Reply to letter to the editor: coronary flow velocity reserve was impaired in chronic hyperhomocysteinemic patients: why?

Abstract

TO THE EDITOR: Hyperhomocysteinemia (HHcy) is considered a potentially modifiable risk factor for coronary artery disease (CAD) and atherosclerosis. The possible mechanisms of accelerated CAD in HHcy include endothelial dysfunction and enhanced oxidative stress (13). However, the precise mechanism by which homocysteine (Hcy) promotes atherosclerosis is not well understood. Hcy could impair coronary microvascular dilated function in healthy individuals. Endothelium-dependent dilation was significantly impaired in acute methionine-induced HHcy patients (1).Noninvasive transthoracic ultrasound imaging of coronary blood flow has been increasingly used to assessment of coronary microcirculation in individuals free of epicardial coronary stenosis (2). Coronary flow velocity reserve (CFVR), which is derived from the ratio of maximal hyperemic to basal coronary blood flow, is an accepted index for assessment of the coronary microcirculation and provides important information about coronary endothelial function. We thank Dr. Kietadisorn et al. (10a) for their interest in our paper (9). We fully agree that CFVR as an independent index of coronary microvascular function has multiple limitations. CFVR is influenced by both epicardial and microvascular factors of the coronary artery. It is also influenced by serious epicardial coronary stenosis, previous myocardial infarction, etc. Pharmacological hyperemic vasodilatation induced by adenosine is a reliable and reproducible technique with which CFVR is evaluated by Doppler echocardiography (3, 10). Adenosine is often used to assess microcirculatory function on the basis of their ability to induce maximal vasodilatation of coronary resistance vessels. This vasodilatation is primarily achieved through effects of adenosine on vascular smooth muscle cells. However, adenosine-induced vasodilatation is partly dependent on the release of nitric oxide (NO) from endothelial cells through the effect of adenosine on endothelial cells and/or via flow-induced shearing force (4, 8). Hence, adenosine-derived CFVR may involve both endothelium-dependent and -independent microcirculatory function. CFVR in response to adenosine may be partly endothelium dependent. In our study, we investigated whether CFVR was damaged in patients with chronic HHcy and, if so, whether this impaired effect was associated with the endothelial dysfunction. Quantification of CFVR was after rest and after adenosine administration by noninvasive Doppler echocardiography. Our results showed that CFVR was significantly lower in the HHcy patients than in the control group (2.76 Ϯ 0.49 vs. 3.09 Ϯ 0.52). In addition, the plasma level of Hcy was negatively correlated with CFVR. Regarding the potential effect of multiple factors on CFVR, the patients with myocardial infarction, CAD (Ͼ50% stenosis as shown on angiography), heart failure, renal function impairment, or a serious illness or who were undergoing nitrate or vitamin treatment that would affect their participation were excluded from our study. Consistent with our f...