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 2 – General characteristics in the hospital phase in younger (<60 y) and older (>60 years) females Parameter Total (n = 333) Younger (<60 years) (n = 111) Older (>60 years) (n = 222) p BMI 26.8 (24.0 – 30.9) 26.8 (24.5 - 31.1) 26.7 (23.8 – 30.8) 0.532 ACS type 0.031 NSTEMI 142 (42.6) 40 (36.0) 102 (45.9) STEMI 77 (23.1) 35 (31.5) 42 (18.9) UA 114 (34.2) 36 (32.4) 78 (35.1) Smoking habits < 0.0001 Current 85 (27.2) 47 (44.3) 38 (18.4) Former 82 (26.3) 28 (26.4) 54 (26.2) Never 145 (46.5) 31 (29.2) 114 (55.3) Hypertension 267 (80.9) 79 (72.5) 188 (85.1) 0.006 Diabetes 148 (45.0) 39 (35.8) 109 (49.5) 0.018 Dyslipidemia 181 (60.7) 48 (48.5) 133 (66.8) 0.002 Glucose 124.0 (103.0 – 175.0) 121.0 (103.0 – 163.0) 128.0 (104.0 – 180.0) 0.381 Triacylglycerol 126.0 (97.0 – 183.0) 151.0 (97.0 – 201.0) 122.0 (93.5 – 174.0) 0.080 Total Cholesterol 170.0 (139.0 – 204.0) 185.0 (157.5 – 215.3) 161.0 (134.0 – 196.0) 0.002 HDL- Cholesterol 39.0 (32.0 – 46.5) 36.0 (32.0 – 45.0) 41.0 (33.0 – 47.2) 0.065 LDL- Cholesterol 99.0 (77.0 – 124.3) 114.0 (89.0 – 134.0) 93.0 (72.0 – 118.0) 0.0004 Netrin-1 44.8 (34.8 – 62.8) 44.8 (33.8 – 65.8) 44.8 (34.7 – 65.0) 0.861 IL-1β 13.8 (7.1 – 29.7) 15.5 (7.9 – 49.7) 13.4 (7.1 – 24.1) 0.037 Values are median (interquartile interval) or n (%).ACS: acute coronary syndrome. BMI: body mass index in kg/m 2 . HDL: high-density lipoprotein. IL-1β: Interleukin - 1beta. LDL: low-density lipoprotein. NSTEMI: non-STsegment elevation Myocardial Infarction. STEMI: ST-segment elevation Myocardial Infarction. UA: unstable angina. Data of plasma glucose, triacylglycerol, 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. Plasma Netrin-1 is a diagnostic biomarker of many cancer types. 17-19 It was verified that the higher gene expression or concentration of Netrin-1 in these tissues was associated with a worse prognosis, probably related to the anti-apoptotic and angiogenic effects of Netrin-1. However, the role of Netrin-1 in atherosclerosis and cardiac remodeling after MI is still controversial. It has been described that netrin-1 could promote or protect against atherosclerosis, in the dependency of environmental conditions. 20 Reduced endogenous levels of Netrin-1 can also lead to deleterious effects since pro-atherogenic factors can reduce the expression of this molecule. 20 In models of MI, netrin-1 administration reduced the severity of myocardium lesion when compared to the non-supplemented controls. 21,22 In our study, it is possible that the "High Netrin-1" group is composed of patients who had a more severe ACS event. Our hypothesis is that the level of Netrin-1 increases in more severe cases of ACS. This hypothesis is based on studies that indicate that the expression of Netrin-1 is induced after cellular injury and can be used as a biomarker for organ damage or disease 23 as seen in the cardiac surgery. 24 Moreover, hypoxia, a condition closely linked to atherosclerosis and ACS is also an inducer of Netrin-1 expression. 25 Moreover, Van Gils et al. 6 observed increased expression of the molecule in cholesterol‑loadedmacrophages promoting the retention of these cells in vitro , which could contribute to amore rapid evolution of the atherosclerotic plaque and consequently increase the chance of thrombus formation and occurrence of infarction. Table 3 – Outcomes according to the Netrin-1 in females Female - Total < 60 years > 60 years 2 years follow-up Low Netrin-1 High Netrin-1 p Low Netrin-1 High Netrin-1 p Low Netrin-1 High Netrin-1 p All-cause mortality 18 (36.0) 32 (64.0) 0.021 2 (66.7) 1 (33.3) 0.612 16 (34.0) 31 (66.0) 0.011 Cardiovascular mortality 12 (35.3) 22 (64.7) 0.052 2 (66.7) 1 (33.3) 0.612 10 (32.3) 21 (67.7) 0.029 Fatal or new non-fatal MI 11 (39.3) 17 (60.7) 0.193 4 (66.7) 2 (33.3) 0.467 7 (31.8) 15 (68.2) 0.066 Values are n (%). MI: myocardial infarction. Chi-square test. 510