Plaque Vulnerability Index Predicts Cardiovascular Events: A Histological Study of an Endarterectomy Cohort

Abstract

Background The balance between stabilizing and destabilizing atherosclerotic plaque components is used in experimental studies and in imaging studies to identify rupture prone plaques. However, we lack the evidence that this balance predicts future cardiovascular events. Here we explore whether a calculated histological ratio, referred to as vulnerability index (VI), can predict patients at higher risk to suffer from future cardiovascular events. Methods and Results Carotid plaques and clinical information from 194 patients were studied. Tissue sections were used for histological analysis to calculate the VI (CD68 [cluster of differentiation 68], alpha‐actin, Oil red O, Movat pentachrome, and glycophorin A). Postoperative cardiovascular events were identified through the Swedish National Inpatient Health Register (2005–2013). During the follow‐up (60 months) 45 postoperative cardiovascular events were registered. Patients with a plaque VI in the fourth quartile compared with the first to third quartiles had significantly higher risk to suffer from a future cardiovascular event ( P =0.0002). The VI was an independent predictor and none of the 5 histological variables analyzed separately predicted events. In the 13 patients who underwent bilateral carotid endarterectomy, the VI of the right plaque correlated with the VI of the left plaque and vice versa ( r =0.7, P =0.01). Conclusions Our findings demonstrate that subjects with a high plaque VI have an increased risk of future cardiovascular events, independently of symptoms and other known cardiovascular risk factors . This strongly supports that techniques which image such plaques can facilitate risk stratification for subjects in need of more intense treatment.

Increased proteolytic cleavage of osteoglycin is associated with a stable plaque phenotype and lower risk of cardiovascular events

“…The ratio was also negatively associated to plaque area of other known plaque vulnerability markers, including CD68 (myeloid cell marker), glycophorin A (intraplaque hemorrhage) and the histological VI. The negative correlations between cleaved osteoglycin, osteoglycin ratio and VI (reflecting the balance between vulnerable and stable plaque components) is of particular interest as the VI has previously been shown to be an independent predictor of future cardiovascular events [10]. Collectively, these findings indicate that osteoglycin may be another proteoglycan that affects plaque phenotype and that its cleavage may affect LDL-retention, inflammatory cell accumulation and plaque cell apoptosis.…”

“…A rabbit IgG polyclonal isotype antibody was used as a control (ab27478, Abcam, Cambridge, UK). A histological vulnerability index (VI) was calculated for each plaque (a ratio between the destabilizing components CD68, Oil Red O, glycophorin A and the stabilizing components α-actin and Movat collagen) as previously published [10]. Subsequently, the stained plaques were scanned using ScanScope Console Version 8.2 (LRI imaging AB, CA, USA) and photographed with Aperio ImageScope v.8.0 (Aperio Technologies Inc, Vista, CA, USA).…”

Vulnerable Atherosclerotic Plaque: Is There a Molecular Signature?

“…The vulnerability index, a calculated histological ratio, was proven an efficient tool to discern between vulnerable and stable atherosclerotic lesions; this index measures the existing elements decisive for plaque rupture: plaque destabilizers (macrophages, hemorrhage, and lipids) and stabilizers (smooth muscle cell and collagen) [ 17 ].…”

Combining IVUS + OCT Data, Biomechanical Models and Machine Learning Method for Accurate Coronary Plaque Morphology Quantification and Cap Thickness and Stress/Strain Index Predictions

“…However, it is of qualitative nature and not convenient for quantitative vulnerability tracking and predictions. Some morphological and biomechanical plaque vulnerability indices (PVIs) have been introduced based on imaging data and biomechanical factors to overcome this limitation [ 4 , 5 ]. Tang et al introduced a stress-based PVI (SPVI) using 34 in vivo magnetic resonance imaging (MRI) slices from 14 human coronary plaque samples.…”