Consolidated and emerging inflammatory markers in coronary artery disease

Coronary artery disease is an event of atherosclerosis characterized by a chronic vascular inflammation. Risk factors like obesity, diabetes mellitus, hypertension,smoking, hypercholesterolemia and positive family history sometimes are not sufficiently adequate to the enhancement of cardiovascular risk assessment. In the past years numerous biomarkers, like C reactive protein,cytokines and adhesion molecules, have been observed to be related to adverse cardiovascular prognosis. Recently,several studies found an association among inflammatory biomarkers and cardiovascular diseases suggesting their utility to identify the risk of an acute ischemic event and the detection of vulnerable plaques. The emerginginflammatory markers are well divided for diagnosis and prognosis and plaque instability of coronary artery disease. Some of them, the lectin-like oxidized low density lipoprotein receptor-1 can be important both in diagnosis and in the evaluation of plaque instability, other are inserted in the above reported classification. The emerging inflammatory markers in acute-phase include amyloid A, fibrinogen and pentraxin 3 while myeloperoxidase, myeloid-related protein 8/14 and pregnancy-associated plasma protein-A are recognize markers of plaque instability. Lastly, some studies demonstrated that circulating mi RNAs are involved in coronary artery disease, acute myocardial infarction and heart failure.

Procoagulant activity of circulating microparticles is associated with the presence of moderate calcified plaque burden detected by multislice computed tomography

Background Circulating microparticles （MPs） have been reported to be associated with coronary artery disease （CAD）. In this study, we explored the relationship between MPs procoagulant activity and characteristics of atherosclerotic plaque detected by 64-slice computed tomography angiography （CTA）. Methods In 127 consecutive patients with CAD but without acute coronary syndrome and who under went 64-slice CTA, MPs procoagulant activity in plasma Coy a thrombin generation test）, soluble form of lectin-like oxidized low-density lipoprotein receptor-1 （sLOX-1） and N（epsilon）-（carboxymethyl） lysine （CML） circulating levels （by ELISA） were measured. A quantitative volumetric analysis of the lumen and plaque burden of the vessel wall （soft and calcific components）, for the three major coronary vessels, was performed. The patients were classified in three groups according to the presence of calcium volume： non-calcified plaque （NCP） group （calcium volume （%） = 0）, moderate calcified plaque （MCP） group （0 〈 calcium volume （%） 〈 1）, and calcified plaque （CP） group （calcium volume （%） 〉 1）. Results MPs procoagulant activity and CML levels were higher in MCP group than in CP or NCP group （P = 0.009 and P = 0.027, respectively）. MPs procoagulant activity was positively associated with CML （r = 0.317, P 〈 0.0001） and sLOX-1 levels （r = 0.216, P = 0.0025）. Conclusions MPs procoagulant activity was higher in the MCP patient group and correlated positively with sLOX-1 and CML levels, suggesting that it may characterize a state of blood vulnerability that may locally precipitate plaque instability and increase the risk of subsequent major cardiovascular events.

Hydroperoxides and cytokines as biomarkers in detecting atherosclerosis predisposition in cigarette smokers

Objectives: Smoking increases oxidative modification of LDL, associated with lower HDL plasma levels, systemic inflammatory response and endothelial dysfunction. We tested the hypothesis that the risk status for coronary atherosclerosis disease (CAD) of cigarettes smokers might be identified by means of serum oxidative levels and vascular inflammation determination. Design and Methods: Oxidative stress levels, cytokines, and the metabolic status were investigated on 499 subjects admitted to our institute. The association between biomarkers and smoking habits in the presence/absence of disease and with the number of vessel affected, was studied. Results: Oxidative stress and inflammatory levels (p < 0.001) were strongly induced by smoking habits. Serum values of the subjects categorised as CAD, non CAD and healthy subjects differed significantly (p < 0.001) only for the degree of oxidative stress. Glycaemia was able to affect C-reactive protein serum levels with a positive association (p < 0.05). The analysis of the study population indicated that serum oxidative stress levels significantly increased with increasing number of vessels affected (p < 0.01). When statistical analysis was performed separately in both smoking groups, smokers did not show any particular difference for both oxidative stress and inflammation markers between the two groups of cardiovascular patients (CAD and non CAD) and the control group, while for non smokers, the differences were evident. Conclusion: These findings indicate that the considered biomarkers, especially oxidative stress, can be useful to predict the biological damage caused by cigarette smoking, as well as to identify subjects characterised by a higher risk of cardiovascular event, but cannot evaluate the presence of disease in subjects with smoking habit.

Enzymatic antioxidant system in vascular inflammation and coronary artery disease

In biological systems there is a balance between the production and neutralization of reactive oxygen species(ROS). This balance is maintained by the presence of natural antioxidants and antioxidant enzymes suchas superoxide dismutase(SOD), catalase and glutathione peroxidase. The enhancement of lipid peroxidation or the decrease of antioxidant protection present in metabolic diseases or bad lifestyle can induce endothelial dysfunction and atherosclerosis.Clinical studies have shown that oxidative stress can increase ROS reducing the formation of antioxidant defences, especially in subjects with coronary artery disease(CAD). Some observation indicated that in the early stages of the disease there is a homeostatic upregulation of the antioxidant enzyme system in response to increased free radicals to prevent vascular damage.As soon as free radicals get to chronically elevated levels, this compensation ceases. Therefore, SOD and the other enzymes may represent a good therapeutic target against ROS, but they are not useful markers for the diagnosis of CAD. In conclusion antioxidant enzymes are reduced in presence of metabolic disease and CAD. However the existence of genes that promote their enzymatic activity could contribute to create new drugs for the treatment of damage caused by metabolic diseases or lifestyle that increases the plasma ROS levels.