Yonsei Med J.  2012 May;53(3):508-516. 10.3349/ymj.2012.53.3.508.

Correlations between Coronary Plaque Tissue Composition Assessed by Virtual Histology and Blood Levels of Biomarkers for Coronary Artery Disease

Affiliations
  • 1Division of Cardiology, Severance Cardiovascular Hospital & Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea. mkhong61@yuhs.ac
  • 2General Hospital of Thanh Hoa Province, Thanh Hoa City, Vietnam.

Abstract

PURPOSE
We investigated correlations of coronary plaque composition determined by virtual histology (VH) intravascular ultrasound (IVUS) and blood levels of biomarkers that represent the vulnerability of coronary plaques.
MATERIALS AND METHODS
Pre- and postprocedural blood levels of high sensitivity C-reactive protein, soluble CD40 ligand (sCD40L), matrix metalloproteinase-9, and neopterin were measured in 70 patients with stable angina (SA) or unstable angina (UA) who were undergoing percutaneous coronary intervention (PCI) for single lesions. We evaluated the data for correlations between these biomarkers and necrotic core contents in PCI target lesions analyzed by VH.
RESULTS
Clinical characteristics, IVUS, VH, and biomarker blood levels were not different between the SA and the UA group except for more frequent previous statin use (52.3% vs. 23.1%, p=0.017) and lower remodeling index in the SA group (0.98+/-0.09 vs. 1.10+/-0.070, p<0.001). Among the biomarkers evaluated, only pre-PCI neopterin level showed a weakly significant correlation with the absolute volume of the necrotic core (r=0.320, p=0.008). Pre- and post-PCI blood levels of sCD40L (r=0.220, p=0.072; r=0.231, p=0.062) and post-PCI blood level of neopterin (r=0.238, p=0.051) showed trends toward weakly positive correlations with the absolute volume of necrotic core.
CONCLUSION
We found a weakly positive correlation between the pre-PCI neopterin level and necrotic core volume in the PCI-target lesion. The clinical implications of our findings need to be investigated in further studies.

Keyword

Atherosclerosis; coronary artery disease; inflammation; intravascular ultrasound

MeSH Terms

Aged
Angina Pectoris/blood
Angina, Stable/blood
Angina, Unstable/blood
Angioplasty, Balloon, Coronary
Biological Markers/blood
C-Reactive Protein/metabolism
CD40 Ligand/blood
Coronary Artery Disease/*blood/*metabolism/ultrasonography
Female
Humans
Male
Matrix Metalloproteinase 9/blood
Middle Aged
Neopterin/blood
Plaque, Atherosclerotic/*blood/*metabolism/ultrasonography
Ultrasonography, Interventional

Reference

1. Finn AV, Nakano M, Narula J, Kolodgie FD, Virmani R. Concept of vulnerable/unstable plaque. Arterioscler Thromb Vasc Biol. 2010. 30:1282–1292.
Article
2. Burke AP, Farb A, Malcom GT, Liang YH, Smialek J, Virmani R. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med. 1997. 336:1276–1282.
Article
3. Libby P, Schoenbeck U, Mach F, Selwyn AP, Ganz P. Current concepts in cardiovascular pathology: the role of LDL cholesterol in plaque rupture and stabilization. Am J Med. 1998. 104:14S–18S.
Article
4. Shah PK, Falk E, Badimon JJ, Fernandez-Ortiz A, Mailhac A, Villareal-Levy G, et al. Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture. Circulation. 1995. 92:1565–1569.
5. Moreno PR, Falk E, Palacios IF, Newell JB, Fuster V, Fallon JT. Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture. Circulation. 1994. 90:775–778.
Article
6. Libby P. Molecular bases of the acute coronary syndromes. Circulation. 1995. 91:2844–2850.
Article
7. Yeh ET, Anderson HV, Pasceri V, Willerson JT. C-reactive protein: linking inflammation to cardiovascular complications. Circulation. 2001. 104:974–975.
8. Burke AP, Tracy RP, Kolodgie F, Malcom GT, Zieske A, Kutys R, et al. Elevated C-reactive protein values and atherosclerosis in sudden coronary death: association with different pathologies. Circulation. 2002. 105:2019–2023.
Article
9. Kai H, Ikeda H, Yasukawa H, Kai M, Seki Y, Kuwahara F, et al. Peripheral blood levels of matrix metalloproteases-2 and -9 are elevated in patients with acute coronary syndromes. J Am Coll Cardiol. 1998. 32:368–372.
Article
10. Gupta S, Fredericks S, Schwartzman RA, Holt DW, Kaski JC. Serum neopterin in acute coronary syndromes. Lancet. 1997. 349:1252–1253.
Article
11. Antoniades C, Bakogiannis C, Tousoulis D, Antonopoulos AS, Stefanadis C. The CD40/CD40 ligand system: linking inflammation with atherothrombosis. J Am Coll Cardiol. 2009. 54:669–677.
12. Nair A, Kuban BD, Tuzcu EM, Schoenhagen P, Nissen SE, Vince DG. Coronary plaque classification with intravascular ultrasound radiofrequency data analysis. Circulation. 2002. 106:2200–2206.
Article
13. Nasu K, Tsuchikane E, Katoh O, Vince DG, Virmani R, Surmely JF, et al. Accuracy of in vivo coronary plaque morphology assessment: a validation study of in vivo virtual histology compared with in vitro histopathology. J Am Coll Cardiol. 2006. 47:2405–2412.
14. Hong MK, Mintz GS, Lee CW, Suh J, Kim JH, Park DW, et al. Comparison of virtual histology to intravascular ultrasound of culprit coronary lesions in acute coronary syndrome and target coronary lesions in stable angina pectoris. Am J Cardiol. 2007. 100:953–959.
Article
15. Kawaguchi R, Oshima S, Jingu M, Tsurugaya H, Toyama T, Hoshizaki H, et al. Usefulness of virtual histology intravascular ultrasound to predict distal embolization for ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2007. 50:1641–1646.
Article
16. Kawamoto T, Okura H, Koyama Y, Toda I, Taguchi H, Tamita K, et al. The relationship between coronary plaque characteristics and small embolic particles during coronary stent implantation. J Am Coll Cardiol. 2007. 50:1635–1640.
Article
17. Mintz GS, Nissen SE, Anderson WD, Bailey SR, Erbel R, Fitzgerald PJ, et al. American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2001. 37:1478–1492.
Article
18. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003. 111:1805–1812.
Article
19. Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation. 2000. 102:2165–2168.
Article
20. Pasceri V, Cheng JS, Willerson JT, Yeh ET. Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation. 2001. 103:2531–2534.
Article
21. Jialal I, Devaraj S, Venugopal SK. C-reactive protein: risk marker or mediator in atherothrombosis? Hypertension. 2004. 44:6–11.
Article
22. Yasojima K, Schwab C, McGeer EG, McGeer PL. Generation of C-reactive protein and complement components in atherosclerotic plaques. Am J Pathol. 2001. 158:1039–1051.
Article
23. Kobayashi S, Inoue N, Ohashi Y, Terashima M, Matsui K, Mori T, et al. Interaction of oxidative stress and inflammatory response in coronary plaque instability: important role of C-reactive protein. Arterioscler Thromb Vasc Biol. 2003. 23:1398–1404.
Article
24. Hermann A, Rauch BH, Braun M, Schrör K, Weber AA. Platelet CD40 ligand (CD40L)--subcellular localization, regulation of expression, and inhibition by clopidogrel. Platelets. 2001. 12:74–82.
Article
25. Zirlik A, Maier C, Gerdes N, MacFarlane L, Soosairajah J, Bavendiek U, et al. CD40 ligand mediates inflammation independently of CD40 by interaction with Mac-1. Circulation. 2007. 115:1571–1580.
Article
26. Schönbeck U, Libby P. CD40 signaling and plaque instability. Circ Res. 2001. 89:1092–1103.
Article
27. Nagase H, Visse R, Murphy G. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res. 2006. 69:562–573.
Article
28. Galis ZS, Sukhova GK, Lark MW, Libby P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest. 1994. 94:2493–2503.
Article
29. Gieseg SP, Crone EM, Flavall EA, Amit Z. Potential to inhibit growth of atherosclerotic plaque development through modulation of macrophage neopterin/7,8-dihydroneopterin synthesis. Br J Pharmacol. 2008. 153:627–635.
Article
30. Avanzas P, Arroyo-Espliguero R, Quiles J, Roy D, Kaski JC. Elevated serum neopterin predicts future adverse cardiac events in patients with chronic stable angina pectoris. Eur Heart J. 2005. 26:457–463.
Article
31. Zouridakis E, Avanzas P, Arroyo-Espliguero R, Fredericks S, Kaski JC. Markers of inflammation and rapid coronary artery disease progression in patients with stable angina pectoris. Circulation. 2004. 110:1747–1753.
Article
32. Prasad A, Tsimikas S. Candidate biomarkers for the detection of coronary plaque destabilization and rupture. Curr Atheroscler Rep. 2008. 10:309–317.
Article
33. Naruko T, Furukawa A, Yunoki K, Komatsu R, Nakagawa M, Matsumura Y, et al. Increased expression and plasma levels of myeloperoxidase are closely related to the presence of angiographically-detected complex lesion morphology in unstable angina. Heart. 2010. 96:1716–1722.
Article
34. Kubo T, Matsuo Y, Hayashi Y, Yamano T, Tanimoto T, Ino Y, et al. High-sensitivity C-reactive protein and plaque composition in patients with stable angina pectoris: a virtual histology intravascular ultrasound study. Coron Artery Dis. 2009. 20:531–535.
Article
35. Otake H, Shite J, Shinke T, Watanabe S, Tanino Y, Ogasawara D, et al. Relation between plasma adiponectin, high-sensitivity C-reactive protein, and coronary plaque components in patients with acute coronary syndrome. Am J Cardiol. 2008. 101:1–7.
Article
36. Park JP, Lee BK, Shim JM, Kim SH, Lee CW, Kang DH, et al. Relationship between multiple plasma biomarkers and vulnerable plaque determined by virtual histology intravascular ultrasound. Circ J. 2010. 74:332–336.
Article
37. Gottsauner-Wolf M, Zasmeta G, Hornykewycz S, Nikfardjam M, Stepan E, Wexberg P, et al. Plasma levels of C-reactive protein after coronary stent implantation. Eur Heart J. 2000. 21:1152–1158.
Article
38. Kim JY, Ko YG, Shim CY, Park S, Hwang KC, Choi D, et al. Comparison of effects of drug-eluting stents versus bare metal stents on plasma C-reactive protein levels. Am J Cardiol. 2005. 96:1384–1388.
Article
39. Kozinski M, Krzewina-Kowalska A, Kubica J, Zbikowska-Gotz M, Dymek G, Piasecki R, et al. Percutaneous coronary intervention triggers a systemic inflammatory response in patients treated for in-stent restenosis -- comparison with stable and unstable angina. Inflamm Res. 2005. 54:187–193.
Article
40. Azar RR, McKay RG, Kiernan FJ, Seecharran B, Feng YJ, Fram DB, et al. Coronary angioplasty induces a systemic inflammatory response. Am J Cardiol. 1997. 80:1476–1478.
Article
41. Quist-Paulsen P. Statins and inflammation: an update. Curr Opin Cardiol. 2010. 25:399–405.
Article
42. Nasu K, Tsuchikane E, Katoh O, Tanaka N, Kimura M, Ehara M, et al. Effect of fluvastatin on progression of coronary atherosclerotic plaque evaluated by virtual histology intravascular ultrasound. JACC Cardiovasc Interv. 2009. 2:689–696.
Article
43. Thim T, Hagensen MK, Wallace-Bradley D, Granada JF, Kaluza GL, Drouet L, et al. Unreliable assessment of necrotic core by virtual histology intravascular ultrasound in porcine coronary artery disease. Circ Cardiovasc Imaging. 2010. 3:384–391.
Article
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