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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 Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada.
⁶ Cardiovascular Division and Division of Laboratory Medicine, Mayo Clinic, Rochester, MN.

^aAddress correspondence to this author at: Hamilton Regional Laboratory Medicine Program, Henderson General Hospital (Core Laboratory Section), 711 Concession St. Hamilton, Ontario, Canada L8V 1C3. Fax 905-575-2581; 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: 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.

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 and recruitment in ACS patients.

The following articles in journals at HighWire Press have cited this article:

				P. A. Kavsak and A. S. Jaffe Peripheral Blood Monocyte Subset Assessment in Non-ST-Segment Elevation Myocardial Infarction Is Required J. Am. Coll. Cardiol., January 12, 2010; 55(2): 169 - 169. [Full Text] [PDF]

				E. Shantsila and G. Y.H. Lip Reply J. Am. Coll. Cardiol., January 12, 2010; 55(2): 170 - 171. [Full Text] [PDF]

				T. Imanishi, H. Tsujioka, and T. Akasaka Reply J. Am. Coll. Cardiol., January 12, 2010; 55(2): 169 - 170. [Full Text] [PDF]

				P. A. Kavsak, A. M. Newman, D. T. Ko, G. E. Palomaki, V. Lustig, A. R. MacRae, and A. S. Jaffe Is a Pattern of Increasing Biomarker Concentrations Important for Long-Term Risk Stratification in Acute Coronary Syndrome Patients Presenting Early after the Onset of Symptoms? Clin. Chem., April 1, 2008; 54(4): 747 - 751. [Abstract] [Full Text] [PDF]