Risk stratification for heart failure and death in an acute coronary syndrome population using inflammatory cytokines and N-terminal pro-brain natriuretic peptide.
BACKGROUND
Inflammation in acute coronary syndrome (ACS) can identify those at greater long-term risks for heart failure (HF) and death. The present study assessed the performance of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) (cytokines involved in the activation and recruitment of leukocytes) in addition to known biomarkers [e.g., N-terminal pro-brain natriuretic peptide (NT-proBNP)] for predicting HF and death in an ACS population.


METHODS
In a cohort of 216 ACS patients, NT-proBNP (Elecsys; Roche) and IL-6, IL-8, and MCP-1 (evidence investigator; Randox) were measured in serial specimens collected early after symptom onset (n = 723). We collected at least 2 specimens from each participant: an early specimen (median 2 h; interquartile range 2-4 h) and a later specimen (9 h; 9-9 h), and used the later specimens' biomarker concentrations for risk stratification.


RESULTS
An increase in both IL-6 and NT-proBNP was observed but not for IL-8 or MCP-1 early after pain onset. Kaplan-Meier analysis demonstrated that individuals with increased NT-proBNP (>183 ng/L) or cytokines (IL-6 > 6.4 ng/L; above upper limit of normal for IL-8 or MCP-1) had a greater probability of death or HF in the following 8 years (P <0.05). In a Cox proportional hazard model adjusted for both CRP and troponin I, increased IL-6, MCP-1, and NT-proBNP remained significant risk factors. Combining all 3 biomarkers resulted in a higher likelihood ratio for death or HF than models restricted to any 2 of these biomarkers.


CONCLUSIONS
IL-6, MCP-1, and NT-proBNP are independent predictors of long-term risk of death or HF, highlighting the importance of identifying leukocyte activation and recruitment in ACS patients.
Kavsak
Peter A
PA
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. kavsakp@mcmaster.ca
Ko
Dennis T
DT
Newman
Alice M
AM
Palomaki
Glenn E
GE
Lustig
Viliam
V
MacRae
Andrew R
AR
Jaffe
Allan S
AS
D054058:Acute Coronary Syndrome / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality; D000368:Aged; D018932:Chemokine CCL2 / Q000097:blood*; D005260:Female; D006333:Heart Failure / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood*; D007962:Leukocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D016209:Interleukin-8; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain