bluuebunny/crossref_metadata_2025_split huggingface dataset:
HSP90 pathway in intermediate mononuclear cells causes plaque erosion via induction of neutrophil hyper-responsiveness
Authors: Ding H R , Qian J , Tong J , Tang J N , Lin H , Chu J P , Zhu G Q , Chen F , Liu X B 
Published: October 2021

Abstract

Aim
To explore the function(s) of HSP90 in intermediate monocyte-mediated plaque erosion.

Materials and methods
We used single-cell RNA sequencing to map cardiac immune response composition in patients with plaque rupture and plaque erosion. By focusing our analyses on CD14 positive monocytes, we obtained a higher resolution identification of the immune cell subsets in patients experiencing plaque erosion and rupture. We interpreted our findings with analyses using gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases and by performing receiver operating characteristic (ROC) curve analysis.

Results
Single-cell sequencing analysis of mononuclear cells in the peripheral blood of five ACS patients experiencing plaque erosion and rupture confirmed that CD14 positive monocytes were the main immune cells leading to ACS. Interestingly, our results suggested a significant increase in the proportion of atypical monocytes (C4 subsets) in patients with plaque rupture, which was a novel finding. This increase may be caused by increased migration of atypical monocytes into a plaque during plaque rupture. We found that intermediate monocyte activation was most obvious in patients with plaque erosion (C1, C10, and C11), and the proportion of C1 subgroup monocytes (FCGR3B/CMTM2 double strong positive; subsequently defined as intermediate monocytes) was very high. To further explore the role of C1 subgroup intermediate monocytes in plaque erosion, GO and KEGG pathway analyses were performed. GO analysis indicated that C1 subgroup intermediate monocytes are highly involved in neutrophil metabolism. Because neutrophils are the main effector cells that induce plaque erosion, we reasonably infer that intermediate monocytes can induce plaque erosion. KEGG pathway analysis indicated that all subtypes of HSP90 were highly expressed in C1 subgroup intermediate monocytes. We thus collected peripheral blood from ACS patients with plaque rupture (n=150) and plaque erosion (n=150) for mononuclear cell transcriptomics and intracellular proteomics analysis. ROC curve analysis demonstrated that the area under the curve for HSP90-based prediction was 0.86, indicating that HSP90 could be used to predict if patients would experience plaque erosion.

Conclusion
Activation of intermediate mononuclear HSP90 expression may be the crucial event that induces neutrophil hyper-responsiveness and leads to plaque erosion.

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): China,Shanghai Science and Technology Commission
Plaque and remodeling markers in coronary thrombi
Authors: Nordeng J , Helseth R , Aakra S , Hoffmann P , Schandiz H , Roald B , Bendz B , Arnesen H , Solheim S , Seljeflot I 
Published: October 2021

Abstract

Background
Matrix Metalloproteinases (MMPs) and their inhibitors are considered to be of importance in development of atherosclerotic coronary artery disease. MMP-9 has been associated with unstable atherosclerotic plaques and rupture, as well as left ventricular remodeling after myocardial infarction (MI), whereas MMP-2 seems to be more related to progression of stable plaques. MMP activity is modulated by Tissue Inhibitors of Metalloproteinases (TIMPs). TIMP-1 has been associated with cardiac remodeling post MI, and TIMP-2 has been discussed to inhibit plaque development and destabilization. The extracellular MMP Inducer, EMMPRIN, stimulates both MMPs and TIMPs, and has been found upregulated on the surface of monocytes in patients with acute MI, and associated with MMP-9 activity.

Purpose
To study whether genes encoding MMP-2, MMP-9, TIMP-1, TIMP-2 and EMMPRIN are expressed in coronary thrombi and in circulating leukocytes from STEMI patients, and whether these are related to the degree of myocardial injury measured by troponin T, and time from symptoms to PCI.

Methods
Intracoronary thrombi were aspirated from 33 patients with ST-elevation myocardial infarction (STEMI) treated with primary PCI. The thrombi were snap-frozen in RNA-later solution for gene expression analyses. Peripheral blood samples with Pax-gene tubes were drawn at end of the PCI procedure. RNA was isolated from the thrombi and leukocytes, and the actual genes relatively quantified by RT PCR. Peak troponin T was collected from clinical records.

Results
Genes coding for the five different markers were present in 84–100% of the thrombi. Median peak troponin T was 3434 m/L. The expression of TIMP-1 in the thrombi correlated significantly to peak troponin T (r=0.393, p=0.026), and dividing peak troponin T values into quartiles, the median value of TIMP-1 mRNA in Q4 was 2.5-fold higher compared to Q1–3 (p=0.107). Peak troponin T also correlated to the expression of TIMP-1 in circulating leukocytes (r=0.469, p=0.006), and in Q4 of troponin T, the median value was 1.6-fold higher compared to Q1–3 (p=0.056). There were no significant correlations between the other measured genes and troponin T, and also no associations of any genes expressed in the thrombi or in circulating leukocytes to time from symptom to PCI (median 152 min).

Conclusion
Genes coding for MMP-2, MMP-9, TIMP-1, TIMP-2 and EMMPRIN were highly expressed in human coronary thrombi. The positive correlation between peak troponin T and the expression of TIMP-1 both in thrombi and in circulating leukocytes at time of PCI in patients with STEMI, may indicate that the role of TIMP-1 is important in cardiac remodeling immediately post-MI.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Stein Erik Hagens Foundation for Clinical Heart Research
The prognostic value of the basal SYNTAX score I after early percutaneous coronary intervention using second generation drug eluting stents in patients with ST elevation myocardial infarction
Authors: Haq A , Tecson K , Aldujeli A , Hamadeh A , Simaityte P , Stalmokaite A , Navickaite I , Rekus A , Briedis K , Jarusevicius G , Unikas R , Zaliaduonyte D , Schussler J 
Published: October 2021

Abstract

Introduction
The SYNTAX score is an angiographic tool used to grade coronary artery disease (CAD) burden and complexity. SYNTAX score predicts 1-year adverse outcomes for patients with multivessel and/or left main CAD who undergo percutaneous coronary intervention (PCI). However, the relationship of the pre-PCI (basal) SYNTAX score to long-term outcomes of patients with ST-elevation myocardial infarction (STEMI) treated with primary PCI is unknown.

Purpose
To evaluate the short-term (in-hospital) and long-term (5-year) prognostic value of basal SYNTAX score in patients with STEMI who were treated with primary PCI.

Methods
We retrospectively reviewed records of consecutive patients presenting with STEMI, admitted from January 2014 to December 2016, who underwent primary PCI. We categorized patients into two groups according to SYNTAX scores: low/intermediate (≤22, 23–32) and high (&gt;33). We utilized the Cochran-Armitage test for trend, Chi-square test, Fisher's Exact test, and Kruskal-Wallis tests to assess differences in baseline characteristics and outcomes as appropriate. We used logistic regression and calculated the area under the receiver operating characteristic curve to determine the prognostic ability of SYNTAX score groups on 5-year outcomes for stroke, myocardial infarction (MI), cardiovascular death, target vessel revascularization (TVR), all-cause mortality, and major adverse cardiovascular events (MACE).

Results
There were 768 patients who met inclusion criteria for this study. 559 (72.8%) patients were in the low/intermediate SYNTAX score group and 209 (27.2%) patients were in the high SYNTAX score group. Baseline characteristics did not differ significantly between the two groups. In-hospital pacemaker implantation, in-hospital stent thrombosis, and in-hospital cardiac arrest and in-hospital death were rare and did not differ according to SYNTAX group (Table 1). However, the odds of experiencing stroke, MI, cardiovascular death, TVR, all-cause mortality, and MACE at 5 years were significantly higher in the high SYNTAX score group, even when adjusted for heart failure, total cholesterol, and age. The associated areas under the receiver operating characteristic curve indicated moderate-to-strong prognostic ability of the basal SYNTAX score (Table 2).

Conclusion
A high SYNTAX score in patients with STEMI who undergo primary PCI is associated poorer long-term outcomes, compared to patients with an intermediate/low score. This work confirms that a high burden of CAD in patients with STEMI portends a poorer long-term prognosis.

Funding Acknowledgement
Type of funding sources: None.
Predictive value of GRACE score combined with BNP and glycosylated hemoglobin for in-hospital cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention
Authors: Guo J D , Zhao Y Y , Wang X P , Liu D , Du Z , Zhang Y , Gao L J , Yuan J Q , Zhao X Y 
Published: October 2021

Abstract

Purpose
To investigate the value of Global Registry of Acute Coronary Events (GRACE) score combined with B-type natriuretic peptide (BNP) and glycosylated hemoglobin (HbA1c) in predicting in-hospital major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI).

Methods
A total of consecutive 675 patients with acute coronary syndrome (ACS) admitted to our hospital from June 2019 to June 2020, and finally, 319 patients treated with the percutaneous coronary intervenion (PCI) were enrolled. Major adverse cardiovascular events (MACE) during hospitalization included cardiac death, cardiogenic shock, congestive heart failure, recurrent ischemic chest pain and malignant arrhythmia. The area under the curve (AUC) was used to evaluate the predictive value of MACE during hospitalization.

Results
Among 319 patients, during hospitalization, 26 patients (8.15%) experienced the MACE. Compared to that of non-MACE group, there were more patients with previous history of heart failure (P&lt;0.001), lower in-admission systolic and diastolic blood pressure (P all&lt;0.05), and higher heart rate, GRACE score, BNP, and HbA1c levels in the MACE group (P all&lt;0.05). Multivariate logistic regression analysis showed that history of heart failure (OR: 1.498, 95% CI: 1.144–2.249), GRACE score (OR: 1.040, 95% CI: 1.017–1.063), BNP (OR: 1.019, 95% CI: 1.012–1.026) and HbA1C (OR: 1.199, 95% CI: 1.043–1.378) were independent risk factors for MACE in patients with ACS after PCI (P all&lt;0.05). The AUC of GRACE score for predicting MACE in ACS patients after PCI was 0.758, while the AUC of BNP and HbA1C was 0.838 and 0.788, respectively. When GRACE score combined with BNP and HbA1c, the AUC was increased to 0.876, which was significantly higher than the GRACE score alone (Z=4.142, P&lt;0.001).

Conclusion
In this study, we reported for the first time, GRACE score combined with BNP and HbA1c significantly improved the predictive value of in-hospital MACE in ACS patients after PCI compared with traditional GRACE score, which can help clinicians identify high risk patients to improve their prognosis in the clinical practice.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): Young and middle-aged talents in the XPCC Science and Technology Project (2020CB012); Key Science and Technology Project of Shihezi (2019ZH09) ROC Curve
Trends in major bleeding events in patients with acute coronary syndrome
Authors: Cordero A , Escribano D , Bertomeu-Gonzalez V , Moreno-Arribas J , Monteagudo M , Lopez Ayala J M , Perez-Berbell P , Quintanilla M A , Zuazola P 
Published: October 2021

Abstract

Background
Bleeding events incidence has gained a crucial role in acute coronary patients (ACS) due to its independent effect prognostic value.

Methods
We assessed the trend of in-hospital and first-year-after-discharge major bleeding events (MB) in all ACS admitted in a single center between January 2009 and Agoust 2019. MB was defined as those fitting definitions 3 or 5 of the BARC consortium. Patients were categorized as high-bleeding risk (HBR) if according to the 2019 Academic Research Consortium HBR consensus if they met at least one major or two minor criteria. Inclusion period was divided in 3 groups: 2009–2012 (n=884; 27.4%), 2013–2015 (n=1,047; 32.5%); 2016–2019 (n=1,294; 40.1%). Post-discharge MB was assessed by competing events regression models, taking all-cause mortality as a competing event, and results are presented as sub-hazard ratio (sHR).

Results
We included 3225 patients, mean age was 68.4 (29.7), 25.7% females, 1,108 32.1% had diabetes and 44.0% STEMI. Radial access was perfume in 92% of the angiographies in the 3 time-periods. A significant decrease in dual antiplatelet treatment (DAPT) before angiography was noted (69.0%; 56.3%; 53.6%; p=0.001) with a decreasing pattern in clopidogrel and increase in ticagrelor and prasugrel. A total of 1,591 (46.2%) were categorized as HBR patients. A non-significant trend to higher incidence of in-hospital MB was noted through the 3 time periods: 1.39%; 1.43%; 2.55% (p=0.056) and it was mainly driven by the significant increase only in HBR patients: 2.21%; 3.55%; 6.26% (p=0.003). Multivariate analysis identified age (OR: 1.06 95% CI 1.03–1.08, p&lt;0.001) and the time period 2016–2019 (OR: 1.96 95% CI 1.01–3.84; p=0.031) as main variables associated to higher in-hospital MB.
In contrast, postdischarge MB did not change overtime (p=0.155) and trends were the same in HBR and non-HBR patients (figure). The competing risk regression analysis, adjusted by age, gender, previous cardiovascular disease, revascularization and medical treatments, identified that the leading factors for postdischarge MB were diabetes (sHR: 1.37; 95% CI 1.01–2.92), time-period 2016–2019 (sHR: 1.52; 95% CI 1.01–2.30), HBR patient (sHR: 1.91; 95% CI 1.28- 2.87) and and previous heart failure (sHR: 2.26; 95% CI 1.264.40)

Conclusions
This continuous 10-year registry highlights the increasing trend of in-hospital mainly driven by the incidence in HBR patients. In contrast, postdischarge MB increased in all patients.

Funding Acknowledgement
Type of funding sources: None. Post-discharge MB incidence
J-shaped relationship between admission diastolic blood pressure and 2-year cardiovascular mortality in elderly patients with acute coronary syndrome
Authors: Jiang C , Wu S , Wang M , Li H , Zhao X 
Published: October 2021

Abstract

Objective
To investigate the relationship between admission diastolic blood pressure (DBP) and subsequent cardiovascular and all-cause mortality in elderly patients with acute coronary syndrome (ACS).

Methods
This is a retrospective observational study. Consecutive patients ≥65 years of age admitted for ACS at a 2,300-bed tertiary hospital from December 2012 to July 2019 were included. The association between admission DBP and cardiovascular and all-cause mortality during hospitalization and over the follow-up period among this population were analyzed using multivariate COX regression model. Results were presented according to DBP quartiles: Q1, less than 67 mm Hg; Q2, from 67 to 72 mm Hg; Q3, from 73 to 80 mm Hg; and Q4, above 80 mm Hg.

Results
A total of 6 785 patients were included in this cohort study. Mean (SD) patient age was 74.0 (6.5) years, and 47.6% were women. Mean (SD) follow-up time was 2.54 (1.82) years. A non-linear relation was observed between DBP at admission and cardiovascular and all-cause mortality during hospitalization and over the follow-up period using restricted cubic splines. After adjustment for potential confounders, patients in Q3 or Q2 had lower risk for 2-year cardiovascular death by Cox proportional hazard model compared with patients in Q4 (hazard ratio [HR] 0.66; 95% confidence interval [CI], 0.48–0.90, P=0.010, for Q3 vs Q4; and HR 0.72; 95% CI, 0.53–0.99, P=0.041, for Q2vs Q4), while patients in Q1 had similar risk for cardiovascular death with that of patients in Q4. Meanwhile, when compared with patients in Q1, patients in Q3 had lower risk for 2-year cardiovascular death (HR, 0.72; 95% CI, 0.53–0.97, P=0.033). However, lower or higher admission DBP was not an independent predictor of 2-year all-cause mortality in this population.

Conclusion
Among patients aged ≥65 years admitted for ACS, there is a J-curve relationship between supine admission DBP and risk for 2-year cardiovascular death, with a nadir at 73–80 mm Hg.

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support Study population and selectionAdjusted multivariate COX regression
5-hydroxymethylcytosine profiles in circulating cell-free DNA as candidate diagnostic and predictive biomarkers for coronary artery disease
Authors: Xu J , Yang Y J , Chen H Y , Dong C R , Lin J , Zhu H B , Yang J G , Wu Y , Yang Y M , Zhang J , Li J , Liang Y , Wang M , Zhao D Y , Zhao R 
Published: October 2021

Abstract

Background
DNA 5-hydroxymethylcytosine (5hmC) modification is an epigenetic marker involved in a range of biological processes. However, little information is available about its role in coronary artery disease (CAD), particularly in the acute phase of acute coronary syndrome (ACS).

Aims
To investigate whether 5hmC modification correlates with the pathogenesis and progression of CAD and whether 5hmC in cfDNA can be used as biomarkers.

Methods
We utilized 5hmC-Seal to generate genome-wide 5hmC profiles in plasma cell-free DNA (cfDNA) of normal coronary artery (NCA, n=200) controls and CAD patients, including stable coronary artery disease (sCAD, n=200) patients and ACS patients (n=371). To investigate the correlation between 5hmC modifications and CAD subtypes, we separated samples into training and validation cohorts and developed a 5hmC-based logistic regression model from the training cohort to predict the progression of CAD in the validation cohort.

Results
We detected a significant difference of 5hmC enrichment in gene bodies from CAD patients compared with NCA individuals. Particularly, our results showed that patients of CAD subgroups can be well separated from NCA individuals by 5hmC markers. The prediction performance of the model established by differentially regulated 5hmC modified genes achieved an AUC of 0.81 (sCAD vs. NCA) and 0.74 (ACS vs. NCA) in validation cohorts.

Conclusions
Our results demonstrated that patients of CAD subtypes and NCA individuals had distinct differences in 5hmC enrichment. 5hmC markers derived from plasma cfDNA may potentially serve as a clinical-applicable, minimally invasive, and liquid biopsy-based approach to diagnose CAD, particularly used to predict the occurrence of fetal ACS.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Chinese Academy of Medical Science (CAMS) Innovation Fund for Medical Sciences Figure 1Figure 2
Association between plasma big endothelin-1 level and the severity of coronary artery disease in patients with non-ST segment-elevated myocardial infarction
Authors: Lyu S , Zhu J , Yu L , Yang Y 
Published: October 2021

Abstract

Background
This study aimed to evaluate the association between plasma big endothelin-1 (ET-1) level and the severity of coronary artery disease assessed by the SYNTAX score (SS) in patient with non-ST segment-elevated myocardial infarction (NSTEMI).

Methods
A total of 766 patients with NSTEMI undergoing coronary angiography were recruited. Patients were divided into divided into three groups: low SS (SS ≤22), intermediate SS (23–32) and high SS group (SS &gt;32). Spearman correlation, smooth curve fitting, logistic regression and Receiver operating characteristic (ROC) curve analysis were performed to evaluated the association between plasma big ET-1 level and the SS.

Results
There was a significant correlation between the big ET-1 and the SS (r=0.378, p&lt;0.001). Smoothing curve indicated a positive correlation between plasma big ET-1 level and the SS, after adjustment for potential confounders. The ROC curve analysis showed that the area under the curve was 0.695 (0.661–0.727) and the optimal cutoff of plasma big ET-1 level were 0.35pmol/l, with a sensitivity of 68.9% and a specificity of 62.9%. Logistic regression showed that elevated big ET-1 was an independent predictor of intermediate-high SS in patients with NSTEMI, no matter entered as a continuous variable [OR (95% CI): 1.110 (1.053–1.170), p&lt;0.001] or as a categorical variable [OR (95% CI): 2.873 (2.016–4.094), p&lt;0.001]. The association between big ET-1 and intermediate-high SS was consistent across subgroups without significant interactions.

Conclusion
In patients presenting with NSTEMI, plasma big ET-1 level was significantly correlated with the SS. Elevated plasma big ET-1 level was an independent predictor for intermediate-high SS.

Funding Acknowledgement
Type of funding sources: None. ROC of big ET-1 for high SYNTAX score
The state of the left ventricular-arterial coupling depending on the left ventricular ejection fraction in patients with acute myocardial infarction
Authors: Salyamova L , Khromova A , Kvasova O , Burko N , Makarova K 
Published: October 2021

Abstract

Objective
To conduct a comparative analysis of the indicators of left ventricular-arterial coupling (LVAC) in patients with primary acute myocardial infarction with ST segment elevation (STEMI), depending on the initial level of the left ventricular ejection fraction (EF).

Methods
The study included 148 patients with STEMI (mean age 51.5 [CI% 50.1; 52.9] years) in the first 24–96 hours from the disease onset. An inclusion criterion was the presence of hemodynamically significant stenosis of only one coronary artery according to the coronary angiography results. On days 7–9th from the disease onset, the patients underwent standard echocardiography on the MyLab device (Esaote, Italy) with the determination of the end diastolic volume (EDV), end systolic volume (ESV), EF and the subsequent calculation of LVAC: arterial elastance (Ea), left ventricular elastance (Ees), including those reduced to body surface area (Ea/BSA and Ees/BSA), LVAC index (Ea/ Ees). In accordance with the LVEF values, the patients were divided into 3 groups. The 1st group included 79 people with preserved EF (≥50%), the 2nd group – 53 patients with mid-range EF (40–49%); Group 3 consisted of 16 patients with reduced EF (&lt;40%). The compared groups were matched by age, sex, anthropometric data, and treatment.

Results
In the 1st group, the Ea indicator was 1.8 [CI% 1.7; 1.9], in group 2 – 2.0 [CI% 1.8; 2.1], in the third group – 2.2 [CI% 1.9; 2.5] mm Hg/ml (p1-3 = 0.01). The Ees indicator in the comparison groups was 2.2 [CI% 2.1; 2.4], 1.7 [CI% 1.5; 1.9] and 1.2 [CI% 0.9; 1.5] mm Hg/ml, respectively (p1-2-3 &lt;0.01). The Ea/BSA index in the 1st group was 0.92 [CI% 0.85; 1.0], in the 2nd group – 1.0 [CI% 0.94; 1.13], in the third group – 1.16 [CI% 0.99; 1.33] mm Hg/ml/m2 (p1–3 = 0.01). The Ees/BSA indicator in the comparison groups was 1.16 [CI% 1.08; 1.24], 0.88 [CI% 0.79; 0.98] and 0.64 [CI% 0.46; 0.82] mm Hg/ml/m2, respectively (p1-2-3 &lt;0.01). The Ea/Ees index was the smallest in the 1st group – 0.8 [CI% 0.8; 0.9]; higher in the 2nd group – 1.2 [CI% 1.1; 1.3]; the maximum values were registered in the 3rd group – 1.9 [CI% 1.7; 2.0] (p1-2-3 &lt;0.0001).

Conclusions
In STEMI patients with mid-range and reduced EF, high values of the LVAC index were revealed, which is due to a decrease in left ventricular elastance due to impaired LV contractility.

Funding Acknowledgement
Type of funding sources: None.