대한내과학회지 : 제 92 권제 3 호 2017 https://doi.org/10.3904/kjm.2017.92.3.269 혈액투석환자에서혈관접근로의동맥미세석회화가관상동맥석회화와심혈관사망률에끼치는영향 가톨릭대학교의과대학 1 신장내과학교실, 2 외과학교실 이영복 1 최보미 1 황현석 1 박훈석 1 박순철 2 김영옥 1 The Impact of Arterial Micro-calcification of the Vascular Access on Coronary Artery Calcification and Cardiovascular Mortality in Incident Hemodialysis Patients Yeong Bok Lee 1, Bo Mi Choi 1, Hyeon Seok Hwang 1, Hoon Suk Park 1, Sun Chul Park 2, and Young Ok Kim 1 1 Division of Nephrology, Departments of Internal Medicine and 2 General Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea Background/Aims: The aim of this study was to explore the relationship between arterial micro-calcification (AMiC) and coronary artery calcification, and to determine the impact of AMiC on cardiovascular mortality in incident hemodialysis patients. Methods: One hundred and nineteen hemodialysis patients who received vascular access surgeries between April 2011 and May 2015 were included in this study. AMiC was diagnosed by pathologic examination of arterial specimens acquired during surgery, using von Kossa stain. All patients underwent multi-detector computed tomography imaging, and coronary artery calcium scores (CACS) were calculated. We evaluated the association between AMiC and CACS in these patients, and examined the incidence of cardiovascular death (through Febraury 2017) in patients with and without AMiC. Results: The mean age of the patient group was 64.3 ± 13.0 years, and 64% were male (n = 76). Of 119 patients, 67 (56.3%) were positive for AMiC of the vascular access. The mean CACS was 430.4 ± 720.2 (0-3,954), and 99 patients were considered positive for CAC (83.1%). By multivariate logistic regression analysis, CACS was independently associated with AMiC. The mean follow-up period was 35.5 ± 17.8 months. During this time there were 26 all-cause deaths, of which 17 were cardiovascular. Kaplan-Meier survival analysis revealed that AMiC was associated with cardiovascular mortality (log rank = 9.0, p < 0.05). Conclusions: AMiC may be associated with coronary artery calcification in incident hemodialysis patients, and may also be a risk factor for cardiovascular mortality. (Korean J Med 2017;92:269-276) Keywords: Coronary atherosclerosis; Vascular calcification; Renal dialysis Received: 2017. 2. 16 Revised: 2017. 4. 13 Accepted: 2017. 5. 1 Correspondence to Young Ok Kim, M.D. Division of Nephrology, Department of Internal Medicine, The Catholic University of Korea, 271 Cheonbo-ro, Uijeongbu 11765, Korea Tel: +82-31-820-3347, Fax: +82-31-847-2719, E-mail: cmckyo@catholic.ac.kr Copyright c 2017 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution - 269 - Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
- The Korean Journal of Medicine: Vol. 92, No. 3, 2017 - 서론혈액투석환자에서심혈관질환은주요사망원인이며, 일반인구집단에비해이환율및사망률이높은것으로알려져있다 [1,2]. 따라서혈액투석환자에서심혈관질환의발생을조기에예측하고진단하는것이임상적예후에중요하다. 그러나혈액투석환자는심혈관질환이발생할때까지무증상인경우가많고일반인구집단에서잘알려진심혈관질환의임상적위험인자들만으로는예측이어려우며심혈관질환발생의바이오마커 (homocysteine, brain natriuretic peptide 등 ) 또한적용이어려워심혈관질환발생의예측과조기진단이어렵다 [3]. 따라서혈액투석환자에서심혈관질환발생의예측과조기진단을위한지표에대한연구가필요하다. 주로영상학적검사로확인되는관상동맥석회화는죽상경화증 (atherosclerosis) 의일환으로나타나기때문에주로내막층에주로발생하나혈액투석환자에서는내막외에도중막층까지확산되어나타나기도한다 [4]. 관상동맥칼슘수치 (coronary artery calcium score, CACS) 는관상동맥질환의비침습적인지표로관상동맥석회화정도를정확하고정량적으로평가할수있는검사이다. 혈관석회화는일반인과혈액투석환자모두에서심혈관사망의독립위험인자로알려져있다 [5-8]. 이에반해혈액투석환자의혈관접근로수술시에수술부위동맥에서조직학적으로조사한동맥미세석회화 (arterial micro-calcification, AMiC) 는동맥경화증 (arteriosclerosis) 의주요소견이다. 혈액투석환자에서혈관접근로수술시에쉽게동맥조직을획득할수있기때문에병리학적변화에대한연구가보고되고있다. 저자들은혈액투석환자에서혈관접근로의 AMiC가심혈관질환사망률증가와관련이있다고보고한바있다 [9]. 혈관접근로의 AMiC가심혈관사망률을증가시키는기전에대해서는현재까지잘알려져있지않다. 저자들은미세석회화가대동맥등의다른부위의동맥경화증과유사하게심혈관사망률의위험인자인동맥경직을증가시킨다고보고한바있다 [10]. 혈관접근로의 AMiC 와 CACS 는석회화의발생기전이다르나혈액투석환자에서흔하게발생하므로관련성이있을것으로추정된다. 이에저자들은첫째, 혈액투석을새로이시작하는환자에서 AMiC, CACS와높은심혈관사망률과의관련성을확인하고, 둘째, 서로다른기전의석회화가관련성이있는지를조사하여이를통해혈관접근로의 AMiC가 어떤기전으로높은심혈관사망률과관련이있는지를규명하기위해본연구를시행하였다. 대상및방법대상본연구는후향적, 단일기관연구로 2011년 4월부터 2015 년 5월까지의정부성모병원에내원한말기신부전환자중혈액투석을시작하고 1개월이내에혈관접근로수술과 CACS 검사를시행한 119명의환자를대상으로하였다. 대상환자들의의무기록분석을통하여연령, 성별, 흡연력, 동반질환및관상동맥질환, 뇌혈관질환등의병력을조사하였으며신장과체중을측정하여체질량지수 (body mass index, BMI) 를구하였다. 본연구는가톨릭중앙의료원임상연구심사위원회 (Institutional Review Board UC13RISSI0137) 의연구승인을받았다. 방법혈관질환의진단은임상적기준과진단검사를기초로하였다. 관상동맥질환은스트레스검사에서양성이었거나급성관상동맥증후군이나심근경색을일으켰거나경피적관상동맥중재술또는관상동맥우회수술을받은경우로정의하였다. 뇌혈관질환의진단은허혈성또는출혈성뇌졸중이나일시적인허혈적발작이있었거나뇌컴퓨터단층촬영또는자기공명영상촬영에서뇌경색이발견된경우로정의하였다. 말초동맥질환의진단은팔다리파행, 허혈성궤양, 절단술의병력, 혈관재개통술또는초음파나혈관조영술에서이전의폐색진단이있는경우로정의하였다. 혈액학적검사대상환자의헤모글로빈, 알부민, 칼슘, 인, 완전한부갑상선호르몬 (intact PTH, ipth), C-반응성단백질 (C-reative protein, CRP) 및총콜레스테롤, 중성지방, 고밀도콜레스테롤및저밀도콜레스테롤등은혈액투석을시작하기전수술당시의검사결과를조사하였다. 혈관접근로 AMiC 의병리학적검사혈관접근로수술중동맥검체는이전에보고한방법과동일한방법으로얻었다 [11]. 요골동맥또는상완동맥의 5 mm 길이방향절편을절개부위에서타원형으로절제하였 - 270 -
- Yeong Bok Lee, et al. Coronary and vascular calcification - 다. 조직절편은 hematoxylin-eosin 로염색하고석회화유무는 von Kossa 염색을하여진단하였다. 환자의임상정보를알지못하는전문병리학자가표본을분석하였다. AMiC 양성은 von Kossa 염색에서붉은색의주위조직에갈색또는검은색으로나타나는칼슘침전물이관찰될때로정의하였다. CACS 측정관상동맥칼슘스캔은베타차단제로맥박수 60회미만으로유지한후 128채널비조영증강다중검출컴퓨터단층촬영 (GE Imatron, South San Francisco, CA, USA) 을시행하였다. 관상동맥은 15초의단일호흡동안심전도에서심장이완기일때 5 mm 두께의 30-40개의연속이미지로영상화되었다. 관상동맥석회화는밀도가 130 hounsfield 단위이상인최소 3개이상의연속픽셀의플라크가있는경우로정의된다. CACS는 Agatston 등 [12] 이기술한바와같이계산하였다. CACS는 4개의주요관상동맥각각의개별병변점수를합산하여나타내었다. CACS 에따른사망률비교를위해환자들은 Rumberger 등 [13] 의제안을변형하여 CACS에따라 0, 1-100, 101-400, > 400의 4군으로나누었다. 임상경과추적대상자의추적조사는 2017년 2월까지의의무기록분석으로조사하였다. 추적소실된경우유선으로환자본인이나가족을통해입원치료여부나사망여부를조사하였다. 심혈관질환사망은급성심근경색, 심부전, 뇌혈관질환및급성심장사로정의하였다. 대상자의추적종료시점은사망, 추적소실, 복막투석으로전환, 신장이식그리고연구종료시점인 2017년 2월까지로하였다. 환자를 AMiC 유무에따라두군으로나누어연구기간동안환자전체사망률과심혈과사망률을비교하였다. 통계분석측정치는변수에따라평균 ± 표준편차로표시하였고 AMiC 유무에따른두군의임상지표를비교하기위해독립표본 T검정과카이제곱검정을이용하였다. AMiC에영향을주는인자들의분석을위해로지스틱회귀분석을이용하였다. AMiC 유무와 CACS 4군에따른생존율추정을위해 Kaplan-Meier 생존분석을이용하였고생존율비교를위해로그순위법을이용하였다. 모든통계의유의성판정은 p < 0.05 일때통계학적으로유의한것으로판정하였다. 결과대상자의특성남녀대상자수는각각 76명 (64%) 과 43명 (36%) 이었고평균나이는 64.3 ± 13.0세였다. 말기신부전의원인질환은당뇨 74명 (62.2%), 고혈압 28명 (23.5%), 만성사구체신염 16명 (13.4%), 다낭성신질환 1명 (0.8%) 이었다. 관상동맥질환의병력이있는환자는 4명 (3.4%), 뇌혈관질환을경험한환자는 14명 (11.8%), 말초혈관질환을가진환자는 1명 (0.8%) 이었다. 혈액검사결과칼슘, 인, 부갑상선호르몬수치는 7.7 ± 1.0 mg/dl, 5.8 ± 2.1 mg/dl, 203.0 ± 139.6 pg/ml였다 (Table 1). CACS, 혈관접근로의 AMiC 평균 CACS는 430.4 ± 720.2였고 0부터 3,954까지분포하였다. CACS에따른 4군의환자수는각각 20명, 32명, 27명, 40명이었고평균 CACS는각각 0, 33.2 ± 5.3, 192.0 ± 13.6, 1,124.3 ± 142.1이었다. 119명의환자중 67명 (56%) 의환자에서 von Kossa 염색에서혈관접근로의 AMiC가관찰되었다. AMiC는 von Kossa 염색으로만검출되었고주로동맥중간막에위치하거나속탄력층바로아래에선형으로침착되어있었다 (Fig. 1). 석회화는조직전체에분산되어있었고일부의경우에는석회화된치밀한플라크가동맥내막에서관찰되었다. AMiC 유무에따른임상인자비교표 1에서 AMiC 유무에따른두군간환자들의임상적요인과검사결과를정리하였다. AMiC 양성인군은음성인군과비교하여고령 (67.6 ± 10.6 vs. 60.0 ± 14.6, p < 0.05) 이었고남자환자의비율 (73.1% vs. 51.9%, p < 0.05) 이높았으며당뇨병의유병률 (79.1% vs. 50.0%, p < 0.05) 이높았다. 혈액검사결과는칼슘 (7.8 ± 0.8 vs. 7.5 ± 1.1, p < 0.05) 수치만이 AMiC 양성인군이음성인군에비해통계학적으로유의하게높았다. 임상적요인중흡연상태, BMI, 고혈압유병률, 심혈관질환의과거력은두군간에유의한차이가없었다. 사구체여과율, 지질프로필, 혈청인및 ipth, CRP 등혈액학적검사결사또한두군간에유의한차이가없었다. AMiC 의위험인자단변수분석에서 AMiC 양성인군은고령 (odds ratio [OR]: 1.020, 95% confidence interval [CI]: 1.018-1.083, p < 0.05), 남 - 271 -
- 대한내과학회지 : 제 92 권제 3 호통권제 676 호 2017 - Table 1. Baseline characteristics of the patients Characteristics Total (n = 119) AMiC (+) (n = 67) AMiC (-) (n = 52) p value Age, yr 64.3 ± 13.0 67.6 ± 10.6 60.0 ± 14.6 < 0.05 * Male gender 76 (63.9) 49 (73.1) 27 (51.9) < 0.05 * Current smoker 21 (17.6) 11 (16.4) 10 (19.2) 0.690 BMI, kg/m 2 23.8 ± 4.8 23.7 ± 4.5 23.9 ± 5.1 0.853 CACS 430.4 ± 720.2 569.9 ± 836.5 134.7 ± 369.2 < 0.05 * Cobormid condition DM Hypertension CAD CVD PAD 79 (66.4) 110 (92.4) 4 (3.4) 14 (11.8) 1 (0.8) 53 (79.1) 64 (95.5) 4 (6.0) 10 (14.9) 0 (1.5) 26 (50.0) 46 (88.5) 0 (0) 4 (7.7) 0 (0) < 0.05 * 0.148 0.073 0.224 0.376 Laboratory findings Hemoglobin, g/dl 9.3 ± 1.4 9.5 ± 1.3 9.1 ± 1.5 0.123 MDRD-eGFR, ml/min 7.9 ± 2.9 8.4 ± 2.9 7.4 ± 2.9 0.058 Albumin, g/dl 3.4 ± 1.0 3.4 ± 1.2 3.3 ± 0.7 0.912 Total cholesterol, mg/dl 167.7 ± 50.0 169.4 ± 47.4 165.5 ± 53.7 0.695 Triglyceride, mg/dl 135.0 ± 76.8 132.3 ± 56.3 138.8 ± 98.6 0.686 HDL-cholesterol, mg/dl 38.9 ± 26.4 37.0 ± 11.5 41.4 ± 38.0 0.471 LDL-cholesterol, mg/dl 102.8 ± 38.1 106.8 ± 36.9 97.5 ± 39.5 0.239 Calcium, mg/dl 7.7 ± 1.0 7.8 ± 0.8 7.5 ± 1.1 < 0.05 * Phosphorus, mg/dl 5.8 ± 2.1 5.8 ± 1.7 6.3 ± 2.5 0.058 Ca P product 44.0 ± 13.5 42.8 ± 12.9 45.4 ± 14.2 0.317 ipth, pg/ml 203.0 ± 139.6 191.6 ± 143.0 217.9 ± 135.5 0.394 CRP, mg/dl 1.0 ± 2.1 1.1 ± 2.3 0.9 ± 1.8 0.521 HbA1c, % 6.6 ± 1.4 6.6 ± 1.4 6.5 ± 1.5 0.731 Values are presented as mean ± standard deviation or n (%). AMiC, arterial micro-calcification; BMI, body mass index; CACS, coronary artery calcium score; DM, diabetes mellitus; CAD, coronary arterial disease; CVA, cerebrovascular accident; PAD, peripheral arterial disease; MDRD-eGFR, modification of diet in renal disease -estimated glomerular filtration rate; LDL, low density lipoprotein; ipth, intact parathyroid hormone; CRP, C-reactive protein. * A significant result. A B 관계를보였다 (Table 2). AMiC 와 CACS 의연관성 Figure 1. Histologic findings at the vascular access ( 200). (A) No calcification. (B) Diffuse brown, von Kossa staining of calcification observed in the medial layer of the vascular access. 성 (OR: 2.521, 95% CI: 1.171-5.426, p < 0.05), 당뇨병 (OR: 3.786, 95% CI: 1.699-8.438, p < 0.05) 및혈청칼슘수치 (OR: 1.544, 95% CI: 1.027-2.321, p < 0.05) 와유의한상관관계를보였다 (Table 2). 위의위험인자에대한다변수조정후에도고령 (OR: 1.039, 95% CI: 1.002-1.087, p < 0.05) 과당뇨 (OR: 2.997, 95% CI: 1.184-7.584, p < 0.05) 는 AMiC와유의한상관 AMiC 양성인군은음성인군과비교해 CACS (569.9 ± 836.5 vs. 134.7 ± 369.2, p < 0.05) 가유의하게높았다 (Table 1). CACS에따른 4군에서 AMiC 양성인환자수의비율은각각 10.0%, 34.4%, 66.7%, 90.0% 로 CACS가높은군일수록혈관접근로의 AMiC 양성의빈도가유의하게높았다 (p < 0.05, Fig 2). 단변수분석에서 AMiC 양성인군은 CACS (OR: 1.003, 95% CI: 1.001-1.004, p < 0.05) 와유의한양의상관관계를보였으며, AMiC의위험인자에대한다변수조정후에도 CACS (OR: 1.002, 95% CI: 1.001-1.004, p < 0.05) 는 AMiC와유의한상관관계를보였다 (Table 2). - 272 -
- 이영복외 5 인. 동맥미세석회화와심혈관사망률 - 심혈관사망률및전체사망률평균 35.5 ± 17.8개월의추적관찰기간동안 119명의환자중전체사망은 26명, 심혈관사망은 17명에서발생하였다 (Table 3). Kaplan-Meier 생존분석에서 AMiC 양성인군이음성인군보다전체사망률 (log rank = 5.7, p < 0.05; Figure 3A) 과심혈관사망률 (log rank = 9.0, p <0.05; Figure 3B) 모두유의하게높았다. 또한, CACS 가높은군일수록전체사망률 (log rank = 8.0, p < 0.05; Figure 4A) 과심혈관사망률 (log rank = 11.5, p <0.05; Figure 4B) 모두유의하게높았다. Figure 2. The proportion of patients positive for arterial micro-calcification, by coronary artery calcium score category. Table 2. Association between arterial micro-calcification and other parameters OR (95% CI) p value Univarate analysis Age 1.020 (1.018-1.083) 0.002 Male 2.521 (1.171-5.426) 0.018 DM 3.786 (1.699-8.438) 0.001 CACS 1.003 (1.001-1.004) 0.001 Calcium 1.544 (1.027-2.321) 0.037 Multivariate logistic regression analysis Age 1.039 (1.002-1.087) 0.040 DM 2.997 (1.184-7.584) 0.020 CACS 1.002 (1.001-1.004) 0.008 OR, odds ratio; CI, confidence interval; DM, diabetes mellitus; CACS, coronary artery calcium score. Table 3. Causes of death Event Total AMiC (+) AMiC (-) All-cause death 26 20 6 Non-CV death 9 5 4 Infection 6 4 2 Malignancy 3 1 2 CV death 17 15 2 Sudden cardiac death 11 9 2 AMI CVA 3 3 0 3 3 0 AMiC, arterial micro-calcification; CV death, cardiovascular death; AMI, acute myocardial infarction; CVA, cerebrovascular disease. 고찰혈액투석환자에서혈관접근로 AMiC 는혈관접근로기능이상뿐만아니라심혈관사망률과도관련이있는것으로알려져있다 [7,8,14]. 혈관접근로 AMiC가어떤기전으로높은심혈관사망률과관련이있는지에대한연구는아직잘알려져있지않다. 본연구는혈액투석을시작하는환자에서흔하게관찰되는혈관접근로 AMiC와심혈관질환발생률과사망률의예측인자로알려진관상동맥석회화와의상관관계및 AMiC 유무와 CACS에따른전체사망률및심혈관사망률을알아보고자하였다. 연구결과 AMiC 양성인군에서 CACS가유의하게높았다. 또한 AMiC 양성인군과 CACS 가높은군에서전체사망률과심혈관사망률이유의하게증가하였다. 그러므로혈액투석환자에서혈관접근로 AMiC 는동맥경직뿐만아니라관상동맥석회화를통하여심혈관사망률을증가시키는것으로사료된다. 국내의최근보고에의하면, 혈액투석환자의 48.3% 에서혈관질환을동반하고있으며 36% 에서심혈관질환으로사망한다 [15]. 따라서혈액투석환자에서심혈관질환의적절한예방과조기진단이임상적예후에중요할것으로보이나고령과당뇨를동반한환자의비율이빠르게증가하는추세로질환이진행할때까지무증상인경우가많고일반인구집단의심혈관질환발생위험인자를그대로적용하여질환발생을예측하는것도어렵다. 따라서역학조사를통한혈액투석환자의심혈관계질환의위험인자분석이나발생을미리예측할수있는검사법을찾기위한연구들이있었다. Adragao 등 [16] 은 123명의유지혈액투석환자를대상으로골반과수부의단순방사선촬영을시행하여혈관석회화정도를점수화한방법으로비교한연구에서혈관석회화점수가높은군이낮은군에비해심혈관발생률및사망률이 - 273 -
- The Korean Journal of Medicine: Vol. 92, No. 3, 2017 - A B Figure 3. Kaplan-Meier survival curves for all-cause mortality and cardiovascular mortality of patients with and without arterial micro-calcification of the vascular access. (A) All-cause mortality (log rank = 5.7, p < 0.05), (B) cardiovascular mortality (log rank = 9.0, p < 0.05). AMiC, arterial micro-calcification. A B Figure 4. Kaplan-Meier survival curves for all-cause mortality and cardiovascular mortality across the four groups defined by coronary artery calcium scores (0, 1-100, 101-400, > 400). (A) All-cause mortality (log rank = 8.0, p < 0.05), (B) cardiovascular mortality (log rank = 11.5, p < 0.05). CACS, coronary artery calcium score. 높았다고보고하였다. 혈관석회화를검사하는다른방법으로 2001년 Blacher 등 [17] 은 110명의혈액투석환자에서초음파를이용하여경동맥, 복부대동맥, 장대퇴골동맥, 하지동맥 4부위의혈관석회화를검사하여점수화한후비교하였는데석회화점수가 1점증가할때전체사망률과심혈관사망률이각각 1.9와 2.6배증가한다고발표하였다. 혈관석회화를평가하는방법으로단순방사선촬영, 전산화단층촬영, 초음파, 맥박파전파속도 (pulse wave velocity) 등이있다. 초음파는방사선노출이없고경동맥이나하지동맥도검사가가능하다는장점이있으나평가가주관적이라는단점이있으며, 반면단순방사선촬영은비용이적게들고쉽게검사가가능하나석회화정도를정량화하는평가방법이체계화되어있지않다 [18]. AMiC 를병리학적으로진단하는것은침습적인검사로동맥조직을획득해야하기때문에임상적으로적용하는것은어려운일이다. 그러나말기신부전환자는혈액투석을위해혈근접근로수술시에동맥조직을획득하는것이추가시술 없이이루어질수있어 AMiC 여부를진단하는것이어렵지않으며영상학적검사법에비해초기단계의석회화를진단할수있어혈액투석을시작하는환자에서임상적예후를예측하는검사로고려할수있다. 혈액투석환자에서 CACS가전원인사망률및심혈관사망률의예측인자임을보고한여러연구들이있다. Matsuoka 등 [7] 과 Shantouf 등 [19] 은혈액투석환자에서 CACS를측정하여임상경과를추적한결과 CACS 가전체또는심혈관사망률의독립적인예측인자라고보고하였다. 영상검사를이용한 CACS 측정은민감도와특이도가높은검사로운동부하검사나심근관류스캔, 심장초음파등다른비침습적인심장검사에비해정확도에서유리하고간단하게시행할수있는검사로혈액투석을시작하는환자에서투석시작당시심혈관질환을동반하고있을가능성이높고고령, 당뇨등심혈관질환의위험인자를동반하고있는경우가많기때문에임상적예후를예측하는검사로유용할것으로생각된다. 혈액투석환자에서혈관접근로수술에가장흔하게사용하는동맥인요골동맥은진행된관상동맥질환환자에서병 - 274 -
- Yeong Bok Lee, et al. Coronary and vascular calcification - 리조직학적검사를시행한결과속유선동맥이나복재정맥보다요골동맥에서중간막석회화의발생률이높은것으로보고된바있다 [20]. Deshpande 등 [21] 은관상동맥우회로수술을시행한 130명의환자를대상으로통로로사용한요골동맥의병리조직학적검사를시행하였고, 이연구에서 130명중 4명의환자에서석회화가관찰되었으며 4명모두기저질환으로당뇨와심한신기능저하가있던환자였다. 이연구들은진행된관상동맥질환과요골동맥석회화간에상관관계가있음을시사한다. 혈관석회화의위험인자로고령, 당뇨, 고혈압, 고지혈증등의고전적인위험인자외높은혈청칼슘및인수치, 염증, 산화스트레스등이알려져있다 [22]. 그러나본연구에서는 AMiC가고령, 남성, 당뇨, 칼슘수치와상관관계를보였으나이전연구에서상관관계가있다고보고된적있는지질대사이상이나혈청인, 칼슘 인수치및 CRP와는상관관계를보이지않았다. 이러한여러연구들의상반된결과들및일반인구집단과다른양상으로인해혈액투석환자에서혈관석회화의위험인자가확실히정립되지않아향후보다많은환자를대상으로추가연구가필요할것으로생각된다. 본연구는다음과같은제한점이있다. 첫째, 대상군의수가적었고둘째, 혈액투석을받는말기신부전환자만을대상으로하였기때문에투석전만성신부전단계에따른 AMiC와 CACS, 혈관석회화의위험인자들간의연관관계를연구하지못하였다. 결론적으로, 혈액투석환자에서혈관접근로의 AMiC와 CACS는심혈관사망의위험인자이며서로유의한상관관계가있었다. 말기신부전환자에서심혈관질환발생의예측이나조기진단을위한위험인자및검사법에대한연구가필요할것으로생각된다. 요약목적 : 혈액투석환자에서혈관접근로의 AMiC와관상동맥석회화간의상관관계및 AMiC 유무가심혈관사망률에미치는영향을조사하였다. 방법 : 2011년 4월부터 2015년 5월까지혈관접근로수술과 CACS 검사를시행한 119명의환자를대상으로하였다. 혈관접근로의 AMiC 는수술중획득한동맥표본의 von Kossa 염색으로진단하였다. 모든환자는비조영증강다중검출컴 퓨터단층촬영을시행하여 CACS를계산하였다. 대상환자에서 AMiC 와 CACS의상관관계를조사하였다. 또한 2017년 2월까지추적조사하였고환자를 AMiC 유무에따라두군으로나누어심혈관사망률을비교하였다. 결과 : 남녀대상자수는각각 76명 (64%) 과 43명 (36%) 이었고평균나이는 64.3 ± 13.0세였다. 67명 (56%) 의환자에서 von Kossa 염색에서혈관접근로의 AMiC가관찰되었고평균 CACS는 430.4 ± 720.2였으며 99명 (83%) 의환자에서관상동맥석회화가관찰되었다. 다중로지스틱회귀분석결과 CACS (OR: 1.002, 95% CI: 1.001-1.004, p < 0.05) 는 AMiC와유의한상관관계를보였다. 추적관찰기간동안전체사망은 26명이었고그중 17명이심혈관사망이었다. Kaplan-Meier 생존분석에서 AMiC 양성인군에서음성인군에비해심혈관사망률 (log rank = 9.0, p < 0.05) 이유의하게높았다. 결론 : 본연구는혈액투석환자에서 AMiC와 CACS와밀접하게연관되어있으며 AMiC와 CACS는심혈관질환사망의위험인자임을시사한다. 중심단어 : 관상동맥죽상경화증 ; 혈관석회화 ; 혈액투석 REFERENCES 1. Causes of death. United States Renal Data System. Am J Kidney Dis 1998;32(2 Suppl 1):S81-S88. 2. Park JT, Oh HJ, Kang SW. Cardiovascular disease in end-stage renal disease. J Korean Med Assoc 2013;56:576-582. 3. Desai AA, Nissenson A, Chertow GM, et al. The relationship between laboratory-based outcome measures and mortality in end-stage renal disease: a systematic review. Hemodial Int 2009;13:347-359. 4. Schwarz U, Buzello M, Ritz E, et al. Morphology of coronary atherosclerotic lesions in patients with end-stage renal failure. Nephrol Dial Transplant 2000;15:218-223. 5. Kramer CK, Zinman B, Gross JL, et al. Coronary artery calcium score prediction of all-cause mortality and cardiovascular events in people with type 2 diabetes: systematic review and meta-analysis. BMJ 2013;346:f1654. 6. Detrano R, Guerci AD, Carr JJ, et al. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med 2008;358:1336-1345. 7. Matsuoka M, Iseki K, Tamashiro M, et al. Impact of high coronary artery calcification score (CACS) on survival in patients on chronic hemodialysis. Clin Exp Nephrol 2004;8:54-58. 8. Block GA, Raggi P, Bellasi A, Kooienga L, Spiegel DM. - 275 -
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