ABC | Volume 114, Nº3, March 2020

Short Editorial Rocha & Aguiar ACS in Elderly Women: Inflammation strikes again Arq Bras Cardiol. 2020; 114(3):515-517 center study enrolling 803 patients with ACS (333 women, with a mean age of 65 years). The authors have found that increased levels of netrin-1 and IL-1 β were independently correlated with all-cause death and/or major cardiovascular events in elderly (> 60 years) women (but not in men) at 2-years of follow-up. Interestingly, compared to their counterparts, elderly women had a higher prevalence of traditional cardiovascular risk factors, hence suggesting that inflammation may have had an add-on decisive role for progressive atherosclerosis, increasing meaningful events in this subgroup. However, this hypothesis needs to be further corroborated, as previous studies have consistently found a prognostic role of IL-1 β regardless of sex, 6 and netrin-1 has not been widely investigated in CAD. In addition, events were scarce in young women (i.e., 3 all-cause deaths and 6 MI), hindering any definite conclusion. Nonetheless, whether these biomarkers may lead to tailored interventions in carefully selected patients (e.g., postmenopausal women) is an interesting concept worth further assessment. Netrin-1 is one of five types of netrins, similar in structure to laminins. They are thought to act as a regulator of neurons and cell migration during development. They may also be involved in angiogenesis (including pathways in cancer development), anti-ischemia reperfusion injury and atherosclerosis. Indeed, a study enrolling 180 patients with CAD and 79 controls without CAD demonstrated that netrin-1 (amongst other inflammatory markers) was more effective than classical biomarkers in the diagnosis (number and severity of lesions) and risk assessment of patients with CAD. 11 IL-1 β is among the first described cytokines, resulting from the purification of proteins responsible for inducing fever. Notable effects of IL-1 β on different cell types include inflammatory activation of endothelial cells participating in the atherogenic process. Furthermore, IL-1 β activity has been shown to be an independent predictor of all-cause mortality, ACS, lower left ventricular ejection fraction, and higher hsCRP levels in the AtheroGene study 12 (prospective registry of 1,337 CAD patients with ACS or stable angina). Leocádio and associates have found a potential prognostic value of increased netrin-1 and IL-1 β in their cohort of patients with ACS, particularly in elderly women, indicating a higher risk of major cardiovascular events even after adjustment for age, type of ACS, diabetes mellitus, hypertension, and dyslipidemia. 10 Future studies will focus on adequately selecting patients with CAD who may benefit most from “anti-inflammatory” drugs in an effective and safe manner. Hence, the role of the cardiologist caring for these patients may eventually include using adequate tools (e.g., plasma biomarkers) to identify “residual” risk in clinical practice and further reduce major cardiovascular events by tackling inflammation. The presented study 7 suggests that netrin-1 and IL-1 β may be of value in stratifying cardiovascular risk in elderly women. 1. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352(16):1685-95. 2. Silvestre-Roig C, Braster Q, Ortega-Gomez A, Soehnlein O. Neutrophils as regulators of cardiovascular inflammation. Nat Rev Cardiol. 2020 Jan 29. [ahead print]. 3. Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017;377(12):1119-31. 4. Ridker PM, MacFadyen JG, Everett BM, Libby P, Thuren T, Glynn RJ, et al. Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from theCANTOSrandomisedcontrolledtrial.Lancet.2018;391(10118):319-28. 5. Tardif JC, Kouz S,Waters DD, BertrandOF, Diaz R,Maggioni AP, et al. Efficacy andSafetyofLow-DoseColchicineafterMyocardial Infarction.NEngl JMed. 2019;381(26):2497-505. 6. Christodoulidis G, Vittorio TJ, FudimM, Lerakis S, Kosmas CE. Inflammation in coronary artery disease. Cardiol Rev. 2014;22(6):279-88. 7. Oikonomou EK, Marwan M, Desai MY, Mancio J, Alashi A, Hutt Centeno E, et al. Non-invasive detection of coronary inflammation using computed tomography and prediction of residual cardiovascular risk (the CRISP CT study): a post-hoc analysis of prospective outcome data. Lancet. 2018;392(10151):929-39. 8. Vergallo R, Porto I, D’Amario D, Annibali G, Galli M, Benenati S, et al. Coronary Atherosclerotic Phenotype and Plaque Healing in Patients With Recurrent Acute Coronary Syndromes ComparedWith PatientsWith Long- term Clinical Stability: An In Vivo Optical Coherence Tomography Study. JAMA Cardiol. 2019;4(4):321-9. 9. Pedicino D, Vinci R, Giglio AF, Pisano E, Porto I, Vergallo R, et al. Alterations of Hyaluronan Metabolism in Acute Coronary Syndrome: Implications for Plaque Erosion. J Am Coll Cardiol. 2018;72(13):1490-503. 10. Leocadio P, Menta P, Dias M, Fraga J, Goulart A, Santos I, et al. Níveis elevados de nitrina e IL-IB em mulheres idosas com SCA: pior prognóstico no acompanhamento de dois anos. Arq Bras Cardiol. 2020; 114(3):507-514 11. Liu T, Han C, Sun L, Ding Z, Shi F, Wang R, et al. Association between new circulating proinflammatory and anti-inflammatory adipocytokines with coronary artery disease. Coron Artery Dis. 2019;30(7):528-35. 12. Schofer N, Ludwig S, Rübsamen N, Schnabel R, Lackner KJ, Ruprecht HJ, et al. Prognostic impact of Interleukin-1 receptor antagonist in patients with documented coronary artery disease. Int J Cardiol. 2018;257:24-9. References 516