Journal of Health Informatics and Statistics Original Article J Health Info Stat 2016;41(1): pissn 2

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1 Original Article J Health Info Stat 2016;41(1): pissn eissn 한국성인남성에서흡연과대사증후군및동맥경화증과의관계 김수영 1, 나은희 1, 조한익 2,3 1 한국건강관리협회 건강증진연구소, 2 서울대학교의과대학진단검사의학과, 3 한국건강관리협회 중앙검사의원 Association between Smoking, Metabolic Syndrome, and Arteriosclerosis in Korean Men Suyoung Kim 1, Eun-Hee Nah 1, Han-Ik Cho 2,3 1 Korea Association of Health Promotion, Health Promotion Research Institute, Seoul; 2 Department of Laboratory Medicine, Collage of Medicine, Seoul National University, Seoul; 3 Korea Association of Health Korea Association of Health Promotion, MEDIcheck Lab, Cheongju, Korea Objectives: Smoking is an important risk factor for metabolic syndrome (Mets) and cardiovascular disease. This study has been designed to investigate the relationship between smoking, metabolic syndrome, and arteriosclerosis among men in South Korea. Methods: We have retrospectively enrolled data of 5,103 men aged over 20 years, who underwent a health check-up including carotid ultrasonography in Smoking status and amount were collected from self-reported questionnaires. The diagnosis of Mets was made using criteria modified NCEP-ATP III. Using multivariate logistic regression analysis, the risk of Mets and arteriosclerosis defined as abnormal carotid intima-media thickness (CIMT) and carotid plaque according to smoking amounts was examined. Results: Both former (29.7%) and current (27.8%) s had a higher prevalence of Mets than never (23.2%) s [OR (95% CI): former, 1.35 (1.14, 1.6); current, 1.63 (1.35, 1.98), respectively]. There had been a significant increase in the risk of Mets, low HDL-cholesterol and high fasting blood sugar among the former and current s who smoke 20 pack-years (PY) (p < 0.001). And there had also been a significant increase in the risk of high triglyceride at all levels in smoking amount. There was a clear dose-dependent relationship between smoking amount and arteriosclerosis especially the risk of carotid plaque (all p < 0.005). In individuals without Mets, smoking consumption in former or current s was positively associated with the risk of CIMT and carotid plaque by adjusted age, BMI, LDL-cholesterol. Conclusions: The former or current smoking status and high level of smoking amount were relation with Mets and arteriosclerosis in men. The smoking was risk factor for arteriosclerosis and that was explained by relationship with metabolic syndrome in part. Key words: Smoking status, Smoking amount, Metabolic syndrome, Arteriosclerosis, Cardiovascular disease 서론 흡연은심혈관계질환의주요위험인자이다 [1]. 이에대한기전은명확하지않지만, 흡연이인슐린저항성을증가시키고이러한인슐린대사의변화가심혈관계질환위험을가속화시킨다고알려져있다 [2]. 복부비만, 혈당이상, 고혈압, 이상지질혈증등대사적이상의조합으로정 의되는대사증후군의경우, 인슐린저항성이증가하여당뇨병혹은심혈관계질환의발생가능성이높아진다 [3]. 이러한특징은흡연이대사증후군발생위험을증가시킴으로써심혈관계질환의위험을증가시킬가능성을시사한다 [4,5]. 또한흡연은대사증후군구성인자중고밀도콜레스테롤을낮추고중성지방을높일뿐아니라, LDL 콜레스테롤 (low-density lipoprotein cholesterol) 수치를높이며, 심혈관계질환의위 Corresponding author: Eun-Hee Nah 350 Hwagok-ro, Gangseo-gu, Seoul 07653, Korea Tel: , cellonah@hanmail.net Received: November 26, 2015 Revised: January 13, 2016 Accepted: January 25, 2016 No potential conflict of interest relevant to this article was reported. How to cite this article: Kim S, Nah EH, Cho HI. Association between smoking, metabolic syndrome, and arteriosclerosis in Korean men. J Health Info Stat 2016;41(1): Doi: It is identical to the Creative Commons Attribution Non-Commercial License ( whichpermit sunrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited

2 Smoking, Syndrome X and Arteriosclerosis 험을증가시키는위험요인으로작용한다 [6,7]. Copenhagen 남성을 8년간추적한조사에서는흡연자에게인슐린대사의변화가있었으며, 이중중성지방과고밀도콜레스테롤변화등지질대사이상을동반한경우심혈관계질환위험이높다고밝혔다 [8]. Ishizaka et al. [9] 은흡연상태에따른대사증후군유병률을비흡연자 8.8%, 과거흡연자 20.4%, 현재흡연자 23.7% 로보고하여, 흡연경험과대사증후군위험의관련성을설명하였다. 또한 Hong et al. [10] 의연구에서, 비흡연자에비해과거및현재흡연자는약 2배이상높은대사증후군위험을보였다. 대사증후군위험과흡연자의누적흡연량은용량반응적관계를갖는다 [11]. 대사증후군위험을증대시키는누적흡연량수준은연구마다차이가있으며, 그범위는 10갑년이상에서 30갑년이상까지다양하다 [9,11,12]. 흡연은신체활동, 식이, 음주등과함께대사증후군의개선가능한위험요인으로간주되며, 이러한이유로흡연을중단하여대사증후군위험을낮출것을권고하였다 [13,14]. 그러나기존연구는대부분현재흡연자로한정하여보고되고있어, 흡연중단자의금연전누적흡연량에따른질환위험수준을정의하는데한계가있다. 심혈관계질환의위험요인으로흡연과대사증후군은매우중요하다. 중국인을대상으로한 Zhang et al. [15] 의연구는대사증후군과흡연요인에따른심혈관계질환위험도를설명하는데있어, 두요인이모두있는집단에서가장높은위험을보였으며, 그수준은그렇지않은집단에비해 17.41배높다고하였다. 또한심혈관계질환위험도를대사증후군과흡연자의누적흡연량수준에따라평가한 He et al. [16] 의연구에서용량반응적관계를확인하였다. 그러므로본연구는높은흡연율을보이는한국남성을대상으로, 과거흡연및현재흡연자에서흡연상태뿐만아니라흡연의수준에따른대사증후군및심혈관계질환위험도를가늠하는동맥경화증과의관련성을확인하고자하였다. 또한흡연이동맥경화증의위험요인으로작용함에있어서대사증후군이어떤역할을하는지그관련특성을알아보고자하였다. 연구방법 연구대상 2014년 1월부터 12월까지서울소재의한건강증진센터에서경동맥초음파검사를포함하여건강검진을실시한 20세이상성인남성을대상으로하였다. 이중뇌졸중혹은심장병으로약을복용하는경우와흡연관련문항에응답하지않거나, 신체계측을포함한필요검사를받지않은경우를제외하여, 최종 5,103명을대상자로포함하였다. 본연구는한국건강관리협회 IRB 위원회의승인을받았다 (IRB No HR-025). 연구방법흡연습관및질환력자기기입식설문조사방법을활용하여흡연습관과질환력을조사하였으며, 흡연상태와함께과거및현재흡연자의흡연기간과용량을조사하였다. 평생총 5갑 (100개비) 이상의담배를피운적이있는가 에대하여지금은끊은경우를과거흡연자, 현재도흡연중인경우를현재흡연자, 담배를피운경험이없는경우를비흡연자로분류하였다. 과거및현재흡연자의담배소비량 ( 갑년, pack-year) 은 [ 총흡연량 ( 개비 )/20] [ 흡연기간 ( 년 )] 으로계산하였으며, 과거흡연자는금연전까지의정보를활용하였다. 이는 20갑년을장기흡연기준으로, 20갑년미만, 갑년미만, 40갑년이상으로구분하였다 [17]. 질병을진단받아현재약물치료를받고있는지를조사하였다. 뇌졸중과심장병으로약물치료를받는경우는제외하였으며, 고혈압, 당뇨병, 이상지질혈증으로약물치료받는경우는대사증후군의각해당요소로분류하였다. 신체계측및혈압체질량지수 (body mass index, BMI) 는체중 (kg)/ 신장 (m)2로계산하였으며, 신장과체중은신발과양말을벗고직립자세에서자동신체계측기로측정하였다. 허리둘레는늑골하단과골반장골능상단사이의중간지점에서줄자로측정하였다. 혈압은 5분이상안정상태를유지한후자동혈압계로측정하였으며, 수축기혈압 140 mmhg 이거나이완기혈압 90 mmhg인경우수은혈압계로다시측정하였다. 혈액화학검사및대사증후군채혈전 10시간공복을유지하였으며, Hitachi 7600 (Hitachi, Nakai, Japan) 을활용하여혈액의혈청에서공복혈당, 중성지방, HDL 콜레스테롤 (high density lipoprotein cholesterol), LDL 콜레스테롤을측정하였다. 혈당, 중성지방, HDL 콜레스테롤은아산시약 (Asan Inc., Hwaseong, Korea) 을, LDL 콜레스테롤은 Daiichi 시약 (Daiichi Pure Chemicals Co., Tokyo, Japan) 을사용하였으며, 모두효소법으로측정하였다. 지질검사의정밀도와정확도는정도관리물질인 Lyphocheck levels Ⅰ, Ⅱ (Bio- Rad Lab., Irvine, USA) 를사용하여평가하였으며, 대한임상검사정도관리협회정도관리사업에참여하였다. National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) 의진단기준을수정하여, 2005년미국심장협회와국립심폐혈관연구소에서제시한 modified ATP Ⅲ를적용하여대사증후군을정의하였다 [18]. 허리둘레, 혈압, 공복혈당, 중성지방, HDL 콜레스테롤등 5개대사항목중 3개이상이해당범위에포함되면대사증후군으로진단하였다. 대사증후군의항목별범위는허리둘레의경우아 19

3 Suyoung Kim, et al. 시아인의복부비만기준인 90 cm를적용하였으며 [19], 수축기혈압 130 mmhg 또는이완기혈압 85 mmhg를고혈압이상, 공복혈당 100 mmhg, 중성지방 150 mmhg, HDL 콜레스테롤 <40 mg/dl을각항목별해당범위로적용하였다. 고혈압, 당뇨병, 이상지질혈증으로약물을복용하는경우는각해당항목이있는것으로정의하였다. 경동맥두께및동맥경화반측정죽상경화는심혈관질환의원인으로알려져있으며, 대표적으로경동맥초음파검사를통해경동맥내중막두께와동맥경화반을측정하여진단한다. 경동맥상태는 B-mode 초음파기 (SONOACE 9900, Medison, Korea) 의 7.5 MHz 선상탐촉자 (linear ultrasound transducer) 를사용하여측정하였다. 경동맥내중막두께의측정은혈관내강과내막의경계부위로부터혈관중막과외막의경계부위까지의거리로정의한다. 비정상경동맥내중막두께 (abnormal carotid intima-media thickness, Abnormal CIMT) 는경동맥내중막두께 1 mm를기준으로그이상인경우로정의하며, 동맥경화반은인접한내중막두께보다 100% 이상혈관내강쪽으로돌출된경우로정의한다. 통계분석일반적특성을포함하여, 임상및대사적특성을평균과표준편차로요약하여제시하였고, 흡연상태에따른차이를비교하기위해일원분산분석 (one-way ANOVA) 을실시였으며, 사후비교 (posthoc comparison) 는 Scheffe s method를활용하였다. 비정상경동맥내중막두께, 동맥경화반의분포와대사증후군및개별대사이상인자별분포는빈도와비율로요약하였으며, 흡연상태에따른차이는 χ2 검정을실시하여통계적으로유의한차이가있는지를분석하였다. 누적흡연량을포함한흡연상태에따른대사증후군및개별대사인자이상, 비정상경동맥내중막두께, 동맥경화반유무등의관련성을알아보기위해, 연령, BMI를보정한다중로지스틱회귀분석을실시하였다. 오즈비 (odds ratio, OR) 와 95% 신뢰구간 (confidence interval, CI) 을제시하였으며, 오즈비의선형경향성 (linear trend) 을확인하기위해경향분석 (test for trend) 을실시하였다. 흡연과비정상경동맥내중막두께및동맥경화반유무의관련성을알아보기위하여, 대사증후군유무로나누어연령, BMI, LDL 콜레스테롤을보정한다중로지스틱회귀분석을실시하였다. 본연구의통계분석은 SAS 9.3 프로그램 (SAS Institute Inc., Cary, NC, USA) 을사용하였으며, 유의수준 0.05를기준으로분석하였다. 연구결과 본연구대상자 5,103 명중과거흡연과현재흡연경험률은각 41.5% (2,115 명 ), 30.5% (1,555명) 로, 10명중 7명이흡연을경험하였다. 대상자의평균연령은과거흡연자 ± 10.18세로가장높았으며, 비흡연자, 현재흡연자순으로나타났다 (p < 0.001). BMI와허리둘레의평균수치는과거흡연자가비흡연자에비해높은수준을보였다 ( 각 p = 0.004, p = 0.001). 평균수축기혈압은흡연상태에따라유의한차이를보여, 비흡연자에비해과거흡연자는높고현재흡연자는낮은데비해, 평균이완기혈압은비흡연자에비해현재흡연자가낮은수준을보였다 ( 각 p < 0.001). 중성지방의평균수치는현재흡연자, 과거흡연자, 비흡연자순으로유의한차이를나타냈으며, HDL 콜레스테롤의평균수치는비흡연자와과거흡연자가유의한차이를보이지않는데비해, 현재흡연자는유의하게낮은수준이었다 ( 각, p < 0.001). 총콜레스테롤평균수치는현재흡연자가가장높았으며, 비흡연자와과거흡연자는유의한차이를보이지않았다 (p < 0.001). 공복혈당의평균수치는과거흡연자가비흡연자보다유의하게높았다 (p = 0.009). 비정상경동맥내중막두께비율은과거흡연자 68.4%, 비흡연자 61.2%, 현재흡연자 55.9% 순으로유의한차이를보였다 (p < 0.001). 동맥경화반의비율은과거흡연자가 52.4% 로현재흡연자 44.9% 와비흡연자 44.0% 에비해유의하게높은수준을보였으며 (p < 0.001), 현재흡연자와비흡연자간비슷한수준을보였다 (Table 1). 본연구에서대사증후군유병률은 27.3% 였으며, 흡연상태에따라과거흡연자가 29.7% 로가장높았고, 현재흡연자 27.8%, 비흡연자 23.2% 로비흡연자가가장낮은수준이었다 (p < 0.001). 대사증후군위험인자의평균개수는과거흡연자 (1.86 ±1.25개 ), 현재흡연자 (1.74 ±1.30개 ), 비흡연자 (1.63 ± 1.26개 ) 순으로높았다 (p < 0.001). 대사증후군의 5가지구성요인별이상범위포함비율은저 HDL 콜레스테롤 14.3% 이며, 복부비만 29.9%, 고중성지방혈증 33.4%, 공복혈당이상 43.7%, 고혈압 54.6% 이었다. 대사증후군위험인자중 HDL 콜레스테롤을제외한모든요인의이상범위에포함된비율은흡연상태에따라유의한차이를보였다. 허리둘레기준의복부비만율은과거흡연과현재흡연에서각 31.9%, 29.7% 로, 비흡연에비해높게나타났다 (p = 0.008). 고혈압과공복혈당이상비율은과거흡연자에서유의하게높은데비해 ( 각, p < 0.001), 고중성지방혈증비율은현재흡연자에서 40.6% 로가장높았다 (p < 0.001). 연령과 BMI를보정한흡연상태에따른대사증후군의오즈비는비흡연자에비해흡연경험이있는경우높았으며, 특히현재흡연자에서가장높았다 [OR (95% CI): 과거흡연자 1.35 (1.14, 1.6), 현재흡연자 1.63 (1.35, 1.98)]. 대사증후군구성인자가운데고중성지방혈증과공복혈당이상위험도는흡연수준이심각할수록높았으며, 특히고중성지방혈증은비흡연자에비해현재흡연자의위험도가 1.95배 (95% CI: 1.66, 2.30) 였다. 허리둘레기준복부비만위험과저 HDL 콜레스테롤위험은 20

4 Smoking, Syndrome X and Arteriosclerosis Table 1. Characteristics of subjects according to smoking status (unit: Mean ± SD) Variables 1 Former 2 Current 3 p-value (n = 1,433) (n = 2,115) (n = 1,555) Age (y) ± b ± a ± c < Body mass index (kg/m 2 ) ± 2.90 b ± 2.73 a ± 3.00 b Waist (cm) ± 8.05 b ± 7.39 a ± Systolic blood pressure (mmhg) ± b ± a ± c < Diastolic blood pressure (mmhg) ± 8.96 a ± 8.60 a ± 8.91 b < Serum lipid data Triglycerides (mg/dl) ± c ± b ± a < HDL-cholesterol (mg/dl) ± a ± a ± b < LDL-cholesterol (mg/dl) ± ± ± Total cholesterol (mg/dl) ± b ± b ± a < Fasting blood sugar (mg/dl) ± b ± a ± Carotid ultrasonography Abnormal carotid intima-media thickness 4 (%) 875 (61.2) 1,443 (68.4) 867 (55.9) < Carotid plaque 5 (%) 631 (44.0) 1,109 (52.4) 698 (44.9) < SD, standard deviation; HDL, high density lipoprotein; LDL, low-density lipoprotein. The frequencies may not add up to 100% due to missing. a,b,c : The same letters indicate non-significant difference, 1 1,433 (20.1%), 2 Former 2,115 (41.5%), 3 Current 1,555 (30.5%), 4 Abnormal carotid intima-media thickness (CIMT) 3,185 (78.4%), 5 Carotid plaque 2,438 (47.8%). Table 2. Logistic regression of metabolic syndrome and its risk factor components according to smoking status (unit: n (%)) Variables Prevalence of total subjects (n = 5,103) (n = 1,433) Former (n = 2,115) Current (n = 1,555) p-value Logistic regression (Unit: OR (95% CI)) Former Current Metabolic syndrome 1,391 (27.3) 332 (23.2) 627 (29.7) 432 (27.8) < (1.14, 1.60) 1.63 (1.35, 1.98) Number of Mets risk factor components 1.63 ± 1.26 c 1.86 ± 1.25 a 1.74 ± 1.30 b < (Mean ± SD) Waist 90 cm 1,524 (29.9) 388 (27.1) 675 (31.9) 461 (29.7) (0.97, 1.47) 1.31 (1.04, 1.65) HDL-cholesterol <40 mg/dl 732 (14.3) 194 (13.5) 292 (13.8) 246 (15.8) (0.80, 1.19) 1.42 (1.15, 1.76) Triglycerides 150 mg/dl 1,704 (33.4) 377 (26.3) 696 (32.9) 631 (40.6) < (1.16, 1.57) 1.95 (1.66, 2.30) Hypertension 1 2,785 (54.6) 797 (55.6) 1,262 (59.7) 726 (46.7) < (0.92, 1.23) 0.84 (0.72, 0.99) Fasting blood sugar 100 mg/dl 2,231 (43.7) 576 (40.2) 1,008 (47.7) 647 (41.6) < (1.12, 1.48) 1.31 (1.12, 1.52) OR, odds ratio; CI, confidence interval; SD, standard deviation; HDL, high density lipoprotein. The frequencies may not add up to 100% due to missing. Data are adjusted for age, body mass index (BMI). a,b,c : The same letters indicate non-significant difference, 1 Hypertension (systolic blood pressure 130 or diastolic blood pressure 85 mmhg). 비흡연자에비해과거흡연자는유의한차이를보이지않은데비해, 현재흡연자는유의하게높았다 [OR (95% CI): 복부비만 1.31 (1.04, 1.65), 저 HDL 콜레스테롤 1.42 (1.15, 1.76)]. 고혈압의오즈비는비흡연자에비해현재흡연자가 0.84배 (95% CI: 0.72, 0.99) 로낮게나타났다 (Table 2). 흡연의양에따른대사증후군의오즈비는과거흡연자와현재흡연자모두 20갑년이상에서비흡연자에비하여통계적으로유의한차이를보였다. 특히같은흡연량수준에서비교할때, 대사증후군위험은과거흡연자보다현재흡연자에서높았다. 흡연량이 20-40갑년미만인경우의대사증후군위험은비흡연에비해과거흡연자가 1.83배 (95% CI: 1.47, 2.27), 현재흡연자가 1.94배 (95% CI: 1.53, 2.48) 였으며, 40갑년이 상의높은흡연량에서는과거흡연자가 1.55배 (95% CI: 1.07, 2.24), 현재흡연자가 2.01배 (95% CI: 1.45, 2.78) 로차이를보였다. 대사증후군위험인자중허리둘레기준복부비만의위험은현재흡연자중 20갑년이상의흡연량을가진경우높았다. 저 HDL 콜레스테롤혈증과공복혈당이상의위험은과거흡연자와현재흡연자모두비흡연자에비해 20갑년혹은 40갑년이상의높은흡연량을경험한경우유의하게높았다. 고중성지방혈증위험은흡연량이많을수록유의하게높았으며, 과거흡연자보다현재흡연자에서높은오즈비를보였다. 고혈압을제외한대사증후군위험인자는모두흡연량에따라유의한경향을보였다 (p < 0.05 for trend). 21

5 Suyoung Kim, et al. Table 3. Adjusted odds ratio of metabolic syndrome and its components, abnormal carotid intima-media thickness and carotid plaque according to smoking amounts Variables Former Current p for trend p for trend Metabolic syndrome 1.08 (0.88, 1.31) 1.83 (1.47, 2.27) 1.55 (1.07, 2.24) < (1.00, 1.66) 1.94 (1.53, 2.48) 2.01 (1.45, 2.78) <0.001 Mets risk factor components Waist 90 cm 0.99 (0.78, 1.25) 1.60 (1.23, 2.09) 1.17 (0.75, 1.85) (0.81, 1.49) 1.43 (1.05, 1.93) 1.62 (1.06, 2.47) HDL-cholesterol 0.78 (0.62, 0.99) 1.20 (0.93, 1.54) 1.50 (1.01, 2.24) (0.89, 1.58) 1.61 (1.23, 2.09) 1.52 (1.06, 2.17) <40 mg/dl Triglycerides 150 mg/dl 1.21 (1.02, 1.44) 1.52 (1.25, 1.86) 1.87 (1.33, 2.63) < (1.41, 2.14) 2.21 (1.79, 2.72) 2.42 (1.81, 3.24) <0.001 Hypertension (0.88, 1.21) 1.18 (0.96, 1.43) 0.97 (0.69, 1.36) (0.64, 0.95) 0.91 (0.75, 1.12) 0.85 (0.64, 1.13) Fasting blood sugar 1.14 (0.98, 1.34) 1.53 (1.26, 1.84) 1.47 (1.06, 2.04) < (0.93, 1.39) 1.34 (1.10, 1.64) 1.65 (1.24, 2.18) < mg/dl Carotid intima-media 1.15 (0.96, 1.39) 1.41 (1.13, 1.77) 1.51 (0.97, 2.35) (1.02, 1.63) 1.54 (1.23, 1.94) 1.48 (1.04, 2.11) <0.001 thickness ( >1 mm) Carotid plaque 1.21 (1.02, 1.44) 1.62 (1.33, 1.98) 1.55 (1.09, 2.21) < (1.27, 2.01) 1.91 (1.54, 2.37) 2.20 (1.62, 3.01) <0.001 PY, pack-years; HDL, high density lipoprotein. Data are odds ratios (95% confidence interval). 1 Hypertension (systolic blood pressure 130 or diastolic blood pressure 85 mmhg). Mets (-) Former Current Mets (-) Former Current Mets (+) Former Current Mets (+) Former Current A B Figure 1. Odds ratios for r according to the smoking status. (A) abnormal carotid intima-media thickness; (B) carotid plaque. Mets, metabolic syndrome. Data are adjusted for age, body mass index, low density lipoprotein cholesterol. p<0.05, p< 비정상경동맥내중막두께의위험은비흡연자에비해 20갑년미만흡연한현재흡연자가 1.3배 (95% CI: 1.02, 1.63) 높았으며, 20갑년이상흡연한현재흡연자는약 1.5배높은수준을보였다 [OR (95% CI): 갑년 1.54 (1.23, 1.94), 40갑년이상 1.48 (1.04, 2.11)]. 과거혹은현재흡연자모두흡연량이증가함에따라동맥경화반위험은유의하게높아지는특징을보였다 (p < for trend). 과거흡연자는흡연량 20갑년을기준으로동맥경화반위험수준이높아졌으며, 현재흡연자는흡연량과비례하는위험도를보였다. 특히 40갑년이상흡연량을경험한현재흡연자의동맥경화반위험수준은비흡연자에비해 2.20배 (95% CI: 1.62, 3.01) 로높았다 (Table 3). 흡연상태에따른죽상동맥경화증위험도는연령, BMI, LDL 콜레스테롤을보정한후, 대사증후군유무로나누어살펴보았다. 비정상경동맥내중막두께의위험도는대사증후군이없는경우비흡연자에비해현재흡연자가 1.30배 (95% CI: 1.05, 1.60) 높은수준이며, 대사증후군 이있는경우흡연상태에따른차이를보이지않았다. 동맥경화반위험도는대사증후군이없는경우와있는경우모두흡연상태에따라유의한차이를보였으며, 흡연상태가심각할수록위험도가높아졌다 [OR (95% CI): 대사증후군이없는경우과거흡연 1.35 (1.13, 1.62) 와현재흡연 1.74 (1.42, 2.12), 대사증후군이있는경우과거흡연 1.36 (1.00, 1.85) 과현재흡연 1.67 (1.19, 2.35)] (Figure 1). 비정상경동맥내중막두께의오즈비는대사증후군이없는경우, 과거흡연과현재흡연모두흡연량이 20-40갑년미만군에서유의하였으며, 비흡연보다높은위험을보였다 [20-40갑년미만군의 OR (95% CI): 과거흡연 1.38 (1.04, 1.83), 현재흡연 1.44 (1.11, 1.88)]. 대사증후군이있는경우는흡연상태및양에따른비정상경동맥내중막두께의위험도가유의하지않았다 (Figure 2). 대사증후군이없는경우, 과거흡연자와현재흡연자의흡연량이많을수록동맥경화반위험이높았다. 과거흡연자의오즈비는흡연량이 22

6 Smoking, Syndrome X and Arteriosclerosis Metabolic syndrome (-) Former Current Metabolic syndrome (+) Former Current A B Figure 2. Odds ratios for abnormal carotid intima-media thickness according to the smoking amounts. (A) without metabolic syndrome; (B) with metabolic syndrome. PY, pack-year. Data are adjusted for age, body mass index, low density lipoprotein cholesterol. p<0.05, p< Metabolic syndrome (-) Former Current Metabolic syndrome (+) Former Current A B Figure 3. Odds ratios for carotid plaque according to the smoking amounts. (A) without metabolic syndrome; (B) with metabolic syndrome. PY, pack-year. Data are adjusted for age, body mass index, low density lipoprotein cholesterol. p<0.05, p< 갑년이상에서유의하였으며, 약 1.7배의높은위험도를보였다 [OR (95% CI): 20-40갑년미만 1.67 (1.31, 2.14), 40갑년이상 1.69 (1.09, 2.63)]. 현재흡연자는흡연량에따라동맥경화반위험도가비례적으로증가하여, 흡연량이많은경우높은위험도를보였다 [OR (95% CI): 20갑년미만 1.37 (1.06, 1.78), 20-40갑년미만 1.89 (1.47, 2.43), 40갑년이상 2.33 (1.59, 3.40)]. 대사증후군이있는경우는동맥경화반위험이현재흡연자에서만유의하였으며, 40갑년미만의흡연량인경우비흡연자에비해높은위험도를보였다 [OR (95% CI): 20갑년미만 1.86 (1.17, 2.96), 20-40갑년미만 1.63 (1.07, 2.48)] (Figure 3). 고찰 성인남성 5,103명을대상으로실시한본단면연구에서, 대사증후군위험은비흡연에비해과거혹은현재흡연인경우와누적흡연량이많을수록증가하였다. 특히 20갑년이상의누적흡연량을경험한과거흡연자와현재흡연자는비흡연자에비해높은대사증후군위험을보였다. 본연구는흡연량과대사증후군간의관계에있어, 과거흡연자와 현재흡연자가비슷한용량수준에서그위험이증가하는결과를보였다. 현재흡연자를대상자로한정한기존연구에서누적흡연량이증가할수록대사증후군위험이비례적으로증가하는관련성을보여주었다 [11,12,20]. 또한과거흡연자의금연전누적흡연량과의관계를확인한 Ishizaka et al. [9] 과 Wada et al. [21] 의연구에서누적흡연량수준이 10갑년과 20갑년이상인경우, 과거흡연자의대사증후군위험이유의하게높아진다고하여, 본연구와유사한결과를보였다. 그러나 Chen et al. [22] 은과거흡연자는대사증후군의위험요인으로유의하지않다고밝혀본연구와차이가있었다. 본연구에서 20갑년이상흡연량을경험한과거흡연자는여전히대사증후군위험이증가하였다. 이는금연후에도질환위험이쉽게감소하지않는기존연구결과와일치한다 [9,23,24]. 과거흡연자와현재흡연자를동일누적흡연량수준에서비교할때, 복부비만, 저 HDL 콜레스테롤혈증, 공복혈당이상의위험도가비슷하게나타났으나, 금연지속기간을반영하지않은본연구에서금연의효과를입증하는데한계가있었다. 또한과거흡연자의대사증후군위험도가누적흡연량 40갑년이상보다 20-40갑년미만에서높은특징을보였으며, 이는흡연과 23

7 Suyoung Kim, et al. 질병의용량반응적관계를고려하면금연지속기간의차이에기인한것으로추정된다. 이전연구에서는금연기간이짧은단기금연자가체중증가와인슐린저항성이지속되어대사증후군위험이금연후쉽게감소하지않는다고하였다 [20,23,25,26]. 또한금연에따른건강수준의향상을기대하기위해서는충분한금연지속기간이필요하다 [27,28]. 금연효과가나타나기위한금연기간은연구자마다차이가있지만, 대체로과거누적흡연량이많을수록더긴금연기간이필요하다고하였다 [24]. 실제한연구에서는 20갑년이상흡연경험이있는과거흡연자는대사증후군위험을낮추기위해최소한 20년이상금연기간을유지해야한다는결과를제시하였다 [21]. 흡연은인슐린저항성을일으키고교감신경활동을증가시켜, HDL 콜레스테롤감소와중성지방증가를유도하는등지질대사에영향을미친다 [14,29]. 이러한변화는대사증후군발생을유도하며, 관상동맥질환의위험을증가시킬수있다. 본연구는대사증후군구성인자중고혈압을제외한복부비만, 저 HDL 콜레스테롤혈증, 고중성지방혈증, 공복혈당이상의위험도가누적흡연량수준이높은경우증가하는것을확인하였다. 이러한특성은과거흡연자와현재흡연자모두동일하였으며, 특히현재흡연자는 20갑년이상에서유의하게대사증후군위험이증가하였다. 누적흡연량이많을수록고중성지방혈증위험도가높아지는비례적관계는현재흡연자에서뚜렷하게나타났다. 다양한기존연구에서흡연과대사증후군간의관계를설명하는인자로서 HDL 콜레스테롤과중성지방을제시하였다 [11,22]. 또한일부단면연구에서공복혈당위험과흡연수준간의유의한결과를도출하지못하였으나 [10,12,23], 공복혈당장애혹은제2형당뇨병발생률과흡연량간의관련성을규명한다양한종단연구는본연구와일치하는결론을보였다 [24,30]. 니코틴은카테콜아민의분비를유도하여혈압을상승시키는역할을한다 [31]. Minami et al. [32] 은흡연자의혈압을 2주간측정하는데, 1주는흡연을유지하여측정하고 1주는흡연을중단하여측정하였으며, 그결과비흡연기간의혈압이흡연기간의혈압보다낮은것을확인하였다. 반면, 흡연여부가혈압간유의한차이를발견하지못한이전연구가있다 [28]. 일부연구는그원인으로흡연자들이검진을실시하기까지단시간흡연을중단하였으며, 이것이교감신경의항진을억제하였을가능성을제시하였다 [23]. 본연구에서도흡연과고혈압간에유의한관계를발견하지못하였으나, 흡연이영향요인으로작용하지않는다고결론내리기에는논란이있으며, 이를규명하기위한추가적인연구가요구된다. 본연구에서대사증후군이있는경우누적흡연량이증가할수록동맥경화반위험이높아졌으며, 이는현재흡연자에서더욱뚜렷한경향으로나타났다. Reaven and Tsao [5] 와 Facchini et al. [33] 은흡연이심혈관계질환의위험성을증가시키는데있어서대사증후군이연결요인 이되며, 이는인슐린저항성에의한것이라고하였다. 이러한결과는흡연과대사증후군이심혈관계질환의위험요인으로작용한다는과거연구결과와일치한다 [9,15]. 또한대사증후군이없는군에서도비흡연자에비해과거흡연, 현재흡연자의비정상경동맥내중막두께와동맥경화반위험이증가하여, 흡연이동맥경화증과부분적으로독립적인연관성을보였다. 본연구는제한점을갖고있다. 첫째, 건강검진실시자를대상으로하여, 과거흡연자의금연기간을알수없었다. 건강상태호전을기대하기위한금연지속기간은누적흡연량에비례하므로, 추가적으로이를반영한결과도출이필요하다. 둘째, 단일조사시점에서자기기입식설문조사를통해흡연량과흡연기간을측정하여, 응답오류및무응답등으로인한일부데이터손실이발생하였다. 셋째, 단면연구로진행된본연구는흡연과대사증후군및죽상동맥경화간의인과관계를규명하는데한계가있었다. 흡연은대사증후군뿐만아니라비정상경동맥내중막두께및동맥경화반등동맥경화증과관련이있었다. 누적흡연량이비슷한수준에서과거흡연자와현재흡연자의질환위험도는비슷하였으며, 누적흡연량이많을수록질환위험이높아지는비례적관계를보였다. 또한대사증후군유무에따라차이를보이는흡연과동맥경화증위험도의관계는흡연이동맥경화증과부분적으로연관성이있음을보여준다. 이는흡연의중단으로인한복합적인이익효과를설명하는주요근거가된다. 그러므로금연후에도지속되는인슐린저항성에의한심혈관계질환위험을낮추기위하여, 식이요법과활동량증가를위한생활습관변화과정이금연프로그램에포함되어야할것으로생각된다. 또한흡연자에서대사증후군의발생은심혈관계질환위험을상승시킬수있으므로, 두위험요인의복합적특성에대한추가적인연구가필요할것으로사료된다. REFERENCES 1. Ambrose JA, Barua RS. The pathophysiology of cigarette smoking and cardiovascular disease. J Am Coll Cardiol 2004;43(10): Facchini FS, Hollenbeck CB, Jeppesen J, Chen YD, Reaven GM. Insulin resistance and cigarette smoking. Lancet 1992;339(8802): Isomaa B, Almgren P, Tuomi T, Forsén B, Lahti K, Nissén M, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes care 2001;24(4): Kong C, Nimmo L, Elatrozy T, Anyaoku V, Hughes C, Robinson S, et al. Smoking is associated with increased hepatic lipase activity, insulin 24

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