Statins, vascular calcification, and vitamin K-dependent proteins: Is there a relation (Zhelyazkova-Savova MD et al.)

The Kaohsiung Journal of Medical Sciences has recently published results of a cross-sectional clinical study that aimed to investigate a probable relation between statin use, coronary calcification, and the vitamin K dependent proteins as a possible mechanism mediating their pro‐calcific action. Based on clinical evidence about efficacy and safety, statins are used on a large scale as first-line therapy in the prevention and treatment of an established atherosclerotic cardiovascular disease. However, heated disputes on safety issues in social media have been raised in the aftermath of finding that intensive statin therapy may increase vascular calcification and accelerate its progression.

Statins are a common recommendation for lowering LDL-C (cholesterol) levels, and their use has been on the rise over the last few decades, even though it is widely known that statins may act as “mitochondrial toxins” with negative effects on the heart and blood vessels not only via the depletion of coenzyme Q10 (CoQ10), but also by inhibiting the synthesis of vitamin K2, the cofactor for matrix Gla-protein activation, which in turn protects arteries from calcification. The authors of this study enrolled 98 patients for the purpose of their enquiry, including those with established CV disease (CVD) and healthy patients at moderate risk for CVD (a control group). The groups were further split into statin users and non‐users. The results revealed that both the presence of CVD and statin use are independently and significantly associated with vascular calcification. Among all the participants in the study, coronary artery calcification score (CACS) was more pronounced in statin users compared to non‐users; the same was found also among the CVD patients and among the controls.

Moreover, the researchers found that statins influenced vitamin K status represented by the activation of osteocalcin (OC), which is vitamin K dependent protein. Inactive OC as well as the ratio of inactive and active form of OC were significantly elevated in statin users, indicating vitamin K deficiency. Statins had also an impact on the international normalized ratio and interacted with vitamin K antagonists.

The authors arrived at a conclusion that their 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.”

“According to this study statins negatively influence vitamin K status. So supplementation with vitamin K2, which can effectively improve vitamin K status and activate extrahepatic vitamin K dependent proteins, might be highly beneficial for statin users,” says Dr. Katarzyna Maresz, president of the International Science and Health Foundation. “Such a recommendation needs to consider by the medical community.”


Zhelyazkova-Savova, MD, Yotov, YT, Nikolova, MN, et al. Statins, vascular calcification, and vitamin K-dependent proteins: Is there a relation? Kaohsiung J Med Sci. 2021; 1– 8.

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