ABC | Volume 111, Nº6, December 2018

Original Article Santos et al OX-LDL and Oral Contraceptives Arq Bras Cardiol. 2018; 111(6):764-770 Table 1 – Clinical and anthropometric characteristics of women using and not using combined oral contraceptives (n = 42) Variables GCOC (n = 21) CG (n = 21) p value Age (years) 23 ± 3.1 23 ± 3.4 0.98* Body mass index (kg/m 2 ) 20 ± 2.1 19 ± 2.8 0.07* Waist circumference (cm) 73 ± 7.8 70 ± 5.9 0.32* Systolic blood pressure (mmHg) 118 ± 8.8 111 ± 9.7 0.02* Diastolic blood pressure (mmHg) 77 (74 – 80) 70 (70 – 80) 0.18 ** C-reactive protein (mg/L) 2.7 (1.8 – 6.4) 0.9 (0.5 – 1.1) < 0.01 ** Blood glucose (mg/dL) 82 ± 6.9 83 ± 5.7 0.57* Pyruvic glutamic Transaminase (U/L) 15 ± 4.2 14 ± 3.4 0.16* Time of use of COC (years) 3.7 ± 2.3 – – GCOC: combined oral contraceptive group; CG: control group; COC: combined oral contraceptive; *Bidirectional Student’s t test for independent samples; **Bidirectional Mann-Whitney test. Ethical aspects Throughout the study the guidelines on human research in the Declaration of Helsinki and Resolution 466/12 of the National Health Council were followed. This study was submitted and approved by the Research Ethics Committee of Faculdade de Tecnologia e Ciência de Salvador – BA with number 3.390/2011. All participants received detailed information about the study objectives, risks and benefits involved in the procedures and signed the informed consent form. Two copies were filled, one being kept with the participants, and the other with the researchers. Results Table 1 presents the clinical and anthropometric characteristics of the sample. Homogeneity between the groups is observed, and the difference between the values of the SBP (p < 0.02) and the CRP (p < 0.01) are highlighted, which are higher in the GCOC. When comparing the lipid fasting variables, and the TG/HDL-cholesterol ratio (Table 2), it is observed that the GCOC presents values of plasma triglycerides (p < 0,01), total cholesterol (p < 0,01), HDL-cholesterol (p < 0,04), VLDL-cholesterol (p < 0,01) and TG/HDL-cholesterol ratio (p < 0,01) higher than the GC. As shown in Figure 1, GCOC women had higher oxidized LDL plasma levels (mU/mL) than the CG, 384 (198-410) versus 283 (208-250) (p < 0.01). In Table 3, the analyses of correlation between oxidized LDL and the variables of the fasting lipid profile, as well as between oxidized LDL and the PCR are presented. Moderate and positive linear correlation was observed between oxidized LDL, and LDL-cholesterol, triglycerides and total cholesterol. In Table 4, we can observe the intergroup analysis of oxidized LDL when categorized based on the value of the median. It can be seen that 71.4% of the women in the GCOC had higher plasma oxidized LDL values than the established cut-off when compared to the CG, which was 28.6% (p < 0.01). Discussion In response to the objectives of this study, we identified that women who use COC have higher oxidized LDL values, with a moderate and positive correlation of oxidized LDL with LDL-cholesterol, total cholesterol and triglycerides. In addition, 71.4% of the women who used COC presented oxidized LDL values above the cutoff point when compared to the control group (28.6%). Thus, although it is not possible to establish a perfect cause-effect relationship due to the method used, to the non-stratification of COC types, and to the effects of regionality, the results presented here are reinforced by the characteristics and homogeneity of the sample, which does not present the classic factors that could be known to induce the increase of oxidized LDL. In this context, although there is no clearly defined mechanism, some hypotheses may explain the elevation of oxidized LDL in women who use COC. It should be noted that, in recent years, scientific evidence has increasingly made the role of oxidized LDL in the pathophysiology of atherosclerosis clearer. 25 However, there is still no clearly defined mechanism, but several hypotheses that help explain the oxidation of LDL-cholesterol in different populations. 8,25 One of these hypotheses demonstrates that the bioavailability of LDL-cholesterol in association with oxidative stress appears to be the main determinant for the formation of oxidized LDL. 8 Thus, although we did not observe a difference in the fasting LDL-cholesterol levels among the groups studied, we suggest that the GCOC has a higher concentration of the more atherogenic LDL-cholesterol subfraction. This particle is small and dense, and has lower concentrations of antioxidants. Taken together, these factors make it more prone to oxidative damage. 26 In this study, the hypothesis in question is based on the TG/HDL-cholesterol ratio result, which we found to be significantly higher in GCOC. In addition, it has been suggested that the TG/HDL-cholesterol ratio may reflect the size of LDL‑cholesterol particles, with values > 1 being indicative of small and dense particles. 26 Consistent with our study, Graaf et al. 6 showed that women who use COC have higher concentrations of atherogenic LDL‑cholesterol subfraction, which may suggest a more atherogenic lipid profile in this population. 766