scholarly journals Innovative Approaches to Assess Intermediate Cardiovascular Risk Subjects: A Review From Clinical to Metabolomics Strategies

2021 ◽  
Vol 8 ◽  
Author(s):  
Aline M. A. Martins ◽  
Mariana U. B. Paiva ◽  
Diego V. N. Paiva ◽  
Raphaela M. de Oliveira ◽  
Henrique L. Machado ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Risk Stratification ◽  
Molecular Mechanisms ◽  
Resonance Spectroscopy ◽  
Clinical Implementation ◽  
Metabolomics Data ◽  
Coronary Syndrome ◽  
Coronary Events ◽  
The Individual ◽  
Asymptomatic Subjects

Current risk stratification strategies for coronary artery disease (CAD) have low predictive value in asymptomatic subjects classified as intermediate cardiovascular risk. This is relevant because not all coronary events occur in individuals with traditional multiple risk factors. Most importantly, the first manifestation of the disease may be either sudden cardiac death or acute coronary syndrome, after rupture and thrombosis of an unstable non-obstructive atherosclerotic plaque, which was previously silent. The inaccurate stratification using the current models may ultimately subject the individual to excessive or insufficient preventive therapies. A breakthrough in the comprehension of the molecular mechanisms governing the atherosclerosis pathology has driven many researches toward the necessity for a better risk stratification. In this Review, we discuss how metabolomics screening integrated with traditional risk assessments becomes a powerful approach to improve non-invasive CAD subclinical diagnostics. In addition, this Review highlights the findings of metabolomics studies performed by two relevant analytical platforms in current use–mass spectrometry (MS) hyphenated to separation techniques and nuclear magnetic resonance spectroscopy (NMR) –and evaluates critically the challenges for further clinical implementation of metabolomics data. We also discuss the modern understanding of the pathophysiology of atherosclerosis and the limitations of traditional analytical methods. Our aim is to show how discriminant metabolites originated from metabolomics approaches may become promising candidate molecules to aid intermediate risk patient stratification for cardiovascular events and how these tools could successfully meet the demands to translate cardiovascular metabolic biomarkers into clinical settings.

scholarly journals Walking Beyond the GRACE (Global Registry of Acute Coronary Events) Model in the Death Risk Stratification During Hospitalization in Patients With Acute Coronary Syndrome

2012 ◽  
Vol 5 (11) ◽  
pp. 1117-1125 ◽  
Author(s):  
Sergio Raposeiras-Roubín ◽  
Emad Abu-Assi ◽  
Pilar Cabanas-Grandío ◽  
Rosa María Agra-Bermejo ◽  
Santiago Gestal-Romarí ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Risk Stratification ◽  
Death Risk ◽  
Coronary Syndrome ◽  
Coronary Events ◽  
Global Registry

scholarly journals Association of Neutrophil Lymphocyte Ratio (NLR) with Global Registry of Acute Coronary Events (GRACE) Scores in Acute Coronary Syndrome

2020 ◽  
Vol 2 (3) ◽  
pp. 162-170
Author(s):  
Baginda Yusuf Siregar ◽  
Refli Hasan ◽  
Rahmad Isnanta
Keyword(s):  
Acute Coronary Syndrome ◽  
Risk Stratification ◽  
Design Data ◽  
Cross Sectional ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Coronary Syndrome ◽  
Coronary Events ◽  
Global Registry ◽  
Grace Score

Background. Inflammation plays an important role in the initiation of atherosclerosis from the beginning of plaque to rupture cause Acute Coronary Syndrome (ACS). Neutrophil Lymphocyte Ratio (NLR) indicator of systemic inflammation in ACS. Risk stratification was needed for assessment and selection of initial invasive strategies and find the best strategy in ACS. The Global Registry of Acute Coronary Events (GRACE) scores recommended risk stratification of ACS. Aims of the study to determine the association and cut-off value NLR with risk stratification GRACE score. Method. This study is analytical with a cross-sectional retrospective design. Data were analyzed after distribution test, then mean difference and correlation test was using the SPPS program where p <0.05 was considered statistically significant. Results. This study showed significantly higher NLR value in the high risk stratification and intermediate-risk compared to low risk stratification (7.9 ± 2.7 vs 3.6 ± 1.7; p=0.001) (5.2 ± 2.3 vs 3.6 ± 1.7; p=0.018). Significant correlation between NLR ​​with GRACE scores (r=0.570; p<0.001). Significant AUC values ​​were obtained (0.782, p <0.001, IK95% 0.674-0.89), and cut-off values NLR 4 ​​with sensitivity (78.8%) and specificity (70.3%) on the GRACE score. Conclusion. The significant association between NLR ​​with GRACE risk score in ACS.

scholarly journals Association of Platelet Lymphocyte Ratio (PLR) and Neutrophil Lymphocyte Ratio (NLR) with Global Registry of Acute Coronary Events (GRACE) Score in Acute Coronary Syndrome

2021 ◽  
Vol 8 (5) ◽  
pp. 1-6
Author(s):  
Baginda Yusuf Siregar ◽  
Refli Hasan ◽  
Rahmad Isnanta
Keyword(s):  
Acute Coronary Syndrome ◽  
High Risk ◽  
Risk Stratification ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Coronary Syndrome ◽  
Platelet Lymphocyte Ratio ◽  
Coronary Events ◽  
Global Registry ◽  
Grace Score

Introduction: Acute Coronary Syndrome (ACS) has morbidity and mortality significantly increase, it requires risk stratification for the assessment and selection of initial invasive strategies. The Global Registry of Acute Coronary Events (GRACE) scores recommended as risk stratification of ACS. Some of studies found that the combination of GRACE scores with other clinical and laboratory parameters can increase predictive value of ACS. Platelet Lymphocyte Ratio (PLR) and Neutrophil Lymphocyte Ratio (NLR) act as parameter of systemic inflammation in ACS. Aims of the study to determine the association between PLR and NLR with risk stratification GRACE score. Method: This study is analytical with a cross-sectional retrospective design. This study included 70 patients with a diagnosis of ACS based on medical record data. Data analysis was performed using the Statistical Package for the Social Sciences (SPSS) 22.0. P-value <0.05 was considered statistically significant. Results: This study was found a positive correlation between PLR and NLR with the GRACE score of patients ACS (r=0.485, p<0.001; r=0.570, p<0.001). The PLR and NLR were both found the significantly higher in the high risk GRACE score respectively (188 ± 47, p < 0.001; 7.9± 2.7, p<0.001). The ROC curve analysis, cutt-off PLR of 123 and above (sensitivity of 72.7 %; specificity of 70.3), while cutt-off NLR of 4 and above (sensitivity of 78.8%; specificity of 70.3%) to detect high risk GRACE score. Conclusion: There is a significant association between PLR and NLR with GRACE score Keywords: Platelet Lymphocyte Ratio, Neutrophil Lymphocyte Ratio, GRACE score, Acute Coronary Syndrome.

scholarly journals Immune and Inflammation in Acute Coronary Syndrome: Molecular Mechanisms and Therapeutic Implications

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Haiming Wang ◽  
Zifan Liu ◽  
Junjie Shao ◽  
Lejian Lin ◽  
Min Jiang ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Cardiovascular Events ◽  
Molecular Mechanisms ◽  
Thrombus Formation ◽  
Unstable State ◽  
Plaque Instability ◽  
Therapeutic Implications ◽  
Atherosclerosis Progression ◽  
Coronary Syndrome ◽  
Coronary Events

Acute coronary syndrome (ACS) is a major cause of acute death worldwide. Both innate and adaptive immunity regulate atherosclerosis progression, plaque stability, and thrombus formation. Immune and inflammation dysfunction have been indicated in the pathogenesis of ACS. The imbalance in the proatherogenic and antiatherogenic immune networks promotes the transition of plaques from a stable to unstable state and results in the occurrence of acute coronary events. The residual inflammatory risk (RIR) has received increasing attention in recent years, and lowering RIR has been expected to improve the outcomes of ACS patients. The CANTOS, COLCOT, and LoDoCo trials verified the benefits of reducing cardiovascular events using anti-inflammation therapies; however, most of the other studies focusing on lowering RIR produced negative or contradicting results. Therefore, restoring the balance in autoimmune regulation is essential because proatherogenic and antiatherogenic immunomodulatory effects are equally important in the complex human immune network. In this review, we summarized the recent evidence of the roles of proatherogenic and antiatherogenic immune networks in the pathogenesis of ACS and discussed how immune and inflammation contribute to atherosclerosis progression, plaque instability, and adverse cardiovascular events. We also provide a “from bench to bedside” perspective of a novel and promising personalized strategy in RIR intervention and therapeutic approaches for the treatment of ACS.

Myocardial Infarction in Systemic Lupus Erythematosus – the Sex Specific Risk Profile

2020 ◽  
Vol 26 ◽  
Author(s):  
Marija Vavlukis ◽  
Daniela Pop-Gjorceva ◽  
Lidija Poposka ◽  
Emilija Sandevska ◽  
Sasko Kedev
Keyword(s):  
Myocardial Infarction ◽  
Systemic Lupus Erythematosus ◽  
Cardiovascular Risk ◽  
Coronary Artery ◽  
Young Women ◽  
Lupus Erythematosus ◽  
Molecular Mechanisms ◽  
Clinical Presentation ◽  
Systemic Lupus ◽  
Antiinflammatory Therapy

Background: Accelerated atherosclerosis is widely present in patients with systemic lupus erythematosus. Objective: The aim of this review is to analyze the relationship between systemic lupus erythematosus and cardiovascular diseases, with the emphasis on acute myocardial infarction. Results: Various molecular mechanisms triggered by infection/inflammation are responsible for endothelial dysfunction and development of atherosclerosis at an earlier age. Contributing factor is the cumulative effect of traditional cardiovascular risk factors interaction with disease related characteristics. Myocardial infarction rates are 2- to 10-fold higher compared to the general population. Young women have the highest relative risk, however, men carry at least 3- fold higher risk than women. Coronary involvement varies from normal coronary artery with thrombosis, coronary microartery vasculitis, coronary arteritis, and coronary atherosclerosis. Typical clinical presentation is observed in men and older women, while atypical is more frequent in young women. Treatment is guided by the underlying mechanism, engaging invasive procedures alone, or accompanied with immunosuppressive and/or antiinflammatory therapy. There are significant gender differences in pathophysiology and clinical presentation. However, they receive the same therapeutic treatments. Conclusion: Systemic lupus erythematosus is a major contributor to atherosclerotic and non-atherosclerotic mechanisms involved in the development of myocardial infarction, which should be taken into account during therapeutic treatment. Although Systemic lupus erythematosus per se is a “female” disease, males are at increased cardiovascular risk and worse outcome. Method: We conducted a literature review through PubMed and Cochrane, using key words: SLE, atherosclerosis, atherothrombosis, coronary artery disease, myocardial infarction, prognosis, sex specifics.

scholarly journals Cryo–electron microscopy structure of the antidiuretic hormone arginine-vasopressin V2 receptor signaling complex

2021 ◽  
Vol 7 (21) ◽  
pp. eabg5628
Author(s):  
Julien Bous ◽  
Hélène Orcel ◽  
Nicolas Floquet ◽  
Cédric Leyrat ◽  
Joséphine Lai-Kee-Him ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Antidiuretic Hormone ◽  
Arginine Vasopressin ◽  
Molecular Mechanisms ◽  
Particle Analysis ◽  
Resonance Spectroscopy ◽  
Gpcr Signaling ◽  
Signaling Complex ◽  
Cryo Electron Microscopy ◽  
V2 Receptor

The antidiuretic hormone arginine-vasopressin (AVP) forms a signaling complex with the V2 receptor (V2R) and the Gs protein, promoting kidney water reabsorption. Molecular mechanisms underlying activation of this critical G protein–coupled receptor (GPCR) signaling system are still unknown. To fill this gap of knowledge, we report here the cryo–electron microscopy structure of the AVP-V2R-Gs complex. Single-particle analysis revealed the presence of three different states. The two best maps were combined with computational and nuclear magnetic resonance spectroscopy constraints to reconstruct two structures of the ternary complex. These structures differ in AVP and Gs binding modes. They reveal an original receptor-Gs interface in which the Gαs subunit penetrates deep into the active V2R. The structures help to explain how V2R R137H or R137L/C variants can lead to two severe genetic diseases. Our study provides important structural insights into the function of this clinically relevant GPCR signaling complex.

scholarly journals Insights into the molecular mechanisms of Huangqi decoction on liver fibrosis via computational systems pharmacology approaches

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Biting Wang ◽  
Zengrui Wu ◽  
Weihua Li ◽  
Guixia Liu ◽  
Yun Tang
Keyword(s):  
Molecular Docking ◽  
Liver Fibrosis ◽  
Molecular Mechanisms ◽  
Docking Simulation ◽  
Chinese Herbs ◽  
Network Pharmacology ◽  
Bipartite Network ◽  
Metabolomics Data ◽  
Metabolic Products ◽  
Compound Target

Abstract Background The traditional Chinese medicine Huangqi decoction (HQD) consists of Radix Astragali and Radix Glycyrrhizae in a ratio of 6: 1, which has been used for the treatment of liver fibrosis. In this study, we tried to elucidate its action of mechanism (MoA) via a combination of metabolomics data, network pharmacology and molecular docking methods. Methods Firstly, we collected prototype components and metabolic products after administration of HQD from a publication. With known and predicted targets, compound-target interactions were obtained. Then, the global compound-liver fibrosis target bipartite network and the HQD-liver fibrosis protein–protein interaction network were constructed, separately. KEGG pathway analysis was applied to further understand the mechanisms related to the target proteins of HQD. Additionally, molecular docking simulation was performed to determine the binding efficiency of compounds with targets. Finally, considering the concentrations of prototype compounds and metabolites of HQD, the critical compound-liver fibrosis target bipartite network was constructed. Results 68 compounds including 17 prototype components and 51 metabolic products were collected. 540 compound-target interactions were obtained between the 68 compounds and 95 targets. Combining network analysis, molecular docking and concentration of compounds, our final results demonstrated that eight compounds (three prototype compounds and five metabolites) and eight targets (CDK1, MMP9, PPARD, PPARG, PTGS2, SERPINE1, TP53, and HIF1A) might contribute to the effects of HQD on liver fibrosis. These interactions would maintain the balance of ECM, reduce liver damage, inhibit hepatocyte apoptosis, and alleviate liver inflammation through five signaling pathways including p53, PPAR, HIF-1, IL-17, and TNF signaling pathway. Conclusions This study provides a new way to understand the MoA of HQD on liver fibrosis by considering the concentrations of components and metabolites, which might be a model for investigation of MoA of other Chinese herbs.

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