RESUMEN
@#The World Health Organization (WHO) released the “Global report on hypertension” on September 19, 2023. This report systematically summarizes the prevalence, mortality, diagnosis and treatment of hypertension in various countries, and elucidates the current situation of hypertension management, and gives a series of suggestions on how to manage hypertension, providing new thinking and inspiration for countries to optimize hypertension management. Through the summary of relevant studies and reports, this paper further reviews the present situation, early identification and management of hypertension.
RESUMEN
AIMS: Resistant hypertension (RH) is a challenging phenotype within the hypertension (HTN) spectrum, requiring careful assessment and follow-up. Evaluation of left atrial function may be clinically informative, but is usually neglected. Advanced Echocardiography Techniques (AETs), such as Strain Analysis and three-dimensional echocardiography (3D ECHO) may be useful complementary tools to assess atrial function in patients with RH. METHODS AND RESULTS: Ninety-six eligible adult patients were categorized into three groups: resistant hypertensive (RH), controlled hypertensive (CH), and normotensive (N), and underwent AETs to identify morphofunctional changes in the left atrium (LA) across different HTN phenotypes. The LA reservoir strain was significantly lower among RH than in N and CH patients (p < .001). Accordingly, LA conduit strain showed a gradient through the groups: higher among N, followed by CH and RH patients (p = .015). LA contraction strain was higher among CH than in N and RH patients (p = .02). Maximum indexed, pre-A, and minimum atrial volumes obtained by 3D ECHO showed differences between N and the others (p < .001), but not between CH and RH. N patients showed a higher fraction of passive emptying of the LA than the others (p = .02), with no difference between CH and RH. Total emptying of the LA only differed between N and RH patients, while active emptying of the LA showed no difference between the groups (p = .82). CONCLUSION: The left atrium may present early functional changes in response to HTN, which are detectable by AETs. AETs, especially S-LA, allowed to identify markers of atrial myocardial damage in both RH and CH patients.
Asunto(s)
Fibrilación Atrial , Ecocardiografía Tridimensional , Hipertensión , Humanos , Ecocardiografía/métodos , Hipertensión/complicaciones , Hipertensión/diagnóstico por imagen , Atrios Cardíacos/diagnóstico por imagenRESUMEN
Background: Portal hypertension monitoring is important throughout the natural course of cirrhosis. Hepatic venous pressure gradient (HVPG), regarded as the golden standard, is limited by invasiveness and technical difficulties. Portal hypertension is increasingly being assessed non-invasively, and hematological indices, imaging data, and statistical or computational models are studied to surrogate HVPG. This paper discusses the existing non-invasive methods based on measurement principles and reviews the methodological developments in the last 20 years. Methods: First, we used VOSviewer to learn the architecture of this field. The publications about the non-invasive assessment of portal hypertension were retrieved from the Web of Science Core Collection (WoSCC). VOSviewer 1.6.17.0 was used to analyze and visualize these publications, including the annual trend, the study hotspots, the significant articles, authors, journals, and organizations in this field. Next, according to the cluster analysis result of the keywords, we further retrieved and classified the related studies to discuss. Results: A total of 1,088 articles or review articles about our topic were retrieved from WoSCC. From 2000 to 2022, the number of publications is generally growing. "World Journal of Gastroenterology" published the most articles (n = 43), while "Journal of Hepatology" had the highest citations. "Liver fibrosis" published in 2005 was the most influential manuscript. Among the 20,558 cited references of 1,088 retrieved manuscripts, the most cited was a study on liver stiffness measurement from 2007. The highest-yielding country was the United States, followed by China and Italy. "Berzigotti, Annalisa" was the most prolific author and had the most cooperation partners. Four study directions emerged from the keyword clustering: (1) the evaluation based on fibrosis; (2) the evaluation based on hemodynamic factors; (3) the evaluation through elastography; and (4) the evaluation of variceal bleeding. Conclusion: The non-invasive assessment of portal hypertension is mainly based on two principles: fibrosis and hemodynamics. Liver fibrosis is the major initiator of cirrhotic PH, while hemodynamic factors reflect secondary alteration of splanchnic blood flow. Blood tests, US (including DUS and CEUS), CT, and magnetic resonance imaging (MRI) support the non-invasive assessment of PH by providing both hemodynamic and fibrotic information. Elastography, mainly USE, is the most important method of PH monitoring.
RESUMEN
Isometric resistance training (IRT) has been shown to reduce resting and ambulatory blood pressure (BP), as well as BP variability and morning BP surge (MBPS). However, there are no data available regarding how long after cessation of IRT these effects are maintained. Therefore, the purpose of this study was to determine the effects of 8 weeks of detraining on resting BP, ambulatory BP and MBPS following 8 weeks of IRT in a population of young normotensive individuals and to further substantiate previously reported reductions in MBPS following IRT. Twenty-five apparently healthy participants with resting BP within the normal range (16 men, age = 23 ± 6 years; 9 women, age = 22 ± 4 years, resting BP: 123 ± 5/69 ± 7 mmHg) were randomly assigned to a training-detraining (TRA-DT, n = 13) or control (CON, n = 12) group. Resting BP, ambulatory BP and MBPS were measured prior to, after 8 weeks of bilateral leg IRT using an isokinetic dynamometer (4 × 2-min contractions at 20% MVC with 2-min rest periods, 3 days/week) and following an 8-week detraining period. There were significant reductions in 24-h ambulatory systolic BP (SBP) and calculated SBP average real variability (ARV) following IRT that were maintained after detraining (pre-to-post detraining, -6 ± 4 mmHg, p = 0.008, -2 ± 1.5 mmHg, p = 0.001). Similarly, the training-induced decreases in daytime SBP and daytime SBP ARV (pre-to-post detraining, -5 ± 6 mmHg, p = 0.001; -2 ± 1.2 mmHg, p = 0.001, respectively), MBPS (pre-to-post detraining, -6 ± 9 mmHg, p = 0.046) and resting SBP (pre-to-post detraining, -4 ± 6 mmHg, p = 0.044) were preserved. There were no changes in night-time or night-time SBP ARV across all time points (pre-to-post detraining, -1 ± 8 mmHg, p = 1.00, -0.7 ± 2.9 mmHg, p = 1.00). These results confirm that IRT causes significant reductions in resting BP, ambulatory BP, ambulatory ARV and MBPS. Importantly, the changes remained significantly lower than baseline for 8 weeks after cessation of training, suggesting a sustained effect of IRT.
RESUMEN
The increased prevalence of hypertensive patients with type 2 diabetes mellitus (T2DM) is evident worldwide, leading to a higher risk of cardiovascular disease onset, which is substantially associated with disabilities and mortality in the clinic. In order to achieve the satisfyingly clinical outcomes and prognosis, the comprehensive therapies have been conducted with a beneficial effect on both blood pressure and glucose homeostasis, and clinical trials reveal that some kind of antihypertensive drugs such as angiotensin converting enzyme inhibitors (ACE-I) may, at least in part, meet the dual requirement during the disease management. As a nonselective ß-blocker, carvedilol is employed for treating many cardiovascular diseases in clinical practice, including hypertension, angina pectoris and heart failure, and also exhibit the effectiveness for glycemic control and insulin resistance. Apart from alleviating sympathetic nervous system activity, several causes, such as lowering oxygen reactive species, may contribute to the effects of carvedilol on controlling plasma glucose levels, suggesting a feature of this drug having multiple targets. Interestingly, numerous distinct K+ channels expressed in pancreatic ß-cells and peripheral insulin-sensitive tissues, which play a sentential role in glucose metabolism, are subjected to extensive modulation of carvdilol, establishing a linkage between K+ channels and drug's effects on the control of glucose. A variety of evidence shows that the impact of carvedilol on different K+ channels, including Kv, KAch, KATP and K2 P, can lead to positive influences for glucose homeostasis, contributing to its clinical beneficial effectiveness in treatment of hypertensive patients with T2DM. This review focus on the control of plasma glucose conferred by carvedilol modulation on K+ channels, providing the novel mechanistic explanation for drug's actions.
Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Hipertensión , Propanolaminas , Antihipertensivos/farmacología , Glucemia/metabolismo , Carbazoles/farmacología , Carbazoles/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Carvedilol/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucosa/uso terapéutico , Humanos , Canales de Potasio , Propanolaminas/farmacología , Propanolaminas/uso terapéuticoRESUMEN
This study aims to investigate whether stabilization of glucagon-like peptide-1 (GLP-1) level reduces angiotensin II (Ang II)-induced cardiac fibrosis and -elevated blood pressure accompanying with inhibition of NADPH oxidase (NOX) expression and preservation of mitochondrial integrity. The study was performed in Sprague-Dawley rat model of Ang II infusion (500 ng/kg/min) using osmotic minipumps for 4 weeks. GLP-1 receptor agonist liraglutide (0.3 mg/kg, injected subcutaneously twice daily) and dipeptidyl peptides-4 inhibitor, linagliptin (8 mg/kg, administered via oral gavage) were selected to preserve GLP-1 level. Blood pressure was measured noninvasively. Heart and aorta were saved for histological analysis. Relative to the animals with Ang II infusion, in the heart, liraglutide and linagliptin comparatively reduced the protein levels of NOX4 and TGFß1 and expression of monocyte chemoattractant protein 1, and attenuated the proliferation of myofibroblasts (15 ± 4 and 13 ± 3 vs. 42 ± 22/HPF in Ang II group). The number of distorted mitochondria in both groups was significantly reduced (8 ± 4 and 10 ± 6 vs. 27 ± 13/HPF in Ang II group), in company with a significant reduction in cardiac fibrosis. In the aorta, treatment with liraglutide and linagliptin significantly downregulated the expression of NOX4 and intercellular adhesion molecule 1, and enhanced endothelial NOS expression. Aortic wall thickness was reduced comparatively (267 ± 22 and 286 ± 25 vs. 339 ± 40 µm in Ang II group). The area of fibrotic aorta was also reduced (13 ± 6 and 14 ± 5 vs. 38 ± 24 mm2 in Ang II group), respectively, in coincidence with a significant reduction in mean blood pressure. Taken together, these results suggest that the conservation of GLP-1 level with exogenous supply of liraglutide or the prevention of endogenous degradation of GLP-1 with linagliptin protects against Ang II-induced injury in the heart and aorta, potentially associated with inhibition of NOX4 expression and preservation of mitochondrial integrity.
Asunto(s)
Angiotensina II , Cardiomiopatías , Péptido 1 Similar al Glucagón , Hipertensión , Mitocondrias , NADPH Oxidasa 4 , Angiotensina II/metabolismo , Animales , Cardiomiopatías/patología , Fibrosis , Péptido 1 Similar al Glucagón/metabolismo , Hipertensión/inducido químicamente , Hipertensión/tratamiento farmacológico , Hipertensión/patología , Linagliptina/farmacología , Liraglutida/farmacología , Mitocondrias/metabolismo , NADPH Oxidasa 4/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Background:In the clinical setting, the effect of intra-abdominal hypertension on the human body is dependent on time, but its role is not yet clear.Objective:To investigate the effect of the duration of intra-abdominal hypertension (IAH) on the prognosis of critically ill patients.Methods:This prospective cohort study enrolled 256 IAH patients who were admitted to the Surgical ICU of 10 Grade A hospitals in Fujian Province from January 2018 to December 2020. The duration of IAH (DIAH) was obtained after monitoring IAP, and ICU length of stay, duration of mechanical ventilation, duration of continuous renal replacement therapy (CRRT) and average daily energy intake from enteral nutrition during ICU stay were observed and recorded. The correlation was analyzed by Spearman rank correlation. The patients were divided into the survival group and the death group according to their survival state at 60 days after enrollment. Thereafter, clinical characteristics between the two groups were compared. Multivariable logistic regression was used to study and validate the relationship between DIAH and 60-day mortality. The receiver operating characteristics (ROC) curve was established to evaluate the predictive abilities of DIAH on the mortality risk.Results:In critically ill patients, DIAH was positively correlated with duration of mechanical ventilation ( r=0.679, P<0.001), duration of CRRT ( r=0.541, P<0.001) and ICU length of stay ( r=0.794, P<0.001), respectively. In addition, there was a negative correlation between DIAH and average daily energy intake from enteral nutrition ( r=-0.669, P<0.001). After multivariable adjustment, DIAH was an independent risk factor for 60-day mortality in critically patients with IAH ( OR=1.05, 95% CI: 1.01-1.12; P = 0.012), and exhibited a linearity change trend relationship with mortality risk. The ROC curve analysis of DIAH showed that the area under ROC curve (AUC) was 0.825 (95% CI: 0.763~0.886, P<0.01). When the cut-off value was 16.5 days, the sensitivity was 78.4% and the specificity was 75.4%. Conclusions:DIAH is an important risk factor for prognosis in critically ill patients. Early identification and rapid intervention for the etiology of IAH should be performed to shorten DIAH.
RESUMEN
Objective:To investigate the status quo of potentially inappropriate medication (PIM) among elderly hypertensive patients in community general practice clinic and related influencing factors.Methods:A total of 767 prescriptions for elderly hypertensive patients in a community health service center in Beijing from October 2020 to August 2021 were reviewed. The prevalence of PIM was assessed based on the criteria of potentially inappropriate medications for older adults in China(2017). Logistic regression analysis was employed to analyze the influencing factors for PIM. Results:The survey showed that 198 elderly patients had PIM with 244 person-doses. The top three drugs with high rate of PIM were benzodiazepine-estazolam (64 person-doses), clopidogrel (53 person-doses) and insulin (35 person-doses). Univariate analysis showed that PIM was significantly associated with types of medication;and underlying diseases hypertension with hyperlipidemia, coronary heart disease, type 2 diabetes, osteoarthritis, upper respiratory tract infection and insomnia (χ 2=82.58, 13.65, 17.74, 7.52, 10.34, 68.19,respectively,all P<0.05). Multivariate logistic regression analysis showed that the types of medication, hypertension complicated with upper respiratory tract infection, and insomnia were independent influencing factors for PIM ( OR=1.55, 2.47, 9.05; P<0.05). Conclusion:The study shows that PIM is more common in elderly hypertensive patients in community general practice clinics,which is associated with types of medication, hypertension complicated with upper respiratory tract infection and insomnia. It is suggested that general practitioner working in community clinics should be aware of PIM, minimize the number of prescription drugs, and choose new drugs or non-drug treatments to reduce the occurrence of PIM.
RESUMEN
Objective@#To investigate the prevalence of dyslipidemia among adults in Moyu County, Hotan Prefecture, Xinjiang Uygur Autonomous Region, so as to provide insights into the management of dyslipidemia.@*Methods@#The physical examination data of permanent residents at ages of 18 years and older were collected from Moyu County from 2018 to 2019, including demographic features, height, body weight, blood pressure and blood biochemical parameter measurements. The epidemiological characteristics of dyslipidemia were analyzed among residents.@*Results@#Totally 166 142 adults were investigated, with a mean age of (41.08±15.72) years. There were 77 744 men (46.76%), 34 728 obese adults (20.90%), 5 776 adults with diabetes (3.48%) and 26 294 adults with hypertension (15.83%). The levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were (1.38±0.98), (4.13±1.19), (1.31±0.41) and (2.25±0.77) mmol/L, respectively. The prevalence of dyslipidemia was 29.72%, and the detection rates of high TG, high TC, low-HDL-C and high LDL-C were 9.73%, 4.59%, 19.65% and 1.99%, respectively. The prevalence of dyslipidemia was higher in men than in women (33.97% vs. 25.98%; χ2=1 264.729, P<0.001), and the prevalence increased with age (χ2=539.382, P<0.001) and body mass index (χ2=3 601.833, P<0.001). The prevalence of dyslipidemia was 35.48% among patients with hypertension (χ2=497.251, P<0.001) and 46.07% among patients with diabetes (χ2=766.142, P<0.001). There were 9 059 adults with two and more abnormal blood lipid indexes (18.35%), and the detection rates of two and more abnormal blood lipid indexes were 26.50%, 24.14% and 33.15% among patients with obesity, hypertension and diabetes, respectively.@*Conclusions@#The prevalence of dyslipidemia among adults in Moyu County is lower than the national level, and low-HDL cholesterolemia is the most common type of dyslipidemia. The prevalence of dyslipidemia is high among patients with obesity, hypertension and diabetes mellitus, in whom abnormality of multiple blood lipid indexes is measured.
RESUMEN
Spleen hemangiomatosis is the most common type of benign vascular tumor, and it is usually associated with other visceral localizations such as the liver, lymph nodes, skin, and bone marrow. The diffuse form of this condition is defined by the number of locations in one organ. We report the case of a 48-year-old female who sought consultation for left hypochondrium chronic pain. Physical examination subsequently revealed splenomegaly. Imaging showed a diffuse capillary spleen hemangiomatosis, hepatic dysmorphia, and several signs of portal hypertension.
RESUMEN
Idiopathic intracranial hypertension,also known as pseudotumor cerebri,is a syndrome characterized by raised intracranial pressure of unknown cause.These patients present normal neuroimaging and cerebrospinal fluid analysis while increased intracranial pressure and associated symptoms and signs.Delay of treatment can cause severe visual impairment.There are some new understandings of this disease,and we will review the pathogenesis,diagnosis,and treatment of idiopathic intracranial hypertension.
Asunto(s)
Hipertensión Intracraneal , Seudotumor Cerebral , Humanos , Neuroimagen , Seudotumor Cerebral/diagnóstico , Seudotumor Cerebral/terapiaRESUMEN
BACKGROUND: Hepatic encephalopathy (HE) remains an enormous challenge in patients who undergo transjugular intrahepatic portosystemic shunt (TIPS) implantation. The preoperative indocyanine green retention rate at 15 min (ICG-R15), as one of the liver function assessment tools, has been developed as a prognostic indicator in patients undergoing surgery, but there are limited data on its role in TIPS. AIM: To determine whether the ICG-R15 can be used for prediction of post-TIPS HE in decompensated cirrhosis patients with portal hypertension (PHT) and compare the clinical value of ICG-R15, Child-Pugh score (CPS), and model for end-stage liver disease (MELD) score in predicting post-TIPS HE with PHT. METHODS: This retrospective study included 195 patients with PHT who underwent elective TIPS at Beijing Shijitan Hospital from January 2018 to June 2019. All patients underwent the ICG-R15 test, CPS evaluation, and MELD scoring 1 wk before TIPS. According to whether they developed HE or not, the patients were divided into two groups: HE group and non-HE group. The prediction of one-year post-TIPS HE by ICG-R15, CPS and MELD score was evaluated by the areas under the receiver operating characteristic curves (AUCs). RESULTS: A total of 195 patients with portal hypertension were included and 23% (45/195) of the patients developed post-TIPS HE. The ICG-R15 was identified as an independent predictor of post-TIPS HE. The AUCs for the ICG-R15, CPS, and MELD score for predicting post-TIPS HE were 0.664 (95% confidence interval [CI]: 0.557-0.743, P = 0.0046), 0.596 (95%CI: 0.508-0.679, P = 0.087), and 0.641 (95%CI: 0.554-0.721, P = 0.021), respectively. The non-parametric approach (Delong-Delong & Clarke-Pearson) showed that there was statistical significance in pairwise comparison between AUCs of ICG-R15 and MELD score (P = 0.0229). CONCLUSION: The ICG-R15 has appreciated clinical value for predicting the occurrence of post-TIPS HE and is a choice for evaluating the prognosis of patients undergoing TIPS.
Asunto(s)
Enfermedad Hepática en Estado Terminal , Encefalopatía Hepática , Derivación Portosistémica Intrahepática Transyugular , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/etiología , Humanos , Verde de Indocianina , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Objective:To summarize the strategy of using extracorporeal membrane oxygenation (ECMO) support during lung transplantation from 2 coronavirus disease 2019 (COVID-19) with end-stage respiratory failure.Methods:Two COVID-19 with end-stage respiratory failure patients were admitted to Nanjing Medical University Affiliated Wuxi People's Hospital in March 2020. As the homoeostasis and vital signs could not be maintained in balance by conventional treatments, lung transplantations were performed. Here, detail information about combined application of peripheral veno-venous ECMO (VV-ECMO) and central veno-arterial ECMO (CVA-ECMO) during the operation will be discussed.Results:Case 1: 59 years old, 172 cm height, 72 kg weight, who received mechanical ventilation for 22 days, tracheotomy tube for 17 days, and VV-ECMO support for 7 days. Case 2: 72 years old, 178 cm height, 71 kg weight, who received mechanical ventilation for 19 days, tracheotomy tube for 17 days, and VV-ECMO support for 18 days. As both of them have severe COVID-19-associated respiratory failure, and the recovery was determined to be unlikely, lung transplantations were performed. Severe pulmonary arterial hypertension (PAH) and cardiac insufficiency were found during the operation. Based on preoperative VV-ECMO, CVA-ECMO was added. The concomitant use of peripheral VV-ECMO and CVA-ECMO offered satisfied intraoperative oxygenation and cardiopulmonary status, the operations run smoothly, and the CVA-ECMO was successfully removed, no ECMO-related complications occurred.Conclusion:The combined use of VV-ECMO and CVA-ECMO is an optimal strategy in the end-stage ARDS patients with severe PAH and cardiac insufficiency, which can offer benefits on respiratory and cardiac functions simultaneously, and ensure surgery safety.
RESUMEN
Idiopathic intracranial hypertension,also known as pseudotumor cerebri,is a syndrome characterized by raised intracranial pressure of unknown cause.These patients present normal neuroimaging and cerebrospinal fluid analysis while increased intracranial pressure and associated symptoms and signs.Delay of treatment can cause severe visual impairment.There are some new understandings of this disease,and we will review the pathogenesis,diagnosis,and treatment of idiopathic intracranial hypertension.
Asunto(s)
Humanos , Hipertensión Intracraneal , Neuroimagen , Seudotumor Cerebral/terapiaRESUMEN
BACKGROUND: This study was conducted to determine the prevalence of metabolic syndrome (Mets) in schizophrenic patients in a 6-month period of treatment with antipsychotic medications. METHODS: In this study, 60 volunteer schizophrenic patients were included. At the onset and 6 months after treatment with antipsychotic medications, fasting blood sugar (FBS), serum triglyceride (TG), high density lipoprotein (HDL), weight, waist circumference (WC), and blood pressure were determined. We defined Mets according to ATPIII criteria. RESULTS: After a 6-month treatment with antipsychotic drugs, the mean WC, serum TG, HDL, systolic and diastolic blood pressure increased but the changes of WC and HDL were statistically significant (p<0.05). We found that the percentage of patients with high WC, low HDL levels, and Mets increased after treatment which was statistically significant (p<0.05). CONCLUSION: It is recommended that nutritional and lifestyle changes intervention should be implanted for schizophrenic patients undergoing treatment.
Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , COVID-19/epidemiología , Hipertensión/tratamiento farmacológico , Adulto , Anciano , Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , China , Femenino , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Tratamiento Farmacológico de COVID-19RESUMEN
BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is a fatal illness. Despite many improvements in the treatment of these patients, there is no unique prognostic variable available to track these patients. The aim of this study was to evaluate the association between fractional exhaled nitric oxide (FeNO) levels, as a noninvasive biomarker, with disease severity and treatment outcome. METHODS: Thirty-six patients (29 women and 7 men, mean age 38.4 ± 11.3 years) with IPAH referred to the outpatient's clinic of Masih Daneshvari Hospital, Tehran, Iran, were enrolled into this pilot observational study. Echocardiography, six-minute walking test (6MWT), FeNO, brain natriuretic peptide (BNP) levels and the functional class of patients was assessed before patients started treatment. Assessments were repeated after three months. 30 healthy non-IPAH subjects were recruited as control subjects. RESULTS: There was no significant difference in FeNO levels at baseline between patients with IPAH and subjects in the control group. There was also no significant increase in FeNO levels during the three months of treatment and levels did not correlate with other disease measures. In contrast, other markers of disease severity were correlated with treatment effect over the three months. CONCLUSION: FeNO levels are a poor non-invasive measure of IPAH severity and of treatment response in patients in this pilot study.
Asunto(s)
Espiración , Hipertensión Pulmonar Primaria Familiar/metabolismo , Óxido Nítrico/análisis , Adulto , Antihipertensivos/uso terapéutico , Biomarcadores/análisis , Estudios de Casos y Controles , Hipertensión Pulmonar Primaria Familiar/tratamiento farmacológico , Femenino , Humanos , Irán , Masculino , Persona de Mediana Edad , Proyectos Piloto , Pronóstico , Resultado del TratamientoRESUMEN
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a difficult disease with high morbidity and mortality rates and lacks an effective treatment. Here, we report the therapeutic effect of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), on hypertension + hyperlipidemia-induced HFpEF in a pig model. METHODS: HFpEF pigs were established by infusing a combination of deoxycorticosterone acetate (DOCA) and angiotensin II (Ang II), and Western diet (WD) feeding for 18 weeks. In the 9th week, half of the HFpEF pigs were randomly assigned to receive additional dapagliflozin treatment (10 mg/day) by oral gavage daily for the next 9 weeks. Blood pressure, lipid levels, echocardiography and cardiac hemodynamics for cardiac structural and functional changes, as well as epinephrine and norepinephrine concentrations in the plasma and tissues were measured. After sacrifice, cardiac fibrosis, the distribution of tyrosine hydroxylase (TH), inflammatory factors (IL-6 and TNF-α) and NO-cGMP-PKG pathway activity in the cardiovascular system were also determined. RESULTS: Blood pressure, total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) were markedly increased in HFpEF pigs, but only blood pressure was significantly decreased after 9 weeks of dapagliflozin treatment. By echocardiographic and hemodynamic assessment, dapagliflozin significantly attenuated heart concentric remodeling in HFpEF pigs, but failed to improve diastolic function and compliance with the left ventricle (LV). In the dapagliflozin treatment group, TH expression and norepinephrine concentration in the aorta were strongly mitigated compared to that in the HFpEF group. Moreover, inflammatory cytokines such as IL-6 and TNF-α in aortic tissue were markedly elevated in HFpEF pigs and inhibited by dapagliflozin. Furthermore, the reduced expression of eNOS and the PKG-1 protein and the cGMP content in the aortas of HFpEF pigs were significantly restored after 9 weeks of dapagliflozin treatment. CONCLUSION: 9 weeks of dapagliflozin treatment decreases hypertension and reverses LV concentric remodeling in HFpEF pigs partly by restraining sympathetic tone in the aorta, leading to inhibition of the inflammatory response and NO-cGMP-PKG pathway activation.
Asunto(s)
Aorta/inervación , Compuestos de Bencidrilo/farmacología , Glucósidos/farmacología , Insuficiencia Cardíaca/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Sistema Nervioso Simpático/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Animales , Biomarcadores/sangre , Presión Sanguínea/efectos de los fármacos , GMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de GMP Cíclico/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Fibrosis , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Hipertensión/sangre , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Mediadores de Inflamación/metabolismo , Lípidos/sangre , Óxido Nítrico/metabolismo , Norepinefrina/metabolismo , Sus scrofa , Sistema Nervioso Simpático/metabolismo , Sistema Nervioso Simpático/fisiopatologíaRESUMEN
One way to control hypertension is inactivation of the Renin- Angiotensin- Aldosterone System (RAAS). Inhibition of renin as a rate-limiting step of this system is an effective way to stop up RAAS. It has been proved that soyasaponin I, an herbal compound obtained from soybeans, has anti-hypertensive effect via renin inhibition, so it has the potential of being an anti-hypertensive drug. Herein, some theoretical approaches such as Docking Simulation, Molecular Dynamics (MD) Simulation and MMPBSA analysis have been used to study how soyasaponin I inhibits renin at the structural level. The results of docking simulation and hydrogen bond pattern show that this ligand is able to bind to the active site of renin and a region near the active site. Results of MD simulation for renin - soyasaponin I complexes confirm that soyasaponin I binds to the active site of renin and has inhibition effect on it via competing with the substrate. Besides, according to MMPBSA analysis, the binding free energy for renin - soyasaponin I complex is -42.61 kcal/mol when it binds to the active site. Comparing to the peptide obtained from angiotensinogen, ΔG = -74.96 kcal/mol, it may inferred that although binding of soyasaponin I to the active site of renin does not have a complete competition with the substrate, it might attenuate the formation of renin - angiotensinogen complex and have partial non-competitive effect. The results of this survey might be helpful to design partial non - competitive renin inhibitors with pharmaceutical capability.