Evidence map›Paper›PMID 40927895›Full record

ArticleProtein & cell2026

Systematic analyses uncover plasma proteins linked to incident cardiovascular diseases.

Yi-Lin Chen, Ji-Jing Wang, Jia You, Ji-Yun Cheng, Ze-Yu Li, Yi-Jun Ge, Bing-Ran Yao, Xiao-Yu He, Yu Guo, Yi Zhang and 11 more

Abstract read
In one paragraph

Article in Protein & cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
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

21 authors.

Yi-Lin ChenDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200433, China.ORCID 0000-0001-5069-7270
Ji-Jing WangDepartment of Neurology, Brigham and Women's Hospital, Mass General Brigham, Boston, MA 02115, United States.
Jia YouInstitute of Science and Technology for Brain-Inspired Intelligence (ISTBI), Fudan University, Shanghai 200433, China.
Ji-Yun ChengDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200433, China.
Ze-Yu LiInstitute of Science and Technology for Brain-Inspired Intelligence (ISTBI), Fudan University, Shanghai 200433, China.
Yi-Jun GeDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200433, China.
Bing-Ran YaoDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200433, China.
Xiao-Yu HeDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200433, China.
Yu GuoDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200433, China.
Yi ZhangDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200433, China.
Shi-Dong ChenDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200433, China.
Liu YangDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200433, China.
Xin-Rui WuDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200433, China.
Bang-Sheng WuDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200433, China.
Ya-Ru ZhangDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200433, China.
Mei CuiDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200433, China.
Qiang DongDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200433, China.
Jian-Feng FengInstitute of Science and Technology for Brain-Inspired Intelligence (ISTBI), Fudan University, Shanghai 200433, China.
Mei TianHuashan Hospital & Human Phenome Institute, Fudan University, Shanghai 200433, China.
Wei ChengDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200433, China.ORCID 0000-0003-1118-1743
Jin-Tai YuDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200433, China.ORCID 0000-0002-2532-383X

Funding

China STI 2030-Major Projects 2021ZD0201806Excellence 2025 Talent Cultivation Program at Fudan University 3030277001Frontiers Center for Brain Science of Ministry of EducationFudan UniversityNational Key R&D Program of China 2021YFC2500100National Natural Science Foundation of China 81971032National Natural Science Foundation of China 82071201National Natural Science Foundation of China 82071997National Natural Science Foundation of China 92249305Research Start-up Fund of Huashan Hospital 2022QD002Science and Technology Innovation 2030 Major Projects 2022ZD0211600Shanghai Center for Brain Science and Brain-Inspired TechnologyShanghai Municipal Science and Technology Major Project 2023SHZDZX02Shanghai Rising-Star Program 21QA1408700State Key Laboratory of NeurobiologyTianqiao and Chrissy Chen InstituteZHANGJIANG LAB
6 · The paper itself

Abstract

Cardiovascular disease (CVD) research is hindered by limited comprehensive analyses of plasma proteome across disease subtypes. Here, we systematically investigated the associations between plasma proteins and cardiovascular outcomes in 53,026 UK Biobank participants over a 14-year follow-up. Association analyses identified 3,089 significant associations involving 892 unique protein analytes across 13 CVD outcomes. The most notable associations included NT-proBNP for atrial fibrillation (P = 6.31 × 10-313), followed by NPPB (P = 1.03 × 10-164) and GDF15 for heart failure (P = 1.21 × 10-166). Among 445 unique proteins significantly linked to 18 cardiovascular metrics, LEP (RVEDV: β = -9.03, P = 2.76 × 10-51) and FABP4 (RVEDV: β = -10.18, P = 2.42 × 10-32) emerged as the strongest correlates of cardiac structure and function. Our integrated prediction model performed excellently across the majority of CVD outcomes, achieving an AUC of 0.86 for abdominal aneurysm. Two-sample Mendelian randomization analysis revealed 225 proteins causally linked to CVDs, with LPA showing the strongest coronary artery disease association (OR = 1.13 [1.10-1.17], P = 2.38 × 10-15), many of which are targets of existing drugs, suggesting repurposing opportunities. Mediation analysis revealed broad-spectrum mediators (e.g., IGFBP4 and GDF15, each influencing 9 cardiovascular outcomes) and outcome-specific protein mediators, with modifiable risk factors such as smoking and BMI predominantly mediating protein-CVD associations.This comprehensive longitudinal study provides unprecedented insights into plasma proteome influences on cardiovascular health interactions, offering novel perspectives for CVD diagnosis, prediction, and prevention.

Indexed as

Blood ProteinsCardiovascular DiseasesAgedBiomarkersFemaleGrowth Differentiation Factor 15HumansMaleMendelian Randomization AnalysisMiddle AgedBiomarkersBlood ProteinsGDF15 protein, humanGrowth Differentiation Factor 15biomarkercardiovascular diseaselongitudinal studyplasma proteinsprediction model

Identifiers

PMID40927895
PMCPMC12987571

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.