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Observational Study
. 2025 Jun 3;85(21):2011-2024.
doi: 10.1016/j.jacc.2025.04.013.

Lipoprotein(a), Cholesterol, Triglyceride Levels, and Vulnerable Coronary Plaques: A PROSPECT II Substudy

David Erlinge  1 , Sotirios Tsimikas  2 , Michael Maeng  3 , Akiko Maehara  4 , Alf Inge Larsen  5 , Thomas Engstrøm  6 , Lars Kjøller-Hansen  7 , Mitsuaki Matsumura  4 , Ori Ben-Yehuda  8 , Hans Erik Bøtker  3 , Ole Fröbert  9 , Jonas Persson  10 , Rune Wiseth  11 , Lisette O Jensen  12 , Jan E Nordrehaug  13 , Thor Trovik  14 , Ulf Jensen  15 , Øyvind Bleie  16 , Elmir Omerovic  17 , Stefan K James  18 , Rebecca Rylance  19 , Tania Sharma  19 , Ziad A Ali  20 , Gregg W Stone  21
Affiliations
Observational Study

Lipoprotein(a), Cholesterol, Triglyceride Levels, and Vulnerable Coronary Plaques: A PROSPECT II Substudy

David Erlinge et al. J Am Coll Cardiol. .

Abstract

Background: Although lipoprotein(a) (Lp[a]) has been associated with acute myocardial infarction (MI), the relationship between Lp(a) and the presence of high-risk "vulnerable" coronary plaques has not been studied.

Objectives: The aim of this study was to investigate whether specific lipoproteins are associated with pancoronary plaque volume and lipid deposition vs the development of non-flow-limiting high-risk vulnerable plaques.

Methods: In PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) II, 3-vessel coronary artery imaging was performed with a combined near-infrared spectroscopy and intravascular ultrasound catheter after treatment of all flow-limiting lesions in patients with recent MI. The relationships of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), HDL-C, Lp(a), and triglycerides to pancoronary plaque volume, pancoronary lipid core burden index (LCBI), and the presence of focal vulnerable plaques (plaque burden ≥70% and maximum LCBI over any 4-mm segment ≥324.7) were assessed in 865 patients.

Results: By multivariable analysis, TC, LDL-C, and non-HDL-C (but not Lp[a]) were associated with pancoronary plaque volume and pancoronary LCBI (P < 0.01 for all), but not with the presence of vulnerable plaque. Conversely, Lp(a) (but not TC, LDL-C, or non-HDL-C) was associated with the presence of focal vulnerable plaques (P = 0.01).

Conclusions: In PROSPECT II, elevated TC, LDL-C, and non-HDL-C were strongly associated with pancoronary atherosclerosis and lipid deposition, whereas elevated Lp(a) was strongly associated with the presence of focal vulnerable plaques. These findings may explain the association between high Lp(a) levels and future MI and suggest a unique role for Lp(a) role in atherosclerosis progression and plaque vulnerability. (PROSPECT II & PROSPECT ABSORB-An Integrated Natural History Study and Randomized Trial; NCT02171065).

Keywords: LDL; lipoprotein(a); myocardial infarction; vulnerable plaque.

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Conflict of interest statement

Funding Support and Author Disclosures PROSPECT II was an investigator-sponsored study, was designed by Dr Erlinge and Dr Stone, and was sponsored and performed by 2 academic research organizations with grant funding from Abbott Vascular, Infraredx, and The Medicines Company. The authors are solely responsible for the design and implementation of this study, all study analyses, the drafting and editing of the paper, and its final content. Dr Tsimikas is supported by National Heart, Lung, and Blood Institute grants R01 HL159156 and HL170224. Dr Erlinge has received speaker fees from Amgen, AstraZeneca, Bayer, and Chiesi; and has received advisory board fees from Bayer, Boehringer Ingelheim, and Sanofi. Dr Tsimikas is a coinventor and receives royalties from patents owned by the University of California, San Diego; is a cofounder and has equity interest in Oxitope and Kleanthi Diagnostics; and has a dual appointment at the University of California-San Diego, and Ionis Pharmaceuticals. The terms of this arrangement have been reviewed and approved by the University of California-San Diego, in accordance with its conflict-of-interest policies. Dr Maeng is supported by a Borregaard Clinical Ascending Investigator grant from the Novo Nordisk Foundation (grant NNF22OC0074083); has received lecture and/or advisory board fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and Novo Nordisk; has received research grants from Philips, Bayer, and Novo Nordisk; has received a travel grant from Novo Nordisk; has ongoing institutional research contracts with Janssen, Novo Nordisk and Philips; and has equity interests in Eli Lilly, Novo Nordisk, and Verve Therapeutics. Dr Maehara has received institutional research grants and consultancy fees from Boston Scientific and Abbott Vascular. Dr Larsen has received speaker fees from Pfizer. Dr Engstrøm has received speaker fees from Abbott, Novo Nordisk, Opsens, and Boston Scientific; has received advisory board fees from Abbott and Novo Nordisk; and has received grants from Novo Nordisk. Dr Matsumura has received consulting fees from Terumo and Boston Scientific. Dr Fröbert has received grants from Sanofi Pasteur. Dr Persson has received unrestricted institutional grants from Abbott Vascular. Dr James has received institutional grants from AstraZeneca, Novartis, Novo Nordisk, Janssen, and Amgen; participates on the data and safety monitoring board for Cardialysis; and has received valve proctoring fees from Medtronic. Dr Ali has received consulting fees from AstraZeneca, Boston Scientific, CathWorks, HeartFlow, Philips, and Johnson & Johnson; and has equity in Elucid, Lifelink, SpectraWAVE, Xenter, and VitalConnect. Dr Stone has received speaker honoraria from Boehringer Ingelheim and Abiomed; has served as a consultant to Daiichi-Sankyo, Robocath, Vectorious, Miracor, Apollo Therapeutics, Abbott, Cardiac Success, Occlutech, Millennia Biopharma, RCE, Ablative Solutions, Valfix, Zoll, HeartFlow, Shockwave Medical, Ancora, Impulse Dynamics, Adona Medical, Oxitope, HighLife, Elixir, Elucid Bio, and Aria; has equity or options in Cardiac Success, Ancora, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Valfix, and Xenter; has received research support to his employer from Shockwave Medical, Biosense Webster, Abbott, Abiomed, Bioventrix, Cardiovascular Systems, Phillips, Vascular Dynamics, Pulnovo Medical, V-Wave, and the Patient-Centered Outcomes Research Institute via Weill Cornell Medical Center. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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