Abstract

BackgroundThe presence of intraplaque haemorrhage (IPH) has been related to plaque rupture, is associated with plaque progression, and predicts cerebrovascular events. However, the mechanisms leading to IPH are not fully understood. The dominant view is that IPH is caused by leakage of erythrocytes from immature microvessels. The aim of the present study was to investigate whether there is an association between atherosclerotic plaque microvasculature and presence of IPH in a relatively large prospective cohort study of patients with symptomatic carotid plaque.MethodsOne hundred and thirty-two symptomatic patients with ≥2 mm carotid plaque underwent cardiovascular magnetic resonance (CMR) of the symptomatic carotid plaque for detection of IPH and dynamic contrast-enhanced (DCE)-CMR for assessment of plaque microvasculature. Ktrans, an indicator of microvascular flow, density and leakiness, was estimated using pharmacokinetic modelling in the vessel wall and adventitia. Statistical analysis was performed using an independent samples T-test and binary logistic regression, correcting for clinical risk factors.ResultsA decreased vessel wall Ktrans was found for IPH positive patients (0.051 ± 0.011 min− 1 versus 0.058 ± 0.017 min− 1, p = 0.001). No significant difference in adventitial Ktrans was found in patients with and without IPH (0.057 ± 0.012 min− 1 and 0.057 ± 0.018 min− 1, respectively). Histological analysis in a subgroup of patients that underwent carotid endarterectomy demonstrated no significant difference in relative microvessel density between plaques without IPH (n = 8) and plaques with IPH (n = 15) (0.000333 ± 0.0000707 vs. and 0.000289 ± 0.0000439, p = 0.585).ConclusionsA reduced vessel wall Ktrans is found in the presence of IPH. Thus, we did not find a positive association between plaque microvasculature and IPH several weeks after a cerebrovascular event. Not only leaky plaque microvessels, but additional factors may contribute to IPH development.Trial registrationNCT01208025. Registration date September 23, 2010. Retrospectively registered (first inclusion September 21, 2010).NCT01709045, date of registration October 17, 2012. Retrospectively registered (first inclusion August 23, 2011).

Highlights

  • The presence of intraplaque haemorrhage (IPH) has been related to plaque rupture, is associated with plaque progression, and predicts cerebrovascular events

  • The predictive value of carotid IPH on cardiovascular magnetic resonance (CMR) for cerebrovascular events was confirmed in several meta-analyses [5,6,7], showing a hazard ratio of 5.7 (95% confidence interval of 3.0 to 10.9) [5]

  • Relative microvessel density could be calculated for all 23 patients, fibrous cap (FC) integrity assessment was only possible in 16/23 patients due to fragmentation of the histological slides due to calcifications

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Summary

Introduction

The presence of intraplaque haemorrhage (IPH) has been related to plaque rupture, is associated with plaque progression, and predicts cerebrovascular events. The presence of intraplaque haemorrhage (IPH) has been identified as a key pathological factor that is associated with plaque rupture, plaque progression, and predicts cerebrovascular events [4,5,6,7,8,9]. Neovessel sprouting from the lumen into the plaque tissue has been identified and could play a contributing role to IPH [12, 13] It has been suggested by us and others that plaque rupture/fissure is important in the development of IPH [2, 14, 15]. Recently we found that IPH occurs often in the proximity of fissures in the fibrous cap (FC) [16]

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