| Title: | Lipoprotein(a)-Associated Proteomic Signature Predicts Cardiovascular Disease in Young Adults |
| Journal: | Journal of Clinical Investigation |
| Published: | 16 Apr 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42012308/ |
| DOI: | https://doi.org/10.1172/jci204287 |
| URL: | http://www.jci.org/articles/view/204287/files/pdf |
Publication 17968
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Abstract
BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is associated with a higher risk of atherosclerotic cardiovascular disease (ASCVD). Although Lp(a) is a genetically determined risk factor, the plasma proteomic features associated with Lp(a) and whether they provide information about ASCVD risk beyond Lp(a) concentration are not well characterized.</p>
OBJECTIVE: We sought to identify plasma proteomic features associated with Lp(a) concentration and to evaluate whether an Lp(a)-associated proteomic signature is associated with ASCVD phenotypes in young, healthy adults.</p>
METHODS: In the Coronary Artery Risk Development in Young Adults (CARDIA) study, we measured Year 7 Lp(a) and 184 cardiovascular proteins using the Olink proximity extension assay in 3,920 participants without prior coronary heart disease. Lp(a)-associated proteomic signatures were derived using LASSO regression in a split-sample design and tested for association with coronary artery calcification (CAC), incident CHD, and hs-CRP over 27 years of follow-up. External replication was performed in the UK Biobank (n=37,996).</p>
RESULTS: Lp(a) was associated with CAC (OR 1.23 [1.13-1.34]; p<0.0001) and incident CHD (HR 1.23 [1.07-1.41]; p=0.004). Lp(a) correlated with proteomic features reflecting immune activation, coagulation, and vascular dysfunction. A quantitative Lp(a) proteomic score was independently associated with incident CAC (standardized beta = 0.40, p<0.0001) and hs-CRP (standardized beta = 0.11, p = 0.00015) after adjustment for Lp(a) concentration. In the UK Biobank, a recalibrated Lp(a)-associated proteomic score was associated with CRP, incident CHD, and all-cause mortality.</p>
CONCLUSIONS: In young adults, Lp(a) is associated with distinct proteomic features that independently predict ASCVD phenotypes beyond Lp(a) concentration, generating hypotheses regarding biological pathways linked to Lp(a)-related cardiovascular risk.</p>
23 Authors
- Sascha N. Goonewardena
- Shanshan Yao
- Tomasz Jurga
- Lanyue Zhang
- Donald Lloyd-Jones
- Dilna Damodaran
- Bharat Thyagarajan
- David R. Jacobs
- Supriya Shore
- Eric J. Brandt
- Clary Clish
- Kahraman Tanriverdi
- Jane E. Freedman
- Chirag J. Patel
- Mark A. Sarzynski
- Brian T. Emmer
- John T. Wilkins
- Ron Do
- Vera Bittner
- Ravi Shah
- Marios K. Georgakis
- Robert S. Rosenson
- Venkatesh Murthy
1 Application
| Application ID | Title |
|---|---|
| 7089 | Exome Sequencing of All Premature Coronary Artery Disease Participants in UK Biobank |
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