Identification of serum soluble ST2 receptor as a novel heart failure biomarker.
BACKGROUND
Using genomic technology, we previously identified an interleukin-1 receptor family member, ST2, as a gene markedly induced by mechanical strain in cardiac myocytes. The soluble receptor form of ST2 is secreted and detectable in human serum. This study tested the hypothesis that soluble ST2 levels in the serum of patients with severe chronic heart failure are increased in patients with neurohormonal activation.


RESULTS
Serum samples, clinical variables, and neurohormone levels from the PRAISE-2 heart failure trial (NYHA functional class III-IV; end point, mortality or transplantation) were analyzed. ST2 serum measurements were performed with ELISA on samples from 161 patients obtained at trial enrollment and from 139 of the same patients obtained 2 weeks after trial enrollment. Baseline ST2 levels were correlated with baseline B-type natriuretic peptide (BNP) levels (r=0.36, P<0.0001), baseline proatrial natriuretic peptide (ProANP) levels (r=0.36, P<0.0001), and baseline norepinephrine levels (r=0.39, P<0.0001). The change in ST2 was significant as a univariate predictor of subsequent mortality or transplantation (P=0.048), as was baseline BNP (P<0.0001) and baseline ProANP (P<0.0001). In multivariate models including BNP and ProANP, the change in ST2 remained significant as a predictor of mortality or transplantation independent of BNP and ProANP.


CONCLUSIONS
Serum soluble ST2 is a novel biomarker for neurohormonal activation in patients with heart failure. In patients with severe chronic NYHA class III to IV heart failure, the change in ST2 levels is an independent predictor of subsequent mortality or transplantation.
Weinberg
Ellen O
EO
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.
Shimpo
Masahisa
M
Hurwitz
Shelley
S
Tominaga
Shin-ichi
S
Rouleau
Jean-Lucien
JL
Lee
Richard T
RT
D000293:Adolescent; D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use; D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain; D018377:Neurotransmitter Agents / Q000097:blood; D018384:Oxidative Stress; D011237:Predictive Value of Tests; D011446:Prospective Studies; D044469:Racial Groups; D011956:Receptors, Cell Surface; D012737:Sex Factors
D015415:Biomarkers; D002121:Calcium Channel Blockers; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008565:Membrane Proteins; D018377:Neurotransmitter Agents; D011956:Receptors, Cell Surface; D020097:Natriuretic Peptide, Brain; D017311:Amlodipine; D009320:Atrial Natriuretic Factor