Abstract 18477: Understanding the Causal Relevance of Apo(a) Isoform Size, Lipoprotein (a) and Oxidized Phospholipids in Coronary Heart Disease

Introduction: The lipoprotein(a) (Lp[a]) pathway is implicated in the etiology of coronary heart disease (CHD). We used a genetic approach to disentangle the relevance to CHD of distinct components of this pathway: apolipoprotein(a) (apo[a]) isoform size, circulating Lp[a]) and oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB). Methods: In up to 9015 CHD patients and 8629 matched controls enrolled in the PROMIS study, apo(a) isoform size was assayed using both genotypic (qPCR) and phenotypic (immunoblotting) methods; Lp(a) concentration was measured using an immunoturbidimetric assay; and OxPL-apoB levels were measured using a chemiluminescent ELISA. We calculated odds ratios (OR) for CHD with apo(a) isoform size and Lp(a) concentration. We identified genetic variants exclusively associated with each Lp(a)-related trait. We compared ORs for CHD per 1-SD differences in measured Lp(a)-related traits with ORs for CHD due to specific genetic variants that produced equivalent differences through an an...