Risk stratification for heart failure and death in an acute coronary syndrome population using inflammatory cytokines and N-terminal pro-brain natriuretic peptide

Peter A. Kavsak, Dennis Ko, Alice M. Newman, Glenn E. Palomaki, Viliam Lustig, Andrew R. MacRae, Allan S Jaffe

Research output: Contribution to journalArticle

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Abstract

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 probrain 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. Conclusion: IL-6, MCP-1, and NT-proBNP are independent predictors of long-term risk of death or HF, high-lighting the importance of identifying leukocyte activation and recruitment in ACS patients.

Original languageEnglish (US)
Pages (from-to)2112-2118
Number of pages7
JournalClinical Chemistry
Volume53
Issue number12
DOIs
StatePublished - Dec 2007

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Natriuretic Peptides
Chemokine CCL2
Brain Natriuretic Peptide
Acute Coronary Syndrome
Interleukin-6
Heart Failure
Biomarkers
Cytokines
Interleukin-8
Population
Leukocytes
Chemical activation
Troponin I
Kaplan-Meier Estimate
Lighting
Proportional Hazards Models
Hazards
Research Personnel
Inflammation
Pain

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Risk stratification for heart failure and death in an acute coronary syndrome population using inflammatory cytokines and N-terminal pro-brain natriuretic peptide. / Kavsak, Peter A.; Ko, Dennis; Newman, Alice M.; Palomaki, Glenn E.; Lustig, Viliam; MacRae, Andrew R.; Jaffe, Allan S.

In: Clinical Chemistry, Vol. 53, No. 12, 12.2007, p. 2112-2118.

Research output: Contribution to journalArticle

Kavsak, Peter A. ; Ko, Dennis ; Newman, Alice M. ; Palomaki, Glenn E. ; Lustig, Viliam ; MacRae, Andrew R. ; Jaffe, Allan S. / Risk stratification for heart failure and death in an acute coronary syndrome population using inflammatory cytokines and N-terminal pro-brain natriuretic peptide. In: Clinical Chemistry. 2007 ; Vol. 53, No. 12. pp. 2112-2118.
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T1 - Risk stratification for heart failure and death in an acute coronary syndrome population using inflammatory cytokines and N-terminal pro-brain natriuretic peptide

AU - Kavsak, Peter A.

AU - Ko, Dennis

AU - Newman, Alice M.

AU - Palomaki, Glenn E.

AU - Lustig, Viliam

AU - MacRae, Andrew R.

AU - Jaffe, Allan S

PY - 2007/12

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N2 - 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 probrain 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. Conclusion: IL-6, MCP-1, and NT-proBNP are independent predictors of long-term risk of death or HF, high-lighting the importance of identifying leukocyte activation and recruitment in ACS patients.

AB - 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 probrain 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. Conclusion: IL-6, MCP-1, and NT-proBNP are independent predictors of long-term risk of death or HF, high-lighting the importance of identifying leukocyte activation and recruitment in ACS patients.

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