Local Atherosclerotic Plaques Are a Source of Prognostic Biomarkers for Adverse Cardiovascular Events

Dominique P. V. de Kleijn*, Frans L. Moll, Willem E. Hellings, Gonen Ozsarlak-Sozer, Jan Peter de Bruin, Pieter A. Doevendans, Aryan Vink, Louise M. Catanzariti, Arjan H. Schoneveld, Ale Algra, Mat J.A.P. Daemen, E. A. Biessen, W. Jager, Huoming Zhang, Jean-Paul P. M. de Vries, Erling Falk, Sai Kiang Lim, Peter J. van der Spek, Siu Kwan Sze, Gerard Pasterkamp

*Corresponding author for this work

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Objective-Atherosclerotic cardiovascular disease is a major burden to health care. Because atherosclerosis is considered a systemic disease, we hypothesized that one single atherosclerotic plaque contains ample molecular information that predicts future cardiovascular events in all vascular territories. Methods and Results-AtheroExpress is a biobank collecting atherosclerotic lesions during surgery, with a 3-year follow-up. The composite primary outcome encompasses all cardiovascular events and interventions, eg, cardiovascular death, myocardial infarction, stroke, and endovascular interventions. A proteomics search identified osteopontin as a potential plaque biomarker. Patients undergoing carotid surgery (n=574) served as the cohort in which plaque osteopontin levels were examined in relation to their outcome during follow-up and was validated in a cohort of patients undergoing femoral endarterectomy (n=151). Comparing the highest quartile of carotid plaque osteopontin levels with quartile 1 showed a hazard ratio for the primary outcome of 3.8 (95% confidence interval, 2.6-5.9). The outcome did not change after adjustment for plaque characteristics and traditional risk factors (hazard ratio, 3.5; 95% confidence interval, 2.0-5.9). The femoral validation cohort showed a hazard ratio of 3.8 (95% confidence interval 2.0 to 7.4) comparing osteopontin levels in quartile 4 with quartile 1. Conclusion-Plaque osteopontin levels in single lesions are predictive for cardiovascular events in other vascular territories. Local atherosclerotic plaques are a source of prognostic biomarkers with a high predictive value for secondary manifestations of atherosclerotic disease. (Arterioscler Thromb Vasc Biol. 2010;30:612-619.)
Original languageEnglish
Pages (from-to)612-U486
JournalArteriosclerosis Thrombosis and Vascular Biology
Issue number3
Publication statusPublished - Mar 2010


  • arterectomy
  • atherosclerosis
  • biomarker
  • plaque

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