Long-term warfarin therapy and biomarkers for osteoporosis and atherosclerosis

Sayaka Namba; Minako Yamaoka-Tojo; Takehiro Hashikata; Yuki Ikeda; Lisa Kitasato; Takuya Hashimoto; Takao Shimohama; Taiki Tojo; Naonobu Takahira; Takashi Masuda; Junya Ako

doi:10.1016/j.bbacli.2015.08.002

Long-term warfarin therapy and biomarkers for osteoporosis and atherosclerosis

BBA Clin. 2015 Aug 12:4:76-80. doi: 10.1016/j.bbacli.2015.08.002. eCollection 2015 Dec.

Authors

Affiliations

¹ Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.
² Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan ; Department of Rehabilitation, Kitasato University School of Allied Health Sciences, Sagamihara, Japan.
³ Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
⁴ Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan ; Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.

Abstract

Background: Stroke prevention by warfarin, a vitamin K antagonist, has been an integral part in the management of atrial fibrillation. Vitamin K-dependent matrix Gla protein (MGP) has been known as a potent inhibitor of arterial calcification and osteoporosis. Therefore, we hypothesized that warfarin therapy affects bone mineral metabolism, vascular calcification, and vascular endothelial dysfunction.

Methods: We studied 42 atrial fibrillation patients at high-risk for atherosclerosis having one or more coronary risk factors. Twenty-four patients had been treated with warfarin for at least 12 months (WF group), and 18 patients without warfarin (non-WF group). Bone alkaline phosphatase (BAP) and under carboxylated osteocalcin (ucOC) and receptor activator of nuclear factor-kappa B ligand (RANKL) were measured as bone metabolism markers. Reactive hyperemia-peripheral arterial tonometry (RH-PAT) index measured by Endo-PAT2000 was used as an indicator of vascular endothelial function.

Results: There were no significant differences in patient background characteristics and other clinical indicators between the two groups. In WF group, the ucOC levels were significantly higher than those in the non-WF group (10.3 ± 0.8 vs. 3.4 ± 0.9 ng/mL; P < 0.01), similarly, the RANKL levels in the WF group were higher than those in the non-WF group (0.60 ± 0.06 vs. 0.37 ± 0.05 ng/mL; P = 0.007). Moreover, RH-PAT index was significantly lower in the WF group compared to those in the non-WF group (1.48 ± 0.11 vs. 1.88 ± 0.12; P = 0.017).

Conclusions: Long-term warfarin therapy may be associated with bone mineral loss and vascular calcification in 60-80 year old hypertensive patients.

Keywords: BAP, bone alkaline phosphatase; BMD, bone mineral density; DXA, dual-energy X-ray absorptiometry; Gas-6, growth arrest specific protein 6; MGP, matrix Gla protein; OC, osteocalcin; Osteoporosis; RANKL; RANKL, receptor activator of nuclear factor-kappa B ligand; RH-PAT index; RH-PAT, reactive hyperemia-peripheral arterial tonometry; Vascular endothelial dysfunction; ucOC; ucOC, under carboxylated osteocalcin.