RESUMO
OBJECTIVES: Experimental studies have shown involvement of Wnt signalling in heart failure (HF). We hypothesized that secreted frizzled-related protein 3 (sFRP3), a modulator of Wnt signalling, is related to the progression of HF. DESIGN: Circulating sFRP3 was measured in 153 HF patients and compared with 25 healthy controls. The association of sFRP3 with mortality was evaluated in 1202 patients (GISSI-HF trial). sFRP3 mRNA expression was assessed in failing human and murine left ventricles (LV), and cellular localization was determined after fractioning of myocardial tissue. In vitro studies were carried out in cardiac fibroblasts subjected to cyclic mechanical stretch. RESULTS: (i) Heart failure patients had significantly raised serum sFRP3 levels compared with controls, (ii) during a median follow-up of 47 months, 315 patients died in the GISSI-HF substudy. In univariable Cox regression, tertiles of baseline sFRP3 concentration were significantly associated with all-cause and cardiovascular mortality. After adjustment for demographic and clinical variables, but not for CRP and NT-proBNP, the associations with mortality remained significant for the third tertile (all-cause, HR 1.45, P = 0.011; cardiovascular, HR 1.66, P = 0.003), (iii) sFRP3 mRNA expression was increased in failing human LV, with a decline following LV assist device therapy. LV from post-MI mice showed an increased sFRP3 mRNA level, particularly in cardiac fibroblasts, and (iv) mechanical stretch enhanced sFRP3 expression and release in myocardial fibroblasts. CONCLUSION: There is an association between increased sFRP3 expression and adverse outcome in HF, suggesting that the failing myocardium itself contributes to an increase in circulating sFRP3.
Assuntos
Modelos Animais de Doenças , Insuficiência Cardíaca , Infarto do Miocárdio/metabolismo , Proteínas , Idoso , Animais , Progressão da Doença , Feminino , Regulação da Expressão Gênica , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miocárdio/patologia , Gravidade do Paciente , Modelos de Riscos Proporcionais , Proteínas/genética , Proteínas/metabolismo , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda/fisiopatologia , Via de Sinalização Wnt/genéticaRESUMO
OBJECTIVE: To study the prognostic value of neutrophil gelatinase-associated lipocalin (NGAL) in chronic heart failure (HF) of ischaemic aetiology. BACKGROUND: Neutrophil gelatinase-associated lipocalin is a marker of kidney injury as well as matrix degradation and inflammation and has previously been shown to be increased in HF. We investigated whether serum NGAL levels could provide prognostic information in chronic HF. METHODS: We assessed NGAL as a predictor of primary outcomes (cardiovascular death, nonfatal stroke and nonfatal myocardial infarction, n = 307) and all-cause mortality (n = 321), cardiovascular mortality (n = 259) and hospitalization (n = 647) as well as the number of hospitalizations during follow-up for all (n = 1934) and CV causes (n = 1204) in 1415 patients with chronic HF (≥60 years, New York Heart Association class II-IV, ischaemic systolic HF) in the CORONA population, randomly assigned to 10 mg rosuvastatin or placebo. Results. Multivariate analysis revealed that NGAL added significant information when adjusting for clinical variables, but was no longer significant when further adjusting for apolipoprotein A-1 (ApoA-1), glomerular filtration rate (GFR), C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP). However, belonging to the highest NGAL tertile was associated with more frequent hospitalization, even after adjusting for clinical variables, GFR and ApoA-1, but not after adjusting for CRP and NT-proBNP. There was no interaction between rosuvastatin treatment and NGAL. Conclusion. Neutrophil gelatinase-associated lipocalin added no significant information to NT-proBNP and GFR in a multivariate model for primary and secondary end-points.
Assuntos
Fluorbenzenos/uso terapêutico , Insuficiência Cardíaca , Lipocalinas/sangue , Proteínas Proto-Oncogênicas/sangue , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Proteínas de Fase Aguda , Idoso , Apolipoproteína A-I/metabolismo , Biomarcadores , Proteína C-Reativa/metabolismo , Doença Crônica , Feminino , Taxa de Filtração Glomerular , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipocalina-2 , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Peptídeo Natriurético Encefálico/metabolismo , Noruega , Readmissão do Paciente/estatística & dados numéricos , Fragmentos de Peptídeos/metabolismo , Valor Preditivo dos Testes , Prognóstico , Rosuvastatina Cálcica , Índice de Gravidade de DoençaRESUMO
Memory and psychophysiological variables in persons with self-reported reactions to dental amalgam (amalgam patients: N=26) and in persons without such symptoms (controls: N=21) were compared. The groups were matched regarding age, education, and amount of amalgam. Wechsler Memory Scale-Revised was obtained for all subjects and compared to amalgam points in a dose-response design. The results demonstrated that amalgam patients function on the same level as the controls regarding memory variables, attention, concentration, and delayed recall. Psychophysiological measures of skin conductance as correlates of attention and basal memory functions, were compared in the two groups. No differences between the two groups were observed and no correlation between memory variables and exposure to amalgam could be detected.