Non-culprit Plaques Research Articles

Abstract 16132: Cardiometabolic Risk Factors and Non-Culprit Plaque Characteristics in Patients With STEMI in REAL-TIMI 63B

Introduction: Greater non-calcified plaque volume (NCPV) measured by coronary CT angiography (CCTA) is associated with higher risk of future myocardial infarction in stable patients. However, NCPV and associations with clinical characteristics in patients presenting with a first acute STEMI are not well described. Methods: The REAL-TIMI 63B trial randomized 593 patients with no prior MI presenting with acute STEMI to intravenous recombinant human lecithin-cholesterol acyltransferase (MEDI6012) or placebo; a subset were to undergo CCTA 48-72h after STEMI. Global NCPV, low-attenuation PV (LAPV), and calcified PV (CPV) were measured by a centralized core laboratory blinded to treatment arm. Revascularized segments were excluded from coronary plaque quantification. Results: 188 patients had a CCTA performed at baseline. Of these, 80.3% had NCPV and 77.4% had LAPV outside of the revascularized segments. Median NCPV was 28.4mm 3 [IQR 1.4-92.1], LAPV 3.8mm 3 [0.1-14.9], and CPV 92.4mm 3 [22.6-201.8]. Among the characteristics examined, male vs. female sex (51.3 mm 3 [3.47-100.3] vs 5.6 mm 3 [0.0-17.3]; p=0.0003), BMI >25 kg/m 2 (overweight or obese) (41.20 mm 3 [2.01-104.50] vs 10.98 mm 3 (0.0-61.5); p=0.01) and diabetes (82.6 mm 3 [59.0-123.4] vs 24.2 mm 3 [1.21-85.2]; p=0.038) were associated with greater NCPV (Figure). Conclusions: Among patients with no prior MI undergoing primary PCI for STEMI, we found that most patients had NCPV and LAPV outside the culprit lesion. Male sex and markers of cardiometabolic disease including higher BMI and diabetes were associated with a greater burden of NCPV. These observations underscore the need for intensive medical therapies that may stabilize vulnerable plaque in patients presenting with acute myocardial infarction.

A Non-Linear Role of Hyperlipidemia on Progression of Intracranial Atherosclerotic Plaques and Acute Downstream Ischemic Events.

Intracranial atherosclerotic stenosis (ICAS) is the leading cause of ischemic stroke worldwide. Hyperlipidemia is a major contributor to atherosclerosis. However, the effect of hyperlipidemia on the evolution of intracranial atherosclerotic plaques and downstream ischemic episodes remains unclear. In this study, we aimed to assess the radiological features of ICAS plaques and to explore the relationship between hyperlipidemia and plaque progression. We included people with ICAS (≥50% stenosis) undergoing high-resolution magnetic resonance imaging. The culprit plaque was defined as the sole, or in case of multiple stenosis, the narrowest plaque on the intracranial artery responsible for acute ischemic stroke. Demographic, clinical data, plaque features on MRI, and lipid parameters were compared between culprit and non-culprit plaques. Plaque enhancement was graded as Grade 0, 1 and 2 by comparing to the adjacent normal vessel wall and pituitary funnel after contrast enhancement on T1-weighted sequences. 162 patients were included (mean age 57.7±12.1 years, male 61.6%), 110 of whom were identified as culprit plaque with an ipsilateral acute stroke. High-grade enhancement was the most prominent MRI feature of the culpable plaque (Grade-2: OR 6.539, 95%CI 1.706-23.707, p=0.006). LDL cholesterol was significantly associated with overall acute ischemic stroke caused by culprit plaque. After stratification by enhancement grading LDL was independently associated with ischemic events in Grade-1 enhancement plaques (OR 6.778, 95%CI 2.122-21.649, p=0.001). In patients with Grade-2 enhancement plaques, however, LDL was not associated with ischemic event; in contrast, Neutrophil/Lymphocyte ratio was independently associated with ischemic events caused by Grade-2 enhancement plaques (OR 2.188, 95%CI 1.209-3.961, p=0.010). LDL was related with ischemia events in intermediate stage of intracranial atherosclerotic plaque progression, an excellent period for intensive lipid-lowering treatment. In advanced stage, inflammatory agents maybe the main contributor to ischemic events.

Higher triglyceride levels are associated with the higher prevalence of layered plaques in non-culprit coronary plaques.

High triglyceride (TG) levels have been recognized as a risk factor for cardiovascular events in patients with coronary artery disease (CAD). This study aimed to clarify the association between TG levels and characteristics of non-culprit coronary plaques in patients with CAD. A total of 531 consecutive patients with stable CAD who underwent percutaneous coronary intervention for culprit lesions and optical coherence tomography (OCT) assessment of non-culprit plaques in the culprit vessel were included in this study. The morphology of the non-culprit plaques assessed by OCT imaging were compared between the higher TG (TG ≥ 150mg/dL, n = 197) and lower TG (TG < 150mg/dL, n = 334) groups.The prevalence of layered plaques (40.1 vs. 27.5%, p = 0.004) was significantly higher in the higher TG group than in the lower TG group, although the prevalence of other plaque components was comparable between the two groups. High TG levels were an independent factor for the presence of layered plaques (odds ratio 1.761, 95% confidence interval 1.213-2.558, p = 0.003) whereas high low-density lipoprotein cholesterol levels (≥ 140mg/dL) and low eicosapentaenoic acid/arachidonic acid ratios (< 0.4) were independently associated with a higher prevalence of thin-cap fibroatheroma and macrophages.Higher TG levels were associated with a higher prevalence of layered plaques in non-culprit plaques among patients with stable CAD. These results may partly explain the effect of TG on the progression of coronary plaques and the increased incidence of recurrent events in patients with CAD.

Achieved low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio predicts the pathophysiological evolution of lipid-rich plaques in acute coronary syndromes: an optical coherence tomography study.

As a novel lipoprotein ratio, baseline low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (LHR) is closely related to the clinical outcomes of acute coronary syndromes (ACS) after percutaneous coronary intervention. However, the pathophysiological impact of achieved LHR (aLHR) on the evolution of non-culprit lipid-rich plaques has not been systematically explored. Between September 2013 and December 2018, ACS patients with both baseline and 1-year follow-up optical coherence tomography (OCT) examinations were included in current study. They were divided into two groups according to the median value of aLHR at 1 year. Overall, 132 patients with 215 lipid-rich plaques were enrolled, with a median aLHR: 1.62. There were thinner fibrous cap thickness (FCT) (133.3 [70.0-180.0] µm vs. 160.0 [100.0-208.3] µm, p = 0.025) and higher prevalence of thin-cap fibroatheroma (TCFA) (24 [22.4%] vs. 13 [12.0%], p = 0.044) and CLIMA-defined high-risk plaques (12 [11.2%] vs. 3[2.8%], p = 0.015) in the high aLHR group at 1 year. Compared with other serum lipid indexes, aLHR showed the best robust correlation with the evolution of plaque vulnerability in both unadjusted and adjusted analyses. Cut-off value of aLHR to predict the progression of maximal lipid arc and FCT was 1.51. In the adjusted model, aLHR ≥1.51 was an independent predictor of TCFA [odds ratio (OR): 3.008, 95% CI: 1.370 to 6.605, p = 0.006] at 1 year. aLHR correlates well with the evolution of lipid-rich plaques and vulnerable phenotypes at 1-year follow-up, which might be an important and convenient serum indicator in the secondary prevention of ACS.

Evaluating Middle Cerebral Artery Plaque Characteristics and Lenticulostriate Artery Morphology Associated With Subcortical Infarctions at 7T MRI.

Lenticulostriate artery (LSA) obstruction is a potential cause of subcortical infarcts. However, MRI LSA evaluation at 3T is challenging. To investigate middle cerebral artery (MCA) plaque characteristics and LSA morphology associated with subcortical infarctions in LSA territories using 7-T vessel wall MRI (VW-MRI) and time-of-flight MR angiography (TOF-MRA). Prospective. Sixty patients with 80 MCA atherosclerotic plaques (37 culprit and 43 non-culprit). 7-T with 3D TOF-MRA and T1-weighted 3D sampling perfection with application-optimized contrast using different flip angle evolutions (SPACE) sequences. Plaque distribution (superior, inferior, ventral, or dorsal walls), LSA origin involvement, LSA morphology (numbers of stems, branches, and length), and plaque characteristics (normalized wall index, maximal wall thickness, plaque length, remodeling index, intraplaque hemorrhage, and plaque surface morphology (regular or irregular)) were assessed. Least absolute shrinkage and selection operator regression, generalized estimating equations regression, receiver operating characteristic curve, independent t-test, Mann-Whitney U test, Chi-square test, Fisher's exact test, and intra-class coefficient. A P value <0.05 was considered statistically significant. Plaque irregular surface, superior wall plaque, longer plaque length, LSA origin involvement, fewer LSA stems, and shorter total and average lengths of LSAs were significantly associated with culprit plaques. Multivariable logistic analysis confirmed that LSA origin involvement (OR, 28.51; 95% CI, 6.34-181.02) and plaque irregular surface (OR, 8.32; 95% CI, 1.41-64.73) were independent predictors in differentiating culprit from non-culprit plaques. A combination of LSA origin involvement and plaque irregular surface (area under curve = 0.92; [95% CI, 0.86-0.98]) showed good performance in identifying culprit plaques, with sensitivity and specificity of 86.5% and 86.0%, respectively. 7-T VW-MRI and TOF-MRA can demonstrate plaque involvement with LSA origins. MCA plaque characteristics derived from 7-T VW-MRI showed good diagnostic accuracy in determining the occurrence of subcortical infarctions. 2 TECHNICAL EFFICACY: Stage 3.

Incremental value of enhanced plaque length for identifying intracranial atherosclerotic culprit plaques: a high-resolution magnetic resonance imaging study

ObjectivesBesides plaque enhancement grade, the incremental value of enhancement-related high-resolution MRI features in defining culprit plaques needs further evaluation. This study was focused on assessing whether plaque enhancement features contribute to culprit plaque identification and further risk stratification.MethodsWe retrospectively studied patients who experienced an acute ischaemic stroke and transient ischaemic attack due to intracranial atherosclerosis from 2016 to 2022. The enhancement features included enhancement grade, enhanced length, and enhancement quadrant. Associations between plaque enhancement features and culprit plaques, as well as diagnostic value, were investigated using logistic regression and receiver operating characteristic analyses.ResultsOverall, 287 plaques were identified, of which 231 (80.5%) and 56 (19.5%) were classified as culprit and non-culprit plaques, respectively. Comparison of the pre- and post-enhancement images revealed enhanced length longer than the plaque length in 46.32% of the culprit plaques. Multivariate logistic regression showed that enhanced length longer than plaque length (OR 6.77; 95% CI 2.47–18.51) and grade II enhancement (OR 7.00; 95% CI 1.69–28.93) were independently associated with culprit plaques. The area under the curve value for the combination of stenosis and plaque enhancement grade for the diagnosis of culprit plaques was 0.787, which increased significantly to 0.825 on the addition of enhanced length longer than the plaque length (p = 0.026 for DeLong’s test).ConclusionsEnhanced length longer than the plaque length and grade II enhancement were independently associated with culprit plaques. The combination of the enhanced plaque features resulted in better culprit plaque identification.

Characteristics of culprit intracranial plaque without substantial stenosis in ischemic stroke using three-dimensional high-resolution vessel wall magnetic resonance imaging.

We aim to analyze the difference in quantitative features between culprit and non-culprit intracranial plaque without substantial stenosis using three-dimensional high-resolution vessel wall MRI (3D hr-vw-MRI). The patients with cerebral ischemic symptoms of the unilateral anterior circulation were recruited who had non-stenotic intracranial atherosclerosis (<50%) confirmed by computed tomographic angiographic (CTA) or magnetic resonance angiography (MRA). All patients underwent 3D hr-vw MRI within 1 month after symptom onset. 3D hr-vw-MRI characteristics, including wall thickness, plaque burden, enhancement ratio, plaque volume and intraplaque hemorrhage, and histogram features were analyzed based on T2-, precontrast T1-, and post-contrast T1-weighted images. Univariate and multivariate logistic regression analysis were used to identify key determinates differentiating culprit and non-culprit plaques and to calculate the odds ratios (ORs) with 95% confidence intervals (CIs). A total of 150 plaques were identified, of which 133 plaques (97 culprit and 36 non-culprit) were in the middle cerebral artery, three plaques (all culprit) were in the anterior cerebral artery (ACA) and 14 (11 culprit and three non-culprit) were in the internal carotid artery (ICA). Of all the quantitative parameters analyzed, plaque volume, maximum wall thickness, minimum wall thickness, plaque burden, enhancement ratio, coefficient of variation of the most stenotic site, enhancement ratio of whole culprit plaque in culprit plaques were significantly higher than those in non-culprit plaques. Multivariate logistic regression analysis found that plaque volume [OR, 1.527 (95% CI, 1.231-1.894); P < 0.001] and enhancement ratio of whole plaque [OR, 1.095 (95% CI, 1.021-1.175); P = 0.011] were significantly associated with culprit plaque. The combination of the two features obtained a better diagnostic efficacy for culprit plaque with sensitivity and specificity (0.910 and 0.897, respectively) than each of the two parameters alone. 3D hr-vw MRI features of intracranial atherosclerotic plaques provided potential values over prediction of ischemic stroke patients with non-stenotic arteries. The plaque volume and enhancement ratio of whole plaque of stenosis site were found to be effective predictive parameters.

42 SEASON VARIABILITY IN ATHEROSCLEROSIS COMPOSITION: INSIGHTS FROM 1848 NON-CULPRIT CORONARY PLQUES

Abstract Background Several environmental and seasonal factors are thought to be crucial in the risk of acute coronary syndromes (ACS), including temperature, latitude, longitude, atmospheric air pressure, wind velocity and circadian period. However differences in coronary plaque composition according to season variation is still poorly understood. Purpose Our study aims to analyse the characteristics of non-culprit coronary plaques in patients undergoing optical coherence tomography evaluation (OCT) evaluation of the left anterior descending artery. Methods We included 1848 non-culprit coronary plaques from 1003 patients of the CLIMA registry. The season of OCT pullback acquisition was collected for each patient. Results Overall, median age was 66 years (56-74), with 24.6% of women and 53.4% of ACS. At patient-level analysis, patients admitted in summer were less frequently affected by hypertension (59.8% vs 69.4% in autumn, 68.5% in winter and 72% in spring; p=0.027) and chronic kidney disease (14.8% vs 15.9% in autumn, 10.3% in winter and 19.4% in spring; p=0.037) in. At lesion-level analysis, similar values of fibrous cap thickness, maximum lipid arc, length of plaques and presence of macrophages were observed (Table 1). Summer plaques had a smaller minimum lumen area than spring plaques (5.7±3.1 vs 5.1±239; p=0.044) and also a less frequent superficial macrophage infiltration (23% vs 36.1% in autumn, 30.5% in winter and 30.6% in spring; p=0.030) and presence of cholesterol crystals (16.7% vs 23.8% in autumn, 28.4% in winter and 22.1% in spring; p=0.037 than three other season). Table 1 Conclusions Coronary plaques during summer had less local sign of inflammation such superficial macrophage infiltration and cholesterol crystals. Further studies are needed to confirm these results and investigate clinical implications.

Pharmaco-invasive therapy: Early implementation of statins and proprotein convertase subtilisin/kexin type 9 inhibitors after acute coronary syndrome.

Elevated LDL-cholesterol (LDL-C) plays a major role in atheroma formation and inflammation. Medical therapy to lower elevated LDL-C is the cornerstone for reducing the progression of atherosclerotic cardiovascular disease. Statin therapy, and more recently, other drugs such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, have proven efficacy in long-term lowering of LDL-C and therefore diminish cardiovascular risk. During an acute coronary syndrome (ACS), a systemic inflammatory response can destabilize other non-culprit atherosclerotic plaques. Patients with these vulnerable plaques are at high risk of experiencing recurrent cardiovascular events in the first few years post-ACS. Initiating intensive LDL-C lowering therapy in these patients with statins or PCSK9 inhibitors can be beneficial via several pathways. High-intensity statin therapy can reduce inflammation by directly lowering LDL-C, but also through its pleiotropic effects. PCSK9 inhibitors can directly lower LDL-C to recommended guideline thresholds, and could have additional effects on inflammation and plaque stability. We discuss the potential role of early implementation of statins combined with PCSK9 inhibitors to influence these cascades and to mediate the associated cardiovascular risk, over and above the well-known long-term beneficial effects of chronic LDL-C lowering.

Impact of the eicosapentaenoic acid to arachidonic acid ratio on plaque characteristics in statin-treated patients with coronary artery disease

BackgroundA low eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio is associated with an increased risk of cardiovascular events in patients with coronary artery disease (CAD). ObjectiveTo clarify the impact of the EPA/AA ratio on the characteristics of non-culprit coronary plaques in statin-treated patients with CAD. MethodsA total of 370 consecutive stable coronary disease patients treated with statins, who underwent percutaneous coronary intervention for the culprit lesion and optical coherence tomography (OCT) imaging of the non-culprit plaque in a culprit vessel were included. The characteristics of non-culprit plaques assessed using OCT were compared between the lower EPA/AA group (EPA/AA <0.4, n = 255) and the higher EPA/AA group (EPA/AA ≥0.4, n = 115). ResultsThe prevalence of lipid-rich plaque (58.8 vs. 41.7%, p = 0.003) and plaque with macrophages (56.5 vs. 31.3%, p <0.001) was significantly higher in the lower EPA/AA group than in the higher EPA/AA group. This association was observed even if the LDL-C level was <100 mg/dL. The prevalence of thin-cap fibroatheroma was significantly higher in patients with lower EPA/AA and higher LDL-C (≥100 mg/dL) than in those with higher EPA/AA and lower LDL-C (<100 mg/dL) (odds ratio: 2.750, 95% confidence interval: 1.182-6.988, p = 0.024). An EPA/AA <0.4 was independently associated with a higher prevalence of lipid-rich plaque, plaque with macrophages, and cholesterol crystals. ConclusionLower EPA/AA ratio was associated with higher prevalence of vulnerable characteristics in non-culprit plaques. The present results suggest the importance of EPA/AA ratio on the secondary prevention of CAD.

Abstract 11923: High Sensitivity C-Reactive Protein is Associated With Vulnerable Characteristics in Coronary Plaques in Patients With Stable Coronary Disease

Introduction: Higher level of high sensitivity C-reactive protein (hsCRP) is associated with an increased risk of cardiovascular events in patients with coronary artery disease (CAD). However, the association between hsCRP and the characteristics of coronary plaques in patients with CAD remains to be elucidated. Hypothesis: Higher hsCRP is associated with a higher prevalence of vulnerable characteristics in coronary plaques in patients with CAD. Methods: A total of 793 consecutive patients with stable coronary disease (SCD), who underwent optical coherence tomography (OCT) imaging of coronary plaques were included. The characteristics of culprit or non-culprit plaque assessed by OCT were compared between the higher hsCRP group (hsCRP ≥ 0.2 mg/dL, n=247) and the lower hsCRP group (hsCRP &lt; 0.2 mg/dL, n=546). Results: In culprit plaques, the prevalence of thin-cap fibroatheroma (TCFA) was significantly higher in the higher hsCRP group than in the lower hsCRP group (23.8% vs. 14.9%, p=0.003) (Panel A). In non-culprit plaques, the prevalence of TCFA (28.6 vs. 18.2%, p=0.014) and plaque with marcophages (56.4 vs. 45.1%, p=0.029) was significantly higher in the higher hsCRP group than in the lower hsCRP group (Panel B). Conclusions: Higher level of hsCRP is associated with a higher prevalence of vulnerable characteristics in culprit and non-culprit plaques in patients with CAD. The present results may partly explain the pathogenesis of an increased incidence of ​recurrent cardiovascular events in patients with CAD.

Triglyceride-glucose index and non-culprit coronary plaque characteristics assessed by optical coherence tomography in patients following acute coronary syndrome: A cross-sectional study.

BackgroundTriglyceride-glucose (TyG) index, a novel surrogate marker of insulin resistance, has been demonstrated to be significantly associated with cardiovascular disease. It remains indistinct regarding the association between TyG index and non-culprit coronary plaque characteristics in patients following acute coronary syndrome (ACS).MethodsThe present study retrospectively recruited patients who were diagnosed with ACS and underwent non-culprit optical coherence tomography (OCT) examination. The study population was divided into 2 groups based on the median of TyG index, which was calculated as Ln [fasting triglyceride (TG) (mg/dL) × fasting blood glucose (FBG) (mg/dL)/2]. The non-culprit plaque characteristics were determined by interpreting OCT images in accordance with the standard of previous consensus.Results110 patients (54.8 ± 12.1 years, 24.5% female) with 284 non-culprit plaques were included in the current analysis. TyG index was closely associated with high-risk plaque characteristics. Elevated TyG index was consistent to be an independent indicator for thin-cap fibroatheroma (TCFA) [odds ratio (OR) for per 1-unit increase 4.940, 95% confidence interval (CI) 1.652–14.767, P = 0.004; OR for taking lower median as reference 2.747, 95% CI 1.234–7.994, P = 0.011] and ruptured plaque (OR for per 1–unit increase 7.065, 95% CI 1.910–26.133, P = 0.003; OR for taking lower median as reference 4.407, 95% CI 1.208–16.047, P = 0.025) in fully adjusted model. The predictive value of TyG index for TCFA and ruptured plaque was moderate–to–high, with the area under the receiver operating characteristic curve (AUC) of 0.754 and 0.699 respectively. The addition of TyG index into a baseline model exhibited an incremental effect on the predictive value for TCFA, manifested as an increased AUC (0.681, 95% CI 0.570–0.793 vs. 0.782, 95% CI 0.688–0.877, P = 0.042), and significant continuous net reclassification improvement (0.346, 95% CI 0.235–0.458, P < 0.001) and integrated discrimination improvement (0.221, 95% CI 0.017–0.425, P = 0.034). TyG index failed to play an incremental effect on predicting ruptured plaque.ConclusionTyG index, which is simply calculated from fasting TG and FBG, can be served as an important and independent risk predictor for high-risk non-culprit coronary plaques in patients following ACS.

Higher triglyceride level is associated with the higher prevalence of layered plaque in nonculprit coronary plaques

Abstract Background The impact of the high triglyceride (TG) level on the characteristics of coronary plaque in nonculprit lesion remains to be elucidated. Purpose To clarify the association between the TG level and the characteristics of nonculprit coronary plaque in patients with stable coronary disease using optical coherence tomography (OCT). Methods A total of 531 consecutive patients who underwent OCT imaging of the nonculprit lesion were included. Patients were classified into either the higher TG group (non-fasting TG ≥150 mg/dL, n=197) or the lower TG group (non-fasting TG &amp;lt;150 mg/dL, n=334). The morphologies of nonculprit plaque assessed by OCT were compared between the two groups. Results The median (interquartile range) of TG in the two groups was 193.0 (168.0–244.0) mg/dL and 95.0 (75.0–120.0) mg/dL, respectively. The prevalence of layered plaque was significantly higher in the higher TG group than the lower TG group (40.1 vs. 27.5%, p=0.004), whereas the prevalence of other plaque components was comparable between the two groups (Figure 1). The prevalence of layered plaque was significantly higher in the higher TG group than in the lower TG group among patients with diabetes mellitus (DM) (44.2 vs. 28.7%, p=0.037) although it was comparable between the two groups among patients without DM (Figure 2). Conclusion A higher TG level was associated with a higher prevalence of layered plaque in nonculprit plaques in patients with stable coronary disease, particularly in patients with DM. The present results may partly explain the impact of TG on the progression of coronary plaque and the increased incidence of recurrent events in patients with coronary artery disease. Funding Acknowledgement Type of funding sources: None.

Lipoprotein (a) levels and vulnerable characteristics in nonculprit plaque in patients with acute coronary syndrome.

High plasma levels of Lp(a) are associated with a worse prognosis in patients with coronary artery disease. The aim of the present study is to clarify the association between high lipoprotein a [Lp(a)] levels and vulnerable characteristics of nonculprit plaques in patients with acute coronary syndrome (ACS). A total of 185 consecutive patients with ACS who underwent optical coherence tomography imaging of nonculprit plaques in the culprit vessels were enrolled. Patients were divided into the high Lp(a) group (≥30mg/dL; 50 nonculprit plaques in 49 patients) or the low Lp(a) group (<30mg/dL; 139 nonculprit plaques in 136 patients). The prevalence of thin-cap fibroatheroma (TCFA) was significantly higher in the high Lp(a) group than in the low Lp(a) group (38.0 vs. 21.6%, p=0.034). Multivariate logistic analysis demonstrated that a high Lp(a) level was independently associated with the prevalence of TCFA (odds ratio, 1.18; 95% confidence interval, 1.01-1.36; p=0.033). The prevalence of TCFA was significantly higher in the high Lp(a) group than in the low Lp(a) group among patients with plaque erosion (50.0 vs. 9.4%, respectively; p=0.027), although the difference was not statistically significant between the two groups in patients with plaque rupture. High Lp(a) levels were associated with a high prevalence of TCFA in nonculprit plaques among patients with ACS, particularly in patients with plaque erosion. The present results may partly explain the pathogenesis of worse clinical outcomes in patients with ACS and a high Lp(a) level as shown in clinical studies.

3D Enhancement Color Maps in the Characterization of Intracranial Atherosclerotic Plaques.

High-resolution MR imaging allows the identification of culprit symptomatic plaques after the administration of gadolinium. Current high-resolution MR imaging methods are limited by 2D multiplanar views and manual sampling of ROIs. We analyzed a new 3D method to objectively quantify gadolinium plaque enhancement. Patients with stroke due to intracranial atherosclerotic disease underwent 7T high-resolution MR imaging. 3D segmentations of the plaque and its parent vessel were generated. Signal intensity probes were automatically extended from the lumen into the plaque and the vessel wall to generate 3D enhancement color maps. Plaque gadolinium (Gd) uptake was quantified from 3D color maps as gadolinium uptake = (µPlaque T1 + Gd -µPlaque T1/SDPlaque T1). Additional metrics of enhancement such as enhancement ratio, variance, and plaque-versus-parent vessel enhancement were also calculated. Conventional 2D measures of enhancement were collected for comparison. Thirty-six culprit and 44 nonculprit plaques from 36 patients were analyzed. Culprit plaques had higher gadolinium uptake than nonculprit plaques (P < .001). Gadolinium uptake was the most accurate metric for identifying culprit plaques (OR, 3.9; 95% CI 2.1-8.3). Gadolinium uptake was more sensitive (86% versus 70%) and specific (71% versus 68%) in identifying culprit plaques than conventional 2D measurements. A multivariate model, including gadolinium uptake and plaque burden, identified culprit plaques with an 83% sensitivity and 86% specificity. The new 3D color map method of plaque-enhancement analysis is more accurate for identifying culprit plaques than conventional 2D methods. This new method generates a new set of metrics that could potentially be used to assess disease progression.

Follow-up assessment of atherosclerotic plaques in acute ischemic stroke patients using high-resolution vessel wall MR imaging.

Data on evolution of intracranial plaques in acute ischemic stroke patients after receiving medical therapy is still limited. We aimed to investigate the plaque features associated with culprit lesions and to explore the plaque longitudinal changes during treatment using high-resolution vessel wall MR imaging (VW-MRI). Twenty-three patients (16 men; mean age, 51.4years ± 11.1) with acute ischemic stroke underwent 3-T VW-MRI for intracranial atherosclerosis and were taken follow-up assessments. Each identified plaque was retrospectively classified as culprit, probably culprit, or nonculprit. Plaque features were analyzed at both baseline and follow-up and were compared using paired t-test, paired Wilcoxon test, or McNemar's test. A total of 87 intracranial plaques were identified (23 [26.4%] culprit, 10 [11.5%] probably culprit, and 54 [62.1%] nonculprit plaques). The median time interval between initial and follow-up MRI scans was 8.0months. In the multiple ordinal logistic regression analysis, plaque contrast ratio (CR) (OR, 1.037; 95% CI, 1.013-1.062; P = 0.002) and surface irregularity (OR, 4.768; 95% CI, 1.064-21.349; P = 0.041) were independently associated with culprit plaques. During follow-up, plaque length, maximum thickness, normalized wall index (NWI), stenosis degree, and CR significantly decreased (all P-values < 0.05) in the culprit plaque group. The plaque NWI and CR dropped in the probably culprit plaques (P = 0.041, 0.026, respectively). In the nonculprit plaque group, only plaque NWI and stenosis degree showed significant decrement (P = 0.017, 0.037, respectively). Follow-up VW-MRI may contribute to plaque risk stratification and may provide valuable insights into the evolution of different plaques in vivo.

Cholesterol crystals in non-culprit plaques of STEMI patients: A 3-vessel OCT study

BackgroundCholesterol crystals (CCs) are regular microstructures found within the necrotic core of atherosclerotic plaques and have been hypothesized to be related to plaque destabilization. We attempted to investigate the potential association between CCs and non-culprit plaque vulnerability in patients with ST-segment elevated myocardial infarction (STEMI) and study morphological features of CCs in ruptured non-culprit plaques. MethodsA total of 261 patients with ST-segment elevation myocardial infarction who underwent 3-vessel optical coherence tomography (OCT) imaging were included. Non-culprit plaques were divided into two groups according to the presence or absence of CCs in the plaque to compare the morphological characteristics of the plaques. The differences in parameters of the non-culprit plaque CCs were explored between ruptured plaques and unruptured plaques. ResultsTotally, 530 non-culprit plaques (29 ruptured plaques and 501 unruptured plaques) were identified by OCT. The incidence of CCs was 21.1%. Compared with non-culprit plaques without CCs, those with CCs had a larger lipid burden. Macrophages (p < 0.001) and spotty calcification (p = 0.002) were more frequently observed in non-culprit plaques with CCs. The frequency of CCs was significantly higher (p = 0.001) and the CCs were larger (p = 0.046) and more superficial (p = 0.005) in ruptured non-culprit plaques than in unruptured non-culprit plaques. The maximum lipid arc and fibrous cap thickness were independent predictors of plaque rupture, but the presence of CCs was not. ConclusionsNon-culprit plaques with CCs have more vulnerable features. CCs are more frequently found in ruptured non-culprit plaques and larger and more superficial CCs are associated with plaque rupture.

Simultaneous assessment of microcalcifications and morphological criteria of vulnerability in carotid artery plaque using hybrid 18F-NaF PET/MRI

BackgroundPrevious studies have suggested the role of microcalcifications in plaque vulnerability. This exploratory study sought to assess the potential of hybrid positron-emission tomography (PET)/magnetic resonance imaging (MRI) using 18F-sodium fluoride (18F-NaF) to check simultaneously 18F-NaF uptake, a marker of microcalcifications, and morphological criteria of vulnerability. Methods and resultsWe included 12 patients with either recently symptomatic or asymptomatic carotid stenosis. All patients underwent 18F-NaF PET/MRI. 18F-NaF target-to-background ratio (TBR) was measured in culprit and nonculprit (including contralateral plaques of symptomatic patients) plaques as well as in other arterial walls. Morphological criteria of vulnerability were assessed on MRI. Mineral metabolism markers were also collected. 18F-NaF uptake was higher in culprit compared to nonculprit plaques (median TBR 2.6 [2.2-2.8] vs 1.7 [1.3-2.2]; P = 0.03) but was not associated with morphological criteria of vulnerability on MRI. We found a positive correlation between 18F-NaF uptake and calcium plaque volume and ratio but not with circulating tissue-nonspecific alkaline phosphatase (TNAP) activity and inorganic pyrophosphate (PPi) levels. 18F-NaF uptake in the other arterial walls did not differ between symptomatic and asymptomatic patients. Conclusions18F-NaF PET/MRI may be a promising tool for providing additional insights into the plaque vulnerability.

Culprit and Non-Culprit Plaque Characteristics With vs. Without a Healed Phenotype in Patients With Acute Myocardial Infarction Caused by Plaque Erosion - A 3-Vessel OCT Study.

Plaque erosion can occur quietly without causing clinical symptoms, followed by a healing process resulting in healed plaque. This study aimed to assess culprit and non-culprit plaque characteristics of patients with acute myocardial infarction (AMI) caused by plaque erosion with vs. without healed phenotype at the culprit plaque using optical coherence tomography (OCT). A total of 117 AMI patients caused by plaque erosion who underwent OCT imaging of 3 coronary arteries were included. Patients were divided into 2 groups based on presence or absence of a healed phenotype at the culprit site. Culprit and non-culprit plaque characteristics were compared between the 2 groups. A healed phenotype at the culprit lesion was identified in 47.9% of AMI patients caused by plaque erosion. Patients with a healed phenotype at the culprit site were more frequently with hyperlipidemia, and had a higher prevalence of macrophage infiltration, microchannels, cholesterol crystals, and calcification at the culprit lesion. Moreover, patients with a healed phenotype at the culprit site had more non-culprit plaques and more characteristics of plaque vulnerability at the non-culprit lesion. In addition, patients with a healed phenotype at the culprit site presented with more severe luminal stenosis at both the culprit and non-culprit lesion. A healed phenotype was identified in 47.9% of AMI patients caused by plaque erosion at the culprit site. A healed phenotype within eroded culprit plaque was associated with signs of pancoronary vulnerability and advanced atherosclerosis.

Coronary Computed Tomography Angiography Analysis of Calcium Content to Identify Non-culprit Vulnerable Plaques in Patients With Acute Coronary Syndrome.

BackgroundAside from the culprit plaque, the presence of vulnerable plaques in patients with acute coronary syndrome (ACS) may be associated with future cardiac events. A link between calcification and plaque rupture has been previously described.AimTo assess whether analysis of the calcium component of coronary plaques using CT angiography, coronary computed tomographic angiography (CCTA) can help to detect additional vulnerable plaques in patients with non-ST elevation myocardial infarction (NSTEMI).Materials And MethodsCross sectional study of consecutive patients referred for NSTEMI from 30 July to 30 August 2018 with CCTA performed before coronary angiography with systematic optical coherence tomography (OCT) analysis of all coronary arteries within 24 h of clinical onset of NSTEMI. Three types of plaques were defined: culprit plaques defined by angiography (vulnerable culprit plaques–VCP) – plaques with a fibrous cap thickness < 65 microns or thrombus in OCT (vulnerable non-culprit plaque–VNCP) – plaques with a fibrous cap thickness ≥ 65 microns in OCT (stable plaque–SP).ResultsA total of 134 calcified plaques were identified in 29 patients (73% male, 59 ± 14 years) with 29(22%) VCP, 28(21%) VNCP and 77(57%) SP. Using CCTA analysis of the calcium component, factors associated with vulnerable plaques were longer calcification length, larger calcification volume, lower calcium mass, higher Agatston score plaque-specific (ASp), presence of spotty calcifications and an intimal position in the wall. In multivariate analysis, ASp, calcification length and spotty calcifications were independently associated to vulnerable plaques. There was no difference between VCP and VNCP.ConclusionsCCTA analysis of calcium component of the plaque could help to identify additional vulnerable plaques in NSTEMI patients.