OBJECTIVE: Omega-3 fatty acids have emerged as a new option for controlling the residual risk for coronary artery disease (CAD) in the statin era. Eicosapentaenoic acid (EPA) is associated with reduced CAD risk in the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention trial, whereas the Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia trial that used the combination EPA/docosahexaenoic acid (DHA) has failed to derive any clinical benefit. These contradictory results raise important questions about whether investigating the antiatherosclerotic effect of omega-3 fatty acids could help to understand their significance for CAD-risk reduction.
METHODS: The Attempts at Plaque Vulnerability Quantification with Magnetic Resonance Imaging Using Noncontrast T1-weighted Technic EPA/DHA study is a single-center, triple-arm, randomized, controlled, open-label trial used to investigate the effect of EPA/DHA on high-risk coronary plaques after 12 months of treatment, detected using cardiac magnetic resonance (CMR) in patients with CAD receiving statin therapy. Eligible patients were randomly assigned to no-treatment, 2-g/day, and 4-g/day EPA/DHA groups. The primary endpoint was the change in the plaque-to-myocardium signal intensity ratio (PMR) of coronary high-intensity plaques detected by CMR. Coronary plaque assessment using computed tomography angiography (CTA) was also investigated.
RESULTS: Overall, 84 patients (mean age: 68.2 years, male: 85%) who achieved low-density lipoprotein cholesterol levels of ＜100 mg/dL were enrolled. The PMR was reduced in each group over 12 months. There were no significant differences in PMR changes among the three groups in the primary analysis or analysis including total lesions. The changes in CTA parameters, including indexes for detecting high-risk features, also did not differ.
CONCLUSIONS: The EPA/DHA therapy of 2 or 4 g/day did not significantly improve the high-risk features of coronary atherosclerotic plaques evaluated using CMR under statin therapy.

BACKGROUND: Psoriasis (PSO) is a skin disorder with systemic inflammation and high coronary artery disease risk. A distinct lipid phenotype occurs in psoriasis, which is characterized by high plasma triglycerides (TGs) with typically normal or even low LDL-C. The extent to which cholesterol on LDL subfractions, such as small dense LDL-C (sdLDL-C), are associated with vulnerable coronary plaque characteristics in PSO remains elusive.
METHODS: A recently developed equation for estimating sdLDL-C from the standard lipid panel was utilized in a PSO cohort (n = 200) with 4-year follow-up of 75 subjects. Coronary plaque burden was assessed by quantitative coronary computed tomography angiography (CCTA). Multivariate regression analyses were used for establishing associations and prognostic value of estimated sdLDL-C.
RESULTS: Estimated sdLDL-C was positively associated with non-calcified burden (NCB) and fibro-fatty burden (FFB), which remained significant after multivariate adjustment for NCB (β = 0.37; P = 0.050) and LDL-C adjustment for FFB (β = 0.29; P < 0.0001). Of note, total LDL-C calculated by the Friedewald equation was not able to capture these associations in the study cohort. Moreover, in the regression modelling estimated sdLDL-C was significantly predicting necrotic burden progression over 4 years follow-up (P = 0.015), whereas LDL-C did not. Finally, small LDL particles (S-LDLP) and small HDL particles (S-HDLP), along with large and medium TG-rich lipoproteins (TRLPs) had the most significant positive correlation with estimated sdLDL-C.
CONCLUSIONS: Estimated sdLDL-C has a stronger association than LDL-C with high-risk features of coronary atherosclerotic plaques in psoriasis patients.
BACKGROUND: URL: https://www.
RESULTS: gov . Unique identifiers: NCT01778569.

OBJECTIVE: Several clinical trials using intravascular ultrasound (IVUS) evaluation have demonstrated that intensive lipid-lowering therapy by statin or a combination therapy with statin and ezetimibe results in significant regression of coronary plaque volume. However, it remains unclear whether adding ezetimibe to statin therapy affects coronary plaque composition and the molecular mechanisms of plaque regression. We conducted this prospective IVUS analysis in a subgroup from the CuVIC trial.
METHODS: The CuVIC trial was a prospective randomized, open, blinded-endpoint trial conducted among 11 cardiovascular centers, where 260 patients with coronary artery disease who received coronary stenting were randomly allocated into either the statin group (S) or the combined statin and ezetimibe group (S＋E). We enrolled 79 patients (S group, 39 patients; S＋E group, 40 patients) in this substudy, for whom serial IVUS images of nonculprit lesion were available at both baseline and after 6-8 months of follow-up.
RESULTS: After the treatment period, the S＋E group had significantly lower level of low-density lipoprotein cholesterol (LDL-C; 80.9±3.7 vs. 67.7±3.8 mg/dL, p=0.0143). Campesterol, a marker of cholesterol absorption, and oxysterols (β-epoxycholesterol, 4β-hydroxycholesterol, and 27-hydroxycholesterol) were also lower in the S＋E group. IVUS analyses revealed greater plaque regression in the S＋E group than in the S group (-6.14% vs. -1.18% for each group, p=0.042). It was noteworthy that the lowering of campesterol and 27-hydroxycholesterol, but not LDL-C, had a significant positive correlation with plaque regression.
CONCLUSIONS: Compared with statin monotherapy, ezetimibe in combination with statin achieved significantly lower LDL-C, campesterol, and 27-hydroxycholesterol, which resulted in greater coronary plaque regression.

OBJECTIVE: To analyse the correlation between the characteristics of coronary plaque in coronary heart disease (CHD) patients with phlegm-blood stasis syndrome (PBS) and blood stasis syndrome (BSS).
METHODS: Patients were divided into different groups based on Chinese medicine (CM) syndrome differentiation. The baseline demographics and clinical variables were collected from the medical records. Additionally, the characteristics of plaque and pathological manifestations in coronary artery were evaluated using intravascular ultrasound (IVUS).
RESULTS: A total of 213 CHD patients were enrolled in two groups: 184 were diagnosed with PBS and the remaining 29 were diagnosed with BSS. There were no significant differences in age, body mass index, proportions of patients with high blood pressure, diabetes mellitus, smoking, hyperlipidemia, history of coronary artery bypass graft and percutaneous coronary intervention, medications, index from cardiac ultrasound image, blood lipids and C-reactive protein between the two groups (P>0.05), except gender, weight and proportions of IVUS observed target vessels (P<0.05 or P<0.01). More adverse events such as acute myocardial infarction (P=0.003) and unstable angina (P=0.048) were observed in BSS. Additionally, dissection, thrombus and coronary artery ectasia were significantly increased in BSS (P<0.05 or P<0.01). In contrast, PBS had more patients with stable angina and chronic total occlusion with significantly higher SYNTAX (synergy between percutaneous coronary intervention with Taxus and coronary artery bypass surgery) scores (P<0.05 or P<0.01). Moreover, dense-calcium was significantly elevated in PBS (P<0.01).
CONCLUSIONS: Coronary plaque characteristics were correlated with different CM syndromes. Patients with PBS were associated with a higher degree of calcified plaque and severe coronary artery stenosis, indicating poor clinical prognosis but with a low probability of acute coronary events. In contrast, the degree of calcified plaque in patients with BSS remained relatively low, and plaque was more vulnerable, resulting in the possibility of the occurrence of acute coronary events remaining high.

Introduction: Mechanical forces are closely associated with plaque progression and rupture. Precise quantifications of biomechanical conditions using in vivo image-based computational models depend heavily on the accurate estimation of patient-specific plaque mechanical properties. Currently, mechanical experiments are commonly performed on ex vivo cardiovascular tissues to determine plaque material properties. Patient-specific in vivo coronary material properties are scarce in the existing literature. Methods: In vivo Cine intravascular ultrasound and virtual histology intravascular ultrasound (IVUS) slices were acquired at 20 plaque sites from 13 patients. A three-dimensional thin-slice structure-only model was constructed for each slice to obtain patient-specific in vivo material parameter values following an iterative scheme. Effective Young\'s modulus (YM) was calculated to indicate plaque stiffness for easy comparison purposes. IVUS-based 3D thin-slice models using in vivo and ex vivo material properties were constructed to investigate their impacts on plaque wall stress/strain (PWS/PWSn) calculations. Results: The average YM values in the axial and circumferential directions for the 20 plaque slices were 599.5 and 1,042.8 kPa, respectively, 36.1% lower than those from published ex vivo data. The YM values in the circumferential direction of the softest and stiffest plaques were 103.4 and 2,317.3 kPa, respectively. The relative difference of mean PWSn on lumen using the in vivo and ex vivo material properties could be as high as 431%, while the relative difference of mean PWS was much lower, about 3.07% on average. Conclusion: There is a large inter-patient and intra-patient variability in the in vivo plaque material properties. In vivo material properties have a great impact on plaque stress/strain calculations. In vivo plaque material properties have a greater impact on strain calculations. Large-scale-patient studies are needed to further verify our findings.

Accurate plaque cap thickness quantification and cap stress/strain calculations are of fundamental importance for vulnerable plaque research. To overcome uncertainties due to intravascular ultrasound (IVUS) resolution limitation, IVUS and optical coherence tomography (OCT) coronary plaque image data were combined together to obtain accurate and reliable cap thickness data, stress/strain calculations, and reliable plaque progression predictions. IVUS, OCT, and angiography baseline and follow-up data were collected from nine patients (mean age: 69; m: 5) at Cardiovascular Research Foundation with informed consent obtained. IVUS and OCT slices were coregistered and merged to form IVUS + OCT (IO) slices. A total of 114 matched slices (IVUS and OCT, baseline and follow-up) were obtained, and 3D thin-layer models were constructed to obtain stress and strain values. A generalized linear mixed model (GLMM) and least squares support vector machine (LSSVM) method were used to predict cap thickness change using nine morphological and mechanical risk factors. Prediction accuracies by all combinations (511) of those predictors with both IVUS and IO data were compared to identify optimal predictor(s) with their best accuracies. For the nine patients, the average of minimum cap thickness from IVUS was 0.17 mm, which was 26.08% lower than that from IO data (average = 0.23 mm). Patient variations of the individual errors ranged from ‒58.11 to 20.37%. For maximum cap stress between IO and IVUS, patient variations of the individual errors ranged from ‒30.40 to 46.17%. Patient variations of the individual errors of maximum cap strain values ranged from ‒19.90 to 17.65%. For the GLMM method, the optimal combination predictor using IO data had AUC (area under the ROC curve) = 0.926 and highest accuracy = 90.8%, vs. AUC = 0.783 and accuracy = 74.6% using IVUS data. For the LSSVM method, the best combination predictor using IO data had AUC = 0.838 and accuracy = 75.7%, vs. AUC = 0.780 and accuracy = 69.6% using IVUS data. This preliminary study demonstrated improved plaque cap progression prediction accuracy using accurate cap thickness data from IO slices and the differences in cap thickness, stress/strain values, and prediction results between IVUS and IO data. Large-scale studies are needed to verify our findings.

BACKGROUND: Recurrent event rates after myocardial infarction (MI) remain unacceptably high, in part because of the continued growth and destabilization of residual coronary atherosclerotic plaques, which may occur despite lipid-lowering therapy. Inflammation is an important contributor to this ongoing risk. Recent studies have shown that the broad-acting anti-inflammatory agent, colchicine, may reduce adverse cardiovascular events in patients post-MI, although the mechanistic basis for this remains unclear. Advances in endovascular arterial wall imaging have allowed detailed characterization of the burden and compositional phenotype of coronary plaque, along with its natural history and responsiveness to treatment. One such example has been the use of optical coherence tomography (OCT) to demonstrate the plaque-stabilizing effects of statins on both fibrous cap thickness and the size of lipid pools within plaque.
METHODS: The Phase 2, multi-centre, double-blind colchicine for coronary plaque modification in acute coronary syndrome (COCOMO-ACS) study will evaluate the effect of colchicine 0.5 mg daily on coronary plaque features using serial OCT imaging in patients following MI. Recruitment for the trial has been completed with 64 participants with non-ST elevation MI randomized 1:1 to colchicine or placebo in addition to guideline recommended therapies, including high-intensity statins. The primary endpoint is the effect of colchicine on the minimal fibrous cap thickness of non-culprit plaque over an 18-month period. The COCOMO-ACS study will determine whether addition of colchicine 0.5 mg daily to standard post-MI treatment has incremental benefits on high-risk features of coronary artery plaques. If confirmed, this will provide new mechanistic insights into how colchicine may confer clinical benefits in patients with atherosclerotic cardiovascular disease.
BACKGROUND: ANZCTR trial registration number: ACTRN12618000809235. Date of trial registration: 11th of May 2018.

BACKGROUND: High-risk coronary atherosclerosis features evaluated coronary CT angiography (CCTA) were suggested to have a prognostic role. The present study aimed to evaluate the association of circulating biomarkers with high-risk plaque features assessed by CCTA.
METHODS: A consecutive cohort of subjects who underwent CCTA because of suspected CAD was screened for inclusion in the CAPIRE study. Based on risk factors (RF) burden patients were defined as having a low clinical risk (0-1 RF with the exclusion of patients with diabetes mellitus as single RF) or an high clinical risk (≥3 RFs). In all patients, measurement of inflammatory biomarkers and CCTA analysis focused on high-risk plaque features were performed. Univariate and multivariate logistic regression analysis were used to evaluate the relationship between clinical and biological variables with CCTA advanced plaque features.
RESULTS: 528 patients were enrolled in CAPIRE study. Older age and male sex appeared to be predictors of qualitative high-risk plaque features and associated with the presence of elevated total, non-calcified and low-attenuation plaque volume. Among circulating biomarkers only hs-CRP was found to be associated with qualitative high-risk plaque features (OR 2.02, p = 0.004 and 2.02, p = 0.012 for LAP and RI > 1.1, respectively) with borderline association with LAP-Vol (OR 1.52, p = 0.076); HbA1c and PTX-3 resulted to be significantly associated with quantitative high-risk plaque features (OR 1.71, p = 0.003 and 1.04, p = 0.002 for LAP-Vol, respectively).
CONCLUSIONS: Our results support the association between inflammatory biomarkers (hs-CRP, PTX- 3), HbA1c and high-risk atherosclerotic features detected by CCTA. Male sex and older age are significant predictors of high-risk atherosclerosis.

OBJECTIVE: Coronary plaque regression is weak in acute coronary syndrome (ACS) patients with diabetes mellitus (DM). We evaluated whether dual lipid-lowering therapy (DLLT) with ezetimibe and atorvastatin attenuates coronary plaques in ACS patients with DM.
METHODS: The prospective, randomized controlled, multicenter PRECISE-IVUS (Plaque Regression with Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound) trial assigned 246 patients undergoing percutaneous coronary intervention to DLLT or atorvastatin monotherapy and evaluated IVUS-derived changes in percent atheroma volume (ΔPAV), at baseline and 9-12-month follow-up, in 126 ACS cases, including 25 DM patients. The atorvastatin dose was up-titrated to achieve low-density lipoprotein cholesterol (LDL-C) ＜70 mg/dL.
RESULTS: In DM patients, the monotherapy group (n=13) and the DLLT group (n=12) showed a similar prevalence of coronary risks and baseline lipid profiles. During the study, the change in LDL-C level was similar between DM and non-DM patients. Compared with non-DM patients, DM patients showed weaker regression of ΔPAV by DLLT than those who underwent monotherapy (DM: -2.77±3.47% vs. -0.77±2.51%, P=0.11; non-DM: -2.01±3.36% vs. -0.08±2.66%, P=0.008). The change in LDL-C level was not correlated with ΔPAV in non-DM patients, but there was significant correlation between the change in LDL-C level and ΔPAV in DM patients (r=0.52, P=0.008).
CONCLUSIONS: ACS patients with DM showed weaker coronary plaque regression than their counterparts. A significant correlation between the change in LDL-C level and ΔPAV in DM patients suggested that more intensive lipid-lowering therapy is required in ACS patients with DM.

BACKGROUND: Cholesterol efflux from atherosclerotic lesion is a key function of high-density lipoprotein (HDL). Recently, we established a simple, high-throughput, cell-free assay to evaluate the capacity of HDL to accept additional cholesterol, which is herein referred to as \"cholesterol uptake capacity (CUC)\".
OBJECTIVE: To clarify the cross-sectional relationship between CUC and coronary plaque properties.
METHODS: We enrolled 135 patients to measure CUC and assess the morphological features of angiographic stenosis by optical coherence tomography (OCT). We estimated the extent of the lipid-rich plaque by multiplying the mean lipid arc by lipid length (lipid index). The extent of the OCT-detected macrophage accumulation in the target plaque was semi-quantitatively estimated using a grading system.
RESULTS: Lipid-rich plaque lesions were identified in 125 patients (92.6%). CUC was inversely associated with the lipid index (R = -0.348, P < 0.0001). In addition, CUC was also inversely associated with macrophage score (R = -0.327, P < 0.0001). Conversely, neither circulating levels of HDL cholesterol nor apoA1 showed a similar relationship.
CONCLUSIONS: We demonstrated that CUC was inversely related to lipid-rich plaque burden and the extent of macrophage accumulation, suggesting that CUC could be useful for cardiovascular risk stratification.