Association of Lipoprotein(a) With Atherosclerotic Plaque Progression.

Background: Lipoprotein(a) [Lp(a)] is associated with increased risk of myocardial infarction, although the mechanism for this observation remains uncertain.
Objectives: This study aims to investigate whether Lp(a) is associated with adverse plaque progression.
Methods: Lp(a) was measured in patients with advanced stable coronary artery disease undergoing coronary computed tomography angiography at baseline and 12 months to assess progression of total, calcific, noncalcific, and low-attenuation plaque (necrotic core) in particular. High Lp(a) was defined as Lp(a) ≥ 70 mg/dL. The relationship of Lp(a) with plaque progression was assessed using linear regression analysis, adjusting for body mass index, segment involvement score, and ASSIGN score (a Scottish cardiovascular risk score comprised of age, sex, smoking, blood pressure, total and high-density lipoprotein [HDL]-cholesterol, diabetes, rheumatoid arthritis, and deprivation index).
Results: A total of 191 patients (65.9 ± 8.3 years of age; 152 [80%] male) were included in the analysis, with median Lp(a) values of 100 (range: 82 to 115) mg/dL and 10 (range: 5 to 24) mg/dL in the high and low Lp(a) groups, respectively. At baseline, there was no difference in coronary artery disease severity or plaque burden. Patients with high Lp(a) showed accelerated progression of low-attenuation plaque compared with low Lp(a) patients (26.2 ± 88.4 mm ³ vs -0.7 ± 50.1 mm ³ ; P = 0.020). Multivariable linear regression analysis confirmed the relation between Lp(a) and low-attenuation plaque volume progression (β = 10.5% increase for each 50 mg/dL Lp(a), 95% CI: 0.7%-20.3%). There was no difference in total, calcific, and noncalcific plaque volume progression.
Conclusions: Among patients with advanced stable coronary artery disease, Lp(a) is associated with accelerated progression of coronary low-attenuation plaque (necrotic core). This may explain the association between Lp(a) and the high residual risk of myocardial infarction, providing support for Lp(a) as a treatment target in atherosclerosis.
Competing Interests: Funding Support and Author Disclosures Drs Kaiser and Stroes were supported by the Netherlands Heart Foundation CVON 2017-20: generating the best evidence-based pharmaceutical targets for atherosclerosis [GENIUS II]). Dr Dey is supported by the National Institute of Health/National Heart, Lung, and Blood Institute grants (1R01HL148787-01A1 and 1R01HL151266). Dr Dweek is supported by the British Heart Foundation (FS/14/78/31020) and is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015 (15/JTA); has received speaker fees from Pfizer and Novartis; and has received consultancy fees from Novartis, Jupiter Bioventures, and Silence therapeutics. Dr Stroes has received research grants/support to his institution from Amgen, Sanofi, Resverlogix, and Athera; and has served as a consultant for Amgen, Sanofi, Esperion, Novartis, and Ionis Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)