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    Local Atherosclerotic Plaques Are a Source of Prognostic Biomarkers for Adverse Cardiovascular Events
    (Lippincott Williams & Wilkins, 2010) de Kleijn, Dominique P. V.; Moll, Frans L.; Hellings, Willem E.; Ozsarlak-Sozer, Gonen; de Bruin, Peter; Doevendans, Pieter A.; Vink, Aryan; Catanzariti, Louise M.; Schoneveld, Arjan H.; Algra, Ale; Daemen, Mat J.; Biessen, E. A.; de Jager, W.; Zhang, Huoming; de Vries, Jean-Paul; Falk, Erling; Lim, Sai K.; van der Spek, Peter J.; Sze, Siu Kwan; Pasterkamp, Gerard
    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.)