title: Growth differentiation factor-15, a novel biomarker related with disease severity in patients with hypertrophic cardiomyopathy.
abstract: BACKGROUND
  The growth differentiation factor 15 (GDF-15) has been shown up-regulated in stress conditions and to have regulatory actions in myocyte hypertrophy. We hypothesized that GDF-15 could be related to disease severity and functional status in patients with hypertrophic cardiomyopathy (HCM).
  
  
  RESULTS
  We performed a study which includes 102 consecutive outpatient HCM subjects, 73% males, aged 47.1±14.6 years. A complete history and clinical examination was performed, including 12-lead electrocardiogram, echocardiography, symptom-limited treadmill exercise, 24-hour ECG-Holter monitoring, and magnetic resonance with Gadolinium. Several biomarkers, associated with myocardial remodeling and damage, were compared to GDF-15 levels. The assays were performed with commercial ELISAs or standardized methods when available. There was a significant association between GDF-15 levels and comorbidities, being higher in hypertension (p=0.001), diabetes (p=0.030), atrial fibrillation (p=0.012), dyspnea (p=0.020) and NYHA≥II functional class (p=0.037). GDF-15 levels were positively correlated with clinical variables (age, worse exercise capacity and mild renal dysfunction) and biomarkers of interstitial remodeling, such as metalloproteinase-2 (r: 0.40; p=0.009), N-terminal pro-B-type natriuretic peptide (r: 0.28; p=0.049), high-sensitivity troponin T (r: 0.30; p=0.003) and von Willebrand factor (r: 0.33; p=0.001). Multivariate analysis was assessed to estimate the involvement of these different factors in the GDF-15 levels, confirming the independent implication of severe dyspnea and functional status.
  
  
  CONCLUSIONS
  The present results show that higher levels of GDF-15 are associated to conditions of severe disease in HCM. Hence, GDF-15 is suggested as a novel marker related to the severity and could represent a further useful tool in monitoring functional capacity of HCM patients.
authors.affiliation: Department of Cardiology, Hospital Universitario Virgen de la Arrixaca, University of Murcia, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Montoro-García
authors.forename: Diana
authors.initials: D
authors.lastname: Hernández-Romero
authors.forename: Eva
authors.initials: E
authors.lastname: Jover
authors.forename: Antonio
authors.initials: A
authors.lastname: García-Honrubia
authors.forename: Juan A
authors.initials: JA
authors.lastname: Vilchez
authors.forename: Teresa
authors.initials: T
authors.lastname: Casas
authors.forename: Pedro
authors.initials: P
authors.lastname: Martínez
authors.forename: Vicente
authors.initials: V
authors.lastname: Climent
authors.forename: Luis
authors.initials: L
authors.lastname: Caballero
authors.forename: Mariano
authors.initials: M
authors.lastname: Valdés
authors.forename: Francisco
authors.initials: F
authors.lastname: Marín
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D018450:Disease Progression; D004452:Echocardiography; D015716:Electrocardiography, Ambulatory; D004797:Enzyme-Linked Immunosorbent Assay; D005080:Exercise Test; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; D055436:Growth Differentiation Factor 15