ABC | Volume 114, Nº3, March 2020

Original Article Leocádio et al. Netrin-1 and IL-1 β : prognosis in ACS Arq Bras Cardiol. 2020; 114(3):507-514 Table 1 – General characteristics in the hospital phase in males and females Parameter Male (n = 470) Female (n = 333) p Age 60 (52 – 71) 65 (56 – 76) < 0.0001 BMI 26.8 (23.8 – 29.6) 26.8 (24.0 – 30.9) 0.128 ACS type 0.027 NSTEMI 191 (40.6) 142 (42.6) STEMI 147 (31.3) 77 (23.1) UA 132 (28.1) 114 (34.2) Smoking habits Current 141 (31.3) 85 (27.2) < 0.0001 Former 198 (43.9) 82 (26.3) Never 112 (24.8) 145 (46.5) Hypertension 339 (73.7) 267 (80.9) 0.018 Diabetes 156 (34.7) 148 (45.0) 0.004 Dyslipidemia 197 (48.0) 181 (60.7) 0.001 Glucose 125.0 (101.0 – 157.0) 124.0 (103.0 – 175.0) 0.652 Triacylglycerol 132.0 (94.0 – 190.3) 126.0 (97.0 – 183.0) 0.685 Total Cholesterol 171.5 (141.0 – 205.0) 170.0 (139.0 – 204.0) 0.720 HDL - Cholesterol 35.0 (30.0 – 44.0) 39.0 (32.0 – 46.5) < 0.0001 LDL - Cholesterol 102.5 (77.0 – 134.3) 99.0 (77.0 – 124.3) 0.386 Netrin-1 44.8 (34.2 – 65.8) 44.8 (34.8 – 62.8) 0.813 IL-1β 15.1 (7.4 - 28.8) 13.8 (7.1 – 29.7) 0.536 Values are median (interquartile interval) or n (%). ACS: acute coronary syndrome. BMI: body mass index in kg/m 2 . HDL: high-density lipoprotein. LDL: low-density lipoprotein. NSTEMI: non-STsegment elevation Myocardial Infarction. STEMI: ST-segment elevation Myocardial Infarction. UA: unstable angina. Data of plasma glucose, triglyceridemia, total cholesterol, HDL and LDL are presented as mg/dL. Netrin-1 and IL-1β are presented as pg/mL. Mann-Whitney test or chi-square test. p-value comparing male and female groups. were more frequent in younger women while more than 50% of the older women never smoked (Table 2). We did not find differences in the median of Netrin-1 between age groups. However, the median of IL-1 β was higher in the younger group. Associations between low and high Netrin-1 or IL1- β and the outcomes, according to the age range were presented in Table 3 and Table 4, respectively. The number of death of all-cause was very low (3 death) in the women younger than 60 years and only 6 cases of the combined outcome, avoiding reliable analyzes in this group. However, in the older (>60 years) group, we found associations between the highest level of Netrin-1 and deaths from all causes and cardiovascular causes. An association between high IL-1 β and death for CVD as also found among older women (p = 0.034). These data showing a worse prognostic in older females with high levels of Netrin-1 and IL-1 β at admission were confirmed by Kaplan-Meier curves. High levels of Netrin-1 showed a lower rate of survival when considering all-cause mortality (p = 0.011, Figure 1A) and also considering only cardiovascular deaths (p = 0.024, Figure 1B). The marker only tended to be associated with fatal MI or new non-fatal MI (p = 0.067, Figure 1C). High levels of IL-1 β also showed a lower rate of survival when considering cardiovascular deaths (p = 0.031, Figure 1E) and tended to be associated with fatal MI or new non-fatal MI (p = 0.064, Figure 1F). The analysis of the hazard ratios (Table 5) showed an increased risk of death from all causes for the high Netrin-1 group that remained significant in the adjusted model. The same results were seen for risk of death from cardiovascular causes. Considering the high levels of IL-1 β , we did not find significant HR in the crude model for all-cause mortality and fatal or new non-fatal MI (Table 5). However, significant HR for all-cause mortality and fatal or new non-fatal MI were observed in the adjusted model. We also observed an increased risk of death from cardiovascular causes for the high IL-1 β group even after model adjustment. Discussion This work is the pioneer in evaluating the prognostic value of Netrin-1 in ACS and presents new information about the prognostic value of IL-1 β in this condition. In our study, we observed an association between the highest levels of Netrin-1 and worse prognosis when all‑cause mortality and cardiovascular mortality were analyzed, in elderly females. 509