The folate puzzle. Part II: folate and cardiovascular disease - the heart of the matter

摘要

Cardiovascular disease is the major cause of death worldwide. Apart from the traditional risk factors/ of smoking, hypertension and diabetes, high homocysteine plasma concentrations have also been suggested as a factor causing atherosclerosis. It has been shown that this amino acid is able to activate the immune system in such a way that monocyte chemo-taxts to the injured vessel wall (a major feature of ath7 erosderosis) is enhanced. In addition, high homocys-teine levels may induce highly reactive oxygen species that inactivate nitric oxide (NO), an important vascular relaxing factor. High homocysteine levels have also been associated with, altered lipid metabolism and increased uptake of modified low-density lipoprotein (LDL) by rnacrophages in the yessel wall. Numerous, observational studies have demonstrated high homocysteine levels in patients with atherosclerotic disease, including myocardial infarction and cerebral stroke. However, over the past two decades, various highly powered, large, randomized, controlled and population-based studies have failed to show a relationship between homocysteine levels arid the risk of vascular diseases, with the exception of stroke, calling into question whether high homocysteine levels represent a risk factor or merely a risk indicator. Furthermore, folic acid treatment alters the methyla-tion potential, which may induce carcinogenesis. A number of well-designed epidemlological studies are still under way and at present it seems best to adhere to a wait-and-see policy.