Predictive Value of Osteoprotegerin for Detecting Coronary Artery Calcification in Type 2 Diabetes Mellitus Patients in Correlation with Extent of Calcification Detected by Multidetector Computed Tomography

Author(s): Sahar Ahmed*, Rasha Sobh

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders

Volume 19 , Issue 6 , 2019

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Graphical Abstract:


Background: Osteoprotegerin (OPG) is a tumor necrosis factor receptor super-family member. It specifically acts on bone by increasing bone mineral density and bone volume. Recent studies have evidenced its close relation to the development of atherosclerosis and plaque destabilization. Elevated OPG level has also been associated with the degree of coronary calcification in the general population and it has been considered to be a marker of coronary atherosclerosis.

Objective: The aim of this study was to determine the relation between OPG levels and Coronary Artery Calcification score (CACs) in Type 2 diabetic patients in comparison to healthy controls.

Methods: Our study included 45 type 2 diabetic patients (mean age 51.7 years; 51.1% male) without evidence of previous CVD and 45 healthy age and sex matched subjects as control. All participants were subjected to full history, full examination and lab investigations. Serum OPG concentration was measured by an enzyme-linked immunosorbent assay (ELISA) and CAC imaging was performed using non contrast Multi detector CT of the heart.

Results: Significant CAC (<10 Agatston units) was seen in 23 patients (51.11 %).

OPG was significantly high in diabetic patients in comparison to controls with mean 12.9±5.7 pmol/l in cases, and 8.6±0.5 pmol/l in controls (P value < 0.001).

The Coronary Artery Calcification Score (CACS) was positively correlated with age and duration of diabetes. The OPG was positively correlated with age, fasting blood sugar and duration of diabetes. The CACS showed a significantly positive correlation with OPG.

Conclusion: Findings suggested that increasing in serum OPG was consistent with CAC and could be used for the early diagnosis of subclinical atherosclerosis.

Keywords: Osteoprotegerin, coronary artery calcification, Type 2 diabetes mellitus, multi detector computed tomography, Cardiovascular disease, Enzyme-linked immunosorbent assay.

Roth, G.A.; Huffman, M.D.; Moran, A.E.; Feigin, V.; Mensah, G.A.; Naghavi, M.; Murray, C.J. Global and regional patterns in cardiovascular mortality from 1990 to 2013. Circulation, 2015, 132(17), 1667-1678.
[] [PMID: 26503749]
Shoback. David, G., Ed.; Greenspan's Basic & Clinical Endocrinology, (9th. ), 2011
McClelland, R.L.; Chung, H.; Detrano, R.; Post, W.; Kronmal, R.A. Distribution of coronary artery calcium by race, gender, and age: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation, 2006, 113(1), 30-37.
[] [PMID: 16365194]
Shah, N.R.; Coulter, S.A. An evidence-based guide for coronary calcium scoring in asymptomatic patients without coronary heart disease. Tex. Heart Inst. J., 2012, 39(2), 240-242.
[PMID: 22740742]
Youssef, G.; Kalia, N.; Darabian, S.; Budoff, M.J. Coronary calcium: new insights, recent data, and clinical role. Curr. Cardiol. Rep., 2013, 15(1), 325.
[] [PMID: 23250661]
Simonet, W.S.; Lacey, D.L.; Dunstan, C.R.; Kelley, M.; Chang, M.S.; Lüthy, R.; Nguyen, H.Q.; Wooden, S.; Bennett, L.; Boone, T.; Shimamoto, G.; DeRose, M.; Elliott, R.; Colombero, A.; Tan, H.L.; Trail, G.; Sullivan, J.; Davy, E.; Bucay, N.; Renshaw-Gegg, L.; Hughes, T.M.; Hill, D.; Pattison, W.; Campbell, P.; Sander, S.; Van, G.; Tarpley, J.; Derby, P.; Lee, R.; Boyle, W.J. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell, 1997, 89(2), 309-319.
[] [PMID: 9108485]
Lieb, W.; Gona, P.; Larson, M.G.; Massaro, J.M.; Lipinska, I.; Keaney, J.F., Jr; Rong, J.; Corey, D.; Hoffmann, U.; Fox, C.S.; Vasan, R.S.; Benjamin, E.J.; O’Donnell, C.J.; Kathiresan, S. Biomarkers of the osteoprotegerin pathway: clinical correlates, subclinical disease, incident cardiovascular disease, and mortality. Arterioscler. Thromb. Vasc. Biol., 2010, 30(9), 1849-1854.
[] [PMID: 20448212]
Chan-Hee Jung. Won-Young Lee; Se-Yeon Kim; Jung-Hwa Jung; Eun-Jung Rhee; Cheol-Young Park; Ji-Oh Mok; Ki-Won Oh; Chul-Hee Kim; Sung-Woo Park; Sun-Woo Kim. The relationship between coronary artery calcification score, plasma osteoprotegerin level and arterial stiffness in asymptomatic type 2 DM. Acta Diabetol., 2010, 47(1), S145-S152.
Anand, D.V.; Lahiri, A.; Lim, E.; Hopkins, D.; Corder, R. The relationship between plasma osteoprotegerin levels and coronary artery calcification in uncomplicated type 2 diabetic subjects. J. Am. Coll. Cardiol., 2006, 47(9), 1850-1857.
[] [PMID: 16682312]
Aoki, A.; Murata, M.; Asano, T.; Ikoma, A.; Sasaki, M.; Saito, T.; Otani, T.; Jinbo, S.; Ikeda, N.; Kawakami, M.; Ishikawa, S.E. Association of serum osteoprotegerin with vascular calcification in patients with type 2 diabetes. Cardiovasc. Diabetol., 2013, 12, 11.
[] [PMID: 23302066]
Aslanabadi, N.; Tarzamni, M.K.; Javadrashid, R.; Ghojazadeh, M.; Ghorbanihaghjo, A.; Sheikhi, S.; Nezami, N. Predictive value of osteoprotegerin for detecting coronary artery calcification in symptomatic patients: Correlation with extent of calcification detected by multidetector computed tomography. J. Anal. Res. Clin. Med, 2016, 4(1), 66-71.
Friedewald, W.T.; Levy, R.I.; Fredrickson, D.S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem., 1972, 18(6), 499-502.
[PMID: 4337382]
Masser, R.E.; Lenhard, M.J. Osteoprotegerin is a better serum biomarker of coronary artery calcification scores than osteocalcin in type 2 diabetes. Endocr. Pract., 2015, 21(1), 14-22.
Schoppet, M.; Al-Fakhri, N.; Franke, F.E.; Katz, N.; Barth, P.J.; Maisch, B.; Preissner, K.T.; Hofbauer, L.C. Localization of osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand, and receptor activator of nuclear factor-kappaB ligand in Mönckeberg’s sclerosis and atherosclerosis. J. Clin. Endocrinol. Metab., 2004, 89(8), 4104-4112.
[] [PMID: 15292354]
Tavintharan, S.; Pek, L.T.; Liu, J.J.; Ng, X.W.; Yeoh, L.Y.; Su, Chi L.; Chee Fang, S. Osteoprotegerin is independently associated with metabolic syndrome and microvascular complications in type 2 diabetes mellitus. Diab. Vasc. Dis. Res., 2014, 11(5), 359-362.
[] [PMID: 25005034]
Sabine, R. Zwakenberg; Yvonne T. van der Schou; Casper, G. S; Annemieke, M. W.; Joline, W. J. Bone markers and cardiovascular risk in type 2 diabetes patients. Cardiovasc. Diabetol., 2018, 17, 45.
Niu, Y.; Zhang, W.; Yang, Z.; Li, X.; Wen, J.; Wang, S.; Zhang, H.; Wang, X.; Zhou, H.; Fang, W.; Qin, L.; Su, Q. Association of plasma osteoprotegerin levels with the severity of lower extremity arterial disease in patients with type 2 diabetes. BMC Cardiovasc. Disord., 2015, 15, 86.
[] [PMID: 26260869]

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Article Details

Year: 2019
Published on: 03 September, 2019
Page: [845 - 851]
Pages: 7
DOI: 10.2174/1871530319666190211122858
Price: $65

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