Evaluación de la disfunción autonómica en un escenario cardiometabólico y su interacción con la edad, la rigidez arterial, la disfunción endotelial y el estrés oxidativo

Abstract

Autonomic dysfunction is associated with an increase in cardiovascular morbidity and mortality and sudden cardiac death. In the genesis of this disorder, three hypotheses are postulated (metabolic, vascular and oxidative) that may not be independent but complementary. There is still a great deal of ignorance about the relationship between autonomic dysfunction, endothelial dysfunction, arterial stiffness and especially with oxidative stress, entities in which the age factor is closely related. Objectives: To evaluate the role of age, arterial stiffness, endothelial dysfunction and oxidative stress as determinants of autonomic dysfunction, noninvasively studied by heart rate variability (HRV) at rest and after stimulation, in a population with a broad spectrum of cardiovascular risk. Likewise, we will analyze the clinical, anthropometric, hemodynamic and metabolic differences of the patients according to the presence or absence of cardiac autonomic neuropathy. Methods: An observational, retrospective cross-sectional study was performed in a population with cardiovascular disease or a classical risk factor that had a study of endothelial dysfunction biomarkers (ADMA, PAI-1), inflammation (adiponectin, rsTNFα 2, resistin and oxidative stress (TBARS), as well as an evaluation of arterial stiffness and autonomic dysfunction during the period from January 2009 to March 2012. The autonomic function was evaluated by HRV in the basal test (resting vagal index -RMSSDn, power in the high and low frequency bands) and in dynamic tests (vagal index in deep breathing - RMSSDp, Valsalva ratio and 30:15 ratio). The population was divided into two groups (according to the presence or absence of age and sex-adjusted neuropathy) for the univariate and multivariate analysis of these variables and others of interest such as C-reactive protein (classical marker of inflammation). Additionally it was stratified in low, medium or high damage according to tertiles of the biomarkers to jointly evaluate oxidative stress and endothelial dysfunction. Statistical analysis: tStudent, U Mann-Whitney, Kolmogorov-Smirnov, Chi square, ANOVA test, linear correlation and multiple linear regression. Results: The final population was N = 87, 32.2% in the baseline test and 26.4% in the dynamic test presented data on autonomic dysfunction. There were no differences according to age since the different autonomic tests were analyzed adjusted for age. There was a significant association (p = 0.046) in the dynamic tests with the female sex (56.5% women in the pathological group vs 23.8% in the normal group). The heart rate was significantly higher in the neuropathy group. There was a trend toward association with diabetes. The association with prediabetes in the baseline test was significant (p = 0.008), unlike A1C in both tests and coronary disease in the dynamic tests (p <0.001). The significant negative correlation between arterial stiffness and RMSSDn, power in the low and high frequency band, and the 30:15 ratio disappeared in the multivariate analysis by including age and sex. The upper tertile of TBARS was associated with lower HRV with RMSSDn and power in the high frequency band significantly (p = 0.017) and regardless of age and sex. The linear correlation between TBARS and rsTNF-α 2 was very significant (p <0.001). In the study of stratified damage by TBARS and rsTNF-α 2, power in the high frequency band showed a tendency to association, as did TBARS and ADMA in the basal tests not explainable by age. In the multivariate analysis, the relationship between power frequency dysfunction in the high frequency band, TBARS and arterial stiffness (measured by IAx-75) was independent of gender and age. The HRV measured by the 30:15 ratio was significantly associated with diabetes, age and sex, regardless of TBARS and arterial stiffness. Autonomic dysfunction was associated with C-reactive protein (CRP) levels significantly in the baseline test, and borderline with sex. Conclusions: Prediabetes and not only diabetes was significantly associated with autonomic dysfunction. This association is a previously unknown finding. Autonomic dysfunction and CRP are associated but significantly only at baseline. Its relation to sex, at the limit of significance, could explain some of the findings previously found in relation to gender, but its non-specificity does not allow us to draw additional conclusions. Their lack of correlation with biomarkers makes us suspect that their potential pathogenic implications are low in terms of autonomic dysfunction. Metabolic hypothesis alone does not explain autonomic dysfunction in a scenario like ours, vascular and oxidative hypotheses are key to understanding the process and prevent it. Arterial stiffness, autonomic dysfunction and endothelial dysfunction constitute the essential triad that would explain that the "age factor" is the one with the greatest cardiovascular impact of all known but the present study shows that there is an interaction between these components of the cardiometabolic domain between each other and each of them with autonomic dysfunction that is independent of age.