The Korean Journal of Medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지

Association of serum osteoprotegerin with coronary artery calcification scores in patients with asymptomatic type 2 diabetes

무증상 제2형 당뇨병 환자에서 관상동맥석회 점수와 혈청 osteoprotegerin농도의 상관 관계

  • Cho, Eun-Hee (Department of Internal Medicine, Kangwon National University School of Medicine) ;
  • Lee, Dong-Gyu (Department of Internal Medicine, Kangwon National University School of Medicine) ;
  • Kim, Sang-Wook (Department of Internal Medicine, Kangwon National University School of Medicine)
  • 조은희 (강원대학교 의학전문대학원 내과학교실) ;
  • 이동규 (강원대학교 의학전문대학원 내과학교실) ;
  • 김상욱 (강원대학교 의학전문대학원 내과학교실)
  • Received : 2010.05.03
  • Accepted : 2010.06.10
  • Published : 2010.08.01
⟨ Previous Next ⟩

Abstract

Background/Aims: Osteoprotegerin (OPG), a member of the tumor necrosis factor (TNF) receptor superfamily, is involved in bone metabolism and vascular calcification. However, the relationship between serum OPG levels and coronary calcification is not well elucidated. The present study investigated whether serum OPG levels are associated with coronary artery calcification scores (CACs) in patients with type 2 diabetes. Methods: A total of 140 type 2 diabetic outpatients without previous evidence of clinical cardiovascular disease were recruited. CACs were obtained using multi-slice spiral computed tomography and categorized as minimal (0), mild (1-99), moderate (100-399), or severe (${\geq}$ 400). Serum OPG levels were measured by enzyme-linked immunosorbent assay. Results: A total of 94 of 140 (67.1%) patients with type 2 diabetes showed coronary calcification. A Pearson's correlation analysis showed a positive correlation between serum OPG levels and CACs. However, multivariate regression analyses revealed that waist circumference, duration of diabetes, and serum creatinine concentration were significant independent determinants of CACs. Conclusions: The present study demonstrates that coronary calcification is common (67.1%), and serum OPG levels are correlated with CACs but are not an independent determinant of CACs in patients with asymptomatic type 2 diabetes.

목적: 본 연구는 심혈관 증상이 없는 제2형 당뇨병 환자에서 불현성 관상동맥 죽상경화증의 유병률을 알아보고, 혈청 OPG 농도와 관상동맥석회 점수와의 상관관계를 분석하여 혈청 OPG가 관상동맥질환의 혈청 표지자로 이용될 수 있을지 알아보았다. 방법: 심혈관 증상이 없는 제2형 당뇨병 환자 140명을 대상으로 MSCT를 이용하여 관상동맥석회 점수를 정량하고 혈청 OPG 농도를 측정하여 상관관계를 분석하였다. 결과: 심혈관 증상이 없는 제2형 당뇨병 환자에서 관상동맥 석회화는 67.1%에서 관찰되었다. 상관분석에서, 관상동맥 석회화 점수와 혈중 OPG농도는 양의 상관관계를 보였으나, 다변량 회귀분석에서는 허리둘레(p=0.003), 당뇨병의 유병기간(p=0.005), 혈청 creatinine 농도(p=0.011)가 관상동맥 석회화의 유의한 독립변수로 나타났으며, 혈청 OPG 농도(p=0.082)는 제외되었다. 결론: 심혈관 증상이 없는 제2형 당뇨병 환자에서 관상동맥 석회화는 흔하게 관찰되며, 혈청 OPG 농도는 관상동맥석회 점수에 비례하여 증가하나, 관상동맥석회 점수의 독립적인 위험인자가 아니므로, 관상동맥 석회화를 반영하는 혈청지표로 이용될 수는 없을 것으로 생각된다.

Keywords

References

  1. Goff DC Jr, Gerstein HC, Ginsberg HN, Cushman WC, Margolis KL, Byington RP, Buse JB, Genuth S, Probstfield JL, Simons- Morton DG. Prevention of cardiovascular disease in persons with type 2 diabetes mellitus: current knowledge and rationale for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol 99:4i-20i, 2007
  2. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 339:229-234, 1998 https://doi.org/10.1056/NEJM199807233390404
  3. Goraya TY, Leibson CL, Palumbo PJ, Weston SA, Killian JM, Pfeifer EA, Jacobsen SJ, Frye RL, Roger VL. Coronary atherosclerosis in diabetes mellitus: a population-based autopsy study. J Am Coll Cardiol 40:946-953, 2002 https://doi.org/10.1016/S0735-1097(02)02065-X
  4. Wackers FJ, Young LH, Inzucchi SE, Chyun DA, Davey JA, Barrett EJ, Taillefer R, Wittlin SD, Heller GV, Filipchuk N, Engel S, Ratner RE, Iskandrian AE. Detection of silent myocardial ischemia in asymptomatic diabetic subjects: the DIAD study. Diabetes Care 27:1954-1961, 2004 https://doi.org/10.2337/diacare.27.8.1954
  5. Shaw LJ, Raggi P, Schisterman E, Berman DS, Callister TQ. Prognostic value of cardiac risk factors and coronary artery calcium screening for all-cause mortality. Radiology 228:826-833, 2003 https://doi.org/10.1148/radiol.2283021006
  6. Mintz GS, Pichard AD, Popma JJ, Kent KM, Satler LF, Bucher TA, Leon MB. Determinants and correlates of target lesion calcium in coronary artery disease: a clinical, angiographic and intravascular ultrasound study. J Am Coll Cardiol 29:268-274, 1997 https://doi.org/10.1016/S0735-1097(96)00479-2
  7. Budoff MJ, Achenbach S, Blumenthal RS, Carr JJ, Goldin JG, Greenland P, Guerci AD, Lima JA, Rader DJ, Rubin GD, Shaw LJ, Wiegers SE. Assessment of coronary artery disease by cardiac computed tomography: a scientific statement from the American Heart Association Committee on Cardiovascular Imaging and Intervention, Council on Cardiovascular Radiology and Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology. Circulation 114:1761-1791, 2006 https://doi.org/10.1161/CIRCULATIONAHA.106.178458
  8. Doherty TM, Fitzpatrick LA, Inoue D, Qiao JH, Fishbein MC, Detrano RC, Shah PK, Rajavashisth TB. Molecular, endocrine, and genetic mechanisms of arterial calcification. Endocr Rev 25:629-672, 2004 https://doi.org/10.1210/er.2003-0015
  9. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Lüthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309-319, 1997 https://doi.org/10.1016/S0092-8674(00)80209-3
  10. Emery JG, McDonnell P, Burke MB, Deen KC, Lyn S, Silverman C, Dul E, Appelbaum ER, Eichman C, DiPrinzio R, Dodds RA, James IE, Rosenberg M, Lee JC, Young PR. Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 273:14363-14367, 1998 https://doi.org/10.1074/jbc.273.23.14363
  11. Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, Tan HL, Xu W, Lacey DL, Boyle WJ, Simonet WS. Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 12:1260-1268, 1998 https://doi.org/10.1101/gad.12.9.1260
  12. Min H, Morony S, Sarosi I, Dunstan CR, Capparelli C, Scully S, Van G, Kaufman S, Kostenuik PJ, Lacey DL, Boyle WJ, Simonet WS. Osteoprotegerin reverses osteoporosis by inhibiting endosteal osteoclasts and prevents vascular calcification by blocking a process resembling osteoclastogenesis. J Exp Med 192:463-474, 2000 https://doi.org/10.1084/jem.192.4.463
  13. Jono S, Ikari Y, Shioi A, Mori K, Miki T, Hara K, Nishizawa Y. Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation 106:1192-1194, 2002 https://doi.org/10.1161/01.CIR.0000031524.49139.29
  14. Anand DV, 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 47:1850-1857, 2006 https://doi.org/10.1016/j.jacc.2005.12.054
  15. 이은정, 이원영, 유태우, 이호철, 김병진, 성기철, 김범수, 강진호, 오기원, 오은숙, 임지애, 백기현. 관상동맥 환자에서 혈청 Osteoprotegerin 농도와 질환 중증도 및 동맥경화 위험 인자와의 연관성. 대한내과학회지 67:365-374, 2004
  16. 오세용, 이은정, 이원영, 전한별, 유태우, 강정묵, 황상태, 김영춘, 김선우, 오기원, 오은숙, 백기현, 강무일. 제2형 당뇨병 환자에서 혈청 Osteoprotegerin 농도와 인슐린 저항성, 심혈관 질환 위험인자 및 골대사의 연관성. 대한내과학회지 68:168-177, 2005
  17. Rumberger JA, Sheedy PF 2nd, Breen JF, Fitzpatrick LA, Schwartz RS. Electron beam computed tomography and coronary artery disease: scanning for coronary artery calcification. Mayo Clin Proc 71:369-377, 1996 https://doi.org/10.4065/71.4.369
  18. Choi EK, Choi SI, Rivera JJ, Nasir K, Chang SA, Chun EJ, Kim HK, Choi DJ, Blumenthal RS, Chang HJ. Coronary computed tomography angiography as a screening tool for the detection of occult coronary artery disease in asymptomatic individuals. J Am Coll Cardiol 52:357-365, 2008 https://doi.org/10.1016/j.jacc.2008.02.086
  19. Rivera JJ, Nasir K, Choi EK, Yoon YE, Chun EJ, Choi SI, Choi DJ, Brancati FL, Blumenthal RS, Chang HJ. Detection of occult coronary artery disease in asymptomatic individuals with diabetes mellitus using non-invasive cardiac angiography. Atherosclerosis 203:442-448, 2009 https://doi.org/10.1016/j.atherosclerosis.2008.07.030
  20. Nitta K, Akiba T, Uchida K, Kawashima A, Yumura W, Kabaya T, Nihei H. The progression of vascular calcification and serum osteoprotegerin levels in patients on long-term hemodialysis. Am J Kidney Dis 42:303-309, 2003 https://doi.org/10.1016/S0272-6386(03)00655-3
  21. Kiechl S, Schett G, Wenning G, Redlich K, Oberhollenzer M, Mayr A, Santer P, Smolen J, Poewe W, Willeit J. Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Circulation 109:2175-2180, 2004 https://doi.org/10.1161/01.CIR.0000127957.43874.BB
  22. 김상욱, 정해혁, 한헌. 혈액투석 중인 말기 신부전증 환자에서 관상동맥혈관 석회화와 혈청 Osteoprotegerin 및 Fetuin-A 농도의 상관관계. 대한내과학회지 72:451-458, 2007
  23. Jung CH, Lee WY, Kim SY, Jung JH, Rhee EJ, Park CY, Mok JO, Oh KW, Kim CH, Park SW, Kim SW. The relationship between coronary artery calcification score, plasma osteoprotegerin level and arterial stiffness in asymptomatic type 2 DM. Acta Diabetol 2009 [Epub ahead of print]
  24. Moe SM, Reslerova M, Ketteler M, O'neill K, Duan D, Koczman J, Westenfeld R, Jahnen-Dechent W, Chen NX. Role of calcification inhibitors in the pathogenesis of vascular calcification in chronic kidney disease (CKD). Kidney Int 67:2295-2304, 2005 https://doi.org/10.1111/j.1523-1755.2005.00333.x
  25. Schoppet M, Sattler AM, Schaefer JR, Herzum M, Maisch B, Hofbauer LC. Increased osteoprotegerin serum levels in men with coronary artery disease. J Clin Endocrinol Metab 88:1024-1028, 2003 https://doi.org/10.1210/jc.2002-020775
  26. Ishiyama M, Suzuki E, Katsuda J, Murase H, Tajima Y, Horikawa Y, Goto S, Fujita T, Takeda J. Associations of coronary artery calcification and carotid intima-media thickness with plasma concentrations of vascular calcification inhibitors in type 2 diabetic patients. Diabetes Res Clin Pract 85:189-196, 2009 https://doi.org/10.1016/j.diabres.2009.04.023
  27. Wannamethee SG, Lowe GD, Rumley A, Cherry L, Whincup PH, Sattar N. Adipokines and risk of type 2 diabetes in older men. Diabetes Care 30:1200-1205, 2007 https://doi.org/10.2337/dc06-2416