia has been identified as an independent risk factor for coronary artery disease. One mechanism is considered to be deteriorated endothelial function that is recovered by vitamin C. However, its direct action on coronary circulation has yet to be examined. This study was designed to test the hypothesis that experimental acute hyperhomocysteinemia would impair coronary flow velocity reserve (CFR) by increasing oxidative stress. Methods Eleven healthy male volunteers (aged 23.3±0.9 years) were enrolled. CFR induced by intravenous 5′-adenosine triphosphate infusion was measured by transthoracic-Doppler echocardiography. Measurements were taken before and 4 h after administration of a placebo, oral methionine (L-methionine 0.1 g/kg) or oral methionine plus vitamin C (2 g) on 3 separate days. Results The baseline average diastolic peak velocity (APV) was similar in all 3 groups. In the methionine group, plasma homocysteine increased (12.9±7.0 to 32.1±9.4 nmol/ml, p<0.0001), while APV under hyperemic conditions (APV-hyp) and CFR significantly decreased (87.2±11.4 cm/sec and 4.02±0.70 to 73.2±10.2 cm/sec and 3.35±0.52, p=0.0022 and 0.0030, respectively). Moreover, there was a significant inverse correlation between the plasma homocysteine and CFR (r=-0.620, p=0.0021). However, upon simultaneous administration of vitamin C, APV-hyp and CVR did not decrease despite an elevation in plasma homocysteine. Conclusions Experimentally induced acute hyperhomocysteinemia significantly decreased CFR, and this decrease was significantly reversed by vitamin C administration. Oxidative stress is suggested to play a major role in the deleterious effects of homocysteine on the coronary microcirculation.