Plasma biomarkers associated with adverse outcomes in patients with calcific aortic stenosis.
Aortic stenosis
Biomarkers
Calcification
Inflammation
Machine learning
Journal
European journal of heart failure
ISSN: 1879-0844
Titre abrégé: Eur J Heart Fail
Pays: England
ID NLM: 100887595
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
29
09
2021
received:
19
04
2021
accepted:
06
10
2021
pubmed:
12
10
2021
medline:
2
4
2022
entrez:
11
10
2021
Statut:
ppublish
Résumé
Enhanced risk stratification of patients with aortic stenosis (AS) is necessary to identify patients at high risk for adverse outcomes, and may allow for better management of patient subgroups at high risk of myocardial damage. The objective of this study was to identify plasma biomarkers and multimarker profiles associated with adverse outcomes in AS. We studied 708 patients with calcific AS and measured 49 biomarkers using a Luminex platform. We studied the correlation between biomarkers and the risk of (i) death and (ii) death or heart failure-related hospital admission (DHFA). We also utilized machine-learning methods (a tree-based pipeline optimizer platform) to develop multimarker models associated with the risk of death and DHFA. In this cohort with a median follow-up of 2.8 years, multiple biomarkers were significantly predictive of death in analyses adjusted for clinical confounders, including tumour necrosis factor (TNF)-α [hazard ratio (HR) 1.28, P < 0.0001], TNF receptor 1 (TNFRSF1A; HR 1.38, P < 0.0001), fibroblast growth factor (FGF)-23 (HR 1.22, P < 0.0001), N-terminal pro B-type natriuretic peptide (NT-proBNP) (HR 1.58, P < 0.0001), matrix metalloproteinase-7 (HR 1.24, P = 0.0002), syndecan-1 (HR 1.27, P = 0.0002), suppression of tumorigenicity-2 (ST2) (IL1RL1; HR 1.22, P = 0.0002), interleukin (IL)-8 (CXCL8; HR 1.22, P = 0.0005), pentraxin (PTX)-3 (HR 1.17, P = 0.001), neutrophil gelatinase-associated lipocalin (LCN2; HR 1.18, P < 0.0001), osteoprotegerin (OPG) (TNFRSF11B; HR 1.26, P = 0.0002), and endostatin (COL18A1; HR 1.28, P = 0.0012). Several biomarkers were also significantly predictive of DHFA in adjusted analyses including FGF-23 (HR 1.36, P < 0.0001), TNF-α (HR 1.26, P < 0.0001), TNFR1 (HR 1.34, P < 0.0001), angiopoietin-2 (HR 1.26, P < 0.0001), syndecan-1 (HR 1.23, P = 0.0006), ST2 (HR 1.27, P < 0.0001), IL-8 (HR 1.18, P = 0.0009), PTX-3 (HR 1.18, P = 0.0002), OPG (HR 1.20, P = 0.0013), and NT-proBNP (HR 1.63, P < 0.0001). Machine-learning multimarker models were strongly associated with adverse outcomes (mean 1-year probability of death of 0%, 2%, and 60%; mean 1-year probability of DHFA of 0%, 4%, 97%; P < 0.0001). In these models, IL-6 (a biomarker of inflammation) and FGF-23 (a biomarker of calcification) emerged as the biomarkers of highest importance. Plasma biomarkers are strongly associated with the risk of adverse outcomes in patients with AS. Biomarkers of inflammation and calcification were most strongly related to prognosis.
Substances chimiques
Biomarkers
0
Peptide Fragments
0
Natriuretic Peptide, Brain
114471-18-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2021-2032Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 European Society of Cardiology.
Références
Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP, Gentile F, Jneid H, Krieger EV, Mack M, McLeod C, O'Gara PT, Rigolin VH, Sundt TM, Thompson A, Toly C. 2020 ACC/AHA Guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2021;77:450-500.
Bonow RO. Asymptomatic aortic stenosis. J Am Coll Cardiol 2015;66:2839-2841.
Chin CWL, Shah ASV, McAllister DA, Cowell SJ, Alam S, Langrish JP, Strachan FE, Hunter AL, Choy AM, Lang CC, Walker S, Boon NA, Newby DE, Mills NL, Dweck MR. High-sensitivity troponin I concentrations are a marker of an advanced hypertrophic response and adverse outcomes in patients with aortic stenosis. Eur Heart J 2014;35:2312-2321.
Lindman BR, Breyley JG, Schilling JD, Vatterott AM, Zajarias A, Maniar HS, Damiano RJ, Moon MR, Lawton JS, Gage BF, Sintek MA, Aquino A, Holley CL, Patel NM, Lawler C, Lasala JM, Novak E. Prognostic utility of novel biomarkers of cardiovascular stress in patients with aortic stenosis undergoing valve replacement. Heart 2015;101:1382-1388.
Bergler-Klein J, Klaar U, Heger M, Rosenhek R, Mundigler G, Gabriel H, Binder T, Pacher R, Maurer G, Baumgartner H. Natriuretic peptides predict symptom-free survival and postoperative outcome in severe aortic stenosis. Circulation 2004;109:2302-2308.
Sinning JM, Wollert KC, Sedaghat A, Widera C, Radermacher MC, Descoups C, Hammerstingl C, Weber M, Stundl A, Ghanem A, Widder J, Vasa-Nicotera M, Mellert F, Schiller W, Bauersachs J, Zur B, Holdenrieder S, Welz A, Grube E, Pencina MJ, Nickenig G, Werner N, Kempf T. Risk scores and biomarkers for the prediction of 1-year outcome after transcatheter aortic valve replacement. Am Heart J 2015;170:821-829.
Lancellotti P, Dulgheru R, Magne J, Henri C, Servais L, Bouznad N, Ancion A, Martinez C, Davin L, Le Goff C, Nchimi A, Pierard L, Oury C. Elevated plasma soluble ST2 is associated with heart failure symptoms and outcome in aortic stenosis. PLoS One 2015;10:e0138940.
Small A, Kiss D, Giri J, Anwaruddin S, Siddiqi H, Guerraty M, Chirinos JA, Ferrari G, Rader DJ. Biomarkers of calcific aortic valve disease. Arterioscler Thromb Vasc Biol 2017;37:623-632.
Chirinos JA, Orlenko A, Zhao L, Basso M, Cvijic ME, Li Z, Spires TE, Yarde M, Wang Z, Seiffert DA, Prenner S, Zamani P, Bhattacharya P, Kumar A, Margulies KB, Car BD, Gordon DA, Moore JH, Cappola TP. Multiple plasma biomarkers for risk stratification in patients with heart failure and preserved ejection fraction. J Am Coll Cardiol 2020;75:1281-1295.
Selvaraj S, Kim J, Ansari BA, Zhao L, Cvijic ME, Fronheiser M, Vanjarapu JMR, Kumar AA, Suri A, Yenigalla S, Satija V, Ans AH, Narvaez-Guerra O, Herrera-Enriquez K, Obeid MJ, Lee JJ, Jehangir Q, Seiffert DA, Car BD, Gordon DA, Chirinos JA. Body composition, natriuretic peptides, and adverse outcomes in heart failure with preserved and reduced ejection fraction. JACC Cardiovasc Imaging 2020;14:203-215.
Hidalgo CA, Klinger B, Barabasi A-L, Hausmann R. The product space conditions the development of nations. Science 2007;317:482-487.
Gross L. From structure to function: mapping the connection matrix of the human brain. PLoS Biol 2008;6:e164.
Olson RS, Urbanowicz RJ, Andrews PC, Lavender NA, Kidd LC, Moore JH. Automating biomedical data science through tree-based pipeline optimization. In: Squillero G, Burelli S, eds. Applications of Evolutionary Computation. 19th European Conference, EvoApplications 2016: Springer; 2016. pp 123-137.
Orlenko A, Moore JH, Orzechowski P, Olson RS, Cairns J, Caraballo PJ, Weinshilboum RM, Wang L, Breitenstein MK. Considerations for automated machine learning in clinical metabolic profiling: altered homocysteine plasma concentration associated with metformin exposure. Pac Symp Biocomput 2018;23:460-471.
Urbanowicz RJ, Moore JH. ExSTraCS 2.0: description and evaluation of a scalable learning classifier system. Evol Intell 2015;8:89-116.
Lindman BR, Clavel MA, Mathieu P, Iung B, Lancelloti P, Otto CM, Pibarot P. Calcific aortic stenosis. Nat Rev Dis Primers 2016;2:16006.
Galante A, Pietroiusti A, Vellini M, Piccolo P, Possati G, De Bonis M, Grillo RL, Fontana C, Favalli C. C-reactive protein is increased in patients with degenerative aortic valvular stenosis. J Am Coll Cardiol 2001;38:1078-1082.
Gunduz H, Akdemir R, Binak E, Tamer A, Keser N, Uyan C. Can serum lipid and CRP levels predict the “severity” of aortic valve stenosis? Acta Cardiol 2003;58:321-326.
Chalajour F, Treede H, Ebrahimnejad A, Lauke H, Reichenspurner H, Ergun S. Angiogenic activation of valvular endothelial cells in aortic valve stenosis. Exp Cell Res 2004;298:455-464.
Swaminathan G, Krishnamurthy VK, Sridhar S, Robson DC, Ning Y, Grande-Allen KJ. Hypoxia stimulates synthesis of neutrophil gelatinase-associated lipocalin in aortic valve disease. Front Cardiovasc Med 2019;6:156.
Sama IE, Woolley RJ, Nauta JF, Romaine SPR, Tromp J, Ter Maaten JM, van der Meer P, Lam CSP, Samani NJ, Ng LL, Metra M, Dickstein K, Anker SD, Zannad F, Lang CC, Cleland JGF, van Veldhuisen DJ, Hillege HL, Voors AA. A network analysis to identify pathophysiological pathways distinguishing ischaemic from non-ischaemic heart failure. Eur J Heart Fail 2020;22:821-833.
Clavel MA, Malouf J, Michelena HI, Suri RM, Jaffe AS, Mahoney DW, Enriquez-Sarano M. B-type natriuretic peptide clinical activation in aortic stenosis. J Am Coll Cardiol 2014;63:2016-2025.
Lindman BR, Dweck MR, Lancellotti P, Genereux P, Pierard LA, O'Gara PT, Bonow RO. Management of asymptomatic severe aortic stenosis. JACC Cardiovasc Imaging 2020;13:481-493.
Tse G, Ip C, Luk KS, Gong M, Ting YY, Lakhani I, Bazoukis G, Li G, Letsas KP, Dong M, Liu T, Wong MCS. Prognostic value of soluble ST2 postaortic valve replacement: a meta-analysis. Heart Asia 2018;10:e010980.
Anker SD. Inflammatory mediators in chronic heart failure: an overview. Heart 2004;90:464-470.
Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, Isakova T, Gutierrez OM, Aguillon-Prada R, Lincoln J, Hare JM, Mundel P, Morales A, Scialla J, Fischer M, Soliman EZ, Chen J, Go AS, Rosas SE, Nessel L, Townsend RR, Feldman HI, St. John Sutton M, Ojo A, Gadegbeku C, Di Marco GS, Reuter S, Kentrup D, Tiemann K, Brand M, Hill JA, Moe OW, Kuro-o M, Kusek JW, Keane MG, Wolf M. FGF23 induces left ventricular hypertrophy. J Clin Invest 2011;121:4393-4408.
Koller L, Kleber ME, Brandenburg VM, Goliasch G, Richter B, Sulzgruber P, Scharnagl H, Silbernagel G, Grammer TB, Delgado G, Tomaschitz A, Pilz S, Berger R, Mortl D, Hulsmann M, Pacher R, Marz W, Niessner A. Fibroblast growth factor 23 is an independent and specific predictor of mortality in patients with heart failure and reduced ejection fraction. Circ Heart Fail 2015;8:1059-1067.
Özkalaycı F, Gülmez Ö, Uğur-Altun B, Pandi-Perumal SR, Altun A. The role of osteoprotegerin as a cardioprotective versus reactive inflammatory marker: the chicken or the egg paradox. Balkan Med J 2018;35:225-232.
DeLeon-Pennell KY, Meschiari CA, Jung M, Lindsey ML. Matrix metalloproteinases in myocardial infarction and heart failure. Prog Mol Biol Transl Sci 2017;147:75-100.
de Oliveira Neves FM, Meneses GC, Sousa NEA, de Menezes R, Parahyba MC, Martins AMC, Liborio AB. Syndecan-1 in acute decompensated heart failure - association with renal function and mortality. Circ J 2015;79:1511-1519.
Eleuteri E, Di Stefano A, Giordano A, Corra U, Genta FT, Gnemmi I, Giannuzzi P. Prognostic value of angiopoietin-2 in patients with chronic heart failure. Int J Cardiol 2016;212:364-368.
Barroso MC, Boehme P, Kramer F, Mondritzki T, Koehler T, Gulker JE, Karoff M, Dinh W. Endostatin a potential biomarker for heart failure with preserved ejection fraction. Arq Bras Cardiol 2017;109:448-456.
van Deursen VM, Damman K, Voors AA, van der Wal MH, Jaarsma T, van Veldhuisen DJ, Hillege HL. Prognostic value of plasma neutrophil gelatinase-associated lipocalin for mortality in patients with heart failure. Circ Heart Fail 2014;7:35-42.
Lindman BR, Clavel M-A, Abu-Alhayja'a R, Cote N, Dagenais F, Novak E, Voisine P, Poulin A, Arsenault BJ, Desmeules P, Dahou A, Taster L, Aldahoun K, Bosse Y, Mathieu P, Pibarot P. Multimarker approach to identify patients with higher mortality and rehospitalization rate after surgical aortic valve replacement for aortic stenosis. JACC Cardiovasc Interv 2018;11:2172-2181.