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Evaluation of Serum Biomarkers for Patients at Increased Risk of Stroke

DOI: 10.1155/2012/906954

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Abstract:

Early recognition of vulnerable patients is an important issue for stroke prevention. In our study, a multiscore analysis of various biomarkers was performed to evaluate its superiority over the analysis of single factors. Study subjects ( ) were divided into four groups: asymptomatic patients with stable ( ) and unstable ( ) plaques and symptomatic patients with stable ( ) and unstable ( ) plaques. Serum levels of MMP-1, -2, -3, -7, -8, -9, TIMP-1, -2, TNF-α, IL-1b, and IL-6, -8, -10, -12 were measured. Multi-score analysis was performed using multiple receiver operating characteristics (ROC) and determination of appropriate cutoff values. Significant differences between the groups were observed for MMP-1, -7, -9 and TIMP-1 in serum of the study subjects ( ). Multiple biomarker analysis led to a significant increase in the AUC (area under curve). In case of plaque instability, positive predictive value (PPV) for up to 86.4% could be correctly associated with vulnerable plaques. Thus, multiscore analysis might be preferable than the use of single biomarkers. 1. Introduction Early recognition of rupture-prone atherosclerotic lesions in patients with high-graded carotid artery stenosis is an important clinical issue to prevent ischemic stroke [1–5]. Various pathophysiological mechanisms are responsible for the plaque progression and vulnerability such as degradation of extracellular matrix components especially by matrix metalloproteinases (MMPs), intensified inflammatory reaction, and neovascularisation [3, 5–7]. These features are the main reason for plaque rupture and consequent neurological symptoms. Thus, MMPs and inflammatory factors might also serve as possible markers for patients with unstable high-graded carotid artery stenosis [2, 8–16]. However, the data that have been achieved up to date are not consistent. Some studies investigated patients with symptomatic versus asymptomatic carotid stenosis or patients with or without emboli [12, 14–17]. Other researchers compared stable versus unstable plaques [2, 18, 19]. Furthermore, only very few investigations evaluated the usefulness of multiple biomarkers to predict rupture-prone atherosclerotic lesions [2, 17, 20, 21]. The aim of this work was the comparison of results of multiple analyses of various relevant biomarkers in patients with stable versus unstable carotid plaques and in individuals with or without neurological symptoms to evaluate whether multiple-score evaluation is superior to the analysis of single factors. 2. Materials and Methods 2.1. Study Patients The retrospective study

References

[1]  P. M. Rothwell, S. A. Gutnikov, and C. P. Warlow, “Reanalysis of the final results of the European carotid surgery trial,” Stroke, vol. 34, no. 2, pp. 514–523, 2003.
[2]  J. Pelisek, M. Rudelius, P. Zepper et al., “Multiple biological predictors for vulnerable carotid lesions,” Cerebrovascular Diseases, vol. 28, no. 6, pp. 601–610, 2009.
[3]  R. Virmani, A. P. Burke, A. Farb, and F. D. Kolodgie, “Pathology of the Vulnerable Plaque,” Journal of the American College of Cardiology, vol. 47, no. 8, pp. C13–C18, 2006.
[4]  C. M. Wahlgren, W. Zheng, W. Shaalan, J. Tang, and H. S. Bassiouny, “Human carotid plaque calcification and vulnerability: relationship between degree of plaque calcification, fibrous cap inflammatory gene expression and symptomatology,” Cerebrovascular Diseases, vol. 27, no. 2, pp. 193–200, 2009.
[5]  J. A. Chalela, “Evaluating the carotid plaque: going beyond stenosis,” Cerebrovascular Diseases, vol. 27, no. 1, pp. 19–24, 2009.
[6]  P. R. Moreno, K. R. Purushothaman, M. Sirol, A. P. Levy, and V. Fuster, “Neovascularization in human atherosclerosis,” Circulation, vol. 113, no. 18, pp. 2245–2252, 2006.
[7]  A. C. Newby, “Dual role of matrix metalloproteinases (matrixins) in intimal thickening and atherosclerotic plaque rupture,” Physiological Reviews, vol. 85, no. 1, pp. 1–31, 2005.
[8]  W. Koenig, “Cardiovascular biomarkers: added value with an integrated approach?” Circulation, vol. 116, no. 1, pp. 3–5, 2007.
[9]  N. Ferri, R. Paoletti, and A. Corsini, “Biomarkers for atherosclerosis: pathophysiological role and pharmacological modulation,” Current Opinion in Lipidology, vol. 17, no. 5, pp. 495–501, 2006.
[10]  L. Lind, “Circulating markers of inflammation and atherosclerosis,” Atherosclerosis, vol. 169, no. 2, pp. 203–214, 2003.
[11]  J. T. Wu and L. L. Wu, “Linking inflammation and atherogenesis: soluble markers identified for the detection of risk factors and for early risk assessment,” Clinica Chimica Acta, vol. 366, no. 1-2, pp. 74–80, 2006.
[12]  M. M. Turu, J. Krupinski, E. Catena et al., “Intraplaque MMP-8 levels are increased in asymptomatic patients with carotid plaque progression on ultrasound,” Atherosclerosis, vol. 187, no. 1, pp. 161–169, 2006.
[13]  B. Alvarez, C. Ruiz, P. Chac?n, J. Alvarez-Sabin, and M. Matas, “Serum values of metalloproteinase-2 and metalloproteinase-9 as related to unstable plaque and inflammatory cells in patients with greater than 70% carotid artery stenosis,” Journal of Vascular Surgery, vol. 40, no. 3, pp. 469–475, 2004.
[14]  P. Sapienza, L. di Marzo, V. Borrelli et al., “Basic fibroblast growth factor mediates carotid plaque instability through metalloproteinase-2 and -9 expression,” European Journal of Vascular and Endovascular Surgery, vol. 28, no. 1, pp. 89–97, 2004.
[15]  K. J. Molloy, M. M. Thompson, E. C. Schwalbe, P. R. Bell, A. R. Naylor, and I. M. Loftus, “Elevation in plasma MMP-9 following carotid endarterectomy is associated with particulate cerebral embolisation,” European Journal of Vascular and Endovascular Surgery, vol. 27, no. 4, pp. 409–413, 2004.
[16]  C. D. Bicknell, D. Peck, N. M. Lau et al., “The relationship between plasma MMP-1, -7, -8 and -13 levels and embolic potential during carotid endoluminal intervention,” European Journal of Vascular and Endovascular Surgery, vol. 28, no. 5, pp. 500–507, 2004.
[17]  P. Heider, J. Pelisek, H. Poppert, and H. H. Eckstein, “Evaluation of serum matrix metalloproteinases as biomarkers for detection of neurological symptoms in carotid artery disease,” Vascular and Endovascular Surgery, vol. 43, no. 6, pp. 551–560, 2009.
[18]  J. N. Redgrave, P. Gallagher, J. K. Lovett, and P. M. Rothwell, “Critical cap thickness and rupture in symptomatic carotid plaques: the oxford plaque study,” Stroke, vol. 39, no. 6, pp. 1722–1729, 2008.
[19]  J. N. E. Redgrave, J. K. Lovett, P. J. Gallagher, and P. M. Rothwell, “Histological assessment of 526 symptomatic carotid plaques in relation to the nature and timing of ischemic symptoms: the Oxford plaque study,” Circulation, vol. 113, no. 19, pp. 2320–2328, 2006.
[20]  T. J. Wang, P. Gona, M. G. Larson et al., “Multiple biomarkers for the prediction of first major cardiovascular events and death,” The New England Journal of Medicine, vol. 355, no. 25, pp. 2631–2639, 2006.
[21]  A. H. Thakore, C. Y. Guo, M. G. Larson et al., “Association of multiple inflammatory markers with carotid intimal medial thickness and stenosis (from the Framingham Heart Study),” American Journal of Cardiology, vol. 99, no. 11, pp. 1598–1602, 2007.
[22]  C. Warlow, B. Farrell, A. Fraser, P. Sandercock, and J. Slattery, “Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European carotid surgery trial (ECST),” The Lancet, vol. 351, no. 9113, pp. 1379–1387, 1998.
[23]  E. R. DeLong, D. M. DeLong, and D. L. Clarke-Pearson, “Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach,” Biometrics, vol. 44, no. 3, pp. 837–845, 1988.
[24]  V. Lemaitre and J. D'Armiento, “Matrix metalloproteinases in development and disease,” Birth Defects Research C, vol. 78, no. 1, pp. 1–10, 2006.
[25]  P. Libby, G. Sukhova, R. T. Lee, and Z. S. Galis, “Cytokines regulate vascular functions related to stability of the atherosclerotic plaque,” Journal of Cardiovascular Pharmacology, vol. 25, no. 2, supplement 2, pp. S9–S12, 1995.
[26]  S. Chaturvedi, A. Bruno, T. Feasby et al., “Carotid endarterectomy—an evidence-based review: report of the therapeutics and technology assessment subcommittee of the American academy of neurology,” Neurology, vol. 65, no. 6, pp. 794–801, 2005.
[27]  T. Ito and U. Ikeda, “Inflammatory cytokines and cardiovascular disease,” Current Drug Targets, vol. 2, no. 3, pp. 257–265, 2003.

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