N-terminal and C-terminal fragments of IGFBP-4 as novel biomarkers for short-term risk assessment of major adverse cardiac events in patients presenting with ischemia.
OBJECTIVE
Pregnancy Associated Plasma Protein A (PAPP-A)-derived N- and C-terminal fragments of IGF-binding protein-4 (NT- and CT-IGFBP-4) released from vulnerable atherosclerotic plaques are proposed to be used for cardiovascular risk assessment.


METHODS
NT- and CT-IGFBP-4 were measured by novel immunoassays in EDTA-plasma of 180 patients admitted to the emergency department with symptoms of myocardial ischemia but without ST-segment elevation. Six-month incidence of major adverse cardiac events (MACE), including myocardial infarction, cardiac death, percutaneous coronary interventions, and coronary artery bypass grafting was recorded.


RESULTS
Sixteen patients met the endpoint. NT- and CT-IGFBP-4 were strong predictors of MACE: area under ROC curve (AUC) 0.856 and 0.809, respectively. NT-IGFBP-4 concentrations≥214μg/L and CT-IGFBP-4 concentrations≥124μg/L were associated with increased risk of future MACE: adjusted hazard ratio 13.79 and 7.93, respectively.


CONCLUSIONS
IGFBP-4 fragments can be utilized as biomarkers for MACE prediction in patients with suspected myocardial ischemia.
HyTest Ltd, Intelligate 6th floor, Joukahaisenkatu 6, 20520 Turku, Finland. Alexander.Postnikov@hytest.fi
A B
AB
Postnikov
T I
TI
Smolyanova
A V
AV
Kharitonov
D V
DV
Serebryanaya
S V
SV
Kozlovsky
Y A
YA
Tryshina
R V
RV
Malanicev
A G
AG
Arutyunov
M M
MM
Murakami
F S
FS
Apple
A G
AG
Katrukha
D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000818:Animals; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D001026:Coronary Artery Bypass; D003429:Cross Reactions; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007118:Immunoassay; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000097:blood*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D008969:Molecular Sequence Data; D017202:Myocardial Ischemia / Q000175:diagnosis* / Q000473:pathology; D010446:Peptide Fragments / Q000097:blood*; D058226:Plaque, Atherosclerotic / Q000378:metabolism; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D059748:Proteolysis; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013997:Time Factors
D015415:Biomarkers; D018974:Insulin-Like Growth Factor Binding Protein 4; D010446:Peptide Fragments; D011266:Pregnancy-Associated Plasma Protein-A