Athero-express: Differential atherosclerotic plaque expression of mRNA and protein in relation to cardiovascular events and patient characteristics. Rationale and design

Abstract

In clinical practice, biological markers are not available to routinely assess the progression of atherosclerotic disease or the development of restenosis following endarterectomy or catheter based interventions. Endarterectomy procedures provide an opportunity to study mechanisms of restenosis and progression of atherosclerotic disease since atherosclerotic tissue is obtained. Athero-Express is an ongoing prospective study, initiated in 2002, with the objective to investigate the etiological value of plaque characteristics for long term outcome. Patients are included who undergo an endarterectomy of the carotid artery. At baseline blood is withdrawn, patients fill in an extensive questionnaire and diagnostic examinations are performed. Atherosclerotic plaques are freshly harvested, immunohistochemically stained and examined for the presence of macrophages, smooth muscle cells, collagen and fat. Parts of the atherosclerotic plaques are freshly frozen to study protease activity and protein and RNA expressions. Patients undergo a duplex follow up to assess procedural restenosis (primary endpoint) at 3 months, 1 year and 2 years. Secondary endpoints encompass major adverse cardiovascular events. In the future, the creation of this biobank with atherosclerotic specimen will allow the design of cross-sectional and follow up studies with the objective to investigate the expression of newly discovered genes and proteins and their interaction with patients and plaque characteristics in the progression of atherosclerotic disease. Objective is to include 1000-1200 patients in 5 years. In January 2004, 289 patients had been included. It is expected that 250 patients will be included yearly.

Sex Is Associated With the Presence of Atherosclerotic Plaque Hemorrhage and Modifies the Relation Between Plaque Hemorrhage and Cardiovascular Outcome

“…We previously hypothesized and confirmed that a local plaque can carry information about the systemic vascular status of a patient 10,14,20 and specifically that PH in carotid plaques is predictive for events in all vascular territories. 10 In the current study, we demonstrate that, independent of cardiovascular risk factors and symptom status before CEA, PH does not predict outcome in women, whereas in men, PH predicts a substantially and significantly increased risk of an event in any vascular territory after CEA.…”

“…14 In summary, all patients undergoing CEA at the University Medical Center, Utrecht, and St Antonius Hospital, Nieuwegein, the Netherlands, were asked to participate consecutively during the study period. There were no exclusion criteria.…”

Atherosclerotic Plaque Vulnerability as an Explanation for the Increased Risk of Stroke in Elderly Undergoing Carotid Artery Stenting

“…16 Medical ethics boards of the 2 participating hospitals (University Medical Center Utrecht and St Antonius Hospital Nieuwegein, The Netherlands) approved the study. All participating patients provided written informed consent.…”

Temporal shifts in clinical presentation and underlying mechanisms of atherosclerotic disease

“…These tandem temporal changes in coronary and cerebral events suggest a systemic rather than a local change in atherosclerotic disease progression. Athero-Express, an ongoing Dutch study, has collected atherosclerotic carotid plaques since 2002 64 . Analyses of retrieved atherosclerotic plaque specimens in the Athero-Express biobank have revealed a clear shift in the characteristics of human atherosclerotic plaques over time 65 ascribed to "stable" plaques occurred in lesions retrieved from either symptomatic or asymptomatic patients.…”