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1 가톨릭대학교의과대학여의도성모병원내과학교실김주연, 김미경, 정우백 Exercise Treadmill Test for Evaluation of Cardiovascular Disease in Diabetic Patients Ju Youn Kim, Mee Kyoung Kim, Woo-Baek Chung Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea Abstract 182 Patients with diabetes mellitus have a greater risk for coronary artery disease (CAD) than the general population, and CAD is the major cause of morbidity and mortality in this population. Therefore, its early detection is very important to improve the prognosis. Especially, in asymptomatic patients, a proper screening test to detect occult CAD is needed. The Treadmill Test, in this sense, is a useful tool which can be easily performed with low cost for screening for the presence of myocardial ischemia associated with diabetes mellitus. (J Korean Diabetes 2012;13: ) Keywords: Exercise test, Coronary artery disease, Diabetes mellitus 서론 본론 혈관의동맥경화성변화로관상동맥이좁아지게되면이로인해심장근육으로의혈액공급의장애가생겨협심증이발생하고, 심한경우심근경색이나심장마비가일어나게된다. 제 2 형당뇨병환자에서이러한급성심근경색이발생할위험성은정상인에비해 2 배이상증가하는것으로알려져있고, 이것은심혈관질환의이환과사망을증가시키는데기여하게된다 [1,2]. 관상동맥질환은기존의알려진심혈관질환의위험인자 ( 나이, 성별, 콜레스테롤, 수축기혈압, 흡연력, 당뇨병 ) 와관련이있으며, 특히당뇨병환자에게있어서여러지침들을통해이러한위험인자의조절을중요시하고있고위험인자에따른선별검사의필요성도제시하고있다. 이에당뇨병환자의심혈관질환평가방법중운동부하심전도의방법과의의, 적응증에대해서자세히알아보고자한다. 1. 운동부하심전도 (1) 목적과의의운동부하심전도는운동을통해심장에부하를주어안정시에는관찰되지않았던심장의이상을평가하여협심증여부나심장질환의정도를알아볼수있다. 심혈관질환의여러가지평가방법중운동부하심전도는적은비용으로비교적간단하게시행할수있는비침습적검사로반복적인검사가가능하며, 방사선이나조영제에대한위험부담없이관상동맥의기능적평가와예후를예측할수있다는장점이있다. 또한관상동맥질환환자에서운동부하심전도는 68% 의민감도와 77% 의특이도를가지고있어추가적인관상동맥조영술및치료의필요성을판단하는데좋은선별검사로알려져있다 [3]. (2) 적응증미국심장학회가이드라인에서는 ( A C C / A H A 교신저자 : 정우백, 서울시영등포구여의도동 62 번지여의도성모병원순환기내과, peace816@catholic.ac.kr

2 Guidelines) 운동부하검사를성별, 나이, 증상에근거하여중등도의관상동맥질환이의심되는환자에게시행할것을권고하고있다 [4]. 저위험군인무증상환자에서는관상동맥질환선별검사로서의진단적가치가제한적이어서권고하지않고있다. 당뇨병은동맥경화의고위험군으로무증상환자에게있어서도적절한선별검사가행해져야한다. 예로, 당뇨병환자가격렬한운동프로그램을시행하기전에운동부하검사를통해관상동맥질환을배제하여운동중급성관상동맥질환이발생하는것을예방할것을권장하고있다. 한연구에서는당뇨병의유병기간이 10 년이상된 60 세이상고령의무증상환자에서운동부하검사를시행했을때관상동맥질환의양성예측률이 87.5% 까지증가한다는보고도있다 [5]. 따라서당뇨병환자에서는나이, 성별, 당뇨병유병기간, 고지혈증, 흡연력등을고려하여무증상환자에서도관상동맥질환이의심되는환자에게운동부하검사를시행해야하며, 이를통해심혈관질환을예측하여이와관련한사망률을낮추고예후를향상시킬수있다. (3) 검사방법및해석운동부하심전도검사방법으로는표준 B r u c e protocol 이가장널리이용되는데, 이는 3 분간격으로운동강도를높이면서각단계에서 12 리드심전도와심박동수, 혈압을측정하게된다. 운동을마친이후에는적어도 5 분에서 10 분동안회복시기를가지고이때에도마찬가지로심전도와, 혈압, 증상을관찰한다 [3]. 운동부하심전도를이용한심질환평가는 ST-Segment 의변화, 심실성부정맥의발생, 혈압의변화, 협심증증상발생등을통해이루어진다. 이검사의객관화와예후예측을위해 Mark 등은 Duke Treadmill (TM) score 를만들었고다음과같은공식으로계산된다. TM score = 운동시간 ( 분 )-(5 x ST-segment 변화 (mm)) - (4 x TM angina index) (TM angina index: 0- 무증상, 1- 운동중증상발생, 2- 증상으로인한검사중단 ) TM score 가 -11 이하에서는 5 년생존율이 72%, +5 이상은 97% 로점수가낮을수록나쁜예후를보인다. 운동부하심전도에서이상을보이는고위험군환자는심혈관질환을강력히시사하는지표가된다 (Table 1)[3]. 이러한 ST-segment 변화를관찰할때안정시심전도에서조기흥분증후군이나영구심박동기리듬, 완전좌각차단또는 1 mm 이상의 ST-segment 저하가나타나면검사의특이도가떨어지기때문에이러한경우에는추가적인영상학적검사등이필요할수있다 (Fig 1)[4]. 2. 당뇨병환자에서운동부하심전도의의미 심혈관질환의증상이없는모든당뇨병환자를대상으로관상동맥질환에대한검사를시행하는데에는어려움이있다. 무증상당뇨병환자를대상으로시행한한연구에서는 6.4% 에서안정시심전도이상을보였고, 이중, 37% 가운동부하검사에서이상을보였다. 반면, 안정시심전도정상을보였던환자군에서는 10.3% 에서운동부하검사이상을나타냈다. 다변량분석을통한관상동맥질환의독립적위험인자로 ST-T 변화가위험도 9.27 로가장높게나타났다 [6]. 이와같이심혈관질환고위험군환자를선별하는것이필요하며, 상대적으로비용효율이높은운동부하심전도가좋은평가방법으로이용되고있다. 당뇨병환자에게있어서동맥경화성변화는당뇨병이환기간과미세혈관성합병증, 말초동맥질환, 자율신경병증의유무와높은상관관계를갖는다. 특히, 자율신경병증과감각신경병증을보이는당뇨병환자는 183 Table 1. Parameters associated with adverse prognosis and multi-vessel disease * Duration of symptom-limiting exercise < 5 METs * Failure to increase systolic blood pressure 120 mm Hg, or a sustained decrease 10 mm Hg, or below rest levels, during progressive exercise * ST-segment depression 2 mm, downsloping ST segment, starting at < 5METs, involving 5 leads, persisting 5 min into recovery * Exercise-induced ST-segment elevation (avr excluded) * Angina pectoris at low exercise workloads * Reproducible sustained (> 30 sec) or symptomatic ventricular tachycardia MET, metabolic equivalent. Adapted from Bonow et al. Bonow: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine; 2011[3].

3 협심증의증상을잘느끼지못할수있으며심근허혈에반응하는적절한혈압이나심박수의변동도나타나지않을수있다. 최근의연구들에서는운동부하검사를통해운동전후의심박수를관찰하여당뇨병환자의자율신경병증을진단할수있다는보고도있다 [7]. 반면, 관상동맥질환이있는당뇨병환자의심근부하에의한심전도변화는비당뇨병환자와차이를보이지않기때문에운동부하심전도는무증상당뇨병환자에게심혈관질환의선별검사로유용하게사용될수있다 [3]. 당뇨병환자에게이러한심혈관질환의조기발견이중요한이유는당뇨병의진행으로혈관내피세포의 기능장애를동반하게되고, 이로인해비당뇨병환자에비해유해심장사건의발생이증가하고나쁜예후를갖기때문이다 [8]. 그러나운동부하심전도가갖는제한점도있는데, 슬관절관절염을동반하거나특히당뇨병환자에서말초동맥질환을동반하는경우운동능력의감소로인해최대운동효과를나타내지못해불완전한검사결과를나타낼수있다. Possible indications for stress testing of patient: 1. Diagnosis of IHD uncertain Assess functional capacity of patient 3. Markely abnormal calcium score on CT Can patient exercise adequately? Yes Are confounding features present on resting ECG? : Left bundle branch block Ventricular hypertrophy Resting ST segment depression Yes No An Imaging study should be performed Pacemaker No Perform treadmill exercise test Fig. 1. Evaluation of the patient with suspected ischemic heart disease. IHD, ischemic heart disease; CT, computed tomography; ECG, electrocardiography. Table 2. Comparisons between treadmill test and cardiac computed tomography (CT) Treadmill test Cardiac CT Costs $ $$$ Usage Easy Difficulty Exposure to radiation None High Exposure to contrast None High Sensitivity 68% 80% Specificity 77% Low Etc. Exercise capacity Coronary artery anatomy, calcium score

4 3. 운동부하심전도와관상동맥컴퓨터단층촬영 (Table 2) 최근에는관상동맥컴퓨터단층촬영 (CT) 도조기선별을위해많이이용되는비침습적검사방법중하나이다. 관상동맥 CT 는운동부하심전도에비해높은민감도와음성예측도를갖지만상대적으로낮은특이도를갖는다. 이러한높은음성예측도로인해관상동맥 C T 는흉통을호소하는환자들에게서관상동맥질환을배제하는데사용될수있다. 또한관상동맥뿐아니라, 판막이나심근, 폐, 대동맥등의해부학적이상이나동반질환에대한정보를제공한다는장점이있다. 관상동맥 CT 는해상도의발전으로비교적정확도가높은검사로자리잡았지만, 여전히방사선노출과조영제사용의부담을가지고있으며, 양질의영상을얻기위해서는베타차단제등의약제를이용하여심박동수를낮춰야한다는단점이있다. 또한, 정확한병변의예측을위해서는특정한기술적인방법이필요하며, 그럼에도불구하고여러요인들의영향을받아일부는해석이불가한경우도있다. 당뇨병환자들에서는특히혈관의석회화가심한경우가많은데관상동맥 CT 는석회화가심한경우관상동맥경화증의지표가될수는있지만협착의정도를평가하는데에는방해가될수있다. 운동부하심전도는기능적인평가방법으로서미세혈관협심증에서도심전도의변화를볼수있는반면, 관상동맥 CT 는영상을통한평가로기능적인면의고려가어렵고, 근위부혈관과비교적큰직경의혈관에서분석이가능하다 [3]. 따라서무증상환자에게는비석회화경화반의발견이어려운경우가많아무증상환자의선별검사로는권고하고있지않다 [3]. 최근에는이러한 CT 의한계점을보완하여관상동맥안에직접도자를넣어혈류량의비율을구해협착부위의기능적평가를할수있는침습적방법인분획혈류예비력 (FFR) 과비침습적검사인 CT 를접목시킨 FFR- CT 등이연구되고있다 [9]. 결론 당뇨병의대혈관합병증중에서도관상동맥질환은사망률과예후에많은영향을미치는인자이다. 당뇨병환자는미세혈관합병증을동반하는경우증상이경미하거나나타나지않을수있으며당뇨병으로인한내피세포의기능장애로인해복수혈관질환을보이는경우가많아조기선별이중요하다. 운동부하심전도는비교적손쉽고예측도가높은기능적평가방법으로이용되고있으며, 증상이없는 고위험군환자에게관상동맥질환의유무를예측하는데유용하게사용될수있다. 생활습관교정및다른위험인자의조절과더불어, 연령, 말초동맥질환유무, 안정시심전도변화등을고려하여적절한고위험군에게적극적인선별검사를시행하여심혈관계합병증과사망률을낮추려는노력이필요할것이다. 참고문헌 01. S Buse JB, Ginsberg HN, Bakris GL, Clark NG, Costa F, Eckel R, Fonseca V, Gerstein HC, Grundy S, Nesto RW, Pignone MP, Plutzky J, Porte D, Redberg R, Stitzel KF, Stone NJ; American Heart Association; American D i a b e tes A ss o c i a t i o n. P r i m a r y p revention o f cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association. Circulation 2007;115: S Young LH, Wackers FJ, Chyun DA, Davey JA, Barrett EJ, Taillefer R, Heller GV, Iskandrian AE, Wittlin SD, Filipchuk N, Ratner RE, Inzucchi SE; DIAD Investigators. Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. JAMA 2009;301: S Bonow RO, Mann DL, Zipes DP, Libby P. Bonow: B r a u n w a l d ' s H e a r t D i s e a s e : A Te x t b o o k o f Cardiovascular Medicine. 9th ed. Philadelphia: Saunders; p168-99, p S Gibbons RJ, Balady GJ, Bricker JT, Chaitman BR, Fletcher GF, Froelicher VF, Mark DB, McCallister BD, Mooss AN, O'Reilly MG, Winters WL, Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK, Russell RO, Smith SC; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Committee to Update the 1997 Exercise Testing Guidelines. ACC/AHA 2002 guideline update for exercise testing: summary article. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). J Am Coll Cardiol 2002;40: S Kim MK, Baek KH, Song KH, Kwon HS, Lee JM, Kang MI, Yoon KH, Cha BY, Son HY, Lee KW. Exercise treadmill test in detecting asymptomatic coronary artery disease in type 2 diabetes mellitus. Diabetes Metab J 2011;35: S Prevalence of unrecognized silent myocardial ischemia and its association with atherosclerotic risk factors in noninsulin-dependent diabetes mellitus. Milan Study on Atherosclerosis and Diabetes (MiSAD) Group. Am J 185

5 Cardiol 1997;79: S HSacre JW, Jellis CL, Coombes JS, Marwick TH. Diagnostic accuracy of heart-rate recovery after exercise in the assessment of diabetic cardiac autonomic neuropathy. Diabet Med 2012;29:e S Poirier P, Després JP, Bertrand OF. Identifying which patients with diabetes should be tested for the presence of coronary artery disease-the importance of baseline electrocardiogram and exercise testing. Can J Cardiol 2006;22 Suppl A:9A-15A. 09.S Koo BK, Erglis A, Doh JH, Daniels DV, Jegere S, Kim HS, Dunning A, DeFrance T, Lansky A, Leipsic J, Min JK. Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve) study. J Am Coll Cardiol 2011;58:

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A 617 Special Issue Diabetic Retinopathy Won Ki Lee, M.D. Department of Ophthalmology The Catholic University of Korea College of Medicine Kangnam St. Mary s Hospital E mail : wklee@catholic.ac.kr Abstract R