RESUMEN
Measures of small and large artery dysfunction have not been investigated in a single cohort for the prediction of cardiovascular (CV) events in patients with nondialysed (ND) chronic kidney disease (CKD). This prospective cohort study aimed to determine whether central pulse wave velocity (cPWV), central pulse pressure (CPP) or microvascular post-occlusive reactive hyperaemia area (PORHHA) independently predict CV events and mortality in CKD-ND. A total of 94 stage 1-5 CKD-ND (65.3±13.1 years; estimated glomerular filtration rate 35.3 (22.8-49.4) ml min(-1) per 1.73 m(2)) patients were followed-up for a median of 52 (36-65) months and had baseline cPWV and CPP measured by applanation tonometry and PORHHA by laser Doppler flowmetry. Multiple failure time Cox regression models were used to determine the predictive role of vascular parameters on CV mortality and events. Based on multiple linear regressions, baseline age, diabetes, CV disease, and systolic blood pressure (SBP) were independently related to cPWV (R(2)=0.3), SBP and PORHHA to CPP (R(2)=0.45), whereas CPP was the only parameter independently related to PORHHA (R(2)=0.16, all P<0.05). During follow-up, 41 CV events occurred (14 CV deaths). In univariate analyses, cPWV (1.07 (1.02-1.13) per m s(-1)), CPP (1.04 (1.01-1.07) per mm Hg) and lnPORHHA (0.70 (0.58-0.85) per ln(PU × s)) were all related to the outcome. Baseline diabetes (HR 3.07 (1.65-5.68)), lnFGF23 (fibroblast growth factor-23; 1.86 (1.13-3.06) per RU ml(-1)) and CPP (1.04 (1.01-1.07) per mm Hg) were independent predictors of CV events. The impaired pulsatile component of large arteries (CPP) independently of other vascular markers (cPWV, PORHHA) predicted CV outcomes in CKD-ND. CPP may integrate the information provided by cPWV and PORHHA.
Asunto(s)
Presión Sanguínea , Tasa de Filtración Glomerular , Riñón/fisiopatología , Microcirculación , Insuficiencia Renal Crónica/fisiopatología , Rigidez Vascular , Anciano , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/fisiopatología , Estudios Transversales , Femenino , Humanos , Hiperemia/fisiopatología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Flujo Pulsátil , Análisis de la Onda del Pulso , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/mortalidad , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
Several hydrazone, oxime, carbazone and semicarbazone derivatives of 14-alkoxycodeinones and 14-alkoxydihydrocodeinones were synthesised [1] and characterised in in vitro radioligand binding assays in rat brain membrane preparations. The tested compounds show the highest affinity for the mu opioid binding sites and most of them have agonist character. Subtype analysis of the binding shows mu2 specificity. However, some of these ligands are able to block partially (40-60%) the high affinity (putative mu1) opioid binding sites while all of them act as reversible ligands at the low affinity (putative mu2) sites.