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 succumbed to fatal acute coronary syndromes. This recognition spawned a generation of research that led to achievement of considerable understanding of how complicated atherosclerotic plaques form and precipitate thrombotic events.In current practice, an increasing number of patients present with non ST-elevation myocardial infarction (NSTEMI) rather than myocardial infarction (MI) with ST-elevation Key points• An increasing number of patients presenting with myocardial infarction (MI) are diagnosed with a non ST-elevated myocardial infarction (NSTEMI) rather than a MI with ST-elevation (STEMI) and consequently survive their first event.• The shift in the clinical presentations of the acute coronary syndromes mandates a critical reassessment of the underlying mechanisms and the concept of the 3 vulnerable plaque.• The change in clinical presentation and warrant critical re-assessment of currently applied cardiovascular risk scores, pre-clinical experiments, and the usefulness of population data and samples harvested before the application of current preventive interventions.4

Mechanisms of erosion of atherosclerotic plaques

“…OCT imaging indicates that up to one-third of ACS in the current era result from erosion rather than rupture. 3,4 …”

The CANTOS Trial

“…Indeed, a ruptured fibrous cap is found in ~2/3 of post-mortem samples from patients dying of an acute coronary syndrome 4 and intravascular imaging has shown that plaque rupture accounts for ~71% and 43% of ST and non-STEMI, respectively. 3 Although the PROSPECT study showed that only 5% of TCFAs resulted in a clinical event in 3.4 years, TCFA plaque morphology was the only independent risk factor that was predictive for a future event. 6 This latter observation emphasizes the point that major adverse cardiovascular events are relatively rare, but they are still much more likely to occur at high-risk TCFAs.…”

“…Current literature would suggest that these factors may skew these patients to be at relatively higher risk for plaque erosion rather than rupture. 3 Further evidence for this trend may be gleaned from the more statistically robust results when unstable angina with urgent revascularization was included in the analysis, suggesting that partially occlusive events like NSTEMI and unstable angina may have disproportionately benefited. Unfortunately, our current experimental models in hypercholesterolemic mice fail to emulate many of the key features of plaque erosion (i.e., endothelial desquamation, neutrophil recruitment, few macrophages, and small necrotic core).…”

Empfehlungen zur Anwendung von intravaskulärer Bildgebung (optische Kohärenztomographie)

“…OCT-Untersuchungen bei ACS-Patienten im Bereich von Culprit-und NonCulprit-Läsionen sind sicher und mit guter Bildqualität durchführbar [24,30,31]. Nachdem bereits neuere histopathologische Daten nahegelegt hatten, dass das weitverbreitete pathophysiologische Verständnis, wonach eine Plaqueruptur ("ruptured fibrous cap", RFC) alleinige einem ACS zugrunde liegende Pathophysiologie ist [32], konnte mit der Plaqueerosion ("intact fibrous cap", IFC) eine weitere koronare Pathologie identifiziert werden, bei der es zu einer intrakoronaren Thrombusformation im Bereich eines strukturell intakten Endothels kommt [20,32]. In der OCTAVIAStudie lag bei rund einem Drittel aller ACS-Patienten mit ST-Hebungen eine Plaqueerosion (IFC-ACS) vor [33].…”