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BACKGROUND: Insulin resistance (IR) plays an important role in the pathophysiology of cardiovascular disease. Recent studies have shown that diabetes mellitus and impaired lipid metabolism are associated with the severity and prognosis of idiopathic pulmonary arterial hypertension (IPAH). However, the relationship between IR and pulmonary hypertension is poorly understood. This study explored the association between four IR indices and IPAH using data from a multicenter cohort. METHODS: A total of 602 consecutive participants with IPAH were included in this study between January 2015 and December 2022. The metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, and triglyceride-glucose-body mass index (TyG-BMI) were used to quantify IR levels in patients with IPAH. The correlation between non-insulin-based IR indices and long-term adverse outcomes was determined using multivariate Cox regression models and restricted cubic splines. RESULTS: During a mean of 3.6 years' follow-up, 214 participants experienced all-cause death or worsening condition. Compared with in low to intermediate-low risk patients, the TG/HDL-C ratio (2.9 ± 1.7 vs. 3.3 ± 2.1, P = 0.003) and METS-IR (34.5 ± 6.7 vs. 36.4 ± 7.5, P < 0.001) were significantly increased in high to intermediate-high risk patients. IR indices correlated with well-validated variables that reflected the severity of IPAH, such as the cardiac index and stroke volume index. Multivariate Cox regression analyses indicated that the TyG-BMI index (hazard ratio [HR] 1.179, 95% confidence interval [CI] 1.020, 1.363 per 1.0-standard deviation [SD] increment, P = 0.026) and METS-IR (HR 1.169, 95% CI 1.016, 1.345 per 1.0-SD increment, P = 0.030) independently predicted adverse outcomes. Addition of the TG/HDL-C ratio and METS-IR significantly improved the reclassification and discrimination ability beyond the European Society of Cardiology (ESC) risk score. CONCLUSIONS: IR is associated with the severity and long-term prognosis of IPAH. TyG-BMI and METS-IR can independently predict clinical worsening events, while METS-IR also provide incremental predictive performance beyond the ESC risk stratification.
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Biomarcadores , Glucemia , Resistencia a la Insulina , Índice de Severidad de la Enfermedad , Triglicéridos , Adulto , Femenino , Humanos , Masculino , Biomarcadores/sangre , Glucemia/metabolismo , China/epidemiología , HDL-Colesterol/sangre , Progresión de la Enfermedad , Hipertensión Pulmonar Primaria Familiar/diagnóstico , Hipertensión Pulmonar Primaria Familiar/sangre , Hipertensión Pulmonar Primaria Familiar/fisiopatología , Hipertensión Pulmonar Primaria Familiar/mortalidad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Triglicéridos/sangreRESUMEN
BACKGROUND: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is largely unknown. Proteomics offers an approach to overview the molecular activities and signal transduction pathways involved in specific disease processes. OBJECTIVES: In this study, the expression of proteins in endarterectomized tissues from patients with CTEPH was investigated in a novel strategy to explore the pathophysiology of this disease. METHODS: We used the iTRAQ (isobaric tag for relative and absolute quantitation) approach combined with a Thermo Scientific Q Exactive MS analysis to compare the protein profiles in endarterectomized tissues from CTEPH patients and that of the control samples (mixture of cultured human pulmonary artery endothelial cells, human pulmonary artery smooth muscle cells, and human pulmonary fibroblasts). GO and KEGG analyses were performed to understand the functional classification and molecular activities of all the tissue-specific proteins, and the involved signal transduction pathways. RESULTS: Six hundred and seventy-nine tissue-specific proteins were detected. Bioinformatic analysis showed that the major biological processes involving these proteins were: response to wounding, defense response, acute inflammatory response, immune response, complement activation, and blood coagulation. The main pathways involved were: complement and coagulation cascade, systemic lupus erythematosus, extracellular matrix-receptor interaction, cell adhesion molecules, FcεRI signaling, and leukocyte transendothelial migration. CONCLUSIONS: The present study revealed that immune and defense response might play an important role in CTEPH.
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Endarterectomía , Hipertensión Pulmonar/metabolismo , Proteoma , Arteria Pulmonar/cirugía , Tromboembolia/metabolismo , Adulto , Proliferación Celular , Células Cultivadas , Enfermedad Crónica , Células Endoteliales/metabolismo , Femenino , Humanos , Hipertensión Pulmonar/patología , Hipertensión Pulmonar/cirugía , Masculino , Persona de Mediana Edad , Músculo Liso Vascular/citología , Músculo Liso Vascular/metabolismo , Transducción de Señal , Tromboembolia/patología , Tromboembolia/cirugía , Adulto JovenRESUMEN
BACKGROUND: Recent research has shown that statins improve pulmonary arterial hypertension (PAH), but their mechanisms of action are not fully understood. This study aimed to investigate the role of RhoA/ROCK1 regulation in the therapeutic effects of simvastatin on PAH. METHODS: For in vivo experiments, rats (N = 40) were randomly assigned to four groups: control, simvastatin, monocrotaline (MCT), and MCT + simvastatin. The MCT group and MCT + simvastatin groups received proline dithiocarbamate (50 mg/kg, i.p.) on the first day of the study. The MCT + simvastatin group received simvastatin (2 mg/kg) daily for 4 weeks, after which pulmonary arterial pressure was measured by right heart catheterization. The protein and mRNA levels of Rho and ROCK1 were measured by immunohistochemistry, Western blot, and PCR. For in vitro experiments, human pulmonary endothelial cells were divided into seven groups: control, simvastatin, monocrotaline pyrrole (MCTP), MCTP + simvastatin, MCTP + simvastatin + mevalonate, MCTP + simvastatin + farnesyl pyrophosphate (FPP), and MCTP + simvastatin + FPP + geranylgeranyl pyrophosphate (GGPP). After 72 h exposed to the drugs, the protein and mRNA levels of RhoA and ROCK1 were measured by Western blot and PCR. RESULTS: The MCT group showed increased mean pulmonary arterial pressure, marked vascular remodeling, and increased protein and mRNA levels of RhoA and ROCK1 compared to the other groups (P < 0.05). In vitro, the MCTP group showed a marked proliferation of vascular endothelial cells, as well as increased protein and mRNA levels of RhoA and ROCK1 compared to the MCTP + simvastatin group. The MCTP + simvastatin + mevalonate group, MCTP + simvastatin+ FPP group, and MCTP + simvastatin + FPP + GGPP group showed increased mRNA levels of RhoA and ROCK1, as well as increased protein levels of RhoA, compared to the MCTP + simvastatin group. CONCLUSIONS: Simvastatin improved vascular remodeling and inhibited the development of PAH. The effects of simvastatin were mediated by inhibition of RhoA/ROCK1. Simvastatin decreased RhoA/ROCK1 overexpression by inhibition of mevalonate, FPP, and GGPP synthesis.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Hipertensión Pulmonar/tratamiento farmacológico , Simvastatina/farmacología , Quinasas Asociadas a rho/antagonistas & inhibidores , Proteína de Unión al GTP rhoA/antagonistas & inhibidores , Animales , Presión Sanguínea/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Células Endoteliales/efectos de los fármacos , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/fisiopatología , Pulmón/metabolismo , Masculino , Ácido Mevalónico/farmacología , Monocrotalina/análogos & derivados , Monocrotalina/farmacología , Fosfatos de Poliisoprenilo/farmacología , ARN Mensajero , Ratas , Sesquiterpenos/farmacología , Transducción de Señal , Simvastatina/uso terapéutico , Remodelación Vascular/efectos de los fármacos , Quinasas Asociadas a rho/genética , Quinasas Asociadas a rho/metabolismo , Proteína de Unión al GTP rhoA/genética , Proteína de Unión al GTP rhoA/metabolismoRESUMEN
BACKGROUND: Pulmonary abnormalities are found in both chronic heart failure (CHF) and pulmonary arterial hypertension (PAH). The differences of pulmonary function in chronic left heart failure and chronic right heart failure are not fully understood. MATERIAL AND METHODS: We evaluated 120 patients with stable CHF (60 with chronic left heart failure and 60 with chronic right heart failure). All patients had pulmonary function testing, including pulmonary function testing at rest and incremental cardiopulmonary exercise testing (CPX). RESULTS: Patients with right heart failure had a significantly lower end-tidal partial pressure of CO2 (PetCO2), higher end-tidal partial pressure of O2 (PetO2) and minute ventilation/CO2 production (VE/VCO2) at rest. Patients with right heart failure had a lower peak PetCO2, and a higher peak dead space volume/tidal volume (VD/VT) ratio, peak PetO2, peak VE/VCO2, and VE/VCO2 slope during exercise. Patients with right heart failure had more changes in ∆PetCO2 and ∆VE/VCO2, from rest to exercise. CONCLUSIONS: Patients with right heart failure had worse pulmonary function at rest and exercise, which was due to severe ventilation/perfusion (V/Q) mismatching, severe ventilation inefficiency, and gas exchange abnormality.
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Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/fisiopatología , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/fisiopatología , Adulto , Dióxido de Carbono/metabolismo , Enfermedad Crónica , Ejercicio Físico , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Análisis de Regresión , Pruebas de Función Respiratoria , DescansoRESUMEN
BACKGROUND: Exercise impairment is common in chronic left heart failure and pulmonary arterial hypertension (PAH). Exercise impairment degree is a strong predictor of clinical outcome. Our purpose was to evaluate differences in exercise capacity using cardiopulmonary exercise testing (CPX) in patients with chronic left and right heart failure, and determine which factors were related to exercise impairment. METHODS: 102 patients with class II/III New York Heart Association were involved in the study (41 with chronic left heart failure, 61 with chronic right heart failure secondary to PAH). All patients underwent CPX to evaluate exercise capacity. RESULTS: Patients with right heart failure had significantly lower peak oxygen uptake (VO2), peak VO2/kg ratio, peak oxygen uptake/heart rate (VO2/HR) ratio and increases in oxygen uptake/increase in work rate (ΔVO2/ΔWR) slope, and had higher minute ventilation/CO2 production ratio and peak dead space volume/tidal volume during exercise. In patients with left heart failure, peak VO2/HR ratio was positively correlated with ΔVO2/ΔWR slope. However, VO2 and VO2/HR ratio were positively correlated with ΔVO2/ΔWR slope in patients with right heart failure. CONCLUSIONS: Compared with left heart failure, patients with right heart failure showed worse exercise capacity resulting from worse pulmonary and cardiovascular adaptation to exercise.
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Ejercicio Físico , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/rehabilitación , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/rehabilitación , Adulto , Enfermedad Crónica , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/complicaciones , Humanos , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/complicaciones , MasculinoRESUMEN
Background: Pulmonary artery dissection (PAD) is an uncommon condition associated with high mortality rates. To date, a comprehensive examination of various underlying causes of PAD remains unexplored. Methods: We used the search words "pulmonary artery dissection," "pulmonary artery dilatation," and "pulmonary artery rupture" in the public database, and examined the medical records of PAD patients treated in our hospital. Data on demographics, aetiology, PAD locations, histopathology, treatments, and outcomes, were collected. Results: A total of 145 patients with PAD (135 cases from the literature and 10 cases from our hospital) were analysed. PAD aetiology was categorized into four groups: congenital heart diseases (CHD) associated with pulmonary arterial hypertension (PAH), non-CHD associated with pulmonary hypertension (PH), aortic dissection-related, and miscellaneous causes. The most frequent cause, accounting for 32.4 % of PAD cases, was congenital heart disease, followed by idiopathic PAH (13 %) and chronic obstructive pulmonary disease (6 %). Patients with CHD were typically younger at the time of PAD diagnosis (median age: 35 years old) when compared with those suffering from aortic dissection, PH-associated conditions, or other causes (median age: 45, 55, and 56 years old, respectively). Imaging of the pulmonary artery proved effective in diagnosing PAD. The outcomes were generally poor. 44.7 % (21/47) of patients with CHD associated with PAH and 47.7 % (21/44) of non-CHD PH-associated diseases died during follow-up. Multidisciplinary team consultations are crucial when making decisions on management of PAD. Characteristic PAD histopathology features included thickened intima and hypertrophied media with atheromatous degeneration, disrupted elastic fibres, and lymphocytic infiltration. Conclusions: PAD aetiology can be divided into four main categories, with CHD associated with PAH being the leading cause. Despite the similar histopathology features, clinical manifestations and outcomes vary according to the aetiology.
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Pulmonary artery (PA) dilatation is commonly observed in patients with pulmonary hypertension (PH). However, the clinical aspects of PA dilatation in various etiology of PH remain unknown. In this study, we investigated the clinical and imaging characteristics of 1018 patients with different subtypes of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). The independent determinants for all-cause death were identified using univariate and multivariate Cox proportional hazard models. PA dilatation was identified in 88.8% of the patients, and 27.2% had a PA diameter/ascending aorta diameter ratio greater than 1.5. PA diameter was shown to be significantly correlated with hemodynamic parameters and symptom duration in idiopathic PAH patients. PA diameter only correlated with pulmonary circulation volume in patients with PAH associated with congenital heart disease. PA diameter correlated with symptom duration and right ventricular end-diastolic dimension in CTEPH patients. PA diameter correlated with right ventricular end-diastolic dimension in patients with PAH associated with connective tissue disease. Only 6-min walk distance, but not PA dilatation, predicts all-cause death independently. In conclusion, PA dilatation is a common finding in PH patients. The clinical feature of PA dilatation varies greatly between PH types. PA dilatation is not associated with all-cause death.
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Background: Patent ductus arteriosus (PDA) can close on its own during childhood. Patent ductus arteriosus with left pulmonary artery (LPA) occlusion is rare. Here, we describe possible aetiologies of this condition and treatment strategies based on recent guidelines. Case summary: A 35-year-old man experienced shortness of breath for 20 years. Physical examination revealed pitting oedema, digital clubbing, and bi-phasic murmur along the left sternal border at the 2nd and 3rd intercostal space. Congenital heart disease was suspected. Echocardiography revealed a severely dilated pulmonary trunk and PDA; however, the LPA was not visible. The patient has undergone PDA ligation surgery >30 years ago, which may have caused accidental LPA ligation; however, extreme elevation of pulmonary pressure led to increased difficulties in performing LPA reconstruction and PDA division. Therefore, pulmonary arterial hypertension (PAH) initial combination therapy with parenteral prostanoids was prescribed. The patient's condition improved gradually. Discussion: Inadvertent ligation of the LPA instead of PDA is a rare and usually fatal complication during ductal ligation. Patients who survive this catastrophic complication usually develop the progressive pulmonary vascular disease with increased pulmonary pressure and impaired lung parenchyma resulting in right heart and respiratory failure. Early and regular follow-up with cardiac imaging studies is important to diagnose this complication. Reconstruction of the ligated LPA and PDA late in the disease course is difficult due to the development of pulmonary arterial hypertension. Initial PAH combination therapy may be valuable for relieving the patients' symptoms at that stage. Heart and lung transplantation can also be considered in suitable patients.
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Índices de Eritrocitos , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/etiología , Embolia Pulmonar/sangre , Embolia Pulmonar/complicaciones , Adulto , Anciano , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Embolia Pulmonar/terapia , Factores de Riesgo , Factores de TiempoRESUMEN
OBJECTIVE: To investigate the role of sodium-calcium exchanger (NCX) on ischemic preconditioning and pharmacological preconditioning. METHODS: Cultured rat neonatal cardiomyocytes were randomly divided into 6 groups: (1) ischemia/reperfusion group (9 h ischemia followed by 1 h reperfusion, I/R), (2) ischemic preconditioning group (1.5 h ischemia/1 h reperfusion + I/R), (3) pharmacologic preconditioning group, adenosine (10 micromol/L) pretreated for 1 h + I/R, (4) calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-93 (0.5 micromol/L for 0.5 h) + ischemic preconditioning group, (5) KN-93 + pharmacologic preconditioning group, (6) control group. The leakage of intracellular lactate dehydrogenase (LDH) in various groups was determined by biochemical autoanalyzer. Semi-quantitative RT-PCR was employed to measure the mRNA levels of sodium-calcium exchanger. Activity of sodium-calcium exchanger (Na(+)-dependent (45)Ca(2+) uptake) was measured by liquid scintillation counting. RESULTS: (1) Compared to the I/R group, the LDH leakages in both ischemic preconditioning group and pharmacologic preconditioning group were significantly reduced (P < 0.05) while significantly increased in the KN-93 + pharmacologic preconditioning group and the KN-93 + ischemic preconditioning group (P < 0.05). (2) The Na(+)-dependent (45)Ca(2+) uptake was significantly increased in the I/R group (P < 0.05) compared to control group and this increase could be significantly attenuated in ischemic preconditioning group and adenosine pretreatment group (P < 0.05). (3) The expression of NCX mRNA in I/R group was also significantly increased (P < 0.05) in the I/R group (P < 0.05) compared to control group and this increase could be significantly attenuated in ischemic preconditioning group and adenosine pretreatment group (P < 0.05), CaMKII inhibitor KN-93 significantly abolished these effects in preconditioning group (P < 0.05) and in adenosine pretreated group (P < 0.05). CONCLUSION: NCX mediated the cardioprotective effects of ischemic preconditioning and pharmacological preconditioning in the neonatal cardiomyocytes I/R model.
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Precondicionamiento Isquémico Miocárdico , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/terapia , Intercambiador de Sodio-Calcio/metabolismo , Animales , Calcio/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/antagonistas & inhibidores , Células Cultivadas , L-Lactato Deshidrogenasa/metabolismo , Miocitos Cardíacos/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is unknown. Histopathologic studies revealed that pulmonary vasculature lesions similar to idiopathic pulmonary arterial hypertension (PAH) existed in CTEPH patients as well. It's well-known that genetic predisposition plays an important role in the mechanism of PAH. So we hypothesized that PAH-causing gene mutation might exist in some CTEPH patients and act as a background to facilitate the development of CTEPH. In this study, we analyzed 7 PAH-causing genes including BMPR2, ACVRL1, ENG, SMAD9, CAV1, KCNK3, and CBLN2 in 49 CTEPH patients and 17 patients recovered from pulmonary embolism (PE) but without pulmonary hypertension(PH). The results showed that the nonsynonymous mutation rate in CTEPH patients is significantly higher than that in PE without PH patients (25 out of 49 (51%) CTEPH patients vs. 3 out of 17 PE without PH patients (18%); p = 0.022). Four CTEPH patients had the same point mutation in ACVRL1 exon 10 (c.1450C>G), a mutation approved to be associated with PH in a previous study. In addition, we identified two CTEPH associated SNPs (rs3739817 and rs55805125). Our results suggest that PAH-causing gene mutation might play an important role in the development of CTEPH.
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Hipertensión Pulmonar Primaria Familiar/genética , Embolia Pulmonar/genética , Adulto , Anciano , China , Enfermedad Crónica , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Mutación Puntual , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction, vascular remodelling, and microthrombotic events. Inflammatory cytokine interleukin (IL-6) may be a key factor in the development of PAH, and glycoprotein 130 (Gp130) is an important signal-transducing subunit of IL-6. The aim of our study was to evaluate the effectiveness of Gp130 inhibitor in reducing inflammation and ameliorating PAH-related vascular remodelling in monocrotaline (MCT)-exposed rats. METHODS: Sprague-Dawley rats (n = 96; weight, 240-250 g) were randomly divided into 3 groups: control, MCT-exposed (MCT), and MCT-exposed plus Gp130 inhibitor (MCT-Gp) administered daily (5 mg/kg) from days 14-28. Eight rats were killed in each group at weeks 1 through 4, with the following measured variables compared across groups on day 28: hemodynamics, right ventricular hypertrophy, morphometric measurements, immunohistochemical results, levels of IL-6, phosphorylated signal transducer and activator of transcription 3, proliferating cell nuclear antigen (PCNA), bone morphogenetic protein receptor-2 (BMPR2), proangiogenic factor, vascular endothelial growth factor (VEGF), proproliferative kinase extracellular signal-regulated kinase (ERK), survivin, Bcl-2, and Bax. RESULTS: Compared with the MCT group, Gp130 inhibitor, after MCT exposure, improved hemodynamics and significantly reduced the severity of inflammation, as estimated by levels of IL-6 (P < 0.0001), and reversed pulmonary arterial remodelling, as assessed by medial wall thickness (P < 0.0001). Gp130 inhibitor upregulated BMPR2 expression in MCT-exposed lungs (P = 0.040) and decreased the expression of PCNA, VEGF, ERK, and survivin (all P < 0.05). CONCLUSIONS: Gp130 inhibitor upregulated BMPR2 expression in MCT-exposed lungs, restored the BMPR2/IL-6 balance, reduced IL-6-associated inflammation, inhibited pulmonary artery smooth muscle cell proliferation, and ameliorated pulmonary vascular remodelling in MCT-induced PH in rats.
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Glicoproteínas/antagonistas & inhibidores , Hipertensión Pulmonar/tratamiento farmacológico , Animales , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/metabolismo , Citocinas/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Pulmón/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Monocrotalina/toxicidad , Antígeno Nuclear de Célula en Proliferación/metabolismo , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/patología , Ratas Sprague-Dawley , Survivin , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Red blood cell distribution width (RDW) has been shown to predict clinical outcomes in cardiopulmonary vascular diseases. We investigated whether RDW is useful to predict responsiveness of acute pulmonary vasodilator testing in patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS: RDW was determined in 167 IPAH patients who underwent acute pulmonary vasodilator testing. All subjects were followed up for 20 ± 10 months. RESULTS: Nineteen out of 167 patients (11.4%) were acute pulmonary vasodilator testing responders. Patients with lower RDW levels ≤ 13.65% (sensitivity 89.5%, specificity 52.7%; AUC: 0.747, 95% CI: 0.632 to 0.861) were more likely to have a positive response. Multivariate logistic regression analysis showed that RDW ≤ 13.65% independently predicted responsiveness of vasodilator testing in patients with IPAH (OR 18.453, 95% CI 2.279-149.391, p = 0.006). RDW correlated with disease severity evaluated by clinical parameters. Patients with increased RDW (> 13.65%) had significantly increased risk of all-cause death (Log-rank p = 0.007). CONCLUSIONS: RDW independently predicts responsiveness of acute pulmonary vasodilator testing in patients with IPAH. RDW is associated with disease severity and all-cause death.
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Índices de Eritrocitos , Eritrocitos/patología , Hipertensión Pulmonar Primaria Familiar/diagnóstico , Hipertensión Pulmonar Primaria Familiar/tratamiento farmacológico , Vasodilatadores/uso terapéutico , Adulto , Biomarcadores Farmacológicos/análisis , Bloqueadores de los Canales de Calcio/uso terapéutico , Digoxina/uso terapéutico , Diuréticos/uso terapéutico , Hipertensión Pulmonar Primaria Familiar/mortalidad , Hipertensión Pulmonar Primaria Familiar/patología , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Masculino , Pronóstico , Curva ROC , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Vasodilatación/efectos de los fármacosRESUMEN
BACKGROUND: The present study aimed to investigate the predictors of changes in blood pressure (BP) with continuous positive airway pressure (CPAP) treatment in hypertensive patients with coronary heart disease (CHD) and obstructive sleep apnea (OSA). METHODS: Seventy-one hypertensive patients with CHD and OSA were enrolled in this study. Daytime systolic BP (SBP), diastolic BP (DBP), Epworth Sleepiness Scale (ESS), and anthropometric characteristics were assessed at baseline and follow-up. RESULTS: Sixty-six patients completed the study. The median follow-up period was 36 months (interquartile range, 24-60 months). The mean duration of CPAP application was 4.3 ± 1.2 hours per night. From baseline to follow-up, SBP and DBP were reduced by 5.6 mm Hg (95% confidence interval [CI], 3.0-8.1) and 3.0 mm Hg (95% CI, 0.8-5.3), respectively. Daytime somnolence was significantly improved (ESS, from 9.5 ± 3.4 at baseline to 3.6 ± 2.0 at follow-up; P < 0.001); the mean improvement in ESS was 6.0 (95% CI, 5.1-6.9). Correlation analysis of the fall in mean BP (MBP) showed that baseline MBP, change in ESS, heart rate, and CPAP compliance showed a positive correlation, whereas the baseline body mass index (BMI) and ESS had an inverse relationship. Stepwise multiple linear regression analysis, however, indicated that only baseline BMI, baseline MBP, and CPAP compliance were independently correlated with the fall in MBP. CONCLUSIONS: Long-term CPAP treatment reduces BP in hypertensive patients with CHD and moderate/severe OSA; baseline BMI, baseline MBP, and CPAP compliance are independent predictors of the decrease in BP with CPAP treatment in these patients.
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Presión Sanguínea/fisiología , Presión de las Vías Aéreas Positiva Contínua/métodos , Enfermedad de la Arteria Coronaria/complicaciones , Hipertensión/complicaciones , Apnea Obstructiva del Sueño/terapia , Enfermedad de la Arteria Coronaria/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/fisiopatología , Factores de TiempoRESUMEN
BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized as the incomplete resolution of emboli after pulmonary embolism (PE) and the subsequent fibrotic organization and remodeling of pulmonary vascular bed. It has been reported that abnormal fibrin probably contributes to the incomplete resolution of emboli. And there is evidence that free iron could convert fibrinogen into fibrin which is remarkably resistant to lysis. Thus, we hypothesized that persistent iron overload might participate in the development of CTEPH. MATERIALS AND METHODS: A case-control study was conducted. Forty-five CTEPH patients were enrolled as cases, and 36 age and sex frequency-matched chronic PE patients without pulmonary hypertension were selected as controls. Levels of free iron, soluble transferrin receptor (sTfR), ferritin, sTfR/ferritin ratio, hepcidin-25, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and malondialdehyde (MDA) were compared between the two groups. Logistic regression analysis was carried out to estimate odds ratios. RESULTS: There was no difference of the levels of free iron, hepcidin-25, sTfR, ferritin, sTfR/ferritin ratio, TNF-α, and MDA between CTEPH patients and the controls. Levels of sTfR and ferritin in both groups were within the normal limits. Levels of IL-6 in CTEPH patients were significantly higher than that in the controls. A negative correlation was observed between hepcidin-25 and sTfR (Spearman's r=-0.438, P<.001), and a positive correlation was observed between hepcidin-25 and ferritin (Spearman's r=0.503, P<.001). In the univariate logistic regression model, there was no association observed between CTEPH and free iron, hepcidin-25, sTfR, ferritin, sTfR/ferritin ratio, TNF-α, IL-6, and MDA. CONCLUSIONS: CTEPH has no association with iron overload. The iron status evaluated by sTfR and ferritin is within the normal limits in this CTEPH population.
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Hipertensión Pulmonar/etiología , Sobrecarga de Hierro/epidemiología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Embolia Pulmonar/complicacionesRESUMEN
INTRODUCTION: The natural history of acute pulmonary embolism (PE) under treatment is about a gradual resolution of the thrombi, and uncommonly, the development of chronic thromboembolic pulmonary hypertension (CTEPH). We hypothesized that ventilatory efficiency parameters during cardiopulmonary exercise testing (CPET) may be able to monitor the process and predict CTEPH. METHODS: 15 patients rehabilitated from acute PE (total resolution of thrombi), 44 patients with chronic PE (with residual thrombi), 66 patients with CTEPH, and 36 sedentary healthy controls performed incremental CPET. RESULTS: The lowest VE/VCO2 was higher in CTEPH patients than that in chronic PE and rehabilitated patients (43.4 L/min vs 29.9 L/min vs 27.1 L/min, p<0.005). The VE/VCO2 slope (48.4 L/min/L/min vs 29.9 L/min/L/min vs 28.0 L/min/L/min, p<0.005) and oxygen uptake efficiency plateau (OUEP) (37.1 L/min vs 27.0 L/min vs 25.2L/min, p<0.005) had the similar changes. In logistic regression analysis, the lowest VE/VCO2 ≥ 34.35 L/min was the best predictor of CTEPH (OR 159.0, 95% CI 36.0-702.3, p<0.001). The lowest VE/VCO2 was higher in chronic PE patients compared with the controls (29.9 L/min vs 26.5 L/min, p<0.05), but there was no difference between the rehabilitated patients and the controls. In multiple linear regression analysis, the percentage of vascular obstruction by ventilation-perfusion lung scanning (PVO) was the most significant independent predictor for indices of ventilatory efficiency in chronic PE and rehabilitated patients. CONCLUSIONS: CTEPH is associated with weakened ventilatory efficiency. The lowest VE/VCO2 ratio has the best capability to predict CTEPH. Ventilatory inefficiency improves along with recovery of acute PE.
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Prueba de Esfuerzo/métodos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/etiología , Embolia Pulmonar/complicaciones , Embolia Pulmonar/diagnóstico , Intercambio Gaseoso Pulmonar , Enfermedad Crónica , Femenino , Humanos , Hipertensión Pulmonar/rehabilitación , Masculino , Persona de Mediana Edad , Embolia Pulmonar/rehabilitación , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
OBJECTIVES: We observed the pulmonary function and exercise capacity of idiopathic dilated cardiomyopathy (IDCM) and idiopathic pulmonary arterial hypertension (IPAH) patients using cardiopulmonary exercise testing (CPX). We evaluated and compared the two groups. BACKGROUND: Pulmonary abnormalities and decreased exercise capacity are common in IDCM and IPAH. Little is known about the differences in these two syndromes. METHODS: Sixty-three patients were involved the study, 23 with IDCM and 40 with IPAH. All patients underwent pulmonary function testing at rest and CPX. RESULTS: Patients with IPAH had a higher peak respiratory frequency (32.40 ± 7.88 vs 29.60 ± 6.50 b/min), peak dead space volume/tidal volume (29.33 ± 4.55 vs 26.30 ± 3.31%), peak end-tidal partial pressure of O2 (125.18 ± 5.88 vs 115.17 ± 6.06 mm Hg), peak minute ventilation/CO2 production (50.14 ± 13.26 vs 33.50 ± 6.80 L/min/L/min), and a lower peak oxygen uptake (1262.70 ± 333.34 vs 742.76 ± 194.72 ml/min), peak minute ventilation (38.20 ± 13.07 vs 45.33 ± 12.31 L), peak oxygen uptake/heart rate (5.11 ± 1.47 vs 9.43 ± 2.79 ml/b) and peak end-tidal partial pressure of CO2 (23.73 ± 5.39 vs 35.30 ± 5.45 mm Hg) during exercise. CONCLUSIONS: Compared to IDCM, patients with IPAH had worse pulmonary function and exercise capacity resulting from severe ventilation/perfusion mismatching and gas exchange abnormalities.
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Cardiomiopatía Dilatada/fisiopatología , Tolerancia al Ejercicio , Hipertensión Pulmonar/fisiopatología , Mecánica Respiratoria , Adulto , Prueba de Esfuerzo , Hipertensión Pulmonar Primaria Familiar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria , Adulto JovenRESUMEN
UNLABELLED: The purpose of this study was to determine the functionality of the transplanted induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) in a rat model of cerebral ischemia with use of (18)F-FDG small-animal PET imaging. METHODS: Middle cerebral artery occlusion was used to establish cerebral ischemia. Twenty-four male rats were randomly assigned to 1 of 3 groups: iPSC treatment, ESC treatment, and the control phosphate-buffered saline (PBS) injection. After neurologic function tests and baseline (18)F-FDG small-animal PET had been performed, 1.0 × 10(6) suspended iPSCs or ESCs were injected stereotactically into the left lateral ventricle. The treatment response was evaluated weekly by (18)F-FDG PET scans and neurologic function tests. Histologic analyses and autoradiographic imaging were performed 4 wk after stem cell transplantation. RESULTS: Compared with the PBS injection group, higher (18)F-FDG accumulation in the ipsilateral cerebral infarction was observed in both the iPSC and the ESC treatment groups during the 4-wk period (P < 0.05). (18)F-FDG accumulation in the ipsilateral cerebral infarction increased steadily over time in the iPSC treatment group. At 1 and 2 wk after stem cell transplantation, significant recovery of glucose metabolism was found in the ESC treatment group (P < 0.05) and then decreased gradually. The neurologic score in both stem cell-treated groups was significantly lower than that in the PBS group, indicating functional improvement. Immunohistochemical analysis demonstrated that transplanted stem cells survived and migrated close to the ischemic region, and most of the stem cells expressed protein markers for cells of interest. CONCLUSION: (18)F-FDG small-animal PET demonstrated metabolic recovery after iPSC and ESC transplantation in the rat model of cerebral ischemia. iPSCs could be considered a potentially better therapeutic approach than ESCs and are worthy of further translational investigation.