Homocysteine and cerebral hemodynamic status

Our results from the health adults showed that Hcy concentrations were not significantly associated with the flow velocity, resistance and total flow volume of the carotid and vertebral artery. To our knowledge, this study is the first to investigate the effect of homocysteine on the flow velocity and volume on the brain vessels.

Homocysteinemia plays an important role for the risk of atherosclerosis and arterial stenosis on the carotid and coronary arteries ^{56, 115}. Some recent studies reported the effects of Hcy on the hemodynamic status 31, 116-120. The relationship between

hemodynamic status and vascular atherosclerosis had been established ^26-28. Zarins et al.

reported quantitative correlation of plaque localization with flow velocity profiles and wall shear stress ²⁶. In viewing of the previous studies about Hcy and the hemodynamic status, significant inverse correlation between Hcy and the flow velocity were reported on the coronary artery and ophthalmic artery ^{31, 121}. High serum Hcy concentrations were associated with the slow flow phenomenon in non-stenotic coronary artery.

Barutcu and colleagues first investigated the relation between Hcy and the coronary slow flow phenomenon ¹²². Other researchers also found elevated levels of plasma Hcy in patients who have angiography proven normal coronary artery with slow flow in symptomatic ^{31, 121} and asymptomatic adults ¹¹⁸. Hyperhomocysteinemia impairs coronary flow velocity reserve in experimental study ¹¹⁶. The mechanisms of coronary slow flow are still not clear. Serum Hcy related endothelial dysfunction and oxidative stress were suggested to be the causes of coronary slow flow ^{31, 116}. Although there were increasing evidence of the Hcy effect on the slow flow, our study demonstrated that such association does not exist on the carotid and vertebral artery in asymptomatic adults.

In viewing the study design among the reports about Hcy and flow hemodynamic status, the aforementioned studies were small case control study ^{31, 121}. The largest study among previous reports had 50 participants in control group and 53 in case group ^{31, 116}. Our study measured the flow velocities and serum Hcy levels in a total of 542 people.

The larger sample size in our study made a greater statistic power. The results that showed no significant association between levels of Hcy concentrations and flow velocity was found after fully adjustment for age and sex and other vascular

confounding factors. These results remained consistent in either statistic method with Hcy analyzed as quartile categories or as a continuous variable. One experienced technician, who was blind to the clinical data, performed all the duplex examination on all the participants in the study without bias of interobserver reliability.

The possible reasons why our study results were different from those in previous reports are discussed as following. First, the study population was different between the studies. Participants of previous reports were selected among those who were suspected to have coronary artery disease while our study subjects were free from symptoms of vascular diseases. Compared with our asymptomatic population, people with coronary symptom may have different life style, risk factors and medications, which may change the effects of Hcy on the blood flow. The effects of Hcy in different category of

population may not be the same. Second, the measurements of the flow velocity on the carotid artery or VA in this study and coronary artery on the other studies are quite different. The coronary flow was measured by angiography 31, 116-118, 122 while flow of the carotid artery or VA in our study was measured by duplex ultrasonography. The absolute values of flow velocity might be different from various methods of

measurements and that possibly made our results different form other studies. As compared to ultrasonography, angiography was more possibly to underestimate the

presence of atherosclerotic plaques ³¹. Besides, flow volume and flow resistance can not be measured in aforementioned coronary studies. Intravascular ultrasonography, which could overcome this limitation, was not performed in these studies 31, 116-118, 122. Our study performed by ultrasonography provided more hemodynamic data than previous reports.

Another possible reason for explaining our results different from others is that our target vessels are the arteries to the brain not to the heart. The hemodynamic patterns of the brain and heart vessels are different because of the different physiological

mechanisms ³⁰. The flow patterns on the duplex of the peripheral vessels, including the heart arteries, are triphasic waveforms with high resistance while the carotid artery and vertebral artery show low resistance flow in order to give adequate blood supply to the brain and the brain has richer collateral circulation than any other organ ³⁰. Besides, the blood flow in the brain is more constant than in the heart among healthy people. This is due to the brain autoregulation system which can prevent people form syncope while the blood pressure fluctuating in daily living ¹²³. The differences of collateral circulation on the brain and the heart might influence the effects of Hcy on the blood flow on these two vital organs. So clinically, the effects of Hcy on the cardiac and cerebral vascular disease might not be the same ^{7, 124}.

The study limitations are as following. First, the arteries we sampled were extracranial carotid and vertebral arteries which may not completely indicate the hemodynamic status of the intracranial cerebral blood flow. The results of our study might not be extrapolated to the whole brain circulation. Second, as compared to the carotid artery which the intima-media thickness and plaques can be easily visualized by duplex study, the examination of the VA is rather difficult, because the image is

interrupted by transverse process of the vertebra body ¹²⁵. Some of our sampled VA may

have plaques hidden behind the transverse process canal. This technical problem can not be overcome by sonography. The hemodynamic patterns may change with plaque

formation. In this study, we could not perform subgroup analyses on the flow parameters of the VA with and without plaques.