Statins, vascular calcification, and vitamin K‐dependent proteins: Is there a relation?

Abstract

The present cross‐sectional clinical study aimed to examine the connection between statin exposure, coronary artery calcification (CAC), and vitamin K‐dependent proteins (VKDPs) in patients with cardiovascular (CV) conditions. Two groups of patients were studied: patients with established CV disease (CVD) and healthy patients at moderate risk for CVD (a control group). The groups were also split into statin users and non‐users. The following VKDPs were measured in plasma: uncarboxylated Matrix Gla‐protein (ucMGP), undercarboxylated (ucOC), and carboxylated osteocalcin (cOC), Gla‐rich protein (GRP). CAC score (CACS) was determined by multislice computed tomography. Among all the participants in the study, CACS was more pronounced in statin users compared to non‐users; the same was found also among the CVD patients and among the controls. While the levels of ucMGP and GRP did not differ between statin users and non‐users, ucOC and ucOC/cOC were significantly elevated in statin users, indicating vitamin K deficiency. There was a positive correlation between the levels of ucOC and CACS in the entire population and in the group of statin users, but not in statin non‐users. No association was found between ucMGP or GRP and CACS. Statins had also an impact on the international normalized ratio and interacted with vitamin K antagonists (VKAs). Our results are in agreement with the existing evidence about positive association between statins and vascular calcification. They enlighten to a certain extent the possible mechanisms through which statins may enhance calcium accumulation in arterial wall, namely, by inhibition of vitamin K dependent proteins and functions involved in vascular protection.