Unstable Plaque Characteristics Research Articles

Postoperative Complications After Carotid Endarterectomy for Free-Floating Thrombus

The standard of care for patients with symptomatic, severe carotid artery stenosis includes carotid endarterectomy (CEA) plus best medical therapy. A rare cause of this etiology is acute thrombus within the internal carotid artery, referred to as free-floating thrombus (FFT). This pathology is reported to have unstable plaque characteristics and an incidence rate of 0.4%-1.5%. Given its rarity, there remains a significant gap in understanding of the management of this condition. Our study sought to bridge this gap through a retrospective chart review of patients who underwent a CEA for symptomatic FFT.

Abstract 754: The Relationship Between Obstructive Sleep Apnea and Coronary Plaque Instability: An Optical Frequency Domain Imaging Study

Background and purpose: Obstructive sleep apnea (OSA) is associated with coronary artery disease (CAD) and with an increased risk of myocardial infarction, stroke or death due to cardiovascular disease. Optical frequency-domain imaging (OFDI) is a useful modality for evaluating the characteristics of atherosclerotic plaque. The purpose of the study was to use OFDI to investigate the association of OSA with coronary plaque characteristics in patients undergoing percutaneous coronary intervention (PCI). Methods: We retrospectively analyzed OFDI data for coronary artery plaques from 15 patients with OSA and 35 non-OSA patients treated between October 2015 and October 2018. Plaque morphology was evaluated for 70 lesions, including 21 from patients with OSA and 49 from non-OSA patients. Results: Compared with the non-OSA group, patients with OSA had significantly higher prevalences of thinned cap fibroatheroma (TCFA) (67% vs. 35%, P=0.014) and microchannels (86% vs. 55%, P=0.014); a significantly higher mean lipid index (1,392±982 vs. 817±699, P=0.021), macrophage grade (8.4±6.4 vs. 4.8±4.5, P=0.030), and maximum number of microchannels (1.5±1.0 vs. 0.7±0.7, P=0.001); and a significantly lower mean minimum fibrous cap thickness (69.4±28.7 vs. 96.1±51.8 μm, P=0.008). Conclusions: This OFDI analysis suggests that OSA is associated with unstable plaque characteristics in patients with CAD. More intensive medical management for stabilization of coronary atherosclerotic plaque is required in patients with OSA.

Obstructive sleep apnea is associated with increased coronary plaque instability: an optical frequency domain imaging study

Obstructive sleep apnea (OSA) is associated with coronary artery disease (CAD) and with an increased risk for myocardial infarction, stroke or death due to cardiovascular disease. Optical frequency-domain imaging (OFDI) is a useful modality for evaluating the characteristics of atherosclerotic plaque. The purpose of the study was to use OFDI to investigate the association of OSA with coronary plaque characteristics in patients undergoing percutaneous coronary intervention (PCI). We retrospectively analyzed OFDI data for coronary artery plaques from 15 patients with OSA and 35 non–OSA patients treated between October 2015 and October 2018. Plaque morphology was evaluated for 70 lesions, including 21 from patients with OSA and 49 from non–OSA patients. Compared with the non–OSA group, patients with OSA had significantly higher prevalences of thinned cap fibroatheroma (TCFA) (67% vs. 35%, P = 0.014) and microchannels (86% vs. 55%, P = 0.014); a significantly higher mean lipid index (1392 ± 982 vs. 817 ± 699, P = 0.021), macrophage grade (8.4 ± 6.4 vs. 4.8 ± 4.5, P = 0.030), and maximum number of microchannels (1.5 ± 1.0 vs. 0.7 ± 0.7, P = 0.001); and a significantly lower mean minimum fibrous cap thickness (69.4 ± 28.7 vs. 96.1 ± 51.8 μm, P = 0.008). This OFDI analysis suggests that OSA is associated with unstable plaque characteristics in patients with CAD. More intensive medical management for stabilization of coronary atherosclerotic plaque is required in patients with OSA.

The clinical significance of echo-attenuated plaque in stable angina pectoris compared with acute coronary syndromes: A combined intravascular ultrasound and optical coherence tomography study

BackgroundEcho-attenuated plaque (EA) on intravascular ultrasound (IVUS) is related to poor outcomes after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) patients. However, the clinical significance of EA in stable angina pectoris (SAP) patients compared with that in ACS patients remains unclear. We assessed the relationships between EA and unstable plaque characteristics in patients with ACS and SAP. MethodsWe investigated 609 coronary lesions in 609 patients (234 with ACS; 375 with SAP) undergoing pre-intervention IVUS and optical coherence tomography (OCT). The differences in plaque morphology and post-PCI outcomes were assessed according to the clinical status of ACS or SAP and the presence or absence of EA. ResultsEA was more frequent in patients with ACS than in those with SAP (44.0% vs. 25.1%, p < 0.001). SAP-EA lesions showed thicker fibrous cap (157 ± 97 μm vs. 100 ± 58 μm, p < 0.001), smaller lipid arc (208 ± 76° vs. 266 ± 99°, p < 0.001), smaller plaque burden (83.0 ± 6.1% vs. 86.5 ± 4.1%, p < 0.001), and lower frequency of transient slow-reflow phenomenon during PCI (21.3% vs. 51.5%, p < 0.001) than ACS-EA lesions, but similar plaque vulnerability compared with ACS-non-EA lesions. SAP-EA lesions had less frequent OCT-thrombus than ACS-non-EA lesions (20.2% vs. 71.2%, p < 0.001). ConclusionsSAP-EA lesions had less plaque vulnerability than ACS-EA lesions, but were comparable to ACS-non-EA lesions. Less frequent thrombus formation might differentiate SAP-EA lesions from ACS-non-EA lesions. A combined IVUS and OCT approach might be useful to assess plaque vulnerability in SAP-EA lesions compared with ACS lesions.

Abstract 2286: Ultrasonographic And Pathological Measurement Of Fibrous Cap In Rupture-prone Carotid Plaques Using Advanced Ultrasound Technology

[Background and Purpose] In carotid stenosis, thin fibrous cap, as one of the characteristics of unstable plaques, have been thought to be an important risk factor for plaque rupture and acute cerebral ischemic events. A study reported there was good agreement between ultrasonographic and pathological fibrous cap thickness(FCT). The fibrous cap of ultrasound image in this study, however, was not measured at the same location in pathology. So, we precisely aligned ultrasonographic images with pathology in carotid plaques by advanced ultrasound with global position system (GPS)-like positon-sensing technology, and examined the characteristics of fibrous cap in rupture-prone plaques. [Methods and Results] 24 patients(symptomatic=18, asymptomatic=6) undergoing carotid endarterectomy for carotid stenosis between June 2010 and January 2011 were subjected in this study. We performed carotid ultrasound using a LOGIQ E9(GE Healthcare) within three days before carotid endarterectomy. Three-dimensinal images with the positonal information were obtained using an electromagnetic transmitter and sensors mounted on a linear probe. Endarterectomy specimens were cut every 3mm from carotid bifurcation in the short axis view. The three-dimensinal images alined with the specimens were extracted every 3mm of the same location in the short axis view. We measured maximal and minimal FCT in these ultrasonographic and pathological images. There was a positive relation(r=0.74) between fibrous cap thickness in pathology(maximal FCT =571μm[93 to 1062]) and ultrasound(maximal FCT =439μm[242 to 809]). Maximal FCT in pathology was significantly less in the pathologically ruptured plaques(n=16) than in the nonrupured plaques(n=8) (456μm VS 803μm, P&lt;0.05). In contrast, maximal FCT in ultrasound had no difference in the two groups(389μm VS 497μm, P=0.09). In pathology fibrous cap was ruptured in 16 patients(67%, minimal FCT=0μm), and thin, restored and sparse though nonruptured in other 5 patients(21%, minimal FCT=177μm[50 to 339]). At the same location, the fibrous cap of ultrasound image disappeared in all these 21 patients. The other 3 patients(13%) without plaque rupture showed thick fibrous cap in pathology(minimal FCT =301μm[279 to 325]) and ultrasound(minimal FCT =283μm[250 to 300]). [Conclusions] Using advanced ultrasound with GPS-like technology, we were able to examine the pathological characteristics of fibrous cap in ultrasound in detail. It is difficult to sort out preoperatively more pathologically unstable plaques only by measuring FCT in ultrasound. Ultrasonographic disappearance of fibrous cap is more significant sign of pathologically unstable plaques.

Adipocyte fatty acid binding protein in atherosclerotic plaques is associated with local vulnerability and is predictive for the occurrence of adverse cardiovascular events

There is an increasing need for translational studies identifying molecular targets contributing to atherosclerotic plaque destabilization. Local molecular plaque markers that are related to plaque vulnerability may hold predictive value to identify patients who are at increased risk to suffer from cardiovascular events. Animal studies revealed that adipocyte fatty acid binding protein (FABP4) is associated with the progression of atherosclerosis; however, FABP4 expression studies in human atherosclerotic plaques are lacking. We investigated FABP4 expression in carotid atherosclerotic lesions in relation to plaque composition and future cardiovascular events. Atherosclerotic plaques were obtained from 561 patients undergoing carotid endarterectomy (CEA). Plaques were analysed for the presence of macrophages, lipid core, smooth-muscle cells, collagen, calcification, and intraplaque haemorrhage. Patients were followed for 3 years after CEA. The primary outcome was defined as the composite of vascular death, vascular event, and surgical or percutaneous vascular intervention. Fatty acid binding protein levels correlated with unstable plaque characteristics and symptomatic lesions. Patients with increased FABP4 plaque levels showed a two-fold increased risk [HR = 1.99, 95% confidence interval (95% CI) (1.30-3.04)] (P = 0.005) to reach the primary outcome during follow-up. Increased FABP4 levels related to primary outcome, independent from general cardiovascular risk factors [HR = 1.33, 95% CI (1.08-1.65)] (P = 0.008). FABP4 levels in atherosclerotic lesions are associated with an unstable plaque phenotype and an increased risk for cardiovascular events during follow-up. Besides risk stratification for adverse future cardiovascular events, the outcome of the present study supports the relevance of exploring FABP4 antagonists as a potential pharmaceutical intervention to treat atherosclerotic disease progression.

Abstract 511: Mrp8 And Mrp14,Endogenous Activators of Toll-lLke Receptor4, are Associated with Rupture-Prone Human Atherosclerotic Plaques

Objectives : Atherosclerosis is a chronic, complex inflammatory process and is the underlying cause of stroke and myocardial infarction due to rupture of the atherosclerotic plaque leading to acute occlusion of the artery in the brain or heart. Macrophages, infiltrating atherosclerotic lesions, abundantly express Mrp8 and Mrp14. Recently Mrp8, Mrp14 and the complex Mrp8/14 have been identified as endogenous ligands of Tlr-4.The role of Tlr-4 in the development and progression of the atherosclerotic plaque is well recognized and it is associated with a rupture-prone plaque phenotype. Expression of Mrps in human plaques and its relation to plaque phenotype is unknown. For this, we investigated the levels of Mrp8, Mrp14 and Mrp8/14 complex in a large number of human atherosclerotic plaques. Methods and results : Mrp8, Mrp14 and Mrp8/14 were quantified by ELISAs in human carotid endarterectomy specimens (186 patients) and plaque phenotype was determined by immunohistochemistry. Mrp levels were higher in the unstable (58 fibro-atheromatous, 64 atheromatous) compared to the stable (64 fibrous) plaques: Mrp8 p = 0.001 ; Mrp14 p = 0.001 ; Mrp8/14 p = 0.01 . Concomitantly, Mrp8, Mrp14 and Mrp8/14 were associated with characteristics of unstable plaques: more macrophages ( p = 0.024; p = 0.002; p = 0.076 ), less smooth muscle cells ( p = 0.041; p = 0.001; p = 0.074 ), larger lipid core ( p = 0.001; p = 0.001; p=0.004 ), less collagen ( p = 0.440; p = 0.011; p = 0.372 ). Furthermore, Mrp plaque levels were positively correlated with the pro-inflammatory cytokines (IL-6 and IL-8) and matrix metalloproteinsases (MMP2, MMP8 and MMP9) plaque levels. EDA, marker of stable plaques, was negatively associated with Mrps plaque levels. Histological analysis revealed that Mrps are expressed by a subgroup of plaque macrophages localized in the plaque cap and shoulder, the most rupture-prone sites of an atherosclerotic plaque. Conclusions: We show that Mrp8, Mrp14 and Mrp8/14 are strongly associated with the histological characteristics and inflammatory status of human rupture-prone plaques and identify Mrps as a potential marker for rupture-prone plaques.