Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter May 19, 2018

Osteocalcin value to identify subclinical atherosclerosis over atherosclerotic cardiovascular disease (ASCVD) risk score in middle-aged and elderly Chinese asymptomatic men

  • Yiting Xu , Xiaojing Ma , Qin Xiong , Xueli Zhang , Yun Shen and Yuqian Bao EMAIL logo

Abstract

Background:

Our study examined whether osteocalcin contributed to identifying carotid intima-media thickness (C-IMT) over the atherosclerotic cardiovascular disease (ASCVD) risk score.

Methods:

We recruited 618 middle-aged and elderly men from communities in Shanghai. Serum osteocalcin levels were determined using an electrochemiluminescence immunoassay. C-IMT was measured by ultrasonography.

Results:

The study included 245 men with low ASCVD risk and 373 men with moderate-to-high ASCVD risk. Serum osteocalcin levels were lower in the moderate-to-high risk vs. low risk men (p=0.042). Multivariate stepwise regression analysis showed that body mass index (BMI) and glycated hemoglobin were predictors for reduced osteocalcin levels (both p<0.001). Among all subjects, the proportion with an elevated C-IMT was higher in the low-osteocalcin group than in the high-osteocalcin group (p=0.042), and the significance of this result was greater when considering only subjects with a moderate-to-high ASCVD risk (p=0.011). The recognition rate of elevated C-IMT was superior with both low osteocalcin and moderate-to-high ASCVD risk vs. either parameter alone (p<0.001 and p=0.015, respectively). Osteocalcin was independently and inversely associated with elevated C-IMT after adjusting for the 10-year ASCVD risk score (p=0.004). The negative relationship remained statistically significant in subjects with a moderate-to-high ASCVD risk in particular (standardized β=−0.104, p=0.044).

Conclusions:

In middle-aged and elderly men, serum osteocalcin levels strengthen identifying subclinical atherosclerosis over ASCVD risk score, especially among subjects with a moderate-to-high ASCVD risk.


Corresponding author: Prof. Yuqian Bao, MD, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, 600 Yishan Road, Shanghai 200233, P.R. China, Phone: +86-21-64369181, Fax: +86-21-64368031
aYiting Xu and Xiaojing Ma contributed equally to this work.
  1. Author contributions: Yuqian Bao conceived and designed the experiments. Yiting Xu, Xiaojing Ma, Qin Xiong, Xueli Zhang and Yun Shen performed the experiments. Yiting Xu and Xiaojing Ma performed the statistical analysis and wrote the paper. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: The authors disclose receipt of the following financial support for the research, authorship and/or publication of this article: This work was funded by the Project of National Natural Science Foundation of China (grant number 31571212) and the innovation foundation of translational medicine of Shanghai Jiao Tong University School of Medicine and Shanghai SJTUSM Biobank [grant number 15ZH4006].

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Kindblom JM, Ohlsson C, Ljunggren O, Karlsson MK, Tivesten A, Smith U, et al. Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res 2009;24:785–91.10.1359/jbmr.081234Search in Google Scholar PubMed

2. Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, et al. Endocrine regulation of energy metabolism by the skeleton. Cell 2007;130:456–69.10.1016/j.cell.2007.05.047Search in Google Scholar PubMed PubMed Central

3. Zhou M, Ma X, Li H, Pan X, Tang J, Gao Y, et al. Serum osteocalcin concentrations in relation to glucose and lipid metabolism in Chinese individuals. Eur J Endocrinol 2009;161:723–9.10.1530/EJE-09-0585Search in Google Scholar PubMed

4. Bao Y, Ma X, Yang R, Wang F, Hao Y, Dou J, et al. Inverse relationship between serum osteocalcin levels and visceral fat area in Chinese men. J Clin Endocrinol Metab 2013;98:345–51.10.1210/jc.2012-2906Search in Google Scholar PubMed

5. Luo Y, Ma X, Hao Y, Xu Y, Xiong Q, Tang J, et al. Association between serum osteocalcin level and visceral obesity in Chinese postmenopausal women. Clin Endocrinol (Oxf) 2015;83:429–34.10.1111/cen.12793Search in Google Scholar PubMed

6. Luo YQ, Ma XJ, Hao YP, Pan XP, Xu YT, Xiong Q, et al. Inverse relationship between serum osteocalcin levels and nonalcoholic fatty liver disease in postmenopausal Chinese women with normal blood glucose levels. Acta Pharmacol Sin 2015;36: 1497–502.10.1038/aps.2015.81Search in Google Scholar PubMed PubMed Central

7. Bao Y, Zhou M, Lu Z, Li H, Wang Y, Sun L, et al. Serum levels of osteocalcin are inversely associated with the metabolic syndrome and the severity of coronary artery disease in Chinese men. Clin Endocrinol 2011;75:196–201.10.1111/j.1365-2265.2011.04065.xSearch in Google Scholar PubMed

8. Yang R, Ma X, Pan X, Wang F, Luo Y, Gu C, et al. Serum osteocalcin levels in relation to metabolic syndrome in Chinese postmenopausal women. Menopause 2013;20:548–53.10.1097/gme.0b013e318271b1daSearch in Google Scholar

9. Holvik K, van Schoor NM, Eekhoff EM, den Heijer M, Deeg DJ, Lips P, et al. Plasma osteocalcin levels as a predictor of cardiovascular disease in older men and women: a population-based cohort study. Eur J Endocrinol 2014;171:161–70.10.1530/EJE-13-1044Search in Google Scholar PubMed

10. Yeap BB, Chubb SA, Flicker L, McCaul KA, Ebeling PR, Hankey GJ, et al. Associations of total osteocalcin with all-cause and cardiovascular mortality in older men. The Health In Men Study. Osteoporos Int 2012;23:599–606.10.1007/s00198-011-1586-1Search in Google Scholar PubMed

11. Yeap BB, Alfonso H, Chubb SA, Byrnes E, Beilby JP, Ebeling PR, et al. Proportion of undercarboxylated osteocalcin and serum P1NP predict incidence of myocardial infarction in older men. J Clin Endocrinol Metab 2015;100:3934–42.10.1210/jc.2015-1899Search in Google Scholar PubMed

12. Yang X, Li J, Hu D, Chen J, Li Y, Huang J, et al. Predicting the 10-year risks of atherosclerotic cardiovascular disease in Chinese population: the China-PAR Project (Prediction for ASCVD Risk in China). Circulation 2016;134:1430–40.10.1161/CIRCULATIONAHA.116.022367Search in Google Scholar PubMed

13. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604–12.10.7326/0003-4819-150-9-200905050-00006Search in Google Scholar PubMed PubMed Central

14. Wang Y, Ma X, Zhou M, Zong W, Zhang L, Hao Y, et al. Contribution of visceral fat accumulation to carotid intima-media thickness in a Chinese population. Int J Obes (Lond) 2012;36:1203–8.10.1038/ijo.2011.222Search in Google Scholar PubMed PubMed Central

15. Huang Y, Bi Y, Wang W, Xu M, Xu Y, Li M, et al. Glycated hemoglobin A1c, fasting plasma glucose, and two-hour postchallenge plasma glucose levels in relation to carotid intima-media thickness in Chinese with normal glucose tolerance. J Clin Endocrinol Metab 2011;96:E1461–5.10.1210/jc.2010-2697Search in Google Scholar PubMed

16. Department of Noncommunicable Disease Surveillance. Report of a WHO Consultation: definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Geneva: World Health Organization, 1999.Search in Google Scholar

17. Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D’Agostino RB, Gibbons R, et al. American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129:S49–73.10.1161/01.cir.0000437741.48606.98Search in Google Scholar PubMed

18. DeFilippis AP, Young R, Carrubba CJ, McEvoy JW, Budoff MJ, Blumenthal RS, et al. An analysis of calibration and discrimination among multiple cardiovascular risk scores in a modern multiethnic cohort. Ann Intern Med 2015;162:266–75.10.7326/M14-1281Search in Google Scholar PubMed PubMed Central

19. Gobardhan SN, Dimitriu-Leen AC, van Rosendael AR, van Zwet EW, Roos CJ, Oemrawsingh PV, et al. Prevalence by computed tomographic angiography of coronary plaques in South Asian and white patients with type 2 diabetes mellitus at low and high risk using four cardiovascular risk scores (UKPDS, FRS, ASCVD, and JBS3). Am J Cardiol 2017;119:705–11.10.1016/j.amjcard.2016.11.029Search in Google Scholar PubMed

20. Goliasch G, Blessberger H, Azar D, Heinze G, Wojta J, Bieglmayer C, et al. Markers of bone metabolism in premature myocardial infarction (≤40 years of age). Bone 2011;48:622–6.10.1016/j.bone.2010.11.005Search in Google Scholar PubMed

21. Yamashita T, Okano K, Tsuruta Y, Akiba T, Nitta K. Serum osteocalcin levels are useful as a predictor of cardiovascular events in maintenance hemodialysis patients. Int Urol Nephrol 2013;45:207–14.10.1007/s11255-012-0156-6Search in Google Scholar PubMed

22. Dou J, Li H, Ma X, Zhang M, Fang Q, Nie M, et al. Osteocalcin attenuates high fat diet–induced impairment of endothelium–dependent relaxation through Akt/eNOS–dependent pathway. Cardiovasc Diabetol 2014;13:74.10.1186/1475-2840-13-74Search in Google Scholar PubMed PubMed Central

23. Szulc P, Kaufman JM, Delmas PD. Biochemical assessment of bone turnover and bone fragility in men. Osteoporos Int 2007;18:1451–61.10.1007/s00198-007-0407-zSearch in Google Scholar PubMed

24. Bullen JW Jr, Bluher S, Kelesidis T, Mantzoros CS. Regulation of adiponectin and its receptors in response to development of diet-induced obesity in mice. Am J Physiol Endocrinol Metab 2007;292:E1079–86.10.1152/ajpendo.00245.2006Search in Google Scholar PubMed

25. Pittas AG, Harris SS, Eliades M, Stark P, Dawson-Hughes B. Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab 2009;94:827–32.10.1210/jc.2008-1422Search in Google Scholar PubMed PubMed Central

26. Okuno S, Ishimura E, Tsuboniwa N, Norimine K, Yamakawa K, Yamakawa T, et al. Significant inverse relationship between serum undercarboxylated osteocalcin and glycemic control in maintenance hemodialysis patients. Osteoporos Int 2013;24:605–12.10.1007/s00198-012-2003-0Search in Google Scholar PubMed

27. Luo Y, Ma X, Hao Y, Xiong Q, Xu Y, Pan X, et al. Relationship between serum osteocalcin level and carotid intima–media thickness in a metabolically healthy Chinese population. Cardiovasc Diabetol 2015;14:82.10.1186/s12933-015-0245-9Search in Google Scholar PubMed PubMed Central

28. Razny U, Goralska J, Zdzienicka A, Fedak D, Masania J, Rabbani N, et al. Relation of the protein glycation, oxidation and nitration to the osteocalcin level in obese subjects. Acta Biochim Pol 2017;64:415–22.10.18388/abp.2017_1627Search in Google Scholar PubMed

29. Verhaeghe J, Suiker AM, Nyomba BL, Visser WJ, Einhorn TA, Dequeker J, et al. Bone mineral homeostasis in spontaneously diabetic BB rats. II. Impaired bone turnover and decreased osteocalcin synthesis. Endocrinology 1989;124:573–82.10.1210/endo-124-2-573Search in Google Scholar PubMed

30. Rico H, Hernandez ER, Cabranes JA, Gomez-Castresana F. Suggestion of a deficient osteoblastic function in diabetes mellitus: the possible cause of osteopenia in diabetics. Calcif Tissue Int 1989;45:71–3.10.1007/BF02561404Search in Google Scholar PubMed

Received: 2018-01-12
Accepted: 2018-04-18
Published Online: 2018-05-19
Published in Print: 2018-10-25

©2018 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 5.3.2024 from https://www.degruyter.com/document/doi/10.1515/cclm-2018-0320/html
Scroll to top button