Keywords
atherosclerosis; coronary imaging; high-risk plaque; OCT; unstable plaque
Abbreviations
CTCA: computed tomography coronary angiography
OCT: optical coherence tomography
IVUS: intravascular ultrasound
MACE: major adverse cardiac events
Take-home messages
- Unstable plaque is not a single phenotype – several mechanisms (rupture, erosion, haemorrhage) coexist.
- Most vulnerable plaques remain clinically silent, contributing to diffuse atherosclerotic progression.
- Intracoronary and CT imaging can detect high-risk morphologies, but their positive predictive value for events is low.
- Management should focus on global risk reduction, not preventive interventions on individual lesions.
From stenosis to instability
For decades, coronary stenosis was considered the culprit of acute coronary syndromes (ACS). However, serial angiographic studies and clinical trials such as FRISC-II have [1] demonstrated that most infarctions arise from lesions of <70% diameter reduction. Histopathological studies revealed that thin-cap fibroatheromas (TCFA), with large lipid cores and thin fibrous caps (<65 µm), are prone to rupture or erosion. Inflammation and macrophage infiltration play a central role in weakening the fibrous cap and triggering thrombosis.
Silent instability: what autopsy and imaging taught us
Autopsy data and modern optical coherence tomography (OCT) imaging show that plaque rupture or erosion often occurs silently, without clinical manifestation. The resulting microthrombosis usually heals, contributing to progressive plaque growth and vascular remodelling [2-4]. This “plaque healing” paradigm shifts our view from acute events to chronic disease activity within the arterial wall.
The limits of prediction
To better characterise the coronary arterial wall, two modalities have driven major advances: intracoronary imaging — an invasive technique using catheter-based devices — and non-invasive cross-sectional imaging with coronary computed tomography (CT). Intracoronary imaging modalities such as OCT (resolution of 13 µm) and intravascular ultrasound (IVUS; 90 µm) allow in vivo identification of TCFA and other high-risk morphologies. Despite strong associations with future events, their absolute predictive value remains low. In the PROSPECT study [5], lesions with vulnerable features increased relative risk but accounted for few subsequent events. Similarly, computed tomography coronary angiography (CTCA) studies (ROMICAT II, PROMISE, PARADIGM) identified high-risk plaque features — low attenuation plaque, positive remodelling, napkin-ring sign — but with low positive predictive value and limited clinical impact [6-8]. Thus, although these two imaging modalities can accurately identify vulnerable plaques, they should be regarded as markers of coronary disease activity rather than a direct therapeutic target for primary prevention.
From lesion to patient management
Other markers of atherosclerotic disease activity can be assessed to better estimate cardiovascular risk, such as the presence of atherosclerosis in other vascular territories (carotid or peripheral arteries) and the overall coronary atheroma burden. Since no study has shown benefit from preventive stenting or local treatment of high-risk plaques, current management should target the patient, not the plaque. A high-risk plaque on CTCA should prompt intensification of secondary prevention — statins, proprotein convertase subtilisin/kexin type 9 inhibitors, blood pressure control, and lifestyle modification — similar to other markers of elevated atherosclerotic burden.
Patient-oriented message
When discussing imaging results with patients, emphasise that a “vulnerable” plaque does not mean an imminent heart attack, but rather a sign of active atherosclerosis requiring stronger risk factor control. The focus should be on overall cardiovascular health, not on removing or “fixing” a single lesion.
Conclusions and impact on practice
In 2026, the concept of unstable plaque has evolved from a morphological curiosity to a systemic marker of disease activity. Most plaques remain silent and heal spontaneously. Intracoronary and CT imaging have improved our understanding of pathophysiology but offer limited prognostic accuracy. The clinical message is clear: focus on comprehensive cardiovascular prevention, not on identifying or treating individual “dangerous” plaques. The future lies in integrating plaque biology, systemic inflammation, and total atheroma burden into personalised strategies of risk reduction.
