Hyperhomocysteinemia and the cardiovascular disease of uremia.

摘要

Homocysteine is a sulfur amino acid whose increase in blood is associated with cardiovascular disease, as demonstrated by a recent large meta-analysis of prospective studies in the general population. Its levels are carefully regulated in pathways related, on one hand, to one-carbon-unit metabolism and folate availability and, on the other hand, to methionine intake and metabolism. Chronic renal failure is a morbid condition with a prevalence of both hyperhomocysteinemia and cardiovascular disease, with a consequence of high mortality rates. The cause of hyperhomocysteinemia is still unknown; however, studies in humans show that renal metabolic extraction depends on the renal plasma flow in the postabsorptive state. Impaired extrarenal metabolism due to uremic toxicity is another possibility. Folate absorption or interconversion seems not to be affected. Consequences of hyperhomocysteinemia in uremia are, among other mechanisms, protein and DNA hypomethylation, with an accompanying alteration in allelic expression of genes regulated through methylation. Intervention trials are underway to test if hyperhomocysteinemia is causally related to cardiovascular disease in the general population and in uremia. In the latter, homocysteine levels can be lowered and normalized only in selected cases through B vitamin therapy (not a mere supplementation), either with folates alone or with the addition of vitamin B6, B12, and possibly riboflavin. In this review, the aforementioned aspects of nutrition in cardiovascular health are discussed as well as the reverse epidemiology theory.