Evaluating the Role of Lipoprotein(a) in Enhancing Risk Stratification for the Presence and Extent of Subclinical Coronary Artery Disease Burden - A BioHEART-CT Study

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dc.contributor.authorFathieh, S.
dc.contributor.authorTang, O.
dc.contributor.authorGray, M.P.
dc.contributor.authorZanchin, C.
dc.contributor.authorVernon, S.T.
dc.contributor.authorGenetzakis, E.
dc.contributor.authorTran, C.
dc.contributor.authorSullivan, D.R.
dc.contributor.authorNicholls, S.J.
dc.contributor.authorCelermajer, D.S.
dc.contributor.authorPsaltis, P.J.
dc.contributor.authorGrieve, S.M.
dc.contributor.authorFigtree, G.A.
dc.date.issued2025
dc.descriptionOnlinePubl. Available online 3 June 2025.
dc.description.abstractAims: Lipoprotein(a) [Lp(a)] has regained attention as an independent cardiovascular risk factor, particularly given emerging therapies entering late-phase clinical trials. Here, we aim to examine the association of Lp(a) with coronary artery disease (CAD) and the potential of Lp(a) as an enrichment criterion for identifying individuals more likely to benefit from screening for subclinical CAD with CT imaging. Methods and results: We analysed data from 1718 adults undergoing computed tomography coronary angiography (CTCA) for suspected CAD enrolled in the BioHEART study. Lp(a) levels were measured, and CAD burden was assessed using coronary artery calcium score (CACS) and Gensini scores. Plaque morphology for the most stenotic plaque of each Gensini segment was classified as calcified, non-calcified, or mixed. Youden’s index with 10 000 bootstraps was used to identify the optimal threshold for increased risk of clinically actionable CAD. Lp(a) was strongly associated with all CTCA measures of CAD examined. Elevated Lp(a) above 22 nmol/L was linked to more advanced multi-segment (ordinal odds ratio (OR) = 1.14 [1.03–1.25]) and multivessel disease (ordinal OR = 1.11 [1.02–1.20]), with a 2.6% increased risk of a CACS > 100 for every 10 nmol/L increment. Lp(a) was most strongly associated with mixed-plaque burden even after adjusting for traditional risk factors (β = 4.75, P = 0.001), but not with non-calcified or calcified plaque. Adding Lp(a) to standard risk models resulted in an overall net reclassification index of 16% [0.06–0.27] and 42% [0.16–0.70] in patients without standard modifiable risk factors. Conclusion: Our findings suggest Lp(a)’s role in a new clinical pathway: screening patients considered low or intermediate risk, particularly those without standard modifiable risk factors for non-invasive imaging to detect subclinical CAD. Lay summary: Our study confirms Lp(a) as an independent risk factor for coronary artery disease (CAD) measured in a stable cohort undergoing computed tomography coronary angiography (CTCA) for screening or symptoms suggestive of CAD, likely resulting in more aggressive and advanced phenotypes over time. Its addition to screening and risk prediction models should become a part of standard clinical practice. •Lp(a) and higher-risk plaque phenotype: Elevated Lp(a) is associated with more extensive multi-segment and multivessel disease and a higher prevalence of mixed plaques. A 10 nmol/L increase beyond the 22 nmol/L cut-off raises clinically actionable CAD risk by 2.6%. •Lp(a) as a non-invasive early screening tool for CAD: Integrating Lp(a) with traditional risk models significantly improves the prediction of CTCA-determined clinically actionable CAD, particularly in low- and intermediate-risk groups, supporting its use in routine screening and triaging for early CT imaging. Our optimal diagnostic cut-off is less than quarter of the currently used threshold in clinical practice.
dc.description.statementofresponsibilitySina Fathieh, Owen Tang, Michael P. Gray, Christian Zanchin, Stephen T. Vernon, Elijah Genetzakis, Collin Tran, David R. Sullivan, Stephen J. Nicholls, David S. Celermajer, Peter J. Psaltis, Stuart M. Grieve, and Gemma A. Figtree
dc.identifier.citationEuropean Journal of Preventive Cardiology (EJPC), 2025; 1-11
dc.identifier.doi10.1093/eurjpc/zwaf323
dc.identifier.issn2047-4873
dc.identifier.issn2047-4881
dc.identifier.orcidPsaltis, P.J. [0000-0003-0222-5468]
dc.identifier.urihttps://hdl.handle.net/2440/147504
dc.language.isoen
dc.publisherOxford University Press
dc.relation.grantNHMRC
dc.rights© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
dc.source.urihttps://doi.org/10.1093/eurjpc/zwaf323
dc.subjectSMuRFless; Coronary artery disease; Lipoprotein(a); Biomarker; CT coronary angiography
dc.titleEvaluating the Role of Lipoprotein(a) in Enhancing Risk Stratification for the Presence and Extent of Subclinical Coronary Artery Disease Burden - A BioHEART-CT Study
dc.typeJournal article
pubs.publication-statusPublished online

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