Circulating Des-gamma-carboxy prothrombin is not associated with cardiovascular calcification or stiffness: The Multi-Ethnic Study of Atherosclerosis (MESA) (Danziger J et al.)

Atherosclerosis recently published a new study that examines the role of vitamin K-dependent protein (VKPD) activity in preventing cardiovascular calcification. While the study has its merits, it is believed flawed parameters and measurements produced negative results and that more study needs to be done.

Using an elevated ankle-brachial index (ABI) as a measure of medial vascular calcification, the authors performed a case-cohort analysis within the Multi-Ethnic Study of Atherosclerosis, measuring Desgamma-carboxy prothrombin (DCP) to estimate VKDP activity. In secondary analyses of the weighted subcohort, they examined the cross-sectional associations between DCP and prevalent vascular calcification of the coronary vessels, aortic and mitral valves, and aortic wall, and with vascular stiffness.

The results showed, in adjusted analysis, cases (n . 104) had 0.21 ng/ml (_0.94e0.52) lower DCP concentrations than the subcohort (n . 613). Furthermore, amongst the 717 participants in the weighted cohort, VKDP activity was not associated with coronary artery, mitral valve, aortic valve or aortic wall calcification, nor was it associated with vascular stiffness.

To that end, the authors conclude “Our negative results do not support a role of circulating VKDP activity in cardiovascular calcification in community-dwelling adults.”

However, Dr. Katarzyna Maresz, president of the International Science and Health Foundation, expressed that this study has a number of flaws that could mislead the public. For example, while this study identifies it examines VKDPs, it only looked at intakes of Vitamin K1, and not Vitamin K2, which was shown in The Rotterdam Study to correlate with improving high cardiovascular calcification and cardiovascular risk.

“Moreover, very interesting will be to see the activity of extrahepatic VKDP such as osteocalcin or dpucMGP, which will correlate with total vitamin K status,” says Dr. Maresz. “It is not surprising for me that hepatic VKDP, such as DCP, does not correlate with cardiovascular calcification or stiffness. The biologic function of DCP is not known. However, DCP is used as a marker of risk assessment of patients with chronic liver disease for development of hepatocellular carcinoma (HCC) and to evaluate K status in, for example, ‘kidney patients.’”

Further, she explains it has been shown before in the case of MGP, the only good marker to evaluate calcification is tucMGP and not, for example, dpucMGP, which correlated with K deficiency. Her opinion is it might be possible to find the correlation between tucMGP and calcification in this population.

“The paper’s conclusion can lead the reader to believe that all VKDP do not correlate with cardiovascular calcification or stiffness, which with huge probability is not true in the case of extrahepatic VKDP,” says Dr. Maresz.


Danziger J, Young RL, Shea KM, Duprez DA, Jacobs DR, Tracey RP, Joachim HI, Jenny NS, Mukamal KJ. Circulating Des-gamma-carboxy prothrombin is not associated with cardiovascular calcification or stiffness: The Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 252 (2016) 68-74.


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