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The role of lipoprotein (a) (Lp[a]) in the development of obstructive coronary artery disease (CAD) and high-risk plaque (HRP) in primary prevention patients with stable chest pain is unknown. We sought to evaluate the relation of Lp(a), independent of low-density lipoprotein cholesterol (LDL-C), with the presence of obstructive CAD and HRP to improve understanding of the residual risk imparted by Lp(a) on CAD. We performed a secondary analysis in Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) Trial participants who had coronary computed tomographic angiography (CTA) performed and Lp(a) data available. Lp(a) concentration was analyzed as a binary variable, with elevated Lp(a) defined as ≥50 mg/100 ml. "Stenosis ≥50%" was defined as ≥50% coronary artery stenosis in any epicardial vessel, and "stenosis ≥70%" was defined as ≥70% coronary artery stenosis in any epicardial vessel and/or ≥50% left main coronary artery stenosis. HRP was defined as presence of plaque on CTA imaging with evidence of positive remodeling, low computed tomography attenuation, or napkin-ring sign. Multivariate logistic regression models were constructed to evaluate the association between Lp(a) and the outcomes of obstructive CAD and HRP stratified by LDL-C ≥100 versus <100 mg/100 ml. Of the 1,815 patients who underwent CTA and had Lp(a) data available, those with elevated Lp(a) were more commonly women and Black than those with lower Lp(a). Elevated Lp(a) was associated with stenosis ≥50% (odds ratio 1.57, 95% confidence interval 1.14 to 2.15, p = 0.005) and stenosis ≥70% (odds ratio 2.05, 95% confidence interval 1.34 to 3.11, p = 0.0008) in the multivariate models, and this relation was not modified by LDL-C ≥100 versus <100 mg/100 ml (interaction p >0.4). Elevated Lp(a) was not associated with HRP when adjusted for obstructive CAD. This study of patients without known CAD found that elevated Lp(a) ≥50 mg/100 ml was independently associated with the presence of obstructive CAD regardless of controlled versus uncontrolled LDL-C but was not independently associated with HRP when stenosis ≥50% or ≥70% was accounted for. Further research is warranted to delineate the role of Lp(a) in the residual risk for atherosclerotic cardiovascular disease that patients may have despite optimal LDL-C lowering., Competing Interests: Declaration of competing interest Dr. Shah reports research grants from Amgen, Janssen, Eli Lily, Novartis, and National Institutes of Health, and service as a consultant/advisor for Merck, Amgen, Norvartis, and New Amsterdam Pharma. Dr. Ferencik reports consulting fees from Cleerly, HeartFlow, Elucid, Siemens Healthineers, and BioMarin, and stock options from Elucid, and is a member of an advisory board for Cleerly. Dr. Lu reports research funding to his institution from the American Heart Association, AstraZeneca, Ionis, Johnson & Johnson Innovation, Kowa Pharmaceuticals America, MedImmune, National Academy of Medicine, National Heart, Lung, and Blood Institute, and Risk Management Foundation of the Harvard Medical Institutions outside the submitted work. Dr. Foldyna reports research grants from National Institutes of Health/National Heart, Lung, and Blood Institute (R01HL170877, 5P30DK040561), AstraZeneca, Cleerly Health, MedImmune, and MedTrace. Dr. Pagidipati reports research support from Alnylam, Amgen, Bayer, Boehringer Ingelheim (Ingelheim, Germany), Eggland's Best, Eli Lilly (Esperion), Novartis, Novo Nordisk, Merck; service on consultation/advisory panels for Amgen, Bayer, Boehringer Ingelheim, CRISPR Therapeutics, Eli Lilly, AstraZeneca, Merck, Novartis, and Novo Nordisk; service as an Executive Committee member for trials sponsored by Novo Nordisk and by Amgen and by AstraZeneca; service on a Data and Safety Monitoring Board for trials sponsored by Johnson & Johnson and Novartis; and service on a medical advisory board for Miga Health. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to explore the expression of miR-665 in acute myocardial infarction (AMI) and evaluate its significance in the diagnosis and prognosis of AMI., Methods: 100 patients with AMI were selected as the study group and 80 healthy subjects were chosen as the control group. The levels of miR-665 were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in the two groups. The diagnostic value of miR-665 expression level in AMI was analyzed by the receiver operator characteristic (ROC) curve. Kaplan-Meier curve and Cox regression were used to evaluate the predictive value of miR-665 for major adverse cardiovascular events (MACEs) in patients with AMI within 30 days after percutaneous coronary intervention (PCI)., Results: The serum miR-665 level of the study group was significantly lower than that of the control group. The level of miR-665 was significantly correlated with clinical indicators of patients with AMI. ROC curve showed that miR-665 has a high diagnostic value for AMI. Survival analysis showed that Gensini score and miR-665 were independent risk factors for the occurrence of MACEs within 30 days after PCI in patients with AMI., Conclusions: Abnormal decrease of serum miR-665 expression level in patients with AMI may increase the risk of MACEs occurrence after PCI., (© 2024. The Author(s).)

Background: Patients with atherosclerotic plaques containing high-risk features have an increased likelihood of events and a worse prognosis. Whether increased levels of Troponin I (TnI) and C-reactive protein (CRP) are associated with the presence of high-risk coronary atherosclerotic plaques (HRP) is not well described. We assessed the association between 1) TnI and 2) CRP with quantified coronary plaque burden, luminal diameter stenosis, and HRP in patients with low/intermediate pre-test probability of obstructive coronary artery disease (CAD) referred for coronary computed tomography angiography (CCTA)., Methods: The CCTA from 1615 patients were analyzed using a semiautomatic software for coronary artery plaque characterization. Patients with high TnI (>6 ​ng/L) and high CRP (>2 ​mg/L) were identified. Associations of TnI and CRP with plaque burden, stenosis (≥50% luminal diameter stenosis on CCTA), and HRP were investigated., Results: TnI and CRP were both positively correlated with total plaque burden (TnI rs ​= ​0.14, p ​< ​0.001; CRP rs ​= ​0.08, p ​< ​0.001). In multivariate logistic regression analyses, high TnI was associated with stenosis (OR 1.43, 95% confidence interval (CI) 1.03-1.99, p ​= ​0.034), the presence of HRP (OR 1.79, 95% CI: 1.17-2.74, p ​= ​0.008), and the subtypes of HRP; low attenuation plaque (OR 1.93, 95% CI: 1.24-3.00, p ​= ​0.003), and positive remodeling (OR 1.51, 95% CI: 1.07-2.13, p ​= ​0.018). For CRP, only stenosis and napkin ring sign correlated significantly., Conclusion: In patients with suspected CAD, TnI and CRP are associated with HRP features. These findings may suggest that inflammatory and particularly ischemic biomarkers might improve early risk stratification and affect patient management., Gov Identifier: NCT02264717., Competing Interests: Declaration of competing interest Nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There may be severe difficulties in determining the severity of LMCA (left main coronary artery) lesions. The use of intravascular ultrasound (IVUS) facilitates decisions about lesion severity in these patients. The aim of this study was to investigate the relationship between the UHR (uric acid to HDL-C ratio) and lesion severity in patients who underwent LMCA IVUS., Methods: This study included 205 patients with ICS (intermediate coronary stenosis) in the LMCA who underwent IVUS. In the IVUS measurements of these patients, the plaque burden (PB) and the minimal lumen area (MLA) showing lesion severity were measured., Results: The patients were separated into two groups according to plaque burden (< 65% and ≥ 65%). The UHR was significantly greater in the high plaque burden group (479.5 vs. 428.6, P = 0.001). When the patients were separated into two groups according to the MLA (< 6mm 2 and ≥ 6mm 2 ), the UHR was determined to be significantly greater in the group with low MLA (476.8 vs. 414.9, P < 0.001). In the ROC analysis performed according to the MLA and plaque burden values, the UHR cutoff value of 450 was found to have similar sensitivity and the same specificity for both parameters., Conclusions: The results of this study suggested that there is a relationship between UHR and MLA < 6mm 2 and plaque burden ≥ 65%, which are independently evaluated as critical in IVUS, and this could predict anatomically significant lesions in patients with a moderate degree of LMCA stricture., (© 2024. The Author(s).)

Background: The atherogenic index of plasma (AIP) is linked to lipid metabolism and has shown considerable prognostic value in cardiovascular disorders. However, its role in myocardial infarction with non-obstructive coronary arteries (MINOCA) has not been investigated. We assessed the relationship between AIP, the severity of coronary stenosis, and prognosis in MINOCA., Methods: We included consecutive patients who were diagnosed with MINOCA. AIP was calculated using the base 10 logarithm of the ratio between the levels of TG and HDL-C. The patients were divided into four groups based on their AIP quartiles: Q1 (AIP<-0.145), Q2 (AIP≥-0.145and≤0.049), Q3 (AIP>0.049and≤0.253), and Q4 (AIP>0.253). All patients underwent follow-up for MACE., Results: The final analysis included 421 patients, with 188 having normal coronaries (0 stenosis) and 233 exhibiting non-obstructive coronary artery disease (CAD) (<50 % stenosis). In the multivariate logistic analysis, highest AIP (Q4) group was significantly associated with increased risk of non-obstructive CAD in MINOCA (OR,1.994;95 % CI:1.075-3.698; P = 0.029). During the follow-up period, MACE occurred in 22.8 % of MINOCA patients. Q4 group exhibited a significantly higher rate of MACE (P = 0.021). Furthermore, when both AIP and coronary stenosis status were considered, the results revealed individuals in the Q4 group with non-obstructive CAD had the highest risk of MACE (log-rank P = 0.027). The adjusted Cox analysis indicated that the Q4 group was associated with a 2.052-fold increase in the HR of MACE., Conclusion: AIP exhibits a notable association with the incidence of MACE in MINOCA patients and serves as a substantial marker for non-obstructive CAD in this patient group., Competing Interests: Declaration of competing interest None., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background and Objective: Disturbed autonomic nervous system (ANS) may promote inflammatory, immune, and oxidative stress responses, which may increase the risk of acute coronary events. S100β has been proposed as a biomarker of neuronal injury that would provide an insightful understanding of the crosstalk between the ANS, immune-inflammatory cells, and plaques that drive atherosclerosis. This study investigates the correlation between S100β, and functional coronary stenosis as determined by quantitative flow ratio (QFR)., Methods: Patients with unstable angina pectoris (UAP) scheduled for coronary angiography and QFR were retrospectively enrolled. Serum S100β levels were determined by enzyme-linked immunosorbent assay. The Gensini score was used to estimate the extent of atherosclerotic lesions and the cumulative sum of three-vessel QFR (3V-QFR) was calculated to estimate the total atherosclerotic burden., Results: Two hundred thirty-three patients were included in this study. Receiver operator characteristic (ROC) curve indicated that S100β>33.28 pg/mL predicted functional ischemia in patients with UAP. Multivariate logistic analyses showed that a higher level of S100β was independently correlated with a functional ischemia-driven target vessel (QFR ≤0.8). This was also closely correlated with the severity of coronary lesions, as measured by the Gensini score (OR = 5.058, 95% CI: 2.912-8.793, p <0.001). According to 3V-QFR, S100β is inversely associated with total atherosclerosis burden (B = -0.002, p <0.001)., Conclusions: S100β was elevated in the functional ischemia stages of UAP. It was independently associated with coronary lesion severity as assessed by Gensini score and total atherosclerosis burden as estimated by 3V-QFR in patients with UAP., (Copyright © 2024. Published by Elsevier Inc.)

Background and Aim: The current study investigated the association between triglyceride-glucose index (TyG) and triglyceride/HDL-C indices and coronary atherosclerosis extent in diabetic and non-diabetic patients., Methods and Results: In this case-control study, 1538 individuals were classified into two groups: diabetic and non-diabetic subjects. Each group was further grouped as follows: (1) angiography+ (2) angiography-and (3) subjects without a history of cardiovascular diseases. The TyG and TG/HDL-C indices were compared between the subgroups of the diabetic (n = 407) and non-diabetic (n = 1131) groups. In both diabetic and non-diabetic patients, there was no significant association in TG/HDL-C; and diabetic subjects, angiography+ and angiography-groups had significantly higher TyG (p < 0.05). A high TyG index was associated with a higher risk of angiography+ (OR: 1.883 (1.410-2.514))., Conclusions: The TyG index, but not the TG/HDL-C, was an independent marker for predicting the severity of coronary stenosis in non-diabetic patients., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Aims: People with HIV (PWH) whose disease is controlled on anti-retroviral regimens remain at an increased risk for coronary artery disease (CAD). Traditional cardiovascular risk factors do not fully explain the residual risk in PWH suggesting contributions from nontraditional factors. Homocysteine (Hcy) may be one of these as prior work in adults without HIV demonstrate that Hcy may impair endothelial function by decreasing the availability of nitric oxide, promoting the development of atherosclerosis. In addition, plasma Hcy levels are higher in PWH than in individuals living without HIV. The aim of this study was to investigate whether Hcy levels influence the association between HIV and coronary stenosis in an inner city African American population., Methods: African Americans from the Heart Study in Baltimore, with and without HIV, recruited from inner-city Baltimore between June 2004 and February 2015, were included in this analysis. Participants underwent coronary CT angiography to evaluate the presence of coronary stenosis, defined as luminal stenosis >10%. Hcy was measured from stored serum samples., Results: In this analysis, the median [IQR] age of the 664 participants was 56 [50-66] years; 68.1% were living with HIV and 43.1% were women. Elevated Hcy (>15 µmol/L) was more prevalent in those with coronary stenosis (23.3%, 95% CI: 18.4%-28.2%) than in those without coronary stenosis (13.1%, 95% CI: 9.7%-16.5%) ( p = 0.0007), and HIV was associated with coronary stenosis in those participants with an elevated Hcy (Prevalence Ratio: 1.94, 95% CI: 1.04-3.64, p = 0.0038) and not in those with a Hcy ≤15 µmol/L (Prevalence Ratio: 1.02, 95% CI: 0.83-1.25, p = 0.87)., Conclusions: Our data suggest an association between elevated Hcy levels (>15 µmol/L) and the prevalence of coronary stenosis in PWH from this inner city African American population., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Aims: The role of fractional flow reserve (FFR) in coronary intermediate lesions is widely recommended by guidelines. The effect of uric acid (UA) on cardiovascular events is also well known. However, the relationship between UA and long-term cardiovascular outcomes in patients who received FFR with intermediate lesions remains unknown., Methods and Results: We retrospectively included 428 patients who underwent both coronary angiography (CAG) and FFR. Participants were stratified into two groups based on the median UA. The primary endpoint was the composite of major adverse cardiovascular and cerebrovascular events (MACCEs), including repeat revascularization, nonfatal stroke, nonfatal myocardial infarction, and all-cause death. A Cox proportional hazards model was utilized to analyze the association between UA and the prevalence of MACCEs. During a median follow-up of 5.8 years, a higher MACCEs rate occurred in the high UA group compared to the low UA group (16.8% vs. 5.1%, p log-rank<0.01). Elevated UA was independently linked to a higher incidence of MACCEs, whether UA was treated as a categorical or continuous variable (hazard ratio [HR] 2.76, 95% confidence interval [CI] 1.27-6.03 or HR 1.01, 95% CI 1.01-1.02). The restricted cubic spline (RCS) analysis illustrated that the HR for MACCEs increased with increasing UA., Conclusion: The present study demonstrates that UA is associated with MACCEs risk and suggests that UA is a reliable predictor of long-term cardiovascular events in coronary intermediate stenosis patients., Competing Interests: Declaration of competing interest Authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Evidence has indicated that serum uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) are positively and negatively associated with coronary artery disease (CAD). The UA to HDL-C ratio (UHR) has recently drawn attention as a new predictor for metabolic syndrome, inflammation and atherosclerosis. However, the association between the UHR and CAD in nondialysis chronic kidney disease (CKD) patients is still unclear., Methods and Results: We retrospectively analysed 733 nondialysis patients with CKD stage 3-5 who received their first coronary artery angiography (CAG), including 510 participants with CAD. All laboratory indicators were collected within one week before CAG. The median UHR of CAD and non-CAD patients was 15.52% and 12.29%, respectively. In multivariate analysis, female patients with a high UHR were 4.7 times more at risk of CAD than those with a lower UHR. Meanwhile, the positive association of the UHR with the severity of coronary artery stenosis (CAS) persisted significantly in female CAD subjects but not in males. In addition, receiver operating characteristic (ROC) curves were constructed for CAD and severe CAS. The area under the curve (AUC) for the UHR was higher than that for UA and HDL-C alone in female patients [UHR (AUC): 0.715 for CAD and 0.716 for severe CAS]., Conclusions: An elevated UHR was independently related to an increased CAD risk and the severity of CAS in nondialysis female patients with CKD stage 3-5, and was more predictive of the onset of CAD and the severity of CAS than UA or HDL-C alone., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Lp-PLA2 is linked to cardiovascular diseases and poor outcomes, especially in diabetes, as it functions as a pro-inflammatory and oxidative mediator., Objectives: This research aimed to explore if there is a connection between the serum levels of Lp-PLA2 and the progression of coronary plaques (PP) in individuals with type 2 diabetes mellitus (T2DM) and those without the condition., Materials and Methods: Serum Lp-PLA2 levels were measured in 137 T2DM patients with PP and 137 T2DM patients with no PP, and in 205 non-diabetic patients with PP and 205 non-diabetic patients with no PP. These individuals met the criteria for eligibility and underwent quantitative coronary angiography at the outset and again after about one year of follow-up. The attributes and parameters of the participants at the outset were recorded., Results: Increased serum levels of Lp-PLA2 were closely associated with coronary artery PP, and also significantly correlated with change of MLD, change of diameter stenosis and change of cumulative coronary obstruction in both diabetic and non-diabetic groups, with higher correlation coefficients in diabetic patients as compared with non-diabetic patients. Moreover, multivariate logistic regression analysis showed that serum Lp-PLA2 level was an independent determinant of PP in both groups, with OR values more significant in diabetic patients than in non-diabetic patients., Conclusions: Levels of serum Lp-PLA2 show a significant association with the progression of coronary atherosclerotic plaque in patients with T2DM and those without, especially among individuals with diabetes., (© 2024. The Author(s).)

Background: Long noncoding RNA GAS5 (lnc-GAS5) and its target microRNA-21 (miR-21) regulate blood lipid, macrophages, Th cells, vascular smooth muscle cells to participate in atherosclerosis, and related coronary heart disease (CHD). The study aimed to further explore the linkage of their circulating expressions with common biochemical indexes, stenosis severity and inflammatory cytokines in CHD patients., Methods: Ninety-eight CHD patients and 100 controls confirmed by coronary angiography were enrolled. Plasma samples were collected for lnc-GAS5 and miR-21 detection by reverse transcription-quantitative polymerase chain reaction and inflammatory cytokines determination by enzyme-linked immunosorbent assay., Results: Lnc-GAS5 was increased in CHD patients compared with controls (2.270 (interquartile range [IQR]: 1.676-3.389) vs. 0.999 ([IQR: 0.602-1.409], p < 0.001), whereas miR-21 showed opposite tread (0.442 [IQR: 0.318-0.698] vs. 0.997 [IQR: 0.774-1.368], p < 0.001). In aspect of their intercorrelation, lnc-GAS5 negatively linked with miR-21 in CHD patients (p < 0.001) instead of controls (p = 0.211). Interestingly, among the common biochemical indexes, lnc-GAS5 related to decreased high-density lipoprotein cholesterol (p = 0.008) and increased C-reactive protein (CRP) (p < 0.001), while miR-21 correlated with lower total cholesterol (p = 0.024) and CRP (p < 0.001) in CHD patients. As stenosis degree, lnc-GAS5 positively correlated with Gensini score (p < 0.001), but miR-21 exhibited negative association (p = 0.003) in CHD patients. In terms of inflammatory cytokines, lnc-GAS5 positively related to tumor necrosis factor α (TNF-α) and interleukin (IL)-17A, while miR-21 negatively linked with TNF-α, IL-1β, IL-6, and IL-17 in CHD patients (all p < 0.05)., Conclusion: Circulating lnc-GAS5 and its target miR-21 exhibit potency to serve as biomarkers for CHD management., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: The expression and clinical significance of IL-20 in coronary artery diseases needs to be analyzed. Methods: IL-20 and its receptors were analyzed in coronary artery tissues. In a separate study, plasma IL-20 was also evaluated. Results: IL-20 and its receptors were significantly higher in coronary artery stenosis tissues from ischemic cardiomyopathy patients than that from controls. T lymphocytes and macrophages were the main source of IL-20 and expressed its receptors abundantly. Plasma IL-20 was significantly higher in acute myocardial infarction patients than that in controls. Conclusion: IL-20 was closely associated with the presence of acute myocardial infarction. IL-20 may participate in the progression of coronary artery stenosis and plaque vulnerability via regulating T lymphocytes and macrophages.

Introduction: The inflammatory hypothesis of atherosclerosis is appealing in acute coronary syndromes, but the dynamics and precise role are not established., Objectives: The study investigates the levels of C reactive protein (CRP), interleukin 1β (IL-1β) and stromal-derived factor 1α (SDF-1α) at the time of acute myocardial infarction (AMI) and at 1 and 6 months afterwards, compared with a control group., Results: In the acute phase of AMI, CRP and SDF-1α were significantly higher, while IL-1β showed lower levels compared with controls. CRP positively correlated with coronary stenosis severity (rho = 0.3, p =.05) and negatively related with left ventricle ejection fraction (LVEF) at 1 month (rho= -0.43, p =.05). IL-1β weakly correlated with the severity of coronary lesions (rho =0.29, p =.02) and strongly with LVEF (rho= -0.8, p =.05). SDF-1α, slightly correlated with LVEF at 1 month (rho = 0.22, p =.01) and with the severity of coronary atherosclerosis (rho= -0.41, p =.003)., Conclusions: CRP, IL-1β and SDF-1α have important dynamic in the first 6 months after AMI and CRP and SDF-1α levels correlated with the severity of coronary lesions and LVEF at 1 month after the acute ischaemic event.

Background: We investigated the role of ANGPTL3 and ANGPTL4 in atherosclerosis development and determined whether plasma concentrations of ANGPTL3 and ANGPTL4 are related to the degree of coronary stenosis., Methods: A total of 305 consecutive patients with angina who underwent diagnostic coronary angiography were enrolled in the study between August 2017 and August 2018. The levels of ANGPTL3 and ANGPTL4 were measured by using competitive ELISA kits., Results: According to the degree of coronary artery stenosis, patients were classified into four types: coronary artery stenosis of < 10%, 10-50%, 50-75, and > 75%. The plasma ANGPTL3 level was higher (51.71 ± 52.67 vs. 24.65 ± 10.32 ng/mL, P < 0.001) and that of ANGPTL4 was lower (454.66 ± 269.05 vs. 875.49 ± 961.15 ng/mL, P < 0.001) in the coronary artery stenosis ≥ 10% group than in the < 10% group. ANGPTL3 and ANGPTL4 levels were significantly associated with the severity of coronary vascular stenosis. ROC curve analyses indicated that ANGPTL3 concentrations above 30.5 ng/mL can predict atherosclerosis with a sensitivity of 71.2% and specificity of 75.3%, and that ANGPTL4 levels below 497.5 ng/mL can predict atherosclerosis with a sensitivity of 63.9% and specificity of 74.5%. ANGPTL3 and ANGPTL4 were determined to be independent risk factors for coronary atherosclerosis with odds ratios (ORs) of 0.189 (95% CI 0.097-0.368, P < 0.001) and 3.625 (95% CI 1.873-7.016, P < 0.001), respectively., Conclusions: Increased ANGPTL3 or decreased ANGPTL4 shows an association with coronary atherosclerosis and, may become a predictor of coronary atherosclerosis in the future., (© 2021. The Author(s).)

Coronary bifurcations are prone to atherosclerotic plaque growth, experiencing regions of reduced wall shear stress (WSS) and increased platelet adhesion. This study compares effects across different rheological approaches on hemodynamics, combined with a shear stress exposure history model of platelets within a stenosed porcine bifurcation. Simulations used both single/multiphase blood models to determine which approach best predicts phenomena associated with atherosclerosis and atherothrombosis. A novel Lagrangian platelet tracking model was used to evaluate residence time and shear history of platelets indicating likely regions of thrombus formation. Results show a decrease in area of regions with pathologically low time-averaged WSS with the use of multiphase models, particularly in a stenotic bifurcation. Significant non-Newtonian effects were observed due to low-shear and varying hematocrit levels found on the outer walls of the bifurcation and distal to the stenosis. Platelet residence time increased 11% in the stenosed artery, with exposure times to low-shear sufficient for red blood cell aggregation (>1.5 s). increasing the risk of thrombosis. This shows stenotic artery hemodynamics are inherently non-Newtonian and multiphase, with variations in hematocrit (0.163-0.617) and elevated vorticity distal to stenosis (+15%) impairing the function of the endothelium via reduced time-averaged WSS regions, rheological properties and platelet activation/adhesion., Competing Interests: The authors have declared that no competing interests exist.

Background: The current study was conducted to explore the effects of chemerin and homocysteine (Hcy) levels and their associations with the occurrence and development of ischemic cerebrovascular disease (ICVD)., Methods: There involved a total of 187 patients with ICVD and 190 healthy people for physical examination in Cangzhou Central hospital from January 2020 to April 2021. The participants enrolled were divided into four groups based on the digital subtraction angiography: mild stenosis group (64 cases, stenosis rate 30-49 %), moderate stenosis group (72 cases, stenosis rate 50-69 %), severe stenosis group (51 cases, stenosis rate 70-99 %) and control group (190 cases, in healthy condition). The laboratory indexes of ICVD group and control group were observed and the four groups were further compared. Pearson linear correlation was applied to analyze the link between chemerin and Hcy levels and the degree of cerebral vascular stenosis in ICVD patients, and multivariate logistic regression was used to analyze the influencing factors of ICVD., Results: No significant difference was found in general information including age, gender, body mass index (BMI), heart rate, systolic blood pressure, diastolic blood pressure, smoking and drinking between the two groups (P > 0.05). Moreover, there was no significant difference in fasting blood glucose (FBG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) levels between the two groups (P > 0.05). However, the levels of triglyceride (TG), low density lipoprotein cholesterol (LDL-C), chemerin and Hcy in ICVD group were significantly higher than those in control group (P < 0.05). When comparing the four groups, there was no significant difference in FBG and TC levels (P > 0.05). The levels of TG, LDL-C, chemerin and Hcy in mild, moderate and severe stenosis groups were higher than those in control group, the above levels in moderate and severe stenosis group were higher than those in mild stenosis group, and severe stenosis group higher than moderate stenosis group (P < 0.05). Chemerin and Hcy levels were positively correlated with the degree of cerebral vascular stenosis in ICVD patients (r = 0.612, 0.519, P < 0.001). ICVD was regarded as the dependent variable, and the abovementioned general data as well as significant laboratory indicators, including TG, LDL-C, chemerin and Hcy, as independent variables. The results of multivariate logistic regression analysis revealed that TG, LDL-C, chemerin and Hcy were independent influencing factors of ICVD., Conclusions: Chemerin and Hcy levels exerted a close link to the occurrence and development of ICVD as independent influencing factors., (© 2021. The Author(s).)

Abstract: We explored the protective effect of spironolactone on cardiac function in the patients undergoing coronary artery bypass grafting (CABG) by determining serum hypoxia-inducible factor-1α (HIF-1α) before and after CABG. We used the propensity score matching method retrospectively to select 174 patients undergoing CABG in our hospital from March 2018 to December 2019. Of the 174 patients, 87 patients taking spironolactone for more than 3 months before CABG were used as a test group and other 87 patients who were not taking spironolactone as a control group. In all patients, serum HIF-1α and troponin I levels were determined before as well as 24 hours and 7 days after CABG, serum N-terminal probrain natriuretic peptide (NT-proBNP) level was determined before as well as 12, 24, and 36 hours after CABG, and electrocardiographic monitoring was performed within 36 hours after CABG. The results indicated that there were no significant differences in the HIF-1α level between the test group and the control group before and 7 days after CABG, but the HIF-1α level was significantly lower in the test group than that in the control group 24 hours after CABG (P < 0.01). The 2 groups were not significantly different in the troponin I level at any time point. There was no significant difference in the serum NT-proBNP level between the test group and the control group before CABG, but NT-proBNP (BNP) levels were all significantly lower in the test group than those in the control group at postoperative 12, 24, and 36 hour time points (all P <0.05). The incidence of postoperative atrial fibrillation was also significantly lower in the test group than that in the control group (P = 0.035). Spironolactone protects cardiac function probably by improving myocardial hypoxia and inhibiting myocardial remodeling., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aims/introduction: Glucose fluctuation (GF) is a residual risk factor for coronary artery disease (CAD). We investigated whether GF influenced clinical outcomes and progression of coronary stenosis in stable CAD patients., Materials and Methods: In this prospective study, 101 consecutive lipid-controlled stable CAD patients underwent percutaneous coronary intervention were enrolled, and GF was expressed as the mean amplitude of glycemic excursion (MAGE) obtained by continuous glucose monitoring before the procedure was evaluated. At 9 months after enrollment, culprit and non-culprit (mild-to-moderate stenosis without ischemia) lesions were serially assessed by angiography. Cardiovascular events (CVE) consisting of cardiovascular death, non-fatal myocardial infarction or ischemia-driven revascularization during 2-year follow up, rapid progression in non-culprit lesions (defined as ≥10% luminal narrowing progression in lesions with stenosis ≥50%, ≥30% luminal narrowing progression in non-culprit lesions with stenosis <50% or normal segment, or progression to total occlusion) were evaluated., Results: CVE occurred in 25 patients, and MAGE was significantly higher in the CVE group (76.1 ± 24.8 mg/dL vs 59.3 ± 23.7 mg/dL; P = 0.003). Multivariate analysis showed that MAGE was an independent predictor of CVE (odds ratio 1.027, 95% confidence interval 1.008-1.047; P = 0.005). The optimal MAGE value to predict CVE was 70.7 mg/dL (area under the curve 0.687, 95% confidence interval 0.572-0.802; P = 0.005). Furthermore, MAGE was independently associated with rapid progression, and with the luminal narrowing progression in all non-culprit lesions (r = 0.400, P < 0.05)., Conclusions: Daily GF might influence future CVE in lipid-controlled stable CAD patients., (© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Proprotein convertase subtilisin/kexin type 9 (Pcsk9) correlated with incidence and prognosis of coronary heart disease. However, it is unclear whether Pcsk9 contributed to coronary artery lesion severity in patients with premature myocardial infarction (PMI). The present study investigated associations between Pcsk9 and coronary artery lesion severity in PMI patients who underwent coronary angiography (CAG)., Methods: This prospective cohort study included young men (age ≤ 45 years, n = 332) with acute MI who underwent CAG between January 2017 and July 2019. Serum Pcsk9 levels and clinical characteristics were evaluated. SYNTAX scores (SYNergy between percutaneous coronary intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) were calculated to quantify coronary artery lesions., Results: Serum Pcsk9 levels were positively associated with SYNTAX scores (r = 0.173, P < 0.05). The diagnostic cutoff value of PSCK9 level was 122.9 ng/mL, yielding an area under the curve (AUC) of 0.63, sensitivity 81%, and specificity 40%. Serum Pcsk9, LDL-C, Apob, NT-proBnp, CK level, and diabetes history were independent predictors of high SYNTAX scores (P < 0.05). After stratifying by serum LDL-C level (cutoff = 2.6 mmol/L), medium-high Pcsk9 levels had increased risk of high SYNTAX scores in patients with high LDL-C (P < 0.05), and higher serum Pcsk9 levels had increased risk of major adverse cardiac events (MACE) after adjusting for confounding factors (P < 0.05)., Conclusion: Serum Pcsk9 levels correlates with severity of coronary artery lesion in PMI patients and may serve as a biomarker for severity of coronary artery stenosis in this patient population, which may contribute to risk stratification.

Background: Emerging evidence demonstrates that the lipid metabolism in acute coronary syndrome (ACS) patients with type 2 diabetes mellitus (T2DM) differs from nondiabetic patients. However, the distinct lipid profiles and their relationships with the severity of coronary artery stenosis and prognosis in patients with T2DM remain elusive., Method and Result: This single-center, prospective cohort study enrolled 468 patients diagnosed with ACS undergoing coronary angiography, consisting of 314 non-DM and 154 DM patients. The HDL-C/apoA-I ratio was significantly higher in DM patients with a multivessel (≥3 affected vessels) lesion than a single-vessel (1-2 affected vessels) lesion. Regression analyses showed that the HDL-C/apoA-I ratio was positively correlated to the number of stenotic coronary arteries in DM patients but not non-DM patients. However, Kaplan-Meier survival analysis revealed no significant difference in the major adverse cardiovascular event rate regarding different HDL-C/apoA-I levels in DM or non-DM ACS patients at the end of the 2-year follow-up., Conclusion: A higher HDL-C/apoA-I ratio is associated with increased severity of coronary artery stenosis in DM patients with ACS but not with the rate of major adverse cardiovascular events at the end of the 2-year follow-up., Competing Interests: There is no conflict of interest regarding the publication of this article., (Copyright © 2021 Lizhe Sun et al.)

Background and Aims: Novel genetic determinants associated with coronary artery disease (CAD) have been discovered by genome wide association studies. Variants encompassing the CELSR2- PSRC1-SORT1 gene cluster have been associated with CAD. This study is aimed to investigate the rs629301 polymorphism association with the extent of CAD evaluated by coronary angiography (CAG), and to evaluate its associations with an extensive panel of lipid and lipoprotein measurements in a large Italian cohort of 2429 patients., Methods and Results: The patients were collected by four Intensive Care Units located in Palermo and Verona (Italy). Clinical Records were filed, blood samples were collected, lipids and apolipoproteins (apo) were measured in separate laboratories. CAD was defined by the presence of stenotic arteries (>50% lumen diameter) by CAG. The presence of CAD was associated with the rs629301 genotype. Patients with CAD were 78% and 73% (p = 0.007) of the T/T vs. T/G + G/G genotype carriers respectively. T/T genotype was also correlated with the number of stenotic arteries, with a 1.29 (1.04-1.61) risk to have a three-arteries disease. T/T genotype correlated with higher levels of LDL-, non-HDL cholesterol, apoB, apoE and apoCIII, and lower HDL-cholesterol. Logistic Regression confirmed that rs629301was associated with CAD independently from the common risk factors, with a risk similar to that conferred by ten years of age [odds ratios were 1.43 (1.04-1.96) and 1.39 (1.22-1.58) respectively]., Conclusions: rs629301 risk allele was independently associated with the extension and severity of CAD and positively with apoE and apoB containing lipoproteins., Competing Interests: Declaration of competing interest The authors have no conflict of interests to declare., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Abstract: Coronary artery disease (CAD) and associated comorbidities such as heart failure (HF) remain the leading cause of morbidity and mortality worldwide attributed to, at least partially, the lack of biomarkers for efficient disease diagnosis. Here, we evaluated the diagnostic potential of serum peptidoglycan recognition protein 1 (PGLYRP1), an important component of the innate immunity and inflammation system, for both CAD and HF. A machine-learning method (random forest) was used to evaluate the clinical utility of circulating PGLYRP1 for diagnosis of CAD and HF in a total of 370 individuals. Causal links of chronic serum PGLYRP1 elevation to both diseases were further explored in ApoE-/- mice. The serum levels of PGLYRP1 were significantly higher in individuals with either chronic CAD or acute coronary syndrome than those in those without coronary artery stenosis (the control group) and even more pronounced in CAD individuals with concomitant HF. Our random forest classifier revealed that this protein performed better than other recommended clinical indicators in distinguishing the CAD from the control individuals. In addition, this protein associates more with the biomarkers of HF including left ventricular ejection fraction than inflammation. Notably, our mice experiment indicated that long-term treatment with recombinant PGLYRP1 could significantly impair the cardiovascular system as reflected from both increased atherogenic lesions and reduced fractional shortening of the left ventricle. Our findings, therefore, supported the circulating levels of PGLYRP1 as a valuable biomarker for both CAD and HF., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Previous studies showed that troponin blood levels may increase after exercise. In this study, we assessed whether, among patients with suspected of having stable angina, the increase in troponin I (TnI) levels after exercise stress test (EST) might help identify those with obstructive coronary artery disease (CAD) and myocardial ischemia., Methods: We performed maximal treadmill EST in 50 patients (age 64 ± 9 years; 38 men) admitted to our Cardiology Department to undergo elective coronary angiography because of a suspicion of stable angina. TnI was measured before and 12 h after EST., Results: TnI increased after EST compared with baseline in the whole population (from 0.44 ± 0.76 to 0.84 ± 1.12 ng/dl, P < 0.001). No difference in TnI increase was observed between patients with obstructive CAD (n = 29; 0.61 ± 0.90-1.13 ± 1.33 ng/dl) and no obstructive CAD (NO-CAD; n = 21; 0.21 ± 0.46-0.44 ± 0.54 ng/dl; P = 0.51). There was also no significant difference in post-EST TnI increase between patients with positive EST (n = 34; 0.56 ± 0.89-1.05 ± 1.28 ng/dl) or negative EST (n = 16; 0.19 ± 0.26-0.39 ± 0.43 ng/dl; P = 0.16). Moreover, no significant difference was observed in the post-EST TnI increase among groups of patients with positive EST and obstructive CAD, positive EST and NO-CAD, negative EST and obstructive CAD and negative EST and NO-CAD (P = 0.12). No clinical or EST variable was associated with post-EST TnI increase, although there was a tendency for a greater increase in those achieving a heart rate more than 85 vs. less than 85% of maximal predicted heart rate during EST (P = 0.075)., Conclusion: TnI increase after EST in patients with suspected stable angina is largely independent of the results of coronary angiography and EST., (Copyright © 2020 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Cardiovascular events can occur after deferred revascularization, and malondialdehyde-modified low-density lipoprotein (MDA-LDL) has been suggested to be an atherogenic marker. We investigated the relationship between serum MDA-LDL levels and clinical outcomes in patients with fractional flow reserve (FFR)-guided deferral of revascularization. Among 3084 patients undergoing coronary angiography, we retrospectively analyzed 127 patients with intermediate stenosis and deferred revascularization based on FFR > 0.80. Median follow-up interval was 30.4 months, and serum MDA-LDL was measured prior to the measurement of FFR. We evaluated the composite of major adverse cardiac events (MACEs), including cardiac death, myocardial infarction, ischemia-driven deferred lesion revascularization, and any revascularization. MACEs occurred in 18 (14.2%) patients. The MACE group presented with significantly higher MDA-LDL levels than the non-MACE group (134.9 ± 33.3 U/L vs. 95.6 ± 32.2 U/L, P < 0.001). In analysis of the receiver operating characteristics curve for the prediction of MACEs, MDA-LDL presented a significantly larger area under the curve than low-density lipoprotein-cholesterol (LDL-C; 0.810 vs. 0.687, P = 0.042). Univariate Cox regression analysis indicated a significant relationship between MACEs and MDA-LDL (per 10 U/L, HR 1.20; P = 0.004), as did the multivariate model (per 10 U/L, HR 1.17; P = 0.019). When compared according to the median LDL-C (98 mg/dL), the MACE group had significantly higher MDA-LDL in both the high (147.2 ± 27.3 U/L vs. 113.9 ± 31.2 U/L, P = 0.001) and low (103.2 ± 27.3 U/L vs. 80.2 ± 24.0 U/L, P = 0.045) LDL-C groups. Serum MDA-LDL levels were associated with cardiac events in patients with deferral of revascularization based on FFR.

The coronary artery disease (CAD) is a chronic inflammatory disease caused by atherosclerosis, in which arteries become clogged due to plaque formation, fat accumulation, and various sorts of immune cells. IL-32 is a proinflammatory cytokine, which enhances inflammation through inducing the secretion of different inflammatory cytokines. The main objective of the current study was to assess the serum levels of IL-32 in subjects with obstructive CAD and its relationship with the serum levels of IL-6 and TNF-α. This study was performed on 42 subjects with obstructive CAD and 42 subjects with non-obstructive CAD. The serum levels of TNF-α, IL-6, and IL-32 were measured using the enzyme-linked immunosorbent assay (ELISA). The serum levels of TNF-α, IL-6, and IL-32 were 3.2, 3.48, and 2.7 times higher in obstructive CAD compared to non-obstructive CAD, respectively. Moreover, the serum levels of TNF-α and IL-32 in obstructive CAD with cardiac arterial stenosis in one major vessel were significantly higher than the levels in obstructive CAD with cardiac arterial stenosis in more than one major vessel. ROC curve analysis revealed that the serum levels of TNF-α, IL-6, and IL-32 were good predictors of obstructive CAD. Moreover, multiple logistic regression analyses suggested that the serum levels of TNF-α, IL-6, IL-32, LDL, and ox-LDL were independently related to the presence of obstructive CAD, while serum levels of HDL were not. TNF-α, IL-32, and IL-6 showed an increase in obstructive CAD, and the serum levels of these cytokines showed a satisfactory ability for predicting obstructive CAD.

Introduction: Aim of this study is to evaluate whether magnetic particle imaging (MPI) is capable of measuring velocities occurring in the coronary arteries and to compute coronary flow reserve (CFR) in a canonical phantom as a preliminary study., Methods: For basic velocity measurements, a circulation phantom was designed containing replaceable glass tubes with three varying inner diameters, matching coronary-vessel diameters. Standardised boluses of superparamagnetic-iron-oxide-nanoparticles were injected and visualised by MPI. Two image-based techniques were competitively applied to calibrate the respective glass tube and to compute the mean velocity: full-duration-at-half-maximum (FDHM) and tracer dilution (TD) method. For CFR-calculation, four necessary settings of the circulation model of a virtual vessel with an inner diameter of 4 mm were generated using differently sized glass tubes and a stenosis model. The respective velocities in stenotic glass tubes were computed without recalibration., Results: On velocity level, comparison showed a good agreement (rFDHM = 0.869, rTD = 0.796) between techniques, preferably better for 4 mm and 6 mm inner diameter glass tubes. On CFR level MPI-derived CFR-prediction performed considerably inferior with a relative error of 20-44%., Conclusions: MPI has the ability to reliably measure coronary blood velocities at rest as well as under hyperaemia and therefore may be suitable for CFR calculation. Calibration-associated accuracy of CFR-measurements has to be improved substantially in further studies., Competing Interests: The authors have declared that no competing interests exist.

Abstract: Cardiovascular disease (CAD) is a devastating illness, but to date there are limited means of predicting a person's coronary stenosis severity and their prognosis. The study was performed to investigate the relationship between dipeptidyl peptidase 4(DPP4) gene polymorphisms and serum lipid profiles, as well as the severity of coronary artery stenosis in patients with CAD and type 2 diabetes (T2DM) for the first time.Herein, 201 patients with CAD and T2DM were enrolled in the Department of Cardiology, Shandong Provincial Qianfoshan Hospital. DPP4 rs3788979 and rs7608798 single nucleotide polymorphisms (SNPs) were genotyped. The general information of all patients was collected, and the associations between DPP4 SNPs and lipid profiles were detected. At the same time, association between SNP polymorphisms and the degree of coronary artery stenosis were analyzed.There was a significant difference in apolipoprotein B (ApoB) levels (P = .011) for the rs3788979 polymorphism, while no difference was identified in other blood lipids or with other mutations. SNP mutation of A to G in rs3788979 was associated with a reduced percentage of severe coronary artery stenosis in female patients (P = .023) as well as those with nosmoking (P = .030), nodrinking (P = 0.007), and nocardiovascular family history (P = 0.015).G allele of rs3788979 is associated with a reduced ApoB level. Besides, we suggest that G allele in rs3788979 may have a cardioprotective effect and prove to be a useful and specific measure when predicting a patient's coronary stenosis severity if diagnosed with CAD and T2DM., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Evidence reveals that microRNA (miRNA) can predict coronary restenosis in patients suffering from coronary heart disease (CHD) after percutaneous coronary intervention (PCI). Perhaps, miRNA-21 is a promising biomarker for the diagnosis of coronary restenosis after PCI. However, the accuracy of miRNA-21 has not been systematically evaluated. Therefore, it is necessary to perform meta-analysis to certify the diagnostic values of miRNA-21 on coronary restenosis after PCI., Methods: China National Knowledge Infrastructure, Wanfang, VIP, and China Biology Medicine disc, PubMed, EMBASE, Cochrane Library, and Web of Science were searched for relevant studies to explore the potential diagnostic values of miRNA-21 on coronary restenosis after PCI from inception to January 2021. All data were extracted by 2 experienced researchers independently. The risk of bias about the meta-analysis was confirmed by the Quality Assessment of Diagnostic Accuracy Studies-2. The data extracted were synthesized and heterogeneity was investigated as well. All of the above statistical analyses were carried out with Stata 16.0., Results: This study proved the pooled diagnostic performance of miRNA-21 on coronary restenosis after PCI., Conclusion: This study clarified confusions about the specificity and sensitivity of miRNA-21 on coronary restenosis after PCI, thus further guiding their promotion and application., Ethics and Dissemination: Ethical approval is not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. This review would be disseminated in a peer-reviewed journal or conference presentations., Osf Registration Number: DOI 10.17605/OSF.IO/356QK., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Lipid and inflammatory molecules play a key role in the development of inflammation. Neutrophil counts are used as markers of inflammation duration, and HDL-C is used as an anti-atherosclerosis component. However, few studies have been found to integrate these two indicators to explore coronary stenosis. We suggested that neutrophil count as a marker of inflammation persistence and HDL-C as an anti-atherosclerotic component should be integrated into a single biomarker NHR to explore its correlation with CAD degree and predict the severity of coronary stenosis among CAD patients., Methods: We examined 404 eligible patients who underwent coronary angiography. Based on the results of coronary angiography, patients in CAD + group (n = 155) were defined as those having angiographic coronary stenosis of at least 50% lumen reduction in at least one major coronary artery (including left anterior descending artery, left circumflex artery, left main coronary artery, right coronary artery). Patients with luminal stenosis but no more than 50% were defined as CAD - group (n = 49), and patients without luminal stenosis (n = 200) were regarded as control group. The relationship between various serum markers and the severity of coronary stenosis was examined by Spearman correlation analysis. Logistic regression analysis was performed to identify the influencing factors of the severity of coronary artery disease., Results: The modified Gensini score was positively correlated with neutrophil HDL-C ratio and negatively correlated with albumin and HDL-C. Multiple regression analysis showed that neutrophil HDL-C ratio were significantly associated with CAD. Neutrophil HDL-C ratio is an independent predictor of CAD. The ROC analysis provided a cut-off value of 1.51 for neutrophil HDL-C ratio to predict CAD with 94.8% sensitivity and 0.024 Yoden index, and area under the ROC curve of 0.617 (95% CI 0.560-0.675, P < 0.001)., Conclusion: Neutrophil HDL-C ratio is not only closely related to coronary artery stenosis, but also an independent predictor of severe coronary stenosis.

Background: ATP-binding cassette transporter A1 (ABCA1) plays a major role in high-density lipoprotein (HDL) metabolism and reverse cholesterol transport (RCT) and exerts anti-inflammatory effects. Increased ABCA1 promoter methylation level may result in the progression of coronary artery disease. Thus, the present study investigated the association between promoter methylation status of ABCA1 and inflammation in the development of premature coronary artery disease (pCAD)., Methods: PCAD patients and healthy individuals (n = 90 each) were recruited from the Characteristic Medical Center of the Chinese People's Armed Police Force from June to December 2019. Using pyrosequencing, the levels of ABCA1 promoter methylation in their blood samples were evaluated. Serum concentrations of lipids, interleukin 1β (IL-1β), C-reactive protein (CRP), and circulating free DNA/Neutrophil extracellular traps (cfDNA/NETs) were also routinely measured and compared between the two groups. P values < 0.05 were considered statistically significant., Results: The mean ABCA1 promoter methylation levels were significantly higher in the pCAD group than in the control group (44.24% ± 3.66 vs. 36.05% ± 2.99, P < 0.001). Based on binary logistic regression analysis, ABCA1 promoter methylation level was identified as an independent risk factor for pCAD development (odds ratio = 2.878, 95% confidence interval: 1.802-4.594, P < 0.001). Furthermore, ABCA1 promoter methylation levels were negatively correlated with HDL levels (r =  - 0.488, P < 0.001) and positively correlated with the levels of CRP, cfDNA/NETs, and IL-1β (r = 0.389, 0.404, 0.385, respectively; P < 0.001). Multiple regression analysis showed that the serum levels of CRP, IL-1β, and cfDNA/NETs independently affect ABCA1 promoter methylation., Conclusions: Our findings indicate that high methylation levels at the ABCA1 promoter are associated with low HDL cholesterol levels and an increased risk of pCAD. Inflammatory factors and NETs may be involved in the progression of pCAD by affecting ABCA1 promoter methylation levels.

Background: Lp(a) and LDL-C are both risk factors of atherosclerotic cardiovascular disease (ASCVD). But there was a contradiction point in LDL-C and Lp(a) control. The appropriate level of LDL-C and Lp(a) in the prevention of ASCVD is still pending., Objective: To investigate the correlation of Lp(a) and coronary atherosclerotic lesion, and find out the balance point in LDL-C and Lp(a) control., Method: 3449 patients were divided to coronary atherosclerotic heart disease (CAHD) Group and Non-CAHD Group based on the result of coronary angiography. The clinical characteristics were compared, and Logistic regressions were applied to find the CAHD risk factors in total, High-LDL-C Group (LDL-C ≥ 100 mg/dL) and Low-LDL-C Group (LDL-C < 100 mg/dL) patients. Spearman correlation analysis of Lp(a), LDL-C and Gensini Score was performed in patients with different LDL-C concentration., Results: Except male and diabetes, the traditional CAHD risk factors were well matched between two groups. But triglyceride, LDL-C and Lp(a) were higher, HDL-C and Apo-A1 were lower in CAHD group (2771). In the Logistic regression analysis, diabetes, LDL-C and Lp(a) are risk factors of CAHD in all patients, while in High-LDL-C Group, they were age, LDL-C, non-HDL-C and ApoB, in Low-LDL-C Group, they were age, Lp(a) and ApoB. Lp(a) correlated with Gensini with coefficient r = 0.41 in all patients, 0.67 in Low-LDL-C Group and 0.32 in High-LDL-C Group. The coefficient r for Lp(a) and Gensini decreased, while the r for LDL-C and Gensini increased with LDL-C concentration increasing. The two fitted lines of rs crossed at LDL-C = 2.7 mmol/L (104 mg/dL)., Conclusion: Lp(a) was the risk factor of CAHD in patients with LDL-C < 100 mg/dL. The correlation between Lp(a) and Gensini was influenced by LDL-C concentration, and the correlation was stronger than LDL-C when LDL-C < 104 mg/dl.

Background: The present study aimed to assess the correlation of fibroblast growth factor (FGF)-23 expression with clinical characteristics, then further explore its value in predicting 2-year in-stent restenosis (ISR) risk in coronary heart disease (CHD) patients underwent percutaneous coronary intervention (PCI) with drug-eluting stent (DES)., Methods: In this prospective, single-center, observational study, totally 214 CHD patients treated by PCI with DES were consecutively recruited, and peripheral blood samples were collected prior to PCI with DES for serum samples isolation. Following, FGF-23 level in the serum samples was detected via enzyme linked-immuno-sorbent Assay. The follow-up coronary angiography was performed at 1 year and 2 years after PCI or if suspected ISR symptoms occurred., Results: FGF-23 was positively correlated with fasting blood-glucose, insulin resistance, serum creatinine, serum uric acid, LDL-C, high-sensitivity C-reactive protein, cardiac troponin I and N-terminal-proB-type natriuretic peptide, while was negatively associated with HDL-C and left ventricular ejection fraction (all P < 0.01). Furthermore, FGF-23 was positively correlated with hypercholesteremia, hyperuricemia and family history of CAD (all P < 0.05). However, it did not correlate with other chronic complications, biochemical indexes, lesion features or PCI parameters (all P > 0.05). Moreover, FGF-23 level was higher in 2-year ISR patients (n = 38) compared to 2-year non-ISR patients (n = 176) (P < 0.001), and receiver operating characteristic curve indicated that FGF-23 was of good value in predicting 2-year ISR risk (AUC 0.828, 95% CI 0.761-0.896)., Conclusion: FGF-23 correlates with endocrine and metabolism dysregulation, worse cardiac and renal function, inflammation level, stenosis degree of target lesion, and serves as an independent risk factor for 2-year ISR risk in CHD patients underwent PCI with DES.

Introduction: Coronary artery disease (CAD) is an ischemic heart disease due to the narrowing of the coronary arteries resulting from atherosclerosis. Blood biomarkers have been well utilized for the diagnosis and prognosis of CAD. However, the value of biomarkers for evaluating coronary atherosclerosis remains to be clarified. This clinical investigation aimed to explore the potential value of biomarkers for evaluating the severity of coronary stenosis in CAD patients., Methods: The extent of coronary atherosclerosis was accessed by the angiography-based quantitative measurement Gensini score (GS). Blood levels of Brain natriuretic peptide, Copeptin (CPP), Phosphodiesterase 9A, and Pentraxin3 (PTX3) were measured in 56 patients divided into three levels as low GS (n = 17), intermediate GS (n = 19) and high GS (n = 20) based on GS tertiles., Results: We found that plasma concentrations of CPP and PTX3 were significantly elevated in patients with high GS compared with the low GS group. In addition, Pearson correlation analysis showed that CPP and PTX3 were positively correlated with the GS. Furthermore, Receiver operating characteristics analysis demonstrated that both CPP and PTX3 exhibited discriminative capacities for evaluating the extent of coronary stenosis., Conclusions: Laboratory tests of CPP and PTX3 via non-invasive means may provide novel information for risk stratification and disease management in CAD patients before invasive angiographic approaches. This study opens the door for enormous opportunities to explore new biomarkers with better efficiency, sensitivity and specificity as alternative/additional methods for evaluating the severity of coronary atherosclerosis in CAD patients in future research., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Dickkopp-3 (DKK3) has been identified to play a protection role against atherosclerosis. However, little is known about the relationship between serum DKK3 levels and subclinical coronary atherosclerosis. We aimed to investigate the association of serum DKK3 with coronary stenosis in an asymptomatic Chinese population. A total of 550 Chinese adults aged 40-60 years and without symptoms or histories of cardiovascular diseases were randomly selected to undergo coronary computed tomography angiography. We defined ≥ 50% luminal narrowing as significant coronary stenosis and measured serum DKK3 levels by an enzyme-linked immunosorbent assay (ELISA). Fifty-nine participants had significant coronary stenosis and 223 had < 50% coronary stenosis. Proportions of significant coronary stenosis were 13.7%, 11.4%, and 7.1% in DKK3 tertiles 1-3, respectively (P trend = 0.0427). In the univariable multinomial logistic regression model, a decreasing DKK3 tertile was associated with significant coronary stenosis with borderline significance (OR: 1.40; 95% confidence intervals (CI): 0.98-1.99, P = 0.0642). In the multivariable regression model, participants in the lowest DKK3 tertile were associated with a 1.42-fold increased risk of significant coronary stenosis than those in the highest DKK3 tertile (OR: 2.42; 95% CI: 1.10-5.33; P = 0.0279) after adjustment for conventional cardiovascular risk factors. In addition, associations between DKK3 and significant coronary stenosis were consistent among subgroups. However, no significant association was found between serum DKK3 levels and < 50% coronary stenosis. Therefore, we have added to the existing evidence that serum DKK3 is inversely associated with the risk of significant coronary stenosis in asymptomatic middle-aged Chinese.

Background: Leptin can have a direct effect on endothelial and vascular smooth muscle cells and high level of leptin is involved in the pathogenesis of atherosclerosis. This study aimed to determine the relationship between leptin/adiponectin (L/A) ratio and the extent and severity of coronary artery disease (CAD)., Methods: This case-control study was conducted in an educational hospital in Ilam, Iran from June 2014 to September 2015. Totally 300 participants including 150 patients with CAD (case group) and 150 healthy individuals (control group) were selected and their plasma leptin, adiponectin and leptin/adiponectin ratio was measured. The extent and severity of coronary artery disease were assayed based on the number of involved vessels and Gensini score (GS) and the relation between scores and L/A findings were compared between cases and controls., Results: Totally, 300 participants including 150 (42.7% male), mean age 59.5 ± 11.4 years as cases and 150 (50.7% male), mean age 59.8 ± 10.7 as controls were analyzed. Plasma level of leptin and L/A ratio were higher in cases compared to controls, but level of adiponectin was significantly lower in CAD patients than the control group. More number of involved coronary vessels was significantly correlated to higher level of plasma leptin, L/A ratio and lower level of adiponectin among case group. Moreover, adiponectin was negatively and leptin or L/A ratio were positively correlated with number of involved vessels. 7.3% of cases had only one involved vessel, 42.7% had two involved vessels, and 50% of total patients had involved vessels and the mean ± SD of GS in the case group was 23.6 ± 6.9., Conclusions: Plasma levels of leptin, and adiponectin can indicate the extent of coronary artery diseases but leptin may be a better marker of extent of CAD than either L/A ratio or adiponectin separately.

Purpose: Acute coronary syndrome presents as unstable angina (UA) or acute myocardial infarction (AMI). We explored the use of exosomal miR-122-5p as a biomarker for UA and AMI and determined whether its expression level is positively correlated with the severity of coronary stenosis., Methods: This study enrolled 34 patients with AMI, 31 patients with UA, and 22 control subjects. qPCR was used to detect the expression levels of serum exosomal miR-122-5p., Results: The expression of serum exosomal miR-122-5p in UA and AMI patients was significantly higher than that in the control group, and expression levels differed between UA and AMI patients. Receiver operating characteristic analysis demonstrated that serum exosomal miR-122-5p might be used as a diagnostic biomarker for AMI and UA. In addition, we also found that serum exosomal miR-122-5p was positively correlated with the severity of coronary artery stenosis for UA patients based on the Gensini score. Serum exosomal miR-122-5p was highly expressed in patients with a coronary artery stenosis severity greater than 80% during acute coronary syndrome., Conclusion: Serum exosomal miR-122-5p might be useful as a diagnostic biomarker for AMI and UA, and increased serum exosomal miR-122-5p levels could be useful to predict the severity of coronary lesions.

Frequencies of circulating T follicular helper (cTfh) functional subsets vary in autoimmune diseases. We evaluated the frequencies and clinical relevance of functional subsets of cTfhs in patients with different degrees of stenosis. Blood samples were collected from high (≥50%) (n = 12) and low (<50%) stenosis (n = 12) groups and healthy controls (n = 6). Three subsets of cTfh cells including cTfh1 (CXCR3 + CCR6 - ), cTfh2 (CXCR3 - CCX6 - ), and cTfh17 (CXCR3 - CCR6 + ) were detected by flow cytometry. The frequency of cTfh1 cells was higher in control (p = .0006) and low-stenosis groups (p = .005) compared to high-stenosis group. The percentages of cTfh2 and cTfh17 cells were increased in high-stenosis compared to low-stenosis (p = .002 and p = .007) and control groups (p = .0004 and p = .0005), respectively. The frequency of cTfh1 cells negatively correlated with cholesterol (p = .040; r = -.44), C-reactive protein (CRP) (p = .015; r = -.68), erythrocyte sedimentation rate (ESR) (p = .002; r = -.79), neutrophil/lymphocyte ratio (NLR) (p = .028; r = -.67), and cTfh17 (p = .017; r = -.7244) in the high-stenosis group. The percentages of cTfh2 and cTfh17 cells positively correlated with cholesterol (p = .025; r = .77 and p = .033; r = .71), CRP (p = .030; r = .61 and p = .020; r = .73), ESR (p = .027; r = .69 and p = .029; r = .70), NLR (p = .004; r = .76 and p = .005; r = .74), and with each other (p = .022; r = .7382), respectively, in the high-stenosis group. The increased frequencies of cTfh2 and cTfh17 subsets and their correlation with laboratory parameters in patients with atherosclerosis may suggest their role in promoting the inflammatory response and atherosclerosis progression., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: To evaluate the coronary plaque characteristics of coronary arteries using computed tomography angiography (CTA) in order to assess the risk of coronary artery disease and the relevance of high sensitivity C reactive protein (hs-CRP) in patients with Diabetes Mellitus (DM)., Methods: The clinical data of 400 DM patients and 400 non-DM patients from January 2017 to December 2019 were collected, including the results of coronaryCTA. The plasma hs-CRP level of the two groups were divided into three groups: CRP ≤ 1, 1 < CRP ≤ 2, CRP > 2. The correlation of the degree of stenosis, the number of plaques, the nature of plaques and hs-CRP value between the two groups was evaluated., Results: Compared with non-DM patients, the incidence of coronary artery plaques and lumen stenosis in DM patients was more higher than that in non-DM patients. DM patients were more likely to have more diseased vessels, especially diffuse vascular disease (12.00% vs 1.75%; P < 0.001). Subjects with high hs-CRP levels were more likely to have any plaque compared with individuals showing normal hs-CRP levels (p<0.01). There was no statistical significance in non calcified plaque with high level of hs-CRP, but the occurrence of plaque types in DM group was statistically significant compared with other hs-CRP levels in non DM group. Subjects with high hs-CRP were observed to be at increased risk for the presence of calcified plaque and severe narrowing in the unadjusted values., Conclusions: Coronary CTA combined with hs-CRP can accurately detect the characteristics of coronary artery stenosis and plaque in DM patients, which has an important clinical value in the risk assessment of coronary heart disease in DM patients.

Objective: Experimental evidence suggests a close link between PARP (poly[ADP-ribose] polymerase) activation and diabetic endothelial dysfunction. Here, we tested whether PARP activity in circulating leukocytes was associated with coronary artery disease (CAD) among patients with type 2 diabetes mellitus (T2DM). Approach and Results: We performed observational and bidirectional Mendelian randomization studies of 3149 Chinese individuals with T2DM who underwent coronary angiography, with leukocyte PARP activity, 16 tag single-nucleotide polymorphisms in PARP1 and PARP2 , and 17 CAD risk single-nucleotide polymorphisms analyzed. Of 3149 participants, 1180 who further received percutaneous coronary intervention were prospectively followed for 1 year to track major adverse cardiovascular and cerebrovascular events. Overall, greater PARP activity was cross-sectionally associated with an odds ratio of 1.23 for obstructive CAD, and prospectively with a hazard ratio of 1.34 for 1-year major adverse cardiovascular and cerebrovascular events after percutaneous coronary intervention (both P <0.001). Using a genetic score of 5 screened single-nucleotide polymorphisms in PARP1 and PARP2 as the instrumental variable, genetically predicted elevation in PARP activity showed a causal association with obstructive CAD (odds ratio=1.35, P <0.001). In contrast, the genetic risk of CAD had no significant effect on PARP activity. Ex vivo and in vitro cultures of human monocytes showed that rs747657, as the lead single-nucleotide polymorphism strongly associated with PARP activity, caused the differential binding of transcription factor GATA2 (GATA-binding protein 2) to an intronic regulatory region in PARP1 , thus modulating PARP1 expression and PARP activity., Conclusions: Greater PARP activity may have causal roles in the development of obstructive CAD among patients with diabetes mellitus.

Background and Aims: Current epidemiologic data suggest beneficial cardiovascular effects of fermented dairy products (FDP). However, the relationship between FDP consumption and angiographic coronary status has not been previously studied. Furthermore, the role of novel metabolomic biomarkers of cardiovascular risk in this context is unclear. We hypothesize that short-chain acylcarnitines (SCA) reflect the link between FDP intake and angiographic extent of stable coronary artery disease (CAD)., Methods and Results: We recruited 1185 patients admitted for suspected CAD [median age 62 years (interquartile range: 54-69); 714 men (60.3%)]. Prior to coronary angiography, each patient completed a validated Food Frequency Questionnaire. In addition, venous blood was collected from each patient for whole blood metabolomic analysis, using targeted mass-spectrometry. CAD was defined by the presence of ≥1 coronary stenosis ≥50%. Patients with CAD (n = 441) reported lower median FDP intake [86.8 g/day (IQR: 53.4-127.6)] than patients without CAD [n = 744; 103.9 g/day (IQR: 62.9-152.7); p < 0.001]. Upon adjustment for relevant confounders, increased circulating SCA, particularly level of acetylcarnitine (C2) associated with both higher CAD probability [SCA:β(SE) = 0.584 (0.235), p = 0.013; C2:β(SE) = 0.575 (0.242), p = 0.017] and decreased FDP consumption [SCA:β/100 g FDP-increment/day (SE) = -0.785 (0.242), p = 0.001; C2:β(SE) = -0.560 (0.230), p = 0.015]. By mediation analysis, neither SCA nor C2 showed relevant mediator effect linking FDP consumption to the risk of CAD., Conclusion: Increased consumption of fermented milk was associated with lower prevalence of CAD and correlated inversely with circulating SCA, in particular with acetylcarnitine. No substantial mediator effect of SCA linking fermented milk intake with risk of CAD was found., Clinical Trial Registry: NCT00497887., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Triglyceride Glucose (TyG) index has been associated with an increased risk in cardiovascular events. Silent coronary disease is common in patients with type 2 diabetes. In Vietnam, a low-middle income country, the burden of cardiovascular disease is growing simultaneously with the epidemiologic transition. Our aim was to assess the prevalence of coronary stenoses (CS) in patients with type 2 diabetes and no history or symptom of cardiovascular disease and to investigate the association between TyG index and cardiovascular risk factors and both the presence and severity of CS. Futhermore, we assessed the value of TyG index in predicting subclinical CS., Methods: This was a cross-sectional observational study. We recruited 166 patients at Ninh Thuan General Hospital, Vietnam. TyG index and HOMA-IR were calculated, and a coronary computed tomography angiography (CCTA) was performed., Results: The population was classified according to tertiles of TyG index. The highest TyG values were associated with higher BMI, waist circumference, total cholesterol, LDL-cholesterol, triglycerides, plasma glucose, HbA1c levels and HOMA-IR, lower HDL-cholesterol, a higher incidence of metabolic syndrome and less frequent physical activity (p < 0.05 to < 0.0001). TyG index correlated with logHOMA-IR (p < 0.0001). CS ≥ 50% were present in 60 participants and 32 had coronary artery stenosis ≥ 70%. TyG index and HOMA-IR were significantly higher in patients with CS ≥ 70%. The number of narrowed coronary arteries and the degree of stenosis were associated with higher TyG index levels (p = 0.04 and < 0.005 respectively). A TyG index ≥ 10 was significantly associated with an increased risk of multiple coronary artery disease and of more severe CS. After adjusting for confounding factors, including logHOMA-IR, these risks remained mostly significant. A TyG index threshold at 10 resulted in 57% sensitivity and 75% specificity for predicting the presence of CS ≥ 70%. In subgroup analysis TyG index ≥ 10 was associated with an increased risk in CS ≥ 70% in patients treated with statin or antiplatelet therapy., Conclusion: More than one third of asymptomatic patients with type 2 diabetes had significant CS on CCTA. TyG index may be considered as a marker for insulin resistance and increased TyG index could identify patients with high risk of coronary artery stenoses and is associated with the number and the severity of artery stenoses.

Background Current noninvasive modalities to diagnose coronary artery disease (CAD) have several limitations. We sought to derive and externally validate a hs-cTn (high-sensitivity cardiac troponin)-based proteomic model to diagnose obstructive coronary artery disease. Methods and Results In a derivation cohort of 636 patients referred for coronary angiography, predictors of ≥70% coronary stenosis were identified from 6 clinical variables and 109 biomarkers. The final model was first internally validated on a separate cohort (n=275) and then externally validated on a cohort of 241 patients presenting to the ED with suspected acute myocardial infarction where ≥50% coronary stenosis was considered significant. The resulting model consisted of 3 clinical variables (male sex, age, and previous percutaneous coronary intervention) and 3 biomarkers (hs-cTnI [high-sensitivity cardiac troponin I], adiponectin, and kidney injury molecule-1). In the internal validation cohort, the model yielded an area under the receiver operating characteristic curve of 0.85 for coronary stenosis ≥70% ( P <0.001). At the optimal cutoff, we observed 80% sensitivity, 71% specificity, a positive predictive value of 83%, and negative predictive value of 66% for ≥70% stenosis. Partitioning the score result into 5 levels resulted in a positive predictive value of 97% and a negative predictive value of 89% at the highest and lowest levels, respectively. In the external validation cohort, the score performed similarly well. Notably, in patients who had myocardial infarction neither ruled in nor ruled out via hs-cTnI testing ("indeterminate zone," n=65), the score had an area under the receiver operating characteristic curve of 0.88 ( P <0.001). Conclusions A model including hs-cTnI can predict the presence of obstructive coronary artery disease with high accuracy including in those with indeterminate hs-cTnI concentrations.

Background: Thrombin, a key enzyme of the clotting system, is involved in thrombus formation, platelet activation, and atherosclerosis, thereby possessing a central role in the pathogenesis of ischemic heart disease. Studies have shown an association between thrombin generation (TG) and cardiovascular morbidity and mortality, but results have been equivocal. Our aim was to study the predictive ability of TG assay in evaluating coronary stenosis severity., Methods: In this prospective study we recruited patients with acute coronary syndrome (ACS) or acute chest pain (without evidence of myocardial injury) planned for coronary angiography. Thrombin generation was evaluated by Calibrated Automated Thrombogram (CAT) prior to angiography. Primary end points were significant coronary stenosis and the Syntax I score evaluated by coronary angiography., Results: From April 2018 through September 2019, we recruited 128 patients. In the primary analysis there was no significant association between TG and significant coronary stenosis nor between TG and syntax I score, however, there was a positive correlation between peak height and troponin peak (Spearman correlation coefficient 0.194, P-value = 0.035). In sub-group analysis, the chest pain group bare no association between TG and coronary stenosis. In unstable angina group there was an association between peak height and significant coronary stenosis (P-value = 0.029), and in non ST-elevation myocardial infarction group, TG values possessed a relatively good predictive ability of significant coronary stenosis (area under the receiver operating characteristic curve of ~65%) and a positive correlation between both lag time and ttpeak with the syntax I score was noticed (Spearman correlation coefficient 0.31, P-value = 0.099 and Spearman correlation coefficient 0.37, P-value = 0.045 respectively)., Conclusion: In patients with acute chest pain, TG values, evaluated by CAT, do not predict severity of coronary stenosis, nor do they possess prognostic value. Yet, in ACS patients, TG may have the ability to predict coronary disease severity., Competing Interests: The authors have declared that no competing interests exist.

Background and Aims: In Portugal, The Azores Archipelago has the highest standardized mortality rate for CAD. Therefore, the aim of this study was to evaluate conventional risk factors, as well as plasma and erythrocyte aminothiol concentration in high-risk Azorean patients undergoing elective coronary angiography and to investigate whether any aminothiol was associated with CAD risk and severity., Methods and Results: 174 subjects with symptomatic CAD (age 56±9y; 68% men) submitted to coronary angiography were split into 2 groups: one formed by CAD patients (≥50% stenosis in at least one major coronary vessel) and the other by non-CAD patients (<50% stenosis). Both groups were age-, sex- and BMI-matched. Plasma and erythrocyte aminothiol profiles were evaluated by RP-HPLC/FLD. CAD patients significantly exhibited both higher concentrations of plasma Cys and hypercysteinemia (Cys ≥ 300 μM) prevalence than those in the non-CAD group (261 ± 58 μM vs. 243 ± 56 μM; 22% vs. 10%, respectively). No differences were observed between groups regarding plasma Hcy levels or hyperhomocysteinemia prevalence. After adjustment for several confounders (including Hcy), subjects in the highest quartile of plasma Cys had a 3.31 (95% CI, 1.32-8.30, p = 0.011) fold risk for CAD, compared with those in the lowest quartiles. Furthermore, plasma Cys levels (but not Hcy) tended to increase with the number of stenotic vessels (1VD: 253 ± 64 μM; 2VD: 262 ± 52 μM; 3VD: 279 ± 57 μM, p = 0.129)., Conclusion: Hypercysteinemia revealed to be a better predictor of CAD than hyperhomocysteinemia. Moreover, plasma Cys showed to be a useful biomarker for CAD both in primary and secondary preventions, seeming to resist better than Hcy to oral medication therapy., Competing Interests: Declaration of Competing Interest The authors declared that they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Coronary artery stenosis induces heart diseases including acute coronary syndrome (ACS). Some studies reported the ceramide species are associated with the ACS and major adverse cardia and cerebrovascular events (MACE). However, few studies investigated the association between plasma ceramide levels and the severity of stenosis, together with the onset of diseases. This aim of the present study was to investigate the association betweencertain ceramide species, coronary artery stenosis and acute coronary syndrome., Methods: Five hundred fifty-three patients with definite or suspected CAD were recruited and received angiography. Subjects were assigned into 4 groups according to the severity of coronary artery stenosis. The measurements of 4 plasma ceramide species, namely, Cer (d18:1/16:0), Cer (d18:1/18:0), Cer (d18:1/24:1), Cer (d18:1/24:0) were carried out by Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the ratio of Cer (d18:1/16:0), Cer (d18:1/18:0) and Cer (d18:1/24:1) to Cer (18:1/24:0), respectively, were calculated as index to evaluate the association between plasma ceramides levels and coronary artery stenosis. Multiple logistic regression analysis was used to establish the prognostic model for the prediction of ACS risk., Results: After the adjustment by multiple clinical risk factors including age, gender, pre-existing myocardial/cerebral infarction, hemoglobin A1c% (HbA1c%), smoking and the diagnosis during index hospitalization, multiple logistic regression analysis showed that the high ratio of Cer (d18:1/24:1) to Cer (d18:1/24:0), female gender, HbA1c%, unstable angina (UAP) and acute myocardial infarction (AMI) diagnosis (compared with atherosclerosis) during index hospitalization were associated with more severe coronary artery stenosis. Furthermore, the prognostic model was established after adjustment of risk factors and the area under curve (AUC) of receiver operating characteristics (ROC) for the prognostic model was 0.732 and 95% CI was 0.642-0.822., Conclusion: The severity of coronary artery stenosis is associated with high ratio of Cer (d18:1/24:1) to Cer (d18:1/24:0), female gender, HbA1c% and AMI. Although the reported prognostic model showed a good discrimination, further investigation on long term MACE is needed to evaluate the role of ceramide for the prediction of MACE risk.

Background: The level of lipoprotein-associated phospholipase A2 (LP-PLA2) in serum is independently correlated to coronary artery diseases (CAD). The aim of the study was to determine whether LP-PLA2 activity is positively associated with the seriousness of CAD., Methods: Amount to 1056 patients suspected of having CAD underwent coronary angiography (CAG) to determine the seriousness of CAD. According to the amount of diseased coronary branches, the 1056 patients were split into three groups: single-vessel stenosis group, multiple-vessels stenosis group (> or = 2 diseased coronary branches),and control group (no diseased coronary branches). According to CAG results, electrocardiography, cardiac biomarker, and clinical presentation, all patients were split into four groups: acute myocardial infarction (AMI), unstable angina (UA), stable angina (SA), and control groups (excluding CAD). The activity of LP-PLA2 was compared statistically among the subgroups. Receiver operating characteristic analysis was applied to investigate the role of LP-PLA2 in evaluating the presence and seriousness of CAD., Results: The level of LP-PLA2 increased in line with the number of diseased coronary branches. The levels of LP-PLA2 in the AMI and UA groups were observably higher when compared with the control and SA groups. LP-PLA2 had 75.6% sensitivity and 67.3% specificity for recognizing CAD, and 53.0% sensitivity and 80.3% specificity for recognizing severe coronary artery lesions., Conclusion: The activity of LP-PLA2 is positively correlated to the seriousness of CAD.

Objective and Design: We performed an experimental, analytical and prospective study to evaluate the systemic activation of inflammasome in atherosclerosis' patients, in order to shed light into responsible mechanisms for plaque formation., Subjects: We included sixty individuals distributed into 3 groups: 2 groups based on the report from the angiography (severe lesions - SL and primary lesions - PL) and 1 group enclosing healthy individuals (HC)., Methods: The expression assays of inflammasome genes NLRP1, NLRC4, CASP-1 and IL-1β were performed using Real Time qPCR, with specific Taqman Assays. IL-1β serum levels were analysed by commercial kit. Were applied the Shapiro-Wilk and Student's T-test as statistical tests. Statistical significance was set to p ≤ 0.05., Results: Upregulation of NLRP1 (+3.47 FC, p = 0.0001), NLRC4 (+7.06 FC, p = 6.792 × 10 -09 ) and IL-1β (+2.43 FC, p = 0.005) was observed in all atherosclerosis patients when compared to HC. According to stenosis severity, patients with primary lesions showed upregulation of inflammasome genes NLRP1 (+2.87 FC, p = 0.0008), NLRC4 (+6.34 FC, p = 4.134 × 10 -07 ) and IL-1β (+3.39 FC, p = 0.0012) with respect to the HC group. No statistical difference was found in IL-1β serum levels according the assessed groups., Conclusions: Inflammasome activation in atherosclerosis's patients can be systemic altered and may be triggered by NLRP1 and NLRC4 receptors. IL-1β gene expression was identified in our study as an important systemic detectable marker of plaque severity., Competing Interests: Declaration of Competing Interest We wish to confirm that there are no know conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property. We further confirm that any aspect of the work covered in this manuscript that has involved human patients has been conducted with the ethical approval of all relevant bodies and that such approvals are acknowledged within the manuscript. We understand that the Corresponding Author is the sole contact for the Editorial process (including Editorial Manager and direct communications with the office). She is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs. We confirm that we have provided a current, correct email address which is accessible by the Corresponding Author and which has been configured to accept email from j.azvedo@gmail.com., (Copyright © 2020. Published by Elsevier GmbH.)

Background and Objectives: The complement system plays an important role in the development of acute coronary syndrome (ACS). Complement C1q is an important initial component of the classical complement pathway and closely related to many chronic inflammatory diseases, including atherosclerosis (AS). We aimed to determine whether there was association between serum complement C1q and the severity of coronary stenosis., Subjects and Methods: 320 patients who underwent coronary arteriography (CAG) were stratified into non-ACS group (control group, n = 74), unstable angina group (UA group, n = 197) and acute myocardial infarction group (AMI group, n = 49) according to the severity of coronary stenosis and clinical manifestations. The severity of coronary stenosis was represented in Gensini score, and serum complement C1q level was compared using immunity transmission turbidity among three groups., Results: The level of complement C1q in AMI group was lower significantly than control group and UA group (P < 0.05), but there was no correlation between serum complement C1q and Gensini score (β=-0.086, P = 0.125). In nitrate-taking patients, serum complement C1q had a negative association with Gensini score (r=-0.275, P = 0.001), and in non-smokers, there was also a negative correlation (β=-0.159, P = 0.036). After calibrating smoking, drinking or statins, the serum complement C1q levels of control group, UA group and AMI group decreased in sequence (P <  0.05). Logistic regression analysis showed that the decreasing of serum complement C1q was an unfavorable factor for acute myocardial infarction (OR=0.984, 95 %CI=0.972∼0.997, P = 0.015) and for ACS (OR=0.984, 95 %CI=0.971∼0.984, P = 0.025) in drinking patients. Regrettably, ROC curve suggested that the accuracy in diagnosing coronary atherosclerotic heart disease by serum complement C1q was low (AUC=0.568, 95 %CI= 0.492-0.644, P = 0.076, sensitivity 73.6 %, specificity 58.1 %)., Conclusion: Serum complement C1q in ACS patients, in particular AMI patients, showed lower level. This finding suggests further decrease of complement C1q level in ACS patients may be a contributory factor to instability or rupture of atherosclerotic plaques. Combined with other clinical indicators, it can be helpful to predict the risk and severity of coronary stenosis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aim: Recent prospective studies have identified distinct plasma ceramides as strong predictors of major adverse cardiovascular events in patients with established or suspected coronary artery disease (CAD). Currently, it is uncertain whether higher levels of distinct plasma ceramides are associated with greater angiographic severity of coronary-artery stenoses in this patient population., Methods: We measured six previously identified high-risk plasma ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] in 167 consecutive patients with established or suspected CAD, who underwent urgent or elective coronary angiography., Results: Approximately 77% of patients had a significant stenosis (≥50%) in one or more of the main coronary arteries, the majority of whom (∼60%) had a significant stenosis in the left anterior descending (LAD) artery. Of the six measured plasma ceramides, higher levels of plasma Cer(d18:1/20:0) (adjusted-odds ratio 1.39, 95%CI 1.0-1.99), Cer(d18:1/22:0) (adjusted-odds ratio 1.57, 95%CI 1.08-2.29) and Cer(d18:1/24:0) (adjusted-odds ratio 1.59, 95%CI 1.08-2.32) were significantly associated with the presence of LAD stenosis≥50%, after adjustment for age, sex, smoking, pre-existing CAD, hypertension, diabetes, dyslipidaemia, lipid-lowering therapy, estimated glomerular filtration rate and plasma C-reactive protein levels. Almost identical results were found even after excluding patients (n=15) with acute ST-elevation myocardial infarction. Similar results were also found when patients were categorized according to the Gensini severity score., Conclusion: Our cross-sectional study shows for the first time that higher levels of specific plasma ceramides are independently associated with a greater severity of coronary-artery stenoses in the LAD artery in patients who had suspected or established CAD., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)