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 214.7 (116.6-297.0) pg / mL, and those belonging to the AMI group had a mean of 164.6 (53.6-602.5) pg / mL. These patients were compared to two more groups: one with stable coronary artery disease (n = 9) and another group (n = 11) without coronary lesions (control group). It was observed that the mean IL-18 levels in the control group (46.8 (34.2-68.2) pg / mL) were significantly different from those with stable angina (85.7 (56.0- 157.7) pg / mL, p <0.01), suggesting that IL-18 concentrations in patients with stable coronary artery disease may be associated with the presence of advanced coronary artery disease. In the group of patients with unstable angina, the mean IL-18 levels were significantly higher than in the control group (p <0.001) or in the group with stable angina (p = 0.001). In the group of patients with AMI, the mean IL-18 levels were also significantly higher than in the control group (p <0.001) or the group with stable angina (p <0.01). IL-18 levels did not significantly differ between the group with unstable angina and the group with AMI. 13 In this same study, it was observed that serum IL-18 levels were significantly correlated with myocardial dysfunction severity, assessed by determining the ventricular ejection fraction (EF); the mean EF between the groups was 55% and mean IL-18 values were 46.8 pg / mL for non-coronary patients, 85.7 pg / mL for patients with stable angina, 214 pg / mL for those with unstable angina and 164.6 pg / mL for patients with acute myocardial infarction. Comparing with the results found in this study, it was observed that the mean EF between the groups was 65.09% and the mean levels of IL-18 were higher in Group I when compared to Group II and Group III; however, in this population (n = 119), systolic function distribution within normality was obtained for all groups, and Group I showed a slight reduction in the prevalence of individuals with normal EF, without statistical significance. It was also observed that the levels of IL-18 in patients with chronic CAD and without coronary lesions were statistically equivalent, not replicating the previous results. Blankenberg et al. 14 showed in their prospective study carried out with a cohort of 1229 patients with documented coronary heart disease and followed for an average of 3.9 years, that 95 patients died from cardiovascular causes and the mean IL-18 serum concentrations were significantly higher in patients with a fatal cardiovascular event than the ones without it (68.4 pg / mL vs. 58.7 pg / mL, p <0.001). This study included patients with stable angina (n = 855) and patients with unstable angina (n = 373) and the predictive value of IL-18 in relation to cardiovascular death was evaluated. It was observed that both groups showed an evident increase in the risk of fatal cardiovascular events according to the mean value of IL-18; however, the group of patients with unstable angina showed a higher value of this marker. The authors draw attention to this last analysis, since the group with unstable angina had a smaller sample size than the group of patients with stable angina; thus, the serum level of IL-18 can be identified as a strong independent predictor of death from cardiovascular causes in patients with CAD, regardless of the clinical status at admission. This result strongly supports the experimental evidence of IL-18-mediated inflammation, allowing the acceleration and vulnerability of atherosclerosis. 14 Studies have shown that the increase in serum IL-18 levels is also associated with some risk factors, such as type 2 DM and metabolic syndrome, in addition to the atherosclerosis severity. 15 Suchanek et al. 16 analyzed the increase in serum IL-18 levels in patients with CAD and type 2 DM. The authors evaluated a group of 130 patients with advanced CAD (at least two coronary lesions, one with stenosis >70%), and 43 were selected, with a previous diagnosis of DM undergoing treatment and another group with 31 healthy patients (control group). The groups were similarly matched for age, BMI, DLP, smoking; a higher level of IL- 18 was observed in patients with CAD (463.48 ± 111.7 pg / mL) when compared to the control group (248.99 ± 103.69 pg / mL), but patients with CAD and DM showed a higher level of IL-18 when compared to CAD patients without DM (500 pg / mL vs. 430 pg / mL, p = 0.04). The mechanisms responsible for the increase in IL-18 levels in diabetic patients are yet to be fully clarified; however, it is believed that deficient glycemic control, diabetic nephropathy, obesity and inflammation are considered possible causes to justify the increase in serum IL-18 levels in this patient profile. 16 In the present study, there was no statistically significant difference when the risk factor DM was compared between the groups of patients associated with the serum level of IL-18, showing that samples from patients with ACS, chronic CAD and healthy patients were similar to each other. In an observational study similar to this, albeit with a prospective analysis, 194 patients, 75 of which were acute and 119 chronic, were compared with 68 controls. The analysis of smooth muscle cells from the aorta showed higher values in patients with coronary disease than in controls and that IL-18 may be an independent risk factor for CAD. 17 In another study with 118 patients with coronary disease undergoing an angiographic study, consisting of 67 in the acute phase and 51 with stable angina, the levels of IL-18 were significantly higher in the acute ones compared to the chronic ones, which is in accordance with the results presented herein. 18 Regarding thrombus formation, Goetze emphasizes the importance of the increase in TpP levels in patients with CAD, highlighting the relevance of having an active thrombosis marker to provide important information in the ongoing ACS. 19 Following the same concept, Mega et al. 20 emphasized the prognostic value of TpP in patients with ACS, showing that increased TpP levels are associated with a higher risk of death and ischemic complications, making it clear that the inclusion of an activated coagulation marker, such as TpP, in patients with established cardiovascular disease and risk factors for CAD can offer a valuable complementary analysis in the risk assessment of ACS. Carried out with 284 healthy patients and 2349 patients with ACS, this study found that the mean level of TpP was higher in patients with ACS (8.9 µg / mL vs. 3.6 µg / mL, p <0.001), which is correlated a worse prognosis. 20 In the present study, it 696