J Korean Diabetes 2019;20:17-23 Vol.20, No.1, 2019 ISSN 2233-7431 말초혈관질환의진단 : 2016 American Heart Association/ American College of Cardiology 및 2017 European Society of Cardiology 가이드라인을중심으로 성균관대학교의과대학삼성서울병원내분비 - 대사내과 Diagnosis of Peripheral Artery Disease: Focus on the 2016 American Heart Association/American College of Cardiology and 2017 European Society of Cardiology Guidelines Kyu Yeon Hur Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Abstract Peripheral artery disease (PAD) is the most frequent cause of reduced perfusion in peripheral arteries. Patients with PAD often have manifestations of atherosclerosis of the lower limb, although both symptomatic and asymptomatic disease is common. The clinical signs of PAD can differ in diabetic and non-diabetic patients. Diabetic patients are at high risk for PAD characterized by symptoms of intermittent claudication or critical limb ischemia. However, the majority of PAD patients are clinically asymptomatic. In addition to history taking, physical examinations including inspection of the skin, palpation of leg and foot pulses, and determination of the ankle-brachial index (ABI) are considered for diagnosis of PAD. The ABI measurement is the easiest and most common investigative technique for PAD. For hemodynamic assessment, additional diagnostic modalities could be considered. Keywords: Ankle brachial index, Diabetes mellitus, Peripheral arterial disease Corresponding author: Kyu Yeon Hur Division of Endocrinology and Metabolism, Department of Medicine, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea, E-mail: ky.hur@samsung.com Received: Feb. 7, 2019; Accepted: Feb. 8, 2019 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/bync/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright c 2019 Korean Diabetes Association The Journal of Korean Diabetes 17
말초혈관질환의진단 서론 말초혈관질환의고위험군은병력청취와증상문진및진찰을통해말초혈관질환이있는지평가해야한다. 말초혈관질환의고위험군이란다음의경우를말한다. 1) 나이 65세이상인경우, 2) 나이가 50~64세이면서죽상경화증의위험인자 ( 예 : 당뇨병, 흡연, 이상지질혈증, 고혈압 ) 를갖고있거나혹은말초혈관질환의가족력이있는경우, 3) 나이가 50세미만이면서당뇨병이있고죽상경화증의위험인자를한개이상갖고있는경우, 4) 다른혈관질환 ( 관상동맥, 경동맥, subclavian, 신장, mesenteric 동맥협착증혹은복부대동맥류 ) 이있음을이미알고있는경우. 임상병력청취상전형적인파행 (claudication), 관절과연관없는움직일때의사지증상 ( 전형적인파행증상은아님 ), 보행기능저하, 휴식기허혈통증등이있으면말초혈관질환을의심해볼수있다 [1]. 말초혈관질환의증상과증후는매우다양하다. 말초혈관질환의전형적인파행이나중증의사지허혈과같은증상을나타내기도하지만 [2-7], 말초혈관질환을진단받은환자들의상당수는전형적인파행이없거나사지허혈과연관된증상이아닌비전형적인사지증상혹은무증상인경우가많다 [2,3]. 말초혈관의진찰은맥박촉진, 대퇴골잡음청진, 다리와발을시진하는것으로이루어진다. 맥박촉진시비정상적이거나맥박이잘만져지지않을경우, 청진시혈관잡음이들릴경우, 시진시사지의상처가잘아물지않은것이관찰되거나하지의괴사등이보이면말초혈관질환을의심해야한다 [6,8,9]. 위와같은병력청취, 증상과증후및진찰을통해말초혈관질환이의심된다면이를확진하기위한검사들을시행할필요가있다. 본론에서말초혈관질환확진을위한검사들에대해서논하고자한다. 최근 2016년 American Heart Association (AHA) and American College of Cardiology (ACC) 가이드라인 [10] 과 2017년 European Society of Cardiology (ESC) and European Society of Vascular Surgery (ESVS) 가이드라인 [11] 을참고로살펴보고자한다. 말초혈관질환에서당뇨병환자와비당뇨병환자의차이는있으나초기진단적접근은크게다르지는않아본론에서는일반적인말초혈관질환의접근법으로언급하고자한다. 본론 1. 말초혈관질환의진단병력청취, 증상, 진찰소견등을통해서말초혈관이의심된다면확진을하기위한검사가필요하다. 1) 휴식기발목-위팔지수 (resting ankle-brachial index) 말초혈관질환진단을위해서휴식기발목-위팔지수 (ankle-brachial index, ABI) 를가장먼저실시할것을권고한다 [12-19]. 매우간단하고비침습적인진단방법이다. 누운자세에서도플러를이용하여양쪽위팔 (brachial arteries) 과양쪽발목 (dorsalis pedis와 posterior tibial arteries) 에서혈압을측정한다. 발목혈압은 dorsalis pedis pressure와 posterior tibial pressure 중높은혈압을선택하고양쪽위팔혈압중높은위팔혈압을선택하여, 발목혈압을위팔혈압으로나눈값으로양쪽각각의발목-위팔지수로채택하면된다 [14]. 휴식기발목-위팔지수결과는비정상 ( 0.90), 경계 (0.91~0.99), 정상 (1.00~1.40), 압축이되지않는혈관 (> 1.40) 으로보고한다 [14,17-20]. 말초혈관질환의고위험군이나병력청취나진찰과정에서의심할만한정황이없다면발목-위팔지수를검사해보는것을권고한다 [2,4,21-24]. 그러나말초혈관질환의고위험군이아니고병력청취나진찰과정에서도의심할만한정황도없다면발목-위팔지수검사를권고하지는않는다 [25-27]. 2) Segmental lower extremity blood pressure and Doppler or plethysmographic waveforms (pulse volume recordings) 이검사는종종발목-위팔지수와함께시행하는경우 18
가많다. 병변이있는부위 (aortoiliac, femoropopliteal, infrapopliteal) 를찾기위해사용할수있다 [28,29]. 3) 생리학적기능평가를위한검사들 1 운동부하시발목-위팔지수 (exercise treadmill anklebrachial index) 하지증상에영향을줄수있는기능적인제한을객관적으로측정할목적으로시행할수있으며, 말초혈관질환의증상은있는데휴식기발목-위팔지수가정상혹은경계의범위에있는경우 (> 0.90 and < 1.40) 에말초혈관질환의진단을확정하기위해시행을권고한다. 또한발목-위팔지수가비정상인경우 (< 0.90) 에서도객관적으로기능을평가하기위해시행할수있다 [29-35]. 2 발가락-위팔지수 (toe-brachial index) 석회화로인해압축이되지않는혈관 (non-compressible arteries, ABI > 1.40) 에서혹은위중한하지허혈 (critical limb ischemia) 이의심되는환자에서관류 (perfusion) 여부를평가할때시행할수있다 [35-38]. 3 경피산소분압 (transcutaneous oxygen pressure, TcPO 2 ) 이나피부관류압 (skin perfusion pressure) 발목-위팔지수가정상이거나경계에해당하나 (> 0.90 and 1.40) 낫지않는상처나괴사가있다면, 위중한하지허혈을진단하기위해파형검사를동반한발가락-위팔지수측정이나경피산소분압혹은피부관류압검사를고려할수있다. 또발목-위팔지수가비정상이면서 ( 0.90) 낫지않는상처나괴사를동반하고있다면국소관류여부를확인하기위해파형검사를동반한발가락-위팔지수측정이나경피산소분압혹은피부관류압검사를고려할수있다 [39-43]. 4) 해부학적위치파악을위한영상검사들 Duplex ultrasound, computed tomography angiography (CTA), magnetic resonance angiography (MRA), invasive angiography 등은증상이있는고위험군환자에서혈관개통 (revascularization) 을고려할경우에시행한다 [44-47]. 이러한방법들은그검사방법에따라시술에따른위험도가있을수도있다. 따라서비침습적혹은침습적인혈관촬영 (CTA 혹은 MRA) 은무증상인환자에서해부학적위치를찾을목적으로시행하지말것을권고한다 [48-50]. 결론 말초혈관질환의진단에관해 2016 AHA/ACC와 2017 ESC 가이드라인을참고로살펴보았다. 이두가지가이드라인을볼때염두에둘것이있는데, 우선 AHA/ACC 가이드라인은말초혈관질환을보게되는모든의사들을대상으로하며하지혈관질환에국한하여설명하고있는반면에 ESC 가이드라인은순환기전문의들을대상으로하며하지혈관질환뿐만아니라다른말초혈관질환도포함하고있다. 또, AHA/ACC 가이드라인은소규모라도잘디자인된비무작위연구도상당부분채택하고고려한반면, ESC 가이드라인은이런연구는증거레벨 C로평가하였다는차이가있다 [51]. 그러나두가이드라인모두말초혈관질환의심시진단적접근에서는큰차이는없다. 첫진단적검사로발목-위팔지수를시행하도록권고하고있으며처음부터해부학적위치를판단하기위한영상검사를하는것은권고하지않는다. 다만, 발목-위팔지수검사만으로는놓치는경우가있어이를위한다른추가적인검사들을고려할수있을것이다. REFERENCES 1. Wassel CL, Loomba R, Ix JH, Allison MA, Denenberg JO, Criqui MH. Family history of peripheral artery disease is associated with prevalence and severity of peripheral artery disease: the San Diego population study. J Am Coll Cardiol 2011;58:1386-92. 2. McDermott MM, Mehta S, Greenland P. Exertional leg symptoms other than intermittent claudication are common in peripheral arterial disease. Arch Intern Med www.diabetes.or.kr 19
말초혈관질환의진단 1999;159:387-92. 3. Hirsch AT, Criqui MH, Treat-Jacobson D, Regensteiner JG, Creager MA, Olin JW, Krook SH, Hunninghake DB, Comerota AJ, Walsh ME, McDermott MM, Hiatt WR. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA 2001;286:1317-24. 4. McDermott MM, Greenland P, Liu K, Guralnik JM, Criqui MH, Dolan NC, Chan C, Celic L, Pearce WH, Schneider JR, Sharma L, Clark E, Gibson D, Martin GJ. Leg symptoms in peripheral arterial disease: associated clinical characteristics and functional impairment. JAMA 2001;286:1599-606. 5. Rose GA. The diagnosis of ischaemic heart pain and intermittent claudication in field surveys. Bull World Health Organ 1962;27:645-58. 6. Khan NA, Rahim SA, Anand SS, Simel DL, Panju A. Does the clinical examination predict lower extremity peripheral arterial disease? JAMA 2006;295:536-46. 7. Criqui MH, Denenberg JO, Bird CE, Fronek A, Klauber MR, Langer RD. The correlation between symptoms and non-invasive test results in patients referred for peripheral arterial disease testing. Vasc Med 1996;1:65-71. 8. Armstrong DW, Tobin C, Matangi MF. The accuracy of the physical examination for the detection of lower extremity peripheral arterial disease. Can J Cardiol 2010;26:e346-50. 9. Cournot M, Boccalon H, Cambou JP, Guilloux J, Taraszkiewicz D, Hanaire-Broutin H, Chamontin B, Galinier M, Ferrières J. Accuracy of the screening physical examination to identify subclinical atherosclerosis and peripheral arterial disease in asymptomatic subjects. J Vasc Surg 2007;46:1215-21. 10. Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE, Fleisher LA, Fowkes FG, Hamburg NM, Kinlay S, Lookstein R, Misra S, Mureebe L, Olin JW, Patel RA, Regensteiner JG, Schanzer A, Shishehbor MH, Stewart KJ, Treat-Jacobson D, Walsh ME. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: executive summary: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Circulation 2017;135:e686-725. 11. Aboyans V, Ricco JB, Bartelink MEL, Björck M, Brodmann M, Cohnert T, Collet JP, Czerny M, De Carlo M, Debus S, Espinola-Klein C, Kahan T, Kownator S, Mazzolai L, Naylor AR, Roffi M, Röther J, Sprynger M, Tendera M, Tepe G, Venermo M, Vlachopoulos C, Desormais I. 2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteriesendorsed by: the European Stroke Organization (ESO)The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J 2018;39:763-816. 12. Clark CE, Taylor RS, Shore AC, Ukoumunne OC, Campbell JL. Association of a difference in systolic blood pressure between arms with vascular disease and mortality: a systematic review and meta-analysis. Lancet 2012;379:905-14. 13. Singh S, Sethi A, Singh M, Khosla K, Grewal N, Khosla S. Simultaneously measured inter-arm and inter-leg systolic blood pressure differences and cardiovascular risk stratification: a systemic review and meta-analysis. J Am Soc Hypertens 2015;9:640-50.e12. 14. Aboyans V, Criqui MH, Abraham P, Allison MA, Creager 20
MA, Diehm C, Fowkes FG, Hiatt WR, Jönsson B, Lacroix P, Marin B, McDermott MM, Norgren L, Pande RL, Preux PM, Stoffers HE, Treat-Jacobson D. Measurement and interpretation of the ankle-brachial index: a scientific statement from the American Heart Association. Circulation 2012;126:2890-909. 15. Premalatha G, Ravikumar R, Sanjay R, Deepa R, Mohan V. Comparison of colour duplex ultrasound and anklebrachial pressure index measurements in peripheral vascular disease in type 2 diabetic patients with foot infections. J Assoc Physicians India 2002;50:1240-4. 16. Allen J, Oates CP, Henderson J, Jago J, Whittingham TA, Chamberlain J, Jones NA, Murray A. Comparison of lower limb arterial assessments using color-duplex ultrasound and ankle/brachial pressure index measurements. Angiology 1996;47:225-32. 17. Lijmer JG, Hunink MG, van den Dungen JJ, Loonstra J, Smit AJ. ROC analysis of noninvasive tests for peripheral arterial disease. Ultrasound Med Biol 1996;22:391-8. 18. Guo X, Li J, Pang W, Zhao M, Luo Y, Sun Y, Hu D. Sensitivity and specificity of ankle-brachial index for detecting angiographic stenosis of peripheral arteries. Circ J 2008;72:605-10. 19. Niazi K, Khan TH, Easley KA. Diagnostic utility of the two methods of ankle brachial index in the detection of peripheral arterial disease of lower extremities. Catheter Cardiovasc Interv 2006;68:788-92. 20. Aboyans V, Ho E, Denenberg JO, Ho LA, Natarajan L, Criqui MH. The association between elevated ankle systolic pressures and peripheral occlusive arterial disease in diabetic and nondiabetic subjects. J Vasc Surg 2008;48:1197-203. 21. Lin JS, Olson CM, Johnson ES, Whitlock EP. The ankle-brachial index for peripheral artery disease screening and cardiovascular disease prediction among asymptomatic adults: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 2013;159:333-41. 22. Diehm C, Allenberg JR, Pittrow D, Mahn M, Tepohl G, Haberl RL, Darius H, Burghaus I, Trampisch HJ. Mortality and vascular morbidity in older adults with asymptomatic versus symptomatic peripheral artery disease. Circulation 2009;120:2053-61. 23. Ankle Brachial Index Collaboration, Fowkes FG, Murray GD, Butcher I, Heald CL, Lee RJ, Chambless LE, Folsom AR, Hirsch AT, Dramaix M, debacker G, Wautrecht JC, Kornitzer M, Newman AB, Cushman M, Sutton- Tyrrell K, Fowkes FG, Lee AJ, Price JF, d'agostino RB, Murabito JM, Norman PE, Jamrozik K, Curb JD, Masaki KH, Rodríguez BL, Dekker JM, Bouter LM, Heine RJ, Nijpels G, Stehouwer CD, Ferrucci L, McDermott MM, Stoffers HE, Hooi JD, Knottnerus JA, Ogren M, Hedblad B, Witteman JC, Breteler MM, Hunink MG, Hofman A, Criqui MH, Langer RD, Fronek A, Hiatt WR, Hamman R, Resnick HE, Guralnik J, McDermott MM. Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis. JAMA 2008;300:197-208. 24. Bundó M, Muñoz L, Pérez C, Montero JJ, Montellà N, Torán P, Pera G. Asymptomatic peripheral arterial disease in type 2 diabetes patients: a 10-year follow-up study of the utility of the ankle brachial index as a prognostic marker of cardiovascular disease. Ann Vasc Surg 2010;24:985-93. 25. Guirguis-Blake JM, Evans CV, Redmond N, Lin JS. Screening for peripheral artery disease using the anklebrachial index: updated evidence report and systematic review for the US preventive services task force. JAMA 2018;320:184-96. 26. O'Hare AM, Glidden DV, Fox CS, Hsu CY. High www.diabetes.or.kr 21
말초혈관질환의진단 prevalence of peripheral arterial disease in persons with renal insufficiency: results from the National Health and Nutrition Examination Survey 1999-2000. Circulation 2004;109:320-3. 27. Criqui MH, Vargas V, Denenberg JO, Ho E, Allison M, Langer RD, Gamst A, Bundens WP, Fronek A. Ethnicity and peripheral arterial disease: the San Diego Population Study. Circulation 2005;112:2703-7. 28. Eslahpazir BA, Allemang MT, Lakin RO, Carman TL, Trivonovich MR, Wong VL, Wang J, Baele HR, Kashyap VS. Pulse volume recording does not enhance segmental pressure readings for peripheral arterial disease stratification. Ann Vasc Surg 2014;28:18-27. 29. Raines JK, Darling RC, Buth J, Brewster DC, Austen WG. Vascular laboratory criteria for the management of peripheral vascular disease of the lower extremities. Surgery 1976;79:21-9. 30. Mahe G, Pollak AW, Liedl DA, Cohoon KP, Mc Carter C, Rooke TW, Wennberg PW. Discordant diagnosis of lower extremity peripheral artery disease using American Heart Association postexercise guidelines. Medicine (Baltimore) 2015;94:e1277. 31. Nicolaï SP, Viechtbauer W, Kruidenier LM, Candel MJ, Prins MH, Teijink JA. Reliability of treadmill testing in peripheral arterial disease: a meta-regression analysis. J Vasc Surg 2009;50:322-9. 32. Stein R, Hriljac I, Halperin JL, Gustavson SM, Teodorescu V, Olin JW. Limitation of the resting ankle-brachial index in symptomatic patients with peripheral arterial disease. Vasc Med 2006;11:29-33. 33. Laing SP, Greenhalgh RM. Standard exercise test to assess peripheral arterial disease. Br Med J 1980;280:13-6. 34. Sumner DS, Strandness DE Jr. The relationship between calf blood flow and ankle blood pressure in patients with intermittent claudication. Surgery 1969;65:763-71. 35. Schröder F, Diehm N, Kareem S, Ames M, Pira A, Zwettler U, Lawall H, Diehm C. A modified calculation of ankle-brachial pressure index is far more sensitive in the detection of peripheral arterial disease. J Vasc Surg 2006;44:531-6. 36. Carter SA, Tate RB. Value of toe pulse waves in addition to systolic pressures in the assessment of the severity of peripheral arterial disease and critical limb ischemia. J Vasc Surg 1996;24:258-65. 37. Ramsey DE, Manke DA, Sumner DS. Toe blood pressure. A valuable adjunct to ankle pressure measurement for assessing peripheral arterial disease. J Cardiovasc Surg (Torino) 1983;24:43-8. 38. Vincent DG, Salles-Cunha SX, Bernhard VM, Towne JB. Noninvasive assessment of toe systolic pressures with special reference to diabetes mellitus. J Cardiovasc Surg (Torino) 1983;24:22-8. 39. Biotteau E, Mahe G, Rousseau P, Leftheriotis G, Abraham P. Transcutaneous oxygen pressure measurements in diabetic and non-diabetic patients clinically suspected of severe limb ischemia: a matched paired retrospective analysis. Int Angiol 2009;28:479-83. 40. Yamada T, Ohta T, Ishibashi H, Sugimoto I, Iwata H, Takahashi M, Kawanishi J. Clinical reliability and utility of skin perfusion pressure measurement in ischemic limbs-- comparison with other noninvasive diagnostic methods. J Vasc Surg 2008;47:318-23. 41. Castronuovo JJ Jr, Adera HM, Smiell JM, Price RM. Skin perfusion pressure measurement is valuable in the diagnosis of critical limb ischemia. J Vasc Surg 1997;26:629-37. 42. Bunte MC, Jacob J, Nudelman B, Shishehbor MH. Validation of the relationship between ankle-brachial and toe-brachial indices and infragenicular arterial patency in critical limb ischemia. Vasc Med 2015;20:23-9. 22
43. Shishehbor MH, Hammad TA, Zeller T, Baumgartner I, Scheinert D, Rocha-Singh KJ. An analysis of IN.PACT DEEP randomized trial on the limitations of the societal guidelines-recommended hemodynamic parameters to diagnose critical limb ischemia. J Vasc Surg 2016;63:1311-7. 44. Burbelko M, Augsten M, Kalinowski MO, Heverhagen JT. Comparison of contrast-enhanced multi-station MR angiography and digital subtraction angiography of the lower extremity arterial disease. J Magn Reson Imaging 2013;37:1427-35. 45. Shareghi S, Gopal A, Gul K, Matchinson JC, Wong CB, Weinberg N, Lensky M, Budoff MJ, Shavelle DM. Diagnostic accuracy of 64 multidetector computed tomographic angiography in peripheral vascular disease. Catheter Cardiovasc Interv 2010;75:23-31. 46. Ota H, Takase K, Igarashi K, Chiba Y, Haga K, Saito H, Takahashi S. MDCT compared with digital subtraction angiography for assessment of lower extremity arterial occlusive disease: importance of reviewing cross-sectional images. AJR Am J Roentgenol 2004;182:201-9. 47. de Vries SO, Hunink MG, Polak JF. Summary receiver operating characteristic curves as a technique for meta-analysis of the diagnostic performance of duplex ultrasonography in peripheral arterial disease. Acad Radiol 1996;3:361-9. 48. Andreucci M, Solomon R, Tasanarong A. Side effects of radiographic contrast media: pathogenesis, risk factors, and prevention. Biomed Res Int 2014;2014:741018. 49. Stacul F, van der Molen AJ, Reimer P, Webb JA, Thomsen HS, Morcos SK, Almén T, Aspelin P, Bellin MF, Clement O, Heinz-Peer G. Contrast induced nephropathy: updated ESUR Contrast Media Safety Committee guidelines. Eur Radiol 2011;21:2527-41. 50. McCullough PA, Capasso P. Patient discomfort associated with the use of intra-arterial iodinated contrast media: a meta-analysis of comparative randomized controlled trials. BMC Med Imaging 2011;11:12. 51. Kithcart AP, Beckman JA. ACC/AHA versus ESC guidelines for diagnosis and management of peripheral artery disease: JACC guideline comparison. J Am Coll Cardiol 2018;72:2789-801. www.diabetes.or.kr 23