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 Table 3 – Linear indices in frequency domain of heart rate variability in each group Group with breast cancer (n = 14) Group without breast cancer (n = 27) p value LF ms 2 b 67.00 ± 46.50 203.00 ± 257.50 0.009 HF ms 2b 70.00 ± 61.50 136.00 ± 264.00 0.008 LF/HF ms 2b 0.47 ± 0.99 0.71 ± 0.66 0.564 Mann Whitney testb: Median ± interquartile range; ms 2 : milliseconds; LF: low frequency; HF: high frequency; VLF: very low frequency. Table 4 – Correlation of heart rate variability indices with the inflammatory marker PCR with and without adjustments for age in woman with breast cancer PCR Without adjustment Adjusted (age) β95% CI p β95% CI p Mean RR ms -8.53 (-20.65; 3.58) 0.149 -6.36 ( -20.21; 7.48) 0.330 SDNN ms -0.92 (-1.98; 0.13) 0.082 -0.92 (-2.17; 0.32) 0.129 Mean HR 1/min 0.81 (-0.34; 1.96) 0.150 0.62 ( -0.70; 1.94) 0.322 RMSSD ms -0.50 (-1.03; 0.02) 0.059 -0.52 ( -1.15; 0.09) 0.089 NN50 count -0.68 (-2.25; 0.88) 0.360 -0.86 (-2.69; 0.95) 0.315 pNN50 % -0.06 (-0.22; 0.08) 0.360 -0.08 (-0.26; 0.09) 0.315 VLF ms 2 0.00 ( -0.00; 0.00) 0.588 0.00 (-0.00; 0.00) 0.685 LF ms 2 -12.40 (-34.90; 10.10) 0.251 -14.94 (-41.16; 11.27) 0.233 HF ms 2 -4.59 (-10.64; 1.45) 0.123 -6.00 (-12.76; 0.76) 0.076 LF/HF ms 2 0.00 (-0.07; 0.07) 0.972 0.01 (-0.09; 0.06) 0.699 RR tri -0.22 (-0.45; -0.00) 0.053 -0.23 (-0.50; 0.04) 0.087 TINN ms -3.07 (-8.00; 1.85) 0.198 -4.28 (-9.76; 1.19) 0.112 SD1 ms -0.36 (-0.74; 0.01) 0.056 -0.37 (-0.81; 0.07) 0.092 SD2 ms -1.26 (-2.74; 0.21) 0.086 -1.27 (-3.15; 0.47) 0.136 PCR: C reactive protein; SDNN: standard deviation of all normal RR intervals, expressed in milliseconds; HR: heart rate; RMSSD: square root of the mean of the squared differences between adjacent normal RR intervals; NN50: number of pairs of successive NNs that differ by more than 50 ms; pNN50: proportion of NN50 divided by total number of NNs; TINN: triangular interpolation of NN interval; VLF: very low frequency; LF: low frequency; HF: high frequency; RR tri: RR triangular; SD1: instantaneous variability of beat-to-beat variability; SD2: long-term standard deviation of continuous RR intervals index; ms: milliseconds. Reduction in global variability and parasympathetic modulation was also observed by Caro-Morán et al. 8 in women with breast cancer undergoing chemotherapy, radiotherapy, and hormone therapy after 1 year of treatment. The authors observed reduced values of SDNN, RMSSD, and HF ms² in the cancer group in relation to the group without the disease. In these women, no significant differences were found in the LF ms² and LF/HF indices, although higher values were found in the cancer group. It is important to note that higher parasympathetic modulation has been reported as an important factor related to a better prognosis for these patients, as observed by Giese-Davis et al., 21 who reported that high baseline HF values were associated with higher survival and lower cardiovascular risk. Greater parasympathetic modulation is generally associated with lower cardiovascular risk, 22 so the reduced parasympathetic modulation found in the present study, observed through lower values of the RMSSD, pNN50, SD1, and HF ms² indices in the cancer group, may indicate higher cardiovascular risk and a worse prognosis in this population. HighHRV is associatedwith higher levels of parasympathetic modulation and longer survival in patients with myocardial infarction and those under palliative care. 21 Regarding cancer, alterations in autonomicmodulation influence the development and prognosis of the disease. In a study carried out with an animal model it was shown that stimulation of the nervous system with the release of catecholamines can activate beta-adrenergic receptors in tumour cells, leading to more aggressive growth and dissemination of malignant cells, whereas in humans the use of beta- has been shown to be beneficial in reducing the risk of recurrence in patients with breast cancer. 23 Regarding parasympathetic modulation, Erin et al. 24 demonstrated that vagal blockade promotes the increase of metastases in mice. 560