Hack, C.E.

Krijnen, P.A.J.

Niessen, H.W.M.

DSpace at VU

Correspondence
Letter by Krijnen et al Regarding Article, “The
sPLA2 Inhibition to Decrease Enzyme Release
After Percutaneous Coronary Intervention
(SPIDER-PCI) Trial”
To the Editor:
Percutaneous coronary intervention (PCI) may induce a variable
amount of myocardial necrosis. It is now well accepted that in-
creased blood levels of the plasma inflammatory marker secretory
phospholipase A2 (sPLA2) correlate with cardiac injury in patients
undergoing PCI,1 and a role for sPLA2 in PCI-related cardiac injury
has been hypothesized. Using the sPLA2 inhibitor varespladib,
Dzavik et al2 tested this hypothesis in the sPLA2 Inhibition to
Decrease Enzyme Release after Percutaneous Coronary Intervention
(SPIDER-PCI) trial. However, their results did not support a cardio-
protective effect of varespladib in patients after PCI, as was
concluded from the course of plasma levels of creatine kinase-MB
and troponin I in patients undergoing PCI with or without sPLA2
inhibitor treatment.
However, we are not convinced that the patient cohort studied was
suitable to test the hypothesis that sPLA2 is involved in PCI-related
cardiac inflammatory injury. Unlike Liu et al,1 in this SPIDER-PCI
cohort, no increase in sPLA2 blood levels was recorded in the placebo
group, and only modest C-reactive protein responses were observed.
Hence, it can be argued that, although varespladib induced an almost
complete inhibition of circulating sPLA2 activity, the drug had no effect
on the release of markers of myonecrosis, because the inflammatory
damage to the heart was marginal in this patient cohort.
Dzavik et al refer to our previous studies for evidence of the
involvement of sPLA2 in cardiac injury.3,4 However, in these studies,
the cardiotoxic role of sPLA2 was investigated in relation to acute
myocardial infarction in which acute-phase blood levels of sPLA2
may increase 10- to 100-fold. For example, levels of this enzyme can
be 200 ng/mL 48 hours after the onset of infarction,5 which is in
sharp contrast to the levels of 2 to 7 ng/mL observed in the study by
Dzavik et al. Although we cannot exclude the possibility that sPLA2
in the levels described after PCI can have cardiotoxic effects, so far,
evidence for this is lacking.
Thus, although the study by Dzavik et al suggests a limited, if any,
cardioprotective role of sPLA2 inhibition in patients undergoing PCI
with normal plasma levels of the enzyme, the cardioprotective effect
of sPLA2 inhibition in patients with acute-phase levels remains to be
established. Hence, we suggest that the hypothesis on the cardiopro-
tective activity of sPLA2 inhibitors be tested in patients developing
an acute-phase response following PCI, or in patients with acute
myocardial infarction.
Disclosures
None.
Paul A.J. Krijnen, PhD
Department of Pathology
Institute for Cardiovascular Research
VU University Medical Center
Amsterdam, The Netherlands
C. Erik Hack, MD, PhD
Department of Immunology
University Medical Center Utrecht
Utrecht, The Netherlands
Hans W.M. Niessen, MD, PhD
Departments of Pathology and Cardiac Surgery
Institute for Cardiovascular Research
VU University Medical Center
Amsterdam, The Netherlands
References
1. Liu PY, Li YH, Tsai WC, Chao TH, Tsai LM, Wu HL, Chen JH.
Prognostic value and the changes of plasma levels of secretory type II
phospholipase A2 in patients with coronary artery disease undergoing
percutaneous coronary intervention. Eur Heart J. 2003;24:1824–1832.
2. Dzavik V, Lavi S, Thorpe K, Yip PM, Plante S, Ing D, Overgaard CB,
Osten MD, Lan J, Robbins K, Miner SE, Horlick EM, Cantor WJ. The
sPLA2 Inhibition to Decrease Enzyme Release After Percutaneous
Coronary Intervention (SPIDER-PCI) trial. Circulation. 2010;122:
2411–2418.
3. Nijmeijer R, Willemsen M, Meijer CJ, Visser CA, Verheijen RH, Gottlieb
RA, Hack CE, Niessen HW. Type II secretory phospholipase A2 binds to
ischemic flip-flopped cardiomyocytes and subsequently induces cell
death. Am J Physiol Heart Circ Physiol. 2003;285:H2218–H2224.
4. Van Dijk A, Krijnen PA, Vermond RA, Pronk A, Spreeuwenberg M,
Visser FC, Berney R, Paulus WJ, Hack CE, Van Milligen FJ, Niessen
HW. Inhibition of type 2A secretory phospholipase A2 reduces death of
cardiomyocytes in acute myocardial infarction. Apoptosis. 2009;14:
753–763.
5. Nijmeijer R, Lagrand WK, Baidoshvili A, Lubbers YT, Hermens WT,
Meijer CJ, Visser CA, Hack CE, Niessen HW. Secretory type II phos-
pholipase A(2) binds to ischemic myocardium during myocardial
infarction in humans. Cardiovasc Res. 2002;53:138–146.
(Circulation. 2011;124:e298.)
© 2011 American Heart Association, Inc.
Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.111.021683
e298


Letter by Krijnen et al regarding article, "The sPLA2 Inhibition to Decrease Enzyme Release after Percutaneous Coronary Intervention (SPIDER-PCI) trial".

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Paul A.J. Krijnen

C. Erik Hack

Hans W.M. Niessen

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Circulation

Letter by Krijnen et al Regarding Article, “The sPLA
            <sub>2</sub>
            Inhibition to Decrease Enzyme Release After Percutaneous Coronary Intervention (SPIDER-PCI) Trial”

Krijnen, P.A.

Niessen, H.W.

Utrecht University Repository

Letter by Krijnen et al regarding article, "The sPLA2 Inhibition to Decrease Enzyme Release after Percutaneous Coronary Intervention (SPIDER-PCI) trial".

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