Evidence map›Paper›PMID 41445622›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Proteomic analysis identifies lipoprotein(a)-associated proteins linked to incident atherosclerotic cardiovascular disease events.

Tiffany R Bellomo, Seyedmohammad Saadatagah, Jiwoo Lee, Emily E Bramel, Layla Abushamat, Anika Misra, Tetsushi Nakao, Satoshi Koyama, Aniruddh P Patel, Sarah Urbut and 2 more

Abstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Tiffany R BellomoProgram in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0001-6884-3117
Seyedmohammad SaadatagahDepartment of Medicine, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0003-4950-8334
Jiwoo LeeProgram in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Emily E BramelProgram in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0003-4602-9506
Layla AbushamatDepartment of Medicine, Baylor College of Medicine, Houston, TX, USA.ORCID 0000-0002-4074-881X
Anika MisraProgram in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Tetsushi NakaoProgram in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0001-9979-2682
Satoshi KoyamaProgram in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0002-9286-0360
Aniruddh P PatelProgram in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Sarah UrbutProgram in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0002-1135-9647
Christie Mp BallantyneDepartment of Medicine, Baylor College of Medicine, Houston, TX, USA.
Pradeep NatarajanProgram in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0001-8402-7435

Funding

THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - COORDINATING CENTER - TASK AREA B.2 AND B.375N92022D00001 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COUPER, DAVID · 2022 to 2025
$13.7M
Using genetic variation to study biology of blood lipids & coronary heart diseaseR01HL127564 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Pradeep Natarajan, Gina Marie Peloso · 2015 to 2026
$7.3M
THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - FIELD CENTER - TASK ORDER 01, TASK AREA A75N92022D00003 · NHLBI · UNIVERSITY OF MINNESOTA · PI LUTSEY, PAMELA L. · 2022 to 2025
$5.1M
THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - FIELD CENTER - TASK ORDER 01, TASK AREA A75N92022D00005 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI WAGENKNECHT, LYNNE · 2022 to 2025
$5.0M
THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - FIELD CENTER - TASK ORDER 01, TASK AREA A75N92022D00004 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI WINDHAM, BEVERLY GWEN · 2022 to 2025
$4.8M
THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - FIELD CENTER - TASK ORDER 01, TASK AREA A75N92022D00002 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI CORESH, JOSEF · 2022 to 2025
$4.7M
Using genomic modifiers to mechanistically link clonal hematopoiesis of indeterminate potential penetrance to coronary artery diseaseK99HL165024 · NHLBI · BROAD INSTITUTE, INC. · PI NAKAO, TETSUSHI · 2023 to 2024
$334k
Genetics of carotid artery disease progression among patients who have failed non-operative managementF32HL174327 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BELLOMO, TIFFANY · 2024 to 2025
$189k
NHLBI NIH HHS 75N92022D00001NHLBI NIH HHS 75N92022D00002NHLBI NIH HHS 75N92022D00003NHLBI NIH HHS 75N92022D00004NHLBI NIH HHS 75N92022D00005NHLBI NIH HHS F32 HL174327NHLBI NIH HHS K99 HL165024NHLBI NIH HHS R01 HL127564
6 · The paper itself

Abstract

Background: The pathways linking lipoprotein(a) (Lp[a]) to atherosclerotic cardiovascular disease (ASCVD) are unclear. This study aimed to discover Lp(a)-associated plasma proteins and estimate their associations with incident ASCVD. Methods: We analyzed 48,859 UK Biobank participants with measured Lp(a) and proteomic profiles, with replication in 9,416 individuals in the Atherosclerosis Risk in Communities (ARIC) study cohort utilizing a separate proteomic platform. Linear models assessed associations between Lp(a) and protein concentrations adjusted for age, sex, cigarette smoking, diabetes diagnosis, body mass index, systolic blood pressure, hypertension, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, estimated glomerular filtration rate, statin prescription, and the first 10 components of genetic ancestry. Multiple testing correction was performed using the Benjamini-Hochberg FDR method (P < 0.05). We examined how the protein effect sizes from the primary analysis using the outcome of Lp(a) aligned with those for the outcomes of an LPA genetic risk score (GRS) and LDL-C. Cox proportional hazards models quantified hazard ratios (HRs) for protein associations with incident ASCVD. Results: Participants were a mean age of 57 years (SD 8.22), 93.9% European, and 53.8% male, with median follow-up of 8.9 years (IQR 8.3-9.7). Of 1,459 circulating proteins, 164 were significantly associated with Lp(a) after FDR correction, with enrichment for lipid degradation, metabolism, and insulin secretion. In the ARIC study, 10 proteins were replicated with consistent effect estimates. Of these replicated proteins, there were no significant associations observed with an Conclusion: Using high-throughput proteomics, we discovered and replicated 10 proteins associated with circulating Lp(a), several of which were independent of genetically-predicted Lp(a). While Lp(a) is highly heritable, these atherogenic proteins represent a non-heritable Lp(a) axis.

Identifiers

PMID41445622
PMCPMC12723966

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.