ABC | Volume 114, Nº4, April 2020

Original Article Scherr et al. Interleukin-18 and thrombus precursor protein in CAD Arq Bras Cardiol. 2020; 114(4):692-698 of the intima and adventitia, intra-plaque hemorrhage, exposure of thrombogenic material to the bloodstream, triggering platelet accumulation, coagulation cascade activation and fibrin deposition. 5 The inflammatory response in atherogenesis consists of functional alterations in endothelial cells, T-lymphocytes, monocyte-derived macrophages, smooth muscle cells and, in the early stages, it is caused by the accumulation of lipids in the arterial walls. 6 The activation of these cells triggers the formation and interaction of several cytokines, adhesion molecules, growth factors, accumulation of lipids and proliferation of smooth muscle cells. In addition to these factors, the inflammatory response can be induced by oxidative stress (oxidation of low-density lipoprotein - LDL). 7,8 Currently, new biomarkers are being studied in association with acute or chronic coronary syndrome and correlated with the prognostic value, which is the objective of this study. Two of them were evaluated in this study: the thrombus precursor protein (TpP) and interleukin 18 (IL-18) in individuals with acute myocardial infarction with and without ST-elevation, unstable angina (UA), chronic coronary artery disease and individuals who had no evidence of obstructive coronary atherosclerotic disease, but in the presence of risk factors for CAD. The choice of biomarkers was based on their involvement with the inflammatory (IL-18) and thrombotic (TpP) processes, within the context of atherosclerosis and aggravation of atherosclerotic disease. TpP is a biomarker used to estimate soluble fibrin polymers. Elevated levels of TpP indicate a pro-thrombotic status and active thrombogenesis. In patients with ACS, increased levels of this biomarker are associated with a higher risk of death and ischemic complications; therefore, TpP has been shown to be an independent marker for adverse cardiovascular outcomes. 9 The IL-18 biomarker is a pro-inflammatory cytokine, closely associated with atherosclerotic plaque instability, and is therefore a good predictor of undesirable events in ACS. 10,11 In an observational study, it was also shown to be a good predictor of adverse cardiovascular events in chronic coronary disease over two years. 12 Studying patients vulnerable to atherosclerotic disease and even being able to have severity parameters in those with the disease already present through new markers has been a challenge for current medical research. In this context, the new biomarkers occupy an important space, considering the morbidity and mortality aspect of coronary disease, which may become predictors of cardiovascular events and thus contribute to the prevention, early detection and screening of CAD. Methods Primary endpoint To evaluate the serum levels of biomarkers: interleukin 18 (IL-18) and thrombus precursor protein (TpP) in patients with acute or chronic coronary syndrome in relation to the control group. Secondary endpoints To verify the association of serum levels of biomarkers interleukin 18 (IL-18) and thrombus precursor protein (TpP) with disease chronicity, worsening of coronary artery disease or absence of obstructive coronary atherosclerotic process. To evaluate the association between epidemiological, anthropometric data and risk factors of the studied population with the biomarkers interleukin 18 (IL-18) and thrombus precursor protein (TpP). In this cross-sectional cohort, 119 patients, of both genders, older than 30 years of age, were stratified into three groups: acute (Group I - n = 39), chronic (Group II - n = 40) and control (Group III - n = 40), according to the inclusion and exclusion criteria established for the study and compared with the quantitative analysis of two biomarkers: IL-18 and TpP. Patients belonging to Group I (acute) were recruited based on the typical clinical history of acute coronary syndrome (NSTEMI, STEMI, and UA), plus electrocardiographic data and cardiac enzymes at admission. Once identified, blood was collected within 48 hours of symptom onset, for subsequent biomarker measurement. The selection was made sequentially, according to the inclusion criteria, as these patients were admitted to the hospital. Patients belonging to Group II were selected sequentially based on the clinical history of chronic CAD confirmed by some imaging method (cardiac catheterization - CAT or coronary angiotomography - Angio- CT) or clinical report of previous AMI (with complementary exams demonstrating the condition - electrocardiogram - ECG and myocardial markers). Group III (control) consisted of patients who had risk factors for CAD in the absence of obstructive coronary lesion at the time of admission to the database. The absence of atherosclerotic obstructive coronary lesion was ruled out through cardiac catheterization or coronary angiotomography. Inclusion criteria • Group I (acute) - ACS (NSTEMI, STEMI and UA) a) AMI with or without ST-elevation demonstrated by the positive curve of myocardial necrosis markers (troponin), associated with ECG. b) UA based on the classically described clinical picture and complementary exams (electrocardiogram - ECG and cardiac catheterization - CAT). c) Measurement of biomarkers performed within the first 48 hours of symptom onset. • Group II (chronic) - chronic CAD a) confirmation by imaging method (cardiac catheterization or coronary angiotomography) or with a clinical history of previous coronary disease - previous AMI (diagnosis over six months before, confirmed by ECG and necrosis markers). • Group III (control) a) Presence or not of one or more risk factors for CAD: SAH, dyslipidemia (DLP), diabetesmellitus (DM), physical inactivity, smoking, ex-smoker, chronic renal failure, obesity. b) Cardiac imaging examination that proved the absence of obstructive coronary lesion: CAT or angio-CT, performed in the last six months prior to admission to the database. 693