대한내과학회지 : 제 79 권제 2 호 2010 무증상제2형당뇨병환자에서관상동맥석회점수와혈청 osteoprotegerin농도의상관관계 강원대학교의학전문대학원내과학교실 조은희 이동규 김상욱 Association of serum osteoprotegerin with coronary artery calcification scores in patients with asymptomatic type 2 diabetes Eun-Hee Cho, M.D., Dong Gyu Lee, M.D., and Sang-Wook Kim, M.D., Ph.D. Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea 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 ( 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. (Korean J Med 79:163-170, 2010) Key Words: Osteoprotegerin; Coronary artery; Calcification; Diabetes mellitus 서론제2형당뇨병환자에서심혈관질환은높은유병률과함께주요한사망원인중의하나로알려져있다 1). Haffner 등 2) 은역학연구를통해제2형당뇨병환자의심근경색발생위험및사망률이심근경색을이미경험한일반인과동등하다고보고한바있다. 또한제2형당뇨병환자에서는무증상심근허혈질환의발생률이높으며 1,3,4), 이를선별할수있는 Received: 2010. 5. 3 Accepted: 2010. 6. 10 Correspondence to Sang-Wook Kim, M.D., Department of Internal Medicine, Kangwon National University School of Medicine, 26 Gangwondaehak-gil, Chuncheon 200-947, Korea E-mail: exoplanet@kangwon.ac.kr - 163 -
- The Korean Journal of Medicine: Vol. 79, No. 2, 2010 - 검사방법으로, 관상동맥에서관찰되는석회를전산화단층촬영을이용하여측정하는방법이널리이용되고있다. 관상동맥석회화는전자선전산화단층촬영 (electron-beam computed tomography) 이나다중박편나선형전산화단층촬영 (multi-slice spiral computed tomography, MSCT) 을통해정량화할수있는데, 이를이용하여얻은관상동맥석회점수 (coronary artery calcification score, CACs) 는죽상경화반의유무및중증도, 심근경색의위험을반영하고, 대규모역학연구에서심혈관질환의독립적인위험인자로알려져있다 5-7). 혈관석회화의발생과진행에는고지혈증이나고혈압, hs-crp (high sensitivity C-reactive protein) 와같은심혈관질환의전통적인위험인자외에 fetuin-a (α2-hereman-schmid Glycoprotein, AHSG) 와같은석회화억제단백질이나 osteoprotegerin (OPG) 과같은골대사관련물질들이혈관석회화와밀접한상관관계를보인다는사실이알려지면서죽상경화증의발생과진행에서비전통적위험인자들이상당한역할을하고있는것으로생각되고있다 8). 관상동맥석회점수는이러한여러인자들의종합적영향으로만들어지는죽상경화반의칼슘을측정하는것이므로유전적, 혈청학적영향을전체적으로반영하는임상적으로유용한지표로생각된다. OPG는종양괴사인자수용체 (tumor necrosis factor receptor) 상과 (super-family) 에속하며골재형성과정에서핵심적인역할을하는단백질로 9), 파골세포의분화및활성화물질로알려진 RANKL (receptor activator of nuclear factor ΚB ligand) 의작용에길항하는유인수용체 (decoy receptor) 로작용해파골세포의분화와성숙을억제하는작용을한다 10). OPG가혈관석회화과정에관여한다는증거로는여러실험연구와역학연구들이있는데, 실험동물에서 OPG 유전자를결손시키면대동맥과신장동맥혈관이석회화되고, 골다공증이유발되며 11), 반대로 OPG 유전자를과발현시켰을경우석회화가예방되었다 12). 사람을대상으로한역학연구 13) 에서는혈청 OPG 농도의증가가관상동맥질환의존재및중증도와상관관계가있다고보고된바있다. 제2형당뇨병환자에서혈청 OPG 농도와혈관석회화의상관성을분석한연구들에서는혈청 OPG의증가가혈관석회화와밀접한상관관계가있다고이미보고된바가있다 14). 우리나라에서도혈청 OPG 농도와혈관석회화의상관관계를분석한연구들이있으나일반인구집단을대상으로하거나 15), 제2형당뇨병환자를대상으로한경우에도관상동맥이아닌대동맥의석회화를석회화의표지자로하여분석한연구 16) 들이어서관상동맥죽상경화증과의직접적인관련성 을증명하기에제한점이있었다. 본연구는위와같은배경에서심혈관증상이없는제2형당뇨병환자를대상으로 MSCT 를이용하여관상동맥석회점수를정량하고혈청 OPG 농도를측정하여, 이들환자에서불현성관상동맥죽상경화증의유병률을알아보고, 혈청 OPG 농도와관상동맥석회점수와의상관관계를분석하여혈청 OPG 농도가관상동맥질환의혈청표지자로이용될수있을지알아보았다. 대상및방법 1. 연구대상 2007년 3월부터동년 7월까지강원대학교병원내분비내과외래를방문한제2형당뇨병환자에서연구의목적과과정에대해설명을듣고연구에참여할것을동의한 150명의환자를대상으로연구를시행하였다. 제2형당뇨병의진단은 1997년에제정된미국당뇨병학회의진단기준에따랐으며, 연구참여당시 30세이상이며당뇨병으로진단된지 1년이상경과한환자를대상으로하였다. 진단당시부터인슐린을사용하였거나케톤산혈증의병력이있는경우는제1형당뇨병으로간주하여제외하였으며, 전형적인허혈성심질환의증상이있거나과거에심혈관조영술이나심혈관중재술을받은경우는이미확립된심혈관질환을가진것으로보아연구에서제외하였다. 만성간질환이나혈청 creatinine이 2.0 mg/dl 이상인만성신장질환, 만성폐쇄성폐질환, 만성관절염등의만성질환이동반된경우도연구에서제외하였으며, 갑상선기능항진증, 갑상선기능저하증, 쿠싱증후군등과같은내분비질환이동반된경우도연구에서제외하였다. 본연구는강원대학교병원임상연구위원회 (IRB) 의승인을받았으며 150명의환자가본연구에동의하였고이들로부터문서화된동의서를받았다. 150명의환자중에서연구에동의한후검사를받지않은 8명과갑상선기능저하증과특발성부갑상선기능저하증이연구종결후확인된 2명을제외한 140명의환자를대상으로결과를분석하였다. 2. 연구방법모든환자에서문진및신체검사를시행하였고의무기록지를조사하였다. 심혈관질환유무, 흡연력, 당뇨병의유병기간을조사하였고, 신장과체중을측정하여체질량지수를구하였으며, 대상자의허리둘레를측정하였다. 환자의혈압 - 164 -
- Eun-Hee Cho, et al. Serum osteoprotegerin and coronary artery calcification scores in type 2 diabetes - 은자동화된혈압측정기 (Omrom, HEM-780) 를이용하여안정상태에서 5분간격으로 2회측정하였고, 평균값을분석에이용하였다. 관상동맥석회화점수 (Coronary artery calcium score, CACs) 는 MSCT (LightSpeed Plus, GE Medical Systems, Milwaukee, USA) 를이용하여면적과부피모두를측정하였으며이중부피로측정한값을통계처리에이용하였다. 혈액채취는 8시간이상공복후일반화학검사, 혈청지질검사를시행하였고, 혈청 hs-crp와혈청 OPG 농도를측정하였다. hs-crp 는최하 0.01 mg/dl까지검출할수있는 Latex agglutination법 (Denka, Tokyo, Japan) 으로측정하였는데급성염증성질환에이환된경우 1개월이내의검사치는분석에서제외하였다. 혈청 OPG 농도는상업화된 ELISA 키트 (Oscotech, Seoul, Korea) 를이용하여측정하였고, 시험내 (intra-assay) 변이계수 (Coefficient of variance, CV) 는 4.8~8%, 시험간 (inter-assay) 변이계수는 4.3~5.6% 이었다. 3. 통계분석모든측정값은평균 ± 표준편차또는중앙값과범위로표시하였다. 관상동맥석회화점수 (CACs), 당뇨병의유병기간, 혈청중성지방, hs-crp, 미세알부민뇨는비정규분포를보이므로로그변환하여분석하였다. 이과정에서 CACs가 0인경우로그변환을시행하면결측치로처리되어분석에서누락되므로 CACs에 1을더한값을로그변환하여통계분석에이용하였다. CACs와혈압, 혈청 creatinine, 혈청 OPG 농도등여러변수들간의상관관계는 Pearson 단순상관분석을이용하여알아보았다. 다변량회귀분석은 CACs를종속변수로하고, Pearson 단순상관분석에서유의한상관관계를보였던연령, 당뇨병유병기간, 허리둘레, 맥압, 혈청 creatinine, 혈청 OPG 농도를입력변수로하여분석하였으며입력선택방법 (enter selection) 을사용하였다. 또한연구대상자들을 Rumberger 등 17) 의제안에따라 CACs가 0인경우 ( 최소 ), 1~99인경우 ( 경미 ), 100~399 ( 중등도 ), 400 이상 ( 중증 ) 으로분류하여분석하였다. 최소또는경미한경우폐쇄성관상동맥질환이있을가능성이낮고, 중등도인경우는관상동맥질환의동반가능성이비교적높으며, 중증인경우는심하고광범위한관상동맥질환이있음을의미한다. CACs 분류에따른임상적, 생화학적인자들의비교는일원배치분산분석 (one-way ANOVA) 을이용하여검증하였다. 통계처리는 SPSS 12.0 소프트웨어를사용하였고, 모든통계치는양측검정으로 p-value가 0.05 미만일때유의한것으로판정하였다. 결 대상자의나이는평균 62.1±8.2세였으며, 당뇨병의유병기간은평균 9.4±7.1년이었다. 혈청 OPG 농도의평균값은 634±370 pg/ml 이었으며, CACs 의중앙값은 16.50 mm 3 ( 사분위수 0.00-128.75) 이었고, 전체 140명의연구대상자중 94명 (67.1%) 에서혈관석회화가관찰되었다. Rumberger 등 17) 의제안에따라대상자를관상동맥석회점수가 0인경우 ( 최소 ), 1~99인경우 ( 경미 ), 100~399인경우 ( 중등도 ), 400 이상인경우 ( 중증 ) 로나누었을때각각의빈도는최소 32.9%, 경미 35.7%, 중등도 22.1%, 중증 9.3% 였다 ( 표 4). 연구대상자들의자세한임상적, 생화학적특성들은표에나타내었다 ( 표 1). Table 1. Baseline characteristics of the study subjects Number 140 Gender (M/F) 80/60 Age (yr) 62.1± 8.2 Duration of diabetes (yr) 8 (1-37) Smoking (N (%)) Non-smoker 76 (54.3%) Ex-smoker 24 (17.1%) Current smoker 40 (28.6%) BMI (kg/m 2 ) 25.3±3.0 Waist circumference (cm) 89.0±7.4 Systolic BP (mmhg) 132±16 Diastolic BP (mmhg) 79±9 Pulse pressure (mmhg) 53±13 FBS (mg/dl) 139±34 HbA1C (%) 7.3±1.1 hs-crp (mg/dl) * 0.08 (0-2.13) Creatinine (mg/dl) 1.0±0.2 Microalbumin (mg/g creatinine) * 14.8 (3.1-719.9) Total cholesterol (mg/dl) 181±31 Triglyceride (mg/dl) * 127 (44-609) HDL-cholesterol (mg/dl) 47±10 LDL-cholesterol (mg/dl) 109±27 Osteoprotegerin (pg/ml) 634±370 CAC scores (mm 3 ) * 17 (0-3,512) BMI, body mass index; FBS, fasting blood sugar; HbA1C, glycated hemoglobin; hs-crp, high sensitivity C-reactive protein; CAC, coronary artery calcification; HDL, high density lipoprotein; LDL, low density lipoprotein. * Data are means ± SD or median and range. 과 - 165 -
- 대한내과학회지 : 제 79 권제 2 호통권제 600 호 2010 - Pearson 단순상관분석에서관상동맥석회점수는혈청 OPG 농도와유의한양의상관관계 (r=0.303, p<0.001) 가있었고, 연령 (r=0.360, p<0.001), 당뇨병의유병기간 (r=0.266, p=0.001), 허리둘레 (r=0.275, p=0.001), 맥압 (r=0.202, p=0.017), 혈청 creatinine 농도 (r=0.251, p=0.003) 가관상동맥석회점수와유의한양의상관관계가있었다 ( 표 2). 또한 Pearson 단순상관분 Table 2. Simple correlation analysis between the coronary artery calcium score * and the clinical and biochemical variables (N=140) Variables Correlation coefficient p-value Age 0.360 < 0.001 BMI 0.110 0.195 Waist circumference 0.275 0.001 Log duration of diabetes 0.266 0.001 Systolic blood pressure 0.146 0.085 Diastolic blood pressure -0.023 0.789 Pulse pressure 0.202 0.017 FBS 0.005 0.952 HbA1C 0.071 0.407 Log hs-crp 0.001 0.994 Creatinine 0.251 0.003 Log microalbumin 0.082 0.333 Total cholesterol -0.050 0.554 Log triglyceride -0.066 0.441 HDL-cholesterol -0.121 0.154 LDL-cholesterol -0.016 0.849 Osteoprotegerin 0.303 < 0.001 BMI, body mass index; FBS, fasting blood sugar; HbA1C, glycated hemoglobin; hs-crp, high sensitivity C-reactive protein; HDL, high density lipoprotein; LDL, low density lipoprotein. * Log (CACs + 1). 석에서혈청 OPG 농도는연령, 당뇨병의유병기간, 맥압과유의한양의상관관계를보였다 (Data were not shown). 이상의상관분석결과에서유의하게나타난변수인연령과당뇨병의유병기간, 허리둘레, 맥압, 혈청 creatinine 농도, 혈청 OPG 농도를입력변수로, CACs를종속변수로한다변량회귀분석에서는허리둘레 (p=0.003), 당뇨병의유병기간 (p=0.005), 혈청 creatinine 농도 (p=0.011) 가유의한독립변수로나타났으며, 혈청 OPG 농도 (p=0.082) 는 CACs와유의한상관관계를보여주지않았다 (p=0.0082). 대상자들을 Rumberger 등 17) 이제안한바와같이 CACs에따라최소, 경미, 중등도, 중증의 4집단으로나누어임상적특성을비교하였을때중증집단에서연령, 허리둘레, 당뇨병의유병기간, 혈청 creatinine 농도, 혈청 OPG 농도가높게나타났으며, HDL 콜레스테롤은유의하게낮았다 ( 표 4). 고찰본연구의결과관상동맥석회화는연구대상자의약 2/3 에서관찰되었고, 관상동맥석회점수는연령, 당뇨병의유병기간, 허리둘레, 맥압, 혈청 creatinine 농도, 혈청 OPG 농도와유의한양의상관관계를보여주었다. 이중허리둘레, 당뇨병의유병기간, 혈청 creatinine 농도는다변량회귀분석에서관상동맥석회점수의독립적인위험인자로나타났으나혈청 OPG 농도는제외되었다. 제2형당뇨병환자에서관상동맥죽상경화증과무증상심근허혈의유병률은일반인구집단과비교하여상당히높은것으로알려져있다 1,3,4). 일반인구집단에서관상동맥석회화의유병률에대해서는최등 18) 이한국인건강검진수진자 1,000 명을대상으로시행한연구에서 18% 라고보고한것이있다. 제2형당뇨병환자에서관상동맥석회화의유병률에대해서 Table 3. Multiple linear regression analysis of variables influencing coronary artery calcium score * (N=140) Unstandardized Coefficients Standardized Coefficients B Standard Error Beta p-value Age 0.019 0.012 0.149 0.112 Pulse pressure -0.002 0.007-0.025 0.767 Waist circumference 0.033 0.011 0.233 0.003 Duration of diabetes 0.033 0.012 0.226 0.005 Creatinine 1.113 0.429 0.200 0.011 Osteoprotegerin 0.000 0.000 0.151 0.082 Dependent variable: Log (CACs+1); independent variables: age, waist circumference, duration of diabetes, creatinine, osteoprotegerin. - 166 -
- 조은희외 2 인. 무증상제 2 형당뇨병환자에서관상동맥석회점수와혈청 osteoprotegerin 농도의상관관계 - Table 4. Coronary artery calcium scores and the clinical and biochemical variables Agatston score Minimal Mild Moderate Severe 0 1 99 100 399 400 p-value Number (%) 46 (32.9%) 50 (35.7%) 31 (22.1%) 13 (9.3%) Age (yr) 58.4±8.3 62.7±7.5 65.7±7.5 64.5±7.4 0.001 Waist circumference (cm) 86.7±6.3 88.9±8.0 90.3±7.0 94.3±7.0 0.006 Duration of diabetes (yr) 6.1±4.0 10.7±6.7 10.5±8.7 13.2±9.5 0.001 hs-crp (mg/dl) 0.14±0.15 0.21±0.38 0.14±0.16 0.17±0.23 0.567 Microalbumin (mg/g creatinine) 30±62 51±128 61±104 74±101 0.430 Creatinine (mg/dl) 1.0±0.2 1.0±0.2 1.1±0.2 1.2±0.3 0.023 HDL-cholesterol (mg/dl) 46±11 49±10 45±9 41± 11 0.047 Osteoprotegerin (pg/ml) 473±302 703±422 696±307 793±360 0.003 hs-crp, high sensitivity C-reactive protein; HDL, high density lipoprotein. 는최근 Rivera 등 19) 이심혈관계증상이없는한국인제2형당뇨병환자 217명을대상으로시행한연구에서 64% 라고보고하였다. 본연구에서는대상환자의 67.1% 에서관상동맥석회화를관찰할수있었는데 Rivera 등이보고한것과일치하는결과로생각된다. 이처럼제2형당뇨병환자들에서불현성죽상경화증은높은유병률을보이고있으나현재까지심혈관증상이없는당뇨병환자들에대한적절한선별검사나치료방법에대해확립된지침은없는상태이다. 현재심혈관증상이없는관상동맥질환의선별검사를위한방법으로답차운동부하검사 (exercise treadmill test), 부하심초음파 (stress echocardiography), 단일광자방출전산화단층촬영 (Single photon emission computed tomography, SPECT), 경동맥내막-중막두께측정 (carotid intima-media thickness, cimt), 관상동맥석회점수 (coronary artery calcification score, CACs) 등의방법들이사용되고있으며, 이중 CACs는관상동맥질환과의연관성이잘알려져있고, 쉽게정량화가가능하며, 높은민감도와음성예측력을가지고있어최근많은연구에서활용되고있다. 혈관석회화와밀접한관련을가지는것으로알려진혈청 OPG 농도는장기간혈액투석치료를받는환자들에서혈관석회화의진행정도, 관상동맥질환의존재유무및중증도, 그리고일반인대상의연구에서는심혈관계위험도와의관련성을보여주었다 13,20,21). 심혈관증상이없는제2형당뇨병환자를대상으로혈장 OPG 농도와관상동맥석회화와의관계를알아본 Anand 등의연구 14) 에서는 OPG 농도의상승은불현성죽상경화증과심혈관계합병증발생의예측인자라고밝히고있으며, 고위험군환자에서 OPG 농도측정이심혈관계위험도에대한적절한평가에도움을줄수있을것이라고 제안하고있다. 하지만본연구에서혈청 OPG 농도는관상동맥석회점수와통계적으로유의한양의상관관계가있었으나독립적인위험인자로나타나지는않았다. 반면, 혈청 creatinine 농도가독립적인위험인자로나타난점은흥미롭다. 투석중인말기신부전증환자를대상으로혈청 OPG 농도와관상동맥석회점수와의상관관계를분석한김등 22) 의연구에서는연구대상자들의혈청 OPG 평균농도는 3,561± 1,160 pg/ml였다. 이는본연구대상자들에서나타난혈청 OPG의평균농도보다약 5배이상높은수치로, 본연구에서혈청 OPG 농도가관상동맥석회점수와유의한상관관계를나타내지못한이유가혈청 OPG의농도가혈관석회화에영향을미치기에는그농도가매우낮았을가능성을시사한다. 이는본연구에서처럼비교적신장기능이정상으로생각되는환자에서는혈청 OPG 농도가혈청표지자로서사용하기에는제한점이있음을보여주는결과로생각된다. 본연구에서혈청크레아티닌이증가하는경우관상동맥석회점수와밀접한양의상관관계를나타내고또독립적위험인자로나타난점은특기할만한사실이다. 본연구는전향적연구가아닌후향적연구로서인과관계를증명할수는없으나, 신장기능이비교적정상일것으로생각되는혈청크레아티닌농도 2.0 mg/dl 이하인경우에도관상동맥혈관석회화가혈청크레아티닌농도와밀접한상관관계가있는반면, 심혈관질환의전통적위험인자로알려진 hs-crp, 저밀도지단백콜레스테롤, 혈압등은오히려통계적으로유의한상관관계를보여주지못한점을생각할때, 관상동맥혈관석회화에는신장기능의이상이중요한위험인자로재평가되어야함을시사하는결과로생각된다. 이를증명하기 - 167 -
- The Korean Journal of Medicine: Vol. 79, No. 2, 2010 - 위해서는정상신기능을가진제2형당뇨병환자를대상으로장기간에걸친전향적연구가필요할것으로생각된다. 한편, OPG 는형질전환생쥐연구 12) 에서혈관석회화를억제하는혈관보호인자의역할을하는것으로밝혀졌지만, 사람을대상으로한여러연구 13,20,21) 에서는 OPG 농도의증가가관상동맥질환의중증도와관련되어있어사람과동물에서상반된결과를보여주고있다. 심혈관증상이없는제 2형당뇨병환자를대상으로한정등의연구에서도 23), 관상동맥혈관석회화와연관된독립인자로스타틴의사용과흡연, 그리고동맥경화도를측정한맥파혈류속도가관련성이있음을보였으나, 혈청 OPG와의연관성은보이지않았다. 이는 OPG가혈관석회화의원인물질이아닐가능성을생각해보게하는데, 연구자에따라혈청 OPG가혈관경직도의상승같은혈관질환의진행에대한반응성또는방어적인자로과잉분비되었을가능성을제시하고있다 24,25). 다변량회귀분석에서허리둘레, 당뇨병의유병기간이독립적인위험인자로나타났는데이는다른역학연구 26) 에서나타난결과와도일치하는결과로생각된다. 허리둘레의증가는중심성비만을시사하며내장지방의증가는제2형당뇨병에서인슐린저항성을높이고심혈관질환발생위험을높인다고알려져있다 27). 본연구의제한점으로는첫째, 본연구는횡단면적연구로관상동맥혈관석회화에영향을미칠것으로추정되는여러위험인자들과의상관관계만을확인할수있었다. 둘째, 일개병원당뇨병외래에내원한환자를대상으로실시한연구로한국인제2형당뇨병환자일반으로확장하여일정한결론을내리기에는무리가있을것으로생각된다. 셋째, 여성환자에서의비스포스포네이트의사용이나에스트로겐사용이관상동맥혈관석회화와연관이있을수있으나이에대한자료가없어제한점이있다. 이상의연구결과를통해관상동맥혈관석회화는연구대상자의 2/3에서관찰되었으며, 허리둘레, 당뇨병의유병기간, 혈청 creatinine 농도가관상동맥혈관석회화의독립적인위험인자임을알수있었다. 혈청 OPG 농도는관상동맥석회화의독립적인위험인자는아니어서관상동맥혈관석회화의혈청표지자로이용할수는없을것으로생각된다. 요약목적 : 본연구는심혈관증상이없는제2형당뇨병환자에서불현성관상동맥죽상경화증의유병률을알아보고, 혈 청 OPG 농도와관상동맥석회점수와의상관관계를분석하여혈청 OPG가관상동맥질환의혈청표지자로이용될수있을지알아보았다. 방법 : 심혈관증상이없는제2형당뇨병환자 140명을대상으로 MSCT 를이용하여관상동맥석회점수를정량하고혈청 OPG 농도를측정하여상관관계를분석하였다. 결과 : 심혈관증상이없는제2형당뇨병환자에서관상동맥석회화는 67.1% 에서관찰되었다. 상관분석에서, 관상동맥석회화점수와혈중 OPG농도는양의상관관계를보였으나, 다변량회귀분석에서는허리둘레 (p=0.003), 당뇨병의유병기간 (p=0.005), 혈청 creatinine 농도 (p=0.011) 가관상동맥석회화의유의한독립변수로나타났으며, 혈청 OPG 농도 (p=0.082) 는제외되었다. 결론 : 심혈관증상이없는제2형당뇨병환자에서관상동맥석회화는흔하게관찰되며, 혈청 OPG 농도는관상동맥석회점수에비례하여증가하나, 관상동맥석회점수의독립적인위험인자가아니므로, 관상동맥석회화를반영하는혈청지표로이용될수는없을것으로생각된다. 중심단어 : 혈청 Osteoprotegerin 농도 ; 관상동맥석회점수 ; 당뇨병 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, Rönnemaa T, Pyörälä 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 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 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 5) Shaw LJ, Raggi P, Schisterman E, Berman DS, Callister TQ. Prognostic value of cardiac risk factors and coronary artery cal- - 168 -
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