title: Temporal shifts in clinical presentation and underlying mechanisms of atherosclerotic disease.
abstract: The concept of the 'vulnerable plaque' originated from pathological observations in patients who died from acute coronary syndrome. This recognition spawned a generation of research that led to greater understanding of how complicated atherosclerotic plaques form and precipitate thrombotic events. In current practice, an increasing number of patients who survive their first event present with non-ST-segment elevation myocardial infarction (NSTEMI) rather than myocardial infarction (MI) with ST-segment elevation (STEMI). The culprit lesions that provide the pathological substrate for NSTEMI can vary considerably from the so-called 'vulnerable plaque'. The shift in clinical presentation of MI and stroke corresponds temporally to a progressive change in the characteristics of human plaques away from the supposed characteristics of vulnerability. These alterations in the structure and function of human atherosclerotic lesions might mirror the modifications that are produced in experimental plaques by lipid lowering, inspired by the vulnerable plaque construct. The shift in the clinical presentations of the acute coronary syndromes mandates a critical reassessment of the underlying mechanisms, proposed risk scores, the results and interpretation of preclinical experiments, as well as recognition of the limitations of the use of population data and samples collected before the application of current preventive interventions.
authors.affiliation: Laboratory of Experimental Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, Netherlands.|Laboratory of Clinical Chemistry, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, Netherlands.
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.affiliation: Laboratory of Experimental Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, Netherlands.
authors.forename: Hester M
authors.initials: HM
authors.lastname: den Ruijter
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB 741G Boston, Massachusetts 02115, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
mesh_terms: D054058:Acute Coronary Syndrome / Q000209:etiology; D006801:Humans; D009203:Myocardial Infarction / Q000175:diagnosis / Q000209:etiology*; D000072658:Non-ST Elevated Myocardial Infarction / Q000175:diagnosis / Q000209:etiology; D058226:Plaque, Atherosclerotic / Q000150:complications* / Q000000981:diagnostic imaging; D012307:Risk Factors