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@ARTICLE{Xie:300191,
author = {R. Xie$^*$ and T. Vlaski$^*$ and S. Sha$^*$ and H.
Brenner$^*$ and B. Schöttker$^*$},
title = {{S}ex-specific proteomic signatures improve cardiovascular
risk prediction for the general population without
cardiovascular disease or diabetes.},
journal = {Journal of advanced research},
volume = {nn},
issn = {2090-1232},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2025-00668},
pages = {nn},
year = {2025},
note = {#EA:C070#LA:C070# / epub},
abstract = {Accurate prediction of 10-year major adverse cardiovascular
events (MACE) is critical for effective disease prevention
and management. Although the SCORE2 model introduced
sex-specific algorithms, opportunities remain to further
refine prediction.To evaluate whether adding sex-specific
proteomic profiles to the SCORE2 model enhances 10-year MACE
risk prediction in the large UK Biobank (UKB) cohort.Data
from 47,382 UKB participants, aged 40 to 69 years without
prior cardiovascular disease or diabetes, were utilized.
Proteomic profiling of plasma samples was conducted using
the Olink Explore 3072 platform, measuring 2,923 unique
proteins, of which 2,085 could be used. Sex-specific Least
Absolute Shrinkage and Selection Operator (LASSO) regression
was used for biomarker selection. Model performance was
assessed by changes in Harrell's C-index (a measure of
discrimination), net reclassification index (NRI), and
integrated discrimination index (IDI).During 10-year
follow-up, 2,163 participants experienced MACE. Overall, 18
proteins were selected by LASSO regression, with 5 of them
identified in both sexes, 7 only in males, and 6 only in
females. Incorporating these proteins significantly improved
the C-index of the SCORE2 model from 0.713 to 0.778 (P <
0.001) in the total population. The improvement was greater
in males (C-index increase from 0.684 to 0.771; Δ = +0.087)
than in females (from 0.720 to 0.769; Δ = +0.049). The WAP
four-disulfide core domain protein (WFDC2) and the
growth/differentiation factor 15 (GDF15) were the proteins
contributing the strongest C-index increase in both sexes,
even more than the N-terminal prohormone of brain
natriuretic peptide (NTproBNP).The derived sex-specific
10-year MACE risk prediction models, combining 12 protein
concentrations among men and 11 protein concentrations among
women with the SCORE2 model, significantly improved the
discriminative abilities of the SCORE2 model. This study
shows the potential of sex-specific proteomic profiles for
enhanced cardiovascular risk stratification and personalized
prevention strategies.},
keywords = {Cardiovascular risk (Other) / Prediction model (Other) /
Proteomics (Other) / SCORE2 (Other) / Sex-specific (Other)},
cin = {C070},
ddc = {500},
cid = {I:(DE-He78)C070-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40154735},
doi = {10.1016/j.jare.2025.03.034},
url = {https://inrepo02.dkfz.de/record/300191},
}