Pathogenesis Of Acute Coronary Syndromes Research Articles

P2651Seasonal variations in the pathogenesis of acute coronary syndromes

Abstract Background Seasonal variations in acute coronary syndrome (ACS) has been known with the winter being the peak in incidence and mortality. However, underlying pathophysiology for this variation has not been studied. Purpose We sought to compare pathobiology of the culprit lesions assessed by optical coherence tomography (OCT) among the four seasons. Methods Patients with ACS who underwent OCT were recruited from 6 countries in the Northern Hemisphere. The prevalence of 3 most common pathologies, plaque rupture, plaque erosion and calcified plaque, and other features of coronary plaques were compared among the four seasons. Results In 1113 patients with ACS, 284 (25%) patients were admitted in spring, 243 (22%) patients in summer, 290 (26%) patients in autumn and 296 (27%) patients in winter. The proportion of underlying 3 pathologies was significantly different in each season (prevalence of plaque rupture, plaque erosion, calcified plaque was 50%, 39%, and 11%, respectively in the spring; 44%, 43%, and 13% in the summer; autumn: 49%, 39%, and 12% in the autumn; 57%, 30%, and 13% in the winter; P=0.039). The proportion of plaque rupture was higher in winter but lower in summer, and that of plaque erosion was higher in summer, but lower in winter. Maximum and minimum temperatures on the day of OCT procedure were significantly lower in the plaque rupture group than in the plaque erosion group (P=0.02 and P=0.012, respectively). In the rupture group, the prevalence of hypertension was significantly higher in winter, but in the erosion group, it was not different among the four seasons. Figure 1. The proportion of culprit lesion characteristics were significantly different among the 4 season groups. (P=0.039) The proportion of plaque rupture was significantly higher in winter but lower in summer. In contrast, the proportion of plaque erosion was higher in summer, but lower in winter. Conclusions Seasonal variation of the underlying mechanisms of ACS reflects different pathobiology. The proportion of plaque rupture is highest in winter and the proportion of plaque erosion is highest in summer. A different approach may be needed for the prevention and treatment of ACS depending on the season of its occurrence.

P6602Plasma signature of apoptotic microparticles in acute coronary syndromes is associated with endothelial dysfunction and plaque rupture

Abstract Background Circulating microparticles (MP) are surrogate biomarkers of atherosclerosis and are elevated in acute coronary syndromes (ACS) but its exact biological role remains unknown. Purpose To explore the diagnostic and biological significance of circulating apoptotic MP signature in patients with ACS. Methods We enrolled 122 ACS patients: n=38 with unstable angina (UA), n=49 with STEMI, 35 with NSTEMI. Flow cytometry analysis was used to quantify circulating apoptotic (annexin+) endothelial cell (EMP), red blood cell (RMP) and platelet (PMP) derived microparticles. Endothelial function was estimated with flow mediated dilation (FMD), and inflammatory status with C-reactive protein (hsCRP). Results The association between EMP, RMP and PMP is shown on a cloud plot (A). Using an unbiased approach, we performed hierarchical clustering (A) of the total population of patients with ACS by using the circulating levels of EMP, RMP and PMP (B). Hierachical clustering identified two discreet clusters of patients (Cluster A and B) without any differences in the presence of traditional risk factors (not shown), but significant differences in the distribution of ACS type (C). STEMI subtype (a surrogate for definite plaque rupture) was significantly increased in Cluster B, which also had significantly decreased FMD (D), but not hsCRP (p=NS). Conclusions Apoptotic MP are involved in the pathogenesis of acute coronary syndromes via promotion of endothelial dysfunction and plaque rupture. The diagnostic and/or predictive value of microparticles' profiling for plaque vulnerability should be explored in future studies.

171Intravascular polarimetry in patients with coronary artery disease: a first-in-human pilot study

Abstract Background Polarization-sensitive (PS-) optical frequency domain imaging (OFDI) measures polarization properties of tissue together with conventional cross-sectional OFDI images of subsurface microstructure. PS-OFDI offers refined insight into plaque morphology and composition, which are implicated in the pathogenesis of acute coronary syndromes (ACS). Purpose This first-in-human pilot study of intravascular polarimetry aimed to investigate birefringence and depolarization features of coronary plaques in patients and to examine the relationship of these features with established structural characteristics available to conventional OFDI and with clinical presentation. Methods 30 patients undergoing PS-OFDI (acute coronary syndrome; ACS, n=12 and stable angina pectoris; SAP, n=18) participated in this study. 342 cross-sectional images evenly distributed along all imaged coronary arteries were classified into one of seven plaque categories according to conventional OFDI. Polarization features averaged over the entire intimal area of each cross-section were compared between plaque types and with structural parameters. Further, we assessed the polarization properties in the fibrous caps of ACS and SAP culprit lesions and compared them with structural features using a generalized linear model. Results The median birefringence and depolarization showed statistically significant differences among plaque types (both p<0.001, one-way ANOVA). Depolarization significantly differed between individual plaque types (p<0.05), except between fibro-fatty and fibro-calcified plaques. Caps of ACS lesions and ruptured caps exhibited lower birefringence than caps of SAP lesions (p<0.01). In addition to clinical presentation, cap birefringence also associated with macrophage accumulation as assessed by normalized standard deviation. Intravascular polarimetry Conclusions Intravascular polarimetry provides quantitative metrics that help to characterize coronary arterial tissues and may offer refined insight into coronary arterial atherosclerotic lesions in patients (Figure). Quantitative assessment of plaque polarization properties by intravascular polarimetry may open new avenues for studying plaque progression and detecting high-risk patients. Acknowledgement/Funding The JSPS Overseas Research Fellowship, the Uehara Memorial Foundation, and the Japan Heart Foundation and Bayer Yakuhin

Thrombocytopenia and Coronary Artery Disease, the Existing Dilemmas

Abstract Background: Platelets play a pivotal role in the pathogenesis of acute coronary syndrome (ACS) and acute or chronic complications following percutaneous coronary intervention (PCI) as well. Platelet inhibition is a cornerstone treatment in the management of these patients. Thrombocytopenia in patients with ACS is uncommon. Idiopathic thrombocytopenic purpura (ITP) is a rare phenomenon; nevertheless, some case series presenting concomitant ACS and ITP have been described in the literature. The safety of antiplatelet therapy and PCI in patients who have ACS and thrombocytopenia is limited. Case summary: We present a case of a 60-year-old patient with ITP who was admitted with unstable angina pectoris. On admission, the platelet count was 23 × 109/L. Coronary CT angiography revealed severe stenosis in the mid portion of RCA. After one-week treatment with high-dose Prednisolone, the platelet count recovered, and coronary catheterization was performed. Successful PCI to the RCA with drug-eluting stent was performed. The patient was discharged on dual antiplatelet therapy. Conclusion: The case suggests that PCI is a suitable treatment for ITP patients with ACS. Hemostasis is the major concern in managing these patients. The treatment strategy may be based on platelet function rather than platelet count alone. Further analysis of antiplatelet therapies as mono or dual therapy are needed.

Clinical utility of mean platelet volume and immature platelet fraction in acute coronary syndrome

BackgroundPlatelets play an important role in the pathogenesis of acute coronary syndrome (ACS). Patients with ACS have an increased mean platelet volume (MPV) and immature platelet fraction (IPF) resulting in elevation of thrombotic ability. In this study, we evaluated the diagnostic performance of MPV and IPF in identifying suspected ACS patients at emergency department. Moreover, we investigated the correlation between MPV or IPF with initial troponin I (TnI), one of the current ACS biomarkers. MethodsThis was a single-center study recruiting suspected ACS patients who had acute chest pain at the emergency department. Whole blood samples were obtained from all participants and MPV and IPF were measured by Sysmex XE-5000 hematology analyzer within 20 min of blood sampling. The diagnostic values of MPV and IPF in identifying ACS were analyzed retrospectively. ResultIn this study, 63 in 104 suspected ACS patients were diagnosed as ACS (65.3%). MPV and IPF were higher in ACS patients compared to non-ACS patients (MPV: 10.7 ± 0.80 fL vs 10.0 ± 0.64 fL, p < 0.001; IPF: 3.7 ± 2.64% vs 3.1 ± 2.69%, p = 0.030). MPV and IPF were similar in unstable angina and acute myocardial infarction patients. We showed that elevation of MPV could be an independent predictive factor of ACS (odds ratio: 5.038). At the optimal cut-off value of 10.55 fL (AUC 95% CI: 0.637–0.836), the diagnostic performance of MPV in predicting ACS had an area under a receiver operating characteristic curve (AUC) of 0.736 with sensitivity and specificity of 54.2% and 82.8%, respectively. Patients with both of initial TnI and MPV higher than the established cut-off value had increased incidence (3.792 fold) for ACS development compared to patients with TnI below the cut-off value. Furthermore, diagnosing ACS with both MPV and initial TnI increased the positive predictive value from 84.2% to 86.7%. No correlation was observed between MPV or IPF and the mortality rate of ACS patients (MPV: 3.8% vs 11.1%, p = 0.300; IPF: 12.0% vs 37.5%, p = 0.054). ConclusionHere we show that ACS patients have higher MPV and IPF compared to non-ACS patients. We further demonstrate that MPV can be utilized as an independent predictor for early diagnosis of low-risk ACS patients who have acute chest pain.

COMPARATIVE EVALUATION OF EFFICACY AND SAFETY OF ASPIRIN + CLOPIDOGREL WITH ASPIRIN+TICAGRELOR IN PATIENTS WITH CARDIOVASCULAR DISEASES. AN OBSERVATIONAL STUDY.

Background: Coronary artery disease (CAD) is one of the most common causes of mortality and morbidity in both developed and developing countries. It is a leading cause of death in India, and its contribution to mortality is rising. Platelets play an essential role in the pathogenesis of acute coronary syndromes (ACS). Therefore an important part of the treatment of ACS, and of primary and secondary preventive measures in coronary heart disease, consists of antiplatelet treatment. Dual antiplatelet therapy (DAPT) provides more intense platelet inhibition than single antiplatelet therapy resulting in incremental reductions in the risk of thrombotic events after percutaneous coronary intervention (PCI) or ACS, but it has been associated with an increased risk of major bleeding. It is interesting to consider that there is no Indian data on the efficacy of recently developed antiplatelet drugs other than in combination with aspirin, and that we remain unaware of the extent to which combinations with aspirin improve efficacy but increase risk.&#x0D; Methodology: Study was prospective, observational clinical study carried out in the Department of Medicine, of Index Medical College Hospital &amp; Research Centre. A total of 80 patients with CAD were enrolled for the study and were equally divided in two groups each of 40 for evaluating efficacy and safety of dual antiplatelet therapy. Follow-up was done at 8 weeks, 16 weeks, and 24 weeks, patients were asked to provide information regarding their current medications, any morbidity and their complications [if any]. Demographic parameters were analyzed by descriptive statistics. Comparison between groups was done by Chi–square Test. Survival analysis was done by suitable statistical method.&#x0D; Result: The median age was 55 years in group 1 and 57 years in group 2. Hypertension was most common associated disorders in group 1 [25 (62.55%)] and group 2 [27 (67.5%)], which was followed by diabetes and dyslipidemia. index events for present study enrolment was unstable angina, non–ST-segment elevation MI, ST-segment elevation MI and others amongs the study groups. With 6 months of follow-up, the rate of the primary event like death from any cause was 7.5 percent in the clopidogrel plus aspirin group and 2.5 percent in the ticagrelor plus aspirin group. The primary safety end point (severe bleeding) was 2.5 % in the clopidogrel plus group 1 and none in group 2.&#x0D; Conclusion: the combination of clopidogrel plus aspirin was found to be non inferior to aspirin plus ticagrelor dual therapy in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes among patients with stable cardiovascular disease or multiple cardiovascular risk factors. The risk of moderate to severe bleeding was increased slightly in both the groups. Our findings do support the use of dual antiplatelet therapy across the broad population tested where single antiplatelet therapy are not giving maximum benefits&#x0D; Keywords: Acute coronary syndrome (ACS), percutaneous coronary intervention (PCI), Coronary artery disease (CAD), Dual antiplatelet therapy (DAPT)

Tissue factor expression on platelets in patients with acute coronary syndrome

Objective To investigate the expression of tissue factor (TF) on platelet monocyte aggregates (PMA) and platelets as a participating factor in pathogenesis of acute coronary syndrome (ACS). Background ACS is due to rupture of an arterial plaque. TF on platelets and PMA may provide potential distal sites for generation of new thrombi. In this study, the expressions of TF on PMA and platelets are investigated as participating factors in pathogenesis of ACS. Patients and methods Twenty-five patients with acute myocardial infarction, 25 patients with stable angina, and 20 clinically healthy patients as control are investigated for TF on PMA, as well as platelet-associated TF by flow cytometry analysis. Results TF on platelets and PMA were highly significant in patients with acute myocardial infarction than those with stable angina and controls. Conclusion The greater expression of TF on platelets and PMA strengthens the link between platelet activation, blood coagulation, and thrombus formation and may further contribute to the hypercoagulability associated with the disease.

The Association of Fractalkine Receptor (T280M) Polymorphism in the Pathogenesis of Acute Coronary Syndrome in the Egyptian Population.

Fractalkine (FKN) in its free and membrane bound-forms and its receptor CX3CR1are reported to have an atherosclerotic effect. The relationship of Single Nucleotide Polymorphisms (SNPs) in FKN and CX3CR1genes with the Coronary Artery Disease (CAD) risk showed conflicting results in different populations. The aim of this study was to investigate the influence of CX3CR1 threonine 280 methionine (T280M) polymorphism in the predisposition of Acute Coronary Syndrome (ACS) in Egyptians. 200 Egyptian subjects were recruited for the study. They were divided into 100 ACS patients and 100 healthy controls. Genotyping of CX3CR1 T280M was performed using a Polymerase Chain Reaction-restriction Fragment Length Polymorphism (PCR-RFLP). Serum FKN was assayed by Enzyme - Linked - Immuno- Sorbent-Assay (ELISA). T and M allele frequencies for CX3CR1gene were not significantly different between ACS and Controls (p=0.76). Moreover, none of the genotypes had an atheroprotective effect. Serum analysis showed higher levels of FKN in ACS patients (p=0.041). FKN levels were not significantly different among genotypes of control and ACS groups (p=0.34) and (p=0.38) respectively. This study shows that CX3CR1 T280M polymorphism does not affect the incidence of ACS the Egyptian population. Moreover, none of the genotypes were associated with higher FKN levels.

English

INTRODUCTION: Diabetes Mellitus is one of the leading cause of morbidity and mortality worldwide. Its Prevalence is gearing up at a faster pace all over the world especially in developing countries like India. It is the most important risk factor in the pathogenesis of Acute Coronary syndrome. Coronary artery disease is one of the most common Macro vascular complications of Diabetes, especially Type 2 diabetes. It is the leading cause of mortality and morbidity in diabetes. In addition, diabetic patients are likely to have Poor treatment outcome compared with non-Diabetic controls. Its occurrence is increasing in younger age group,causing premature coronary artery disease and premature death inflicting economic burden to the family and to the society. Recently studies are focussing on serum Fibrinogen and its role in the pathogenesis of Coronary artery disease in Diabetes. Fibrinogen being an acute phase reactant is also a pro-coagulant. It plays a major role in coagulation of blood. It has a significant role in Athero-thrombosis. Hence its role in adverse cardiac events in Diabetics and its prognostic value is currently the study of interest. AIMS & OBJECTIVES: 1. To determine the concentration of Fibrinogen in diabet ic CAD and its causal relationship to adverse cardiac events. 2. To ascertain serum fibrinogen‟spredictive value of major adverse cardiac events in Diabetic CAD. 3. To ascertain the prognostic value of serum fibrinogen in Diabetic patients presenting with subs equent major adverse cardiac events. 4. To evaluate the relation between serum Fibrinogen and other factors that cause adverse cardiac events. MATERIALS AND METHODS: Study site: Department of General Medicine, Government Stanley Medical College and Hospital, Chennai. Collaborating Departments: Department of Cardiology and Department of Medical Biochemistry. Study Design: Cross sectional study. Study Period: June 2012 to November 2012. Selection of study population: Inclusion criteria: Diabetic inpatients with past history or evidence of Coronary artery disease. Sample size: • Using the above mentioned criteria 50 subjects were Recruited. Sampling method: • Convenience sampling method was adopted. Exclusion Criteria: • Disseminated intravascular coagulation. • Pregnancy. • Liver disease. • Sepsis. • Drug abuse like OCP,Antifibrinolytic, hormones. • Dysfibrinogenemia. CONCLUSION: The summary of results obtained is as follows: The study included 50 diabetic patients with coronary artery disease. • Age varied from 44 to 78 years. • 52% of the patients suffered from major adverse cardiac events(recurrent angina and congestive cardiac failure). • Older patients had more severe forms of major adverse cardiac events. • There is no significance between gender of patients and severity of major adverse cardiac events. • Longer the duration of diabetes more severe the major adverse cardiac events. • Higher blood sugar levels and poorer glycemic control leads to severe major adverse cardiac events. • No correlation between mean serum fibrinogen level and age or gender of the patient. • Mean serum fibrinogen levels was significantly higher in patients with longer duration of diabetes, higher blood sugars and poor glycemic control. • Increase in severity of major adverse cardiac events correlates with increase in serum fibrinogen titres.

More, More, More: Reducing Thrombosis in Acute Coronary Syndromes Beyond Dual Antiplatelet Therapy-Current Data and Future Directions.

Common to the pathogenesis of acute coronary syndromes (ACS) is the formation of arterial thrombus, which results from platelet activation and triggering of the coagulation cascade.[1][1] To attenuate the risk of future thrombotic events, patients with ACS are treated with dual antiplatelet therapy

Dynamic thiol/disulphide homeostasis and its prognostic value in patients with non-ST elevation-acute coronary syndromes

Cardiovascular diseases are still one of the leading causes of death in industrialised countries, and oxidative stress plays an important role in the pathogenesis of acute coronary syndromes (ACS). The dynamic thiol/disulphide homeostasis plays an important role in maintaining the oxidant-antioxidant balance. We aimed to demonstrate the relationship between dynamic thiol/disulphide homeostasis parameters and non-ST elevation ACS (NSTE-ACS). Patients with NSTE-ACS (n = 210) and a control group (n = 185) were included in the study. The GRACE risk score and the development of major adverse cardiovascular event (MACE) were used to evaluate the prognosis. Native thiol, total thiol, disulphide/native thiol, disulphide/total thiol, and native thiol/total thiol levels were found to be lower in the NSTE-ACS group (p < 0.001). There was a statistically significant difference between native and total thiol levels in the GRACE risk score subgroups (p < 0.001). There was a correlation between MACE and native thiol levels (p = 0.04). Consequently, the dynamic thiol/disulphide homeostasis parameters were significantly different in the NSTE-ACS group and may be used to predict prognosis in this patient group.

Where Does Inflammation Fit?

This review focuses on the complex relationship between inflammation and the onset of acute coronary syndrome and heart failure. In the last few years, two important lines of research brought new and essential information to light in the pathogenesis of acute coronary syndrome: a) the understanding of the immune mediate mechanisms of inflammation in Ischemic Heart Disease (IHD) and b) evidence that the inflammatory mechanisms associated with atherosclerosis and its complications can be modulated by anti-inflammatory molecules. A large amount of data also suggests that inflammation is a major component in the development and exacerbation of heart failure (HF), in a symbiotic relationship. In particular, recent evidence underlies peculiar aspects of the phenomenon: oxidative stress and autophagy; DAMPS and TLR-4 signaling activation; different macrophages lineage and the contribution of NLRP-3 inflammasome; adaptive immune system. A possible explanation that could unify the pathogenic mechanism of these different conditions is the rising evidence that increased bowel permeability may allow translation of gut microbioma product into the circulation. These findings clearly establish the role of inflammation as the great trigger for two of the major cardiovascular causes of death and morbidity. Further studies are needed, to better clarify the issue and to define more targeted approaches to reduce pathological inflammation while preserving the physiological one.

Reticulated platelets in acute coronary syndrome patients

Objective The aim of this study was to evaluate reticulated platelets (RP) as a predicting factor of the outcome in acute coronary syndrome (ACS) patients. Background ACS is due to rupture of an arterial plaque. RPs are newly formed platelets with a greater mass, residual amount of RNA, and an increased prothrombotic potential compared with mature platelets. In this study, the RPs were investigated as participating factors in the pathogenesis of ACS. Patients and methods A total of 50 patients with ACS [33 acute myocardial infarction (AMI) and 17 unstable angina] and 15 clinically healthy individuals as controls were investigated for RPs by means of flowcytometry analysis. Results RPs were highly significantly increased in AMI than in unstable angina and controls. Conclusion High levels of RPs are found in ACS patients and it can be used as a predictor for adverse outcome. Moreover, it can participate in the development of AMI due to its high thrombogenic potential.

Antiplatelet and antithrombotic treatment for secondary prevention in ischaemic heart disease.

Platelets play a key role in the pathogenesis of acute coronary syndromes and this is why antiplatelet drugs are essential, both in the acute phase and in the long-term follow-up in preventing recurrent myocardial infarction, stroke and cardiovascular death. Aspirin is the most used agent and still remains the first choice drug for lifelong administration in secondary prevention after myocardial infarction. Dual antiplatelet therapy, targeting more than one pathway of platelet activation, has significantly improved the outcome of patients with acute coronary syndromes despite an increased risk of bleeding complications. The aim of this article is to provide an overview of the evidence from randomized clinical trials with a focus on the best association between aspirin and a P2Y12 inhibitor such as clopidogrel, prasugrel or ticagrelor, on the selection of the appropriate agent based on the revascularization strategy and on the optimal duration of such an intensive treatment. We will also provide the latest evidence regarding new antithrombotic agents, such as vorapaxar or low dose rivaroxaban, that could be associated with dual antiplatelet therapy in high risk patients with the aim of further reducing the rate of major ischaemic complications. Finally we will address the issue of patients presenting with atrial fibrillation and a concomitant acute coronary syndrome who frequently need a percutaneous coronary intervention, with a specific focus on the combination therapy of antiplatelet and anticoagulant agents and on the current recommendations of the guidelines.

Anti-thrombotic therapy in non-ST elevation acute coronary syndrome KAA Fox

Platelet activation and thrombin generation are implicated in the pathogenesis of acute coronary syndrome, in the development of major thrombotic complications of the condition, and in the interventional treatments to treat obstructive coronary lesions (principally, percutaneous coronary intervention). Despite treatment with aspirin and heparin there remained a clinically important risk of thrombotic complications both in hospital and following discharge. Newer anti-platelet therapies (thienopyridines and glycoprotein IIb/IIIa inhibitors) reduced platelet mediated complications, but with an increase in bleeding risk. Similarly, low molecular weight heparins reduced thrombotic complcations but with a modest increase in bleeding. Newer anti-thrombins (anti Xa inhibitors and direct thrombin inhibitors) demonstrate similar or improved efficacy, but with reduced bleeding. Insufficient attention has been paid to reducing bleeding complications and recent evidence suggests that major bleeding conveys a significant increase in the risk of death. In addition, clearance of antithrombotic agents by the kidney is impaired in those with renal dysfunction, including in the elderly, and this may contribute to the risks of bleeding. In unselected populations with non-ST elevation ACS more than half the population have a creatinine clearance below 60 ml/min. Reducing the doses of anti-thrombins in patients with renal dysfunction may reduce bleeding complications. The optimal anti-thrombotic strategy in patients with non-ST elevation ACS requires the clinician to consider not only the risk of the patient for thrombotic complcations, but also the hazards of bleeding. Newer anti-thrombotic agents, for the first time, offer potential benefits in bleeding risk with similar or improved efficacy.

The Role of Some Inflammatory Markers (IL-6 and CRP) in the Pathogenesis of Acute Coronary Syndrome in Iraqi CCU for Heart Diseases

In this work an enzyme linked immunosorbent assay (ELISA) technique has been used for detection of some inflammatory markers in serum of acute coronary syndrome (ACS)-Patients Admitted to the cardiac care unit (CCU) of Iraqi Centre For Heart Diseases and Ibn AlNafees Teaching Hospital. The present method includes quantitative measurement of interleukine-6 (IL-6) and C-reactive protein (CRP), as their increase during symptoms may be responsible for identifying the mechanism of myocardial damag, in addition to their best performance than other quantitative tests perhaps due to their association with atherosclerotic process that belongs to the endothelial dysfunction. Aim of this study is to estimate the prevalence and correlation of IL-6 with CRP in ACS- patients presented with unstable angina/ non-ST elevation myocardial infarction (UA/NSTEMI) symptoms to be as new diagnostic parameters in Iraqi CCU. Seventy (70) ACS- patients with mean age (58.55 year ± 9.98), from Jun.2009 to Feb. 2010 with diagnosis of UA/NSTEMI were included in this study. Proper history, physical examination, electrocardiograph (ECG), and Echocardiography (ECHO) were performed for all patients in addition to the routine laboratory works including fasting blood glucose, lipid profile, assay of transaminases activity (Aspartate and Alanine transaminase),and biomarkers analysis as cardiac troponin I and T, creatine kinase (CK and CK-MB) and myoglobin. Blood sample was collected from all patients for quantitative assay of IL-6 and CRP. All patients underwent diagnostic coronary angiography, were 66 of them with abnormal coronary outcome and four patients have normal coronary arteries, study include 39- male and 31 female. Seventeen of 67 patients (25.4%) had elevated serum level of IL-6 and fifty four of 62 patients (87.1%) had elevated serum level of CRP. Statistically found strong and significant (SS) correlation between IL-6 and CRP (assessed by Spearman's rho correlation coefficient, P&lt;0.01). The significant proportion of UA/NSTEMI patients that had elevated serum levels of IL-6 and/or CRP, in addition to the strong correlation with coronary angiographic findings make these inflammatory markers to be considered as risk stratification factors and good predictors for coronary artery disease independent of other traditional risk factors for cardiovascular disease (CVD).&#x0D; Key words: ACS. IL-6. CRP.

Different origins of lysophospholipid mediators between coronary and peripheral arteries in acute coronary syndrome

Lysophosphatidic acids (LysoPAs) and lysophosphatidylserine (LysoPS) are emerging lipid mediators proposed to be involved in the pathogenesis of acute coronary syndrome (ACS). In this study, we attempted to elucidate how LysoPA and LysoPS become elevated in ACS using human blood samples collected simultaneously from culprit coronary arteries and peripheral arteries in ACS subjects. We found that: 1) the plasma LysoPA, LysoPS, and lysophosphatidylglycerol levels were not different, while the lysophosphatidylcholine (LysoPC), lysophosphatidylinositol, and lysophosphatidylethanolamine (LysoPE) levels were significantly lower in the culprit coronary arteries; 2) the serum autotaxin (ATX) level was lower and the serum phosphatidylserine-specific phospholipase A1 (PS-PLA1) level was higher in the culprit coronary arteries; 3) the LysoPE and ATX levels were significant explanatory factors for the mainly elevated species of LysoPA, except for 22:6 LysoPA, in the peripheral arteries, while the LysoPC and LysoPE levels, but not the ATX level, were explanatory factors in the culprit coronary arteries; and 4) 18:0 and 18:1 LysoPS were significantly correlated with PS-PLA1 only in the culprit coronary arteries. In conclusion, the origins of LysoPA and LysoPS might differ between culprit coronary arteries and peripheral arteries, and substrates for ATX, such as LysoPC and LysoPE, might be important for the generation of LysoPA in ACS.

Interplay between PAPP-A, inflammation and adiposity in patients with angiographically proven acute coronary syndrome (ACS).

Introduction Studies conducted in the recent past have demonstrated the role of inflammation, obesity and dysfunctional insulin signaling as contributing factors in the pathogenesis of acute coronary syndrome (ACS). However, pharmacological interventions targeting a single pathway have not proven useful in the long run. This indicates that a synergism occurs between the various risk factors and hence calls for a combinatorial approach. This study was planned to study the interplay, if any, between pregnancy associated plasma protein-A (PAPP-A), inflammation and adiposity in patients with ACS. Materials and methods The study was conducted in a tertiary care hospital in Delhi. The study population consisted of 128 subjects, divided into two groups. The control group consisted of 64 healthy subjects without ACS. Cases consisted of 64 subjects with angiographically proven ACS cases. PAPP-A and high sensitivity C-reactive protein (hs-CRP) were estimated by enzyme-linked immunosorbent assay (ELIZA) kits. Results The mean level of PAPP-A and hs-CRP were significantly higher in cases as compared to the controls. A positive correlation of PAPP-A was observed with hs-CRP, insulin, ApoB and Lp(a). The relative risk for ACS was 14.2 with a p value of <0.001 when all the three parameters - hs-CRP, PAPP-A and body mass index (BMI) were considered together. This was significantly higher when each risk factor was assessed standalone. Conclusions Our study results suggest a possible interplay between chronic inflammation, obesity and plaque instability among patients with ACS. This interaction can accelerate the process of plaque rupture in patients with increased BMI as compare to those patients with low/normal BMI.

Abstract 13144: MicroRNA Sequencing Highlights Regulatory Networks Upstream of Osteopontin and B-type Natriuretic Peptide in Acute Coronary Sydrome

Introduction: The genomic regulatory networks underlying the pathogenesis of acute coronary syndrome (ACS) are incompletely understood. As intermediate traits, circulating protein biomarkers report on underlying disease severity and are powerfully prognostic in ACS. We hypothesized that integration of dense microRNA (miRNA) profiling with measurement of biomarkers would highlight potential regulatory pathways. Methods: We studied 186 patients enrolled in the biomarker substudy of the TRILOGY clinical trial of ACS. MiRNA sequencing was performed on RNA extracted from whole blood, and seven known prognostic protein biomarkers were measured from plasma (N-terminal pro B-type natriuretic peptide [NT-proBNP], C-reactive protein, osteopontin [OPN], myeloperoxidase, growth differentiation factor 15, monocyte chemoattractant protein 1, and neopterin). MiRNAs were tested for association with these biomarkers using generalized linear models. Target genes putatively regulated by the associated miRNAs were examined using pathway analysis. Results: Fourteen miRNAs, including cardiac-related miRs 20b-5p and 320a,b and d, were associated with OPN levels (min. p=1.1x10 -4 ), and five miRNAs, including cardiac-related miRs 25-3p and 423-3p, were associated with NT-proBNP levels (min. p=3.4x10 -4 ); no other biomarkers showed significant associations. Sixty-three KEGG pathways were enriched in the target genes of either NT-proBNP- or OPN-associated miRNAs, with five pathways found in the top ten for both biomarkers: prion diseases, fatty acid biosynthesis, lysine degradation, protein processing in endoplasmic reticulum, and viral carcinogenesis. Conclusions: By integrating large-scale microRNA profiling with circulating biomarkers as intermediate traits, we identified associations of known cardiac-related and novel miRs with two prognostic biomarkers (OPN and NT-proBNP), and identified potential genomic regulatory networks underlying these biomarkers. We further identified novel non-cardiac genomic pathways associated with these biomarkers. These results may inform future studies delineating genomic pathways underlying ACS outcomes.

Лейкоцитарно-тромбоцитарные комплексы в патогенезе острого коронарного синдрома. Часть 2

Лейкоцитарно-тромбоцитарные комплексы в патогенезе острого коронарного синдрома. Часть 2