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The complex of activated protein C and Protein C inhibitor (APC-PCI)
in diabetics treated with atorvastatin.

C. Kluft, CJM van Leuven, P. Meijer, MA van de Ree, HMG. Princen, MV.Huisman on Behalf of the Dali-study
Good Biomarker Sciences,. Department of General Internal Medicine, Leiden University Medical Centre, TNO-Quality of
Life, Leiden, The Netherlands.


b) Atorvastatin effect on APC-PCI and s-TM
In steady state, the complex of activated protein C and Protein C inhibitor (APC-PCI) is considered to reflect the formation of activated protein C. We studied whether or not APC-PCI is related to diabetic or inflammation markers of the liver and endothelium and to fibrinolysis variables. In addition the effect of atorvastatin treatment was Figure 2A,B: % Changes in APC-PCI (A) and s-TM (B) for 3 dose groups: placebo, 10 and 80 mg atorvastatin A total of 24 type II diabetics (m/v 50/50) without manifest cardiovascular disease, mean age 59 y, mean Six month placebo, 10 or 80 mg atorvastatin BMI 31 were studied (DALI-study 1). APC-PCI was resulted in median changes in APC-PCI of +3%; -9% measured by EIA (Bioporto Diagnostics, Sweden). (n.s) and -12% (p= 0.012, Wilcoxon signed ranks Results
s-TM changed: -4.05% ; +2.3 (p=0.01) and + 5.2 % a) Baseline metabolic correlations for APC-PCI
APC-PCI is normally distributed: Mean (SD) 0.63 c) Further haemostatic changes.
No correlation with: • age and gender (σ²<6%) • lipids (LDL; HDL; TG; FFA; apoA , B ; σ²<6%) • endothelial markers: s-VCAM, s-selectin, vWF, Negative correlation with fibrinogen: Figure 3A,B. Associations between changes in s-TM,
APC-PCI, d-dimer 1, and PAI-1 1 analysed by
association (figA: σ²) and factor analysis (fig B).
The data in figure 3 indicate that associations between
changes follow two mechanisms.
Figure 3 suggests that the changes follow the model: Figure 1: pre-treatment fibrinogen vs APC-PCI The negative correlation with fibrinogen is supported by negative trends for IL-6 and SAA (σ²>10%). This collectively indicates reduced thrombin formation.
decreased thrombin formation. Increase in s-TM • By another mechanism fibrinolysis is enhanced.

It is suggested that reduced coagulation and increased fibrinolysis collectively associate with the reduced Szczeklik et al. JACC 33(1999) 1286 and Dangas et al. AJC 84(1999) 639 venous thrombosis rate under statin treatment Lind et al. Arch Intern Med 169 (2009) 1210.


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INTERNATIONAL HEADACHE SOCIETY Company limited by guarantee, registered in England no.2988368 The International Classification of Headache Disorders 2nd Edition (1st revision, May 2005) Abbreviated pocket version for reference by professional users only, prepared by the Headache Classification Subcommittee of the International Headache Society Hans-Christoph Diene

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