Post-methionine-load hyperhomocysteinemia and increased lipoprotein(a) are associated with renal metabolic dysfunction: a hypothesis

Previous studies have shown that homocysteine influences the structure of lipoprotein(a) [Lp(a)] and its affinity to fibrin, and that there is an increased risk of vascular disease when both homocysteine and Lp(a) are elevated. The aim of this study was to determine whether there is a correlation between increased total homocysteine (tHCY) and high Lp(a) concentrations, and whether increased concentrations of tHCY affect the concentration of unbound serum apolipoprotein(a) [Apo(a)]. Forty-seven male subjects recruited from a primary prevention screening program with normal serum creatinine and Lp(a) concentrations above 30 mg/dL were included and underwent a standardized oral methionine-loading test to increase the plasma tHCY concentration. This increase might lead to a modification of the Apo(a) structure, thus possibly influencing the serum concentration of unbound Apo(a). Fasting blood samples were taken before the tests and after 6 hours. The median values of tHCY increased about 4-fold after the methionine-loading test. Fasting tHCY did not show an association with Apo(a) and a post-methionine load increase of unbound Apo(a) was not observed. Backward multiple linear regression analysis, however, revealed that only post-load tHCY was independently and significantly influenced by Lp(a). Furthermore, Lp(a) correlated significantly with post-load tHCY, but not with fasting tHCY. Subdividing the subjects according to the Lp(a) concentration showed a significantly higher median concentration of tHCY after methionine load in subjects with Lp(a) over 50 mg/dL compared to subjects with Lp(a) under 50 mg/dL (P =.009). A similar cut-off was seen for post-load Apo(a) at 7.3 mg/dL (P =.04). Factors such as age, C677T-methylene-tetrahydrofolate-reductase (MTHFR) mutation, folate, vitamin B(12), and creatinine showed no significant influence on post-load tHCY in the different subgroups. The reasons for our findings remain partially unclear. However, considering our results and the current knowledge on the association of tHCY and Lp(a) concentration with the renal function, we hypothesize that both parameters may be linked by commencing renal metabolic dysfunction. It should be stressed that our hypothesis is speculative and that further studies will be necessary to improve the understanding of the interrelation of tHCY and Lp(a) concentration.