Abstract 17123: Association of Apolipoprotein(a) Isoforms With Coronary Heart Disease is Mediated Through Plasma Lipoprotein(a) Levels
Background: Increased plasma levels of lipoprotein(a) (Lp(a)) and smaller apolipoprotein(a) (apo(a)) isoforms have both been associated with higher risks of coronary heart disease (CHD), but their independent relevance is uncertain.
Methods: The apo(a) isoform size, as measured by the number of Kringle IV-2 (KIV-2) repeats, was measured in 1000 cases and 1000 controls matched for age, sex, and country of recruitment for whom plasma levels of Lp(a) were also available. Logistic regression analyses were used to assess the associations of quintiles of Lp(a) levels with risk of CHD, before and after adjustment for KIV-2 repeats. The analyses also assessed the converse associations of quintiles of KIV-2 repeats with risk of CHD, before and after adjustment for Lp(a).
Results: Plasma levels of Lp(a) were inversely correlated with the number of KIV-2 repeats (ρspearman= -0.58). The geometric mean Lp(a) level was higher in cases than controls (15.6 mg/dL [95% CI: 14.5-16.8] vs 11.7 mg/dL [95% CI: 11.0-12.5]) and the median number of KIV-2 repeats was lower (25 in cases vs 26 in controls). Individuals in the top quintile of Lp(a) levels had a 2.5-fold higher risk of CHD compared with those in the bottom quintile, which was materially unaltered by adjustment for KIV-2 repeats. Individuals in the bottom quintile of KIV-2 repeats also had a 2.5-fold higher risk of CHD compared with those in the top quintile, but this increase in risk was completely attenuated after adjustment for plasma levels of Lp(a) (p=0.19).
Conclusions: While higher plasma levels of Lp(a) are strongly and inversely correlated with smaller isoforms and both are strongly related to CHD risk, these results suggest that the association of Lp(a) levels with CHD risk is independent of KIV-2 repeats, and that the effect of apo(a) isoform size is mediated through the effect on plasma levels of Lp(a).
- © 2010 by American Heart Association, Inc.