title: Growth differentiation factor 15, ST2, high-sensitivity troponin T, and N-terminal pro brain natriuretic peptide in heart failure with preserved vs. reduced ejection fraction.
abstract: OBJECTIVE
  Growth differentiation factor 15 (GDF15), ST2, high-sensitivity troponin T (hsTnT), and N-terminal pro brain natriuretic peptide (NT-proBNP) are biomarkers of distinct mechanisms that may contribute to the pathophysiology of heart failure (HF) [inflammation (GDF15); ventricular remodelling (ST2); myonecrosis (hsTnT); and wall stress (NT-proBNP)].
  
  
  RESULTS
  We compared circulating levels of GDF15, ST2, hsTnT, and NT-proBNP, as well as their combinations, in compensated patients with clinical HF with reduced ejection fraction (HFREF) (n = 51), HF with preserved ejection fraction (HFPEF) (n= 50), and community-based controls (n = 50). Compared with controls, patients with HFPEF and HFREF had higher median levels of GDF15 (540 pg/mL vs. 2529 and 2672 pg/mL, respectively), hsTnT (3.7 pg/mL vs. 23.7 and 35.6 pg/mL), and NT-proBNP (69 pg/mL vs. 942 and 2562 pg/mL), but not ST2 (27.6 ng/mL vs. 31.5 and 35.3 ng/mL), adjusting for clinical covariates. In receiver operating characteristic curve analyses, NT-proBNP distinguished HFREF from controls with an area under the curve (AUC) of 0.987 (P < 0.001); GDF15 distinguished HFPEF from controls with an AUC of 0.936 (P < 0.001); and the combination of NT-proBNP and GDF15 distinguished HFPEF from controls with an AUC of 0.956 (P < 0.001). NT-proBNP and hsTnT levels were higher in HFREF than in HFPEF (adjusted P < 0.04). The NT-proBNP:GDF15 ratio distinguished between HFPEF and HFREF with the largest AUC (0.709; P < 0.001).
  
  
  CONCLUSIONS
  Our study provides comparative data on physiologically distinct circulating biomarkers in HFPEF, HFREF, and controls from the same community. These data suggest a prominent role for myocardial injury (hsTnT) with increased wall stress (NT-proBNP) in HFREF, and systemic inflammation (GDF15) in HFPEF.
authors.affiliation: Cardiovascular Research Institute, National University of Singapore, Singapore.
authors.forename: Rajalakshmi
authors.initials: R
authors.lastname: Santhanakrishnan
authors.forename: Jenny P C
authors.initials: JP
authors.lastname: Chong
authors.forename: Tze P
authors.initials: TP
authors.lastname: Ng
authors.forename: Lieng H
authors.initials: LH
authors.lastname: Ling
authors.forename: David
authors.initials: D
authors.lastname: Sim
authors.forename: Kui Toh G
authors.initials: KT
authors.lastname: Leong
authors.forename: Poh Shuan D
authors.initials: PS
authors.lastname: Yeo
authors.forename: Hean Y
authors.initials: HY
authors.lastname: Ong
authors.forename: Fazlur
authors.initials: F
authors.lastname: Jaufeerally
authors.forename: Raymond
authors.initials: R
authors.lastname: Wong
authors.forename: Ping
authors.initials: P
authors.lastname: Chai
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Low
authors.forename: Arthur Mark
authors.initials: AM
authors.lastname: Richards
authors.forename: Carolyn S P
authors.initials: CS
authors.lastname: Lam
mesh_terms: D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015150:Echocardiography, Doppler; D004562:Electrocardiography; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006333:Heart Failure / Q000097:blood* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000503:physiopathology; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D009336:Necrosis / Q000097:blood / Q000503:physiopathology; D010446:Peptide Fragments / Q000097:blood*; D011446:Prospective Studies; D012372:ROC Curve; D011956:Receptors, Cell Surface / Q000097:blood*; D012846:Singapore; D013318:Stroke Volume / Q000502:physiology; D020107:Troponin T / Q000097:blood*; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D015415:Biomarkers; D055436:Growth Differentiation Factor 15; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain