Local atherosclerotic plaques are a source of prognostic biomarkers for adverse cardiovascular events.
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.
de Kleijn
Dominique P V
DP
Experimental Cardiology (G02523), UMC, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands.
Moll
Frans L
FL
Hellings
Willem E
WE
Ozsarlak-Sozer
Gonen
G
de Bruin
Peter
P
Doevendans
Pieter A
PA
Vink
Aryan
A
Catanzariti
Louise M
LM
Schoneveld
Arjan H
AH
Algra
Ale
A
Daemen
Mat J
MJ
Biessen
E A
EA
de Jager
W
W
Zhang
Huoming
H
de Vries
Jean-Paul
JP
Falk
Erling
E
Lim
Sai K
SK
van der Spek
Peter J
PJ
Sze
Siu Kwan
SK
Pasterkamp
Gerard
G
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
D015415:Biomarkers; D053495:Osteopontin