Homocysteine and the Risk of Vascular Diseases

• Main Authors: Yu Sun, 孫瑜
• Other Authors: Kuo-Liong Chien
• Format: Others
• Language: en_US
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/21984879017916723040

博士 === 國立臺灣大學 === 預防醫學研究所 === 97 === Background The relationship between elevated plasma homocysteine (Hcy) and vascular disease is stronger in retrospective than in prospective studies. We proposed the following 4 hypotheses: 1. Hcy may influence the hemodynamic flow of cerebral arteries and then may further induce atherosclerotic change; 2. Hcy may induce microangiopathy and lead to cerebral white matter change which may be related to future stroke and dementia; 3. Baseline Hcy may be related to future vascular event; 4. Hcy-lowering therapy with vitamin supplementation might be benefit for persons with dementia. Material and methods We conducted a cross-sectional study to explore the relationship between Hcy and the hemodynamic status of carotid and vertebral artery; a case-control study for Hcy and cerebral white matter lesions; a cohort study for Hcy and long-term vascular events; an experimental randomized control trial study for Hcy-lowering therapy on dementia. Results Hcy was not associated with the hemodynamic change on the extracranial cerebral arteries. However, Hcy is an independent risk factor for cerebral white matter change (multivariate RR 1.15, 95% CI 1.01-1.31). In the prospective cohort study with median 11.95 years of follow-up, participants with Hcy more than 9.47 µmol/L had a 2.3-fold risk for cardiovascular events (95% CI, 1.24-4.18, p=0.008), and participants with Hcy more than 11.84 µmol/L had a 2.4 fold risk for death (95% CI, 1.76-3.32, p<0.0001). Multivitamin supplements significantly elevated the concentration of vitamin B12 (p<0.0001) and folic acid (p<0.0001) and lowered the plasma homocysteine concentration (p=0.004) after 26 weeks’ treatment. However, no significant differences between the vitamin and placebo groups in the scores of cognition and activities of daily living were found. Conclusions Hcy was not associated with the hemodynamic change on the large extracranial cerebral arteries. The effects of Hcy on the brain may be related to cerebral microangiopathy. Homocysteine was significantly related to the cardiovascular events and all-cause death, with optimal cutpoint values as 9.47µmol/L and 11.84µmol/L respectively. Oral supplements by over-the-counter multi-vitamins containing B6, B12, and folic acid decreased Hcy concentration in patients with mild to moderate Alzheimer’s dementia. However, there were no statistically significant beneficial effects on cognition and function for daily living.