Inflammation Thrombosis Research Articles

Association between laboratory markers, clinical and radiological findings in patients with idiopathic intracranial hypertension: case–control study

BackgroundIdiopathic intracranial hypertension (IIH) is a disease of raised intracranial pressure. Contribution of inflammatory mediators has been suggested in IIH pathophysiology. The aim of this study was to estimate certain serum inflammatory markers in IIH patients compared to normal subjects. Also, to examine the correlation between these laboratory parameters and the clinical and radiological characteristics of IIH patients.ResultsBody mass index (BMI) was significantly higher among IIH patients compared to controls. Serum LDH, CRP, NLR and PLR were significantly higher, whereas serum iron was significantly lower in IIH patients compared to healthy controls. IIH patients with stenosis in brain MRV had significantly higher mean serum CRP compared with patients with normal MRV. There was a statistically significant positive correlation between serum CRP and the presence of stenosis in MRV, between serum LDH level and grade of papilledema, and between CRP, TIBC, and NLR with BMI.ConclusionsThere is a significant elevation of inflammatory markers in IIH patients. Moreover, cerebral venous sinus stenosis and BMI were positively associated with higher markers of inflammation as CRP, LDH and NLR indicating the role of inflammation in thrombosis and obesity associated with IIH.

Angiogenesis in Chronic Thromboembolic Pulmonary Hypertension: A Janus-Faced Player?

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare form of pulmonary hypertension characterized by the presence of organized thrombi that obstruct pulmonary arteries, ultimately leading to right heart failure and death. Among others, impaired angiogenesis and inflammatory thrombosis have been shown to contribute to the progression of CTEPH. In this review, we summarize the 2-faced nature of angiogenesis in both thrombus formation and resolution in the context of CTEPH and highlight the dual role of angiogenesis and neovascularization in resolving venous thrombi. Furthermore, we discuss relevant in vitro and in vivo models that support the benefits or drawbacks of angiogenesis in CTEPH progression. We discuss the key pathways involved in modulating angiogenesis, particularly the underexplored role of TGFβ (transforming growth factor-beta) signaling in driving fibrosis as an integral element of CTEPH pathogenesis. We finally explore innovative treatment strategies that target angiogenic pathways. These strategies have the potential to pioneer preventive, inventive, or alternative therapeutic options for patients with CTEPH who may not qualify for surgical interventions. Moreover, they could be used synergistically with established treatments such as pulmonary endarterectomy or balloon pulmonary angioplasty. In summary, this review emphasizes the crucial role of angiogenesis in the development of in fibrothrombotic tissue, a major pathological characteristic of CTEPH.

Associations between neutrophil-lymphocyte ratio and monocyte to high-density lipoprotein ratio with left atrial spontaneous echo contrast or thrombus in patients with non-valvular atrial fibrillation

BackgroundThe importance of inflammation in thrombosis is increasingly appreciated. Neutrophil-lymphocyte ratio (NLR) and monocyte to high-density lipoprotein ratio (MHR) are important indicators of systemic inflammation. This study aimed to investigate the associations between NLR and MHR with left atrial appendage thrombus (LAAT) and spontaneous echo contrast (SEC) in patients with non-valvular atrial fibrillation.MethodsThis retrospective, cross-sectional study enrolled 569 consecutive patients with non-valvular atrial fibrillation. Multivariable logistic regression analysis was used to investigate independent risk factors of LAAT/SEC. Receiver operating characteristic (ROC) curves were used to evaluate the specificity and sensitivity of NLR and MHR in predicting LAAT/SEC. Subgroup and Pearson correlation analyses were used to assess the correlations between NLR and MHR with the CHA2DS2-VASc score.ResultsMultivariate logistic regression analysis showed that NLR (OR: 1.49; 95%CI: 1.173–1.892) and MHR (OR: 2.951; 95%CI: 1.045–8.336) were independent risk factors for LAAT/SEC. The area under the ROC curve of NLR (0.639) and MHR (0.626) was similar to that of the CHADS2 score (0.660) and CHA2DS2-VASc score (0.637). Subgroup and Pearson correlation analyses showed significant but very weak associations between NLR (r = 0.139, P < 0.05) and MHR (r = 0.095, P < 0.05) with the CHA2DS2-VASc score.ConclusionGenerally, NLR and MHR are independent risk factors for predicting LAAT/SEC in patients with non-valvular atrial fibrillation.

Regulation of VWF (Von Willebrand Factor) in Inflammatory Thrombosis.

Increasing evidence indicates that inflammation promotes thrombosis via a VWF (von Willebrand factor)-mediated mechanism. VWF plays an essential role in maintaining the balance between blood coagulation and bleeding, and inflammation can lead to aberrant regulation. VWF is regulated on a transcriptional and (post-)translational level, and its secretion into the circulation captures platelets upon endothelial activation. The significant progress that has been made in understanding transcriptional and translational regulation of VWF is described in this review. First, we describe how VWF is regulated at the transcriptional and post-translational level with a specific focus on the influence of inflammatory and immune responses. Next, we describe how changes in regulation are linked with various cardiovascular diseases. Recent insights from clinical diseases provide evidence for direct molecular links between inflammation and thrombosis, including atherosclerosis, chronic thromboembolic pulmonary hypertension, and COVID-19. Finally, we will briefly describe clinical implications for antithrombotic treatment.

Relationship between the Soluble F11 Receptor and Annexin A5 in African Americans Patients with Type-2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is characterized by endothelial dysfunction, increased thrombogenicity, and inflammation. The soluble human F11 receptor (sF11R) and annexin A5 (ANXA5) play crucial roles in inflammatory thrombosis and atherosclerosis. We examined the relationship between circulating sF11R and ANXA5 and their impact on endothelial function. The study included 125 patients with T2DM. Plasma levels of sF11R and ANXA5 were quantified by ELISA. Microvascular function was assessed using the vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasound imaging. The mean age of patients in the study was 59.7 ± 7.8 years, 78% had hypertension, 76% had dyslipidemia, and 12% had CKD. sF11R correlated positively with ANXA5 levels (β = 0.250, p = 0.005), and correlated inversely with VRI and total nitic oxide (NO), (β = −0.201, p = 0.024; β = −0.357, p = 0.0001, respectively). Multivariate regression analysis revealed that sF11R was independently associated with ANXA5 in the total population and in patients with HbA1c > 6.5% (β = 0.366, p = 0.007; β = 0.425, p = 0.0001, respectively). sF11R and ANXA5 were not associated with vascular outcome, suggesting that they may not be reliable markers of vascular dysfunction in diabetes. The clinical significance of sF11R/ANXA5 association in diabetes warrants further investigation in a larger population.

COVID-19 coagulopathy - what should we treat?

New Findings What is the topic of this review? Overview of the coagulation abnormalities, including elevated D‐dimers widely reported with COVID‐19, often labelled as COVID coagulopathy. What advances does it highlight? The review highlights the changes in bronchoalveolar haemostasis due to apoptosis of alveolar cells, which contributes to acute lung injury and acute respiratory distress syndrome; the pathophysiological mechanisms, including endothelial dysfunction and damage responsible for thrombosis of pulmonary microcirculation and potential contribution to the hypoxaemia of COVID‐19 acute lung injury; and changes in coagulation proteins responsible for the hypercoagulability and increased risk of thrombosis in other venous and arterial beds. The rationale for anticoagulation and fibrinolytic therapies is detailed, and potential confounders that might have led to less than expected improvement in the various randomised controlled trials are considered. Coronavirus disease 19 (COVID‐19) causes acute lung injury with diffuse alveolar damage, alveolar–capillary barrier disruption, thrombin generation and alveolar fibrin deposition. Clinically, hypoxaemia is associated with preserved lung compliance early in the disease, suggesting the lack of excessive fluid accumulation typical of other lung injuries. Notably, autopsy studies demonstrate infection of the endothelium with extensive capillary thrombosis distinct from the embolic thrombi in pulmonary arteries. The inflammatory thrombosis in pulmonary vasculature secondary to endothelial infection and dysfunction appears to contribute to hypoxaemia. This is associated with elevated D‐dimers and acquired hypercoagulability with an increased risk of deep vein thrombosis. Hypercoagulability is secondary to elevated plasma tissue factor levels, von Willebrand factor, fibrinogen, reduced ADAMTS‐13 with platelet activation and inhibition of fibrinolysis. Multi‐platform randomised controlled studies of systemic therapeutic anticoagulation with unfractionated and low molecular mass heparins demonstrated a survival benefit over standard care with full‐dose anticoagulation in patients with non‐severe disease who require supplemental oxygen, but not in severe disease requiring ventilatory support. Late intervention and the heterogeneous nature of enrolled patients can potentially explain the apparent lack of benefit in severe disease. Improvement in oxygenation has been demonstrated with intravenous fibrinolytics in small studies. Inhaled anticoagulants, thrombolytic agents and non‐specific proteolytic drugs in clinical trials for decreasing alveolar fibrin deposition might benefit early disease. Essentially, COVID‐19 is a multi‐system disorder with pulmonary vascular inflammatory thrombosis that requires an interdisciplinary approach to combination therapies addressing both inflammation and intravascular thrombosis or alveolar fibrin deposits to improve outcomes.

Neuroprotective Effects of Quercetin on Ischemic Stroke: A Literature Review.

Ischemic stroke (IS) is characterized by high recurrence and disability; however, its therapies are very limited. As one of the effective methods of treating acute attacks of IS, intravenous thrombolysis has a clear time window. Quercetin, a flavonoid widely found in vegetables and fruits, inhibits immune cells from secreting inflammatory cytokines, thereby reducing platelet aggregation and limiting inflammatory thrombosis. In pre-clinical studies, it has been shown to exhibit neuroprotective effects in patients with ischemic brain injury. However, its specific mechanism of action remains unknown. Therefore, this review aims to use published data to elucidate the potential value of quercetin in patients with ischemic brain injury. This article also reviews the plant sources, pharmacological effects, and metabolic processes of quercetin in vivo, thus focusing on its mechanism in inhibiting immune cell activation and inflammatory thrombosis as well as promoting neuroprotection against ischemic brain injury.

Vascular complications of Behçet disease.

Behçet disease is a multi-systemic complex vasculitis with unknown etiology characterized by different clinical involvements, including mucocutaneous, ocular, vascular, articular, neurological, and gastrointestinal manifestations. Growing evidence supports that different phenotypes, characterized by clusters of co-existing involvements, can be distinguished. Namely, the vascular phenotype identifies a specific group of patients who suffer from recurrent inflammatory thrombosis and arterial involvement. Vascular disease develops in up to 40% with a definite male preponderance and is usually an early manifestation. Venous involvement is significantly more common than arterial disease, and lower extremity deep vein thrombosis is its most frequent manifestation. Arterial disease involves mostly pulmonary arteries and aorta and manifests mainly in the form of aneurysms. Glucocorticoids and immunosuppressants are the recommended first-line treatments in vasculo-Behçet. Furthermore, controlled trials are still needed to assess the role of adding anticoagulation to the treatment regimen, with an accent on new oral anticoagulants. Treatment with anti-TNF alpha agents seems promising, but the management strategies are not clear yet.

Pathology of lung‐specific thrombosis and inflammation in COVID‐19

BackgroundInfection by SARS‐CoV‐2 produces significant pulmonary pathology including endothelial damage with resultant thrombotic events. While pathologic features were described, there are limited data on the relationship of these changes to the inflammatory response and the production of thromboses. ObjectiveTo investigate pathology of COVID‐19‐related immunothrombosis. Patients/MethodsTissue samples from lung, kidney, brain and heart that were collected from 45 patients who died of COVID‐19. Histopathological examination was performed after H&E and Picro‐Mallory staining in combination with (immuno)fluorescence to visualize neutrophil extracellular traps. Ultrastructural alterations in lungs were studied with scanning and transmission electron microscopy. ResultsInflammatory changes and thrombosis were substantially more pronounced in the lung than in the kidney, heart, and brain. The most common pathologic finding was diffuse alveolar damage. In addition, most lung samples showed thrombi in vessels. The cause of death in single cases was massive pulmonary embolism. Ultrastructural examination revealed neutrophils attached to endothelium, perhaps as a step towards transendothelial migration. In addition, platelets were identified in the midst of fibrin as individual procoagulant balloon‐like cells. Ultrastructural examination demonstrated numerous virion‐like particles. ConclusionsStudying (ultra)structural features of the autopsy lung samples from patients with COVID‐19 has provided evidence for a pathogenic link between inflammation and thrombosis. The major features in the lungs of COVID‐19 patients comprised primary inflammatory thrombosis associated with diffuse alveolar damage. The lungs had pronounced circulatory changes with inflammation‐dependent intravascular blood clotting, whereas heart, brain, and kidneys had predominantly degenerative changes that were distinct from the lung pathology.

A Survey on Cardiac Complications of COVID-19 in Infants

Congenital heart disease (CHD) may have serious effects on the course of COVID-19. Limited data were available on CHD in neonates with COVID-19. This study aimed to review the cardiac complications in neonates infected with COVID-19. Some studies showed that myocardial injury in adult patients is often correlated with a fatal outcome. But, scientific evidence in infants is rare, although several reports were published with the description of cardiac involvement in COVID-19 pediatric patients. In these young subjects, a background of surgically treated CHD seems to be a predisposing factor. Numerous studies showed Multisystem inflammatory syndrome in children (MIS-c) is a deadly demonstration of COVID-19 with cardiac involvement. The underlying pathophysiology of COVID-19-associated cardiovascular complications is not fully understood, although direct viral infection of the myocardium, systemic inflammatory response, coagulation abnormalities and thrombosis and hypoxia have been suggested as possible mechanisms of cardiac complications. It seems COVID-19 can affect different parts of the heart; however, the myocardium is more involved. The mechanisms of pathogenesis of cardiovascular implications in adults and infants are similar but CHD and MIS-c in infants are more important. Further studies on the effects of COVID-19 on the neonatal cardiovascular system are needed.

The Management of Ischemic Limb in Thromboangiitis Obliterans (Buerger’s Disease)

Thromboangiitis obliterans is a segmental, progressive and recurrent inflammation thrombosis and re-canalisation of medium- and small-sized arteries and veins. The disease has a worldwide spread, and smoking appears to be the most important risk factor in these patients; cessation of smoking has been associated with improved limb salvage rates. Diagnosis is elusive, and treatment options are not fully standardised by well-proven randomised case control studies.

COVID-19 как системное заболевание

COVID-19 usually manifests by respiratory symptoms. However, it would be an erroneous simplification to consider it as a local respiratory disease. The nervous system and intestines are often involved even in patients with mild infection, although the risk of dissemination of the infectious process and the development of severe systemic disease is mainly associated with lung damage. The addition of infectious thrombotic microvasculitis (endothelitis) to bronchopneumonia-alveolitis not only forms a substrate for respiratory failure, but also increases a risk of viruses entry into the bloodstream. Viral sepsis develops, whereas inflammatory thrombosis damages new areas of the vascular bed. These mechanisms or direct viral invasion can result in involvement of many tissues and organs in the pathological process. This review examines the molecular, cellular and clinical manifestations and complications of the new coronavirus disease.

Interleukin 1α: a comprehensive review on the role of IL-1α in the pathogenesis and treatment of autoimmune and inflammatory diseases.

The interleukin (IL)-1 family member IL-1α is a ubiquitous and pivotal pro-inflammatory cytokine. The IL-1α precursor is constitutively present in nearly all cell types in health, but is released upon necrotic cell death as a bioactive mediator. IL-1α is also expressed by infiltrating myeloid cells within injured tissues. The cytokine binds the IL-1 receptor 1 (IL-1R1), as does IL-1β, and induces the same pro-inflammatory effects. Being a bioactive precursor released upon tissue damage and necrotic cell death, IL-1α is central to the pathogenesis of numerous conditions characterized by organ or tissue inflammation. These include conditions affecting the lung and respiratory tract, dermatoses and inflammatory skin disorders, systemic sclerosis, myocarditis, pericarditis, myocardial infarction, coronary artery disease, inflammatory thrombosis, as well as complex multifactorial conditions such as COVID-19, vasculitis and Kawasaki disease, Behcet's syndrome, Sjogren Syndrome, and cancer. This review illustrates the clinical relevance of IL-1α to the pathogenesis of inflammatory diseases, as well as the rationale for the targeted inhibition of this cytokine for treatment of these conditions. Three biologics are available to reduce the activities of IL-1α; the monoclonal antibody bermekimab, the IL-1 soluble receptor rilonacept, and the IL-1 receptor antagonist anakinra. These advances in mechanistic understanding and therapeutic management make it incumbent on physicians to be aware of IL-1α and of the opportunity for therapeutic inhibition of this cytokine in a broad spectrum of diseases.

Endothelial CD40 Mediates Microvascular von Willebrand Factor-Dependent Platelet Adhesion Inducing Inflammatory Venothrombosis in ADAMTS13 Knockout Mice.

von Willebrand factor (vWF) plays an important role in platelet activation. CD40-CD40 ligand (CD40L) induced vWF release has been described in large vessels and cultured endothelium, but its role in the microcirculation is not known. Here, we studied whether CD40 is expressed in murine microvessels in vivo, whether CD40L induces platelet adhesion and leukocyte activation, and how deficiency of the vWF cleaving enzyme ADAMTS13 affects these processes. The role of CD40L in the formation of beaded platelet strings reflecting their adhesion to ultralarge vWF fibers (ULVWF) was analyzed in the murine cremaster microcirculation in vivo. Expression of CD40 and vWF was studied by immunohistochemistry in isolated and fixed cremasters. Microvascular CD40 was only expressed under inflammatory conditions and exclusively in venous endothelium. We demonstrate that CD40L treatment augmented the number of platelet strings, reflecting ULVWF multimer formation exclusively in venules and small veins. In ADAMTS13 knockout mice, the number of platelet strings further increased to a significant extent. As a consequence extensive thrombus formation was induced in venules of ADAMTS13 knockout mice. In addition, circulating leukocytes showed primary and rapid adherence to these platelet strings followed by preferential extravasation in these areas. CD40L is an important stimulus of microvascular endothelial ULVWF release, subsequent platelet string formation and leukocyte extravasation but only in venous vessels under inflammatory conditions. Here, the lack of ADAMTS13 leads to severe thrombus formation. The results identify CD40 expression and ADAMTS13 activity as important targets to prevent microvascular inflammatory thrombosis.

血管内皮LOX-1は、炎症下の血栓形成を促進する

血管内皮LOX-1は、炎症下の血栓形成を促進する

RELATIONSHIP BETWEEN SOLUBLE F11 RECEPTOR, TOTAL NITRIC OXIDE LEVELS, AND VASCULAR FUNCTION IN AFRICAN AMERICANS WITH TYPE II DIABETES

Human F11 receptor (F11R) is an important cell adhesion molecule implicated in inflammatory thrombosis. F11R is associated with the presence and severity of cardiovascular disease. Endothelial dysfunction in diabetes has been attributed to lack of bioavailability of nitric oxide (NO), another key

Abstract WMP82: Brain-Derived Microparticles Mediate Cardiac Dysfunction After Stroke

Background and Purpose: Brain injury may induce cardiac damage. Microparticles (MPs, size between 0.1-1mm) are involved in intercellular communication and regulate thrombosis and inflammation. In this study, we investigate whether Brain-derived MPs (BDMP) after stroke contribute to stroke induced heart dysfunction. Method: 1) Human study: Serum GFAP+MP levels measured by Flow cytometry were obtained from acute stroke patients (≤ 3d post stroke) and normal subjects (n=15/group). 2) Animal study: Adult (8-9m) male C57BL/6J mice were subjected to distal middle cerebral artery occlusion (dMCAo) or sham control. BDMP were extracted from ischemic brain 24h after dMCAo by ultracentrifugation. BDMP (1.5х10 8 ) were injected (iv) into normal 8-9 m old C57BL/6J mice daily for 3 consecutive days (n=10). PBS was injected as control (n=9). Using Echocardiography, cardiac function was measured 3 and 30 days after injection. 3) In vitro study: Cultured primary cardiomyocytes were treated with: A) control; B-C) BDMP derived from sham or dMCAo mice; D-E) serum-MP derived from sham or dMCAo mice. Immunostaining, PCR, Western blot and LDH measurements were employed. Result: 1) Human study: Stroke patients exhibited significant increase of GFAP+MP levels in serum compared to normal subjects. 2) Animal-study: Compared with PBS control group, injection of BDMP results in a significant (p&lt;0.01): A) decrease in cardiac function identified by decreasing LVEF (left ventricular ejection fraction), LVSF (LV systolic fraction) at 3 and 30d post injection; B) increases cardiac fibrosis identified by Sirius Red Staining and increases of cardiac thrombosis measured by CD41, as well as increases leukocyte infiltration in the heart. 3) In vitro study: BDMP and serum-MP derived from dMCAo mice significantly induce cardiomyocyte death, and cardiomyocyte inflammatory factors (MCP1, VCAM1, ICAM, TNFα and TLR2) gene expression compared to sham BDMP or sham serum-MP, respectively; BDMP induces significantly increased cardiomyocyte death, and cardiomyocyte inflammatory factor compared with serum-MP. Conclusion: BDMP mediate cardiac dysfunction after stroke. BDMP induced cardiac dysfunction may be associated with increased inflammatory response and thrombosis in the heart.

Usefulness of thrombosis and inflammation biomarkers in chronic thromboembolic pulmonary hypertension-sampling plasma and surgical specimens.

Chronic thromboembolic pulmonary hypertension (CTEPH) results from persistent pulmonary vascular obstructions, presumably due to inflammatory thrombosis. Because estimates of thrombus volume at diagnosis have no predictive value, we investigated the role of the thrombosis marker, D-dimer, and the inflammation marker, C-reactive protein (CRP), for predicting outcomes in CTEPH. A total 289 consecutive patients with CTEPH were followed for 57 (median 45 to 69) months. One hundred fifty-seven of these patients underwent surgical pulmonary endarterectomy (PEA). D-dimer and CRP were collected at the time of CTEPH diagnosis and their impact on outcome was analyzed using Cox and logistic regression models. Their association with thrombus composition was analyzed utilizing HistoQuest. D-dimer and CRP levels were separately and independently predictive of death or need for lung transplantation (p = 0.012 and p = 0.025, respectively). For example, 5-year survival was 90% (confidence limits 84% to 96%) in patients with D-dimer levels <0.5 µg/ml and CRP <1 mg/dl at diagnosis, as compared with 50% (36% to 64%) for patients with D-dimer ≥0.5 µg/ml and CRP ≥1 mg/dl (p < 0.001). D-dimer and CRP both decreased significantly after PEA (p < 0.01). The amount of fresh red thrombus in thrombendarterectomy specimens correlated positively with D-dimer levels at diagnosis (r = 0.37, p = 0.003). D-dimer and CRP at the time of diagnosis are independent and significant predictors of outcome in CTEPH, available at the time of diagnosis. This observation suggests an important role for fibrin turnover and inflammation in the pathogenesis of CTEPH and the associated complications.

Heatstroke with rhabdomyolysis resulting in ischemic brain stroke and myocardial infarction

We report a case of heatstroke with rhabdomyolysis and myoglobinuria, which was complicated by cerebrovascular accident and myocardial infarction. Heatstroke can cause multiple serious systemic complications ranging from rhabdomyolysis to disseminated intravascular coagulation with multi-organ failure. However, it is also critical to consider its potential deleterious effects on the central nervous and cardiovascular systems. The complications of heatstroke can be explained by the combination of hypoperfusion and other mechanisms causing increased inflammatory response and thrombosis.

The Relationship between ABO Blood Group and Coronary Artery Disease: A Systematic Review and Meta-Analysis

Background: The coronary artery disease (CAD) is an important risk which causes death and disability. ABO blood group is genetically transmitted through chromosome, which has some role not only in the cholesterol balance and lipid homeostasis but also inflammatory markers and thrombosis. It is supposed to have a role in developing CAD. But the relationship between CAD and ABO blood group is still controversial. Here we conducted a metaanalysis aim to evaluate the role of each blood group on CAD. Method: We searched the related articles from PubMed and Embase which record the patients with CAD and themselves blood group. We compared the risk between each group with the others to evaluate the significance of each group to CAD. Result: In our analysis, the O group is more frequent in coronary artery disease followed by A, B and AB group successively, which is partly different with previous meta-analysis. Compared with A blood group, O group is more subjected to CAD (OR=0.97, 95% CI=0.83 TO 1.14, p=0.73) and AB group seem to be a protective factor (OR=6.52, 95% CI=4.83 to 8.81, p<0.00001). Conclusion: The statistical significance between A and O is unclear, but there are reasons to believe that blood group influences the incidence of CAD. O and A are served as risk factors of CAD, when AB group may be the protective factor. The subsequent mutual comparisons in B, AB and O have the similar results.