Interleukin-6 and the risk of adverse outcomes in patients after an acute coronary syndrome

Observations from the SOLID-TIMI 52 (stabilization of plaque using darapladib-thrombolysis in myocardial infarction 52) trial

Christina L. Fanola, David A. Morrow, Christopher P. Cannon, Petr Jarolim, Mary Ann Lukas, Christoph Bode, Judith S. Hochman, Erica L. Goodrich, Eugene Braunwald, Michelle L. O'Donoghue

Research output: Contribution to journalArticle

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Abstract

Background-Interleukin-6 (IL-6) is an inflammatory cytokine implicated in plaque instability in acute coronary syndrome (ACS). We aimed to evaluate the prognostic implications of IL-6 post-ACS. Methods and Results-IL-6 concentration was assessed at baseline in 4939 subjects in SOLID-TIMI 52 (Stabilization of Plaque Using Darapladib-Thrombolysis in Myocardial Infarction 52), a randomized trial of darapladib in patients ≤30 days from ACS. Patients were followed for a median of 2.5 years for major adverse cardiovascular events; cardiovascular death, myocardial infarction, or stroke) and cardiovascular death or heart failure hospitalization. Primary analyses were adjusted first for baseline characteristics, days from index ACS, ACS type, and randomized treatment arm. For every SD increase in IL-6, there was a 10% higher risk of major adverse cardiovascular events (adjusted hazard ratio [adj HR] 1.10, 95% confidence interval [CI] 1.01-1.19) and a 22% higher risk of cardiovascular death or heart failure (adj HR 1.22, 95% CI 1.11-1.34). Patients in the highest IL-6 quartile had a higher risk of major adverse cardiovascular events (adj HR Q4:Q1 1.57, 95% CI 1.22-2.03) and cardiovascular death or heart failure (adj HR 2.29, 95% CI 1.6-3.29). After further adjustment for biomarkers (high-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2 activity, high-sensitivity troponin I, and B-type natriuretic peptide), IL-6 remained significantly associated with the risk of major adverse cardiovascular events (adj HR Q4:Q1 1.43, 95% CI 1.09-1.88) and cardiovascular death or heart failure (adj HR 1.79, 95% CI 1.22-2.63).Conclusions-In patients after ACS, IL-6 concentration is associated with adverse cardiovascular outcomes independent of established risk predictors and biomarkers. These findings lend support to the concept of IL-6 as a potential therapeutic target in patients with unstable ischemic heart disease.

Original languageEnglish (US)
Article numbere005637
JournalJournal of the American Heart Association
Volume6
Issue number10
DOIs
StatePublished - Oct 1 2017

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Acute Coronary Syndrome
Interleukin-6
Myocardial Infarction
Confidence Intervals
Heart Failure
Biomarkers
1-Alkyl-2-acetylglycerophosphocholine Esterase
Troponin I
darapladib
Brain Natriuretic Peptide
C-Reactive Protein
Myocardial Ischemia
Hospitalization
Cytokines
Therapeutics

Keywords

  • Acute coronary syndrome
  • Atherosclerosis
  • Biomarker
  • Inflammation
  • Vascular biology

Cite this

Interleukin-6 and the risk of adverse outcomes in patients after an acute coronary syndrome : Observations from the SOLID-TIMI 52 (stabilization of plaque using darapladib-thrombolysis in myocardial infarction 52) trial. / Fanola, Christina L.; Morrow, David A.; Cannon, Christopher P.; Jarolim, Petr; Lukas, Mary Ann; Bode, Christoph; Hochman, Judith S.; Goodrich, Erica L.; Braunwald, Eugene; O'Donoghue, Michelle L.

In: Journal of the American Heart Association, Vol. 6, No. 10, e005637, 01.10.2017.

Research output: Contribution to journalArticle

Fanola, Christina L. ; Morrow, David A. ; Cannon, Christopher P. ; Jarolim, Petr ; Lukas, Mary Ann ; Bode, Christoph ; Hochman, Judith S. ; Goodrich, Erica L. ; Braunwald, Eugene ; O'Donoghue, Michelle L. / Interleukin-6 and the risk of adverse outcomes in patients after an acute coronary syndrome : Observations from the SOLID-TIMI 52 (stabilization of plaque using darapladib-thrombolysis in myocardial infarction 52) trial. In: Journal of the American Heart Association. 2017 ; Vol. 6, No. 10.
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title = "Interleukin-6 and the risk of adverse outcomes in patients after an acute coronary syndrome: Observations from the SOLID-TIMI 52 (stabilization of plaque using darapladib-thrombolysis in myocardial infarction 52) trial",
abstract = "Background-Interleukin-6 (IL-6) is an inflammatory cytokine implicated in plaque instability in acute coronary syndrome (ACS). We aimed to evaluate the prognostic implications of IL-6 post-ACS. Methods and Results-IL-6 concentration was assessed at baseline in 4939 subjects in SOLID-TIMI 52 (Stabilization of Plaque Using Darapladib-Thrombolysis in Myocardial Infarction 52), a randomized trial of darapladib in patients ≤30 days from ACS. Patients were followed for a median of 2.5 years for major adverse cardiovascular events; cardiovascular death, myocardial infarction, or stroke) and cardiovascular death or heart failure hospitalization. Primary analyses were adjusted first for baseline characteristics, days from index ACS, ACS type, and randomized treatment arm. For every SD increase in IL-6, there was a 10{\%} higher risk of major adverse cardiovascular events (adjusted hazard ratio [adj HR] 1.10, 95{\%} confidence interval [CI] 1.01-1.19) and a 22{\%} higher risk of cardiovascular death or heart failure (adj HR 1.22, 95{\%} CI 1.11-1.34). Patients in the highest IL-6 quartile had a higher risk of major adverse cardiovascular events (adj HR Q4:Q1 1.57, 95{\%} CI 1.22-2.03) and cardiovascular death or heart failure (adj HR 2.29, 95{\%} CI 1.6-3.29). After further adjustment for biomarkers (high-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2 activity, high-sensitivity troponin I, and B-type natriuretic peptide), IL-6 remained significantly associated with the risk of major adverse cardiovascular events (adj HR Q4:Q1 1.43, 95{\%} CI 1.09-1.88) and cardiovascular death or heart failure (adj HR 1.79, 95{\%} CI 1.22-2.63).Conclusions-In patients after ACS, IL-6 concentration is associated with adverse cardiovascular outcomes independent of established risk predictors and biomarkers. These findings lend support to the concept of IL-6 as a potential therapeutic target in patients with unstable ischemic heart disease.",
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AU - Fanola, Christina L.

AU - Morrow, David A.

AU - Cannon, Christopher P.

AU - Jarolim, Petr

AU - Lukas, Mary Ann

AU - Bode, Christoph

AU - Hochman, Judith S.

AU - Goodrich, Erica L.

AU - Braunwald, Eugene

AU - O'Donoghue, Michelle L.

PY - 2017/10/1

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N2 - Background-Interleukin-6 (IL-6) is an inflammatory cytokine implicated in plaque instability in acute coronary syndrome (ACS). We aimed to evaluate the prognostic implications of IL-6 post-ACS. Methods and Results-IL-6 concentration was assessed at baseline in 4939 subjects in SOLID-TIMI 52 (Stabilization of Plaque Using Darapladib-Thrombolysis in Myocardial Infarction 52), a randomized trial of darapladib in patients ≤30 days from ACS. Patients were followed for a median of 2.5 years for major adverse cardiovascular events; cardiovascular death, myocardial infarction, or stroke) and cardiovascular death or heart failure hospitalization. Primary analyses were adjusted first for baseline characteristics, days from index ACS, ACS type, and randomized treatment arm. For every SD increase in IL-6, there was a 10% higher risk of major adverse cardiovascular events (adjusted hazard ratio [adj HR] 1.10, 95% confidence interval [CI] 1.01-1.19) and a 22% higher risk of cardiovascular death or heart failure (adj HR 1.22, 95% CI 1.11-1.34). Patients in the highest IL-6 quartile had a higher risk of major adverse cardiovascular events (adj HR Q4:Q1 1.57, 95% CI 1.22-2.03) and cardiovascular death or heart failure (adj HR 2.29, 95% CI 1.6-3.29). After further adjustment for biomarkers (high-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2 activity, high-sensitivity troponin I, and B-type natriuretic peptide), IL-6 remained significantly associated with the risk of major adverse cardiovascular events (adj HR Q4:Q1 1.43, 95% CI 1.09-1.88) and cardiovascular death or heart failure (adj HR 1.79, 95% CI 1.22-2.63).Conclusions-In patients after ACS, IL-6 concentration is associated with adverse cardiovascular outcomes independent of established risk predictors and biomarkers. These findings lend support to the concept of IL-6 as a potential therapeutic target in patients with unstable ischemic heart disease.

AB - Background-Interleukin-6 (IL-6) is an inflammatory cytokine implicated in plaque instability in acute coronary syndrome (ACS). We aimed to evaluate the prognostic implications of IL-6 post-ACS. Methods and Results-IL-6 concentration was assessed at baseline in 4939 subjects in SOLID-TIMI 52 (Stabilization of Plaque Using Darapladib-Thrombolysis in Myocardial Infarction 52), a randomized trial of darapladib in patients ≤30 days from ACS. Patients were followed for a median of 2.5 years for major adverse cardiovascular events; cardiovascular death, myocardial infarction, or stroke) and cardiovascular death or heart failure hospitalization. Primary analyses were adjusted first for baseline characteristics, days from index ACS, ACS type, and randomized treatment arm. For every SD increase in IL-6, there was a 10% higher risk of major adverse cardiovascular events (adjusted hazard ratio [adj HR] 1.10, 95% confidence interval [CI] 1.01-1.19) and a 22% higher risk of cardiovascular death or heart failure (adj HR 1.22, 95% CI 1.11-1.34). Patients in the highest IL-6 quartile had a higher risk of major adverse cardiovascular events (adj HR Q4:Q1 1.57, 95% CI 1.22-2.03) and cardiovascular death or heart failure (adj HR 2.29, 95% CI 1.6-3.29). After further adjustment for biomarkers (high-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2 activity, high-sensitivity troponin I, and B-type natriuretic peptide), IL-6 remained significantly associated with the risk of major adverse cardiovascular events (adj HR Q4:Q1 1.43, 95% CI 1.09-1.88) and cardiovascular death or heart failure (adj HR 1.79, 95% CI 1.22-2.63).Conclusions-In patients after ACS, IL-6 concentration is associated with adverse cardiovascular outcomes independent of established risk predictors and biomarkers. These findings lend support to the concept of IL-6 as a potential therapeutic target in patients with unstable ischemic heart disease.

KW - Acute coronary syndrome

KW - Atherosclerosis

KW - Biomarker

KW - Inflammation

KW - Vascular biology

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