Received on April 19, 2007
Accepted on September 17, 2007

Proteomics and Protein Markers

Risk Stratification for Heart Failure and Death in An Acute Coronary Syndrome Population Using Inflammatory Cytokines and N-Terminal Pro-Brain Natriuretic Peptide

¹ Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
² Institute for Clinical Evaluative Sciences, University of Toronto, Toronto, Ontario, Canada
³ Department of Pathology, Women and Infants Hospital, Providence, RI
⁴ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
⁵ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada, and Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada
⁶ Cardiovascular Division and Division of Laboratory Medicine, Mayo Clinic, Rochester, MN

^* To whom correspondence should be addressed. E-mail: kavsakp{at}mcmaster.ca.

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^TM; 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: Both IL-6 and NT-proBNP, but not IL-8 or MCP-1, were increased in the early samples after onset of symptoms. 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.

Conclusion: 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 or recruitment in ACS patients.