A proinflammatory monocyte response is associated with myocardial injury and impaired functional outcome in patients with ST-segment elevation myocardial infarction : Monocytes and myocardial infarction - 14/12/11

Doi : 10.1016/j.ahj.2011.09.002

Anja M. van der Laan, MD ^a,^{^{i
On behalf of the Hebe investigators.}}, Alexander Hirsch, MD, PhD ^a,^{^{i
On behalf of the Hebe investigators.}}, Lourens F.H.J. Robbers, MD ^b,^{^{i
On behalf of the Hebe investigators.}}, Robin Nijveldt, MD, PhD ^b,^{^{i
On behalf of the Hebe investigators.}}, Ingrid Lommerse ^c,^{^{i
On behalf of the Hebe investigators.}}, Ronak Delewi, MD ^a,^d,^{^{i
On behalf of the Hebe investigators.}}, Pieter A. van der Vleuten, MD, PhD ^e,^{^{i
On behalf of the Hebe investigators.}}, Bart J. Biemond, MD, PhD ^f,^{^{i
On behalf of the Hebe investigators.}}, Jaap Jan Zwaginga, MD, PhD ^c,^g,^{^{i
On behalf of the Hebe investigators.}}, Wim J. van der Giessen, MD, PhD ^h,^{^{i
On behalf of the Hebe investigators.},}^{^{j
In memoriam.}}, Felix Zijlstra, MD, PhD ^h,^{^{i
On behalf of the Hebe investigators.}}, Albert C. van Rossum, MD, PhD ^b,^{^{i
On behalf of the Hebe investigators.}}, Carlijn Voermans, PhD ^c,^{^{i
On behalf of the Hebe investigators.}}, C. Ellen van der Schoot, PhD ^c,^{^{i
On behalf of the Hebe investigators.}}, Jan J. Piek, MD, PhD ^a,^{^⁎,}^{^{i
On behalf of the Hebe investigators.}}
^a Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
^b Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands
^c Department of Experimental Immunohematology, Sanquin Research, and Landsteiner Laboratory, Amsterdam, The Netherlands
^d Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands
^e Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands
^f Department of Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
^g Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
^h Department of Cardiology, Erasmus University Medical Center, Rotterdam, The Netherlands

^⁎Reprint requests: Jan J. Piek, MD, PhD, Academic Medical Center, Department of Cardiology, Room B2-250, PO Box 22600, 1100 DD Amsterdam, The Netherlands.

Résumé

Background

In patients with ST-segment elevation myocardial infarction (STEMI), the importance of a well-balanced inflammatory reaction has been recognized for years. Monocytes play essential roles in regulating inflammation. Hence, we investigated the association between inflammatory characteristics of monocytes and myocardial injury and functional outcome in patients with STEMI.

Methods

Using flow cytometry, the levels of classical (CD14⁺⁺CD62L⁺) and nonclassical (CD14⁺CD62L⁻) monocytes were analyzed in peripheral blood in 58 patients with STEMI at a median of 5 days (4-6 days) after primary percutaneous coronary intervention. In addition, the monocytic expression of several surface molecules and formation of monocyte-platelet complexes were measured. All patients underwent cardiovascular magnetic resonance imaging at baseline and 4-month follow-up.

Results

At baseline, patients with high levels of classical monocytes had impaired left ventricular (LV) ejection fraction (P = .002), larger infarct size (P = .001), and, often, presence of microvascular obstruction (P = .003). At follow-up, high levels of classical monocytes were negatively associated with the regional systolic LV function independent of the transmural extent of infarction. In contrast, positive associations for the levels of nonclassical monocytes were observed. Finally, up-regulation of macrophage 1 by blood monocytes and increased formation of monocyte-platelet complexes were associated with enhanced myocardial injury at baseline and impaired LV function at follow-up.

Conclusions

This study shows an association between a proinflammatory monocyte response, characterized by high levels of classical monocytes, and severe myocardial injury and poor functional outcome after STEMI. Future studies are required to investigate the biologic nature of this association and therapeutic implications.

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Plan

Methods

Patient selection and study procedures

Characterization of monocytes by flow cytometry

Cardiovascular magnetic resonance protocol

Cardiovascular magnetic resonance data analysis and definitions

Statistical analysis

Results

Patient characteristics

High blood levels of classical monocytes are related to enhanced myocardial injury and impaired LV function at baseline and at follow-up

High blood levels of classical monocytes are associated with impaired recovery of the regional myocardial function independent of transmural extent of infarction

Expression of Mac-1 on monocytes and formation of monocyte-platelet complexes are related to myocardial injury and LV function at baseline and at follow-up

Discussion

Study limitations

The trial is financially supported by funds provided by the Interuniversity Cardiology Institute of the Netherlands and the Netherlands Heart Foundation (grant no. 2005T101) and by unrestricted grants from Biotronik, Boston Scientific, Guerbet, Abbott, Medtronic, Novartis, Pfizer, and Sanofi-Aventis.

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Vol 163 - N° 1

P. 57 - janvier 2012 Retour au numéro

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A proinflammatory monocyte response is associated with myocardial injury and impaired functional outcome in patients with ST-segment elevation myocardial infarction : Monocytes and myocardial infarction - 14/12/11

Résumé

Background

Methods

Results

Conclusions

Plan

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