ABSTRACT
Introduction: Patients with coronary artery disease (CAD) have a higher risk of developing cognitive impairment and mental health disorders compared to the general population. Physical exercise might improve their brain health. The overall goal of the HEART-BRAIN randomized controlled trial (RCT) is to investigate the effects of different types of exercise on brain health outcomes in patients with CAD, and the underlying mechanisms. Methods: This three-arm, single-blinded RCT will include 90 patients with CAD (50-75 years). Participants will be randomized into: (1) control group-usual care (n = 30), (2) aerobic high-intensity interval training (HIIT) (n = 30), or (3) HIIT combined with resistance exercise training (n = 30). The 12-week intervention includes 3 supervised sessions (45-min each) per week for the exercise groups. Outcomes will be assessed at baseline and post-intervention. The primary outcome is to determine changes in cerebral blood flow assessed by magnetic resonance imaging. Secondary outcomes include changes in brain vascularization, cognitive measures (i.e., general cognition, executive function and episodic memory), and cardiorespiratory fitness. Additional health-related outcomes, and several potential mediators and moderators will be investigated (i.e., brain structure and function, cardiovascular and brain-based biomarkers, hemodynamics, physical function, body composition, mental health, and lifestyle behavior). Conclusion: The HEART-BRAIN RCT will provide novel insights on how exercise can impact brain health in patients with CAD and the potential mechanisms explaining the heart-brain connection, such as changes in cerebral blood flow. The results may have important clinical implications by increasing the evidence on the effectiveness of exercise-based strategies to delay cognitive decline in this high-risk population. Clinical trial registration: ClinicalTrials.gov, identifier [NCT06214624].
ABSTRACT
INTRODUCTION: A patient's response to sepsis is influenced by their genetic background. Our objective was to use plasma markers, such as protein C (PC), D-dimer, Plasminogen Activator Inhibitor-1 (PAI-1) levels, and the PAI-1 rs1799889 4G/5G and Tumor Necrosis Factor-α rs1800629 G/A polymorphisms to improve classical intensive care unit (ICU) scores. METHODOLOGY: We studied 380 subjects, 166 with sepsis. We performed coagulation tests: plasma PAI-1 and PC levels were evaluated by chromogenic methods; and D-dimer was evaluated by immunoturbidimetric assay. Polymorphisms were performed using for polymerase chain reactions followed by digest with specific restriction enzyme. We acquired the APACHE and SOFA scores (time zero), sex, age, body mass index, associated co-morbidities, length of ICU stay (days), the severity of sepsis (sepsis, severe sepsis or septic shock), the HIV status and the ICU outcome (survival or death). RESULTS: We found significant differences between patients who died (n=80) and those who survived (n=86) in terms of the ICU length of stay (6 vs. 10 days), septic shock (64 versus 24%), age (51 versus 38 years old), HIV+ condition (34 versus 16%), SOFA (7 versus 4), APACHE (19 versus 13), D-dimer (4.32 versus 2.88 mg/ml), PC (46.0 versus 63.5 %) and PAI-1 (33.0 versus 16.5 UA/l). When we used a regression analysis with dichotomized variables, only the SOFA4, PAI-116, HIV status and the PAI-1 4G allele proved to be predictors of death at time zero. CONCLUSIONS: In the future, ICU scores may be further improved by adding certain genomic or plasma data.
Subject(s)
Biomarkers/blood , Plasma/chemistry , Plasminogen Activator Inhibitor 1/genetics , Sepsis/diagnosis , Sepsis/genetics , Tumor Necrosis Factor-alpha/genetics , APACHE , Adult , Argentina , Clinical Laboratory Techniques , Clinical Medicine/methods , Genetic Predisposition to Disease , Humans , Intensive Care Units , Middle Aged , Polymerase Chain Reaction , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Time FactorsABSTRACT
INTRODUCCION: En Argentina se reportan alrededor de 11.000 casos nuevos de tuberculosis (TB) por año. El tratamiento con drogas anti-TB produce daño hepático en una gran proporción de los pacientes, y la isoniacida (INH) es la principal inductora de hepatotoxicidad. Algunos polimorfismos de las enzimas NAT-2 y CYP2E1, involucradas en el metabolismo de INH, estarían directamente asociados con el desarrollo de hepatotoxicidad.OBJETIVO: Analizar la distribución de las variantes alélicas *4, *5, *6, *7 y *14 de NAT-2 y c1/c2 de CYP2E1 en población sana argentina y en pacientes con TB que concurren a hospitales públicos de la ciudad de Buenos Aires y estudiar su asociación con el desarrollo de la hepatotoxicidad.METODOS: Se estudiaron 152 pacientes con TB tratados con drogas anti-TB. La distribución de frecuencias alélicas y genotípicas fue determinada por PCR-RFLP, y los resultados fueron comparados entre pacientes con TB con o sin desarrollo de hepatotoxicidad, usando un análisis de regresión logística binaria.RESULTADOS: El estado acetilador lento resultó la única variable independiente en la predicción de hepatotoxicidad relacionada con las drogas anti-TB (p = 0,019; OR = 2,971).CONCLUSIONES: El presente estudio demuestra que, dada la alta prevalencia del estado acetilador lento en la población argentina y su asociación al riesgo de desarrollar hepatotoxicidad, junto con el aumento en los casos de TB y los costos que conllevan las internaciones por daño hepático asociado a drogas anti-TB, el análisis del estado acetilador previo al tratamiento anti-TB podría ser clave.
INTRODUCTION: In Argentina, about 11.000 new cases of tuberculosis (TB) are reported per year. Treatment with anti-TB drugs produces liver damage in a large proportion of patients, being isoniazid (INH) the main responsible for hepatotoxicity. Some polymorphisms of the enzymes NAT-2 and CYP2E1, which are involved in the metabolism of INH, might be directly associated with the development of hepatotoxicity.OBJECTIVE: To analyze the distribution of NAT-2 variants *4, *5, *6, *7 and *14, and CYP2E1 alleles c1 and c2 in a healthy population from Argentina and in patients with TB who attend public hospitals in Buenos Aires city, and to stude their association with the development of hepatotoxicity.METHODS: The study included 152 patients with TB treated with anti-TB drugs. The allelic and genotypic frequency distribution was determined by PCR-RFLP, and the results were compared between TB patients with or without development of hepatotoxicity using a binary logistic refression analysis.RESULTS: The slow acetylator status was the only independent variable in the prediction of hepatotoxicity associated with anti-TB drugs (p = 0.019; OR = 2.971).CONCLUSIONS: This study shows that, given the high prevalence of slow acetylator status in Argentine population and its association with the risk of hepatotoxicity, together with the increase in TB cases and the hospitalization costs due to liver damage associated with anti-TB drugas, the analysis of acetylator status before anti-TB treatment could be fundamental.
Subject(s)
Tuberculosis , Antitubercular Agents , Cytochrome P-450 CYP2E1 , Arylamine N-Acetyltransferase , Isoniazid , Chemical and Drug Induced Liver Injury , Public Health , ArgentinaABSTRACT
INTRODUCCION: En Argentina se reportan alrededor de 11.000 casos nuevos de tuberculosis (TB) por año. El tratamiento con drogas anti-TB produce daño hepático en una gran proporción de los pacientes, y la isoniacida (INH) es la principal inductora de hepatotoxicidad. Algunos polimorfismos de las enzimas NAT-2 y CYP2E1, involucradas en el metabolismo de INH, estarían directamente asociados con el desarrollo de hepatotoxicidad.OBJETIVO: Analizar la distribución de las variantes alélicas *4, *5, *6, *7 y *14 de NAT-2 y c1/c2 de CYP2E1 en población sana argentina y en pacientes con TB que concurren a hospitales públicos de la ciudad de Buenos Aires y estudiar su asociación con el desarrollo de la hepatotoxicidad.METODOS: Se estudiaron 152 pacientes con TB tratados con drogas anti-TB. La distribución de frecuencias alélicas y genotípicas fue determinada por PCR-RFLP, y los resultados fueron comparados entre pacientes con TB con o sin desarrollo de hepatotoxicidad, usando un análisis de regresión logística binaria.RESULTADOS: El estado acetilador lento resultó la única variable independiente en la predicción de hepatotoxicidad relacionada con las drogas anti-TB (p = 0,019; OR = 2,971).CONCLUSIONES: El presente estudio demuestra que, dada la alta prevalencia del estado acetilador lento en la población argentina y su asociación al riesgo de desarrollar hepatotoxicidad, junto con el aumento en los casos de TB y los costos que conllevan las internaciones por daño hepático asociado a drogas anti-TB, el análisis del estado acetilador previo al tratamiento anti-TB podría ser clave.
INTRODUCTION: In Argentina, about 11.000 new cases of tuberculosis (TB) are reported per year. Treatment with anti-TB drugs produces liver damage in a large proportion of patients, being isoniazid (INH) the main responsible for hepatotoxicity. Some polymorphisms of the enzymes NAT-2 and CYP2E1, which are involved in the metabolism of INH, might be directly associated with the development of hepatotoxicity.OBJECTIVE: To analyze the distribution of NAT-2 variants *4, *5, *6, *7 and *14, and CYP2E1 alleles c1 and c2 in a healthy population from Argentina and in patients with TB who attend public hospitals in Buenos Aires city, and to stude their association with the development of hepatotoxicity.METHODS: The study included 152 patients with TB treated with anti-TB drugs. The allelic and genotypic frequency distribution was determined by PCR-RFLP, and the results were compared between TB patients with or without development of hepatotoxicity using a binary logistic refression analysis.RESULTS: The slow acetylator status was the only independent variable in the prediction of hepatotoxicity associated with anti-TB drugs (p = 0.019; OR = 2.971).CONCLUSIONS: This study shows that, given the high prevalence of slow acetylator status in Argentine population and its association with the risk of hepatotoxicity, together with the increase in TB cases and the hospitalization costs due to liver damage associated with anti-TB drugas, the analysis of acetylator status before anti-TB treatment could be fundamental.
Subject(s)
Antitubercular Agents , Arylamine N-Acetyltransferase , Chemical and Drug Induced Liver Injury , Isoniazid , Tuberculosis , Argentina , Public HealthABSTRACT
No disponible