Acquired Hyperhomocysteinemia in Heart Transplant Recipients (Editorial‪)‬

The etiology and clinical significance of hyperhomocysteinemia are under intense investigation. Although nongenetic (1) and genetic (2-4) factors influence plasma homocysteine concentrations, the etiology of moderate to intermediate hyperhomocysteinemia (15-50 [micro]mol/L), commonly found in patients with coronary artery disease, cerebrovascular disease, peripheral vascular disease, and in patients with end-stage renal disease, is often unclear. The causes are likely to be multifactorial, involving both acquired and genetic components. There is strong evidence that hyperhomocysteinemia is an independent risk factor for cardiovascular disease (1, 5-7), but there are conflicting reports as well (8-10). Some individuals cannot afford to wait the several years it may take before definitive results are available from intervention studies. These include patients with end-stage renal disease, renal transplant recipients, and heart transplant recipients. Immediate treatment of their hyperhomocysteinemia may be more prudent. Homocysteine is an easily modifiable risk factor that responds well to benign intervention strategies using water-soluble B complex vitamins (11-13). It is derived from methionine in a three-step pathway (14). Homocysteine may be cytotoxic, and low intracellular steady-state concentrations are maintained by remethylation back to methionine (to complete the cycle), conversion to cystathionine in the transsulfuration pathway, and export to the circulation. The transsulfuration pathway appears to be highly organ-specific (14), and the betaine-dependent remethylation pathway is found only in the liver and kidneys (15). The transsulfuration pathway requires pyridoxal phosphate ([B.sub.6]), whereas the ubiquitous remethylation pathway requires pyridoxal phosphate ([B.sub.6]), flavin adenine dinucleotide ([B.sub.2]), cobalamin ([B.sub.12]), and folate.