ABC | Volume 112, Nº5, May 2019

Original Article Gonzaga et al Cardiac autonomic modulation in breast cancer Arq Bras Cardiol. 2019; 112(5):555-563 Estrogen is indicated as the main cardioprotective factor for women and its reduction inmenopause is related to the increase in sympathetic activity; a circumstance that may be aggravated in women with breast cancer due to treatment of the disease with AI. 19 In this context, the present study presents important results regarding the clinical framework of these patients. Regarding the correlation between HRV indices and cardiovascular biochemical variables, no correlation was observed with CRP, fasting glycemia, or HDL-Cholesterol. CRP has been highlighted, since elevated levels of this protein are associated with an increased risk of peripheral arterial disease, myocardial infarction, stroke, and sudden death, 25 and high levels of CRP are predictive of poor prognosis for cancer patients, regardless of lifestyle, menopausal status, and the presence of CVD. 12 Although no statistically significant negative correlations were observed between HRV and CRP levels, indices reflecting overall variability and parasympathetic modulation presented marginal statistical values in relation to the correlation with CRP levels of the cancer group (SDNN – β 95% CI = 0.92, p = 0.082; SD2 – β 95% CI = 1.26, p = 0.136; RMSSD – β 95% CI = -0.50, = 0.089; SD1 – β 95% CI = 0.36, p = 0.092). Regarding the correlation between HRV and the triglyceride indices, we observed an inversely proportional correlation of triglycerides with the HFms 2 index β 95% CI = -0.53; p = 0.045) and, although not significant, the SD1 index presented similar behavior ( β 95% CI = -0.03; p = 0.095). In addition, the indices that reflect global variability, SDNN and SD2, also presented inversely proportional correlations with the triglycerides (SDNN – β 95% CI = -0.09; p = 0.045; SD2 – β 95% CI = - 0.13; p = 0.044), suggesting that changes in autonomic modulation in women with breast cancer, characterized by a reduction in HRV, may be associated with a worse lipid profile. Studies show that ANS imbalance is associated with hormonal and metabolic alterations since this system plays a fundamental role in metabolic control. 26 The study presents some methodological points to be raised. In the analyzes, we did not take into account associated heart diseases or the use of medications which could alter cardiac activity. In addition, the sample size considered for correlation analyzes may not have been sufficient for correlations between CRP, blood glucose, HDL-Cholesterol and HRV to be considered statistically significant. Despite this, the study presents an important clinical implication regarding alterations in the autonomic modulation of women with breast cancer who use AI and the inversely proportional relationship between HRV and triglyceride values in this population, suggesting a higher risk of CVD and a worse prognosis for these women. This information reinforces the need to use preventive strategies that are safe and effective in the clinical approach of these patients. Conclusion Based on our findings, women with breast cancer who use AI present reductions in HRV compared to women without cancer and in these women HRV indices are inversely correlated with triglyceride values. Author contributions Conception and design of the research: Paulo TRS, Viezel J, Freitas Jr. IF; acquisition of data: Paulo TRS, Viezel J; analysis and interpretation of the data: Gonzaga, LA, Vanzella LM; statistical analysis: Gonzaga, LA, Vanzella LM, Vanderlei LCM; writing of the manuscript: Gonzaga, LA, Paulo TRS, Vanzella LM; critical revision of the manuscript for intellectual content: Freitas Jr. IF, Vanderlei LCM. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. Sources of Funding There were no external funding sources for this study. Study Association This article is part of the thesis of Doctoral submitted by Thais Reis Silva de Paulo, from Programa de Pós graduação em Ciências da Motricidade - UNESP. Ethics approval and consent to participate This study was approved by the Ethics Committee of the Faculdade de Ciências e Tecnologia - UNESP under the protocol number 672.7715.1.00005402/2015. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study. 1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69-90. 2. WorldHealthOrganization.Breastcancer:preventionandcontrol [Internet]. Geneva: World Health Organization; 2018 [citado nov. 2018]. Disponível em: http://www.who.int/cancer/detection/breastcancer/en/ 3. Vance V, Mourtzakis M, McCargar L, Hanning R. Weight gain in breast cancer survivors: prevalence , pattern and health consequences. Obes Rev. 2011;12(4):282-94. 4. GaoQ, Patani N, Dunbier AK, Ghazoui Z, Zvelebil M, Martin LA, et al. Effect of aromatase inhibition on functional gene modules in estrogen receptor- positive breast cancer and their relationshipwith antiproliferative response. Clin Cancer Res. 2014;20(9):2485-94. 5. Mao H, Bao T, Shen X, Li Q, Seluzicki C, Im EO, et al. Prevalence and risk factors for fatigue among breast cancer survivors on aromatase inhibitors. Eur J Cancer. 2018 Sep;101:47-54. 6. MendelsohnME. Protective effects of estrogen on the cardiovascular system. Am J Cardiol. 2002;89(12A):12E-17. References 562