Growth differentiation factor-15, a novel biomarker related with disease severity in patients with hypertrophic cardiomyopathy

Eur J Intern Med. 2012 Mar;23(2):169-74. doi: 10.1016/j.ejim.2011.08.022. Epub 2011 Sep 15.

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).

Methods and 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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Cardiomyopathy, Hypertrophic / blood
  • Cardiomyopathy, Hypertrophic / diagnosis*
  • Cardiomyopathy, Hypertrophic / physiopathology
  • Disease Progression
  • Echocardiography
  • Electrocardiography, Ambulatory
  • Enzyme-Linked Immunosorbent Assay
  • Exercise Test
  • Exercise Tolerance / physiology*
  • Female
  • Follow-Up Studies
  • Growth Differentiation Factor 15 / blood*
  • Humans
  • Magnetic Resonance Imaging, Cine
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Ventricular Remodeling*

Substances

  • Biomarkers
  • Growth Differentiation Factor 15