OC 32.2 - Pleiotropic influence of rosuvastatin on apolipoproteins and their association with coagulation factor levels: results from the START trial

Monday, July 11, 2022

11:00 AM – 11:15 AM

Location: ExCel Center, S11B

Presentation Format: In-Person

Presenting Author(s)

Eleonora Camilleri, MD

MD PhD student
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
Leiden, Zuid-Holland, Netherlands

Co-Author(s)

Nienke van Rein, PharmD PhD

Post doc, PhD PharmD
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
Leiden, Zuid-Holland, Netherlands
Bv

Bart J.M. van Vlijmen

Associate professor
Department of Internal Medicine, Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Leiden, Zuid-Holland, Netherlands
JB

Joseph S. Biedermann

MD PhD
Department of Haematology, Erasmus MC, Erasmus University Medical Center, Rotterdam, the Netherlands
Rotterdam, Zuid-Holland, Netherlands
MK

Marieke J.H.A. Kruip

Associate professor, hematologist, MD, PhD
Department of Hematology, Erasmus MC, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
Frank W.G. Leebeek, MD, PhD

Professor and Head of Department of Hematology
Erasmus MC, University Medical Center Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
Fv

Felix van der Meer

MD, PhD
Department of Thrombosis and Hemostasis, Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands
Christa M. Cobbaert, PhD

Professor
,Leiden University Medical Center, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands
SC

Suzanne C. Cannegieter, MD PhD

Professor
Department of Clinical Epidemiology, Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands
WL

Willem Lijfering

Associate Professor
Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands

Background: Rosuvastatin decreases coagulation factors (F), among which FVIII, in venous thrombosis patients, but the mechanism is unknown. Apolipoproteins, which are responsible for the lipoprotein metabolism, may mediate this decrease through shared mechanisms of synthesis or regulatory pathways, as they have been associated with coagulation factors levels.

Aims: To investigate whether apolipoproteins are associated with statin-related decrease of coagulation factors.

Methods: We measured levels of serum apolipoproteins (apo)A-I, A-II, A-IV, (a), B-100, C-I, C-II, C-III and E and plasma coagulation factors (FVII, FVIII, FIX, FXI, von Willebrand factor[vWF]) in 126 patients randomized to 28 days of rosuvastatin use from the STAtin Reduces Thrombophilia trial. We studied the association between apolipoproteins and coagulation factor at baseline and the mean difference of apolipoprotein levels between baseline and day 28. We also determined the association between coagulation factor changes and the changes between apolipoprotein levels caused by rosuvastatin use (day 28 minus baseline) and adjusted for potential confounders (age, sex, body mass index). We estimated mean differences and 95% confidence intervals (CIs) using linear regression.

Results: At baseline, levels of all apolipoproteins, except apo(a), were positively associated with FVII, FIX and FXI. Apolipoprotein levels, except for apoA-I, (a) and A-IV, had decreased after rosuvastatin use (Figure 1). ApoB-100 showed the biggest decrease of -0.43g/L (95%CI -0.46 to -0.40). Decreasing apoA-IV, C-I and C-III levels were associated with decreasing FVII levels, whereas decreasing apoA-II and B-100 was associated with FXI decrease (Table 1). In contrast, apolipoprotein decrease was not associated with a FVIII and vWF decrease.

Conclusion(s): Rosuvastatin decreased the level of several apolipoproteins. This decrease was associated only with the decrease of liver-derived coagulation factors FVII and FXI and not with FVIII/vWF, while the latter two showed the biggest decrease during rosuvastatin treatment. This suggests that rosuvastatin might decrease coagulation factors through other mechanisms than via apolipoproteins.