ABC | Volume 111, Nº1, July 2018

Original Article Bassi et al T2DM and HTN on HRV and cardiorespiratory status Arq Bras Cardiol. 2018; 111(1):64-72 physiologic measurements related to the ability to respond to aerobic exertion synergistically. In the present study these indices were shown as important markers of cardiocirculatory limitation to exercise in DMT2 and HTN. Effects of the coexistence of DMT2 and HTN on linear and nonlinear HRV dynamics HRV is reduced in patients with DMT2 31 as well as in patients with HTN 32 and its reduction is associated with poor cardiovascular prognosis. 33 Autonomic imbalance may be a final common pathway to increased morbidity and mortality in the presence of various conditions, including CVD. 34 Although time and frequency-domain HRV parameters have been shown to be more sensitive in a previous study, 35 in the present study we did not find significant alterations in these parameters. Roy and Ghatak 36 in their study with diabetic type 1 patients diagnosed ≥ 5 years earlier, showed that HRV spectral indices were better indicators of the prevalence of CAN than cardiovascular reflex tests. 36 Meanwhile, the use of HRV spectral analysis only to diagnose CAN should be carefully considered, since previous studies 30,37 showed low reproducibility of HRV assessment by spectral analysis. The presence of CAN is closely associated with macrovascular complications, mortality due to fatal cardiac arrhythmia, severe hypoglycemia, and sudden death. 38 However, nonlinear indices have been shown to be better than conventional methods for identifying subtle changes in cardiac autonomic modulation in various pathological conditions such as cardiovascular artery disease. 39 Nonlinear analysis has provided new insight into the HRV dynamics in various physiological and pathophysiological conditions, providing additional prognostic and analytical information to conventional approaches. 40 In the currently study, nonlinear indices were found to be reduced in the DMT2+HTN group when compared to the DMT2 group. Additionally, we observed that nonlinear indices of HRV were more sensitive in detecting differences in the autonomic impairment between patients with diabetes and patients with diabetes associated to HTN. ApEn and SE indicated changes that suggest that the coexistence of both diseases is associated to reduced complexity. 41 In the same way, Roy and Ghatak 36 showed that nonlinear analytical methods were effective to find differences in HRV patterns between diabetic patients and healthy matched controls. Recently, our group verified that patients with DMT2 with poor glycemic control are more susceptible to poor autonomic nervous control of HR, demonstrated by linear and nonlinear indices. 31 However, the present study is the first to analyze the coexistence of HTN and DMT2 by means of linear and nonlinear HRV analysis. The Diabetes Control and Complications Trial (DCCT) showed that glycemic control can reduce the incidence of CAN. 42 Previous studies evidenced that a reduction around 11% in the HbA1c improved HRV in patients with type 1 diabetes. 43 Additionally, Vinik et al., 4 showed that the CAN prevalence and mortality rates were higher among individuals with DMT2, probably because of the longer duration of glycemic abnormalities before diagnosis. Our findings showed that, even after a short period from the DMT2 diagnosis, both groups demonstrate poor glycemic control, which might negatively affect HRV and, consequently, increase the patients’ cardiovascular risk. Effects of the coexistence of HTN and DMT2 on CPET CPET represents an easy and non-invasive way to obtain information on the impairment of exercise capacity and of cardiopulmonary fitness. 44 Ugur-Altun et al. 45 demonstrated a negative correlation between insulin resistance and peak exercise capacity in diabetic patients. Interestingly, in our study we could not find any differences between groups in peak exercise capacity, maybe because both groups had poor glycemic control, as showed by HbA1c, even though the DMT2+HTN group has shown higher insulin resistance than the DMT2 group. CP, which is related to the cardiac output and the mean arterial blood pressure at peak exercise, is considered a more powerful predictor of mortality than peak oxygen consumption. 46 In our study, we have not found differences in CP and VP between groups; however, negative correlations were shown of CP and VP with nonlinear indices of HRV. Castello-Simões et al. 16 studied patients with CVD (without heart failure) and demonstrated that both CP and VP might hold value as screening tools in assessing not only functional significance but also exercise tolerance, as the impairment of autonomic nervous modulation is related to reduced CP and VP. The present study has some limitations that need to be stated. First, some relevant information, including DMT2 and HTN diagnostic date and physical activity status were self-reported by the patients and this could introduce a recall bias. Moreover, only the BMI was used to characterize the patients’ body type. However, in order to provide a complete description, other body composition measurements should be considered. Secondly, in the present study a control group comprised of individuals without diabetes mellitus or arterial hypertension could be better clarify the potential influence of these risk factors on HRV indices. Conclusion In summary, cardiac autonomic alteration in the coexistence of DMT2 and HTN was observed when compared to matched DMT2 patients. In addition, the alteration of nonlinear HRV dynamics observed in resting conditions may have negative consequences on these patients’ cardiopulmonary and cardiocirculatory responses. Author contributions Conception and design of the research: Bassi D, Cabiddu R, Mendes RG, Arakelian VM, Caruso FCR, Borghi-Silva A; Acquisition of data: Bassi D, Mendes RG, Arakelian VM, Caruso FCR, Bonjorno Júnior JC, Borghi-Silva A; Analysis and interpretation of the data: Bassi D, Mendes RG, Tossini N, Arakelian VM, Arena R, Borghi-Silva A; Statistical analysis: Bassi D, Mendes RG, Arakelian VM, Arena R, Borghi‑Silva A; Obtaining financing: Bassi D, Borghi-Silva A; Writing of the manuscript: Bassi D, Cabiddu R, Mendes RG, Tossini N, Arakelian VM, Caruso FCR, Bonjorno Júnior JC, 70