Increased Peripheral Arterial Calcification in Patients Receiving Warfarin (Han KH and O’Neill WC)

Matrix Gla Protein (MGP) is a vitamin K-dependent protein that is considered the one of the greatest modulators of arterial calcification, a common cardiovascular disease associated with poorer health outcomes. The role of MGP has raised concerns about possible effects of warfarin on vascular calcification in humans

Researchers Han and O’Neill recently demonstrated a 50% increase in prevalence that was independent of other cardiovascular risk factors in a large cohort of women with current or past warfarin use. This new retrospective-matched, cohort study was designed to test the hypothesis that use of warfarin is associated with increased arterial calcification in the lower extremities and in men.

To demonstrate that the results are generalizable to other arteries and to men, researchers performed a similar study of arterial calcification in lower extremities detected on standard radiographs. This study assessed 430 patients with radiographs performed during or after warfarin therapy. Each patient was matched to a patient without warfarin exposure based on age, sex, and diabetes status. Radiographs were reviewed visually for arterial calcification.

The prevalence of arterial calcification was 44% greater in patients with versus without warfarin use (30.2% versus 20.9%, P=0.0023), but not on radiographs performed before warfarin therapy (26.4% versus 22.4%, n=156) or prior to 5 years of warfarin therapy. The increase was noted only in the ankle and foot, was limited to a medial pattern of calcification, and was similar in men and women.

The results demonstrated a greater prevalence of peripheral arterial calcification in patients receiving warfarin. These results proved that the association of warfarin use with vascular calcification is present in men as well as women. The effect of warfarin was similar to the 50% increase observed previously in breast arterial calcification and was dependent on duration, with only durations of >5 years showing an increased prevalence of peripheral arterial calcification. The prevalence of arterial calcification was much lower in patients aged 60 years.

The researchers concluded, “Warfarin use is associated with lower extremity arterial calcification in both men and women independent of age, sex, diabetes status, and other patient characteristics. This may have implications for the choice of therapies for long-term anticoagulation.”


Han KH, O’Neill WC. Increased Peripheral Arterial Calcification in Patients Receiving Warfarin. J Am Heart Assoc. 2016;5:e002665 doi: 10.1161/JAHA.115.002665.

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