Relation of Serum Osteocalcin Level to Risk of Coronary Heart Disease in Chinese Adults

doi:10.1016/j.amjcard.2010.07.013

The American Journal of Cardiology

Volume 106, Issue 10, 15 November 2010, Pages 1461-1465

https://doi.org/10.1016/j.amjcard.2010.07.013 Get rights and content

Osteocalcin, a bone-derived polypeptide, was recently found to have hormonal function associated with metabolic disorders and atherosclerosis. Few studies have examined the association between circulating osteocalcin and coronary heart disease (CHD) risk. The aim of the present study was to investigate whether serum osteocalcin concentration was associated with CHD risk and metabolic profiles in Chinese adults. A total of 461 subjects (243 with CHD and 218 without CHD) who underwent coronary angiography were included. Serum osteocalcin, glucose, lipid profiles, and other biochemical markers were measured. Severity of coronary atherosclerosis was estimated by number of diseased vessels. Results showed that serum osteocalcin levels were significantly lower in the CHD group (12.2 ng/ml, 9.5 to 15.1) than in the non-CHD group (13.6 ng/ml, 10.7 to 18.0, p = 0.001) and were significantly decreased with the increasing of number of diseased vessels (p = 0.005). Serum osteocalcin concentration was inversely correlated with fasting and post load 2 hour plasma glucose and hemoglobin A_1c (p = 0.044, 0.043, and 0.011, respectively), adjusting for CHD status. Odds ratios (95% confidence intervals) of CHD across increasing quartiles of serum osteocalcin were 0.68 (0.42 to 1.12), 0.59 (0.36 to 0.98), and 0.40 (0.23 to 0.69). The test for trend was significant (p = 0.0007). Adjusting for age, body mass index, and other conventional risk factors for CHD did not appreciably change the results. Spline regression analyses indicated a linear relation between serum osteocalcin level and CHD risk. In conclusion, our data indicate that serum osteocalcin level was associated with decreased risk of CHD and protective metabolic changes in Chinese adults.

Section snippets

Methods

The present study included 461 consecutive patients (299 men and 162 women, age ranges 39 to 84 and 41 to 85 years, means 61.7 and 63.3, respectively) who were referred to the department of cardiology in Ruijin Hospital (Shanghai, China) because of symptoms in the chest such as chest pain, chest heaviness, periodic discomfort, and palpitations from January 2005 to December 2007. In all subjects, coronary angiography for diagnosis of CHD was performed. Those with medical illnesses such as acute

Results

Clinical characteristics of the CHD and non-CHD groups are listed in Table 1. Of participants included in this study, 243 (53%) were found to have CHD and 218 (47%) were found not to have CHD. Smoking history, alcohol use, type 2 diabetes percentage, HbA_1c, post load 2h serum insulin, and high-sensitivity C-reactive protein levels were significantly higher in the CHD group than in the non-CHD group (different at p ≤0.05).

Serum osteocalcin levels in the CHD group were significantly lower (12.2

Discussion

The present study for the first time evaluated associations of serum osteocalcin level with direct parameters of atherosclerosis and metabolic phenotype in Chinese adult patients who underwent coronary angiography. We found a significant association between serum osteocalcin level and a decreased risk of CHD. We also found that number of stenotic coronary arteries was associated with decreasing serum osteocalcin levels.

Our present findings are in accordance with a recent study by Kanazawa et al

References (24)

P. von der Recke et al.
The association between low bone mass at the menopause and cardiovascular mortality
Am J Med
(1999)
N.K. Lee et al.
Endocrine regulation of energy metabolism by the skeleton
Cell
(2007)
J.A. Im et al.
Relationship between osteocalcin and glucose metabolism in postmenopausal women
Clin Chim Acta
(2008)
L. Lieben et al.
Bone and metabolism: a complex crosstalk
Horm Res
(2009)
E.S. Strotmeyer et al.
Diabetes mellitus, bone mineral density, and fracture risk
Curr Opin Endocrinol Diabetes Obes
(2007)
P. Ravn et al.
Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal womenEarly Postmenopausal Intervention Cohort (EPIC) study group
J Bone Miner Res
(1999)
L.J. Zhao et al.
Relationship of obesity with osteoporosis
J Clin Endocrinol Metab
(2007)
S.I. McFarlane et al.
Osteoporosis and cardiovascular disease: brittle bones and boned arteries, is there a link?
Endocrine
(2004)
L.B. Tanko et al.
Relationship between osteoporosis and cardiovascular disease in postmenopausal women
J Bone Miner Res
(2005)
S.S. Srivatsa et al.
Increased cellular expression of matrix proteins that regulate mineralization is associated with calcification of native human and porcine xenograft bioprosthetic heart valves
J Clin Invest
(1997)

P.V. Hauschka et al.

Osteocalcin and matrix protein: vitamin K-dependent proteins in bone

Physiol Rev

(1989)

A.J. Lee et al.

Measurement of osteocalcin

Ann Clin Biochem

(2000)

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Osteoblast MR deficiency protects against adverse ventricular remodeling after myocardial infarction
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Mineralocorticoid receptor (MR) antagonists have been clinically used to treat heart failure. However, the underlying cellular and molecular mechanisms remain incompletely understood.
Using osteoblast MR knockout (MR^obko) mouse in combination with myocardial infarction (MI) model, we demonstrated that MR deficiency in osteoblasts significantly improved cardiac function, promoted myocardial healing, as well as attenuated cardiac hypertrophy, fibrosis and inflammatory response after MI. Gene expression profiling using RNA sequencing revealed suppressed expression of osteocalcin (OCN) in calvaria from MR^obko mice compared to littermate control (MR^fl/fl) mice with or without MI. Plasma levels of undercarboxylated OCN (ucOCN) were also markedly decreased in MR^obko mice compared to MR^fl/fl mice. Administration of ucOCN abolished the protective effects of osteoblast MR deficiency on infarcted hearts. Mechanistically, ucOCN treatment promoted proliferation and inflammatory cytokine secretion in macrophages. Spironolactone, an MR antagonist, significantly inhibited the expression and secretion of OCN in post-MI mice. More importantly, spironolactone decreased plasma levels of ucOCN and inflammatory cytokines in heart failure patients.
MR deficiency in osteoblasts alleviates pathological ventricular remodeling after MI, likely through its regulation on OCN. Spironolactone may work through osteoblast MR/OCN axis to exert its therapeutic effects on pathological ventricular remodeling and heart failure in mice and human patients.
Assessment of the synergistic association of serum concentration of vitamin D, vitamin K and osteocalcin with coronary atherosclerosis in patients undergoing angiography
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Citation Excerpt :
A higher percentage of EPCs expresses OC in patients with coronary atherosclerosis as compared with the subjects having a normal endothelial function [10]. The data from other investigation showed that serum osteocalcin level was associated with decreased risk of CAD in Chinese adults [11]. Furthermore, observational studies have shown an inverse association between the intake of vitamin k2 and cardiovascular disease [12–14].
The aim of this study was to assess the association between serum concentration of vitamin D, vitamin K, and osteocalcin with coronary atherosclerosis in patients undergoing angiography.
In this case-control study, 138 people who referred to Bushehr Heart Center for routine examination participated. Demographic information of the participants was registered by using a standard questionnaire. Before undergoing the angiographic processes, venous blood samples were obtained via venipuncture from the antecubital vein into gel and clot activator tubes and stored at – 80 °C until the analysis. After the angiography process was over, the normal participants entered the control group and those with coronary atherosclerosis plaque placed in the case group. Finally, serum levels of vitamin K2 and Osteocalcin were measured in the samples, by using ELISA kits and the serum level of vitamin D was measured by using HPLC.
serum levels of vitamin D in the case group were significantly lower than in the control (p = 0.009) and, serum levels of osteocalcin in the case group were significantly higher than in the control (P = 0.019). There was no difference in K2 level between the two groups (P = 0.84). By separating the three factors like age, sex and T2DM in the two groups, a significant synergistic was found between the concentration of osteocalcin, vitamin D (just in <20 ng/ml) and coronary atherosclerosis (p = 0.025, p = 0.029 respectively). Further, an association was observed between vitamin D level and the severity of atherosclerosis (P = 0.041).).
the results of this study suggest that the increase in the level of osteocalcin and the deficiency of vitamin D is significantly associated with coronary atherosclerosis but, not with vitamin k2. Moreover, serum vitamin D concentration is associated with severity of coronary atherosclerosis.
Osteoprotegerin is a better serum biomarker of coronary artery calcification than osteocalcin in type 2 diabetes
2015, Endocrine Practice
Coronary artery calcification (CAC) is a prominent feature of atherosclerosis and is associated with cardiovascular events. In vitro studies have suggested that osteoprotegerin (OPG) and osteocalcin (OC) exert anticalcification potential in the vessel wall. The objective of this study was to investigate the association of CAC and serum bone biomarkers in persons with type 2 diabetes.
We examined 50 individuals with type 2 diabetes. CAC imaging was performed by multidetector computed tomography. CAC scores > 10, expressed in Agatston units, were considered abnormal. OC, undercarboxylated OC (ucOC), and OPG levels were determined by enzyme-linked immunosorbent assay.
Abnormal CAC scores were found for 64% of the study cohort. OPG levels were significantly elevated (5.5 ± 2.0 pmol/L vs. 4.2 ± 1.7 pmol/L; P = .026) for those with abnormal CAC scores. No univariate differences were found for OC or ucOC. Logistic regression analyses revealed that an increase in serum OPG level was significantly associated with an increase in CAC score (odds ratio, 3.324; 95% confidence interval, 1.321 to 8.359; P = .011). Longer duration of diabetes was a significant covariate (P = .026), whereas nonsignificant covariates in the final model were age, gender, systolic blood pressure, body mass index, insulin resistance determined by the homeostasis model assessment for insulin resistance, leptin, adiponectin, and glycemic control. The Nagelkerke R² for the model was 0.66. Neither OC nor ucOC were significantly associated with elevated CAC scores.
Our results suggest that OPG is a more useful serum biomarker than OC or ucOC for identifying those at increased risk of arterial calcification in type 2 diabetes. (Endocr Pract. 2015;21:14-22)
Vitamin K2 protects mice against non-alcoholic fatty liver disease induced by high-fat diet
2024, Scientific Reports
Extrahepatic Vitamin K-Dependent Gla-Proteins–Potential Cardiometabolic Biomarkers
2024, International Journal of Molecular Sciences
Association of Bone Turnover Biomarkers and Subclinical Atherosclerosis in Subjects with Type 2 Diabetes: A Case-Control Study
2024, Clinical Diabetology

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: This study was supported by Grant 2006 AA 02A409 from the 863 Project, Beijing/China, Grants 30971077 and 30890043 from the National Natural Science Foundation of China, Beijing/China, Grant Shdc12007309 from the Shanghai Shenkang Hospital Development Center, Shanghai/China, Grant 2008ZX09312/019 from the National Key New Drug Creation and Manufacturing Program, Beijing/China, and Grant 2008BAI52B03 from the National Key Technologies Research and Development Program, Beijing/China.

^†: Dr. Zhang and Dr. Qi contributed equally to this work.

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Preventive cardiologyRelation of Serum Osteocalcin Level to Risk of Coronary Heart Disease in Chinese Adults

Section snippets

Methods

Results

Discussion

Am J Med

Cell

Clin Chim Acta

Bone and metabolism: a complex crosstalk

Horm Res

Diabetes mellitus, bone mineral density, and fracture risk

Curr Opin Endocrinol Diabetes Obes

Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal womenEarly Postmenopausal Intervention Cohort (EPIC) study group

J Bone Miner Res

Relationship of obesity with osteoporosis

J Clin Endocrinol Metab

Osteoporosis and cardiovascular disease: brittle bones and boned arteries, is there a link?

Endocrine

Relationship between osteoporosis and cardiovascular disease in postmenopausal women

J Bone Miner Res

Increased cellular expression of matrix proteins that regulate mineralization is associated with calcification of native human and porcine xenograft bioprosthetic heart valves

J Clin Invest

Osteocalcin and matrix protein: vitamin K-dependent proteins in bone

Physiol Rev

Measurement of osteocalcin

Ann Clin Biochem

Preventive cardiology
Relation of Serum Osteocalcin Level to Risk of Coronary Heart Disease in Chinese Adults