Utility of mass spectrometry for the diagnosis of the unstable coronary plaque.

Mass spectrometry is a powerful technique that is used to identify unknown compounds, to quantify known materials, and to elucidate the structure and chemical properties of molecules. Recent advances in the accuracy and speed of the technology have allowed data acquisition for the global analysis of lipids from complex samples such as blood plasma or serum. Here, mass spectrometry as a tool is described, its limitations explained and its application to biomarker discovery in coronary artery disease is considered. In particular an application of mass spectrometry for the discovery of lipid biomarkers that may indicate plaque morphology that could lead to myocardial infarction is elucidated

Proteomics in cardiovascular disease: recent progress and clinical implication and implementation

Introduction: Although multiple efforts have been initiated to shed light into the molecular mechanisms underlying cardiovascular disease, it still remains one of the major causes of death worldwide. Proteomic approaches are unequivocally powerful tools that may provide deeper understanding into the molecular mechanisms associated with cardiovascular disease and improve its management. Areas covered: Cardiovascular proteomics is an emerging field and significant progress has been made during the past few years with the aim of defining novel candidate biomarkers and obtaining insight into molecular pathophysiology. To summarize the recent progress in the field, a literature search was conducted in PubMed and Web of Science. As a result, 704 studies from PubMed and 320 studies from Web of Science were retrieved. Findings from original research articles using proteomics technologies for the discovery of biomarkers for cardiovascular disease in human are summarized in this review. Expert commentary: Proteins associated with cardiovascular disease represent pathways in inflammation, wound healing and coagulation, proteolysis and extracellular matrix organization, handling of cholesterol and LDL. Future research in the field should target to increase proteome coverage as well as integrate proteomics with other omics data to facilitate both drug development as well as clinical implementation of findings

Circulating interleukin-10 and risk of cardiovascular events: a prospective study in the elderly at risk

<p><b>Objective:</b> The goal of this study was to examine the association of the antiinflammatory interleukin-10 (IL-10) with risk of cardiovascular disease (CVD).</p> <p><b>Methods and Results:</b> In the PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) cohort, we related baseline concentrations of circulating IL-10 to risk of CVD events in a nested case (n=819)-control (n=1618) study of 3.2 years of follow-up. Circulating IL-10 showed few strong associations with classical risk factors but was positively correlated with IL-6 and C-reactive protein. IL-10 was positively associated with risk of CVD events (odds ratio [OR] 1.17, 95% CI 1.05 to 1.31 per unit increase in log IL-10) after adjusting for classical risk factors and C-reactive protein. Furthermore, IL-10 was associated more strongly with CVD risk among those with no previous history of CVD (OR 1.42, 95% CI 1.18 to 1.70), compared with those with previous CVD (OR 1.04, 95% CI 0.90 to 1.19; P=0.018). Overall, IL-10 showed a modest ability to add discrimination to classical risk factors (C-statistic +0.005, P=0.002).</p> <p><b>Conclusion:</b> Baseline circulating levels of the antiinflammatory IL-10 are positively associated with risk of CVD among the elderly without prior CVD events, although the association is less evident in those with a history of CVD. Additional epidemiological and mechanistic studies investigating the role of IL-10 in CVD are warranted.</p&gt

Role of biomechanical forces in the natural history of coronary atherosclerosis.

Atherosclerosis remains a major cause of morbidity and mortality worldwide, and a thorough understanding of the underlying pathophysiological mechanisms is crucial for the development of new therapeutic strategies. Although atherosclerosis is a systemic inflammatory disease, coronary atherosclerotic plaques are not uniformly distributed in the vascular tree. Experimental and clinical data highlight that biomechanical forces, including wall shear stress (WSS) and plaque structural stress (PSS), have an important role in the natural history of coronary atherosclerosis. Endothelial cell function is heavily influenced by changes in WSS, and longitudinal animal and human studies have shown that coronary regions with low WSS undergo increased plaque growth compared with high WSS regions. Local alterations in WSS might also promote transformation of stable to unstable plaque subtypes. Plaque rupture is determined by the balance between PSS and material strength, with plaque composition having a profound effect on PSS. Prospective clinical studies are required to ascertain whether integrating mechanical parameters with medical imaging can improve our ability to identify patients at highest risk of rapid disease progression or sudden cardiac events.This work was supported by the British Heart Foundation (FS/13/33/30168), Heart Research UK (RG2638/14/16), the Cambridge NIHR Biomedical Research Centre, and the BHF Cambridge Centre for Research Excellence.This is the author accepted manuscript. The final version is available from Nature Publishing Group at http://dx.doi.org/10.1038/nrcardio.2015.203

Role of immunoturbidimetric plasma fibrin D-dimer test in patients with coronary artery disease as well as ischemic heart disease in emergency medicine

The aim of the present was to assess the value of the ELISA D-dimer (hemostatic marker) assay in patients with coronary artery disease as well as ischemic heart disease presenting to the emergency department with chest pain syndrome. Methods: We measured levels of D-dimers (µg/ml by immunoturbidimetric assay) in 120 patients with angiographically proved CAD, consecutive outpatients with chest pain, arterial fibrillation, acute coronary syndromes and 240 age and sex matched healthy controls. Demographic characteristics were assessed by a standardized questionnaire, and a complete lipid profile was performed for all subjects. In addition to this inflammatory marker C- reactive protein was also measured. Result: The distribution of D-dimer levels skewed to the right, and plasma mean levels were higher in cases than in control (mean: 2.51±3.60 vs .41±.59 µg/ml; p<0.001). In contrast, correlation of D-dimer was found with C-reactive protein (p<0.001) and is higher in cases than controls. Conclusion: Plasma D-dimer levels are strongly and independently associated with the presence of CAD in patients with stable angina. These results support the concept of a contribution of intravascular fibrin to atherothrombogenesis

Arterial Stiffness as A Predictor of Future Cardiovascular Events: Methods of Measurement and Clinical Implications

Arterial stiffness has recently emerged as strong predictor of cardiovascular events, including coronary heart disease. The cardio-ankle vascular index (CAVI) is a novel index that measures the overall stiffness of the artery all the way from the point where it branches off from the aorta to the ankle. CAVI's ability to provide accurate results regardless of the patient's blood pressure at the moment of measurement is without a doubt its most valuable characteristic. CAVI is related to many cardiovascular risk factors, including hypertension, diabetes mellitus, dyslipidemia, and smoking. It also increases with age and in many arteriosclerotic diseases, such as coronary artery disease, carotid arteriosclerosis, chronic kidney disease, and cerebrovascular disease. CAVI also increases in patients who have cerebrovascular disease. Controlling conditions such as diabetes mellitus and hypertension, in addition to quitting smoking, may also reduce the risk of CAVI. This indicates that CAVI is a physiological surrogate measure of atherosclerosis, and it also implies that it might be a signal of lifestyle change. Recent research has shown that CAVI and numerous functions of the left ventricle are linked to one another, which points to a linkage between the heart muscle and vascular function. This study discusses the fundamentals of CAVI as well as our present understanding of the measurement, with a particular emphasis on its functions and potential future use. 

Comparison of coronary risk scoring systems to predict the severity of coronary artery disease using the SYNTAX score

Background: Reliable risk scoring systems that can predict the severity of coronary artery disease (CAD) are necessary to implement effective management strategies in high-risk patients. Atherosclerotic vascular disease and with cardiovascular morbidity and mortality risk are patients who would benefit most from a change in patients at high risk factors. Framingham Risk Score, the Prospective Cardiovascular Münster (PROCAM) score and Systematic Coronary Risk Evaluation (SCORE) risk scores are used for this purpose. The severity of the CAD as detected by coronary angiography can be estimated using the SYNTAX score. In this study, it is aimed to assess the relation between SYNTAX score and the Framingham, PROCAM and SCORE scores in the context of their utility for the determination of the severity of the CAD. Methods: A total of 205 patients with documented CAD who underwent coronary angiography due to a diagnosis of stable angina pectoris were included in this study. Coronary risk scores were determined for each patient. The relation between the SYNTAX score and the results of coronary risk scoring systems were analyzed. Results: A positive relationship between the SYNTAX score, which reflects the severity of the CAD and coronary risk scores was found. However, Framingham and SCORE were superior, i.e., had more predictive value, regarding their ability to predict the SYNTAX score (p = 0.029, 0.033 and 0.002, respectively). Conclusions: Examination of the distribution of SYNTAX score across low, intermediate and high-risk groups showed a significantly higher predictive value of SCORE for high-risk patients (p = 0.005).

The Role of Costimulatory Receptors of the Tumour Necrosis Factor Receptor Family in Atherosclerosis

Atherosclerosis is a chronic inflammatory disease that is mediated by both the innate and adaptive immune responses. T lymphocytes, that together with B cells are the cellular effectors of the adaptive immune system, are currently endowed with crucial roles in the development and progression of atherosclerosis. Costimulatory receptors are a class of molecules expressed by T lymphocytes that regulate the activation of T cells and the generation of effector T-cell responses. In this review we present the roles of costimulatory receptors of the tumour necrosis factor receptor (TNFR) superfamily in atherosclerosis and discuss the implications for future therapies that could be used to specifically modulate the immune response of pathogenic T cells in this disease

Value of Manchester Acute Coronary Syndromes Decision Rule in the Detection of Acute Coronary Syndrome; a Systematic Review and Meta-Analysis

Introduction: There is still no consensus on the value of Manchester Acute Coronary Syndromes (MACS) decision rule in detecting acute coronary syndrome (ACS). Therefore, the purpose of the present systematic review and meta-analyzes is to summarize the clinical evidence in the evaluation of  the value of MACS in the diagnosis of ACS.Methods: A literature search was performed on the Medline, Embase, Scopus, and Web of Science databases. Outcomes included acute myocardial infarction (AMI) and major adverse cardiac event (MACE).  Data were analyzed in the STATA 14.0 statistical program and the results were reported as summary receiver operating characteristics (SROC), sensitivity, specificity, positive and negative likelihood ratio, and diagnostic odds ratio with 95% confidence interval (95% CI).Results: Finally, 8 articles included in the meta-analysis. The area under the SROC of MACS was excellent in rule out of AMI (AUC = 0.99, 95% CI: 0.97 to 0.99) and MACE (AUC = 0.97, 95% CI: 0.95 to 0.98). The sensitivity and specificity of the troponin-only MACS/history electrocardiogram alone MACS (HE-MACS) in the rule out of AMI were0.99 (95% CI: 0.98-0.99) and 0.22 (95% CI: 0.11-0.37), respectively, and for  the original MACS were in order 0.99 (95% CI: 0.98-0.99) and 0.26 (95% CI: 0.20-0.34),. The sensitivity and specificity of the troponin-only MACS / HE-MACS in the rule out of MACE were 0.94 (95% CI: 0.92-0.96) and 0.22 (95% CI: 0.12-0.39) compared to the 0.99 (95% CI: 0.98-0.99) and 0.27 (95% CI: 0.22-0.33) for the original MACS.Conclusion: The findings of this study showed that original MACS, troponin-only MACS, and HE-MACS are able to rule out AMI and MACE. However, further studies are needed in developing countries to confirm its external validity