RESUMO
BACKGROUND AND AIMS: In the field of cardiovascular diseases, elevated levels of serum uric acid (UA) reflect a marked activation of the xanthine oxidase pathway with increase in free radicals production; it is often associated with an inflammatory state, oxygen consumption and endothelial dysfunction. All these associations have been also confirmed in heart failure (HF) but the pathophysiological role of UA in this setting is not well understood. The aim of this study was to evaluate the prognostic role of UA in outpatients enrolled in the Italian Registry of Congestive Heart Failure (IN-CHF). METHODS AND RESULTS: All patients met the European Society of Cardiology (ESC) criteria for diagnosis of HF. We considered patients with complete clinical data and UA level available at the baseline and at 1-year follow-up. The study population was composed of 877 patients aged 63 ± 12 years. One-year mortality was 10.8% and dead patients had a higher level of UA than survivors (7.1 mg dl⻹ vs 6.6 mg dl⻹, p < 0.0207). In multivariable full model of analysis, UA did not result in an independent predictor of death in overall population, but only in patients with low body mass index (BMI) (≤22 kg m⻲) (hazard ratio (HR): 2.38, 95% confidence interval (CI) 1.36-4.18). In this subgroup, a statistically significant gradual relationship between UA and survival was detected starting from values higher than 8 mg dl⻹. CONCLUSION: Elevated level of UA is not an independent predictor of mortality in chronic HF, but it markedly worsens outcome if associated with low level of BMI. This association is likely an indicator of chronic inflammatory and catabolic state.
Assuntos
Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Hiperuricemia/complicações , Hiperuricemia/etiologia , Magreza/complicações , Ácido Úrico/sangue , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial , Índice de Massa Corporal , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Hiperuricemia/fisiopatologia , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Mortalidade , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de SobrevidaRESUMO
BACKGROUND AND AIMS: Chronic heart failure (HF) is characterised by a neurohormonal dysfunction associated with chronic inflammation. A role of metabolic derangement in the pathophysiology of HF has been recently reported. Adiponectin, an adipose-tissue-derived cytokine, seems to play an important role in cardiac dysfunction. We investigated the variation of circulating adiponectin in patients with coronary artery disease (CAD), with or without HF, in order to identify its independent predictors. METHODS AND RESULTS: A total of 107 outpatients with CAD were enrolled in the study and divided into three groups: CAD without left ventricular systolic dysfunction (group 1); CAD with left ventricular dysfunction without HF symptoms (group 2) and CAD with overt HF (group 3). Plasma adiponectin was determined by enzyme-linked immunosorbent assay. Adiponectin concentrations increased progressively from group 1 (7.6 ± 3.6 ng ml⻹) to group 2 (9.1 ± 6.7 ng ml⻹) and group 3 (13.7 ± 7.6 ng ml⻹), with the difference reaching statistical significance in group 3 versus 1 and 2 (p < 0.001). A multivariable model of analysis demonstrated that the best predictors of plasma adiponectin were body mass index, N-terminal pro-brain natriuretic peptide and high-density lipoprotein cholesterol. However, even after adjusting for all three independent predictors, the increase of adiponectin in group 3 still remained statistically significant (p = 0.015). CONCLUSION: Our data confirm the rise of adiponectin in overt HF. The levels of circulating adipokine seem to be mainly predicted by the metabolic profile of patients and by biohumoral indicators, rather than by clinical and echocardiographic indexes of HF severity.
Assuntos
Adiponectina/sangue , Doença da Artéria Coronariana/sangue , Insuficiência Cardíaca/sangue , Pacientes Ambulatoriais , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Índice de Massa Corporal , Distribuição de Qui-Quadrado , HDL-Colesterol/sangue , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/fisiopatologia , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Análise de Regressão , Medição de Risco , Fatores de Risco , Sístole , Regulação para Cima , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular EsquerdaRESUMO
Nuclear receptors regulate target gene expression in response to steroid and thyroid hormones, retinoids, vitamin D and other ligands. These ligand-dependent transcription factors function by contacting various nuclear cooperating proteins, called coactivators and corepressors, which mediate local chromatin remodeling as well as communication with the basal transcriptional apparatus. Nuclear receptors and their coregulatory proteins play a role in cancer and other diseases, one leading example being the estrogen receptor pathway in breast cancer. Coregulators are often present in limiting amounts in cell nuclei and modifications of their level of expression and/or structure lead to alterations in nuclear receptor functioning, which may be as pronounced as a complete inversion of signaling, i.e. from stimulating to repressing certain genes in response to an identical stimulus. In addition, hemizygous knock-out of certain coactivator genes has been demonstrated to produce cancer-prone phenotypes in mice. Thus, assessment of coactivator and corepressor expression and structure in tumors may turn out to be essential to determine the role of nuclear receptors in cancer and to predict prognosis and response to therapy.