RESUMEN
BACKGROUND AND OBJECTIVE: Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) and acquired angioedema related to angiotensin-converting enzyme (ACE) inhibitors (ACEI-AAE) are types of bradykinin-mediated angioedema without wheals characterized by recurrent swelling episodes. Recent evidence suggests that a state of "vascular preconditioning" predisposes individuals to attacks, although no data are available on possible structural alterations of the vessels. Objective: This study aims to compare the features of nailfold capillaries to highlight possible structural anomalies between patients affected by C1-INH-HAE and controls and between patients with ACEI-AAE and hypertensive controls. METHODS: We used nailfold videocapillaroscopy (NVC) to assess the following: apical, internal, and external diameter; loop length; intercapillary distance; and capillary density, distribution, and morphology. Plasma levels of vascular endothelial growth factor (VEGF) A, VEGF-C, angiopoietin (Ang) 1, and Ang2 were also measured. RESULTS: Compared with healthy controls (n=28), C1-INH-HAE patients (n = 34) were characterized by significant structural alterations of the capillaries, such as greater intercapillary distance (216 vs 190 µm), increased apical, internal, and external diameter (28 vs 22 µm; 22 vs 20 µm; and 81 vs 65 µm, respectively), decreased density (4 vs 5 capillaries/mm2), more irregular capillary distribution, and more tortuous morphology. Apical diameter was enlarged in patients with ≥12 attacks per year. In ACEI-AAE patients, NVC showed no alterations with respect to hypertensive controls. NVC performed in 2 C1-INH-HAE patients during attacks showed no changes compared with the remission phase. CONCLUSIONS: We detected major structural capillary alterations in C1-INH-HAE patients, thus confirming the involvement of microcirculation in the pathogenesis of angioedema.
Asunto(s)
Angioedema , Angioedemas Hereditarios , Bradiquinina , Proteína Inhibidora del Complemento C1 , Humanos , Angioscopía Microscópica , Factor A de Crecimiento Endotelial VascularRESUMEN
Background: Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) and acquired angioedema related to angiotensin-converting enzyme (ACE) inhibitors (ACEI-AAE) are types of bradykinin-mediated angioedema without wheals characterized by recurrent swelling episodes. Recent evidence suggests that a state of vascular preconditioning predisposes individuals to attacks, although no data are available on possible structural alterations of the vessels. Objective: This study aims to compare the features of nailfold capillaries to highlight possible structural anomalies between patients affected by C1-INH-HAE and controls and between patients with ACEI-AAE and hypertensive controls.Methods: We used nailfold videocapillaroscopy (NVC) to assess the following: apical, internal, and external diameter; loop length; intercapillary distance; and capillary density, distribution, and morphology. Plasma levels of vascular endothelial growth factor (VEGF) A, VEGF-C, angiopoietin (Ang) 1, and Ang2 were also measured. Results: Compared with healthy controls (n=28), C1-INH-HAE patients (n = 34) were characterized by significant structural alterations of the capillaries, such as greater intercapillary distance (216 vs 190 μm), increased apical, internal, and external diameter (28 vs 22 μm; 22 vs 20 μm; and 81 vs 65 μm, respectively), decreased density (4 vs 5 capillaries/mm2), more irregular capillary distribution, and more tortuous morphology. Apical diameter was enlarged in patients with ≥12 attacks per year. In ACEI-AAE patients, NVC showed no alterations with respect to hypertensive controls. NVC performed in 2 C1-INH-HAE patients during attacks showed no changes compared with the remission phase. Conclusions: We detected major structural capillary alterations in C1-INH-HAE patients, thus confirming the involvement of microcirculation in the pathogenesis of angioedema (AU)
Antecedentes: Tanto el angioedema hereditario con deficiencia de inhibidor del C1 (C1-INH-HAE) como el angioedema adquiridorelacionado con los inhibidores de la ECA (ACEI-AAE), son dos tipos de angioedema mediados por bradicinina que cursan con episodiosde inflamación recurrente sin acompañarse de habones. Existe evidencia de la existencia de un estado de "preacondicionamiento vascular"que predispone a estos pacientes a los ataques, pero no hay datos disponibles sobre las posibles alteraciones estructurales de los vasos.Objetivo: Este estudio tiene como objetivo el evaluar las características de los capilares de la base ungueal para identificar posiblesanomalías estructurales en los pacientes afectados por C1-INH-HAE en comparación con la población sana, y en los pacientes con ACEIAAE en comparación con controles con hipertensión arterial.Métodos: Mediante videocapilaroscopia de la base ungueal (NVC), se evaluaron: los diámetros apical, interno y externo, la longitud delasa, la distancia intercapilar, la densidad capilar, su distribución y su morfología. También se midieron los niveles plasmáticos del factorde crecimiento endotelial vascular (VEGF)-A, VEGF-C, angiopoyetina (Ang)1 y Ang2.Resultados: En los pacientes con C1-INH-HAE (n = 34) se observaron alteraciones estructurales de los capilares significativas, en comparacióncon los controles sanos (n = 28): mayor distancia intercapilar (216 frente a 190 µm), aumento del diámetro apical, interno y externo(28 frente a 22 µm; 22 frente a 20 µm; y 81 frente a 65 µm, respectivamente), disminución de la densidad (4 frente a 5 capilares/mm2),distribución capilar más irregular y una morfología más tortuosa. El diámetro apical fue mayor en aquellos pacientes con ≥12 ataques/año. En los pacientes con ACEI-AAE, las NVC no mostraron alteraciones al ser comparadas con las de los controles hipertensos. Las NVC realizadas en dos pacientes ...(AU)
Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Angioedema/diagnóstico , Proteína Inhibidora del Complemento C1 , Factor A de Crecimiento Endotelial Vascular , Angioscopía Microscópica , Estudios de Casos y ControlesRESUMEN
BACKGROUND AND OBJECTIVE: Angiotensin-converting enzyme inhibitor-associated angioedema (ACEI-AAE) affects 0.1%-0.7% of patients treated with ACEIs. While previous research suggests that angioedema attacks result from increased vascular permeability, the pathogenesis is not completely understood. Objective: This study aimed to describe the clinical, genetic, and laboratory parameters of ACEI-AAE patients and to investigate the role of vascular endothelial growth factors A and C (VEGF-A and VEGF-C), angiopoietins 1 and 2 (Ang1/Ang2), and secretory phospholipase A2 (sPLA2) in the pathogenesis of ACEI-AAE. METHODS: The clinical and laboratory data of ACEI-AAE patients were collected from 2 angioedema reference centers. Healthy volunteers and ACEI-treated patients without angioedema were enrolled to compare laboratory parameters. Genetic analyses to detect mutations in the genes SERPING1, ANGPT1, PLG, and F12 were performed in a subset of patients. RESULTS: A total of 51 patients (57% male) were diagnosed with ACEI-AAE. The average time to onset of symptoms from the start of ACEI therapy was 3 years (range, 30 days-20 years). The most commonly affected sites were the lips (74.5%), tongue (51.9%), and face (41.2%). Switching from ACEIs to sartans was not associated with an increased risk of angioedema in patients with a history of ACEIAAE. VEGF-A, VEGF-C, and sPLA2 plasma levels were higher in ACEI-AAE patients than in the controls. Ang1/2 concentrations remained unchanged. No mutations were detected in the genes analyzed. CONCLUSIONS: Our data suggest that sartans are a safe therapeutic alternative in ACEI-AAE patients. Increased concentrations of VEGF-A, VEGF-C, and sPLA2 in ACEI-AAE patients suggest a possible role of these mediators in the pathogenesis of ACEI-AAE.
Asunto(s)
Angioedema/inmunología , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antígenos de Plaqueta Humana/sangre , Factor A de Crecimiento Endotelial Vascular/sangre , Factor C de Crecimiento Endotelial Vascular/sangre , Adulto , Anciano , Anciano de 80 o más Años , Angiopoyetina 1/sangre , Angiopoyetina 2/sangre , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Riesgo , Cambio de Tratamiento , Regulación hacia ArribaRESUMEN
Left ventricular hypertrophy (LVH) is prognostically relevant, associated with major cardiovascular risk factors and with atherosclerosis. However, whether LVH is independently associated with impaired coronary flow reserve (CFR) and with endothelial dysfunction is disputed. We assessed the relationship of LV mass and systolic function to CFR and endothelial function in new discovered never treated subjects with essential arterial hypertension, but without coronary artery disease or microalbuminuria. LVH, ejection fraction (EF) and stress-corrected midwall shortening (MWS, a measure of myocardial contractility) were assessed by echocardiography. CFR was assessed by single-photon emission computed tomography and dipyridamole infusion. Endothelial function was evaluated by assessing 1-min postischaemic flow-mediated dilatation of the brachial artery (FMD); nitroglycerine-mediated dilatation (NMD) of the same brachial artery was used as measure of nonendothelium-dependent vasodilatation. In approximately 1 year, we enrolled 21 subjects who met stringent inclusion criteria (47+/-10 years old, 26.6+/-2.8 kg/m2, 78% men). Five patients showed LVH. Multivariate analyses showed a significant negative correlation of LV mass index with FMD (beta=-0.61, P<0.05) but not with NMD, neither with CFR. Stress-corrected MWS showed independent correlation with CFR (beta=0.51, P<0.05). Thus, in clinically healthy, new discovered hypertensive subjects, never treated and mostly in the early stage of arterial hypertension, LVH can be associated with endothelial dysfunction while maximal dipyridamole- dependent CFR may be preserved; nevertheless, a cardiac phenotype presenting with tendency to impaired myocardial contractility, assessed by stress-corrected MWS, showed association with lower CFR in the early stage of arterial hypertension.
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Circulación Coronaria , Endotelio Vascular/fisiopatología , Ventrículos Cardíacos/patología , Hipertensión/patología , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/fisiopatología , Femenino , Humanos , Hipertensión/complicaciones , Hipertrofia Ventricular Izquierda/complicaciones , Masculino , Persona de Mediana Edad , SístoleRESUMEN
BACKGROUND AND AIMS: The association between left ventricular (LV) mass (M) and variables described as features of the insulin resistance syndrome, such as obesity and measures o lipid and carbohydrate metabolisms, has been reported in hypertensives. The aim of the present study was to investigate in a large, population based group of non hypertensive people, the prevalence of LV hypertrophy (H) and the relationship of LVM with some of the variables described in the insulin resistance syndrome, independently of obesity. For this reason we investigated the normotensive subjects in the age range 45-54 yrs (n = 435) of the total population of participants in the Gubbio Population Study. METHODS AND RESULTS: Serum lipids, cholesterol (Chol), triglyceride (Tg), HDL cholesterol, fasting blood glucose (FBG), blood pressure (BP), body weight and height were measured and body mass index (BMI) was calculated; LVM was assessed by M-mode echocardiography. Using a normalization criterion not related to body weight (g/m2.7) and the cut-off of 49.2 g/m2.7 for men and 46.7 g/m2.7 for women, LVH was found in 25% of the sample whilst, when LVM was corrected by body surface area (cut-off 116 g/m2 for men and 104 g/m2 for women), the prevalence of LVH was quite lower (10.3%). In the univariate analyses LVMi was closely related to BP, BMI and metabolic variables whilst in the multivariate analysis only BP, BMI, and age were detected as independent predictors of LVMi. When the sample was divided into obese and non-obese subjects on the basis of BMI (cut-off 30 kg/m2), no difference in metabolic variables was seen between subjects with and without LVH within each BMI class. Regarding left ventricular geometry, RWT was positively related to triglycerides and blood glucose and inversely to HDL-chol. CONCLUSIONS: The present study in the middle age normotensive sample of the general population of Gubbio extends to normotensives the relationship between left ventricular mass and metabolic parameters already seen in hypertensives. BMI seems to account for most of the increases in LVM since the prevalence of LVH, which was definitely high when LVM was not normalized to body weight, fell to approximately 4% when the influence of body weight was excluded. Moreover differences in metabolic values between subjects with and without LVH disappeared when the subjects were stratified by BMI. Left ventricular geometry, on the other hand, seems to be related to some metabolic variables.
Asunto(s)
Glucemia/análisis , Índice de Masa Corporal , Hipertrofia Ventricular Izquierda/sangre , Lípidos/sangre , Glucemia/metabolismo , Presión Sanguínea , Peso Corporal/fisiología , Colesterol/sangre , Estudios de Cohortes , Ecocardiografía , Femenino , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/epidemiología , Italia/epidemiología , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Obesidad/sangre , Obesidad/complicaciones , Obesidad/epidemiología , Prevalencia , Factores de Riesgo , Triglicéridos/sangreRESUMEN
Ambulatory blood pressure monitoring allows a better understanding of blood pressure fluctuations over 24 h than simple clinic measurements. In this way the diagnosis of "white coat" versus "sustained" hypertension and that of "dipper" (patient with blood pressure fall during nighttime > 10% of daytime levels) versus "nondipper" status were made possible. This pilot study has been undertaken to investigate whether patients with recently discovered, never-treated, mild, sustained hypertension have cardiovascular abnormalities according to their dipper/nondipper status. Patients with long-standing (n = 123) and newly discovered (n = 56) sustained hypertension were classified according to their nighttime blood pressure fall, and compared with normotensive controls. Ambulatory blood pressure monitoring was performed noninvasively. Parameters of left ventricular structure, cardiac systolic and diastolic function, and carotid anatomy were determined noninvasively by echographic methods. Significant increases in parameters of cardiac structure as well as abnormalities in diastolic function were observed in patients with long-standing hypertension, regardless of their dipper status. In the group with newly discovered hypertension, left atrium (3.4+/-0.3, 3.7+/-0.5, 3.2+/-0.4 cm in dippers, nondippers, and controls, respectively), end-diastolic diameter index (2.9+/-0.3, 3.0+/-0.2, 2.8+/-0.2 cm/m), and atrial filling fraction (0.50+/-0.07, 0.52+/-0.05, 0.42+/-0.04) were significantly altered only in the nondipper subgroup, in comparison with controls. Significant changes in cardiac structure and diastolic function were observed in nondipper patients with recently discovered hypertension, who, at variance with dippers, show changes similar to those in patients with long-standing hypertension. Hypertensives with the observed abnormalities may benefit from active antihypertensive treatment, which appears, therefore, justified even in an early phase of mild hypertension, in terms of potential reduction of end-organ complications as well as cost-effectiveness.
Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial , Hipertensión/complicaciones , Hipertrofia Ventricular Izquierda/etiología , Adulto , Anciano , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Sueño/fisiologíaRESUMEN
Arterial hypertension is frequently associated with metabolic abnormalities. Hyperinsulinemia and insulin resistance are found in obese patients, in non-insulin-dependent diabetics and in some hypertensive patients, irrespective of whether the patients are overweight or have diabetes mellitus. Membrane transport abnormalities, such as increased sodium-lithium exchange associated with hypertension are also significantly related to disturbances in lipid metabolism. Increased sympathetic nervous system activity is a well established feature of arterial hypertension and this may also affect glucose and lipid metabolism. The possibility of these metabolic alterations in the hypertensive patient must be taken into account when deciding upon treatment. Attention to diet is mandatory and includes advice to reduce energy, salt and saturated fat intakes and to increase the intake of less digestible fiber and of potassium; alcohol consumption should be limited. Energy expenditure by regular aerobic physical exercise should be encouraged and continuous effort is necessary to help patients stop smoking. In patients with high blood pressure and abnormalities in lipid and glucose metabolism, it is wise to start pharmacological treatment with drugs that are known to be neutral in their metabolic effects, such as calcium antagonists, angiotensin converting enzyme inhibitors or alpha-blocking agents.
Asunto(s)
Antihipertensivos/uso terapéutico , Complicaciones de la Diabetes , Hiperinsulinismo/complicaciones , Hiperlipidemias/complicaciones , Hipertensión/tratamiento farmacológico , Humanos , Hipertensión/complicacionesRESUMEN
Certain acute and chronic metabolic effects of nicardipine have been studied in 20 patients with non-insulin dependent diabetes (NIDD). An intravenous glucose tolerance test (i.v. GTT, glucose 0.33 g/kg as a bolus) and the corresponding insulin response were assessed at the end of a 4 week placebo period, after the first dose and on administration for 12 weeks of nicardipine 20 mg t.i.d. The glucose and insulin responses to the i.v.GTT, evaluated as incremental AUCs, did not change significantly (glucose 30.5 mg/dl.90 min on placebo, 33.1 mg/dl.90 min acutely and 31.4 mg/dl.90 min on chronic administration of nicardipine; insulin 2.08 microU/ml.90 min on placebo, 1.87 microU/ml.90 min acutely and 1.93 microU/ml.90 min after chronic nicardipine). Glucose removal rate (KG) following the i.v.GTT was 0.73%/min on placebo 0.75%/min on acute administration and 0.8%.min-1 with chronic nicardipine. Active treatment produced a significant reduction of blood pressure (from 187/96 mm Hg on placebo to 166/89 mm Hg acutely and 152/83 mm Hg after 12 weeks of nicardipine treatment). It is concluded that the calcium antagonist nicardipine was an effective antihypertensive drug, and that it did not cause deterioration of metabolic control in hypertensive patients with NIDD.