Targeted proteomics improves cardiovascular risk prediction in secondary prevention.
ASCVD
C-reactive protein
Machine learning
NLRP3
Proteomics
Risk score
Journal
European heart journal
ISSN: 1522-9645
Titre abrégé: Eur Heart J
Pays: England
ID NLM: 8006263
Informations de publication
Date de publication:
19 04 2022
19 04 2022
Historique:
received:
22
09
2021
revised:
19
01
2022
accepted:
25
01
2022
pubmed:
10
2
2022
medline:
23
4
2022
entrez:
9
2
2022
Statut:
ppublish
Résumé
Current risk scores do not accurately identify patients at highest risk of recurrent atherosclerotic cardiovascular disease (ASCVD) in need of more intensive therapeutic interventions. Advances in high-throughput plasma proteomics, analysed with machine learning techniques, may offer new opportunities to further improve risk stratification in these patients. Targeted plasma proteomics was performed in two secondary prevention cohorts: the Second Manifestations of ARTerial disease (SMART) cohort (n = 870) and the Athero-Express cohort (n = 700). The primary outcome was recurrent ASCVD (acute myocardial infarction, ischaemic stroke, and cardiovascular death). Machine learning techniques with extreme gradient boosting were used to construct a protein model in the derivation cohort (SMART), which was validated in the Athero-Express cohort and compared with a clinical risk model. Pathway analysis was performed to identify specific pathways in high and low C-reactive protein (CRP) patient subsets. The protein model outperformed the clinical model in both the derivation cohort [area under the curve (AUC): 0.810 vs. 0.750; P < 0.001] and validation cohort (AUC: 0.801 vs. 0.765; P < 0.001), provided significant net reclassification improvement (0.173 in validation cohort) and was well calibrated. In contrast to a clear interleukin-6 signal in high CRP patients, neutrophil-signalling-related proteins were associated with recurrent ASCVD in low CRP patients. A proteome-based risk model is superior to a clinical risk model in predicting recurrent ASCVD events. Neutrophil-related pathways were found in low CRP patients, implying the presence of a residual inflammatory risk beyond traditional NLRP3 pathways. The observed net reclassification improvement illustrates the potential of proteomics when incorporated in a tailored therapeutic approach in secondary prevention patients.
Identifiants
pubmed: 35139537
pii: 6525629
doi: 10.1093/eurheartj/ehac055
pmc: PMC9020984
doi:
Substances chimiques
C-Reactive Protein
9007-41-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1569-1577Commentaires et corrections
Type : CommentIn
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.
Références
Arch Biochem Biophys. 2018 Feb 15;640:47-52
pubmed: 29336940
Heart. 2013 Jun;99(12):866-72
pubmed: 23574971
Eur J Prev Cardiol. 2021 Sep 20;28(11):1279-1289
pubmed: 33580789
Eur Heart J. 2016 Jun 7;37(22):1720-2
pubmed: 26908943
Arterioscler Thromb Vasc Biol. 2004 Mar;24(3):399-404
pubmed: 14699019
Am J Epidemiol. 2012 Sep 15;176(6):473-81
pubmed: 22875755
Eur J Epidemiol. 2004;19(12):1127-33
pubmed: 15678794
N Engl J Med. 2016 Jul 28;375(4):311-22
pubmed: 27295427
N Engl J Med. 2019 Jan 3;380(1):11-22
pubmed: 30415628
N Engl J Med. 2008 Nov 20;359(21):2195-207
pubmed: 18997196
Eur Heart J. 2018 Jul 14;39(27):2546-2550
pubmed: 29236976
EBioMedicine. 2019 Jan;39:109-117
pubmed: 30587458
Cell Tissue Res. 2012 Jan;347(1):155-75
pubmed: 21626289
N Engl J Med. 2016 Nov 10;375(19):1834-1844
pubmed: 27633186
Circulation. 2020 Nov 17;142(20):1996-1998
pubmed: 32864998
Nat Med. 2011 May;17(5):581-8
pubmed: 21516086
JAMA. 2016 Jun 21;315(23):2532-41
pubmed: 27327800
Eur Heart J. 2020 Nov 1;41(41):3998-4007
pubmed: 32808014
Circulation. 2016 Nov 8;134(19):1441-1443
pubmed: 27682884
Nat Rev Drug Discov. 2021 Aug;20(8):589-610
pubmed: 33976384
JACC Basic Transl Sci. 2021 Jul 26;6(7):610-623
pubmed: 34368511
N Engl J Med. 2015 Nov 26;373(22):2117-28
pubmed: 26378978
N Engl J Med. 2018 Nov 29;379(22):2097-2107
pubmed: 30403574
Arterioscler Thromb Vasc Biol. 2018 Oct;38(10):2505-2518
pubmed: 30354202
Eur J Epidemiol. 1999 Oct;15(9):773-81
pubmed: 10608355
N Engl J Med. 2020 Nov 5;383(19):1838-1847
pubmed: 32865380
N Engl J Med. 2017 May 4;376(18):1713-1722
pubmed: 28304224
Circulation. 2016 Nov 8;134(19):1419-1429
pubmed: 27682883
BMJ. 2020 Mar 18;368:m441
pubmed: 32188600
Nat Med. 2019 Dec;25(12):1851-1857
pubmed: 31792462
Front Physiol. 2015 Feb 03;6:11
pubmed: 25698971
J Am Coll Cardiol. 2018 Dec 25;72(25):3320-3331
pubmed: 30415883
Eur Heart J. 2015 May 14;36(19):1163-70
pubmed: 25586123
N Engl J Med. 2017 Sep 21;377(12):1119-1131
pubmed: 28845751
Nucleic Acids Res. 2019 Jan 8;47(D1):D607-D613
pubmed: 30476243
JACC Cardiovasc Imaging. 2018 Feb;11(2 Pt 1):221-230
pubmed: 28624395
Eur Heart J. 2015 Jun 7;36(22):1405-14
pubmed: 25660055
Circulation. 2015 Sep 1;132(9):852-72
pubmed: 26195497
PLoS One. 2014 Jan 06;9(1):e84935
pubmed: 24400123
J Clin Invest. 1992 Dec;90(6):2251-7
pubmed: 1469085
JAMA. 2018 Jul 17;320(3):272-280
pubmed: 29998297
N Engl J Med. 2017 Oct 5;377(14):1319-1330
pubmed: 28844192
JAMA. 2007 Feb 14;297(6):611-9
pubmed: 17299196
J Lipid Res. 2014 Apr;55(4):747-57
pubmed: 24534704
Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10732-7
pubmed: 15247411
N Engl J Med. 2006 Dec 21;355(25):2631-9
pubmed: 17182988