Features Of Plaque Vulnerability Research Articles

Clinical Course of Optical Coherence Tomography-Detected Lipid-Rich Coronary Plaque After Optimal Medical Therapy

Background: The aim of this study was to evaluate optical coherence tomography (OCT)-detected lipid-rich coronary plaques (LRCPs) with coronary computed tomography angiography (CCTA) 10 months after optimal medical therapy (OMT). Methods and Results: Baseline OCT detected 28 LRCPs in non-culprit lesions. High-risk plaque features (HRPFs), such as positive remodeling, very low attenuation plaques, napkin-ring sign, and spotty calcification, were observed in 67.9%, 67.9%, 21.4%, and 64.3% of LRCPs, respectively, at the 10-month follow-up CCTA. Lesions with ≥3 HRPFs were defined as high-risk LRCPs (n=12); the remaining were defined as low-risk LRCPs (n=16). The maximum lipid arc on baseline OCT was larger in high- than low-risk LRCPs (221±62° vs. 179±44°, respectively; P=0.04). Receiver operating characteristic curve analysis indicated that a maximum lipid arc >154° on baseline OCT was the optimal cut-off value to predict high-risk LRCPs 10 months after OMT. Patients with high-risk LRCPs had worse clinical outcomes, defined as a composite of cardiac death, target lesion-related myocardial infarction, and target lesion-related revascularization, during follow-up than those with low-risk LRCPs (33.3% vs. 0%; P=0.01). Conclusions: A high-risk LRCP at follow-up CCTA was correlated with a larger maximum lipid arc on baseline OCT. Further aggressive treatment for patients with large LRCPs may reduce vulnerable plaque features and prevent future cardiac events.

ZEB2 Shapes the Epigenetic Landscape of Atherosclerosis.

Smooth muscle cells (SMCs) transition into a number of different phenotypes during atherosclerosis, including those that resemble fibroblasts and chondrocytes, and make up the majority of cells in the atherosclerotic plaque. To better understand the epigenetic and transcriptional mechanisms that mediate these cell state changes, and how they relate to risk for coronary artery disease (CAD), we have investigated the causality and function of transcription factors at genome-wide associated loci. We used CRISPR-Cas 9 genome and epigenome editing to identify the causal gene and cells for a complex CAD genome-wide association study signal at 2q22.3. Single-cell epigenetic and transcriptomic profiling in murine models and human coronary artery smooth muscle cells were used to understand the cellular and molecular mechanism by which this CAD risk gene exerts its function. CRISPR-Cas 9 genome and epigenome editing showed that the complex CAD genetic signals within a genomic region at 2q22.3 lie within smooth muscle long-distance enhancers for ZEB2, a transcription factor extensively studied in the context of epithelial mesenchymal transition in development of cancer. Zeb2 regulates SMC phenotypic transition through chromatin remodeling that obviates accessibility and disrupts both Notch and transforming growth factor β signaling, thus altering the epigenetic trajectory of SMC transitions. SMC-specific loss of Zeb2 resulted in an inability of transitioning SMCs to turn off contractile programing and take on a fibroblast-like phenotype, but accelerated the formation of chondromyocytes, mirroring features of high-risk atherosclerotic plaques in human coronary arteries. These studies identify ZEB2 as a new CAD genome-wide association study gene that affects features of plaque vulnerability through direct effects on the epigenome, providing a new therapeutic approach to target vascular disease.

Optical Coherence Tomographic Features of Pancoronary Plaques in Patients With Acute Myocardial Infarction Caused by Layered Plaque Rupture Versus Layered Plaque Erosion

Atherosclerotic plaque instability could occur on the basis of healed plaque which has a layered appearance on optical coherence tomography. This study aimed to investigate pancoronary plaque features of layered plaque rupture (LPR) and layered plaque erosion (LPE) in patients with acute myocardial infarction. Among 388 patients with acute myocardial infarction who underwent preintervention optical coherence tomography imaging of three coronary arteries, 190 patients with layered culprit plaque (49.0%) were identified and further divided into 2 groups: LPR group and LPE group. Clinical characteristics, pancoronary plaque features and clinical outcomes were compared between the 2 groups. Patients with LPR were older, less often male and current smoker, and had a lower coronary flow grade than those with LPE. At the culprit lesion, LPR group had a higher prevalence of lipid plaque, thin-cap fibroatheroma (TCFA), macrophage, and microchannel, and presented with more severe lumen area stenosis than LPE group. At nonculprit lesions, LPR group had a higher prevalence of TCFA and had greater layered tissue thickness and area than LPE group. The ischemia-driven revascularization rate was higher in LPR group. Moreover, we found that TCFA, diameter stenosis >56.5%, and mean lipid arc >179.1° were predictors for layered culprit plaque. In conclusion, patients with LPR had more vulnerable plaque features at culprit and nonculprit lesions and had higher incidence of ischemia-driven revascularization than those with LPE. TCFA, diameter stenosis >56.5%, and mean lipid arc >179.1° were predictors of layered culprit plaque.

Fully Automated Characterisation of Vulnerable Plaque Features on Cardiac CT Using Deep Learning Techniques

Invasive methods are traditionally used for the identification of vulnerable plaques (VP) in coronary arteries. Coronary computed tomography angiography (CCTA) has emerged as a reliable non-invasive surrogate to assess VP. However, VP assessment on CCTA is time-consuming and requires specialised training limiting its clinical translation. We aim to develop and test a fully automated deep learning (DL) system capable of accurate VP characterisation on CCTA.

246 Air pollution and coronary plaque vulnerability and instability: an optical coherence tomography study

Abstract Aims Air pollution is an emerging key player in determining the residual risk of coronary events. However, pathophysiological mechanisms linking air pollution and coronary events have been not adequately investigated. We aimed at assessing the relationship between exposure to air pollutants and mechanisms of coronary instability evaluated by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS). Methods and results ACS patients undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT, and the presence of macrophage infiltrates (MØI) and thin-cap fibroatheroma (TCFA) at the culprit site was also assessed. Based on each case’s home address, exposure to several pollutants was evaluated, including particulate matter 2.5 (PM2.5), particulate matter 10 (PM10), and carbon monoxide (CO). Only patients with >2 years of available data on air pollution exposure prior to ACS were enrolled. We included 126 patients [median age 67.0 years (55.5–76.0), 97 (77.0%) male]. Sixty-six patients (52.4%) had PR as mechanism of plaque instability. Patients with PR were exposed to significantly higher PM2.5 levels compared to IFC, and PM2.5 was independently associated with PR [odds ratio per unit = 1.194, 95% CI: (1.036–1.377), P = 0.015]. Moreover, exposure to higher levels of PM2.5 was independently associated with the presence of TCFA and of MØI at the culprit site. Interestingly, PM2.5, PM10, and CO levels were positively and significantly correlated with serum levels of C-reactive protein. ROC curves were constructed to assess the ability of PM2.5 to predict the presence of plaque rupture, TCFA or MØI. The AUC for PM2.5 to predict plaque rupture was 0.62 (95% CI: 0.52–0.71, P = 0.018), for TCFA was 0.71 (95% CI: 0.61–0.80, P <0.001) and for MØI was 0.80 (95% CI: 0.71–0.88, P <0.001). Using a PM2.5 cut-off value of 13.40 μg/m3, the sensitivity and specificity for MØI were 81% and 66%, respectively. Conclusions We provide novel insights into the missing link between air pollution and increased risk of coronary events. In particular, exposure to higher concentrations of air pollutants is a risk factor for vulnerable plaque features and for plaque rupture as mechanism of coronary instability mediated by systemic and local plaque inflammation. Of importance, the thresholds of air pollutants that predicted the presence of vulnerable plaque features are far lower than commonly accepted safety thresholds used to start preventive measures for public health, suggesting that further efforts are needed in order to reduce the adverse effects on the cardiovascular system.

233 Prognostic implications of the automated detection of lipid core burden index at optical coherence tomography: post hoc analysis of the CLIMA study

Abstract Aims Plaque vulnerability features are associated with major coronary events and poor outcomes. However, routinary and reproducible manual assessment of plaque vulnerability features at optical coherence tomography (OCT) is still challenging. We recently developed and validated an OCT-derived automated approach that can identify the intra-plaque lipid core burden index (LCBI). Our aim was to investigate the association between the automated detection of OCT-derived LCBI and clinical events. Methods and results We conducted a post hoc analysis of the CLIMA study, a large prospective observational, multicentre registry recruiting all consecutive patients undergoing assessment of the proximal left anterior descending artery (LAD) segment by OCT in the context of clinically indicated coronary angiography. The automated detection of maximum LCBI was carried out in 4 mm of intervention-naïve proximal LAD segment (maxLCBI4mm) by using the validated software. The mean and median value of LCBI in all study population (n = 1003) was 407.6 and 411.1, respectively. Patients with higher LCBI (≥400) were more frequently male (P = 0.016) and affected by insulin-dependent diabetes mellitus (0.046). Furthermore, they showed more frequently at OCT analysis the vulnerable plaque characteristics investigated in the CLIMA study (Table 1). At Cox regression analysis, a maxLCBI4mm ≥400 predicted at 1 year both a hard endpoint of cardiac death and target-vessel myocardial infarction [hazard ratio (HR): 2.56, 95% confidence interval (CI): 1.2–5.3, P 0.011], as well as a composite endpoint of cardiac death, any myocardial infarction and target vessel revascularization (HR: 1.87, 95% CI: 1.1–3.1, P = 0.011). Conclusions In our study, the automated detection of LCBI at OCT was feasible and related to poorer clinical outcome at 1-year follow-up.

Mannose as a biomarker of coronary artery disease: Angiographic evidence and clinical significance

BackgroundHigh mannose has previously associated with insulin resistance and cardiovascular disease (CVD). Our objective is to establish whether mannose is associated with anatomical evidence of coronary artery disease (CAD). MethodsPlasma mannose concentrations were measured by liquid chromatography/tandem mass spectrometry in a discovery cohort (n = 513) and a validation cohort (n = 221) of carefully phenotyped individuals. In both cohorts CAD was quantitated using state-of-the-art imaging techniques (coronary computed coronary tomography angiography (CCTA), invasive coronary angiography and optical coherence tomography). Information on subsequent CVD events/death was collected. Associations of mannose with angiographic variables and biomarkers were tested using univariate and multivariate regression models. Survival analysis was performed using the Kaplan-Meier estimator. ResultsMannose was related to indices of CAD and features of plaque vulnerability. In the discovery cohort, mannose was a marker of quantity and quality of CCTA-proven CAD and subjects with a mannose level in the top quartile had a significantly higher risk of CVD events/death (p = 3.6e-5). In the validation cohort, mannose was significantly associated with fibrous cap thickness < 65 μm (odds ratio = 1.32 per each 10 μmol/L mannose change [95% confidence interval, 1.05–1.65]) and was an independent predictor of death (hazard ratio for mannose≥vs < 84.6 μmol/L: 4.0(95%CI, 1.4–11.3), p = 0.006). ConclusionThe current data add novel evidence that high mannose is a signature of CAD with a vulnerable plaque phenotype, consistently across measures of severity of vessel involvement and independent of the traditional correlates of CVD, and that it is an independent predictor of incident adverse outcomes.

Abstract 11071: Increased Circulating Raas Activity is Related to Functionally Significant Coronary Artery Disease as Defined by Ffr and [ 15 O]h2o Pet Perfusion as Well as Vulnerable Plaque Characteristics on CT Angiography

Introduction: Renin-angiotensin-aldosterone-system (RAAS) activity has been linked to coronary artery disease (CAD) and coronary microvascular dysfunction (CMD), opening potential frontiers for treatment. In this study we investigated if increased RAAS activation is related to CAD, high risk plaque (HRP), myocardial perfusion, and CMD in chest pain patients. Methods: Renin as a measure for RAAS activation, was quantified by immunoradiometric assay in 205 patients (64% men; age 58 ± 9 years) with suspected CAD. Patients underwent 256-slice coronary CT angiography for (quantitative) plaque analysis and coronary artery calcium (CAC) scoring, [ 15 O]H2O PET perfusion imaging and invasive FFR measurements in all coronary arteries. A total of 585 vessels were stratified upon four categories based on [ 15 O]H2O PET perfusion and invasive pressure measurements. Vessels with a FFR &gt;0.80 but with an ischemic hyperemic MBF below 2.3 ml/min/g were defined as CMD. Results: In univariable analysis, renin associated positively with the CAC score, total plaque volume (TPV) and impaired perfusion (p&lt;0.01 for all). Patients with HRP displayed higher levels of renin (p=0.04). As expected, renin (p&lt;0.01) was elevated in males. After correction for baseline characteristics including sex, renin associated positively with CAC score and TPV (p&lt;0.01 and p=0.03), but not with HRP and perfusion (p=0.14 and p=0.40). Figure 1 shows that vessels with a significant flow limiting stenosis (FFR+, PET+; p=0.04) occur in patient with elevated renin levels, while vessels defined as CMD (FFR-, PET+) do not, except for patient without RAAS inhibition. Conclusion: RAAS activation is associated with CAD defined by FFR and [ 15 O]H2O PET and HRP. Future studies should clarify whether RAAS activation and CAD are causally related and represent modifiable targets. Figure 1. Intergroup p values are depicted for significant p values only. The upper and lower whiskers represent the 10 th and 90 th percentile.

Trans-Myocardial Blood Interleukin-6 Levels Relate to Intracoronary Imaging-Defined Features of Plaque Vulnerability and Predict Procedure-Induced Myocardial Infarction

BackgroundIntravascular imaging has defined various vulnerable plaque (VP) phenotypes that predict future clinical events. Atherosclerosis is an inflammatory process and inflammation, measured by systemic biomarkers can also predict events and anti-inflammatory therapy is beneficial. We were interested to assess the relationship between plaque phenotypes and key inflammatory biomarkers, measured close to the coronary. MethodsNinety-two patients scheduled for elective percutaneous coronary intervention (PCI) underwent virtual histology intravascular ultrasound, optical coherence tomography, pressure wire and blood sampling from the guide catheter (GC), coronary sinus (CS) to determine trans-myocardial gradient (TMG = CS-GC) and from peripheral blood. Procedure related troponin release was assessed at 6-hours post-PCI from peripheral venous blood. Biomarker data were analysed and compared with coronary data. ResultsInterleukin (IL)-6 was associated with increased levels of tumour necrosis factor (TNF)-α and C-reactive protein (CRP) and the pre-PCI IL-6 TMG correlated with plaque features of vulnerability: plaque burden - PB (r = 0.253, p = 0.04) and minimal lumen area - MLA (r = −0.438, p = 0.007), although no relationship existed for thin-capped fibroatheroma defined by either imaging modality. Peripheral IL-6 levels had no correlation with post PCI troponin, although the pre-PCI IL-6 TMG was related (r = 0.334, p = 0.006), as was PB (r = 0.27, p = 0.029). ConclusionIL-6 TMG pre-PCI correlates with plaque burden and MLA that have been shown to predict future clinical events and is correlated with post-PCI troponin release. These associations were not apparent from peripheral blood and suggest that local coronary biomarker signatures may help further define vulnerability and risk.

Air Pollution and Coronary Plaque Vulnerability and Instability: An Optical Coherence Tomography Study

ObjectivesWe assessed the relationship between exposure to air pollutants and mechanisms of coronary instability evaluated by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS). BackgroundAir pollution is an emerging key player in determining the residual risk of coronary events. However, pathophysiological mechanisms linking air pollution and coronary events have been not adequately investigated. MethodsPatients with ACS undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT, and the presence of macrophage infiltrates (MØI) and thin-cap fibroatheroma (TCFA) at the culprit site was also assessed. Based on each case’s home address, exposure to several pollutants was evaluated, including particulate matter 2.5 (PM2.5), PM10, and carbon monoxide (CO). Only patients with >2 years of available data on air pollution exposure prior to ACS were enrolled. ResultsWe included 126 patients (median age: 67.0 years of age; IQR: 55.5-76.0; 97 male patients [77.0%]). Sixty-six patients (52.4%) had PR as the mechanism of plaque instability. Patients with PR were exposed to significantly higher PM2.5 levels than to IFC, and PM2.5 was independently associated with PR (odds ratio: 1.194; 95% CI: 1.036 to 1.377; P = 0.015). Moreover, exposure to higher levels of PM2.5 was independently associated with the presence of TCFA and of MØI at the culprit site. Interestingly, PM2.5, PM10, and Co levels were positively and significantly correlated with serum levels of C-reactive protein. ConclusionsWe provide novel insights into the missing link between air pollution and increased risk of coronary events. In particular, exposure to higher concentrations of air pollutants is associated with the presence of vulnerable plaque features and with plaque rupture as a mechanism of coronary instability. An enhanced systemic and plaque inflammatory activation may explain these findings.

Coronary lipid-rich plaque characteristics with acute coronary syndrome and chronic coronary syndrome: a near infrared spectroscopy and intravascular ultrasound study

Abstract Background Asians have a much lower incidence of adverse coronary events than Caucasians, and the characteristics of vulnerable plaque might be different among the ethnics. Purpose The aim of this study was to investigate the clinical characteristics of lipid-rich plaque (LRP) in the Asian population and we also aimed to distinguish the characteristics of an acute coronary syndrome (ACS) culprit lesion and a chronic coronary syndrome (CCS) culprit lesion. Furthermore, we evaluated the association between lipid core burden index (LCBI) and cardiovascular risk factors, lipid profiles, and inflammatory biomarkers, as determined in vivo by near infrared spectroscopy intravascular ultrasound (NIRS-IVUS) imaging in patients undergoing percutaneous coronary intervention (PCI). Methods We evaluated 207 patients (ACS, n=75; CCS, n=132) who underwent PCI under NIRS-IVUS. Plaque characteristics and the extent of LRP [defined as a long segment with a 4-mm maximum LCBI (maxLCBI4mm)] on NIRS in de-novo culprit and non-culprit segments were analyzed. Results The mean age was 65 years old and 82% of patients were male. The ACS culprit lesions had a significantly higher maxLCBI4mm (median [interquartile range (IQR)]: 533 [385–745] vs. 361 [174–527], p&amp;lt;0.001) than the CCS culprit lesions. Whereas, no significant difference was seen in maxLCBI4mm between ACS and CCS non-culprit lesion segments (246 [53, 342] vs. 185 [37, 350], p=0.47) (Figure 1). Receiver-operating characteristic analysis showed that the NIRS maxLCBI4mm could distinguish the ACS culprit segment from the CCS culprit segment, with a sensitivity of 73% and a specificity of 69% (c-statistic = 0.69; p&amp;lt;0.001, cut-off value of max LCBI4mm = 408) (Figure 2). On multivariate logistic analysis, a large LRP (defined as maxLCBI4mm ≥400) was the strongest independent predictor of the ACS culprit segment (odds ratio, 3.87; 95% confidence interval, 1.95–8.02). In non-culprit segments, 19.8% of patients had at least one large LRP without a small lumen. No significant correlation was found between the extent of LRP and circulating lipid profiles and inflammatory makers biomarkers (hs-CRP, IL-6, TNF-α) in both the culprit and non-culprit lesion segments, whereas the extent of LRP was positively correlated with IVUS plaque burden (r=0.24, p&amp;lt;0.001). Conclusions We confirmed that NIRS-IVUS plaque assessment could be useful to differentiate ACS from CCS culprit lesions, and that a threshold maxLCBI4mm ≥400 was clinically suitable in Japanese patients. No systemic surrogate markers were found to be associated with the extent of LRP by NIRS in culprit and non-culprit segments. Consequently, we believe that direct intravascular evaluation of coronary plaque characteristics remains important for identification of high-risk LRP. Funding Acknowledgement Type of funding sources: None. Figure 1. The difference of maxLCBI4mmFigure 2. ROC curve

Adoption of a new automated optical coherence tomography software to obtain a lipid plaque spread-out plot

Abstract Background Near infrared spectroscopy – intravascular ultrasound (NIRS-IVUS) imaging can provide a fully automated estimation of lipid burden, providing a two-dimensional spread-out plot, the Lipid Core Burden Index (LCBI), which has been associated with higher incidence of cardiac events. Optical coherence tomography (OCT) can identify lipid component with high accuracy and it is therefore potentially capable of measuring its longitudinal extension in a dedicated two-dimensional LCBI spread-out plot. Purpose The present study has been designed to validate a novel automated approach to assess OCT images, able of providing a dedicated LCBI spread-out plot plus other features of plaque vulnerability. Methods We compared the results obtained with a novel automated OCT alghorithm, developed utilising a convolutional neural network, with those obtained with conventional (manual) OCT and with NIRS-IVUS in a consecutive series of 40 patients with coronary artery disease. We tested and validated our new OCT algorithm to calculate the lipid core longitudinal extension in a dedicated two-dimensional LCBI spread-out plot. In each coronary plaque, the following measurements were obtained with NIRS-IVUS: 1) minimum lumen area (MLA), 2) vessel area at MLA site, 3) plaque burden (%) at MLA site, 4) NIRS-defined lipid pool arch and 5) maximum LCBI measurement within a 4 mm length. The following OCT features were obtained: 1) the MLA cross section, 2) the minimum fibrous cap thickness (FCT) in presence of lipid components and measured as the average of three measurements obtained in the same cross-section and 3) maximum LCBI within a 4 mm length. Results Three lesions groups were identified according to the studied lesions: 1) culprit lesions in patients with acute coronary syndrome (ACS, n=16), 2) non-culprit lesions in patients with ACS (n=12) and 3) lesions in patients with stable angina (n=12). OCT conventional assessment showed for the culprit ACS plaques a trend for a larger lipid arc and a significant thinner FCT (p=0.028). Consistently, NIRS-IVUS showed for culprit ACS plaques a more complex anatomy. A strong trend for increased maximum LPBI in 4mm segments was found in the culprit ACS group, regardless of the adopted imaging modality, either NIRS-IVUS or automated OCT (p=0.184 and p=0.066, respectively, figure 1). A fair correlation was obtained for the maximum 4 mm LCBI measured by NIRS-IVUS and automated OCT (r=0.75). The sensitivity and specificity of automated OCT to detect significant LCBI, applying a validated 400 cut off were 90.5 and 84.2 respectively. Conclusions We developed an automated approach, comparable to NIRS, to assess OCT images that can provide a dedicated lipid plaque spread-out plot to address plaque vulnerability. The automated OCT software can promote and improve OCT clinical applications for the identification of patients at risk of hard events. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): CLI - Centro Lotta all'Infarto Spread-out plot by IVUS-NIRS and OCT

Long-term exposure to ambient air pollution portends a higher risk of coronary plaque vulnerability and instability in patients with acute coronary syndrome: an optical coherence tomography study

Abstract Background Air pollution is an emerging key player in determining the residual risk of coronary events. However, pathophysiological mechanisms linking air pollution and coronary events have been not adequately investigated. Purpose We assessed the relationship between exposure to air pollutants and mechanisms of coronary instability evaluated by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS). Methods ACS patients undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT, and the presence of macrophage infiltrates (MØI) and thin-cap fibroatheroma (TCFA) at the culprit site was also assessed. Based on each case's home address, exposure to several pollutants was evaluated, including particulate matter 2.5 (PM2.5), particulate matter 10 (PM10), and carbon monoxide (CO). Only patients with &amp;gt;2 years of available data on air pollution exposure prior to ACS were enrolled. Results We included 136 patients [median age 67.0 years (56.2–76.0), 104 (76.5%) male]. Sixty-six patients (48.5%) had PR as mechanism of plaque instability. Patients with PR were exposed to significantly higher PM2.5 levels compared to IFC, and PM2.5 was an independent predictor for PR (OR=1.133, 95% CI [1.020–1.258], p=0.019). Moreover, exposure to higher levels of PM2.5, PM10 and CO was an independent predictor for the presence of TCFA, while PM2.5 and CO levels predicted the presence of MØI. Interestingly, PM2.5, PM10 and CO levels were positively and significantly correlated with serum levels of C-reactive protein. ROC curves were constructed to assess the ability of PM2.5 to predict the presence of plaque rupture, TCFA or MØI. The AUC for PM2.5 to predict plaque rupture was 0.62 (95% CI: 0.52–0.71, p=0.018), for TCFA was 0.71 (95% CI: 0.61–0.80, p&amp;lt;0.001) and for MØI was 0.80 (95% CI: 0.71–0.88, p&amp;lt;0.001). Using a PM2.5 cut-off value of 13.40 μg/m3, the sensitivity and specificity for MØI were 81% and 66%, respectively. Conclusions We provide novel insights into the missing link between air pollution and increased risk of coronary events. In particular, exposure to higher concentrations of air pollutants is a risk factor for vulnerable plaque features and for plaque rupture as mechanism of coronary instability mediated by systemic and local plaque inflammation. Of importance, the thresholds of air pollutants that predicted the presence of vulnerable plaque features are far lower than commonly accepted safety thresholds used to start preventive measures for public health, suggesting that further efforts are needed in order to reduce the adverse effects on the cardiovascular system. Funding Acknowledgement Type of funding sources: None. Air pollutants exposure and OCT featuresROC curve analysis

Optical coherence tomography-defined vulnerable plaque characteristics in relation to functional severity of coronary stenoses stratified by quantitative flow ratio

Abstract Background The functional severity and morphological features of epicardial lesions are both related to plaque vulnerability and adverse coronary events. However, their relationship remains controversial, especially in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Purpose This study aimed to examine whether quantitative flow ratio (QFR), an angiography-based computation of fractional flow reserve, was associated with optical coherence tomography (OCT)-defined vulnerable plaques such as thin-cap fibroatheromas (TCFAs) in a board spectrum of population, including patients presenting stable angina and NSTE-ACS. Methods We identified patients who underwent OCT examinations from 2 prospective cohorts and then assessed interrogated vessels with QFR. Lesions were divided into tertiles: QFR-T1 (QFR &amp;lt;0.85)&amp;lt;qfr),&amp;gt;, QFR-T2 (0.85 to 0.93) and QFR-T3 (QFR &amp;gt;0.93). Results This post-hoc analysis included 83 lesions from 79 patients (mean age: 61.5±9.8 years, males: 58%). Patients with NSTE-ACS accounted for the majority of the population (67%). The median % diameter stenosis and median QFR value were 42% (36 to 49%) and 0.88 (0.83 to 0.95), respectively. The prevalence of OCT-TCFA was significantly higher in QFR-T1 (50%) than in QFR-T2 (14%) and QFR-T3 (19%) (p=0.003 and 0.018, respectively). Overall significant differences were observed among tertiles in maximum lipid arc, thinnest fibrous cap thickness (FCT), and minimal lumen area (MLA) (p=0.017, 0.040, and &amp;lt;0.001, respectively). The Spearman's correlation analysis showed that QFR was significantly related to MLA (ρ = 0.537, p&amp;lt;0.001), % area stenosis (ρ = –0.512, p&amp;lt;0.001), maximum lipid arc (ρ = –0.360, p=0.002), lipid length (ρ = –0.242, p=0.038), lipid index (ρ = –0.333, p=0.004), and thinnest FCT (ρ = 0.315, p=0.006). In the multivariable analysis, QFR ≤0.80 remained as a significant determinant of TCFAs regardless of the presence of NSTE-ACS and the level of low-density lipoprotein cholesterol (adjusted odds ratio = 4.387, 95% confidence interval: 1.297 to 14.839, p=0.017). In addition, QFR demonstrated moderate predictive ability for OCT-TCFA (area under the curve = 0.72, 95% confidence interval: 0.58 to 0.86, p=0.003) with the best cutoff of ≤0.86 (sensitivity: 65%; specificity: 73%; negative predictive value: 85%; accuracy: 71%). Conclusions Lower QFR was related to OCT-TCFA and other vulnerable plaque characteristics in angiographically mild-to-intermediate stable lesions and culprit lesions from NSTE-ACS. The QFR might be a useful tool for ruling out high-risk, rupture-prone plaques without using any pressure wires or vasodilators. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Jiangsu Provincial Key Research and Development Program Flow diagram of patient selectionOCT findings according to QFR tertiles

The Course of Carotid Plaque Vulnerability Assessed by Advanced Neurosonology.

Background: Carotid artery atherosclerosis is a major risk factor for ischemic stroke. This risk is related to plaque vulnerability and is characterized by plaque morphology, intraplaque neovascularization, and cerebral microembolization. Advanced neurosonology can identify vulnerable plaques and aid in preventing subsequent stroke. We aimed to assess the time course of cerebral microembolization and intraplaque neovascularization during 6 months of follow-up and to explore the utility of advanced neurosonology in patients with acute cerebral ischemia.Methods: Fifteen patients with acute cerebral ischemia and carotid artery plaques underwent comprehensive extra- and intracranial ultrasound examinations, including microemboli detection and contrast-enhanced ultrasound. The examinations were repeated after 3 and 6 months.Results: We examined 28 plaques in 15 patients. The ultrasonographic features of plaque vulnerability were frequent in symptomatic and asymptomatic plaques. There were no significant differences in stenosis degree, plaque composition, plaque surface, neovascularization, or cerebral microembolization between symptomatic and asymptomatic plaques, but symptomatic plaques had a higher number of vulnerable features. None of the patients had recurrent clinical stroke or transient ischemic attack during the follow-up period. We observed a decrease in cerebral microembolization at 6 months, but no significant change in intraplaque neovascularization.Conclusions: In patients with acute cerebral ischemia and carotid artery plaques, cerebral microembolization decreased during 6 months of follow-up, indicating plaque stabilization.Clinical Trial Registration:ClinicalTrial.gov, identifier NCT02759653.

Genetic variant RS2275888 from HACD4 gene, confers risk for ischemic stroke in male patients with carotid plaque

Background and Aims: Carotid plaque (CP) burden is atherosclerotic manifestation entailing predisposition for ischemic stroke (IS). Ulceration is a CP surface characteristic, which represents an important feature of plaque vulnerability and is associated with neurologic symptoms. Common genetic variants rs36212560 and 2275888 in HACD gene (9p21.3) have recently been associated with the risk for CP occurrence among males. We aimed to test HACD4 genetic variants association with IS and ulceration among patients with CP.

Diagnostic Accuracy of Optical Frequency Domain Imaging for Identifying Necrotic Cores with Intraplaque Hemorrhage in Advanced Human Carotid Plaques

This study investigated whether optical frequency domain imaging (OFDI) can identify carotid artery vulnerable plaque characteristics, focusing on lipid-rich necrotic core (NC) and intraplaque hemorrhage (IPH). Fourteen patients scheduled for carotid endarterectomy underwent OFDI scan during preoperative angiography. Atherosclerotic plaque specimens obtained from carotid endarterectomy were cut every 3-4 mm into 4-μm transverse cross-sections and stained with standard methods. Each cross-section was matched with OFDI, and histologically classified into either fibrous, calcific, pathological intimal thickening (PIT), and NC. Of 75 histologic cross-sections, 6 were categorized as fibrous (8%), 18 as calcific (24%), 9 as PIT (12%), and 42 as NC (56%). Tissues categorized as NC had significantly higher OFDI signal attenuation rates than the other tissues (p <0.001), followed by PIT, calcific, and fibrous tissues. The receiver operating characteristic analysis indicated that attenuation rates of >0.023 and >0.031 predicted the presence of NC and IPH with high areas under the curve of 0.91 and 0.88, respectively. OFDI provides potential capability for the detection of NCs with IPH of carotid artery plaques by quantitatively analyzing the attenuation rate.

Vulnerable atherosclerotic plaque features: findings from coronary imaging.

Pathological studies have suggested that features of vulnerable atherosclerotic plaques likely to progress and lead to acute cardiovascular events have specific characteristics. Given the progress of intravascular coronary imaging technology, some large prospective studies have detected features of vulnerable atherosclerotic plaques using these imaging modalities. However, the rate of cardiovascular events, such as acute coronary syndrome, has been found to be considerably reduced in the limited follow-up period available in the statin era. Additionally, not all disrupted plaques lead to thrombus formation with clinical presentation. If sub-occlusive or occlusive thrombus formation does not occur, a thrombus on a disrupted plaque will organize without any symptoms, forming a “healed plaque”. Although vulnerable plaque detection using intracoronary imaging is focused on “thin-cap fibroatheroma” leading to plaque rupture, superficial plaque erosion is increasingly recognized; however, the underlying mechanism of thrombus formation on eroded plaques is not well understood. One of intravascular imaging, optical coherence tomography (OCT) has the highest image resolution and has enabled detailed characterization of the plaque in vivo. Here, we reviewed the status and limitations of intravascular imaging in terms of detecting vulnerable plaque through mainly OCT studies. We suggested that vulnerable plaque should be reconsidered in terms of eroded plaque and healed plaque and that both plaque and circulating blood should be assessed in greater detail accordingly.

The Association Between Quantitative Flow Ratio and Intravascular Imaging-defined Vulnerable Plaque Characteristics in Patients With Stable Angina and Non-ST-segment Elevation Acute Coronary Syndrome.

Background: This study aimed to examine whether quantitative flow ratio (QFR), an angiography-based computation of fractional flow reserve, was associated with intravascular imaging-defined vulnerable plaque features, such as thin cap fibroatheroma (TCFA) in patients with stable angina, and non-ST-segment elevation acute coronary syndrome.Methods: Patients undergoing optical coherence tomography (OCT) or intravascular ultrasound (IVUS) examinations were identified from two prospective studies and their interrogated vessels were assessed with QFR. Lesions in the OCT cohort were classified into tertiles: QFR-T1 (QFR ≤ 0.85), QFR-T2 (0.85 < QFR ≤ 0.93), and QFR-T3 (QFR > 0.93). Lesions in the IVUS cohort were classified dichotomously as low or high QFR groups.Results: This post-hoc analysis included 132 lesions (83 for OCT and 49 for IVUS) from 126 patients. The prevalence of OCT-TCFA was significantly higher in QFR-T1 (50%) than in QFR-T2 (14%) and QFR-T3 (19%) (p = 0.003 and 0.018, respectively). Overall significant differences were also observed among tertiles in maximum lipid arc, thinnest fibrous cap thickness, and minimal lumen area (p = 0.017, 0.040, and <0.001, respectively). Thrombus was more prevalent in QFR-T1 (39%) than in QFR-T2 (3%), and QFR-T3 (12%) (p = 0.001 and 0.020, respectively). In the multivariable analysis, QFR ≤ 0.80 remained as a significant determinant of OCT-TCFA regardless of the presence of NSTE-ACS and the level of low-density lipoprotein cholesterol (adjusted OR: 4.387, 95% CI 1.297–14.839, p = 0.017). The diagnostic accuracy of QFR was moderate in identifying lesions with OCT-TCFA (area under the curve: 0.72, 95% CI 0.58–0.86, p = 0.003). In the IVUS cohort, significant differences were found between two groups in minimal lumen area and plaque burden but not in the distribution of virtual histology (VH)-TCFA (p = 0.025, 0.036, and 1.000, respectively).Conclusions: Lower QFR was related to OCT-defined plaque vulnerability in angiographically mild-to-intermediate lesions. The QFR might be a useful tool for ruling out high-risk plaques without using any pressure wire or vasodilator.

Lipoprotein(a) levels and atherosclerotic plaque characteristics in the carotid artery: The Plaque at RISK (PARISK) study

Background and aimsLipoprotein(a) is an independent risk factor for cardiovascular disease and recurrent ischemic stroke. Lipoprotein(a) levels are known to be associated with carotid artery stenosis, but the relation of lipoprotein(a) levels to carotid atherosclerotic plaque composition and morphology is less known. We hypothesize that higher lipoprotein(a) levels and lipoprotein(a)-related SNPs are associated with a more vulnerable carotid plaque and that this effect is sex-specific. MethodsIn 182 patients of the Plaque At RISK study we determined lipoprotein(a) concentrations, apo(a) KIV-2 repeats and LPA SNPs. Imaging characteristics of carotid atherosclerosis were determined by MDCTA (n = 161) and/or MRI (n = 171). Regressions analyses were used to investigate sex-stratified associations between lipoprotein(a) levels, apo(a) KIV-2 repeats, and LPA SNPs and imaging characteristics. ResultsLipoprotein(a) was associated with presence of lipid-rich necrotic core (LRNC) (aOR = 1.07, 95% CI: 1.00; 1.15), thin-or-ruptured fibrous cap (TRFC) (aOR = 1.07, 95% CI: 1.01; 1.14), and degree of stenosis (β = 0.44, 95% CI: 0.00; 0.88). In women, lipoprotein(a) was associated with presence of intraplaque hemorrhage (IPH) (aOR = 1.25, 95% CI: 1.06; 1.61). In men, lipoprotein(a) was associated with degree of stenosis (β = 0.58, 95% CI: 0.04; 1.12). Rs10455872 was significantly associated with increased calcification volume (β = 1.07, 95% CI: 0.25; 1.89) and absence of plaque ulceration (aOR = 0.25, 95% CI: 0.04; 0.93). T3888P was associated with absence of LRNC (aOR = 0.36, 95% CI: 0.16; 0.78) and smaller maximum vessel wall area (β = -10.24, 95%CI: -19.03; -1.44). ConclusionsIn patients with symptomatic carotid artery stenosis, increased lipoprotein(a) levels were associated with degree of stenosis, and IPH, LRNC, and TRFC, known as vulnerable plaque characteristics, in the carotid artery. T3888P was associated with lower LRNC prevalence and smaller maximum vessel wall area. Further research in larger study populations is needed to confirm these results.