DOI: 10.1161/circ.148.suppl_1.18686 ISSN: 0009-7322

Abstract 18686: Distinct Proteomic Signatures in Subjects With Elevated Lipoprotein(a) Levels With and Without Coronary Artery Disease

Sascha N Goonewardena, Waqas Malick, DILNA DAMODARAN, Jay Krishna Katragadda, Olga Grushko, Gillian Cady, Venkatesh L Murthy, Robert S Rosenson
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Introduction: Genetic and observational studies suggest a causal link between an elevated lipoprotein(a) [Lp(a)] and coronary artery disease (CAD). Although Lp(a) is one of the strongest genetic risk factors for CAD, not all subjects with an elevated Lp(a) develop CAD.

Hypothesis: We hypothesized that in subjects with an elevated Lp(a) (>150nmol/L), proteomic signatures could differentiate between those with and without CAD.

Methods: Outpatients with known Lp(a) levels and a coronary CT between April 2021 to April 2023 were enrolled and circulating biomarkers were measured using Olink proteomic platform. This study was approved by the IRB at the Icahn School of Medicine, New York, NY.

Results: First we analyzed clinical markers and proteomic signatures in subjects with and without CAD. An elevated Lp(a) level was a critical feature between the two groups. We then focused our analysis on differences in clinical and proteomic signatures in subjects with an elevated Lp(a). High Lp(a) subjects with (n=28) and without CAD (n=7) were well matched with respect to clinical characteristics including age (66 vs 52y; NS) and median Lp(a) levels (228; [203-270] vs 222; [204-323]). Additionally, hsCRP and LDL-C levels were well matched between groups. 2907 unique proteomic markers were detected and there were 29 markers that were significantly different in high Lp(a) subjects with CAD compared with those without CAD. An unsupervised principal component analysis was performed, and we found that markers of thrombosis (PARP1, tissue factor), inflammation (CCL3, CD40) were key proteomic markers that separated high Lp(a) subjects with and without CAD, suggesting a bidirectional relationship between inflammatory and thrombotic pathways in Lp(a)-driven CAD.

Conclusions: To our knowledge, this is the first prospective study to examine proteomic differences in high Lp(a) subjects with and without CAD. Profiling over 3000 unique proteomic markers, we found that in high Lp(a) subjects, there were differences in thrombotic and inflammatory markers in those with CAD compared to those without CAD. These findings have important implications to understanding the mechanisms through which Lp(a) drives CAD and in risk stratifying high Lp(a) subjects susceptible to CAD.

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