ABC | Volume 111, Nº6, December 2018

Original Article Elevation of Oxidized Lipoprotein of Low Density in Users of Combined Oral Contraceptives Alan Carlos Nery dos Santos, 1,2 Jefferson Petto, 1,2,4 Diego Passos Diogo, 1,2 Candice Rocha Seixas, 1 Lunara Horn de Souza, 3 Wagner Santos Araújo, 1 Ana Marice Teixeira Ladeia 1 Escola Bahiana de Medicina e Saúde Pública, 1 Salvador, BA – Brazil Universidade Salvador (UNIFACS), 2 Feira de Santana, BA – Brazil Faculdade Adventista da Bahia (FADBA), 3 Cachoeira, BA – Brazil Faculdade Social da Bahia (FSBA), 4 Salvador, BA – Brazil Mailing Address: Alan Carlos Nery dos Santos • Av. Dom João VI, 275. CEP 40290-000, Brotas, Salvador, BA – Brazil E-mail: alansantos.pos@bahiana.edu.br , allannery.santos@hotmail.com Manuscript received August 10, 2017, revised manuscript June 11, 2018, accepted July 02, 2018 DOI: 10.5935/abc.20180194 Abstract Background: The use of combined oral contraceptive (COC) has been related to changes in glycemic, lipid metabolism, increased oxidative stress, and systemic blood pressure, which could suggest a higher oxidation of low-density lipoprotein cholesterol (LDL-cholesterol) in women on use of COC. Objective: To test the hypothesis that there is a difference in the plasma values of oxidized LDL among women who use and do not use COC, as well as to evaluate the correlation between it and the lipid profile and high-sensitivity C-reactive protein (hs-CRP). Methods: Forty-two women with ages between 18 and 35 years old, who were eutrophic, irregularly active, with triglycerides < 150 mg/dL, blood glucose < 100 mg/dL, and who used or did not use COC were selected. These women were allocated in the COC group, formed by 21 women on COC use for at least 1 year; and a control group (CG), consisting of 21 women who had not used any type of hormonal contraceptive for at least 1 year. A significance level of 5% was adopted for statistical analyses. Results: It was observed that GCOC showed higher values of oxidized LDL than the CG, respectively 384 mU/mL versus 283 mU/mL (p < 0.01). A positive correlation between oxidized LDL and LDL-cholesterol (r = 0.3, p < 0.05), with total cholesterol (r = 0.47, p < 0.01) and with triglycerides (r = 0.32, p < 0.03) was observed, and there was no correlation with the hs-CRP. In the categorized analysis of oxidized LDL, 71.4% of GCOC women, and 28.6% of the CG remained above the established cutoff point. Conclusion: Women who use COC have higher plasma levels of oxidized LDL, and there is a positive correlation between oxidized LDL and other lipid variables. (Arq Bras Cardiol. 2018; 111(6):764-770) Keywords: Cardiovascular Diseases/complications; Contraceptives, Oral, Combined; Lipid Metabolism Disorders; Oxidative Stress; Atherosclerosis; C-Reactive Protein. Introduction Studies have shown that women of reproductive age who use combined oral contraceptives (COCs) present changes in glycemic, 1 lipid metabolism, 2 oxidative stress, 3 and chronic subclinical inflammation. 4,5 Also, an increase in the atherogenic subfractions of low-density lipoprotein (LDL‑cholesterol) 6 and elevated systemic blood pressure (SBP) 7 were identified. Together, these alterations are associated with LDL-cholesterol oxidation, which has been strongly related to a more atherogenic lipid profile. 8 Once oxidized, LDL-cholesterol presents several actions in vascular physiology, among them, it inhibits the expression of the endothelial nitric oxide synthetase enzyme mRNA, resulting in a decrease in the production of nitric oxide and favoring the atherosclerotic process. 9 Furthermore, it also impairs cell proliferation, cell motility and endothelial stem cells action, which are key mechanisms in the endothelialization of damaged areas in the atherosclerotic process. 10,11 It has also been suggested that higher oxidized LDL values, even within the limits of normal, are associated with an increased risk of future cardiovascular events and metabolic syndrome. 1,12-14 In addition, in Brazil, 33.8% of women aged 18-49 years used oral contraceptives, and of these, more than 13% (95% CI, 10.9-15.7%) had risk factors, such as smoking, systemic arterial hypertension, dyslipidemias and obesity. 15 These factors, associated with the use of COCs, can significantly increase the risk of atherothrombotic events, even in women of reproductive age. 16,17 However, to our knowledge, there are still no studies that have investigated the oxidation of LDL-cholesterol in young women using COC, without other factors that justify their oxidation. Thus, the hypothesis that there is a difference in the plasma values of oxidized LDL among women who 764