Undercarboxylated Osteocalcin Is a Biomarker of Carotid Calcification in Patients with Essential Hypertension

Abstract

The development of vascular calcification is an active, highly regulated process with similarities to bone formation. Osteocalcin (OC), a vitamin K-dependent protein expressed by osteoblasts, contains 3 γ-carboxyglutamic acid residues derived from the vitamin K-dependent posttranslational modification of glutamic acid residues. Circulating undercarboxylated OC (ucOC) is increased in vitamin K deficiency and serum ucOC is reported to be a clinical marker of vitamin K status. Vitamin K deficiency is associated with vascular calcification as well as osteoporosis. We evaluated the relationship between ucOC and carotid artery calcification in 92 patients with essential hypertension. Ultrasound of the common carotid artery was performed to identify vascular calcification and subjects were divided into 2 groups: a calcification (+) group and a calcification (–) group. Serum creatinine and ucOC levels were higher in the calcification (+) group than in the calcification (–) group and serum ucOC correlated with serum creatinine. To identify the independent determinant factor for carotid artery calcification, we applied both ucOC and estimated glomerular filtration rate as independent factors in logistic regression analysis. Serum ucOC was an independent determinant of carotid calcification, suggesting that circulating ucOC may be an important biomarker of carotid artery calcification.

Serum levels of undercarboxylated osteocalcin are related to cardiovascular risk factors in patients with type 2 diabetes mellitus and healthy subjects

“…These data suggest that serum levels of ucOC could be related to CVRF in both HS and T2D patients. These findings agree with the higher ucOC serum levels found by Okura et al[35] in hypertensive patients with carotid calcification than in those without carotid calcification, suggesting that ucOC might be a potential biomarker for carotid artery calcification. Our work also agrees with the results published by Kanazawa et al[23] who found that total serum OC concentration was negatively associated with atherosclerotic parameters (intima-media thickness and ankle-brachial pulse-wave velocity) independent of other CVRF in diabetic men.…”

Association between the Circulating Total Osteocalcin Level and the Development of Cardiovascular Disease in Middle-aged Men: A Mean 8.7-year Longitudinal Follow-up Study

“…The percentage of CD34 /KDR and CD34 /CD133 / KDR endothelial progenitor cells costaining for osteocalcin has been reported to be significantly increased in patients with severe multi-vessel coronary artery disease as well as those with normal coronary arteries with endothelial dysfunction compared to that observed in control patients 28) . Furthermore, another study reported that the undercarboxylated osteocalcin levels were higher in the common carotid artery calcification group than in non-calcification group among 92 patients with essential hypertension 29) . Collectively, there may be a link between osteocalcin and atherosclerosis and/or vascular calcification.…”

Osteocalcin, Vascular Calcification, and Atherosclerosis: A Systematic Review and Meta-analysis

“…OC was measured using luminometry in one study (63). ucOC was measured in five studies (22, 31, 32, 41, 44), cOC in one study (44), and total OC was measured in the remaining studies (Table 1). OC positive mononuclear cells, endothelial progenitor cells (EPCs), or osteoprogenitor cells (OPCs) were examined by seven studies (37, 38, 40, 42, 52, 61, 62).…”

“…In seven studies that measured ucOC and markers of atherosclerosis or calcification, two positive outcomes were reported (31, 32), three negative outcomes (22, 29), and four non-significant outcomes (41, 44, 60). Fifty-four percent of studies did not adjust for any confounding variables (Table 1).…”