The aim of the study was to evaluate the ability of following biomarkers as diagnostic tools and risk predictors of AAA: C-reactive protein, interleukin-6, pentraxin-3, galectin-3, procollagen type III N-terminal peptide, C-terminal telopeptide of type I collagen, high-sensitive troponin I, and brain natriuretic peptide. Seventy-two patients with an AAA and 100 healthy individuals were enrolled into the study. We assessed individual biomarker performance and correlation between the AAA diameter and biomarker levels, and also, a multivariate logistic regression was used to design a possible predictive model of AAA growth and rupture risk. We identified following four parameters with the highest potential to find a useful place in AAA diagnostics: galectin-3, pentraxin-3, interleukin-6, and C-terminal telopeptide of type I. The best biomarkers in our evaluation (galectin-3 and pentraxin-3) were AAA diameter-independent. With the high AUC and AAA diameter correlation, the high-sensitive troponin I can be used as an independent prognostic biomarker of the upcoming heart complications in AAA patients. Authors recommend to add biomarkers as additional parameters to the current AAA patient management. Main addition value of biomarkers is in the assessment of the AAA with the smaller diameter. Elevated biomarkers can change the treatment decision, which would be done only based on AAA diameter size. The best way how to manage the AAA patients is to create a reliable predictive model of AAA growth and rupture risk. A created multiparameter model gives very promising results with the significantly higher efficiency compared with the use of the individual biomarkers.

Department of Immunochemistry Diagnostics University Hospital and Faculty of Medicine in Pilsen Pilsen Czech Republic

Department of Immunochemistry Diagnostics University Hospital Pilsen Dr E Benese 1128 13 305 99 Pilsen Czech Republic

Department of Research Innlandet Hospital Trust Brumunddal Norway

Department of Rheumatology Hospital for Rheumatic Diseases 2609 Lillehammer Norway

Department of Surgery University Hospital and Faculty of Medicine in Pilsen Pilsen Czech Republic

Division of Cardiology Department of Medicine Brigham and Women's Hospital Boston MA USA

Zobrazit více v PubMed

Tang W, Yao L, Roetker NS, Alonso A, Lutsey PL, Steenson CC, Lederle FA, Hunter DW, Bengtson LG, Guan W, Missov E, Folsom AR. Lifetime risk and risk factors for abdominal aortic aneurysm in a 24-year prospective study: the ARIC study (atherosclerosis risk in communities) Arterioscler Thromb Vasc Biol. 2016;36:2468–2477. doi: 10.1161/ATVBAHA.116.308147. PubMed DOI PMC

Stackelberg O, Wolk A, Eliasson K, Hellberg A, Bersztel A, Larsson SC, Orsini N, Wanhainen A, Björck M. Lifestyle and risk of screening-detected abdominal aortic aneurysm in men. J Am Heart Assoc. 2017;6:e004725. doi: 10.1161/JAHA.116.004725. PubMed DOI PMC

Oliver-Williams C, Sweeting MJ, Turton G, Parkin D, Cooper D, Rodd C, Thompson SG, Earnshaw JJ, Gloucestershire and Swindon Abdominal Aortic Aneurysm Screening Programme Lessons learned about prevalence and growth rates of abdominal aortic aneurysms from a 25-year ultrasound population screening programme. Br J Surg. 2018;105:68–74. doi: 10.1002/bjs.10715. PubMed DOI

de Jesus-Silva SG, de Oliveira VR, de Moraes-Silva MA, Krupa AE, Cardoso RS. Risk factors and short and medium-term survival after open and endovascular repair of abdominal aortic aneurysms. J Vasc Bras. 2018;17:201–207. doi: 10.1590/1677-5449.011717. PubMed DOI PMC

Tang W, Yao L, Hoogeveen RC, Alonso A, Couper DJ, Lutsey PL, Steenson CC, Guan W, Hunter DW, Lederle FA, Folsom AR. The association of biomarkers of inflammation and extracellular matrix degradation with the risk of abdominal aortic aneurysm: the ARIC study. Angiology. 2018;70:130–140. doi: 10.1177/0003319718785278. PubMed DOI PMC

Ying AJ, Affan ET. Abdominal aortic aneurysm screening: a systematic review and meta-analysis of efficacy and cost. Ann Vasc Surg. 2019;54:298–303.e3. doi: 10.1016/j.avsg.2018.05.044. PubMed DOI

van Schaik TG, Yeung KK, Verhagen HJ, de Bruin JL, van Sambeek MRHM, Balm R, Zeebregts CJ, van Herwaarden JA, Blankensteijn JD, Grobbee DE, Blankensteijn JD, Bak AAA, Buth J, Pattynama PM, Verhoeven ELG, van Voorthuisen AE, Blankensteijn JD, Balm R, Buth J, Cuypers PWM, Grobbee DE, Prinssen M, van Sambeek MRHM, Verhoeven ELG, Baas AF, Hunink MG, van Engelshoven JM, Jacobs MJHM, de Mol BAJM, van Bockel JH, Balm R, Reekers J, Tielbeek X, Verhoeven ELG, Wisselink W, Boekema N, Heuveling LM, Sikking I, Prinssen M, Balm R, Blankensteijn JD, Buth J, Cuypers PWM, van Sambeek MRHM, Verhoeven ELG, de Bruin JL, Baas AF, Blankensteijn JD, Prinssen M, Buth J, Tielbeek AV, Blankensteijn JD, Balm R, Reekers JA, van Sambeek MRHM, Pattynama P, Verhoeven ELG, Prins T, van der Ham AC, van der Velden JJIM, van Sterkenburg SMM, ten Haken GB, Bruijninckx CMA, van Overhagen H, Tutein Nolthenius RP, Hendriksz TR, Teijink JAW, Odink HF, de Smet AAEA, Vroegindeweij D, van Loenhout RMM, Rutten MJ, Hamming JF, Lampmann LEH, Bender MHM, Pasmans H, Vahl AC, de Vries C, Mackaay AJC, van Dortmont LMC, van der Vliet AJ, Schultze Kool LJ, Boomsma JHB, van Dop HR, de Mol van Otterloo JCA, de Rooij TPW, Smits TM, Yilmaz EN, Wisselink W, van den Berg FG, Visser MJT, van der Linden E, Schurink GWH, de Haan M, Smeets HJ, Stabel P, van Elst F, Poniewierski J, Vermassen FEG. Long-term survival and secondary procedures after open or endovascular repair of abdominal aortic aneurysms. J Vasc Surg. 2017;66:1379–1389. doi: 10.1016/j.jvs.2017.05.122. PubMed DOI

Schermerhorn ML, Cronenwett JL. The UK small aneurysm trial. J Vasc Surg. 2001;33:443. doi: 10.1067/mva.2001.111985. PubMed DOI

Golubnitschaja O, Baban B, Boniolo G, Wang W, Bubnov R, Kapalla M, Krapfenbauer K, Mozaffari MS, Costigliola V. Medicine in the early twenty-first century: paradigm and anticipation—EPMA position paper 2016. EPMA J. 2016;7:23. doi: 10.1186/s13167-016-0072-4. PubMed DOI PMC

Ohno T, Aoki H, Ohno S, Nishihara M, Furusho A, Hiromatsu S, Akashi H, Fukumoto Y, Tanaka H. Cytokine profile of human abdominal aortic aneurysm: involvement of JAK/STAT pathway. Ann Vasc Dis. 2018;11:84–90. doi: 10.3400/avd.oa.17-00086. PubMed DOI PMC

Kucera R, Smid D, Topolcan O, Karlikova M, Fiala O, Slouka D, Skalicky T, Treska V, Kulda V, Simanek V, Safanda M, Pesta M. Searching for new biomarkers and the use of multivariate analysis in gastric cancer diagnostics. Anticancer Res. 2016;36:1967–1971. PubMed

Golubnitschaja O, Costigliola V, EPMA General report & recommendations in predictive, preventive and personalised medicine 2012: white paper of the European Association for Predictive, Preventive and Personalised Medicine. EPMA J. 2012;3:14. doi: 10.1186/1878-5085-3-14. PubMed DOI PMC

Urbonavicius S, Urbonaviciene G, Honoré B, Henneberg EW, Vorum H, Lindholt JS. Potential circulating biomarkers for abdominal aortic aneurysm expansion and rupture—a systematic review. Eur J Vasc Endovasc Surg Off J Eur Soc Vasc Surg. 2008;36:273–280. doi: 10.1016/j.ejvs.2008.05.009. PubMed DOI

Groeneveld ME, Meekel JP, Rubinstein SM, Merkestein LR, Tangelder GJ, Wisselink W, Truijers M, Yeung KK. Systematic review of circulating, biomechanical, and genetic markers for the prediction of abdominal aortic aneurysm growth and rupture. J Am Heart Assoc. 2018;7:e007791. doi: 10.1161/JAHA.117.007791. PubMed DOI PMC

Lindberg S, Zarrouk M, Holst J, Gottsäter A. Inflammatory markers associated with abdominal aortic aneurysm. Eur Cytokine Netw. 2016;27:75–80. PubMed

Dawson J, Cockerill GW, Choke E, Belli A-M, Loftus I, Thompson MM. Aortic aneurysms secrete interleukin-6 into the circulation. J Vasc Surg. 2007;45:350–356. doi: 10.1016/j.jvs.2006.09.049. PubMed DOI

Treska V, Topolcan O, Pecen L. Cytokines as plasma markers of abdominal aortic aneurysm. Clin Chem Lab Med. 2000;38:1161–1164. doi: 10.1515/CCLM.2000.178. PubMed DOI

Arao K, Fujiwara T, Taniguchi Y, Jinnouchi H, Sasai H, Matsumoto M, Funayama H, Ako J, Momomura SI. Implications of pentraxin 3 levels in patients with acute aortic dissection. Heart Vessel. 2015;30:211–217. doi: 10.1007/s00380-014-0470-2. PubMed DOI

Zhou Q, Chai X-P, Fang Z-F, Hu X-Q, Tang L. Association of plasma pentraxin-3 levels on admission with in-hospital mortality in patients with acute type a aortic dissection. Chin Med J. 2016;129:2589–2595. doi: 10.4103/0366-6999.192785. PubMed DOI PMC

Sawada H, Naito Y, Oboshi M, Soyama Y, Nishimura K, Eguchi A, Ando T, Okuhara Y, Morisawa D, Iwasaku T, Hirotani S, Mano T, Mitsuno M, Miyamoto Y, Masuyama T. Increment of pentraxin3 expression in abdominal aortic aneurysm. Int J Cardiol. 2015;195:281–282. doi: 10.1016/j.ijcard.2015.05.177. PubMed DOI

Papaspyridonos M, McNeill E, de Bono JP, Smith A, Burnand KG, Channon KM, Greaves DR. Galectin-3 is an amplifier of inflammation in atherosclerotic plaque progression through macrophage activation and monocyte chemoattraction. Arterioscler Thromb Vasc Biol. 2008;28:433–440. doi: 10.1161/ATVBAHA.107.159160. PubMed DOI

Leone M, Iacoviello M. The predictive value of plasma biomarkers in discharged heart failure patients: role of galectin-3. Minerva Cardioangiol. 2016;64:181–194. PubMed

Fashanu OE, Folsom AR, Oyenuga A, Ballantyne CM, Lutsey PL, Tang W. Galectin-3 and the incidence of abdominal aortic aneurysm: the atherosclerosis risk in communities (ARIC) study. Am J Cardiovasc Dis. 2017;7:114–121. PubMed PMC

Fernandez-García C-E, Tarin C, Roldan-Montero R, Martinez-Lopez D, Torres-Fonseca M, Lindhot JS, Vega de Ceniga M, Egido J, Lopez-Andres N, Blanco-Colio LM, Martín-Ventura JL. Increased galectin-3 levels are associated with abdominal aortic aneurysm progression and inhibition of galectin-3 decreases elastase-induced AAA development. Clin Sci Lond Engl. 2017;1979:2707–2719. doi: 10.1042/CS20171142. PubMed DOI

Martufi G, Gasser TC. Turnover of fibrillar collagen in soft biological tissue with application to the expansion of abdominal aortic aneurysms. J R Soc Interface. 2012;9:3366–3377. doi: 10.1098/rsif.2012.0416. PubMed DOI PMC

Lindholt JS, Heickendorff L, Vammen S, Fasting H, Henneberg EW. Five-year results of elastin and collagen markers as predictive tools in the management of small abdominal aortic aneurysms. Eur J Vasc Endovasc Surg Off J Eur Soc Vasc Surg. 2001;21:235–240. doi: 10.1053/ejvs.2001.1329. PubMed DOI

Ormezzano O, Baguet J-P, Thony F, Blin D, Chavanon O, Toussaint B, Trocmé C, Vanzetto G, Faure P. Aminoterminal propeptide of type III procollagen (PIIINP) is associated with ascending aortic aneurysm growth rate. Int J Cardiol. 2010;145:379–380. doi: 10.1016/j.ijcard.2010.02.051. PubMed DOI

Tambyraja AL, Dawson ARW, Murie JA, Chalmers RTA. Cardiac troponin I predicts outcome after ruptured abdominal aortic aneurysm repair. Br J Surg. 2005;92:824–827. doi: 10.1002/bjs.4995. PubMed DOI

Li G, Wu X-W, Lu W-H, Cheng J, Wu X-Y, Ai R, Zhou ZH, Tang ZZ, Liao YH. High-sensitivity cardiac troponin T: a biomarker for the early risk stratification of type-A acute aortic dissection? Arch Cardiovasc Dis. 2016;109:163–170. doi: 10.1016/j.acvd.2015.09.007. PubMed DOI

Acosta S, Gottsäter A, Engström G, Melander O, Zarrouk M, Nilsson PM, Smith JG. B-type natriuretic peptide for prediction of incident clinically significant abdominal aortic aneurysm: a population-based prospective study. Vasc Med Lond Engl. 2018;23:46–51. doi: 10.1177/1358863X17745150. PubMed DOI

Taimour S, Zarrouk M, Holst J, Melander O, Engström G, Smith JG, Gottsäter A. No relation between biomarkers at age 47–49 and aortic diameter after 14–19 years of follow-up—a population-based study. Vasa. 2017;46:291–295. doi: 10.1024/0301-1526/a000632. PubMed DOI

Lu M, Zhan X. The crucial role of multiomic approach in cancer research and clinically relevant outcomes. EPMA J. 2018;9:77–102. doi: 10.1007/s13167-018-0128-8. PubMed DOI PMC

Cheng T, Zhan X. Pattern recognition for predictive, preventive, and personalized medicine in cancer. EPMA J. 2017;8:51–60. doi: 10.1007/s13167-017-0083-9. PubMed DOI PMC

Golubnitschaja O, Polivka J, Jr, Yeghiazaryan K, Berliner L. Liquid biopsy and multiparametric analysis in management of liver malignancies: new concepts of the patient stratification and prognostic approach. EPMA J. 2018;9:271–285. doi: 10.1007/s13167-018-0146-6. PubMed DOI PMC

Abdominal aortic aneurysm in prostate cancer patients: the "road map" from incidental detection to advanced predictive, preventive, and personalized approach utilizing common follow-up for both pathologies

Inflammatory cell infiltrates, hypoxia, vascularization, pentraxin 3 and osteoprotegerin in abdominal aortic aneurysms - A quantitative histological study