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 (nϭ574) 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 (nϭ151). 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. Key Words: arterectomy Ⅲ atherosclerosis Ⅲ biomarker Ⅲ plaque A dvanced atherosclerotic cardiovascular disease continues to be a major burden to health care expenditures and requires exhaustive forms of medical treatment. A pressing need exists for prognostic biomarkers to identify high-risk patients for aggressive treatment.
Conclusion-PlaqueProteins in the plasma are easily accessible and can serve as a surrogate measure of atherosclerotic disease progression, but existing circulating biomarkers do not provide an accurate value of predictive patient risk. 1,2 The main focus toward identifying patients with rapidly progressive advanced atherosclerotic disease is based on the known characteristics of the vulnerable or recently ruptured plaque with typically a large lipid core, thin fibrous cap, a high number of inflammatory cells, and thrombus. [3][4][5][6] The pathological definition of the vulnerable plaque is founded on cross-sectional studies. Subsequently, molecular and cellular features associated with the vulnerable plaque are considered potential diagnostic imaging markers for plaque rupture and plaque thrombosis. However, longitudinal studies supporting the predictive power of these pathological markers have not been executed, and information about the natural history of atherosclerotic disease is therefore incomplete. The systemic nature of atherosclerotic disease, however, is well-established 7-9 through histopathologic observations demonstrating that inflammation, 10 morphology, 11 and lipid content 12 correlate between different arterial segments within 1 individual. This gave rise to the hypothesis that local plaqu...