Abstract 16589: First Demonstration That Small Lp(a) Particles, With Kringle IV Repeats of 24 or Less, but Not Large Lp(a) Particles (More Than 24 Kringle IV Repeats), Are Atherogenic

Abstract

Introduction: It has been demonstrated using statistical methods that smaller lipoprotein (a) [Lp(a)] particles are more strongly associated with atherosclerosis. However, the exact relationship between Lp(a) size (defined by the number of kringle IV repeats) and atherogenicity has not been elucidated. Hypothesis: We hypothesized that smaller, but not larger, Lp(a) particles are atherogenic, with a clear size cut-point. Methods: We determined Lp(a) levels and precise isoform size (defined by number of kringle IV repeats) in 340 subjects in the GLOBAL clinical study (NCT01738828). Atherosclerosis was quantitatively phenotyped using cardiovascular computed tomography angiography, analyzed in central core laboratory. We generated cumulative incidence curves (CIC) to assess relationship between isoform size, concentrations and atherosclerosis. Once we determined cut-point for small vs. large Lp(a), we compared levels by Mann-Whitney test; p<0.05 was significant. Results: Mean age was 56.2±0.72; 49% were male. Lp(a)-mass, particle number and Lp(a)-cholesterol were significantly higher in those with atherosclerosis (Table). In 12 patients who had single isoform only, there was sharp stepdown in atherogenicity with >24 kringle IV repeats (Figure; A); median isoform size was 26 vs. 16 in Controls vs. Atherosclerosis (p<0.05) (Figure; B). Small Lp(a) (24 kringle IV repeats or less) levels were significantly higher in Atherosclerosis; large Lp(a) levels were not different (Figure; D). Increasing levels of small, but not large, Lp(a) particles was associated with atherosclerosis (Figure; E, F). Conclusions: We demonstrated for the first time that 24 kringle IV repeats represent a sharp demarcation between small/atherogenic and large, non-atherogenic Lp(a) particles in humans.