Hyperhomocyst(e)inemia is an important risk factor for vascular disease in subjects with high-molecular weight apo(a) isoforms

Abstract

Background: Homocyst(e)ine is reported to increase the binding of lipoprotein(a) [Lp(a)] to fibrin, which may increase the thrombogenic effects of Lp(a) in vivo. The aim of this study was to investigate whether there is a relationship between homocyst(e)ine and Lp(a) levels and vascular disease risk, and if the relationship depends on the apo(a) isoforms. Methods: A case-control study was performed in 91 Caucasian male subjects with vascular disease due to athersclerosis, and in 100 healthy age- and sex-matched control subjects. Results: Both hyperhomocyst(e)inemia and elevated Lp(a) were significantly more prevalent in patients. Concordant elevated Lp(a) and hyperhomocyst(e)inemia were not associated with increased vascular disease risk (relative odds 2.96; 95% CI: 0.90-9.80), while hyperhomocyst(e)inemia in the absence of elevated Lp(a) was associated with increased vascular disease risk (relative odds 7.20; 95% CI: 2.37-21.91). Hyperhomocyst(e)inemia in individuals with high-molecular weight apo(a) isoforms [smaller apo(a) isoform > S3] was observed to be associated with increased vascular disease risk (relative odds 11.02; 95% CI: 3.54-34.30), while vascular disease risk in subjects with low-molecular weight apo(a) isoforms [smaller apo(a) isoform < S3] was not significantly increased, the relative odds being 1.92; 95% CI: 0.51-7.24. Conclusions: We conclude that hyperhomocyst(e)inemia is an important risk factor in individuals with highmolecular weight apo(a) isoforms.