대한진단검사의학회지 : 제 25 권제 4 호 2005 Korean J Lab Med 2005; 25: 임상화학 뇌경색위험인자로서의혈청호모시스테인 이명희 서울보훈병원진단검사의학과 Hyperhomocysteinemia as a Risk Factor for Ce

대한진단검사의학회지 : 제 25 권제 4 호 2005 Korean J Lab Med 2005; 25: 234-40 임상화학 뇌경색위험인자로서의혈청호모시스테인 이명희 서울보훈병원진단검사의학과 Hyperhomocysteinemia as a Risk Factor for Cerebral Infarction Myung Hee Lee, M.D. Department of Laboratory Medicine, Seoul Veterans Hospital, Seoul, Korea Background : Homocysteine (Hcy) is known to increase the risk of cerebrovascular disease. I investigated this association in cerebral infarction (CI) and established reference intervals for serum total Hcy concentrations among individuals aged 40 or over in Korea. Methods : I measured Hcy concentrations in the sera from 93 healthy controls (male 74, female 19) and 742 patients with CI (male 616, female 126) by a fluorescent polarization immuno assay technique using Axsym system (Abbott Laboratories, IL, USA). Results : In CI group, the following parameters were significantly higher (P<0.001) than in normal control (NC): the serum Hcy level (13.4±6.6 vs. 10.3±2.6 mol/l), age (67.1±9.0 vs. 62.6±9.9 years), C-reactive protein (10.2±22.2 vs. 5.5±6.4 mg/dl), and the prevalence of hypertension (69 vs. 33%) and diabetes mellitus (DM) (38 vs. 5%). The serum folate level in CI group was significantly lower than in NC group (7.5±4.1 vs. 8.8±5.0 ng/ml, P=0.037). The mean and upper reference limit of Hcy in male control (10.7 and 14.9 mol/l) were significantly higher than in female control (8.1 and 10.8 mol/l). The risk of CI was higher in subjects with old age ( 60 years), hypertension, DM, hyperhomocysteinemia, high creatinine, and in the highest Hcy quartile ( 15.1 mol/l) compared to the lowest Hcy quartile (<9.6 mol/l) with the crude odds ratios of 2.1, 4.3, 10.5, 7.4, 3.0, and 6.6, respectively; in multivariate analysis, the risk of CI was independently associated with hypertension, DM, hyperhomocysteinemia and adjusted odds ratios were 3.6, 5.3, and 7.1, respectively. In CI group, Hcy exhibits negative correlations (P<0.001) with folate (r=-0.356) and vitamin B12 (r=-0.256). Conclusions : Hyperhomocysteinemia may represent an independent risk factor for cerebrovascular disease. (Korean J Lab Med 2005; 25: 234-40) Key Words : Homocysteine, Cerebrovascular disease, Hyperhomocysteinemia, Cerebral infarction, Risk, Adjusted odds ratio, Correlation 서 론 1962 년 Carson 과 Neill 등 [1] 은정신지체아의소변에서호모시 접수 : 2005년 1월 11일접수번호 : KJLM1829 수정본접수 : 2005년 6월 15일교신저자 : 이명희우 134-791 서울시강동구둔촌동 6-2 서울보훈병원진단검사의학과전화 : 02-2225-1448, Fax: 02-2225-1448 E-mail: myung220@hanmail.net * 본논문은 2004년서울보훈병원임상연구비지원으로연구되었음. 스테인농도가증가된것을처음으로보고하였고 1969년 McCully[2] 가이들환자에서평활근증식, 진행성동맥협착, 지혈작용변화등의혈관병리에대해기술한이래로호모시스테인과질병과의연관성에대해많은연구가있었고폐쇄성동맥질환이나정맥혈전증 [3, 4], 울혈성심부전 [5] 의강력하고독립적인위험인자로서, 중풍 [6], 죽상경화증 [7], 자연조기유산이나태반의혈관병증 [8], 신경관결손 [9], 심장기형, 갈림입술, 갈림입천장등의선천적기형 [10], 인지수행부전 [11], 치매 [12], 우울증과여러신경정신과적인질환 [13, 14], 암형성 [15] 등과고호모시스테인 234

뇌경색위험인자로서의혈청호모시스테인 235 혈증이관련이있다고보고되었다. 또한임신중에엽산을보충하면신경관결손이나다른선천적기형, 자연유산같은임신합병증의빈도를줄일수있고 [16] 가벼운인지장애가있는노인에서호모시스테인의농도를낮추면인지수행에긍정적인영향을미치고뇌혈류를증가시킨다고하였으며 [17] 비타민치료가죽상경화증의진행속도에영향을미치고내피의혈류를증가시킨다 [18] 고하여엽산이나비타민 B 6, 비타민 B 12 등의보조인자투여로혈중호모시스테인의농도를감소시킴으로이들질환을치료및예방할수있으리라는가능성이제기되어왔다 [19, 20]. 기존의호모시스테인측정은일반적인검사실에서이용하기에는어려움이많은 high performance liquid chromatography (HPLC) 를이용하여왔으나근래에는형광면역측정법 (fluorescence polarization immunoassay, FPIA) 이도입되어보다간단한방법으로측정이가능해졌으며검체도혈장대신혈청을사용할수있게되었다. 저자는뇌혈관질환의위험인자로서혈청호모시스테인을평가하고 40세이상의한국인에서혈청검체를대상으로호모시스테인의참고치를구하고자본연구를시행하였다. 대상및방법 1. 대상 2003년 6월부터 2004년 10월까지서울보훈병원에서뇌경색으로진단받은 40세이상의환자 742명 ( 남자 616명, 여자 126명 ) 을질환군으로하였고호모시스테인의농도에영향을주는 methotrexate, carbamazepine, phenytoin, nitrous oxide 등의약물을복용한사람은제외하였다. 40세이상의건강검진자중빈혈이없고혈액화학검사에서간장및신장기능에이상이없는 240명 ( 남자 120명, 여자 120명 ) 을대상으로혈청호모시스테인을측정하여참고범위를구하였고이들중다른검사가가능했던 93명 ( 남자 74명, 여자 19명 ) 만을정상대조군으로통계분석에포함하였다. 2. 방법금식상태에서혈액 3 ml를 gel이들어있는 sereum seperator tube (SST) 에채혈하여한시간이내에 1,000 g에서 15분간원심분리한후혈청을분리하여분석전까지냉장고에보관하였다가당일검사하였으며대조군과실험군사이에혈청분리전까지소요된시간의차이는없었다. 호모시스테인은형광편광면역법으로제조사의지시에따라 Axsym (Abbott Laboratories, IL, USA) 장비로측정하였다. 즉혈청단백이나기타물질에결합되어있는호모시스테인을 dithiothreitol을이용하여유리형으로환원한다음아데노신과결합시켜 s-adenosylhomocysteine으로변화시키고이에대한단클론항체와형광물질을결합한추적자를반응시켜편광된형광의광도 로총호모시스테인의농도를측정하였다. 엽산과비타민 B 12 는 전기화학발광면역법을이용하는 Modular analytics E170 (Roche diagnostics, Mannheim, Germany) 장비로, 총콜레스테롤 (Eiken, Tokyo, Japan), 고밀도지단백콜레스테롤과저밀도지단백콜레 스테롤 (Kyowamedex co., Tokyo, Japan) 등은효소법, 중성지방 은 glycerol 소거법 (Wako, Osaka, Japan), 크레아티닌은 Jaffe 법 (Roche diagnostics, Mannheim, Germany), CRP 는 CRP(II) latex X2 (Denka Seiken, Tokyo, Japan) 시약을사용하여 TBA- 200 FR (Toshiba, Tokyo, Japan) 자동화학분석기로측정하였다. 본병원에서현재사용하는총콜레스테롤 200 mg/dl, 중성지방 160 mg/dl, 저밀도지단백콜레스테롤 130 mg/dl, 고밀도지단백콜레스테롤 40 mg/dl, 크레아티닌 1.2 mg/dl, CRP 3.3 mg/dl를참고치의기준으로사용하였다. 3. 통계분석 통계패키지프로그램은 SPSS for Windows, version 11.0 (SPSS Inc., Chicago, Illinois, USA) 을사용하여 P 값이 0.05 미만인경우통계학적으로유의하다고판정하였다. 정상대조군과뇌경색환자군간에각종검사의평균치가유의한차이가있는지독립표본 T검정을실시하였고교차분석을통하여각요인에대한승산비와위험도를계산하였으며단변량분석에서통계학적으로유의한인자들을대상으로로지스틱회귀분석을이용하여다변량분석을시행하였다. 각종검사간에유의한상관관계가있는지는 Pearson 상관계수를구하여분석하였다. 결 1. 건강대조군과뇌경색환자군의임상소견및각종생화학적검사결과 (Table 1) 뇌경색환자중고혈압, 당뇨병, 관상동맥질환, 울혈성심부전등이동반된환자는각각 69%, 38%, 20%, 6% 등이었으나정상대조군은 33% 에서고혈압을, 5% 에서당뇨병을동반하였고연령도 67.1±9.0세 ( 평균 ± 표준편차 ) 로대조군의 62.6±9.9세에비해유의하게높았다 (P<0.001). 혈청엽산의농도는환자군에서 7.5±4.1 ng/ml로대조군의 8.8±5.0 ng/ml에비해유의하게낮았고 (P=0.037) CRP는환자군에서 10.2±22.2 mg/dl로대조군의 5.5±6.4 mg/dl에비해유의하게높았다 (P<0.001). 과 2. 뇌경색환자군과대조군의혈청호모시스테인농도 (Table 2) 전체뇌경색환자의혈청호모시스테인농도는 13.4±6.6 mol/

236 이명희 L로대조군의 10.3±2.6 mol/l에비해유의하게높았고남자뇌경색환자군에서 14.0±6.9 mol/l, 여자뇌경색환자군에서 Table 1. Characteristics of the study group Normal control (N=93) Cerebral infarction (N=742) P value Age (year) 62.6±9.9* 67.1±9.0 <0.001 Male, n (%) 74 (79.6) 616 (83.0) NS Hypertension, n (%) 31 (33.3) 510 (68.7) <0.001 Diabetes, n (%) 5 (5.4) 278 (37.5) <0.001 Ischemic heart disease, n (%) 0 152 (20.5) <0.001 Congestive heart failure, n (%) 0 41 (5.5) <0.001 Serum homocysteine ( mol/l) 10.3±2.6 13.4±6.6 <0.001 Folate (ng/ml) 8.8±5.0 7.5±4.1 0.037 Vitamin B12 (pg/ml) 767.3±472.0 725.6±387.7 NS C-reactive protein (mg/dl) 5.5±6.4 10.2±22.2 <0.001 Creatinine (mg/dl) 0.9±0.2 1.5±6.7 NS Total cholesterol (mg/dl) 179.8±39.1 178.4±39.4 NS Triglyceride (mg/dl) 135.8±72.9 133.5±83.1 NS LDL-cholesterol (mg/dl) 112.0±32.1 112.4±32.6 NS HDL-cholesterol (mg/dl) 57.5±10.6 45.7±12.7 NS *Values are mean standard deviation; P>0.05; tested by student t-test. Abbreviation: NS, statistically non-significant. 10.1±3.7 mol/l, 남자대조군에서 10.7±2.6 mol/l, 여자대조군에서 8.1±1.6 mol/l로두군모두에서남자의혈청호모시스테인농도가유의하게높았다 (P<0.001). 연령과혈청호모시스테인의농도사이에는통계학적으로유의한상관관계를관찰할수없었다. Table 2. The concentrations of homocysteine according to age and sex in normal control and cerebral infarction group No. Control M±SD ( mol/l) Cerebral infarction P value *male vs. female in control and cerebral infarction group, P<0.001; tested by student t-test. Abbreviation: See Table 1. No. M±SD ( mol/l) Age 40-49 8 8.9±2.8 22 12.7±9.3 NS 50-59 33 10.4±2.9 180 13.0±6.4 0.022 60-69 22 9.8±2.7 169 12.8±6.3 0.030 70-79 28 11.0±2.1 328 13.9±6.9 <0.001 80-89 2 10.2±0.2 40 13.3±4.4 NS 90-0 3 12.8±4.9 Sex Male 74 10.7±2.6* 616 14.0±6.9* <0.001 Female 19 8.1±1.6 126 10.1±3.7 0.042 Total 93 10.3±2.6 742 13.4±6.6 <0.001 Table 3. Odds ratio for cerebral infarction associated with selective risk factors Risk factors Number (%) Odds ratio (95% confidence interval) Crude Adjusted Risk factors Number (%) Odds ratio (95% confidence interval) Crude Adjusted Total CI NC Total CI NC Age (years) 60 592 (71) 540 (73) 52 (56) 2.1 (1.4-3.3) <60 243 (29) 202 (27) 41 (44) 1.0 Sex Male 690 (83) 616 (83) 74 (80) 1.3 (0.7-2.2) Female 145 (17) 126 (17) 19 (20) 1.0 Hypertension (+) 536 (64) 505 (68) 31 (33) 4.3 3.6 (2.7-6.7) (1.8-7.0) (-) 299 (36) 237 (32) 62 (67) 1.0 1.0 DM (+) 283 (34) 278 (37) 5 (5) 10.5 5.3 (4.2-26.3) (1.8-15.3) (-) 552 (66) 464 (63) 88 (95) 1.0 1.0 Homocysteine Increased* 224 219 (30) 5 (5) 7.4 7.1 (3.0-18.3) (2.4-21.2) Normal 611 523 (70) 88 (95) 1.0 1.0 Folate <4.2 ng/ml 103 (18) 98 (19) 5 (10) 2.1 (0.8-5.4) 4.2 ng/ml 467 (82) 422 (81) 45 (90) 1.0 Vit B12 <243 pg/ml 25 (4) 23 (4) 2 (4) 1.1 (0.3-4.8) 243 pg/ml 549 (96) 501 (96) 48 (96) 1.0 CRP >3.3 mg/dl 277 (36) 253 (37) 24 (31) 1.3 (0.8-2.1) 3.3 mg/dl 487 (64) 434 (63) 53 (69) 1.0 Creatinine >1.2 mg/dl 96 (20) 92 (21) 4 (8) 3.0 (1.1-8.7) 1.2 mg/dl 393(80) 347(79) 46(92) 1.0 Total cholesterol 200 mg/dl 210 (28) 195 (29) 15 (19) 1.7 (0.9-3.0) <200 mg/dl 549 (72) 487 (71) 62 (81) 1.0 Triglyceride >160 mg/dl 199 (29) 176 (28) 23 (33) 0.8 (0.5-1.4) 160 mg/dl 489 (71) 443 (72) 46 (67) 1.0 HDL-cholesterol <40 mg/dl 8 (28) 7 (32) 1 (14) 2.8 (0.3-27.9) 40 mg/dl 21 (72) 15 (68) 6 (86) 1.0 *Homocysteine level >14.9 mol/l in male, >10.8 mol/l in female; P=0.001; P<0.001; P=0.037; P=0.002. Abbreviations: CI, cerebral infarction; NC, normal control.

뇌경색위험인자로서의혈청호모시스테인 237 Table 4. Odds ratio of cerebral infarction according to homocysteine quartile group Quartile group Mean ( mol/l) Odds ratio (95% CI) P value <9.6 8.1 1 9.6-11.8 10.8 1.3 (0.7-2.2) NS 11.9-15.0 13.1 1.4 (0.8-2.5) NS 15.1 21.4 6.6 (2.7-16.1) <0.001 Abbreviations: CI, confidence interval; NS, statistically non-significant. 3. 뇌경색발생의위험인자들에대한위험도검토 (Table 3) 정상대조군 240명을대상으로혈청호모시스테인을측정한결과 2.5백분위수는남녀모두 5.4 mol/l, 97.5백분위수는남자 14.9 mol/l, 여자 10.8 mol/l이었기때문에이를고호모시스테인혈증의기준으로삼았다. 연령, 성별, 고혈압, 당뇨병, 혈청호모시스테인농도, 엽산, 비타민 B 12, CRP, 크레아티닌, 총콜레스테롤, 중성지방, 고밀도지단백콜레스테롤등에대하여단변량분석을시행하였는데 60세이상의고령, 고혈압, 당뇨병, 고호모시스테인혈증, 크레아티닌의증가등이통계학적으로유의한뇌경색의위험인자로평가되었고, 위험도는음성인군에비해각각 2.1배, 4.3배, 10.5배, 7.4배, 3.0 배만큼높았다. 단변량분석에서통계학적으로유의한인자들만을대상으로다변량분석을시행한결과고혈압, 당뇨, 고호모시스테인혈증등만이각각교차비 3.6배, 5.3배, 7.1배로유의한결과를보여뇌경색의독립적인위험인자로평가되었다. 4. 혈청호모시스테인농도에따른뇌경색의위험도 (Table 4) 혈청호모시스테인의분포는 95백분위수, 90백분위수, 75백분위수, 50백분위수, 25백분위수가각각 23.8 mol/l, 19.3 mol/l, 15.1 mol/l, 11.8 mol/l, 9.6 mol/l이었고최대값은 50 mol/l, 최소값은 4.3 mol/l 이었다. 혈청호모시스테인의농도를사분위로나누어보았을때농도가가장높은군 ( 15.1 mol/ L) 의뇌경색에대한위험도는가장낮은농도의군 (<9.6 mol/ L) 에비해 6.6배높았으나 (P<0.001), 11.9-15.0 mol/l인군과 9.6-11.8 mol/l인군의위험도는각각 1.4배와 1.3배로통계학적으로유의하지않았다. 5. 혈청호모시스테인농도와다른검사들간의상관관계 (Table 5) 혈청호모시스테인의농도와엽산, 비타민 B 12, CRP, 크레아티닌, 총콜레스테롤, 중성지방, 저밀도지단백콜레스테롤, 고밀도지단백콜레스테롤, 연령등과의상관관계를분석한결과정상대조군에서혈청호모시스테인의농도는크레아티닌 (r=0.547, P< 0.001), 중성지방 (r=0.263, P=0.029) 등과양의상관관계를, 비타민 B 12 와음의상관관계 (r=-0.392, P=0.005) 를보였고뇌경색 Table 5. Correlation coefficient of various parameters in cerebral infarction patients and in normal controls Items Homocysteine Folate Creatinine NC CI NC CI 환자군에서는엽산 (r=-0.356, P<0.001), 비타민 B 12 (r=-0.256, P<0.001) 등과음의상관관계를보였다. 고 호모시스테인은음식물을통해섭취된 methionine이체내에서탈메틸화되어생성된아미노산으로서 methione으로재메틸화되거나 glutathione의전구체인 cysteine으로대사된다. 이들대사과정에관여하는 methionine synthase, methyltetrahydrofolate reductase (MTHFR), cystathione -synthase 등의효소에유전적결함이있거나엽산, 비타민 B 6, 비타민 B 12 등의보조인자가결핍될때에는고호모시스테인혈증이나호모시스테인뇨증 (homocystinuria) 을초래한다. 재메틸화가감소하면핵산, 단백질, 인지질, myelin, 다당류, choline, 카테콜아민등의메틸화에필요한메틸기를제공할수없기때문에세포의성장, 분화, 기능에막대한지장을초래하고중요한내인성항독소인 glutathione의생성이감소하면세포성분이산화로손상되는것을방지하거나혈관을보호하는역할을할수없게되며어떤형태의호모시스테인은그자체가산화와단백질손상을초래할수있다 [21]. 호모시스테인의혈중농도는연령의증가와더불어증가하는데이는노년층에흔한위축성위염으로인한흡수장애, 불충분한비타민과영양공급, 대사속도와신장기능의감소, 기타나이에따른생리적요인, 보조인자의흡수를방해하거나비타민의이화작용을촉진하는약물, 호모시스테인대사에영향을미치는각종질환등때문이며흡연, 음주, 커피, 육체적인활동의부족, 비만, 스트레스등의생활양식에따라서도차이가있다 [15]. 호모시스테인의측정을위한검체는항응고제를사용하면즉시혈장분리를할수있기때문에전통적으로혈장을사용하도록권장되어왔고적혈구와분리하지않으면적혈구로부터호모시스테인이방출되어실온에서는시간당약 1 mol/l씩증가한다 [22] 고알려져있기때문에혈청을검체로사용하면혈장검체보다약 5-10% 높게측정된다 [23]. 따라서호모시스테인의증가를방지하기위해서는채혈즉시적혈구와분리하거나원심분리전까지검체를냉장보관하거나 gel이들어있는 SST를사용하여즉각원심분리 찰 Cholesterol NC CI Folate -0.356 Vit B12-0.392* -0.256 0.219 Creatinine 0.547 Triglyceride 0.263 0.282 LDL cholesterol 0.883 0.789 HDL cholesterol -0.516 *P=0.005; P<0.001; P=0.029; P=0.034 Abbreviations: See Table 3.

238 이명희 를시켜놓아야하는데본연구에서는 gel이든 SST를사용하고검사실에도착한후 1시간이내에분리하기는하였지만채혈후검사실로운반되기까지약 1-2시간지체되었을가능성을완전히배제할수는없었다. 본연구에서호모시스테인의참고치상한이여성인경우 10.8 mol/l, 남성인경우 14.9 mol/l이었는데이는혈장을검체로사용한오등 [24] 의 10.6 mol/l, 14.9 mol/ L와비슷했으나, Wu 등 [25] 의 15.43 mol/l, Selhub 등 [20] 의 11.6 mol/l, 15.3 mol/l, 제조사의 12.44 mol/l, 15.01 mol/ L보다는약간낮았다. 고호모시스테인혈증이관상동맥, 뇌혈관, 말초혈관의죽상경화증과관련이있다는사실을확인하는연구결과 [26, 27] 가많이발표되었는데 Welch[4] 나 Stein 등 [7] 은일반인의 5-7%, 관상동맥질환을가진환자의 30%, 뇌혈관질환을가진환자의 42% 에서호모시스테인이증가되었다고하였고, Briani 등 [12] 은뇌혈관질환자의 54.2% 에서호모시스테인이증가되었다고하였는데본연구에서는뇌경색환자의 25% 에서호모시스테인이증가되어있어서김등 [28] 의 20.4% 와비슷하였다. 27개의논문을분석한 Boushey 등 [4] 은호모시스테인이증가된사람은정상인사람에비해관상동맥질환의위험도가 1.7배, 뇌졸증의위험도가 2.5배, 말초혈관질환의위험도가 6.8배, 호모시스테인의농도가 5 mol/ L씩증가할때마다뇌혈관질환에걸릴위험도가 1.9배라고하였고 Bautista 등 [29] 은 14개의논문을분석하여고호모시스테인혈증이심장질환의위험도를 1.49배, 허혈성뇌졸중의위험도를 1.37배높인다고하였으며 Moller 등 [30] 은호모시스테인의농도가 95 백분위수이상인경우뇌혈관질환의위험도가 3.97배라고하였는데본연구에서는호모시스테인의농도가증가된경우정상인군에비해뇌경색의위험도가 7.4배였고 75백분위수이상인경우에는 25백분위수이하인경우에비해뇌경색의위험도가 6.6 배로약간높게분석되었다. 단변량분석에서 60세이상의고령, 고혈압, 당뇨병, 크레아티닌의증가, 호모시스테인의증가등이통계학적으로유의한위험인자로평가되었는데엽산과고밀도지단백콜레스테롤의감소는교차비는각각 2.1과 2.8로높았으나분석에포함된검체수가적어서인지통계학적으로는유의하지않았고단변량분석에서유의하다고분석된인자들을대상으로한다변량분석결과고혈압, 당뇨병, 고호모시스테인혈증만이독립적인위험인자로사료되었다. Selhurb 등 [20] 은호모시스테인이엽산이나비타민의혈중농도가감소된것을알수있는예민한지표이며호모시스테인이증가된사람의 2/3에서엽산이나비타민 B 12 가감소했는데 40세미만인사람에서는 75% 에서, 60세이상인사람에서는 30% 에서엽산이나비타민 B 12 가감소되었다고하면서노인층에서는호모시스테인이증가하는원인으로비타민감소이외에도신장기능의감소등다른원인이작용하기때문이라고설명하고있다. 본연구에서도호모시스테인이증가된사람중 28% (53/187) 에서엽산이감소되었고 6% (11/187) 에서비타민 B 12 가감소되었으며 32% (59/187) 에서엽산이나비타민 B 12 가감소되어있었다. Bates 등 [31] 과 Nygard 등 [32] 은호모시스테인과엽산, 호모시스테인과비타민 B 12 간에는유의한역상관관계가있다고하였는데본연구에서도뇌경색환자군에서는호모시스테인과엽산 (r=-0.356), 호모시스테인과비타민 B 12 (r=-0.256) 간에통계학적으로유의한 (P<0.001) 역상관관계가있었으나정상대조군에서는호모시스테인과비타민 B12 간에만유의한역상관관계 (r=-0.392) 가있었고엽산과는유의한상관관계를관찰할수없었다. 요약배경 : 호모시스테인은뇌혈관질환의위험을높인다고알려져있다. 이에저자는뇌경색의위험인자로서혈청호모시스테인을평가하고 40세이상의한국인에서혈청호모시스테인의참고치를구하고자본연구를시행하였다. 방법 : 서울보훈병원에서뇌경색으로진단받은 40세이상의환자 742명 ( 남자 616명, 여자 126명 ) 과 40세이상의건강검진자 93명 ( 남자 74명, 여자 19명 ) 을대상으로하였고혈청호모시스테인은형광편광면역법을이용하는 Axsym (Abbott Laboratories, IL, USA) 장비로측정하였다. 결과 : 뇌경색환자군의호모시스테인평균농도 (M±SD), 평균연령, CRP, 고혈압과당뇨병유병률은각각 13.4±6.6 mol/l, 67.1±9.0세, 10.2±22.2 mg/dl, 69%, 38% 로정상대조군의 10.3 ±2.6 mol/l, 62.6±9.9세, 5.5±6.4 mg/dl, 33%, 5% 에비해유의하게높았고 (P<0.001) 엽산의평균농도는뇌경색환자군 (7.5±4.1 ng/ml) 에서정상대조군 (8.8±5.0 ng/ml) 에비해유의하게낮았다 (P=0.037). 정상대조군에서평균호모시스테인의농도는남자 (10.7±2.6 mol/l) 에서여자 (8.1±1.6 mol/l) 보다높았고남녀의참고치상한은각각 14.9, 10.8 mol/l였다. 60세이상의고령, 고혈압, 당뇨병, 고호모시스테인혈증, 크레아티닌의증가등이정상대조군에비해각각 2.1배, 4.3배, 10.5배, 7.4배, 3.0배만큼높은위험도를보였고이들을대상으로다변량분석을실시한결과고혈압, 당뇨병, 고호모시스테인혈증등만이각각 3.6배, 5.3배, 7.1배의위험도를보여뇌경색의독립적인위험인자로평가되었다. 혈청호모시스테인사분위수중가장높은농도의군 ( 15.1 mol/l) 의뇌경색에대한위험도는가장낮은농도의군 (<9.6 mol/l) 에비해 6.6배만큼높았다. 뇌경색환자군에서호모시스테인은엽산 (r=-0.356, P<0.001), 비타민 B 12 (r=-0.256, P=<0.001) 등과음의상관관계를보였다. 결론 : 혈청호모시스테인농도의증가는뇌혈관질환의독립적인위험인자로사료되었다. 참고문헌 1. Carson NA, Cusworth DC, Dent CE, Field CM, Neill DW, Westall

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