Involvement of enhanced expression of classical complement C1q in atherosclerosis progression and plaque instability: C1q as an indicator of clinical outcome.

Activation of the classical complement pathway plays a major role in regulating atherosclerosis progression, and it is believed to have both proatherogenic and atheroprotective effects. This study focused on C1q, the first protein in the classical pathway, and examined its potentialities of plaque progression and instability and its relationship with clinical outcomes. To assess the localization and quantity of C1q expression in various stages of atherosclerosis, immunohistochemistry, western blotting, and real-time polymerase chain reaction (PCR) were performed using abdominal aortas from eight autopsy cases. C1q immunoreactivity in relation to plaque instability and clinical outcomes was also examined using directional coronary atherectomy (DCA) samples from 19 patients with acute coronary syndromes (ACS) and 18 patients with stable angina pectoris (SAP) and coronary aspirated specimens from 38 patients with acute myocardial infarction. C1q immunoreactivity was localized in the extracellular matrix, necrotic cores, macrophages and smooth muscle cells in atherosclerotic lesions. Western blotting and real-time PCR illustrated that C1q protein and mRNA expression was significantly higher in advanced lesions than in early lesions. Immunohistochemical analysis using DCA specimens revealed that C1q expression was significantly higher in ACS plaques than in SAP plaques. Finally, immunohistochemical analysis using thrombus aspiration specimens demonstrated that histopathological C1q in aspirated coronary materials could be an indicator of poor medical condition. Our results indicated that C1q is significantly involved in atherosclerosis progression and plaque instability, and it could be considered as one of the indicators of cardiovascular outcomes.

Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial.

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

An extracellular vesicle epitope profile is associated with acute myocardial infarction.

The current standard biomarker for myocardial infarction (MI) is high-sensitive troponin. Although powerful in clinical setting, search for new markers is warranted as early diagnosis of MI is associated with improved outcomes. Extracellular vesicles (EVs) attracted considerable interest as new blood biomarkers. A training cohort used for diagnostic modelling included 30 patients with STEMI, 38 with stable angina (SA) and 30 matched-controls. Extracellular vesicle concentration was assessed by nanoparticle tracking analysis. Extracellular vesicle surface-epitopes were measured by flow cytometry. Diagnostic models were developed using machine learning algorithms and validated on an independent cohort of 80 patients. Serum EV concentration from STEMI patients was increased as compared to controls and SA. EV levels of CD62P, CD42a, CD41b, CD31 and CD40 increased in STEMI, and to a lesser extent in SA patients. An aggregate marker including EV concentration and CD62P/CD42a levels achieved non-inferiority to troponin, discriminating STEMI from controls (AUC = 0.969). A random forest model based on EV biomarkers discriminated the two groups with 100% accuracy. EV markers and RF model confirmed high diagnostic performance at validation. In conclusion, patients with acute MI or SA exhibit characteristic EV biomarker profiles. EV biomarkers hold great potential as early markers for the management of patients with MI.

Healed Plaques in Patients With Stable Angina Pectoris.

OBJECTIVE: Healed plaques, signs of previous plaque destabilization, are frequently found in the coronary arteries. Healed plaques can now be diagnosed in living patients. We investigated the prevalence, angiographic, and optical coherence tomography features of healed plaques in patients with stable angina pectoris. Approach and Results: Patients with stable angina pectoris who had undergone optical coherence tomography imaging were included. Healed plaques were defined as plaques with one or more signal-rich layers of different optical density. Patients were divided into 2 groups based on layered or nonlayered phenotype at the culprit lesion. Among 163 patients, 87 (53.4%) had layered culprit plaque. Patients with layered culprit plaque had more multivessel disease (62.1% versus 44.7%, P=0.027) and more angiographically complex culprit lesions (64.4% versus 35.5%, P<0.001). Layered culprit plaques had higher prevalence of lipid plaque (83.9% versus 64.5%, P=0.004), macrophage infiltration (58.6% versus 35.5%, P=0.003), calcifications (78.2% versus 63.2%, P=0.035), and thrombus (28.7% versus 14.5%, P=0.029). Lipid index (P=0.001) and percent area stenosis (P=0.015) were greater in the layered group. The number of nonculprit plaques, evaluated using coronary angiograms, tended to be greater in patients with layered culprit plaque (4.2±2.5 versus 3.5±2.1, P=0.053). Nonculprit plaques in patients with layered culprit lesion had higher prevalence of layered pattern (P=0.002) and lipid phenotype (P=0.005). Lipid index (P=0.013) and percent area stenosis (P=0.002) were also greater in this group. CONCLUSIONS: In patients with stable angina pectoris, healed culprit plaques are common and have more features of vulnerability and advanced atherosclerosis both at culprit and nonculprit lesions.

Prevalence and Clinical Significance of Layered Plaque in Patients With Stable Angina Pectoris　- Evaluation With Histopathology and Optical Coherence Tomography.

BACKGROUND: Healed plaques are identified as a layered pattern with optical coherence tomography (OCT) imaging, but the exact relationship between healed plaques and the development of significant coronary stenosis in stable angina pectoris (SAP) is not fully understood.Methods and Results:A retrospective clinincal study investigated the OCT characteristics of culprit lesions of SAP patients (n=205), and a prospective study examined the histopathological characteristics of layered plaque in directional coronary atherectomy (DCA) samples (42 samples from 18 SAP patients). In the retrospective study, layered plaque was observed in 36.6% of the SAP culprit lesions. Compared with patients with non-layered plaque, male sex and smoking were more frequent, and HbA1c level was significantly higher in the patients with layered plaque (81.3% vs. 65.9%, P<0.05; 62.7% vs. 41.8%, P<0.05; 6.6±1.3% vs. 6.2±1.0%, P<0.05, respectively). Furthermore, layered plaque was accompanied by higher plaque vulnerability and smaller minimal lumen area. In the histopathological study, the layered plaques had a significantly higher rate of intramural thrombus and macrophages infiltration than non-layered plaques (75.0% vs. 14.3%, P<0.05; 75.0% vs. 38.1%, P<0.05, respectively). CONCLUSIONS: Healed plaque containing intramural thrombus is identified as layered plaque by OCT, and was frequently observed, even in SAP patients. Intramural thrombus might play an important role in the development of coronary plaque with a high degree of stenosis in SAP patients.

Expression profiles and potential functions of long non-coding RNA in stable angina pectoris patients from Uyghur population of China.

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nt that are involved in cardiovascular diseases (CVDs). To determine whether lncRNAs are involved in stable angina pectoris (SAP), we analysed the expression profile of lncRNAs and mRNAs on a genome-wide scale in SAP of Uyghur population. Five pairs of SAP patients and healthy controls were screened by an Agilent microarray (human lncRNA + mRNA Array V4.0). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the lncRNA expression levels in 50 SAP and 50 controls. Data analyses were performed using R and Bioconductor. A total of 1871 up- and 231 down-regulated lncRNAs were identified to be differentially expressed in the peripheral blood mononuclear cells (PBMCs). Microarray analysis results identified the lncRNAs NR_037652.1, ENST00000607654.1, ENST00000589524.1 and uc004bhb.3, which were confirmed by qRT-PCR. Among screened lncRNAs, the annotation result of their co-expressed mRNAs showed that the most significantly related pathways were the NF-κB signalling pathway, apoptosis and the p53 signalling pathway, while the main significantly related diseases were the cholesterol, calcium and coronary disease. Our study indicated that clusters of lncRNAs were significantly differentially expressed between SAP patients and matched controls. These lncRNAs may play a significant role in SAP development and could serve as biomarkers and potential targets for the future treatment of SAP.

Coronary Atherosclerotic Phenotype and Plaque Healing in Patients With Recurrent Acute Coronary Syndromes Compared With Patients With Long-term Clinical Stability: An In Vivo Optical Coherence Tomography Study.

Importance: At one end of the coronary artery disease (CAD) spectrum, there are patients with multiple recurrent acute coronary syndromes (rACS), and at the other end there are those with long-standing clinical stability. Predicting the natural history of these patients is challenging because unstable plaques often heal without resulting in ACS. Objective: To assess in vivo the coronary atherosclerotic phenotype as well as the prevalence and characteristics of healed coronary plaques by optical coherence tomography (OCT) imaging in patients at the extremes of the CAD spectrum. Design, Setting, and Participants: This is an observational, single-center cohort study with prospective clinical follow-up. From a total of 823 consecutive patients enrolled in OCT Registry of the Fondazione Policlinico A. Gemelli-IRCCS, Rome, Italy, from March 2009 to February 2016, 105 patients were included in the following groups: (1) patients with rACS, defined as history of at least 3 acute myocardial infarctions (AMIs) or at least 4 ACS with at least 1 AMI; (2) patients with long-standing stable angina pectoris (ls-SAP), defined as a minimum 3-year history of stable angina; and (3) patients with a single unheralded AMI followed by a minimum 3-year period of clinical stability (sAMI). Data were analyzed from January to August 2018. Exposures: Intracoronary OCT imaging of nonculprit coronary segments. Main Outcomes and Measures: Coronary plaque features and the prevalence of healed coronary plaques in nonculprit segments as assessed by intracoronary OCT imaging. Results: Of 105 patients, 85 were men (81.0%); the median (interquartile range) age was 68 (63-75) years. Median (interquartile range) time of clinical stability was 9 (5.0-15.0) years in the ls-SAP group and 8 (4.5-14.5) years in the sAMI group. Patients in the rACS and sAMI groups showed similar prevalence of lipid-rich plaque and thin-cap fibroatheroma, which was significantly higher than in those with ls-SAP (lipid-rich plaque 80.0% [n = 24 of 30] vs 76.3% [n = 29 of 38] vs 37.8% [n = 14 of 37], respectively; P < .001; thin-cap fibroatheroma 40.0% [n = 12 of 30] vs 34.2% [n = 13 of 38] vs 8.1% [n = 3 of 37], respectively; P = .006). Spotty calcifications were more frequently observed in patients with rACS than in those with ls-SAP and sAMI (70.0% [n = 21 of 30] vs 40.5% [n = 15 of 37] vs 44.7% [n = 17 of 38], respectively; P = .04). Healed coronary plaques were rarely observed in patients with rACS, whereas their prevalence was significantly higher in patients with ls-SAP and sAMI (3.3% [n = 1 of 30] vs 29.7% [n = 11 of 37] vs 28.9% [n = 11 of 38], respectively; P = .01). Conclusions and Relevance: Patients with rACS have a distinct atherosclerotic phenotype compared with those with ls-SAP, including higher prevalence of thin-cap fibroatheroma and lower prevalence of healed coronary plaques, suggesting that atherosclerotic profile and plaque healing may play a role in leading the natural history of patients with CAD.

Association of plasma apolipoprotein CIII, high sensitivity C-reactive protein and tumor necrosis factor-α contributes to the clinical features of coronary heart disease in Li and Han ethnic groups in China.

BACKGROUND: Apolipoprotein CIII (apoCIII) is an independent risk for coronary heart disease (CHD). In this study, we investigated the associations among plasma apoCIII, hs-CRP and TNF-α levels and their roles in the clinical features of CHD in the Li and Han ethnic groups in China. METHODS: A cohort of 474 participants was recruited (238 atherosclerotic patients and 236 healthy controls) from the Li and Han ethnic groups. Blood samples were obtained to evaluate apoCIII, TNF-α, hs-CRP and lipid profiles. Chi-squared, t-tests, and Kruskal-Wallis or Wilcoxon-Mann-Whitney tests, Pearson or Spearman correlation tests and multiple unconditional logistic regression were employed to analyze lipid profiles and variations in plasma apoCIII, TNF-α, hs-CRP in subgroups of CHD and their contributions to CHD using SPSS version 20.0 software. RESULTS: Compared to healthy participants, unfavorable lipid profiles were identified in CHD patients with enhanced systolic pressure, diastolic pressure, fasting blood sugar (FBS), TG, TC, LDL-C, apoB, Lp(a) (P < 0.05, TC and Lp(a); P < 0.01, FBS, TG, LDL-C, apoB); and lower HDL-C and apoAI (P < 0.05). Plasma apoCIII, TNF-α and hs-CRP levels were higher in CHD individuals (16.77 ± 5.98 mg/dL vs. 10.91 ± 4.97 mg/dL; 17.23 ± 6.34 pg/mL vs. 9.49 ± 3.88 pg/mL; 9.55 ± 7.32 mg/L vs. 2.14 ± 1.56 mg/L; P < 0.01 vs. healthy participants). Identical patterns were obtained in the Li and Han groups (16.46 ± 6.08 mg/dL vs. 11.72 ± 5.16 mg/dL; 15.71 ± 5.52 pg/mL vs. 9.74 ± 4.31 pg/mL; 8.21 ± 7.09 mg/L vs. 2.15 ± 1.51 mg/L in Li people; 17.05 ± 5.90 mg/dL vs. 10.07 ± 4.63 mg/dL; 18.59 ± 6.73 pg/mL vs. 9.23 ± 3.38 pg/mL; 10.75 ± 7.44 mg/L vs. 2.12 ± 1.63 mg/L in Han people; P < 0.01). Paired comparisons of subgroups with stable angina, unstable angina, and acute myocardial infarction (AMI) revealed significant variation in plasma levels of apoCIII, TNF-α and hs-CRP (P < 0.01), but not among subgroups with mild, moderate and severe stenosis (P > 0.05). Plasma apoCIII, TNF-α and hs-CRP contributed to the development of CHD (OR = 2.554, 7.252, 6.035, P < 0.01) with paired correlations in CHD patients (apoCIII vs. TNF-α, r = 0.425; apoCIII vs. hs-CRP, r = 0.319; TNF-α vs. hs-CRP, r = 0.400, P < 0.01). CONCLUSIONS: Association among plasma apoCIII, hs-CRP and TNF-α interacts with unfavorable lipid profiles to contribute to the clinical features of CHD with stable angina, unstable angina, and AMI in the Li and Han ethnic groups in China.

Comparison of serum levels of IL-6, IL-8, TGF-ß and TNF-α in coronary artery diseases, stable angina and participants with normal coronary artery.

Cytokines, which typically regulate the immune responses, play a role in cardiovascular diseases such as coronary artery diseases (CAD) and ischemic heart diseases (IHD). The aims of this study were to evaluate serum levels of IL-6, IL-8, TGF-ß and TNF-α in patients with or without CAD, as well as stable angina, and to assess the effects of drug administration on the serum levels of these cytokines. Serum levels of the cytokines were analyzed in the three groups: patients with acute coronary syndrome, stable angina and participants with normal coronary arteries as controls. Cohort study of the patients showed that Nitrocontin was the only drug used in a significantly different pattern between the groups where it was used less frequently in patients with stable angina compared to the acute coronary syndrome or control groups. Serum levels of the evaluated cytokines were not different neither between the studied groups nor between the groups with variable Gensini scores. However, IL-8 in controls that were not engaged in regular exercise was higher than the controls performing regular exercise. In the stable angina group, TNF-α in non-smokers was higher than the smokers. It was revealed that serum levels of pro-inflammatory cytokines are not associated with atherosclerosis and stable angina in patients from the South-East of Iran. However, suppressed expression of TGF-ß, may increase the risk of CAD. Exercise can reduce the risk of CAD through downregulation of pro-inflammatory cytokines.

Plasma MicroRNA-126-5p is Associated with the Complexity and Severity of Coronary Artery Disease in Patients with Stable Angina Pectoris.

BACKGROUND: Coronary artery disease (CAD) is a major problem worldwide. As an endothelium-enriched microRNA (miRNA), miR-126 has been reported to serve as a potential biomarker of acute myocardial infarction. However, the relationship between miR-126 and the severity of CAD remains unknown. This study was designed to test whether circulating miR-126 levels are associated with the severity of CAD. METHODS: The present study enrolled 40 patients who had risk factors for CAD without angiographically significant CAD, and 110 patients presenting with stable angina pectoris, who were validated left main coronary artery disease (LMCA) and/or multi-vessel disease by coronary angiography. The expression levels of plasma miR-126-5p from all enrolled subjects were estimated by quantitative real-time polymerase chain reaction (qRT-PCR). Then, the relationships between plasma miR-126-5p levels, number of diseased vessels and the corresponding Synergy between PCI with Taxus and Cardiac surgery (SYNTAX) score were analyzed. RESULTS: The expression of circulating miR-126-5p was affected by some CAD risk factors including aging, dyslipidemia and DM. Furthermore, plasma miR-126-5p levels were significantly down-regulated in CAD patients with multi-vessel disease, higher SYNTAX score, rather than isolated LMCA and low SYNTAX score. CONCLUSION: Circulating miR-126-5p has emerged as a potential biomarker for complexity and severity of CAD in patients with stable angina pectoris.

Circulating Microparticles and Coronary Plaque Components Assessed by Virtual Histology Intravascular Ultrasound of the Target Lesion in Patients with Stable Angina.

High levels of microparticles (MPs) circulate in the blood of patients with atherosclerotic diseases where they can serve as potential biomarkers of vascular injury and cardiovascular outcome. We used virtual histology intravascular ultrasound (VH-IVUS) to evaluate the relationship between the levels of circulating MPs and the coronary plaque composition in patients with stable angina. We included 35 patients with stable angina (22 men, age 64 ± 9 years) and a de novo target lesion. Preintervention gray-scale and VH-IVUS analysis was performed across the target lesion. Volumetric analysis was performed over a 10-mm-long segment centered at the minimum luminal site. Blood samples were obtained from the femoral artery before coronary angioplasty. MPs were measured using a solid-phase capture assay from a commercial kit. We divided participants into either a low MPs group or high MPs group based on the median value of MPs. There was no significant difference in baseline characteristics between the groups. The plaque burden and remodeling index were similar between the groups. The presence of VH-IVUS-derived thin-cap fibroatheroma was not different between the groups. The percentage of the necrotic core (NC) was significantly higher in the high MPs group than in the low MPs group, both in planar (17.0 ± 8.8% vs. 24.1 ± 6.9%, p = 0.012) and volumetric analyses (17.0 ± 4.8% vs. 22.1 ± 4.3%, p = 0.002). Circulating MPs were positively correlated with the percentage of the NC area at the minimal luminal site (r = 0.491, p = 0.003) and the percentage of the NC volume (r = 0.496, p = 0.002). Elevated levels of circulating MPs were associated with the amount of NC in the target lesion in those with stable angina, suggesting a potential role of circulating MPs as a biomarker for detecting unstable plaque in patients with stable angina.

Enhanced expression of hemoglobin scavenger receptor CD163 in accumulated macrophages within filtered debris between acute coronary syndromes and stable angina pectoris.

Coronary intraplaque hemorrhage up-regulates hemoglobin scavenger receptor CD163 expression on macrophages, and has an association with vulnerable plaque development. During percutaneous coronary intervention, mechanical plaque disruption exposes potentially embolic atheromatous contents from culprit plaque.In 37 patients with stable angina pectoris (SAP, n = 20) or acute coronary syndrome (ACS, n = 17), atherothrombotic debris was collected using a filter-based distal embolic protection device. We immunohistochemically determined CD14-positive macrophages and CD163-positive macrophages in filtered debris. We also examined the relation of CD14- and CD163-positive macrophages with culprit plaque volume and components evaluated with ultrasonic tissue characterization (VH-IVUS).The only significant difference in clinical characteristics between the two groups was in hs-CRP. In ACS, the percentage of CD14- and CD163-positive macrophages to the whole cells (%CD14 and %CD163, respectively) was significantly higher than that in SAP (20.1 ± 8.2 versus 8.8 ± 6.8%, P < 0.001 and 32.6 ± 18.9 versus 9.0 ± 3.8%, P < 0.001, respectively). In IVUS indices of culprit plaque, the remodeling index was significantly higher in ACS than in SAP. However, necrotic core component (%NC) in ACS was significantly higher than that in SAP. Furthermore, fibrotic component (%Fibrous) in ACS was significantly lower than that in SAP (56.1 ± 4.7 versus 60.1 ± 3.3%, P = 0.03). %CD14 and %CD163 had a significant positive correlation with %NC (%CD14: r = 0.40, P = 0.01 and %CD163: r = 0.45, P = 0.01), but only %CD163 was negatively correlated with %Fibrous (%CD163: r = -0.48, P = 0.01).These findings suggest that the presence of CD14- and CD163-positive macrophages may reflect plaque inflammation, NC expansion, and plaque vulnerability in patients with coronary heart disease.

Expansion of myeloid-derived suppressor cells in patients with acute coronary syndrome.

AIM: The aim of this study was to explore whether the circulating frequency and function of myeloid-derived suppressor cells (MDSCs) are altered in patients with acute coronary syndrome (ACS). METHODS: The frequency of MDSCs in peripheral blood was determined by flow cytometry, and mRNA expression in purified MDSCs was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR). The suppressive function of MDSCs isolated from different groups was also determined. The plasma levels of certain cytokines were determined using Bio-Plex Pro™ Human Cytokine Assays. RESULTS: The frequency of circulating CD14(+)HLA-DR(-/low) MDSCs; arginase-1 (Arg-1) expression; and plasma levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and IL-33 were markedly increased in ACS patients compared to stable angina (SA) or control patients. Furthermore, MDSCs from ACS patients were more potent suppressors of T-cell proliferation and IFN-γ production than those from the SA or control groups at ratios of 1:4 and 1:2; this effect was partially mediated by Arg-1. In addition, the frequency of MDSCs was positively correlated with plasma levels of IL-6, IL-33, and TNF-α. CONCLUSIONS: We observed an increased frequency and suppressive function of MDSCs in ACS patients, a result that may provide insights into the mechanisms involved in ACS.

Plasma levels of C1q/TNF-related protein 1 and interleukin 6 in patients with acute coronary syndrome or stable angina pectoris.

BACKGROUND: C1q/TNF-related protein 1 (CTRP-1), a novel adipocyte factor, may participate in the mechanisms of metabolism and inflammation. Interleukin 6 (IL-6) is a proinflammatory cytokine that is correlated with the severity of coronary heart disease (CHD). In this study, we focused on the levels of CTRP-1 and IL-6 in patients with CHD. METHODS: Circulating CTRP-1 and IL-6 levels were measured using enzyme-linked immunosorbent assay in 81 patients with acute coronary syndrome (n=41) or stable angina pectoris (n=40). CTRP-1 and IL-6 levels were also examined in 30 healthy individuals (control group). We examined the correlations between the levels of CTRP-1 and IL-6 and cardiac risk factors in CHD. Logistic regression analysis was performed to screen for factors that predict CHD. RESULTS: Both CTRP-1 and IL-6 concentrations were increased in the acute coronary syndrome or stable angina pectoris group compared with the control group (P<0.01). Both plasma levels of CTRP-1 and IL-6 in the single-, double- and triple-vessel lesion group were higher compared with the control group (P<0.01). CTRP-1 levels were positively correlated with IL-6 (r=0.667, P<0.01) and high-sensitivity C-reactive protein levels (r=0.520, P<0.01) and negatively correlated with HDL-C (r=-0.432, P<0.01). The logistic regression analysis showed that increases in CTRP-1 and IL-6 levels may be powerful predictors of CHD. CONCLUSIONS: The variation of plasma CTRP-1 and IL-6 concentrations may play an important role in reflecting the degree of inflammation in CHD and the severity of coronary arterial atherosclerosis. This potential suggests that evaluating CTRP-1 and IL-6 in combination may aid in predicting the occurrence of CHD.

Differences determined by optical coherence tomography volumetric analysis in non-culprit lesion morphology and inflammation in ST-segment elevation myocardial infarction and stable angina pectoris patients.

BACKGROUND: While the current methodology for determining fibrous cap (FC) thickness of lipid plaques is based on manual measurements of arbitrary points, which could lead to high variability and decreased accuracy, it ignores the three-dimensional (3-D) morphology of coronary artery disease. OBJECTIVE: To compare, utilizing optical coherence tomography (OCT) assessments, volumetric quantification of FC, and macrophage detection using both visual assessment and automated image processing algorithms in non-culprit lesions of STEMI and stable angina pectoris (SAP) patients. METHODS: Lipid plaques were selected from 67 consecutive patients (1 artery/patient). FC was manually delineated by a computer-aided method and automatically classified into three thickness categories: FC < 65 µm (i.e., thin-cap fibroatheroma [TCFA]), 65-150 µm, and >150 µm. Minimum thickness, absolute categorical surface area, and fractional luminal area of FC were analyzed. Automated detection and quantification of macrophage was performed within the segmented FC. RESULTS: A total of 5,503 cross-sections were analyzed. STEMI patients when compared with SAP patients had more absolute categorical surface area for TCFA (0.43 ± 0.45 mm(2) vs. 0.15 ± 0.25 mm(2) ; P = 0.011), thinner minimum FC thickness (31.63 ± 17.09 µm vs. 47.27 ± 26.56 µm, P = 0.012), greater fractional luminal area for TCFA (1.65 ± 1.56% vs. 0.74 ± 1.2%, P = 0.046), and greater macrophage index (0.0217 ± 0.0081% vs. 0.0153 ± 0.0045%, respectively, P < 0.01). CONCLUSION: The novel OCT-based 3-D quantification of the FC and macrophage demonstrated thinner FC thickness and larger areas of TCFA coupled with more inflammation in non-culprit sites of STEMI compared with SAP.

Comparison of morphologic findings obtained by optical coherence tomography in acute coronary syndrome caused by vasospasm and chronic stable variant angina.

This study used optical coherence tomography (OCT) to evaluate morphologic changes in vasospastic lesions, which can cause acute coronary syndrome (ACS) or chronic stable VA. Thirty-nine patients (52.4 ± 9.0 years, 33 males) with vasospasm-induced ACS who presented with chest pain and displayed transient ST segment elevation on electrocardiography were included in the ACS group. Forty-one patients (49.3 ± 7.7 years, 33 males) who presented with chronic stable variant angina were included in the VA group. The clinical characteristics and morphologic OCT results of the two groups were compared. There were no differences in baseline characteristics, including the proportions of hypertension, diabetes mellitus, and smoking, between the two groups. Intimal tear, erosion, and intra-luminal thrombi were more frequent in the ACS group than the VA group (P < 0.001, P < 0.001, and P = 0.006, respectively). High-sensitivity C-reactive protein level was higher in the ACS group than the VA group (1.33 ± 1.93 vs 0.48 ± 0.50 mg/l, P = 0.011). Maximal intima thickness of spastic segment (0.38 ± 0.06 vs 0.31 ± 0.05 mm, P < 0.001) was significantly greater in the ACS group than in the VA group. In patients with vasospasm-induced ACS, intimal tear, intimal erosion, and microthrombi are major abnormal morphologic findings of OCT compared with patients with chronic stable VA.

Prognostic usefulness of IL-6 and VEGF for the occurrence of changes in coronary arteries of patients with stable angina and implanted stents.

AIM: The aim of this study was to determine the prognostic significance of interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) in patients with chronic coronary artery disease treated who underwent percutaneous coronary intervention with stent implantation, for assessing the risk of restenosis and the occurrence of de novo lesions. PATIENTS AND METHODS: 498 patients with stable angina were examined during 18 months. 50 patients with significant (> 70%) stenosis of one coronary artery, eligible for the implantation of one stent, were enrolled to the study. Il-6 and VEGF level was measured using ELISA immunoassays during the initial coronary angiography with simultaneous angioplasty and stent implantation and 4 weeks after stent implantation. Coronary angiography was carried out 8-12 months after stent implantation. RESULTS: Statistically significant increase in IL-6 (from 4.02 ± 4.40 to 10.90 ± 8.23) and VEGF (from 310.13 ± 50.90 to 392.32 ± 106.84) level was observed 4 weeks after stent implantation in the group with restenosis. CONCLUSIONS: Increased levels of IL-6 and VEGF in the peripheral blood of patients with chronic stable angina pectoris, measured 4 weeks after coronary angioplasty with stent implantation, may indicate an increased risk of angiographic restenosis and de novo coronary artery lesions.

Expression of stanniocalcin-1 in culprit coronary plaques of patients with acute myocardial infarction or stable angina.

BACKGROUND: Stanniocalcin-1 (STC1) is involved in fundamental biological processes such as angiogenesis, inflammation and wound healing, but little is known about its expression in human coronary atherosclerotic plaques or its relationship to plaque instability. OBJECTIVE: STC1 expression was examined in the culprit coronary plaques of 70 patients with acute myocardial infarction (AMI; n=49) or stable angina (n=21) who underwent directional coronary atherectomy. METHODS: The specimens were stained with H&E, STC1-specific antibodies, and endothelial cells, macrophages and smooth muscle cell markers. RESULTS: The baseline characteristics of the two groups of patients were largely similar. CD31-immunopositive and CD68-immunopositive areas, indicative of the presence of endothelial cells and macrophages, respectively, were proportionately larger while areas immunopositive for α-actin, as a smooth muscle cell marker, were proportionately smaller in the AMI group than in the stable angina group. The proportion of STC1-immunopositive areas was significantly greater in the AMI group than in the stable angina group (20.0% (8.2-29.0%) vs 8.8% (3.9-19.4%), p=0.022). Areas positive for STC1 were independently correlated with those immunopositive for CD31 (r=0.42, p<0.001) and CD68 (r=0.40, p<0.001). STC1 immunoreactivity co-localised with CD31-immunopositive and CD68-immunopositive cells. CONCLUSIONS: STC1 is differentially expressed in the culprit coronary plaques of patients with AMI versus those with stable angina. STC1 may play a role in plaque instability.

An unusual pattern of three major components of the cardiovascular system: multimodality imaging and review of the literature.

INTRODUCTION: Coronary artery anomalies are found in 0.4% to 1.4% of patients who undergo coronary angiography. Anomalous origin of left coronary artery from the right sinus of Valsava is the rarest, with a reported prevalence of 0.02 -0.03% according to angiographic studies. CASE PRESENTATION: We present the rare case of a 42-year-old-man suffering from stable angina with unusual development of 3 major components of the cardiovascular system Coronary angiography revealed an anomalous origin of the left coronary artery from the ostium of the right coronary artery. Magnetic resonance angiography depicted an anomalous origin of the left common carotid artery from the innominate artery and an aneurysm of descending thoracic aorta. Coronary computed tomography angiography revealed the course of left coronary artery between aortic root and conus arteriosus at the level of the right ventricular outflow tract. In this report we attempt to highlight the rarity of this vascular anatomy. CONCLUSION: Anomalous origins of the coronary arteries are rare, but may cause myocardial ischemia and sudden death. Thus, their reliable identification is a matter of paramount importance possibly evaluating the effects of therapeutic intervention. Newer imaging modalities improve the illumination of vascular system anatomy, shedding light to diagnostic dilemmas that come up in daily medical practice.

Macrophage heterogeneity of culprit coronary plaques in patients with acute myocardial infarction or stable angina.

We investigated the polarization states of macrophages in coronary atherectomy tissues retrieved from patients with acute myocardial infarction (AMI, n = 52) or stable angina pectoris (SAP, n = 22). The specimens were analyzed immunohistochemically using antibodies specific to CD11c (M1 marker), CD206 (M2 marker), and to markers of endothelial cells, macrophages, and smooth muscle cells. Baseline characteristics were similar in the 2 groups. The proportion of areas immunopositive for α smooth muscle actin was similar, but those positive for CD31 and CD68 were larger in the AMI group compared with the SAP group. In addition, AMI had significantly greater areas immunopositive for CD11c (P = .007) than did SAP, but CD206 (P = .102) positivity was not different in the 2 groups. In conclusion, M1 macrophage infiltration, not M2 macrophage infiltration, was increased in culprit plaques of patients with AMI. Macrophage heterogeneity may therefore be related to plaque instability.