JNN Scientific Statement pissn 2635-425X eissn 2635-4357 https://doi.org/10.31728/jnn.2018.00025 경부혈관초음파표준검사지침. 2 부 - 임상적유용성 이종윤 1*, 최혜연 1, 이성익, 황양하, 조아현, 서우근, 이승재, 유성욱, 홍지만 #, 안성환 **, 정슬기, 김상범, 최재철, 한상원, 고임석 *, 황성희, 이용석, 이준홍, 석승한, 김용재 ##, 송희정 ***, 권형민 2, 박종호 2 국립중앙의료원신경과 *, 강동경희대병원신경과, 원광대학교의과대학산본병원신경과, 경북대학교병원신경과, 가톨릭대학교여의도성모병원신경과, 성균관대학교의과대학삼성서울병원신경과, 순천향대학교의과대학부천병원신경과, 고려대학교의과대학안암병원신경과, 아주대학교병원신경과 #, 조선대학교병원신경과 **, 정슬기신경과의원, 제주대학교병원신경과, 인제대학교상계백병원신경과, 한림대학교강남성심병원신경과, 서울대학교보라매병원신경과, 국민건강보험공단일산병원신경과, 이화여자대학교목동병원신경과 ##, 충남대학교병원신경과 ***, 한양대학교명지병원신경과 Extracranial Carotid Duplex Ultrasonography. Part II - Clinical Utility of Carotid Duplex Ultrasound Jong Yun Lee 1*, Hye-Yeon Choi 1, Sung Ik Lee, Yang-Ha Hwang, A-Hyun Cho, Woo-Keun Seo, Seung-Jae Lee, Sungwook Yu, Ji Man Hong #, Seong Hwan Ahn **, Seul-Ki Jeong, Sang-Beom Kim, Jay Chol Choi, Sang Won Han, Im Seok Koh *, Sung-Hee Hwang, Yong-Seok Lee, Jun Hong Lee, Seung-Han Suk, Yong-Jae Kim ##, Hee-Jung Song ***, Hyung-Min Kwon 2, Jong-Ho Park 2 Departments of Neurology, National Medical Center *, Kyung Hee University Hospital at Gangdong, Wonkwang University College of Medicine, Kyungpook National University College of Medicine, Catholic University of Korea Yeouido St. Mary s Hospital, Samsung Medical Center, Sungkyunkwan University School of Medicine, Soonchunhyang University College of Medicine, Korea University College of Medicine, Ajou University College of Medicine #, Chosun University College of Medicine **, JSK Neurology Clinic, Jeju National University School of Medicine, Inje University College of Medicine, Hallym University College of Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Ilsan Hospital, National Health Insurance Service, Ehwa Women s University College of Medicine ##, Chungnam National University Hospital ***, Myongji Hospital, Hanyang University College of Medicine, Korea Carotid duplex ultrasonography (CDU) is noninvasive and easy to use for evaluation of various carotid artery diseases. Carotid atherosclerosis is a major indication for CDU. CDU can determine the degree of stenosis, plaque characteristics, and intima-media thickness for evaluation and estimation of carotid atherosclerosis, and can be used as a screening and follow-up tool after carotid revascularization. Here, we summarize the clinical indications and utility of CDU based on established evidence. The main topics include: 1) Evaluation and management of symptomatic and asymptomatic carotid atherosclerotic stenosis; 2) surveillance after carotid artery revascularization; 3) screening for cardiovascular risk; 4) perioperative evaluation; 5) evaluation of other diseases including cervical artery dissection, temporal arteritis, Takayasu s disease, and subclavian artery steal syndrome; and 6) diagnosis of dizziness, vertigo, and syncope. This special review will discuss rational indications and utility of CDU, and will be of interest to clinicians who provide care for patients with various extracranial carotid/vertebral artery diseases. Key Words: Carotid duplex ultrasonography; Clinical indication; Clinical utility 1 Jong Yun Lee and Hye-Yeon Choi contributed equally to this work as first author. 2 Jong-Ho Park and Hyung-Min Kwon contributed equally to this work as corresponding author. Received: September 21, 2018 Revised: October 26, 2018 Accepted: November 20, 2018 Address for correspondence: Jong-Ho Park Department of Neurology, Myongji Hospital, Hanyang University College of Medicine 55 Hwasu-ro 14beon-gil, Deogyang-gu, Goyang 10475, Korea Tel: +82-31-810-5460 Fax: +82-31-969-0500 E-mail: jhpark619@hanyang.ac.kr Hyung-Min Kwon Department of Neurology, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, 20 Boramae-ro 5-gil, Dongjak-gu, Seoul 07061, Korea Tel: +82-2-870-2475 Fax: +82-2-831-2826 E-mail:hmkwon@snu.ac.kr Copyright 2018 The Korean Society of Neurosonology This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
JNN Lee JY and Choi HY, et al. Clinical Utility of Carotid Duplex Ultrasound 서론 경동맥이중초음파 (carotid duplex ultrasonography) 는검사영역이국한적이고, 석회화가심한경우평가가어려운한계점이있으나, 죽상판의유무뿐아니라그형태도평가할수있는장점이있다. 또한, 무엇보다상대적으로경제적이며, 안전한비침습적검사로써경동맥질환을진단하고추적하는데유용한검사로많이활용되고있다. 1 그러나검사의대상이되는경동맥질환및검사의유용성에대하여아직까지체계적으로정립되어있지않다. 대한신경초음파학회에서는 2016년에경두개도플러초음파검사의기준을마련하기위하여가이드라인을제시한바있다. 2,3 이번에는경동맥이중초음파검사의가이드라인으로마련하고자 1부에서경동맥과경정맥초음파의기본원리및표준검사방법을제시하였고, 본 2부에서는폭넓은문헌고찰을통하여임상에서경동맥이중초음파가필요한질환, 검사의유용성그리고검사시기등에대해서총괄적으로다루고자한다. 경동맥협착 1. 증후성경동맥협착 증후성경동맥협착 (symptomatic carotid stenosis) 은죽상경화로인한내경동맥의협착으로인하여해당내경동맥의혈관영역에서허혈증상이발생하는경우를의미한다. 경동맥질환과연관된허혈질환으로는동측안구의일과성흑암시 (amaurosis fugax), 중심또는가지망막동맥폐색 (central or branch retinal artery occlusion), 허혈시신경병증 (ischemic optic neuropathy) 등의눈증상혹은다양한대뇌반구증상을동반한뇌경색혹은일과성허혈발작 (transient ischemic attack) 이포함된다. 증후성경동맥협착이있는환자에서뇌졸중의재발위험도는연간약 8-13% 로알려져있으며, 무증 상성경동맥협착이 50% 이상인경우이로인하여추후발병하는뇌경색이전체뇌경색환자의약 7-15% 에이른다. 4,5 경동맥협착이뇌경색을유발하는기전은죽상경화판에서발생한혈전에의한동맥-동맥색전, 죽상경화판에서기인한콜레스테롤크리스탈등에의한색전, 두개외혈관의죽상경화판의파열로인한급성폐색, 두개외혈관의박리나내피내혈전, 협착에의한뇌관류저하등이제시되고있다. 6 증후성경동맥협착은적극적인치료를할경우에도증상재발률이높다고알려져있다. 내과적치료와경동맥내막절제술을비교한 European Carotid Surgery Trial (ECST) 연구에서는 3년이경과할때까지내과적치료군에서는약 25.9% 에서, 경동맥내막절제술을시행할경우에는약 14.9% 에서뇌졸중이재발하였고, 7 North American Symptomatic Carotid Endarterectomy Trial (NASCET) 에서는내과적치료만시행한경우 3-5년이경과할때약 25% 의환자에서, 경동맥내막절제술을시행한경우에는약 10-15% 에서뇌경색이재발하였다. 8 이와같은높은재발률은최근의연구에서는다소감소하고있는데, 경동맥내막절제술과경동맥스텐트삽입술을비교한 International Carotid Stenting Study (ICSS) 의장기간연구에서는경동맥내막절제술혹은경동맥스텐트삽입술을시행한경우 5년재발률이각각약 9.4% 및 15.2% 였다. 9 1) 증후성경동맥협착증에서의경동맥이중초음파검사의유용성 (1) 협착정도의진단경동맥협착을평가하는방법으로는 NASCET법과 ECST법이있으나, 수술및시술을결정할때주로 NASCET법을사용하고있다. 증후성경동맥협착증에서의협착정도를초음파를통하여평가한연구에따르면, 내경동맥의최고수축기속도 (peak systolic velocity) 210 cm/sec를기준으로하였을때민감도 94%, 특이도 77%, 양성예측도 68%, 음성예측도 96% 및정확도 83% 로 70% 이상의협착을진단할수있 Table 1. Parameters used in carotid Duplex ultrasound for estimating the degree of carotid artery stenosis 11 Degree of stenosis*, % Primary parameters Additional parameters ICA PSV, cm/s Plaque estimate, % ICA/CCA PSV ratio ICA EDV, cm/s Normal <125 None <2.0 <40 <50 <125 <50 <2.0 <40 50 to 69 125 to 230 50 2.0 to 4.0 40 to 100 70 but less than near occlusion >230 50 >4.0 >100 Near occlusion High, low, or undetectable Visible Variable Variable Total occlusion Undetectable Visible, no detectable lumen Not applicable Not applicable ICA; internal carotid artery, CCA; common carotid artery, PSV; peak systolic velocity, EDV; end-diastolic velocity. *Based on conventional angiography. Plaque estimate (diameter reduction) with gray-scale and color Doppler ultrasound. 62 http://www.j-nn.org
Vol. 10 / No. 2 / December 2018 Journal of Neurosonology and Neuroimaging 다. 10 하지만대부분의경동맥초음파검사실에서는 Society of Radiologists in Ultrasound에서제시한 consensus criteria 를사용하고있다 (Table 1). 11 이기준에서는내경동맥의최고수축기속도를기반으로죽상경화판의유무, 확장말기속도 (end diastolic velocity), 내경동맥과총경동맥의최고수축기속도의비등을종합하여경동맥협착을 <50%, 50-69%, 70% 및완전폐색으로진단하도록권장하고있으며, 대부분의연구에서이기준에따라수술및시술을결정하고있다. 미국의경우경동맥내막절제술을받는환자들의 80% 에서수술전평가도구로경동맥이중초음파가주로이용되고있다. 11 비침습적인검사인경동맥초음파, 자기공명혈관조영술 (MR Angiography) 및 CT혈관조영술의진단적가치를비교한메타연구에서는경동맥초음파검사가다른비침습적인검사들에비하여비슷한정도의정확도를보이며, 특히 70-99% 의협착은 84%, 50-69% 의협착은 91% 로높은특이도를보였다. 12 하지만경동맥협착 60% 이상에서는경동맥이중초음파의특이도가 68-86% 이므로 13 경동맥내막절제술이필요할것으로판단될경우불필요한수술을시행할오류를최소화하기위하여조영증강자기공명혈관조영술 (contrast-enhanced MRA) 을고려해야하고자기공명혈관조영술에서도결론을내지못할경우 CT혈관조영술이판정에도움이될것이다. 14 따라서, 수술이나시술의결정에있어서는자기공명혈관조영술, CT혈관조영술을병행하여검사하거나혹은다른검사자가경동맥초음파를재검할것을권고한다. 1,12 (2) 경동맥재개통술의합병증예측경동맥이중초음파는경동맥내막절제술혹은경동맥스텐트삽입술등의재개통술과정에서발생할수있는다양한합병증을예측하는데유용하게사용될수있다. 212명의환자에서이루어진 228예의경동맥스텐트삽입술의시행결과를분석한연구에서시술전시행한경동맥초음파의회색조중앙값 (gray scale median, GSM) 은시술전후의합병증이발생한군과발생하지않은군사이에유의한차이를보였다. 또한 GSM은향후재협착병변에서낮은결과를보여주었다. 15 경동맥스텐트삽입술의경우죽상판을제거하지않고혈관벽측면으로밀어내는과정이므로경동맥초음파는죽상판의형태를파악하는데중요한정보를줄수있다. 즉, 죽상판의표면 ( 매끄러운지, 불규칙한지 ) 과구조 ( 균질한지, 비균질한지, 출혈동반여부, 석회화여부, 에코음영정도 ) 에대한정보를통하여뇌졸중발생에대한위험도를제시해준다. 실제로다기관 Imaging in Carotid Angioplasty and Risk of Stroke (ICAROS) 연구에서뇌혈관조영술을통한경동맥스텐트삽입술시행에앞서경동맥초음파에서무에코 (echolucent) 죽상판을보일경우시술중뇌졸중발생과높은연관성을보여주었다. 16 하지만경동맥이중초음파는선별검사용으로수술적치료를결정할만큼위험도를측정하지는못한다. 왜냐하면검사에죽 상판형태분석이기본적으로시행되는것이아닐뿐만아니라이러한분석을통한표준화된데이터가없기때문이다. 또다른단점으로대뇌관류를측정할수없고, 뇌내측부순환이나동맥류같은혈관모양의정보는제공하지못한다. (3) 경동맥재개통술이후추적검사경동맥내막절제술이나경동맥스텐트삽입술등의경동맥재개통술을시행한경우에는경동맥초음파에서혈류속도가빠르게측정될수있어해석에주의가필요하다. 경동맥내막절제술을시행한경우시술부위의혈관은상당히넓어지지만, 원위부혈관은좁은채로남아있어국소적인혈류속도가빠르게측정될수있고, 특히수술중협착부위에인조혈관을이용한재개통술을시행할경우이러한소견이크게나타난다. 17 경동맥스텐트삽입술의경우에도스텐트에의하여경동맥의경화도가증가함에따라서이부위를지나는혈류의속도가증가하는경향을보일수있다. 18 아직까지경동맥재개통술이후에경동맥이중초음파검사소견에대한적절한해석기준은확립되어있지는않다. 다만, 여러연구에서 50% 의협착을예측하는기준으로내경동맥의최고수축기속도 150-224 cm/sec 정도로보고하고있으며, 19-21 각검사실에서는그검사실의기준을설정하고이를정기적으로검증하는과정이필요하다. 종래에 9개의임상시험결과를체계분석한결과에따르면, 시술후경동맥초음파를시행하는시기는시술직후보다는약 1년정도경과한후에시행하는것이더다양한정보를제공하는것으로알려졌다. 22 1 경동맥스텐트삽입술후추적검사경동맥스텐트삽입술후스텐트내재협착 (in-stent restenosis) 은흔히발생하는것으로알려져있으며, 시술 5년내 80% 이상으로진행하는경우는 6.4% 이다. 23 이러한가능성을확인하고뇌졸중재발방지를위한감시를위해서경동맥초음파의활용이필요하다. 하지만스텐트가삽입된경동맥은혈류와혈관탄성 (compliance) 이변화되어협착정도가과평가될소지가있다. 16,18-20,24,25 이러한문제를보완하기위하여경동맥스텐트삽입술을받은경동맥의스텐트내재협착에대한추적관찰에적용할수정혈류속도기준임계치 (modified velocity criteria thresholds) 가제시되었다 (Table 2). 20,26 스텐트내재협착을모니터하기위하여경동맥스텐트삽입술이후퇴원전, 3개월후, 이후로는 6개월간격으로 3회경동맥초음파검사를시행하도록하며, 2년동안스텐트내재협착이없을경우에는이후 1년마다평가할것을권장한다. 27 2 경동맥내막절제술후추적검사경동맥내막절제술후재협착은 1-37% 까지보고되었지만뇌졸중재발을보인경우는 8% 미만이다. 28-30 경동맥내막절제술후경동맥초음파를통한추적검사를얼마 http://www.j-nn.org 63
Lee JY and Choi HY, et al. Clinical Utility of Carotid Duplex Ultrasound Table 2. Two modified criteria for diagnosis of in-stent restenosis after carotid artery stenting AbuRahma et al. 20 Lal et al. 26 Stenosis*, % PSV, cm/s ICA/CCA ratio Stenosis*, % PSV, cm/s ICA/CCA ratio 0 to 29 <154 <1.5 0 to 19 <150 <2.15 30 to 49 154 to 223 20 to 49 150 to 219 50 to 79 224 to 324 3.4 50 to 79 220 to 339 2.7 80 to 99 >325 4.5 80 to 99 >340 4.15 ICA; internal carotid artery, CCA; common carotid artery, PSV; peak systolic velocity. *Based on conventional angiography. 나해야하는지는아직까지의견이분분하다. 수술부위를일차봉합 (primary closure) 하는경우보다부분혈관성형 (patch angioplasty) 을거친경우재협착이더적다고알려져있다. 31 따라서일차봉합을한경우경동맥초음파검사추적검사는 1개월, 6개월, 이후 1년마다시행할것을권고하고있고, 32 부분혈관성형의경우 6개월째추적검사에서정상일때에는정기적인추적검사가권장되지않는다. 33 (4) 회색조중앙값 (grey-scale median, GSM) 앞에기술한바와같이경동맥초음파에서 GSM이낮은경우나, 스텐트삽입술후최고수축기속도가 120 cm/sec 이상으로증가를보일경우재협착이잘발생하는것으로알려져있어경동맥초음파는혈관의협착정도를측정할수있을뿐아니라향후재협착을예측하는데에도유용하게사용될수있다. 15,34 2. 무증상경동맥협착 무증상경동맥협착 (asymptomatic carotid artery stenosis) 은증상없이우연히검사에서발견되는협착을말하며, 협착경동맥영역의뇌허혈또는일과성허혈증상을경험하지않았거나, 뇌허혈증상을경험하였더라도증상발생이후 6개월이상경과된환자로정의할수있다. 일반인구에서무증상경동맥협착의유병률은 2-8% 로다양하게보고되었다. 35 무증상경동맥협착과연관된위험인자로는나이, 성별 ( 남성 ), 당뇨병, 대사증후군, 고혈압, 이상지질혈증, 흡연등이알려져있으며, 나이와성별이가장강력한위험인자이다. 무증상경동맥협착은협착의정도에따라허혈뇌졸중또는일과성허혈발작을유발할수있어세심한평가및추적관찰이요구된다. 1) 무증상경동맥협착증에서경동맥이중초음파검사의유용성 Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) 연구는최대 7년동안 1,101명의무증상경동맥협착환자의자연경과를추적관찰한대규모관찰연구로, 경동 맥협착정도와뇌졸중발생률의상관관계를확인할수있다. 36 이연구에서는경동맥협착정도가협착동측허혈뇌졸중발생과연관이있음을확인하였고, 협착정도에따라뇌졸중발생위험도를다음과같이분류하였다 : (1) 저위험군 (50-79% 협착 ): 연간뇌졸중발생위험 1-2%; (2) 중간위험군 (70-89% 협착 ): 연간뇌졸중발생위험 2-4%; (3) 고위험군 (90-99%): 연간뇌졸중발생위험 4-6%. 이러한뇌졸중발생의위험은시간이지나더라도사라지지않으며, 약 20% 정도의무증상경동맥협착환자들은추적검사에서협착정도가진행하는것으로보고되었다. 37 특히, 무증상경동맥협착의정도가 80% 이상으로진행하는경우진행하지않는경우에비하여, 일과성허혈발작또는허혈뇌졸중위험이약 3배증가하는것으로보고되었다. 37 상기결과들을종합해보면무증상경동맥협착이 80% 이상인경우에는뇌졸중위험성이증가되어경동맥내막절제술이나경동맥스텐트삽입술과같은경동맥재개통술의대상이될수있다. 무증상경동맥협착환자에서경동맥초음파의 B방식영상을통한죽상경화판의에코성상또한뇌졸중발생의위험을가늠할수있는방법으로인자로알려져있다. 무에코또는저에코경화판 (echolucent or hypoechoic plaque) 은조직학적으로지방질이풍부하고괴사조직을포함하며또한죽상판내출혈 (intraplaque hemorrhage) 을시사하는소견으로, 죽상판의불안정성 (plaque instability) 과연관된다. 고에코죽상판 (echodence or hyperechoic plaque) 은지방질에비하여칼슘침착이높으며죽상판의안정성 (plaque stability) 과연관되어, 주로오랜기간동안증상이없는무증상경동맥협착환자들에서관찰된다. 35 무증상일반인을대상으로평균 3년간추적관찰한 Cardiovascular Health 연구에의하면저에코죽상경화판은약 2배가량뇌졸중발생위험을증가시키고, 경동맥협착이 50% 이상이고저에코죽상경화판이동반된경우에는약 2.3배뇌졸중위험이증가하는것으로보고하였다. 38 2014년미국질병예방국특별조사단 (United States Preventive Services Task Force, USPSTF) 에서무증상경동맥죽상경화는건강한성인인구에서뇌졸중으로발병하는경우가적기때문에경동맥초음파의선별검사는권장하지않고있 64 http://www.j-nn.org
Vol. 10 / No. 2 / December 2018 Journal of Neurosonology and Neuroimaging 다. 39 하지만죽상경화증에관한위험인자 ( 예, 나이, 흡연, 고 혈압, 당뇨 ) 를적어도 2개이상가지고있거나관상동맥질환이나말초혈관질환진단을받은경우경동맥협착에대한선별검사를권장할수있다. 32 경동맥죽상경화증 과거에는경동맥죽상경화판의치료기준을임상증상이유발된병소이면서혈관내강의협착이큰경우로정하였지만, 최근에는대뇌관류 (perfusion), 죽상판의형태 (plaque morphology), 뇌내측부순환 (intracranial collateralization) 상태를고려하여위험도를측정하고치료원칙을정하고있다. 지질핵심 (lipid core) 이크고, 얇은섬유성덮개 (fibrous cap) 를갖는경우파열하기쉬운죽상판 (vulnerable plaque) 의특징적소견으로, 40 특히큰포식세포 (macrophage) 와세포외지질성분의지질이 40% 이상을차지하고민무늬근육세포 (smooth muscle cell) 와아교질 (collagen) 로구성된섬유근육요소 (fibromuscular component) 가보일경우불안정죽상판으로정의되는데, 41 이는뇌졸중을초래할위험이높기때문에적극적인치료대상이된다. 심혈관질환의위험도예측 1. 경동맥내중막두께 경동맥초음파를통하여 B방식으로내중막두께 (intima-media thickness, IMT) 와경동맥죽상판 (carotid plaque) 을측정하는것은무증상혈관질환과심뇌혈관질환위험을평가하는방법으로입증된, 비침습적이고민감도가높으며재현가능한검사법이다. 기존가이드라인에서경동맥내중막두께는관상동맥심장질환위험을평가하는데도움이되는것으로언급되었다. 42,43 무증상환자의경동맥내중막두께와심혈관질환위험도를평가하였을때, 경동맥내중막두께가심근경색, 뇌졸중, 심혈관사망각각및전체조합과유의한연관성을보였다. 이러한경동맥내중막두께의위험도예측능력은다른전통적위험인자와는독립적이었다. 2010년 American Heart Association/American College of Cardiology (AHA/ACC) 가이드라인에서는, 중등도의심혈관질환위험을가진무증상성인에서심혈관질환위험도를평가할때관상동맥칼슘점수 (coronary calcium score) 와함께경동맥내중막두께를측정할것을권유하였다. 44 경동맥내중막두께와심혈관질환위험에관한연구결과들을 Table 3에요약하였다. 대부분의연구에서경동맥내중막두께는심근경색, 뇌졸중, 관상동맥질환사망, 그조합의위험 Table 3. Carotid IMT as prognostic indicator of cardiovascular events Follow-up Carotid US parameters Plaque Endpoints CIMT, RR (95% CI) Sample size No. Study AMI CCA-IMT increment, 0.1mm; RR 2.14 (1.08-4.26) CCA-IMT Focal calcified plaque not included IKHD 100 1,257 1 month to 2.5 yrs Highest tertile RR 1.84 (1.54-2.20) CHS 101 5,020 5 days to 12 yrs CCA and ICA-IMT Plaque included MI, Stroke, CV death, all-cause mortality ARIC 102 12,841 Mean, 15.1 yrs CCA, bulb, ICA IMT Plaque included MI, CV death IMT 1.0 mm; women: HR 5.07 (3.08-8.36), men 1.85 (1.28-2.69) CAPS 103 5,056 Mean, 4.2 yrs CCA, bif, bulb Not specified MI, stroke, death RR for 1SD: RR 1.17 for CCA-IMT MDCS 104 5,163 Median, 7 yrs Right distal CCA Plaque included MI, CV death RR for highest tertile: 1.5 (0.81-2.59) Rotterdam study 105 6,389 7-10 yrs CCA-IMT Not specified MI RR 1.95 (1.19-3.19) LILAC 106 298 Mean, 1,152 days CCA-IMT Not specified All-cause mortality 0.3 mm increase in left IMT, RR 1.65 (1.08-2.5); right IMT RR 3.3 (1.4-7.7) HR for fifth quintile 0.8 (0.5-1.2) Three-city study 51 5,895 Median, 5.4 yrs CCA-IMT Plaque excluded MI, angina, CV death, revascularization http://www.j-nn.org 65
Lee JY and Choi HY, et al. Clinical Utility of Carotid Duplex Ultrasound Table 3. Continued Study Sample size No. Follow-up Carotid US parameters Plaque Endpoints CIMT, RR (95% CI) IMPROVE 53 3,703 Median, 36.2 month CCA, ICA, buf-imt Plaque included MI, SCD, angina, stroke, TIA, heart failure, revascularization HR for 1SD increase: mean CCA-IMT 1.33 (1.18-1.5) MESA 107 6,814 Median, 7.6 yrs Right CCA-IMT Plaque excluded MI, revascularization, SCD, CV death HR 1.17 (0.95-1.45) The Edinburgh Artery 1,007 12 yrs CCA-IMT Not specified MI, stroke, angina, study 108 claudication IMT 0.9 mm, OR 1.59 (1.07-2.37) Framingham Offspring 2,965 Mean, 7.2 yrs CCA, ICA-IMT Plaque excluded MI, angina, CV death, stroke, study 109 claudication, heart failure HR for 1SD mean CCA-IMT 1.13 (1.02-1.24) Charlottesville 727 Mean, 4.78 yrs CCA, bulb, ICA-IMT Plaque included MI, revascularization, stroke, study 110 TIA OR for highest quartile of carotid bulb IMT:5.8 (1.3-26.6) FATE 111 1,574 Mean, 7.2 yrs Right CCA-IMT Plaque excluded CV death, revascularization, MI, angina, stroke HR 1.45 (1.15-1.83) OSACA2 112 574 Mean, 2.6 yrs CCA, bif, ICA- IMT Plaque included MI, CABG, angioplasty, PAD, stroke For 1SD increase RR:1.57 (1.11-2.20) Tromsø study 113 6,226 6 yrs Right CCA-IMT Plaque included MI Highest IMT quartile 1.73 (0.98-3.06) in men and 2.86 (1.07-7.65) in women CCCC 114 2,190 Median, 10.5 yrs CCA-IMT Plaque excluded MI, CV death, PCI, CABG RR 1SD 1.38 (1.12-1.70) APSIS 115 558 Median, 3.0 yrs Left CCA-IMT Not specified CV death, MI, revascularization IMT >1.02 mm RR: 0.78 (0.36-1.70) for CV death or MI; RR 1.07 (0.56-2.04) for revascularization Cournot et al 116 2,561 2-10 yrs CCA, ICA-IMT Plaque excluded CV death, MI, angina IMT >0.64 mm; HR 2.26 (1.35-3.79) AMI; acute myocardial infarction, APSIS; the Angina Prognosis Study in Stockholm, BIF; bifurcation, CABG; coronary artery bypass graft, CCA; common carotid artery, CCCC; Chin-Shan Community Cardiovascular Cohort Study, CI; confidence interval, CV; cardiovascular, ICA; internal carotid artery, FATE; firefighters and Their Endothelium study, IMT; intima-media thickness, HR; hazard ratio, MDCS; Malmo DIe and Cancer Study, MI; myocardial infarction, NOMAS; Northern Manhattan Study, OR; odds ratio, OSACA2; Osaka Follow-up Study for Carotid Atherosclerosis, PCI; percutaneous coronary intervention, PAD; peripheral artery disease, RR; relative risk, SCD; sudden cardiac death, TIA; transient ischemic attack, SD; standard deviation. 66 http://www.j-nn.org
Vol. 10 / No. 2 / December 2018 Journal of Neurosonology and Neuroimaging 을증가시켰고심혈관질환위험인자, 심혈관질환발생, 죽상경화의정도와유의한연관성을보였다. 내중막두께가증가하였을때보이는세포분자변화가죽상경화의진행에서도나타나기때문에내중막두께와죽상경화증이연관성은있지만, 내중막두께는무증상죽상경화증과동일한것은아니다. 특히죽상판이없는내중막두께증가는죽상경화증과동일하지는않다. 다시말해단순내중막두께증가는무증상혈과질환으로써, 위험인자이자심혈관질환의표지자로볼수있다. 2. 내경동맥내중막두께와죽상판 총경동맥내중막두께를측정할때, 내경동맥내중막두께, 경동맥죽상판을함께관찰하게되며, 심혈관질환의위험도를예측할때이를함께고려해볼수있다. 미국심초음파협회 (American Society of Echocardiography, ASE) consensus statement에서총경동맥내중막두께가성별, 나이, 인종을고려한 75백분위수보다두터울경우를비정상소견으로간주하지만, 45 초음파영상기법이발전함에따라내경동맥내중막두께를측정하기쉽게되었고, 연구결과내경동맥내중막두께가총경동맥내중막두께에비하여심혈관질환상대위험도가보다높았다. 46 Mannheim Consensus Report에의하면경동맥죽상판의정의는주변내중막두께의 50% 이상또는 0.5 mm 이상혈관내강으로튀어나온국소조직이거나, 또는내중막두께가 1.5 mm 이상두터워진경우를말한다. 47 경동맥죽상판이심혈관질환의예측, 예후인자임을보여주는여러연구들이있다 (Table 4). 11개의인구집단연구들 (population-based studies) 을메타분석한결과경동맥죽상판은경동맥내중막두께에비교하여볼때향후심근경색을예측하는데보다높은진단적정확성을보였다. 48,49 전통적위험인자와죽상판, 평균경동맥내중막두께를함께고려하였을때남성에서관상동맥심장질환위험예측정도가더높았다. 50 고식적위험인자, 경동맥내중막두께, 죽상판이합쳐진모델을고식적위험인자만을포함한모델과비교할때중등도위험군에서 net reclassification index (NRI) 가 21.7%, 전체집단에서 9.9% 였다. 이러한연구는죽상판을내중막두께와함께고려할때관상동맥심장질환의발생위험도를보다더잘예측할수있음을보여준다. 50 The Three-City Study에의하면총경동맥내중막두께가아닌경동맥죽상판이심장질환발생을예측하는독립적인인자로밝혀졌다. 한군데존재하는경우 HR 1.5 (1.0 to 2.2), 두군데존재할경우 HR 2.2 (1.6 to 3.1) 였다. 전통적위험인자에경동맥죽상판을더고려할경우심장질환위험예측도가더증가하였다. 51 The Tromsø study에서는경동맥팽대부 (carotid bulb) 의내중막두께를분석에서뺄경우에는내중막두께가심근경색예측인자가아니었고, 내중막두께가아닌경동맥죽상판이허혈뇌졸중의위험인자였다. 내중막두께의두터운정도와뇌졸중위험도와연관성이없 었다. 52 IMPROVE study에서는총경동맥내중막두께보다내경동맥내중막두께가관상동맥또는심혈관질환을더잘예측하였다. 53 3. 심혈관질환위험을평가하기위한경동맥이중초음파의적용 중등도의심혈관질환위험을가진환자에서심혈관질환위 험도를보다더잘평가하는데경동맥내중막두께측정과경동맥죽상판측정이유용하다. 이외에다음과같은환자들도또한심혈관질환위험을평가하기위한경동맥초음파검사의대상으로고려된다. 1) 직계가족중조기심혈관질환이있는사람, 2) 하나의확실한위험인자 ( 예, 유전성이상지질혈증 ) 가있는 60세미만환자, 3) 두개이상위험인자 ( 예, 고혈압, 당뇨병, 조기심혈관질 환가족력 [ 직계가족 ], 만성신장질환, 비만 ) 를가진 60세미만여자. 그러나이미알려진죽상경화성혈관질환이있거나, 검사결과가치료에영향을미치지않을때, 또는단순히악화나호전을보기위한상습적목적으로하는경우에는추천하지않는다. 4. 추적검사 주기적검사의필요성은부족하다. 일반인집단에서경동맥내중막두께의시간에따른진행 ( 증가 ) 과심혈관질환발생위험이연관성이있는지는아직입증되지않았다. 54 5. 검사와임상예후 경동맥내중막두께측정과경동맥죽상판존재로위험을예측하는것이환자의예후향상에도움이되는가는아직연구가부족하며관찰연구가있을뿐이다. 또한, 일반인집단에서경동맥내중막두께진행과심혈관질환발생위험이연관성이있는지는아직입증되지않았다. 54 경동맥내중막두께나경동맥죽상판을치료하는것이심혈관질환의예후을향상시키는지는아직확실하지않다. 다만 METEOR study에서관상동맥위험을가지거나 Framingham risk score가 10% 이내로낮은평균 57세인 984명의중년성인을대상으로 rosuvastatin 40 mg을 2년이상투여하였을때경동맥내중막두께의증가가현저히감소되었다. 55 수술과관련된뇌졸중위험예측 수술후발생할수있는뇌졸중은사망률을높이고심각한 http://www.j-nn.org 67
Lee JY and Choi HY, et al. Clinical Utility of Carotid Duplex Ultrasound Table 4. Carotid plaque as prognostic indicator of cardiovascular events Study Sample size, No. Follow-up Definition of plaque Endpoints Plaque RR (95% CI) Tromsø study 113 6,226 6 yrs Localized protrusion of the vessel wall into the lumen APSIS 115 558 Median, 3.0 yrs Distinct area with IMT more than twice that of neighboring sites KIHD 100 1,288 1 mo to 2.5 yrs Area with mineralization or focal protrusion into the lumen, measured at the carotid bulb Rotterdam study 105 6,389 7-10 yrs Focal widening relative to adjacent segments with protrusion into the lumen ARIC 50 13,145 Mean, 15.1 yrs Plaque defined as meeting 2 of 3 criteria: 1) CIMT >1.5 mm; 2) protrusion into the lumen; and 3) abnormal wall texture MI Highest plaque tertile, RR 1.56 (1.04-2.36) in men and RR 3.95 (2.16-7.19) in women CV death, MI Presence of plaque, RR 1.83 (0.96-3.51) MI Small plaque, RR:4.15 (1.51-11.47), large plaque, 6.71 (1.33-33.91) MI HR for severe plaque 1.83 (1.27-2.62) MI, CV death, revascularization HR varied depending on risk factors. Model with plaque and CIMT improved are under the curve from 0.742 to 0.755 MDCS 104 5,163 Median, 7 yrs Focal IMT >1.2 mm MI, CV death RR for presence of plaque 1.81 (1.14-2.87) Cournot et al. 116 2,561 2-10 yrs Focal protrusion into the vessel lumen CV death, MI, angina RR for the presence of plaque 2.81 (1.84-4.29) CCCC 112 2,190 Median 10.5 yrs Graded based on stenosis. Grade 1, <30%; grade 2, 30-49%; grade 3, 50-99%; grade 4, 100% NOMAS 117 1,118 Mean 2.7 yrs >50% increase in thickness compared with neighboring wall. Characterized as noncalcified plaques and calcified plaques Three-city study 51 5,895 Median 5.4 yrs Wall thickening 50% compared with surrounding vessel wall CHS 101 5,020 5 days to 12 yrs High-risk plaques were defined as markedly irregular, ulcerated surface, hypodense, heterogenous plaques >50% of total plaque volume MI, CV death, PCI, CABG, stroke 1-point increase in plaque score, RR 1.11 (0.99-1.24) Stroke, MI, CV death Calcified plaque, RR 2.4 (1.0-5.8); noncalcified plaques, RR 1.5 (0.7-3.4) MI, angina, CV death, revascularization MI, stroke, CV death and allcause mortality Framingham offspring 2,965 7.2 yrs ICA-IMT 1.5 mm MI, angina, CV death, stroke, study 109 claudication, heart failure Prati et al. 118 1,348 12 yrs Focal structure encroaching into the lumen with maximal thickness >1.5 mm Any plaques HR 1.5 (1.0-2.2); plaques at 2 sites HR 2.2 (1.6-3.1) High-risk plaque, RR 1.38 (1.14-1.67) Presence of plaque, HR 1.91 (1.49-2.47) Vascular death, stroke Event incidence for group with high total plaque score 68 http://www.j-nn.org
Vol. 10 / No. 2 / December 2018 Journal of Neurosonology and Neuroimaging 후유증을남길수있는무서운합병증이다. 뇌졸중의위험요소 Table 4. Continued Study Sample size, No. Follow-up Definition of plaque Endpoints Plaque RR (95% CI) CV death RR 1.16 (1.03-1.31) Stork et al. 119 403 48 months Focal widening with protrusion into the lumen Xie et al. 120 3,258 5 yrs IMT 1.5 mm IMT 1.5 mm Event rate by class: class I, 0.1%; class II, 8.6%; class III, 39.28%; class IV, 81.5% MI, CV death, revascularization CAFES-CAVE 121 10,000 10 yrs Class I, normal; class II, IMT >1 mm; class III, plaque defined as IMT 1 mm with irregular increased echogenicity; class IV, stenotic plaque with stenosis >50% Plaque >0%, HR 1.67 (1.33-2.10); plaque 25%, HR 1.67 (1.3-2.13) CHD, stroke, death after stroke MESA 109 6,562 Mean, 7.8 yrs 0%, 1-24% narrowing, 25-49% narrowing, and >50% narrowing (defined as peak systolic velocities 125 cm/s) CAFES-CAVE; carotid-femoral morphology and cardiovascular events, CHD; coronary heart disease, CVA; cerebrovascular accident, other abbreviations as in Table 3. 중하나인경동맥협착을발견하기위하여수술전검사로경동맥초음파검사가도움이될수있다. 또한, 경동맥초음파는협착여부뿐만아니라, 뇌졸중발생과연관이있는죽상경화판신생혈관형성, 복합죽상판 (complex plaque), 죽상판궤양, 무에코음영죽상판 (plaque echolucency) 및죽상판내움직임 (intraplaque motion) 등죽상경화판의성질을파악할수있는장점이있다. 56 관상동맥우회로조성술 (coronary artery bypass surgery) 예정인환자를대상으로비선택적으로시행한경동맥초음파에서 50% 이상협착은 9% 에서, 80% 이상은 7% 환자에서발견되어일상적으로검사를시행하는것은비용효율적이지못하다. 57 여러연구에서고령, 여성, 경동맥잡음 (carotid bruit), 흡연, 당뇨, 좌주간부관상동맥질환 (left main coronary artery disease), 뇌졸중의과거력, 말초혈관질환등이의미있는경동맥협착의위험요소로확인되었으며, 이중고령, 뇌졸중과거력과말초혈관질환이가장많이확인된인자이다. 58 한연구에서는 65세이상, 뇌졸중과거력이나경동맥잡음이있는경우검사를권유하였으며, 이경우민감도는 83%, 특이도는 41% 라고하였다. 59 또다른연구에서는흡연, 당뇨, 고혈압, 뇌졸중과거력, 말초혈관질환, 좌주간부관상동맥질환, 경동맥질환의과거력중한가지라도있는경우민감도는 100%, 특이도는 30% 라하였다. 60 미국심장학회관상동맥우회로조성술진료지침에는 65세이상, 좌주간부관상동맥협착, 말초혈관질환, 뇌혈관질환의과거력, 고혈압, 흡연, 당뇨가있는경우검사를권유한다. 61 일반적인수술인경우수술후뇌졸중발생률은 1% 미만이며, 고위험군인심장수술중관상동맥우회로조성술에서는 1.4-3.8%, 판막수술에서는 4.8-8.8% 정도이다. 62 관상동맥우회로조성술후뇌졸중발생증가와관계가있는인자는고령, 뇌졸중이나일과성허혈발작의과거력, 말초혈관질환, 불안정협심증, 장시간에걸친심폐우회술 (prolonged cardiopulmonary bypass), 수술후심방세동, 경동맥협착등이다. 63 예측인자중경동맥잡음 (OR 3.6, 95% CI 2.8 to 4.6), 뇌졸중이나일과성허혈발작의과거력 (OR 3.6, 95% CI 2.7 to 4.9) 및심한경동맥협착이나폐색 (OR 4.3, 95% CI 3.2 to 5.7) 이위험도가높았다. 57 경동맥의유의한협착이없는경우수술후뇌졸중위험은 2% 미만이었으며, 협착정도에따라무증상동측 50-99% 협착은 3%, 양측 50-99% 협착은 5%, 경동맥폐색은 7-11% 로수술후뇌졸중위험이증가하였다. 57 다른연구에서는무증상동측 50% 이상협착에서는뇌졸중위험이 2% 이하인데반하여증후성동측경동맥협착환자에서는 18%, 양측협착에서는 26% 로증후성협착에서수술후뇌졸중위험이더높았다. 64,65 그러나수술후뇌졸중이발생한환자 50% 에서의미있는경동맥협착은없었으며, 영역뇌경색 (territorial infarction) 의 60% 에서경동맥질환외에다 http://www.j-nn.org 69
Lee JY and Choi HY, et al. Clinical Utility of Carotid Duplex Ultrasound 른인자들도연관성을보였다. 57 다른연구에서도예방적경동 맥내막절제술이나경동맥스텐트를하지않은 23,557명의관상동맥우회로조성술환자중뇌줄중이발생한 476명의 95% 는경동맥협착이원인이아니었다. 66-68 실제로심장수술후발행하는뇌졸중의 60% 가색전으로인한것으로, 수술중심장이나, 대동맥을다루는과정, 심장세동, 수술후발생하는응고병증 (coagulopathy) 등이원인이된다. 62 한연구에서는비심장성수술인경우경동맥협착과수술후뇌졸중은연관이없다고하였다 (OR 1.0 [95% CI 0.99 to 1.02] for a 10-unit increase, p=0.55). 69 이러한상황에서수술전예방적경동맥재개통 (carotid revascularization) 은신중하게생각해야한다. 경동맥스텐트후관상동맥우회로조성술을메타분석한연구에서는전체 30일사망 / 뇌졸중위험은 7.9%, 사망 / 뇌졸중 / 심근경색은 8.8% 였으며, 무증상성협착을가진환자에서는사망 / 뇌졸중위험 6.7%, 사망 / 뇌졸중 / 심근경색은 8.5% 였다. 증후성경동맥협착환자에서는시술관련뇌졸중발생률은 15%, 사망 / 뇌졸중은 10-23% 였다. 그외경동맥내막절제술이나경동맥스텐트삽입술을수술전후또는동시에한여러연구에서경동맥내막절제술과심폐우회 (cardiopulmonary bypass) 하지않는관상동맥우회로조성술을동시에한경우를제외 (2.2, 3.6%) 하고 30일사망 / 뇌졸중은 5.6-8.6%, 사망 / 뇌졸중 / 심근경색은 5-11.5% 정도였다. 70 유럽의진료지침에서는관상동맥우회로조성술에앞서 6개월이내뇌졸중이나일과성허혈발작이있었던 50-99% 경동맥협착환자나, 무증상성양측 70-99% 경동맥협착또는 70-99% 협착과반대측폐색이있는경우에예방적경동맥재개통술을권장하고있다. 1 기타질환에서경동맥이중초음파 1. 혈관박리 경부동맥박리 (cervical artery dissection) 는모든연령대에서발생할수있으나, 특히젊은연령에서뇌혈관질환의중요한원인이다. 71 혈관내막손상으로혈관이좁아지면서다양한혈관내외의변화를동반한다. 가벼운외상에의해내막의손상이시작될수있고, 외상없이자발적으로발생할수도있다. 20% 에서는섬유근형성이상 (fibromuscular dysplasia) 을동반한다. 71 내막파열 (intimal tear) 이발생하고, 시간이지나면서내막 (intima) 과중막 (media) 사이로벽속혈종 (intramural hematoma) 이만들어진다. 혈관벽내의출혈이증가하면다양한정도의협착와폐색을유발한다. 71,72 시간이경과하면서벽속혈종이흡수되고, 막히거나좁아진혈관이재개통 (recanalization) 된다. 바깥막하출혈 (subadventitial hemorrhage) 은혈관조영술에서거짓꽈리 (pseudoaneurysm) 로나타나고, 원위부의내막손상이발생하면이중내강 (double lumen) 으로보인다. 71,72 박리된혈관은초음파영상에서혈관벽이저에코음영 (hypo-echogenic) 으로두껍게관찰된다 (hypo-echogenic thickening of the vessel wall). 이전에는침습적인혈관조영술을이용하여진단하였으나영상기술이발전하면서자기공명영상과컴퓨터단층촬영을이용한혈관검사로도진단이가능하다. 전형적인혈관조영술소견은혈관을따라길게진행하는협착이나폐색 (tapered stenosis/occlusion) 이다. 특히거짓꽈리, 이중내강혹은내막판 Fig. 1. Computed tomography angiography (left) and duplex sonography (right) of a patient with the left internal carotid artery dissection show tapered occlusion (arrow), and hypo-echogenic occlusion and stump flow without plaque. 70 http://www.j-nn.org
Vol. 10 / No. 2 / December 2018 Journal of Neurosonology and Neuroimaging (intimal flap) 이보이면확진가능하다. 71 1) 내경동맥박리 뇌경색을동반하는박리의경동맥초음파민감도는 91-100% 이다. 73,74 반면, 뇌경색을동반하지않는박리의초음파 민감도는 70% 이다. 74 뇌경색을동반하지않는통증과호너증 후군에서박리가의심된다면, 경동맥초음파가정상이라도박리를배제하기위하여추가적인경부자기공명혈관촬영술이나 CT혈관조영술이필요하다. 75 내경동맥박리는경도의불완전협착 (subtotal stenosis) 부터완전폐색까지다양한정도의협착을동반한다. 초음파에서는죽상경화판이거의없는저에코혈관벽이원위부로길게가늘어지며진행하는협착 / 폐색 (tapered stenosis/occlusion) 이관찰된다 (Fig. 1). 박리의초음파소견은대부분비특이적인협착이나폐색으로, 특징적인내막박리판, 이중내강혹은거짓꽈리가관찰되는경우는오히려드물다. 76 초음파는비침습적으로혈관내재개통을확인하고항혈전제 (antithrombotics) 의치료기간을결정할수있는장점이있다. 초음파를이용한추적검사에서 48명의 50예의혈관박리를추적하였는데, 34예 (68%) 에서 51일째에재개통이관찰되었다. 77 다른연구에서는 43명의환자를추적하였을때 63% 가재개통되었으나 37% 에서는폐색이지속되었다. 73 2) 척추동맥박리 척추동맥박리의초음파의민감도는 75-86% 이다. 72,78 초음파에서불규칙한협착, 낮은 (hypo-) 혹은같은에코음영 (iso-echogenic) 의두꺼워진혈관벽, 박리판 (dissection flap), 이중내강, 거짓꽈리와원위부로점차적으로가늘어지는폐색이보인다. 전형적인소견으로척추동맥에서국소혈관의확장, 협착혹은폐색등이동반되거나혈관내저박동과혈관내에코의존재 (decreased pulsatility and presence of intravascular echoes) 이다. 72,79 한추적연구에서, 두개외척추기저동맥박리의경우 80% (8/10) 에서협착이호전되었고 29% (2/7) 에서폐색이재개통되었다. 72 다른연구에서는두개외척추기저동맥박리 7명중협착은 50% (3/6), 폐색은 33% (1/3) 에서호전되었고, 두개내척추기저동맥혈관박리 9명중협착의 60% (6/10) 와폐색의 33% (1/3) 가좋아졌다. 78 2. 측두동맥염 (temporal arteritis) 과다카야수동맥염 (Takayasu s arteritis) 측두동맥염은 50대이상의여자에서주로발생한다. 임상적으로측두염증부위의압통 (tenderness), 전신무력감과통증, 경미한열, 턱관절의파행과증가된적혈구침강속도 (erythrocyte sedimentation rate) 가관찰되면의심할수있다. 치료가늦으면안동맥 (ophthalmic artery) 을침범하여실명까지이어질수있다. B방식에서균일하고두터워진저에코음영의혈관벽이보인다. 급성기에는팽창되고두꺼워진염증성혈관의가로영상 (transverse image) 에서저에코음영의달부리 (halo) 가보인다. 80 초음파의이상소견은스테로이드치료에의하여서서히호전된다. 81 다카야수동맥염은대동맥과연결된주요동맥을우선적으로침범하는육아종염증 (granulomatous inflammation) 으로젊은아시아여성에서호발한다. 대부분총경동맥 (common carotid artery) 을침범한다. 82,83 초기에는발열, 체중감소, 피로감, 어지럼증, 관절통, 실신등비특이적인증상이나타날수있어진단이어렵다. 진단검사로침습적인혈관조영술, 자기공명혈관촬영술이나 CT혈관조영술이필요하다. 하지만질병이발생하는초기의혈관벽의조직학적변화를확인할수없어서위음성을보일수있다. 82 그러나경동맥초음파에서혈관벽에 Fig. 2. Carotid duplex ultrasonography in a patient with Takayasu s arteritis. The longitudinal duplex B-mode image shows long segmental, circumferential and mid-echogenic thickenings of intimal and medial layers (Macaroni sign, arrows). Fig. 3. Duplex sonography of a left subclavian steal phenomenon shows the reversed flow of blood in the left vertebral artery. http://www.j-nn.org 71
Lee JY and Choi HY, et al. Clinical Utility of Carotid Duplex Ultrasound 고르게퍼진비후 (Macaroni sign, homogenous circumferential intima-media thickening) 소견 (Fig. 2) 을관찰할수있어서혈관염을초기에진단할수있다. 82 다카야수혈관염은측두동맥염혈관벽의저에코음영 (hypo-echogenic) 보다밝은에코음영 (iso-echogenic) 으로보이고, 혈관벽의부종이적다. 81 3. 쇄골하혈류전환증후군 (subclavian steal syndrome) 쇄골하혈류전환은쇄골하동맥의척추동맥기시부이전의협착혹은폐색에의하여혈류의압력이낮아져 (Bernoulli s principle), 척추동맥의혈류가역류하여쇄골하동맥으로흐르는현상을일컫는다. 84 주된원인은죽상경화증이고대부분은무증상으로발견되나임상적으로팔운동에의하여유발되는척추기저동맥혈류부전 (vertebro-basilar insufficiency) 이동반된다. 84,85 초음파의도플러효과를이용하여척추동맥의혈류역류현상을확인하면쉽게진단할수있다 (Fig. 3). 완전한혈류역전의단계가아니라면교대혈류 (alternating flow pattern) 나수축기중간의급격한감속 (prominent mid-systolic deceleration) 이전단계 (pre-steal) 로관찰되어 85 혈압계커프를이용한충혈검사 (hyperemia test) 로혈류역전을유발하여잠복쇄골하혈류전환 (latent steal phenomenon) 을진단할수있다. 85 어지럼증, 현훈, 이명또는실신환자의선별검사로서의경동맥이중초음파 환자가어지럼증 / 현훈, 이명, 혹은실신으로신경과로의뢰되거나내원하였을때경동맥초음파의진단적유용성은명확하지않다. 이러한증상으로내원하여경동맥초음파를시행한 650명의환자들을분석한연구에서 60% 이상의경동맥협착을가진환자는없었다. 86 이러한환자들의수술전평가에서뇌졸중이나사망에대한위험성을증가시킨다는근거는없고, 경동맥내막절제술시행에대한장기적이익또한없다. 87 실신에대한진단검사에서신경초음파의진단적가치는높지않다. 88 어지럼증이나현훈의원인이될수있는척추-기저동맥질환의평가에경동맥초음파의가치는높지않다. 89 신경학적이상이없는 단순 실신으로대학병원에내원하여경동맥초음파를시행받은 313명 ( 평균나이 73.6±12.4세 ) 의의무기록을분석한최근의연구에서 50% 이상의경동맥협착을보인경우는 48명 (15%) 이었고이는실신과무관하였다. 90 전체환자중 7명 (2%) 만이향후뇌졸중에대비하는약물치료를받았고, 1명 (0.3%) 만이경동맥스텐트삽입술을받았다. 90 즉, 실신으로내원한환자가뇌졸중발생위험이높은고령에 해당하더라도국소신경학증상, 증후를보이지않거나경동맥잡음이없다면경동맥초음파의비용대비진단적가치는낮기때문에기본검사로권장되지않는다. 90,91 약물치료에있어서경동맥이중초음파의유용성 죽상경화증의치료에있어서적절한약물치료는매우중요하다. 특히, 경동맥협착환자에있어스타틴을사용한약물치료는필수적인요소라할수있다. 경동맥초음파를이용하여스타틴치료효과를평가한연구들이있다. METEOR 연구는관상동맥질환의위험도가낮은 (Framingham risk score <10%) 무증상죽상경화증환자를대상으로 B방식초음파로경동맥내중막두께를측정하여 rosuvastatin의효과를평가하였다. 55 984명의환자를대상으로 rosuvastatin 40 mg 또는위약을복용하게하여약 2년간관찰하였다. 일차종결목표로최대내중막두께의변화속도를살펴보았는데, 위약군에서는 +0.0131 mm/yr로진행을하였고투약군에서는 LDL-C이약 49% 감소하면서내중막두께는 -0.0014 mm/yr로호전을보였다 (p<0.0001). ENHANCE 연구는 simvastatin 80 mg + ezetimibe 10 mg의병합요법과 simvastatin 80 mg의단독요법이내중막두께에미치는영향을비교한것이다. 92 조기관상동맥질환의위험이높고유년기부터내중막두께증가속도가높은 720명의가족성고콜레스테롤혈증환자를대상으로 2년간일차종결목표인내중막두께를서로비교하였다. 연구종결시점에측정한평균 LDL-C은 simvastatin 그룹에서 192.7±60.3 mg/dl였고병합요법그룹에서는 141.3±52.6 mg/dl였다 (p<0.01). 이러한 LDL-C 의차이에도불구하고내중막두께의변화는유의한차이가없었다 (p=0.29). 경동맥죽상판이있는사람들을대상으로스타틴으로치료한결과초음파의에코발생도 (ecogenicity) 가어떻게변화되는지를본최근메타분석이있다. 93 이분석에서는경동맥죽상판의에코성을보는지표로 GSM 또는 integrated back scatter (IBS) 값을사용하였다. 스타틴치료후평균 7개월이지난시점에서경동맥죽상판의에코성은일정하게증가하였는데, 이는 high-sensitivity C-reactive protein (hs-crp) 의변화와밀접한연관이있었으며 LDL-C이나 HDL-C의변화와는연관이없었다. 이는스타틴치료가불안정한죽상판을보다더안정화된죽상판으로변화시킬수있음을보여주는것이라할수있다. 스타틴사용은 LDL-C 감소효과뿐아니라경동맥죽상경화증의진행을늦춘다는결과도있다. 94 2,974명의건강인을대상으로한 Tromsø 연구는경동맥초음파로 13년간내중막두께와죽상판을추적관찰하였는데, 종류와용량에관계없는스타틴치료는경동맥죽상경화의진행을늦추었다. 특히, 5년이상의장기간스타틴투여군에서내중막두께 72 http://www.j-nn.org
Vol. 10 / No. 2 / December 2018 Journal of Neurosonology and Neuroimaging (β= 0.0387 mm; p=0.002) 와전체죽상판면적 (β= 0.400 mm 2 ; p=0.006) 에서진행을억제하는보호효과가있었다. 건강인 이아닌뇌졸중을경험한경동맥협착환자에서도스타틴치료는죽상판안정화에효과를주었다. 한연구에서경동맥초음파에서죽상판영상을얻은후이미지소프트웨어를사용하여 GSM 값을구하여 atorvastatin 40 mg과 80 mg 치료전과치료 1년후를비교하였다. 최종적으로 atorvastatin 저용량과고용량은위약군에비하여용량의존적으로죽상판을안정화시켰으며고용량에서가장큰효과를보였다. 95 3) 관상동맥우회로조성술시행예정인 65 세이상의환자와좌주간부관상동맥협착, 말초동맥협착, 흡연, 뇌졸중이나일과성허혈발작의병력, 또는경동맥잡음환자에서선별검사를고려할수있다. 58-61,70 4) 죽상경화증의근거가없는무증상환자에서고혈압, 고지혈증, 흡연, 60 세미만직계가족의죽상경화증, 또는뇌경색가족력 2 개이상의위험요인을가진경우에선별검사를고려할수있다. 32 경부혈관초음파의임상적적용 - 표준검사지침요약 32,39,96-98 지금까지의논거한결과들을바탕으로임상에서시행할경동맥초음파의표준검사지침을요약적으로제시하고자한다. 경동맥초음파는양측경동맥과척추동맥을모두검사하는것을원칙으로하고 B방식과도플러속도검사가포함되어야한다. 경동맥초음파의필요여부는대상자의임상증상, 병력, 다른검사결과등을토대로결정한다. 일반적으로관련증상, 병력이없는사람에서선별검사의목적으로경동맥초음파를시행하는것은권고하지않는다. 39,99 다음과같은경우에경동맥초음파를시행하거나, 고려할수있다. 5) 심혈관질환위험을평가하기위하여다음과같은환자에서경동맥초음파검사를고려할수있다. (1) 중등도의심혈관질환위험을가진사람, (2) 직계가족중조기심혈관질환이있는사람, (3) 하나의확실한위험인자가있는 60 세미만환자, (4) 두개이상의위험인자를가진 60 세미만여자. 2. 추적검사 1) 이미경동맥이상이진단되었으나, 혈관재개통술은시행받지않은경우 70-99% 의경동맥협착환자에서는 6개월마다추적검사를시행하는것이적절하다 50-69% 의경동맥협착환자에서 1년마다추적검사를시행하는것이적절하다. 1. 초기검사 1) 경동맥이나척추동맥의병변이의심되는경우 전방순환계의이상으로인한것으로추정되는신경학적 증상이새로생겼거나, 기존증상이악화된경우 후방순환계의이상으로인한것으로추정되는신경학적 증상이새로생겼거나, 기존증상이악화된경우 팔운동을과하게하였을때발생하는어지럼증, 두통, 시야장애등의증상으로쇄골하혈류전환증후군이의심되는경우 목에박동성병변이있는환자에서자발성경동맥박리에 대한평가 망막검사에서 Hollenhorst plaque 이관찰되는경우 경동맥잡음이들리고이전에경동맥검사를시행한적이 없는경우 2) 이미경동맥이나척추동맥이상이진단되었으나, 혈관재개통술은시행받지않은경우 2) 이미경동맥이나척추동맥이상이진단되고, 혈관재개통술을시행받은경우 새로운신경학적증상이발생하거나기존증상이악화되는경우 경동맥스텐트삽입술이후퇴원전, 3개월후, 이후로는 6개 월간격으로 3회경동맥초음파를시행하도록하며, 2년동안스텐트내재협착이없을경우에는이후 1년마다평가하기를권장한다. 27 경동맥내막절제술에서일차봉합을한경우추적검사는 1개 월, 6 개월, 이후 1 년마다시행할것을권고하고, 32 부분혈 관성형의경우 6개월째추적검사에서정상일때에는정기적인추적검사가권장되지않는다. 33 추적검사에서이상을보이는경우에는혈관재개통술을 다시시행할지여부에대하여 6개월마다추적검사를해서결정하는것이적절하다. 더이상시술의대상이아니라고판단되면추적검사를종료할수있다. http://www.j-nn.org 73
Lee JY and Choi HY, et al. Clinical Utility of Carotid Duplex Ultrasound 3) 이전에시행한경동맥초음파에서정상이었던경우에추적검사를시행하는것은적절하지않다. 4) 죽상경화판은있으나협착이없는경우 1 년이내에추적검사를시행하는것은적절하지않다. 5) 50% 미만의경동맥협착의경우추적검사를 1-2 년이상의간격으로시행하는것에대한근거는불충분하다. 6) 두개외경동맥섬유근육형성이상환자에서매년추적검사를시행하는것은타당하나, 예후에대한효과는불분명하다. 혈관병변이안정적인소견일경우, 추적검사간격을조정할수있다. Sources of Funding None Conflicts of Interest None REFERENCES 1. Naylor AR, Ricco JB, de Borst GJ, Debus S, de Haro J, Halliday A, et al. Editor's choice - management of atherosclerotic carotid and vertebral artery disease: 2017 clinical practice guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg. 2018;55:3-81. 2. Lee JY, Yu S, Lee SI, Jung KH, Seo WK, Park JM, et al. Transcranial Doppler ultrasound: practice standards part I. Test performance and interpiretation. J Neursonology. 2016;8:1-13. 3. Jung KH, Seo WK, Park JM, Lee JY, Yu S, Lee SI, et al. Transcranial Doppler ultrasound: practice standards part II. Clinical indications and utility. J Neursonology. 2016;8:14-29. 4. Naylor AR. Why is the management of asymptomatic carotid disease so controversial? Surgeon. 2015;13:34-43. 5. White H, Boden-Albala B, Wang C, Elkind MS, Rundek T, Wright CB, et al. Ischemic stroke subtype incidence among whites, blacks, and hispanics: the Northern Manhattan study. Circulation. 2005;111:1327-1331. 6. Brott TG, Halperin JL, Abbara S, Bacharach JM, Barr JD, Bush RL, et al. 2011 ASA/ACCF/AHA/AANN/AANS/ACR/ ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American Stroke Association, American Association of Neuroscience Nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery. Developed in collaboration with the American Academy of Neurology and Society of Cardiovascular Computed Tomography. Catheter Cardiovasc Interv. 2013;81:E76-E123. 7. Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery trial (ECST). Lancet. 1998;351:1379-1387. 8. North American Symptomatic Carotid Endarterectomy Trial Collaborators, Barnett HJM, Taylor DW, Haynes RB, Sackett DL, Peerless SJ, et al. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med. 1991;325:445-453. 9. Bonati LH, Dobson J, Featherstone RL, Ederle J, van der Worp HB, de Borst GJ, et al. Long-term outcomes after stenting versus endarterectomy for treatment of symptomatic carotid stenosis: the International Carotid Stenting Study (ICSS) randomised trial. Lancet. 2015;385:529-538. 10. Carpenter JP, Lexa FJ, Davis JT. Determination of duplex Doppler ultrasound criteria appropriate to the North American Symptomatic Carotid Endarterectomy Trial. Stroke. 1996;27:695-699. 11. Grant EG, Benson CB, Moneta GL, Alexandrov AV, Baker JD, Bluth EI, et al. Carotid artery stenosis: gray-scale and Doppler us diagnosis--society of Radiologists in Ultrasound Consensus Conference. Radiology. 2003;229:340-346. 12. Wardlaw JM, Chappell FM, Stevenson M, De Nigris E, Thomas S, Gillard J, et al. Accurate, practical and cost-effective assessment of carotid stenosis in the UK. Health Technol Assess. 2006;10:iii-iv, ix-x, 1-182. 13. AbuRahma AF, Srivastava M, Stone PA, Mousa AY, Jain A, Dean LS, et al. Critical appraisal of the Carotid Duplex Consensus criteria in the diagnosis of carotid artery stenosis. J Vasc Surg. 2011;53:53-59; discussion 59-60. 14. Byrnes KR, Ross CB. The current role of carotid duplex ultrasonography in the management of carotid atherosclerosis: foundations and advances. Int J Vasc Med. 2012;2012:187872. 74 http://www.j-nn.org
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