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

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 arelationship 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 high-molecular weight apo(a) isoforms.