Thromb Haemost 2009; 101(01): 48-54
DOI: 10.1160/TH08-07-0488
Review Article
Schattauer GmbH

Biobanks and the search for predictive biomarkers of local and systemic outcome in atherosclerotic disease

Rob Hurks
1   Experimental Cardiology Laboratory, University Medical Center Utrecht, Utrecht, The Netherlands
2   Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
,
Wouter Peeters
1   Experimental Cardiology Laboratory, University Medical Center Utrecht, Utrecht, The Netherlands
3   Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands
,
Wouter J. M. Derksen
1   Experimental Cardiology Laboratory, University Medical Center Utrecht, Utrecht, The Netherlands
,
Willem E. Hellings
1   Experimental Cardiology Laboratory, University Medical Center Utrecht, Utrecht, The Netherlands
2   Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
,
Imo E. Hoefer
1   Experimental Cardiology Laboratory, University Medical Center Utrecht, Utrecht, The Netherlands
,
Frans L. Moll
2   Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
,
Dominique P. V. de Kleijn
1   Experimental Cardiology Laboratory, University Medical Center Utrecht, Utrecht, The Netherlands
3   Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands
,
Gerard Pasterkamp
1   Experimental Cardiology Laboratory, University Medical Center Utrecht, Utrecht, The Netherlands
› Author Affiliations
Further Information

Publication History

Received: 29 July 2008

Accepted after minor revision: 13 September 2008

Publication Date:
23 November 2017 (online)

Summary

Multiple risk factors have been associated with progression of atherosclerosis. To identify the individual patient who is at risk for disruption of a vulnerable plaque, leading to a cardiovascular event, remains a major challenge. Current screening methods, based on traditional risk factors, do not allow risk stratification on an individual level. The discovery of new biomarkers would aid in identifying specific patient groups at risk for adverse cardiovascular events due to atherosclerotic disease progression. The current definition of the vulnerable plaque, e.g. atheromatous inflammatory plaque with a thin fibrous cap, has been based on cross-sectional post-mortem studies. The predictive value of these histological characteristics of the vulnerable plaque is likely to be low, because they are also frequently observed at multiple locations in symptomatic and asymptomatic patients. The Athero-express study follows a new concept to search for the atherosclerotic patient who may suffer from adverse events. In this study, we investigate the predictive value of local plaque composition for adverse events in other vascular territories, regarding the plaque as a concentrated expression of this systemic disease. First results from this longitudinal biobank study show that the local plaque hides strong predictive value for cardiovascular events elsewhere in the vascular tree. Longitudinal biobank studies will facilitate the identification of novel local plaque markers. The search for the plaque protein signature that is predictive for adverse events might enable patient stratification that will allow individualized tailor made medicine and subsequently guide the choice for therapeutic interventions.

 
  • References

  • 1 Lopez AD, Mathers CD, Ezzati M. et al. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 2006; 367: 1747-1757.
  • 2 Yusuf S, Reddy S, Ounpuu S. et al. Global burden of cardiovascular diseases: part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation 2001; 104: 2746-2753.
  • 3 Dawber TR, Meadors GF, Moore Jr. FE. Epidemiological approaches to heart disease: the Framingham Study. Am J Public Health Nations Health 1951; 41: 279-281.
  • 4 Yuille M, van Ommen GJ, Brechot C. et al. Bio-banking for Europe. Brief Bioinform 2008; 09: 14-24.
  • 5 Schaar JA, De Korte CL, Mastik F. et al. Characterizing vulnerable plaque features with intravascular elastography. Circulation 2003; 108: 2636-2641.
  • 6 Hellings WE, Peeters W, Moll FL. et al. From vulnerable plaque to vulnerable patient: the search for biomarkers of plaque destabilization. Trends Cardiovasc Med 2007; 17: 162-171.
  • 7 Davies MJ, Richardson PD, Woolf N. et al. Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. Br Heart J 1993; 69: 377-381.
  • 8 Escaned J, van Suylen RJ, MacLeod DC. et al. Histologic characteristics of tissue excised during directional coronary atherectomy in stable and unstable angina pectoris. Am J Cardiol 1993; 71: 1442-1447.
  • 9 Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation 1995; 92: 657-671.
  • 10 Fernandez-Ortiz A, Badimon JJ, Falk E. et al. Characterization of the relative thrombogenicity of athero-sclerotic plaque components: implications for consequences of plaque rupture. J Am Coll Cardiol 1994; 23: 1562-1569.
  • 11 Moreno PR, Falk E, Palacios IF. et al. Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture. Circulation 1994; 90: 775-778.
  • 12 Schaar JA, Muller JE, Falk E. et al. Terminology for high-risk and vulnerable coronary artery plaques. Report of a meeting on the vulnerable plaque, June 17 and 18, 2003, Santorini, Greece. Eur Heart J 2004; 25: 1077-1082.
  • 13 Nighoghossian N, Derex L, Douek P. The vulnerable carotid artery plaque: current imaging methods and new perspectives. Stroke 2005; 36: 2764-2772.
  • 14 Yock PG, Linker DT. Intravascular ultrasound. Looking below the surface of vascular disease. Circulation 1990; 81: 1715-1718.
  • 15 Tearney GJ, Yabushita H, Houser SL. et al. Quantification of macrophage content in atherosclerotic plaques by optical coherence tomography. Circulation 2003; 107: 113-119.
  • 16 Yabushita H, Bouma BE, Houser SL. et al. Characterization of human atherosclerosis by optical coherence tomography. Circulation 2002; 106: 1640-1645.
  • 17 Burke AP, Kolodgie FD, Farb A. et al. Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression. Circulation 2001; 103: 934-940.
  • 18 Davies MJ, Bland JM, Hangartner JR. et al. Factors influencing the presence or absence of acute coronary artery thrombi in sudden ischaemic death. Eur Heart J 1989; 10: 203-208.
  • 19 Farb A, Burke AP, Tang AL. et al. Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death. Circulation 1996; 93: 1354-1363.
  • 20 Pasterkamp G, Schoneveld AH, van der Wal AC. et al. Inflammation of the atherosclerotic cap and shoulder of the plaque is a common and locally observed feature in unruptured plaques of femoral and coronary arteries. Arterioscler Thromb Vasc Biol 1999; 19: 54-58.
  • 21 Svindland A, Torvik A. Atherosclerotic carotid disease in asymptomatic individuals: An histological study of 53 cases. Acta Neurol Scand 1988; 78: 506-517.
  • 22 Vink A, Schoneveld AH, Poppen M. et al. Morpho-metric and immunohistochemical characterization of the intimal layer throughout the arterial system of elderly humans. J Anat 2002; 200: 97-103.
  • 23 Vink A, Pasterkamp G. Atherosclerotic plaques: how vulnerable is the definition of “the vulnerable plaque”?. J Interv Cardiol 2003; 16: 115-122.
  • 24 Naghavi M, Libby P, Falk E. et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. Circulation 2003; 108: 1664-1672.
  • 25 Naghavi M, Libby P, Falk E. et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II. Circulation 2003; 108: 1772-1778.
  • 26 Liuzzo G, Biasucci LM, Gallimore JR. et al. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med 1994; 331: 417-424.
  • 27 Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001; 69: 89-95.
  • 28 Heinrich J, Schulte H, Schonfeld R. et al. Association of variables of coagulation, fibrinolysis and acute-phase with atherosclerosis in coronary and peripheral arteries and those arteries supplying the brain. Thromb Haemost 1995; 73: 374-379.
  • 29 Koenig W, Khuseyinova N. Biomarkers of athero-sclerotic plaque instability and rupture. Arterioscler Thromb Vasc Biol 2007; 27: 15-26.
  • 30 Haverkate F, Thompson SG, Pyke SD. et al. Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet 1997; 349: 462-466.
  • 31 Nissen SE, Tuzcu EM, Schoenhagen P. et al. Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med 2005; 352: 29-38.
  • 32 Danesh J, Wheeler JG, Hirschfield GM. et al. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 2004; 350: 1387-1397.
  • 33 Koukkunen H, Penttila K, Kemppainen A. et al. C-reactive protein, fibrinogen, interleukin-6 and tumour necrosis factor-alpha in the prognostic classification of unstable angina pectoris. Ann Med 2001; 33: 37-47.
  • 34 Aukrust P, Yndestad A, Smith C. et al. Chemokines in cardiovascular risk prediction. Thromb Haemost 2007; 97: 748-754.
  • 35 Wang TJ, Gona P, Larson MG. et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med 2006; 355: 2631-2639.
  • 36 Musunuru K, Blumenthal RS. Biomarkers for prediction of cardiovascular events. N Engl J Med 2007; 356: 1472 author reply 1474–1475.
  • 37 Zethelius B, Berglund L, Sundstrom J. et al. Use of multiple biomarkers to improve the prediction of death from cardiovascular causes. N Engl J Med 2008; 358: 2107-2116.
  • 38 Austin MJ, Heneghan MA. Multiple biomarkers and cardiovascular risk. N Engl J Med 2008; 359: 760-761 author reply 761.
  • 39 Verhoeven BA, Velema E, Schoneveld AH. et al. Athero-express: differential atherosclerotic plaque expression of mRNA and protein in relation to cardiovascular events and patient characteristics. Rationale and design. Eur J Epidemiol 2004; 19: 1127-1133.
  • 40 Verhoeven B, Hellings WE, Moll FL. et al. Carotid atherosclerotic plaques in patients with transient ischemic attacks and stroke have unstable characteristics compared with plaques in asymptomatic and amaurosis fugax patients. J Vasc Surg 2005; 42: 1075-1081.
  • 41 Hellings WE, Pasterkamp G, Verhoeven BA. et al. Gender-associated differences in plaque phenotype of patients undergoing carotid endarterectomy. J Vasc Surg 2007; 45: 289-297.
  • 42 Hellings WE, Moll FL, de Vries JP. et al. Histological characterization of restenotic carotid plaques in relation to recurrence interval and clinical presentation: a cohort study. Stroke 2008; 39: 1029-1032.
  • 43 Hellings WE, Moll FL, De Vries JP. et al. Athero-sclerotic plaque composition and occurrence of restenosis after carotid endarterectomy. J Am Med Assoc 2008; 299: 547-554.
  • 44 Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005; 352: 1685-1695.
  • 45 Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med 1999; 340: 115-126.
  • 46 Naghavi M, Falk E, Hecht HS. et al. From vulnerable plaque to vulnerable patient--Part III: Executive summary of the Screening for Heart Attack Prevention and Education (SHAPE) Task Force report. Am J Cardiol 2006; 98: 2H-15H.
  • 47 Maier W, Altwegg LA, Corti R. et al. Inflammatory markers at the site of ruptured plaque in acute myocardial infarction: locally increased interleukin-6 and serum amyloid A but decreased C-reactive protein. Circulation 2005; 111: 1355-1361.
  • 48 Lombardo A, Biasucci LM, Lanza GA. et al. Inflammation as a possible link between coronary and carotid plaque instability. Circulation 2004; 109: 3158-3163.
  • 49 Mauriello A, Sangiorgi G, Fratoni S. et al. Diffuse and active inflammation occurs in both vulnerable and stable plaques of the entire coronary tree: a histopathologic study of patients dying of acute myocardial infarction. J Am Coll Cardiol 2005; 45: 1585-1593.
  • 50 Rothwell PM, Villagra R, Gibson R. et al. Evidence of a chronic systemic cause of instability of athero-sclerotic plaques. Lancet 2000; 355: 19-24.
  • 51 Pasterkamp G, Hellings WE, De Kleijn DP. et al. Local plaque characteristics are predictive for systemic cardiovascular events. Results from the ongoing Athero-Express study: a longitudinal study in 667 patients undergoing carotid endarterectomy. Eur Heart J 2007; 28: 256.
  • 52 Sanz J, Fayad ZA. Imaging of atherosclerotic cardiovascular disease. Nature 2008; 451: 953-957.
  • 53 Artemov D, Bhujwalla ZM, Bulte JW. Magnetic resonance imaging of cell surface receptors using targeted contrast agents. Curr Pharm Biotechnol 2004; 05: 485-494.
  • 54 Mulder WJ, Strijkers GJ, Vucic E. et al. Magnetic resonance molecular imaging contrast agents and their application in atherosclerosis. Top Magn Reson Imag 2007; 18: 409-417.
  • 55 Asslaber M, Zatloukal K. Biobanks: transnational, European and global networks. Brief Funct Genomic Proteomic 2007; 06: 193-201.