Plaque In Acute Coronary Syndrome Research Articles

Analysis of risk factors in high-risk plaque in acute coronary syndrome based on LASSO regression

Abstract Background The CLIMA Study (Relationship between OCT Coronary Plaque Morphology and Clinical Outcome) put forward the concept of High-risk plaque (HRP) and demonstrated that HRP were correlated with the high risk of major coronary events[1, 2]. HRP were defined as the presence of four simultaneous characteristics: minimum lumen area (MLA) <3.5mm2, fibrous cap thickness (FCT) <75 μm, lipid arc circumferential extension >180°, and the presence of macrophage infiltration. Early prediction of HRP formation are of great significance for the prevention and treatment of Acute Coronary Syndrome (ACS), but there are no relevant studies. Purpose To identify the risk factors related to OCT HRP in ACS and establish risk prediction model for HRPs in ACS. Methods A prospective observational cohort study was carried out on the patients with ACS from September 2019 to August 2022. A total of 169 patients were divided into OCT HRP (n=55) and OCT non-HRP (n=114) groups. Clinical information, laboratory examination and the OCT characteristics of the patients were collected. LASSO regression was used to screen variables, and multivariate logistic regression was used to establish risk prediction model. A nomogram was formulated, use the ROC curve to evaluate the discrimination of the model and the Bootstrap method to internally validate the model. Results The most frequently observed HRP characteristic was Lipid plague>180°(147 patients），followed by MLA<3.5mm2(141 patients), macrophages(127 patients), FCT<75μm(64 patients). The LASSO regression model was used to screen variables and construct an HRP risk factor model. This final model included age, BMI≥25, TC, LDL-C and Log NT-proBNP. The model is well differentiated (AUC 0.780, 95%CI 0.705-0.855) and calibrated. Decision Curve Analysis shows that the model has good net benefits. Conclusion This prediction model can accurately predict the risk of OCT HRP in patients with ACS, and is expected to assist clinicians in diagnosis and prevention of plaque stability.

Association of non-HDL cholesterol with plaque burden and composition of culprit lesion in acute coronary syndrome. An intravascular ultrasound-virtual histology study

ObjectiveLipids play key role in coronary atherosclerosis. The role of non-high-density lipoprotein cholesterol (non-HDL-C) in atherosclerotic plaques using intravascular imaging remains unclear. This study aimed to assess its relationship with coronary plaque features using intravascular ultrasound (IVUS) in acute coronary syndrome (ACS). MethodsA total of 601 patients divided into two groups: normal non-HDL-C≤130 mg/dl (n = 410) and high non-HDL cholesterol >130 mg/dl (n = 191). IVUS performed before coronary intervention. ResultsMean age 53.18 ± 12.29 years. No significant differences in hypertension, diabetes, and smoking between groups. Plaque burden was significantly higher among normal versus high non-HDL-C groups (79.59 ± 9.98 % vs. 81.61 ± 5.39 %; p = 0.001). At minimal luminal site, fibrofatty percentage was higher in normal non-HDL-C group (p = 0.027), while necrotic core greater in high non-HDL-C group (p = 0.033). Segmental analysis, necrotic core was significantly higher in percentage (p = 0.006) and volumes (p = 0.011) in normal versus high non-HDL-C groups. Total cholesterol (r = 0.099, p = 0.015), LDL-C (r = 0.081, p = 0.046), triglycerides (r = 0.083, p = 0.041),and non-HDL-C (r = 0.099, p = 0.015) positively correlated with plaque burden. Total cholesterol (r = 0.115, p = 0.005), LDL-C (r = 0.107, p = 0.009), and non-HDL-C (r = 0.105, p = 0.010) positively correlated with necrotic core volume. Linear regression analysis showed age and non-HDL-C as predictors of higher plaque burden. Multiple linear regression analysis; age, body mass index, and non-HDL-C were predictors of larger necrotic core volume. ConclusionNon-HDL-C levels were positively associated with plaque burden, measure of extent of atherosclerosis. It is closely associated with and is a predictor of necrotic core volume; a marker of plaque vulnerability. This IVUS study demonstrates potential role of non-HDL-C in causation of plaque in ACS.

Comparison of high-risk characteristics of non-culprit plaques in relation to plaque severity in acute coronary syndrome

IntroductionPatients with acute coronary syndrome (ACS) have high event rates related to non-culprit (NC) lesions, therefore plaque composition of these lesions is of great interest. Although marginal atherosclerotic lesions were studied extensively, more significant lesions might have more high-risk characteristics. AimTo compare differences in high-risk lesion characteristics between significant versus non-stenotic NC plaques in ACS and the discrepancies with chronic coronary syndrome (CCS) patients. MethodsNon-culprit vessels of 26 ACS patients with 26 angiographically significant lesions and 37 patients (17 ACS and 20 CCS) with 48 non-stenotic lesions were investigated with intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS). Overall, 74 segments of 30 mm length were analyzed in 1 mm intervals. External elastic lamina (EEM), plaque burden (PB), minimal luminal area (MLA), percent atheroma volume (PAV) and lipid core burden index maximum 4 mm (maxLCBI4mm) were determined for each segment. ResultsCardiovascular risk factors were similar in all groups. PB was higher and MLA smaller in significant non-culprit ACS lesions vs non-stenotic lesions: PB 73.5% (IQR 68.7–78.5) vs 59.2 (IQR 49.6–71.5), p = 0.003, MLA 3.0 mm2 (IQR 2.3–3.9) vs 4.0 mm2 (IQR 2.8–4.7). MaxLCBI4mm was similar 308.1 (±155.4) vs 287.8 (±165.7), p = 0.67.Among non-stenotic plaques, MaxLCBI4mm was comparable between ACS and CCS patients, 275.7 (±151.5) in CCS patients vs 287.8 (±165.7) in ACS patients, p = 0.79. ConclusionAlthough visually significant non-culprit lesions had a higher plaque burden compared to non-stenotic lesions, a significant relation between MaxLCBI4mm and hemodynamic significance of the plaques couldn’t be established.

Fractal geometry of culprit coronary plaque images within optical coherence tomography in patients with acute coronary syndrome vs stable angina pectoris.

The main cause of acute coronary syndrome (ACS) is plaque rupture and thrombus formation. However, it has not been fairly successful to identify vulnerable plaque to rupture using conventional parameters of intravascular imaging modalities. Fractal analysis is one of the mathematical models to examine geometrical features of picture image using a specific parameter called as fractal dimension (FD) which suggests geometric complexity of the image. This study examined FD of the optical coherence tomography (OCT)-derived images of the culprit plaque in patients with ACS vs stable angina pectoris (SAP) to evaluate the feasibility of FD for identifying vulnerable coronary plaques prone to provoke ACS distinguished from stable plaques only provoking SAP. We examined 65 cases (34 ACS patients, 31 SAP patients) in which the culprit lesion was imaged by OCT before percutaneous coronary intervention in patients with ACS and SAP. The culprit plaque lesion in the ACS group had a significantly larger mean lipid arc (203.8 ± 39.4° vs 152.3 ± 34.5°, p < 0.001) and a larger lipid plaque length (12.6 ± 5.1mm vs 7.7 ± 2.7mm, p < 0.001) and a thinner fibrous cap thickness (75.3 ± 22.3μm vs 134.8 ± 53.2μm, p < 0.001) than those in the SAP group. The prevalence of OCT-derived macrophage infiltration (Mph) in the entire culprit coronary vessel as well as that of the OCT-derived thin-cap fibroatheroma (TCFA) at the culprit lesion were significantly greater in the ACS group than those in the SAP group, respectively (Mph: 61.8% vs 35.5%, p = 0.048; TCFA: 44.1% vs 6.4%, p < 0.001). The FD of culprit plaque in the ACS group was significantly greater than in the SAP group (2.401 ± 0.073 vs 2.341 ± 0.051, p < 0.001). In multivariate regression analysis, the presence of Mph was a significant determinant of FD (regression coefficient estimate 0.049, CI 0.018-0.079, p = 0.002). The FD of OCT-derived image of culprit coronary plaque in the ACS group was significantly greater than that in the SAP group, indicating that the culprit plaque in ACS were structurally more complex. Therefore, fractal analysis of coronary OCT images might be clinically useful for identifying coronary plaques prone to provoke ACS.

Single-Cell RNA Sequencing Reveals an Immune Landscape of CD4+ T Cells in Coronary Culprit Plaques With Acute Coronary Syndrome in Humans-Brief Report.

Acute coronary syndrome (ACS) involves plaque-related thrombosis, causing primary ischemic cardiomyopathy or lethal arrhythmia. We previously demonstrated a unique immune landscape of myeloid cells in the culprit plaques causing ACS by using single-cell RNA sequencing. Here, we aimed to characterize T cells in a single-cell level, assess clonal expansion of T cells, and find a therapeutic target to prevent ACS. We obtained the culprit lesion plaques from 4 patients with chronic coronary syndrome (chronic coronary syndrome plaques) and the culprit lesion plaques from 3 patients with ACS (ACS plaques) who were candidates for percutaneous coronary intervention with directional coronary atherectomy. Live CD45+ immune cells were sorted from each pooled plaque samples and applied to the 10× platform for single-cell RNA sequencing analysis. We also extracted RNA from other 3 ACS plaque samples and conducted unbiased TCR (T-cell receptor) repertoire analysis. CD4+ T cells were divided into 5 distinct clusters: effector, naive, cytotoxic, CCR7+ (C-C chemokine receptor type 7) central memory, and FOXP3 (forkhead box P3)+ regulatory CD4+ T cells. The proportion of central memory CD4+ T cells was higher in the ACS plaques. Correspondingly, dendritic cells also tended to express more HLAs (human leukocyte antigens) and costimulatory molecules in the ACS plaques. The velocity analysis suggested the differentiation flow from central memory CD4+ T cells into effector CD4+ T cells and that from naive CD4+ T cells into central memory CD4+ T cells in the ACS plaques, which were not observed in the chronic coronary syndrome plaques. The bulk repertoire analysis revealed clonal expansion of TCRs in each patient with ACS and suggested that several peptides in the ACS plaques work as antigens and induced clonal expansion of CD4+ T cells. For the first time, we revealed single cell-level characteristics of CD4+ T cells in patients with ACS. CD4+ T cells could be therapeutic targets of ACS. URL: https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000046521; Unique identifier: UMIN000040747.

Sodium-Glucose Cotransporter-2 Inhibitors Stabilize Coronary Plaques in Acute Coronary Syndrome With Diabetes Mellitus

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are widely used in cardiology and are effective in treating acute coronary syndrome (ACS). Their effects on unstable plaque in patients with ACS remains unclear. This study aimed to examine the effectiveness of SGLT2is in coronary plaque based on optical coherence tomography (OCT) images and the prognosis of ACS with type 2 diabetes mellitus. This retrospective study included 109 patients in the total cohort and 29 patients in the OCT cohort. Based on SGLT2i administration after ACS, the total cohort was categorized into non-SGLT2i (n = 69) and SGLT2i (n = 40) groups. The OCT cohort had 15 and 14 patients in the non-SGLT2i and SGLT2i groups, respectively. The OCT images of unstable plaque were analyzed in nonstented lesions during ACS catheterization and at the 6-month follow-up. The total cohort was assessed after 1 year for major adverse cardiovascular events, including all-cause mortality, revascularization, cerebrovascular disease, and heart failure hospitalization. SGLT2is improved unstable lesions with a significantly thicker fibrous cap (48 ± 15 μm vs 26 ± 24 μm, p = 0.005), reduced lipid arc (-29 ± 12° vs -18 ± 14°, p = 0.028), higher % decrease in total lipid arc (-35 ± 13% vs -19 ± 18%, p = 0.01), and lower major adverse cardiovascular event incidence (log-rank p = 0.023, hazard ratio 4.72 [1.08 to 20.63]) and revascularization rate (adjusted hazard ratio 6.77 [1.08 to 42.52]) than the non-SGLT2i group. In conclusion, SGLT2is can improve the markers of plaque stability and may improve the prognosis in patients with type 2 diabetes mellitus.

Dynamic natural components and morphological changes in nonculprit subclinical atherosclerosis in patients with acute coronary syndrome and mild chronic kidney disease at the 1-year follow-up and clinical significance at the 5-year follow-up.

The natural outcome of coronary plaque in acute coronary syndrome (ACS) patients with chronic kidney disease (CKD) is unique, which can be analyzed quantitatively by optical flow ratio (OFR) software. A total of 184 ACS patients with at least one nonculprit subclinical atherosclerosis (NSA) detected by optical coherence tomography (OCT) at baseline and 1-year follow-up were divided into non-CKD group (n = 106, estimated glomerular filtration rate (eGFR)> 90 mL/(min×1.73 m2)) and mild CKD group (n = 78, 60≤eGFR<90 mL/(min×1.73 m2)). Changes of normalized total atheroma volume (TAVn) of NSA was the primary endpoint at the 1-year follow-up. Patients with mild CKD showed more TAVn progression of NSA than non-CKD (p = 0.019) from baseline to the 1-year follow-up, which was mainly due to an increase in calcium TAVn (p<0.001). The morphological change in the maximal calcification thickness (p = 0.026) was higher and the change in the distance from the calcified surface to the contralateral coronary media membrane (ΔC-to-M) at the maximal cross-sectional calcium area was lower (p<0.001) in mild CKD group than in non-CKD group. Mild CKD had more NSA related MACEs at the 5-year follow-up than non-CKD (30.8% vs. 5.8%, p = 0.045). Mild CKD patients had more plaque progression of NSA which showed the increase of calcium component with more protrusion into the lumen morphologically at the 1-year follow-up and a higher corresponding incidence of NSA-related MACEs at the 5-year follow-up. Clinical Trial registration ClinicalTrials.gov. NCT02140801. https://classic.clinicaltrials.gov/ct2/show/NCT02140801.

Impact of Intensive Low-Density Lipoprotein Cholesterol-Lowering Therapy on Coronary Artery Plaques in Acute Coronary Syndrome

Acute coronary syndrome (ACS) is associated with a high incidence of unstable plaques beyond the culprit lesion, leading to early recurrence of cardiovascular events. Coronary computed tomography angiography (CCTA) can be used to noninvasively observe plaques throughout the coronary arteries. To evaluate the impact of intensive low-density lipoprotein cholesterol (LDL-C)-lowering therapy on quantitative changes in coronary plaque, assessed using CCTA in a study population with ACS. In total, 81 consecutive patients with ACS who underwent CCTA at discharge and at 1-year follow-up from April 2018 to March 2020 were analyzed. The patients were divided into 2 groups: those who achieved LDL-C <70 mg/100 ml and those who did not. Changes in plaque morphology within and between the 2 groups were compared using CCTA. A total of 198 vessels were analyzed. The calcified plaque volume was significantly increased in the LDL-C <70 group (65.8 ± 80.1 mm3 to 73.6 ± 83.7 mm3, p=0.007), whereas no significant change was observed in the LDL-C ≥70 group (106.9 ± 161.7 mm3 to 105.7 ± 137.5 mm3, p=0.552). Percent change in low-attenuation plaque volume in the LDL <70 group was significantly lower than in the LDL-C ≥70 group (17.2 ± 90.9% vs 84.4 ± 162.6%, p=0.020). Receiver operating characteristic curve analysis demonstrated that the target LDL-C level for low-attenuation plaque volume regression was 64 mg/100 ml. In conclusion, noninvasive CCTA demonstrated that intensive LDL-C lowering in high-risk patients with ACS could potentially lead to plaque stabilization.

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.

Distinctive Morphological Patterns of Complicated Coronary Plaques in Acute Coronary Syndromes: Insights from an Optical Coherence Tomography Study.

Optical coherence tomography (OCT) is an ideal imaging technique for assessing culprit coronary plaque anatomy. We investigated the morphological features and mechanisms leading to plaque complication in a single-center observational retrospective study on 70 consecutive patients with an established diagnosis of acute coronary syndrome (ACS) who underwent OCT imaging after coronary angiography. Three prominent morphological entities were identified. Type I or intimal discontinuity, which was found to be the most common mechanism leading to ACS and was seen in 35 patients (50%), was associated with thrombus (68.6%; p = 0.001), mostly affected the proximal plaque segment (60%; p = 0.009), and had no distinctive underlying plaque features. Type II, a significant stenosis with vulnerability features (inflammation in 16 patients, 84.2%; thin-cap fibroatheroma (TCFA) in 10 patients, 52.6%) and a strong association with lipid-rich plaques (94.7%; p = 0.002), was observed in 19 patients (27.1%). Type III, a protrusive calcified nodule, which was found to be the dominant morphological pattern in 16 patients (22.9%), was found in longer plaques (20.8 mm vs. 16.8 mm ID vs. 12.4 mm SS; p = 0.04) and correlated well with TCFA (93.8%; p = 0.02) and inflammation (81.3%). These results emphasize the existence of a wide spectrum of coronary morphological patterns related to ACS.

Role of up-regulation of oxidative stress biomarkers in thrombotic transformation of atherosclerotic plaque in Acute Coronary Syndrome (ACS) patients from a lower middle income country

Background: In response to oxidative stress, reactive oxygen species aggravate and activate different signaling mechanism and stimulate the release of different inflammatory mediators, and provoke the generation of oxidative stress, all of which can promote the development of acute coronary syndrome. Methodology: The study sample comprised of 76 ACS patients and 76 healthy controls. Blood samples of ACS patients and controls were collected to determine the serum concentration of antioxidants, and the serum levels of inflammatory biomarkers. Spectrophotometric method and ELISA kit method was used to measure these variables accordingly. Results: The results indicated a significant rise in the levels of IL-1, IL-6, IL-8, TNF-α, MMP-11, ICAM-1 and VCAM-1 in ACS patients compared to controls whereas significant decrease was recorded in GSH, CAT, SOD, GRx and HDL levels in patients with ACS compared to controls. Conclusion: The present study indicated that the increased serum concentration of inflammatory cytokines and antioxidant reduction may influence the pathogenesis of ACS. Keywords: Acute coronary syndrome, oxidative stress , antioxidants

Abstract 13026: What Causes Speedy Growth (Within 3 to 6 Months) of Vulnerable Plaques in Acute Coronary Syndrome: An Angiographic and Machine Learning Analysis

Introduction: Based on damages by flow abnormalities seen in pipes, our research is built on the hypothesis that the flow disturbances start and grow atherosclerotic plaques. Our strategy is to use knowledge and practice of fluid mechanics to identify the different types of abnormal coronary flows and correlate them with the appearance and growth of lesions. Hypothesis: In patient with fast tract ACS when a normal segment becomes severely stenotic in a matter of 3 to 6 months, what kind of abnormal flow could trigger this speedy growth of a plaque ? Methods: Patients were selected if there was a near normal segment in the first angiogram and severe lesion in the 2nd angiogram 3 to 6 months later. LDL cholesterol level and HbA1c were also measured. In our cardiac catheterization laboratories, in the past 5 years, all patients underwent a special new dynamic coronary angiogram protocol. The contrast was injected until the coronary artery was completely opacified. As the injection of contrast stopped, the blood in white color moved in and displaced the contrast in black. The morphologies, movements and interactions of the blood flow in white color above a black background were reviewed frame by frame by investigators. The main measurements were the types of flow, their durations and direction at the index segment of the 1rst angiogram. At the same time, an artificial intelligence (AI) program (mainly Machine Learning (ML) algorithm) searched by 2 models built on Python. Model 1 was based on U-net and Densenet-121 for vessel segmentation. Model 2 was used for classification of flow (laminar, turbulent, antegrade, retrograde or stagnant). Model 2 was trained based on the convolutional neural network. Results: Ten dual angiograms were selected. At the index segment of the 1st angiogram, 80% showed turbulent and retrograde flow. The duration of this turbulent flow lasted 80% of one cardiac cycle (diastole and systole). The duration of retrograde flow lasted 90% of one systolic phase. A high level of LDL cholesterol (120mg%) was statistically significant while the HbA1c was not. Conclusions: In patient with fast tract ACS when a near normal segment became severely stenotic in a matter of 3 to 6 months, prolonged turbulent and retrograde flow with high LDL cholesterol were the culprits.

Ct Radiomics Of Coronary Artery Calcification Distinguish Vulnerable Plaques In Acute Coronary Syndrome- A Propensity-matched Study With Asymptomatic Subjects With Same Calcified Plaque Burden

Introduction: Measurement of coronary artery calcium (CAC) using Agatston score (AS) is widely used to predict the risk of acute coronary syndrome (ACS). However, many ACS victims have AS < 100, while many asymptomatic subjects have AS > 400. We hypothesize that CT radiomics can distinguish the vulnerability of CAC in subjects with similar AS.

CT Radiomics Of Coronary Artery Calcification Distinguish Vulnerable Plaques In Acute Coronary Syndrome: A Propensity-matched Study With Asymptomatic Subjects With Same Calcified Plaque Burden

Introduction: Measurement of coronary artery calcium (CAC) using Agatston score (AS) is widely used to predict the risk of acute coronary syndrome (ACS). However, many ACS victims have AS < 100, while many asymptomatic subjects have AS > 400. We hypothesize that CT radiomics can distinguish the vulnerability of CAC in subjects with similar AS.

Persistent Cigarette Smoking Attenuates Plaque Stabilization in Response to Lipid-Lowering Therapy: A Serial Optical Coherence Tomography Study.

Objective: This study aimed to investigate the effect of smoking on morphological changes in non-culprit plaques in acute coronary syndrome (ACS) patients at 1 year after percutaneous coronary intervention (PCI), using optical coherence tomography (OCT).Background: Cigarette smoking is an important risk factor for coronary artery disease. However, the reasons for the high risk of re-infarction and worsened health among patients who continue to smoke after PCI remain unclear.Methods: A total of 129 non-culprit plaques were identified from 97 ACS patients who underwent OCT imaging at the time of PCI and at 1-year follow-up. Patients were divided into the following three groups according to their smoking status at 1-year follow-up: persistent smoking group (n = 26), smoking cessation group (n = 29), and nonsmoking group (n = 42). Medical history, serum cholesterol level, coronary angiography data, and OCT-determined plaque morphology were analyzed among the three groups.Results: Relative to baseline levels, the total cholesterol and low-density lipoprotein cholesterol levels significantly decreased in all three groups at 1-year follow-up after statin therapy (p < 0.05). The persistent smoking group had a relatively smaller fibrous cap thickness (FCT) and a higher incidence of thin-cap fibroatheroma (TCFA) than the other two groups at 1-year follow-up (p < 0.05), although the FCT increased and the incidence of TCFA decreased in all three groups.Conclusions: Persistent smoking is associated with an attenuated effect of statin therapy on plaque stabilization in ACS patients.

Coronary artery echo-attenuated plaques in acute coronary syndromes: a serial intravascular ultrasound imaging study

Abstract Background Echo attenuation of atherosclerotic plaque (EAP) identified with intravascular ultrasound (IVUS) has been shown to correlate with vulnerable plaque morphologies and their presence is predictive of future cardiovascular events. EAP have predominantly been assessed at a single time point and their natural history in the immediate post acute coronary syndrome (ACS) period remains unknown. We aimed to assess this and whether their presence correlated with a more modifiable plaque composition in the immediate post-ACS setting. Methods Serial IVUS imaging was performed in non-culprit vessels of 270 patients undergoing angiogram for ACS and at 3 month follow up. IVUS analysis of plaque burden and EAP was performed. Results Baseline characteristics are described in Table 1. EAP were present at baseline in 62 patients (23%) with these patients more likely to be male (89.1% vs. 76.7%, p=0.03) but no differences in other atherosclerotic risk factors. There was no difference in baseline plaque burden between patients with EAP and those without (Percent atheroma volume [PAV] 38.9% vs. 37.8%, p=0.32). At follow up IVUS change in PAV was not statistically significantly different between patients with baseline EAP and those without (ΔPAV 0.09% vs. −0.36%, p=0.43), and neither was there a difference in the frequency of plaque regressors (42.7% vs 50%, p=0.31). EAP had resolved in 25 patients (40%) within 3 months at the follow up IVUS. Despite contemporary post-ACS therapy 18 patients who had not had EAP present at baseline (9%) developed new EAP at the follow up IVUS. Conclusion EAP were present in a quarter of ACS patients and were not associated with baseline plaque burden or a more modifiable plaque phenotype. In the setting of contemporary ACS treatments the natural history of high risk IVUS plaque characteristics such as EAP is dynamic with significant change even over a 3 month period in the post ACS setting. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Royal Adelaide Hospital Research Fund AR Clarkson Scholarship

Effects of Fatty Acid Therapy in Addition to Strong Statin on Coronary Plaques in Acute Coronary Syndrome: An Optical Coherence Tomography Study.

BACKGROUNDVascular healing response associated with adjunctive n‐3 polyunsaturated fatty acid therapy therapy in patients receiving strong statin therapy remains unclear. The aim of this study was to evaluate the effect of polyunsaturated fatty acid therapy with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) in addition to strong statin therapy on coronary atherosclerotic plaques using optical coherence tomography.METHODS AND RESULTSThis prospective multicenter randomized controlled trial included 130 patients with acute coronary syndrome treated with strong statins. They were assigned to either statin only (control group, n=42), statin+high‐dose EPA (1800 mg/day) (EPA group, n=40), statin+EPA (930 mg/day)+DHA (750 mg/day) (EPA+DHA group, n=48). Optical coherence tomography was performed at baseline and at the 8‐month follow‐up. The target for optical coherence tomography analysis was a nonculprit lesion with a lipid plaque. Between baseline and the 8‐month follow‐up, fibrous cap thickness (FCT) significantly increased in all 3 groups. There were no significant differences in the percent change for minimum FCT between the EPA or EPA+DHA group and the control group. In patients with FCT <120 µm (median value), the percent change for minimum FCT was significantly higher in the EPA or EPA+DHA group compared with the control group.CONCLUSIONSEPA or EPA+DHA therapy in addition to strong statin therapy did not significantly increase FCT in nonculprit plaques compared with strong statin therapy alone, but significantly increased FCT in patients with thinner FCT.RegistrationURL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN 000012825.

Female sex impact on culprit plaque at optical coherence tomography analysis in the setting of acute coronary syndrome in OCT-FORMIDABLE registry.

Aim: To evaluate sex difference in culprit plaque features at optical coherence tomography (OCT) and major adverse cardiovascular events at follow-up. Patients and methods: We analyse data from the OCT-FORMIDABLE (OCT-Features Of moRphology, coMposItion anD instABility of culprit and pLaquE in acute coronary syndrome [ACS] patients) registry. A total of 285 patients (20%, 58 females) were included. Results:Females with ST segment elevation myocardial infarction showed a longer ruptured area of the plaque (8.6±7.6 vs 4.6±5.4;p=0.003) and a major necrotic core macrophage infiltration (43 vs 17%;p=0.017). Females with non-ST segment elevation-ACS had less lipidic plaques (62 vs 80%;p=0.04). No between-group sex differences in major adverse cardiovascular events emerged at follow-up (5 vs 9%;p=0.88 in ST segment elevation myocardial infarction group and 19 vs 15%;p=0.6 in non-ST segment elevation-ACS group). At multivariate analysis, female sex was not a major risk of plaque rupture (hazard ratio [HR]: 1.59, CI: 0.44-5.67;p=0.48). Conclusion: Female sex seems to have no significant impact. ClincalTrial. gov registration number: NCT02486861.

MicroRNA‐9 overexpression suppresses vulnerable atherosclerotic plaque and enhances vascular remodeling through negative regulation of the p38MAPK pathway via OLR1 in acute coronary syndrome

Acute coronary syndrome (ACS) is characterized by atherosclerotic plaque rupture with a high incidence of recurrent ischemic events. Several microRNAs are found to be aberrantly expressed in atherosclerotic plaques. This study aims to investigate the effects of microRNA-9 (miR-9) on vulnerable atherosclerotic plaque and vascular remodeling in ACS and underlying mechanisms. Microarray-based gene expression profiling was used to identify differentially expressed genes related to ACS and regulatory miRNAs. Oxidized low-density lipoprotein (lectin-like) receptor 1 (OLR1) was identified to be aberrantly activated in ACS and regulated by miR-9. OLR1 was verified as a target gene of miR-9 by bioinformatics prediction and dual luciferase reporter gene assay. The atherosclerotic models were induced in ApoE-/- mice, in which the agomir or antagomir of miR-9, or small interfering RNA (siRNA) against OLR1 were separately introduced. Serum lipid levels and expression of vascular remodeling and inflammatory response-related factors were determined, respectively. On the basis of the obtained results, in the atherosclerosis mice treated with theagomir of miR-9 and siRNA against OLR1, the p38-mitogen-activated protein kinase (p38MAPK) pathway was inhibited; levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, tumor necrosis factor-α, interleukin-6, and vascular endothelial growth factor were reduced, but the high-density lipoprotein cholesterol level was increased, along with decreased vulnerable atherosclerotic plaque area and enhanced vascular remodeling. Taken together, these findings suggested an inhibitory role miR-9 acts in the formation of vulnerable atherosclerotic plaques in ACS mice, along with a promoted vascular remodeling, via a negative feedback regulation of OLR1-mediated p38MAPK pathway.

The changes and clinical significance of plasma lipoprotein-associated phospholipase A2, C-reactive protein and cardiac troponin I in patients with acute coronary syndrome

Objective To investigate the relationship between lipoprotein associated phospholipase A2 (Lp-PLA2) and atherosclerotic plaque instability in patients with acute coronary syndrome (ACS), and to provide theoretical basis for diagnosis and treatment of ACS. Methods From September 2015 to February 2016, 80 patients with ACS in Shidao People's Hospital of Rongcheng were selected as the study group, including 38 cases in unstable angina group(UAP group), 24 cases in non ST segment elevation myocardial infarction group (NSTEMI group), 18 cases in ST segment elevation myocardial infarction group(STEMI group). Forty patients with stable angina pectoris(SAP group) and 40 healthy subjects(healthy group) were selected as control group.Each group was collected 8 hours fasting morning blood sample, the levels of Lp-PLA2, C reactive protein(CRP), troponin I, and low density lipoprotein were detected, in order to compare the differences among the groups and the correlation between Lp-PLA2 and ACS plaque instability was analyzed. Results The levels of Lp-PLA2, CRP, troponin I and low density lipoprotein in the ACS group were (312.63±11.14)ng/mL, (21.98±7.83)mg/L, (0.720±0.490)μg/L, (174.76±30.82)mg/dL, respectively, which were significantly higher than those of the healthy group [(141.14±12.30)ng/mL, (2.38±1.68)mg/L, (0.010±0.003)μg/L, (79.24±17.80)mg/Ml], and stable angina pectoris group[(176.42±12.44)ng/mL, (4.22±3.68)mg/L, (0.010±0.004)μg/L, (96.54±19.41)mg/mL]. There were statistically significant differences among all groups(F=3.07, 1.99, 2.43, 3.25, all P<0.01). The levels of CRP, Lp-PLA2 and cTnI in ACS patients with different types of the STEMI group, NSTEMI group, UAP group had statistically significant differences, which of the STEMI group were higher than those of the NSTEMI group, which of the NSTEMI group were higher than those of the UAP group(F=5.15, 3.47, 2.43, all P<0.05). Correlation analysis showed that the level of Lp-PLA2 was positively correlated with low density lipoprotein(r=0.625, P<0.01) and lipoprotein a(r=0.532, P<0.01). logistic regression analysis showed that Lp-PLA2 and CRP were significant independent risk factors of ACS, Lp-PLA2(OR=1.613, 95%CI: 1.292-1.992, P<0.01), CRP(OR=1.452, 95%CI: 1.210-1.782, P<0.01). Conclusion Lp-PLA2 is independent risk factor of ACS.Lp-PLA2 is involved in the inflammatory reaction of ACS, and is strongly associated with the stability of atherosclerotic plaque. Key words: Acute coronary syndrome; Lipoprotein-associated phospholiase A2; C-reactive protein; cardiac troponin I; Regression analysis