P26 Soluble programed cell death ligand-1 is associated with acute coronary syndrome

2020 ◽  
Vol 41 (Supplement_1) ◽  
Author(s):  
K Fujisue ◽  
E Yamamoto ◽  
D Sueta ◽  
M Takae ◽  
T Nishihara ◽  
...  

Abstract Background Immune checkpoint by programmed cell death (PD)-1 and its ligand (PD-L1) play crucial role in T cell tolerance toward vascular wall antigens. PD-L1 is widely expressed on a number of cells including immune cells and vascular endothelium. It was reported that increased expression of PD-L1 in dendritic cells implicates upregulated inflammation in atherosclerotic lesions that is associated with plaque instability. Although plaque rupture in coronary atherosclerosis is an important pathogenesis of acute coronary syndrome (ACS), the association between PD-L1 and ACS is still unknown. Purpose We hypothesize that circulating PD-L1 might be associated with ACS, reflecting endothelial damage and coronary plaque rupture. To elucidate this hypothesis, we compared serum levels of soluble PD-L1 (sPD-L1) in stable coronary artery disease (CAD) patients with those in ACS patients. Methods Serum levels of sPD-L1 were measured by using commercially available ELISA kit (Human PD-L1/B7-H1 DuoSet, R&D Systems) in consecutive patients with CAD admitted to our University Hospital from February 2016 to March 2017. Patients with any malignant disease or severe inflammatory disease were excluded from this study. Serum levels of sPD-L1 and clinical backgrounds were compared between stable-CAD and ACS patients. Results In total, 269 patients with CAD were enrolled (28 cases [10.4 %] with ACS and 241 cases [89.6 %] with stable-CAD). PD-L1 had no correlation to C-reactive protein, cardiac troponin, and classical atherosclerotic risks such as age, body mass index, estimated glomerular filtration rate, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, and hemoglobin A1c. Although age, sex, history of smoking, and the prevalences of hypertension, diabetes mellitus and dyslipidemia were comparable between both groups, the level of LDL-C was significantly higher in patients with ACS compared with those with stable-CAD (94.0 [77.0–112.0] mg/dL vs. 78.5 [65.0–97.0] mg/dL, P = 0.008). Also serum level of sPD-L1 was significantly increased in patients with ACS compared with those with stable-CAD (106.1 [60.9–157.7] pg/mL vs. 64.8 [30.9–102.5] pg/mL, P = 0.003). Univariate logistic regression analysis identified that serum levels of both sPD-L1 and LDL-C were independently associated with ACS. Moreover, multivariable logistic regression analysis with factors from univariate analysis identified that serum level of sPD-L1 was significantly and independently associated with ACS (odds ratio: 1.006, 95 % confidence interval: 1.001–1.012, P = 0.03). Conclusions This is the first study to elucidate that the increased serum levels of sPD-L1 was associated with ACS. This study suggests that sPD-L1 could be a risk marker and therapeutic target for ACS.

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Tianyu Chi ◽  
Quchuan Zhao ◽  
Peili Wang

Background. Upper gastrointestinal bleeding (UGIB) is a common critical disease with a certain fatality rate. Acute coronary syndrome (ACS), another critical ill condition, is a regular occurrence in the UGIB. We identified risk factors for ACS in UGIB. Methods. 676 patients diagnosed with UGIB were enrolled retrospectively. We assessed the occurrence of ACS in UGIB patients and identified the risk factors for ACS by logistic regression analysis and random forest analysis. Results. After propensity score matching (PSM), the ACS group ( n = 69 ) and non-ACS group ( n = 276 ) were analyzed. Logistic regression analysis showed that syncope ( P = 0.001 ), coronary heart disease history ( P = 0.001 ), Glasgow Blatchford score ( P ≤ 0.001 ), Rockall risk score ( P = 0.004 ), red blood cell distribution width (RDW) ( P ≤ 0.001 ), total bilirubin (TBil) ( P = 0.046 ), fibrinogen ( P ≤ 0.001 ), and hemoglobin ( P = 0.001 ) had important roles in ACS patients. With Mean Decrease Gini (MDG) sequencing, fibrinogen, RDW, and hemoglobin were ranked the top three risk factors associated with ACS. In ROC analysis, fibrinogen ( AUC = 0.841 , 95% CI: 0.779-0.903) and RDW ( AUC = 0.826 , 95% CI: 0.769-0.883) obtained good discrimination performance. According to sensitivity > 80 %, the pAUC of fibrinogen and RDW were 0.077 and 0.101, respectively, and there was no significant difference ( P = 0.326 ). However, according to specificity > 80 %, the pAUC of fibrinogen was higher than that of RDW (0.126 vs. 0.088, P = 0.018 ). Conclusion. Fibrinogen and RDW were important risk factors for ACS in UGIB. Additionally, combination with coronary heart disease, syncope, hemoglobin, and TBil played important roles in the occurrence of ACS. Meanwhile, it was also noted that Rockall score and Glasgow Blatchford score should be performed to predict the risk.


2018 ◽  
Vol 15 (1) ◽  
pp. 15-21
Author(s):  
Đỗ Hữu Chí ◽  
Nguyễn Thị Minh Phương ◽  
Bùi Thị Huyền ◽  
Nguyễn Tiến Dũng ◽  
Phạm Đình Minh ◽  
...  

Acute Coronary Syndrome (ACS) is one of the foremost causes of mortality and morbidity worldwide as well as Vietnam. ACS was evoked by rupture or erosion of atherosclerotic plaques that was divided into Non–ST-segment elevation Acute Coronary Syndrome (NSTEACS) and ST-segment elevation myocardial infarction groups (STEMI). The matrix metalloproteinase (MMPs) is an enzyme family with fucntioning in the degradation of extracellular matrix and disruption of basement membranes. Of the MMPs, MMP-9 is expressed in the atherosclerotic plaques and plays a key role in the rupture of vulnerable atherosclerotic plaques. In this work, we measured the serum MMP-9 level in 205 patients with acute coronary syndrome (including 103 of NSTE-ACS and 102 of STEMI patients) and 101 healthy participants by sandwich Elisa method. The results showed that the MMP-9 level was significantly higher in NSTE-ACS and STEMI compared to the control group (208.59 ± 100.47 ng/mL, 189.98 ± 112.81 ng/mL vs 168.50 ± 79.52 ng/mL, respectively, P=0.014). However, a logistic regression analysis indicated that the MMP-9 level was only significantly higher in patients with NSTE ACS (OR= 1.0048, CI 95%= 1.000-1.009; P= 0.018). The serum MMP-9 level is correlated with traditional risk factors such as glucose, Cholesterol and Triglyceride by multiple logistic regression analysis. Conclusion: Our study suggests that the serum MMP-9 level is significantly associated with the NSTEACS and is a potential marker for dianogsis of ACS in the Vietnamese patients


2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Rehab Ibrahim Yaseen ◽  
Mohamed Hesham El-Leboudy ◽  
Hend Mohammed El-Deeb

Abstract Background Apolipoprotein B is considered the primary protein constituent of low-density lipoprotein. LDL contains variable quantities of cholesterol, but each lipoprotein contains a single ApoB protein. Thus, ApoB is a better index for the LDL circulation if compared to LDL cholesterol. On the contrary, apolipoprotein A-1 is a main structural protein of high-density lipoprotein. It has a major role in reversing cholesterol flow and cellular cholesterol homeostasis once detected. The aim of the study is to measure apo B/apo A-1 ratio in patients with acute coronary syndrome and assess its relationship with the severity of CAD. A total of 90 patients were enrolled in the study and subdivided into 3 groups: 30 patients of STEMI, 30 patients of NSTEMI, and 30 patients presented with unstable angina. Serum levels of apolipoprotein A-1 and apolipoprotein B were properly measured upon admission, and apo B/apo A-1 ratio was calculated. Results Both of Apo B and Apo B/Apo A1 ratio correlated significantly with Gensini scores (P value <0.001). High Gensini score patients had significantly high Apo B/Apo A1 ratio with the best cutoff value of 0.8 with sensitivity of 90% and specificity of 70%. Conclusion Apo B is an independent risk predictor for the severity of CAD in patients with acute coronary syndromes. Moreover, the Apo B/Apo A1 ratio remains highly significant in patients with high Gensini score.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Lingling Qian ◽  
Lei Zhang ◽  
Liang Wu ◽  
Jing Zhang ◽  
Qichen Fang ◽  
...  

Background. Recent studies have suggested that cell death might be involved in the pathophysiology of metabolic disorders. The cytokeratin 18 (CK18) fragment, as a cell death marker, plays an important role in nonalcoholic fatty liver disease (NAFLD). However, only a limited number of studies have found elevated serum levels of CK18 in patients with type 2 diabetes. Moreover, no studies have been conducted yet to investigate the role of CK18 in hypertension or dyslipidemia. In particular, CK18 M65ED is a more sensitive marker of cell death, and its role in cardiometabolic disorders has not been revealed yet. Methods. A total of 588 subjects were enrolled from the local communities of Shanghai. Serum CK18 M65ED were determined using the enzyme-linked immunosorbent assay. A cardiometabolic disorder was identified by the presence of at least one of the components including overweight or central obesity, diabetes, dyslipidemia, and hypertension. Results. Subjects with cardiometabolic disorders exhibited significantly higher serum levels of CK18 M65ED than those without cardiometabolic disorders (197.36 (121.13–354.50) U/L versus 83.85 (52.80–153.75) U/L, respectively, P<0.001). Increased serum CK18 M65ED quartiles were associated with the increased prevalence of cardiometabolic disorders and its components (P<0.001 for all components). Multiple stepwise regression analysis also revealed that diastolic blood pressure, glycated hemoglobin A1c, alanine transaminase, and high-density lipoprotein cholesterol were independently correlated with serum CK18 M65ED levels (all P<0.01). In addition, logistic regression analysis showed that the serum CK18 M65ED levels were positively correlated with cardiometabolic disorders and in an independent manner. Further, CK18 M65ED was revealed to be an indicator of cardiometabolic disorders in a NAFLD-independent manner. Conclusions. Elevated levels of CK18 M65ED, a sensitive cell death marker, were independently and positively correlated with cardiometabolic disorders, even after the adjustment for the presence of NAFLD and other cardiovascular risk factors.


2013 ◽  
Vol 33 (4) ◽  
pp. 396-402 ◽  
Author(s):  
JCE Piccoli ◽  
V Manfredini ◽  
D Faoro ◽  
FM Farias ◽  
LC Bodanese ◽  
...  

Atherosclerosis is morphologically an inflammatory disease, where endothelial dysfunction plays a key role in all the stages. The nitric oxide (NO) synthase 3 ( NOS3) gene is responsible for the synthesis of endothelial NO synthase (eNOS) in humans and some genetic polymorphisms are considered “polymorphisms associated with risk” for the development of coronary artery diseases, such as acute coronary syndrome. Thus, the present study aimed to evaluate the influence of the -786T>C polymorphism of the eNOS gene on inflammatory and oxidative process. A prospective cohort study of 125 consecutive patients with clinical diagnosis of non-ST-elevation acute coronary syndromes was conducted. Patients were assessed using a standardized questionnaire. Blood samples were drawn to measure serum levels of high-sensitivity C-reactive protein, soluble CD40 ligand, interleukin-6 (IL-6), N-terminal prohormone of brain natriuretic peptide, immunoglobulin G antibodies against oxidized low-density lipoprotein. The genotypes for the -786T>C polymorphism in the 5′-flanking region of eNOS gene were determined. The -786C allele was found in 92 of 250 alleles (38.8%). No statistical association was observed between demographic and clinical characteristics and distribution of eNOS- 786T>C polymorphism. We found that -786CC was associated with lower levels of IL-6. No significant differences were observed between the distribution of -786T>C polymorphism and other investigated markers.


2013 ◽  
Vol 36 (4) ◽  
pp. 234 ◽  
Author(s):  
Cong-Lin Liu ◽  
De-Liang Shen ◽  
Kui Zhu ◽  
Jun-Nan Tang ◽  
Qi-Min Hai ◽  
...  

Purpose: The purpose of this study was to investigate the levels of interleukin-33 (IL-33) and interleukin-6 (IL-6) in patients with acute coronary syndrome or stable angina. Methods: Serum IL-33 and IL-6 were measured with Enzyme Linked Immuosorbent Assay (ELISA) in patients with acute coronary syndrome (ACS, n = 40), and stable angina pectoris (SAP, n = 43). IL-33 and IL-6 were also determined in 30 healthy subjects (control group). Results: The serum level of IL-33 in the ACS group (78.60 ± 44.84 ng/L) was lower than in the SAP (102.58 ± 37.21 ng/L, P < 0.01) or control groups (130.24 ± 10.17 ng/L, P < 0.01). The serum level of IL-6 in the ACS group (39.90 ± 12.64 ng/L) was higher than in the SAP (18.68 ± 11.89 ng/L, P < 0.05) or control groups (6.28 ± 17.72 ng/L, P < 0.05). There were no differences in serum levels of IL-33 and IL-6 among the single-, double- and triple-vessel lesion groups. IL-33 and IL-6 levels were negatively correlated with each other in the ACS (r = -0.871, P < 0.01) and SAP groups (r = -0.788, P < 0.01). Conclusion: The serum level of IL-33 was lower in patients with ACS or SAP and was negatively correlated with the serum level of IL-6. Thus, IL-33 and IL-6 may be used as biomarkers for evaluating inflammatory response and severity of coronary heart disease in patients with ACS or SAP.


2021 ◽  
Vol 10 (23) ◽  
pp. 5567
Author(s):  
Sandeep Kumar ◽  
Wahid Ali ◽  
Sridhar Mishra ◽  
Akshyaya Pradhan ◽  
Rishi Sethi ◽  
...  

Background: Cardiac troponin is the best marker to diagnose acute coronary syndrome (ACS). However, early diagnosis using markers for plaque instability may be of significance. Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) plays an important role in the pathogenesis of atherosclerosis plaque rupture and may be a potential biomarker of coronary artery disease (CAD), including ACS. The current study aims to evaluate sLOX-1 levels in the sera of patients with ACS as an independent marker of CAD with other established diagnostic markers and assess its level before and after percutaneous intervention (PCI) in predicting the risk of future recurrence of ACS. Methods: Peripheral blood was obtained from a total of 160 patients, including patients who underwent coronary angiography (n = 18, group I), patients of stable CAD who underwent percutaneous intervention (n = 50, group II), patients of the acute coronary syndrome (n = 64, group III), and healthy controls (n = 28, group IV). A serum sLOX-1 concentration was measured by the enzyme-linked immunosorbent assay (ELISA). Results: The results obtained showed a statistically significant raised level of sLOX-1 in pre/post PCI patients of stable CAD/ACS with male preponderance. The area under the curve for sLOX-1 was 0.925 for cases that are discriminated from controls with sensitivity and specificity of 87.88 and 100%, respectively. SLOX-1 showed 100% sensitivity and specificity in the discrimination of the stable CAD that underwent PCI vs. control with an AUC of 1.00. The recurrence of coronary artery disease was observed in 9 out of 132 (6.8%) cases. The post-interventional sLOX-1 level was significantly different and higher in recurrent cases (p = 0.027) of ACS/CAD. Conclusions: sLOX-1 was a useful biomarker of stable CAD/ACS and has a potential in the risk prediction of a future recurrence of coronary artery disease.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hyungdon Kook ◽  
Duck Hyun Jang ◽  
Jong-Ho Kim ◽  
Jae-Young Cho ◽  
Hyung Joon Joo ◽  
...  

AbstractSoluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), neutrophil gelatinase-associated lipocalin (NGAL), and matrix metalloproteinase-9 (MMP-9) are inflammatory biomarkers involved in plaque destabilization resulting in acute coronary syndrome (ACS). This study aimed to investigate the diagnostic value of a combination of biomarkers to discriminate plaque ruptures in the setting of ACS. Eighty-five ACS patients with optical coherence tomography (OCT) images of the culprit plaque were included and categorized into two groups: ACS with plaque rupture (Rupture group, n = 42) or without plaque rupture (Non-rupture group, n = 43) verified by OCT. A discriminative model of plaque rupture using several biomarkers was developed and validated. The Rupture group had higher white blood cell (WBC) counts and peak creatine kinase-myocardial band (CK-MB) levels (13.39 vs. 2.69 ng/mL, p = 0.0016). sLOX-1 (227.9 vs. 51.7 pg/mL, p < 0.0001) and MMP-9 (13.4 vs. 6.45 ng/mL, p = 0.0313) levels were significantly higher in the Rupture group, whereas NGAL showed a trend without statistical significance (59.03 vs. 53.80 ng/mL, p = 0.093). Receiver operating characteristic curves to differentiate Rupture group from Non-rupture group calculated the area under the curve for sLOX-1 (p < 0.001), MMP-9 (p = 0.0274), and NGAL (p = 0.0874) as 0.763, 0.645, and 0.609, respectively. A new combinatorial discriminative model including sLOX-1, MMP-9, WBC count, and the peak CK-MB level showed an area under the curve of 0.8431 (p < 0.001). With a cut-off point of 0.614, the sensitivity and specificity of plaque rupture were 62.2% and 97.6%, respectively. The new discriminative model using sLOX-1, MMP-9, WBC count, and peak CK-MB levels could better identify plaque rupture than each individual biomarker in ACS patients.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y.N Gao ◽  
W Liu ◽  
Y.J Zhou ◽  
S.J Wu

Abstract Background It has been demonstrated that high sensitive-C reactive protein (hs-CRP) and low density lipoprotein cholesterol (LDL-C) are independently associated with major adverse cardiovascular events (MACEs). Whether the level of LDL has impact on plaque characteristics in acute coronary syndrome (ACS) patients with normal hs-CRP are still unknown. Methods We retrospectively enrolled ACS patients with the level of hs-CRP&lt;2mg/L on admission from 1st January, 2017 to 31st December,2017, from our hospital. All patients underwent pre-intervention optical coherence tomography (OCT) to evaluate the plaque characteristics. Residual cholesterol risk (RCR) was defined as LDL-C≥1.8mmol/L, while hs-CRP&lt;2mg/L. According to the level of baseline LDL-C, patients were divided into RCR group and non-RCR group. Results A total of 90 patients (94 vessels) were included, with 50 patients in RCR group and 40 patients in non-RCR group. Compared with non-RCR group, patients in RCR group had higher levels of total cholesterol (4.39±0.89 vs 3.05±0.48, p=0.000), LDL-C (2.56±0.57 vs 1.54±0.22, p=0.000), triglycerides (1.11±1.12 vs 1.02±0.74, p=0.003). Patients in RCR group were younger (54.0±11.04 vs 58.4±9.59, p=0.049) and had higher rate of multivessel disease (6.0% vs 2.5%, p=0.028) than those in non-RCR group. With regard to plaque characteristics, fibrous plaque (0.0% vs 12.5%, p=0.003) was less seen and atherosclerotic plaque (79.6% vs 50.0%, p=0.028) was more seen in RCR group. In addition, patients in RCR group had significantly higher rate of plaque rupture than that in non-RCR group (24.1% vs 5%, p=0.008). To be noticed, cholesterol crystal and thin-cap fibroatheroma (TCFA) were more commonly in RCR group, though the difference was not statistical. Conclusion Patients with RCR have a great extent of plaque rupture, indicating more vulnerable plaque phenotype. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): China Youth Clinical Research Foundation-VG Foundation


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