Development Of Plaque Rupture Research Articles

Usefulness of WBC Count to Mean Platelet Volume Ratio in Predicting Short-Term (30 Days) Major Adverse Cardiac Events in Patients Presenting with Acute Coronary Syndrome and its Comparison in Males and Females

Abstract Background: Among cardiovascular illnesses, acute coronary syndrome (ACS) events are associated with higher mortality and morbidity. The mechanism of inflammation involved in the ACS includes atherosclerotic plaque development, followed by development of plaque rupture and thrombosis. The present study is to determine whether white blood cell count to mean platelet volume ratio (WMR) can predict short-term (30 days) major adverse cardiac events (MACE) in ACS patients, and also compare WMR and MACE in males and females. Aim: To detect usefulness of white blood cell (WBC) count to WMR in predicting short term (30 days) MACE in patients presenting with ACS and compare values and MACE events in males and females. Material and Methods: The present study was conducted in a tertiary-care hospital from September 2020 to December 2020. A total of 60 patients, who presented with ACS and were undergoing percutaneous coronary intervention (PCI), fulfilled the selection criterion; hence, a total of 60 patients were selected for the study after taking informed consent. The clearance from the Institutional Ethical committee (IEC) was obtained prior to the initiation of the study. All the necessary investigations were done in patients who fulfilled the inclusion criteria. The results of the study were systematically selected and analysis done statistically. The study included all patients with clinical suspicion of ACS for more than 18 years and excluded non-ACS patients, patients with malignancy history, inflammatory diseases, autoimmune disorders, infections, and those who are immunosuppressed. Results: In the present study, receiver operating characteristic (ROC) curve showed cutoff value of WMR as 1059 with area under curve (AUC) of 0.6 (95% CI 0.4–0.9). MACE occurred in 12 patients and mortality occurred in 6 patients. Among MACE, recurrent myocardial infarction (REMI) occurred in 7 (35%) cases, arrhythmias occurred in 5 (25%), and cardiogenic shock occurred in 8 (40%) cases. WMR with a cutoff value of 1059 was significant and highly accurate in predicting MACE, with sensitivity of 91.6%, specificity of 87.5%, PPV of 64.7%, NPV of 97.6%, and diagnostic accuracy of 88.3%. Compared to males, females have less sensitivity to, high specificity to, and high diagnostic accuracy of WMR ratio in predicting MACE. MACE did not show any gender predilection. Conclusion: In patients, who presented with ACS, high WMR values were associated with worse short-term outcomes and independently predicted short-term MACE. Compared to males, females have less sensitivity to, high specificity to, and high diagnostic accuracy of WMR ratio in predicting MACE.

Roles of Growth Differentiation Factor 15 in Atherosclerosis and Coronary Artery Disease.

The majority of acute cardiovascular events (CVE) in patients are caused by occlusive thrombosis because of rupture or erosion of atherosclerotic plaques.1 Growth differentiation factor 15 (GDF‐15), a stress‐responsive member of the transforming growth factor‐β (TGF‐β) cytokine superfamily, has been shown to be a strong and independent predictor of mortality and disease progression in patients with atherosclerosis and coronary artery disease (CAD), such as acute coronary syndromes (ACS) and stable angina pectoris.2 The development of atherosclerosis is dependent upon a high‐inflammatory content, which has been shown to modulate lesion initiation, progression, and potentially devastating thrombotic complications.3 Angiogenesis plays an important role in the progression of atherosclerotic plaque and complications.4, 5, 6 Atherosclerosis and cancer arise from multiple factors and are consolidated from the very early stages of development up to the advanced forms in inflammatory processes. Uncontrolled cell proliferation and oxidative stress and angiogenesis appear to be unifying causal factors in both diseases.7 A local inflammatory state occurring in atherosclerotic lesions has been implicated in angiogenesis through activation of endothelial cells, release of chemokines, cytokines, growth factors, lipid mediators, proteases, and increase of endothelial metabolic rate. The angiogenesis allows extravasation of the plasma component, leading to future thromboembolic events.8, 9, 10, 11 GDF‐15 might be an acute phase modifier of TGF‐βRII‐dependent proinflammatory responses to atherosclerotic plaque rupture and thrombus formation12 (Figure). Although the exact biological functions of GDF‐15 are still poorly understood, it has been shown to regulate inflammatory and angiogenesis pathways (Figure). GDF‐15 exhibits differing and even opposing functions under various circumstances. For instance, GDF‐15 has proapoptosis, antiapoptosis, proangiogenesis, antiangiogenesis, proinflammatory, and anti‐inflammatory properties.12, 13 Therefore, GDF‐15 exhibits a complex pattern with beneficial and harmful functions. GDF‐15 promoter contains p53‐transcription factor binding sites that are required and sufficient for the induction of GDF‐15 expression.14 Activation of p53 is a fundamental cellular response to inflammation, oxidative stress, hypoxia, telomere erosion, and oncogene activation. The circulating levels of GDF‐15 reflect these acute and chronic inflammatory conditions linked with atherosclerosis and CAD. Open in a separate window Figure 1 Schematic overview of a vulnerable plaque in advanced atherosclerosis. Plaque formation is initiated by endothelial cell dysfunction and subsequent angiogenesis and release of proinflammatory factors mediated by GDF‐15, contributing to the progression of atherosclerotic lesions and the development of plaque rupture and thrombus formation in atherosclerotic status. CRP indicates C‐reactive protein; GDF‐15, growth differentiation factor 15; MAPK, mitogen‐activated protein kinase; M‐CSF, macrophage colony‐stimulating factor; TGF‐βRII, transforming growth factor‐βRII; TNF‐α, tumor necrosis factor‐α.

Molecular Imaging of Inflammation in Ischemic Heart Disease.

Ischemic heart disease is caused by atherosclerosis, the build-up of plaque in the coronary arteries, which can lead to the development of heart attacks and heart muscle damage. Despite the advent of medical and surgical therapy to prevent and treat atherosclerosis and its adverse clinical effects, ischemic heart disease remains a leading cause of morbidity and mortality. Recent studies have suggested that the immune system may play a greater role in the development of plaque rupture and adverse left ventricular remodeling after myocardial infarction. Understanding the molecular processes by which inflammation contributes to the pathophysiology of ischemic heart disease is, therefore, worthwhile. This review focuses on new molecular imaging techniques to visualize immune cells to study their contribution to ischemic heart disease. A common technique applied to imaging inflammation in ischemic heart disease is targeting the up-regulation and trafficking of immune cells, which may contribute to the adverse consequences associated with atherosclerosis. In the past five years, advances in cell labeling for imaging with PET and MRI, including radioisotopes and nanoparticles, have confirmed that inflammatory cells can be visualized in vivo and in greater abundance in unstable cardiovascular disease and in areas of ischemic damage. The major criticisms of these studies to date include their small sample size, lack of histological correlation, limited association with long-term outcomes, and bias toward macrophage imaging. While much progress has been made in imaging inflammation in ischemic heart disease over the past five years, additional studies in larger cohorts with histological validation and outcome correlation are needed. Nevertheless, imaging inflammation using PET or MRI has the potential to become an important adjunct tool to improve the diagnosis, risk stratification, and therapeutic monitoring of patients with ischemic heart disease.

Optical Coherence Tomography For the Detection of the Vulnerable Plaque

Morphological characteristics of the atheromatous plaque have been associated with the development of plaque rupture and the pathogenesis of acute coronary syndromes (ACS). Plaques with a specific morphological phenotype that are at high risk of causing ACS are called vulnerable plaques, and can be identified in vivo through the use of intracoronary imaging. Optical coherence tomography (OCT) is a high-resolution intravascular imaging modality that enables detailed visualization of atheromatous plaques. Consequently, OCT is a valuable research tool for examining the role of morphological characteristics of atheromatous plaques in the progression of coronary artery disease and plaque destabilisation, which leads to the clinical manifestation of ACS. This article summarises the pathophysiological insights obtained by OCT imaging in the formation and rupture of the vulnerable plaque.

Circulating cytokines reflect the expression of pro-inflammatory cytokines in atherosclerotic plaques

Inflammation is a key factor in the development of plaque rupture and acute cardiovascular events. Although imaging techniques can be used to identify vulnerable atherosclerotic plaques, we are lacking non-invasive methods, such as plasma markers of plaque inflammation that could help to identify presence of vulnerable plaques. The aim of the present study was to investigate whether increased plasma levels of pro-inflammatory cytokines reflects inflammatory activity within atherosclerotic plaques. Cytokines were measured using Luminex immunoassay in 200 homogenized plaque extracts and plasma, obtained from 197 subjects undergoing carotid surgery. Plasma levels of macrophage inflammatory protein-1β (MIP-1β), tumor necrosis factor- α (TNF-α) and fractalkine correlated significantly, not only with plaque levels of the same cytokines but also with the abundance of several pro-inflammatory and atherogenic cytokines assessed in plaque tissue. High plasma levels (upper tertile) of MIP-1β, TNF-α and fractalkine identified the presence of a plaque with high inflammation (above median of a score based on the plaque content of MIP-1β, TNF-α, interferon-γ (IFN-γ) and fractalkine) with a sensitivity between 65 and 67% and a specificity between 78 and 83%. Furthermore, this study shows that high plasma levels of MIP-1β, TNF-α and fractalkine predict future transient ischemic attacks. Our findings show that the plasma levels of MIP-1β, TNF-α and fractalkine reflect the levels of several pro-atherogenic cytokines in plaque tissue and might be possible plasma markers for a vulnerable atherosclerotic disease. We thereby propose that these cytokines can be used as surrogate markers for the identification of patients with high-risk plaques.

C-reactive protein induces endothelial cell apoptosis and matrix metalloproteinase-9 production in human mononuclear cells: Implications for the destabilization of atherosclerotic plaque

C-reactive protein (CRP) has been suggested to directly induce the inflammatory response leading to the progression of atherosclerosis. However, recent in vitro studies raised the possibility that the effects of CRP are caused by biologically active contaminants such as sodium azide and endotoxin. In this study, we tested whether azide- and endotoxin-free CRP induces endothelial cell apoptosis and production of proinflammatory mediators. In human endothelial cells, CRP significantly inhibited cell proliferation and increased endothelial cell apoptosis evaluated by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling and caspase-3 activity assay, which is reversed by a function-blocking antibody to FcgammaRIIIB by 78%. Western blot analysis showed that CRP significantly attenuated flow-mediated activation of Akt, a key molecule for endothelial cell survival pathways. In human mononuclear cells, CRP-induced production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and matrix metalloproteinase-9 (MMP-9) in a concentration-dependent manner. This CRP-induced MMP-9 production was significantly inhibited by function-blocking antibodies to TNF-alpha, IL-1beta, and FcgammaRIIA. These findings suggest that CRP itself induces endothelial cell apoptosis and production of proinflammatory mediators. Because endothelial cell apoptosis and MMP-9 production are critical for the destabilization of atherosclerotic plaque, this study may provide insight into a role of CRP in the development of plaque rupture.

Levels of serum IL-1beta, IL-2, IL-8 and tumor necrosis factor-alpha in patients with unstable angina pectoris.

Inflammation is the most important mechanism of plaque disruption playing an essential role in acute coronary syndromes. It is controversial whether the inflammatory mediators are the cause or the result in the development of plaque rupture. Stimulation of interleukins increases adhesion molecules, fibrinogen and plasminogen activator inhibitors,which cause the activation of inflammation and thrombosis. However, the importance of interleukins in acute coronary syndromes has not been clearly defined. We did not find any article concerning relations between the levels of serum interleukin(IL)-1beta, IL-2, IL -8 and tumor necrosis factor (TNF)-alpha in patients with unstable angina pectoris (UAP). So the aim of this study was to determine the levels of serum I -1b, IL-2, IL-8 and TNF-alpha during the early stage of UAP. Thirty-seven patients with UAP(12 females and 25 males; mean age, 57.5 +/- 9.7 years) within 6 h of admission and 20 healthy volunteers(eight females and 12 males; mean age, 51.3 +/- 6.3 years) were included in the study. IL-1beta, IL-2, IL-8 and TNF-alpha levels were measured using the enzyme-linked immunosorbent assay method. Patients with acute or chronic inflammation, renal failure or chronic heart failure were excluded from the study. The age, gender and risk factors of the study and control groups were similar. The levels of IL-1beta, IL-8 and TNF-alpha were significantly increased (p < /0.0001, p < /0.001 and p < /0.016, respectively) in patients with UAP. There was no difference of IL-2 levels between the UAP group and controls. We detected high levels of IL-1beta, IL-8 and TNF-alpha in patients with UAP during early phase. We suggest that proinflammatory cytokines (e.g. IL-1beta,IL-8, TNF-alpha) may play an important role in the development of atherosclerosis and its complications.

Sudden cardiac death

The rate of cardiac deaths that are sudden is approximately 50%, and decreases with age. The causes of sudden cardiac death are diverse, and are a function of age. In children and adolescents, coronary anomalies, hypertrophic cardiomyopathy and myocarditis are frequent substrates for lethal arrhythmias; in adults, coronary atherosclerosis and acquired forms of cardiomyopathy are the most common findings at autopsies of sudden cardiac death. This review focuses on coronary causes of sudden cardiac death, especially congenital coronary artery anomalies, which result in sudden death almost exclusively in adults younger than age 35, and coronary thrombosis. The most lethal coronary artery anomaly is the left coronary artery arising from the right sinus of Valsalva; this anomaly often results in fatal arrhythmias, often with exercise. The right coronary artery arising from the left sinus of Valsalva may also be lethal in adolescents and young adults, but, unlike the anomalous left, is more often an incidental finding at autopsy. Approximately 60% of sudden coronary death is caused by coronary thrombosis, the rest die with severe coronary disease in the absence of thrombosis. The two major substrates of coronary thrombosis are plaque rupture and plaque erosion, and are not only different pathologically, but are seen in patients with divergent risk factor profiles. Plaque rupture is the most common cause of fatal coronary thrombus, and is characterized by necrotic core with a thin fibrous cap, infiltrated by macrophages. The factors that result in plaque instability and rupture are largely unknown, and are under intense scrutiny; morphologic studies have identified serum lipid abnormalities as a key risk factor in the development of plaque rupture. Plaque erosion, in contrast to plaque rupture, is seen in younger men and women, is not associated with lipid abnormalities, and does not result from exposure of the lipid core to the lumen. The heterogeneity of the atherosclerotic plaque and the diverse mechanics of plaque progression and thrombosis have only been relatively recently explored, and are largely elucidated by autopsy studies of victims of sudden coronary death.

Sudden cardiac death

The rate of cardiac deaths that are sudden is approximately 50%, and decreases with age. The causes of sudden cardiac death are diverse, and are a function of age. In children and adolescents, coronary anomalies, hypertrophic cardiomyopathy and myocarditis are frequent substrates for lethal arrhythmias; in adults, coronary atherosclerosis and acquired forms of cardiomyopathy are the most common findings at autopsies of sudden cardiac death. This review focuses on coronary causes of sudden cardiac death, especially congenital coronary artery anomalies, which result in sudden death almost exclusively in adults younger than age 35, and coronary thrombosis. The most lethal coronary artery anomaly is the left coronary artery arising from the right sinus of Valsalva; this anomaly often results in fatal arrhythmias, often with exercise. The right coronary artery arising from the left sinus of Valsalva may also be lethal in adolescents and young adults, but, unlike the anomalous left, is more often an incidental finding at autopsy. Approximately 60% of sudden coronary death is caused by coronary thrombosis, the rest die with severe coronary disease in the absence of thrombosis. The two major substrates of coronary thrombosis are plaque rupture and plaque erosion, and are not only different pathologically, but are seen in patients with divergent risk factor profiles. Plaque rupture is the most common cause of fatal coronary thrombus, and is characterized by necrotic core with a thin fibrous cap, infiltrated by macrophages. The factors that result in plaque instability and rupture are largely unknown, and are under intense scrutiny; morphologic studies have identified serum lipid abnormalities as a key risk factor in the development of plaque rupture. Plaque erosion, in contrast to plaque rupture, is seen in younger men and women, is not associated with lipid abnormalities, and does not result from exposure of the lipid core to the lumen. The heterogeneity of the atherosclerotic plaque and the diverse mechanics of plaque progression and thrombosis have only been relatively recently explored, and are largely elucidated by autopsy studies of victims of sudden coronary death.