Resumen de 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
- español
La disfunción autonómica se asocia con un aumento de morbimortalidad cardiovascular y muerte súbita cardíaca. En su génesis se postulan tres hipótesis (metabólica, vascular y oxidativa) que podrían ser complementarias. Existe gran desconocimiento sobre la relación entre disfunción autonómica, disfunción endotelial, rigidez arterial y estrés oxidativo, entidades en las que la edad está estrechamente relacionada. Ante estos hechos, se planteó evaluar la edad, rigidez arterial, disfunción endotelial y estrés oxidativo como determinantes de disfunción autonómica estudiada mediante variabilidad de la frecuencia cardíaca (VFC).
Se diseñó un estudio observacional, retrospectivo, transversal en una población de amplio espectro cardiovascular a la que se le había realizado análisis de biomarcadores de disfunción endotelial, inflamación y estrés oxidativo, así como evaluación de rigidez arterial y disfunción autonómica (VFC en test basal y dinámicos). Se establecieron dos grupos según la presencia de neuropatía ajustada por edad y sexo. Para la evaluación conjunta de estrés oxidativo y disfunción endotelial se estratificó el daño según terciles de biomarcadores.
La población final fue de 87 pacientes, 32,2% en test basal y 26,4% en test dinámicos presentaron disfunción autonómica. Hubo asociación significativa en test dinámicos con el sexo mujer. La frecuencia cardíaca fue significativamente mayor en el grupo con neuropatía. Hubo tendencia a la asociación con la diabetes y significativa con prediabetes en test basal, con A1C en ambos test y con enfermedad coronaria en test dinámicos. El tercil superior de TBARS se asoció a menor VFC por test basal significativa e independientemente de edad y sexo. La correlación entre TBARS y rsTNF-¿2 resultó muy significativa. Hubo tendencia a asociación entre el daño estratificado por TBARS y rsTNF-¿2, y por TBARS y ADMA con la VFC en test basal no explicables por la edad. La relación entre VFC en test basal, TBARS y rigidez arterial fue independiente de edad y sexo. La VFC por ratio 30:15 se asoció independiente y significativamente con diabetes, edad y sexo. La proteína C reactiva se asoció significativamente con disfunción autonómica en test basal y limítrofe con el sexo.
Como conclusiones más relevantes podemos destacar que: 1. La prediabetes y no solo la diabetes se asoció significativamente a disfunción autonómica, hallazgo previamente no conocido.
2. Disfunción autonómica y PCR están asociadas aunque significativamente solo en situación basal. Se sospecha una baja implicación patogénica de la PCR en la disfunción autonómica debido a su falta de correlación con los biomarcadores.
3. La hipótesis metabólica sola no explica la disfunción autonómica, las hipótesis vascular y oxidativa son claves para entender y prevenir dicho proceso.
4. La rigidez arterial, la disfunción autonómica y la disfunción endotelial constituyen la triada esencial que explicaría que el ¿factor edad¿ sea el de mayor impacto cardiovascular de los conocidos pero este trabajo revela que hay una interacción entre estos componentes del ámbito cardiometabólico entre sí y de cada uno de ellos con la disfunción autonómica que es independiente de la edad.
- English
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.
