title: Glycosylated haemoglobin is associated with neurohormonal activation and poor outcome in chronic heart failure patients with mild left ventricular systolic dysfunction.
abstract: OBJECTIVE
  We aimed to evaluate the impact of glycometabolic imbalance as assessed by glycosylated haemoglobin [HbA(1c)] on neurohormonal activation and outcome in chronic heart failure (CHF).
  
  
  RESULTS
  Nine hundred and twenty CHF patients (65 ± 12 years, left ventricular ejection fraction 33 ± 10%, 29% diabetic patients) underwent a thorough humoral and clinical characterization, including HbA(1c), and were then followed up for the endpoint of cardiac death. In the whole population, diagnosis of diabetes resulted in no difference in neurohormonal or echocardiographic data, or in outcome. Conversely, the diabetic patients with HbA(1c) above 7% showed, in comparison to both diabetic patients with HbA(1c) below 7% and non-diabetic individuals, higher plasma renin activity (1.81, 0.48-5.68 vs. 1.23, 0.43-2.8 and 1.29, 0.44-5 ng/ml/h, respectively; P < 0.01 for both), N-terminal pro-brain natriuretic peptide (NT-pro-BNP) (1602, 826-3498 vs. 1022, 500-3543 and 1134, 455-3545 ng/l, respectively; P < 0.01 for both) and worse symptoms with a higher rate of cardiac mortality vs. both diabetic patients with HbA1(c) below 7% and non-diabetic individuals (P < 0.05 for both). In the left ventricular ejection fraction 38-50% tertile (mild left ventricular dysfunction), elevated HbA(1c) was associated with higher NT-pro-BNP and PRA (P < 0.01), and, alongside NT-pro-BNP, resulted the only independent predictor of outcome beyond diagnosis of diabetes. HbA(1c) failed to show up differences in neuroendocrine activation or in outcome in moderate and severe left ventricular dysfunction tertiles.
  
  
  CONCLUSIONS
  Glycometabolic imbalance, as represented by HbA(1c), is associated with neurohormonal activation and poor prognosis in CHF patients, beyond diabetes. The impact of metabolic derangement on prognosis appears greater at the early stages of CHF, when it might exacerbate neurohormonal activation.
authors.affiliation: aDivision of Cardiovascular Medicine, Fondazione G. Monasterio CNR-Regione Toscana, Pisa bDepartment of Heart and Vessels, University of Florence, Florence, Italy.
authors.forename: Luigi Emilio
authors.initials: LE
authors.lastname: Pastormerlo
authors.forename: Chiara
authors.initials: C
authors.lastname: Mammini
authors.forename: Alberto
authors.initials: A
authors.lastname: Giannoni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Valleggi
authors.forename: Concetta
authors.initials: C
authors.lastname: Prontera
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gabutti
authors.forename: Roberta
authors.initials: R
authors.lastname: Poletti
authors.forename: Luigi
authors.initials: L
authors.lastname: Padeletti
authors.forename: Michele
authors.initials: M
authors.lastname: Emdin
authors.forename: Claudio
authors.initials: C
authors.lastname: Passino
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis*; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D012083:Renin / Q000097:blood; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000209:etiology* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; D020097:Natriuretic Peptide, Brain; D010446:Peptide Fragments; D012083:Renin; C517652:hemoglobin A1c protein, human; C109794:pro-brain natriuretic peptide (1-76)