Hyperhomocysteinemia in Chronic Renal Failure is an Evolving Risk Factor for Ischemic Heart Disease

Background: Accelerated atherosclerosis in ESRD contributes to a high incidence of mortality rate due to cardiovascular disease as compared with the general population. In turn, further studies are needed to unravel the risk factors by which uremia leads to increased cardiovascular events. Hyperhomocysteinemia has been hypothesized to supply more information about the unexplained atherosclerosis in end stage renal disease (ESRD). Aim: A trial to determine the possible role of hyperhomocysteinemia in induction of coronary artery occlusive disease (CAD) in CRF. Also the state of folic acid and vitamin B12 would be clarified in both CRF and CAD. Subjects and Methods: 30 patients with single chronic renal failure (CRF) and 15 cases with ischemic heart disease (IHD) as well as 15 patients with both diseases together (CRF+IHD) were enrolled to investigate the status of plasma total homocyteine (by chemiluminescence) concentration in each of them. Also the concentration of plasma folic acid and vitamin B12 (by RIA) were determined in these patients. Results: Plasma tHcy median concentrations (mol/L) were significantly higher in noncardiac CRF, non uremic IHD and combined CRF+IHD groups than control group. The t-Hcy value in CRF+IHD group was significantly higher than in the noncardiac CRF category and the non-uremic ischemic heart disease (IHD) group indicating additive effects. Meanwhile, there was significant difference between uremic and nonuremic IHD group. Plasma folic acid and vitamin B12 median concentrations were significantly lower in the noncardiac CRF, non uremic IHD and CRF+IHD groups than the control group. At the same time, there was no significant difference in between the medians of the different diseased groups. In noncardiac CRF, nonuremic IHD and combined CRF + IHD, significantly positive correlations were noted between plasma folic acid and vitamin B12- On the other hand, there was significantly inverse correlation between plasma folic acid and tHcy. Conclusion: In patients with ESRD hyperhomocysteinemia was a universal finding. Folic acid and cobalamin are the determinant of fasting plasma total homocysteine (tHcy) levels in patients with CRF and/or IHD. Subsequently the high concentration of tHcy provokes the events of CAD in CRF. It appears that each disease (CRF or IHD) has its confounders, the activity of which determine the magnitude of the associated hyperhomocysteinemia.