title: Local atherosclerotic plaques are a source of prognostic biomarkers for adverse cardiovascular events.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Experimental Cardiology (G02523), UMC, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands.
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
authors.forename: Willem E
authors.initials: WE
authors.lastname: Hellings
authors.forename: Gonen
authors.initials: G
authors.lastname: Ozsarlak-Sozer
authors.forename: Peter
authors.initials: P
authors.lastname: de Bruin
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Aryan
authors.initials: A
authors.lastname: Vink
authors.forename: Louise M
authors.initials: LM
authors.lastname: Catanzariti
authors.forename: Arjan H
authors.initials: AH
authors.lastname: Schoneveld
authors.forename: Ale
authors.initials: A
authors.lastname: Algra
authors.forename: Mat J
authors.initials: MJ
authors.lastname: Daemen
authors.forename: E A
authors.initials: EA
authors.lastname: Biessen
authors.forename: W
authors.initials: W
authors.lastname: de Jager
authors.forename: Huoming
authors.initials: H
authors.lastname: Zhang
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: de Vries
authors.forename: Erling
authors.initials: E
authors.lastname: Falk
authors.forename: Sai K
authors.initials: SK
authors.lastname: Lim
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van der Spek
authors.forename: Siu Kwan
authors.initials: SK
authors.lastname: Sze
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
mesh_terms: D000368:Aged; D001157:Arterial Occlusive Diseases / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D002339:Carotid Arteries / Q000473:pathology; D016893:Carotid Stenosis / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D005263:Femoral Artery / Q000473:pathology; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D053495:Osteopontin / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D053495:Osteopontin