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1 Review pissn eissn Epidemiologic Characteristics of Dyslipidemia in Korea Kyoung Hwa Ha 1,2, Hyuk-Sang Kwon 3, Dae Jung Kim 1,2 JLA 1 Department of Endocrinology and Metabolism, Ajou University School of Medicine, 2 Cardiovascular and Metabolic Disease Etiology Research Center, Ajou University School of Medicine, Suwon, 3 Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary s Hospital, The Catholic University of Korea, Seoul, Korea 우리나라이상지질혈증의역학적특성 하경화 1,2, 권혁상 3, 김대중 1,2 아주대학교의과대학내분비대사내과학교실 1, 아주대학교의과대학심뇌혈관및대사질환원인연구센터 2, 가톨릭대학교의과대학여의도성모병원내분비대사내과 3 Cardiovascular disease is a major cause of mortality and disability worldwide and in Korea as well. Dyslipidemia is considered as a major and modifiable risk factor of cardiovascular disease. In Korea, the prevalence of dyslipidemia in people aged 30 years or older was 47.8% in 2013, with prevalence increasing as age increases. Men had higher prevalence of dyslipidemia than women (men, 57.6%; women, 38.3%). However, the prevalence of dyslipidemia in women increased rapidly after menopause. Furthermore, dyslipidemia is also rising in childhood and adolescents. The prevalence of hypo-hdl cholesterolemia and hypertriglyceridemia were higher than hyper-ldl cholesterolemia. However, hyper-ldl cholesterolemia also has been increasing due to the westernized diet and other lifestyle changes. Atherogenic dyslipidemia, which is the combination of these lipoprotein abnormalities, seems to be increasing. The prevalence of dyslipidemia was higher in obese people, and the prevalence of the metabolic syndrome, which included dyslipidemia as a component of abnormalities, also increased in accordance with dyslipidemia. Also, dyslipidemia in patients with diabetes increased from 27.8% in 2006 to 49.5% in The awareness and treatment rate of dyslipidemia were lower in comparison with other chronic diseases. By providing information about the risk of dyslipidemia, primary prevention such as weight loss, dietary treatment, and quit smoking and secondary prevention such as early detection and drug treatment are required for reducing the development of cardiovascular disease. Key Words: Diabetes, Dyslipidemia, Epidemiology, Metabolic syndrome, Obesity 서론 세계질병부담연구 (Global Burden of Disease) 2010 년보고서에따르면세계적으로연간 1,560만명이심혈관계질환으로사망하며, 전체사망원인의 29.6% 에달한다. 1 또한, 심혈관계질 환에의한장애보정생존연수 (disability-adjusted life years, DALYs) 는 1990년 8,500만 DALYs에서 2020년 1억 5,000만 DALYs으로증가할것으로예측하였다. 2 우리나라에서도사망자의 19.0% 가심혈관계질환에의한사망으로, 10년간심장질환사망률은약 1.4배증가하였으며, 인구 10만명당뇌혈관질환 Received: Revised: Accepted: December 11, 2015 December 18, 2015 December 18, 2015 Corresponding Author: Dae Jung Kim, Department of Endocrinology and Metabolism, Ajou University School of Medicine, 164, World Cup-ro, Yeongtong-gu, Suwon 16499, Korea Tel: , Fax: , djkim@ajou.ac.kr This is an Open Access article distributed under the terms of the creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright c 2015 The Korean Society of Lipidology and Atherosclerosis 93

2 J Lipid Atheroscler 2015;4(2):93-99 JOURNAL OF LIPID AND ATHEROSCLEROSIS Fig. 1. Age-specific prevalence rates of dyslipidemia in the Korea National Health and Nutrition Examination Survey (KNHANES) The definition of dyslipidemia was made according to the presence of one or more of the following criteria: hyper-low density lipoprotein (LDL) cholesterolemia (LDL cholesterol 160 mg/dl or use of lipid-lowering drugs); hypertriglyceridemia (triglyceride 200mg/dL); and hypo-high density lipoprotein (HDL) cholesterolemia (HDL cholesterol <40 mg/dl in both sexes). 사망자수는 OECD 평균보다높은것으로보고되었다. 3,4 이러한심혈관계질환의발생은식사습관의서구화와인구고령화에따라향후지속적으로증가할것으로예상된다. 이상지질혈증이란한국지질 동맥경화학회의이상지질혈증치료지침진단기준에따르면고콜레스테롤혈증 ( 240 mg/dl), 고중성지방혈증 ( 200 mg/dl), 고 low-density lipoprotein (LDL) 콜레스테롤혈증 ( 160 mg/dl), 저 high-density lipoprotein(hdl) 콜레스테롤혈증 (<40 mg/dl) 중하나이상이존재할때로정의된다. 5 이상지질혈증은비만, 대사증후군, 제2형당뇨병환자에서주로관찰되며, 심혈관계질환발생위험을증가시키는중요한인자로알려져있다. 6 Multiple Risk Factor Intervention Trial (MRFIT) 연구에의하면, 고콜레스테롤혈증인경우관상동맥질환사망률이 3.4배증가하였고, 고콜레스테롤혈증의허혈성심장질환인구집단기여위험도 (population attributable risk, PAR) 는 43% 로가장높았다. 7,8 또한, 29개의연구를메타분석한결과중성지방이높은경우관상동맥질환의위험이증가하였으며, Quebec cardiovascular study 에서 HDL 콜레스테롤이높으면서 LDL 콜레스테롤이낮은경우에비해 HDL 콜레스테롤이낮으면서 LDL 콜레스테롤이높을경우허혈성심장질환발생위험은 3.4 배증가하였다. 9,10 Korean Heart Study에서는 LDL 콜레스테롤이 130 mg/dl 미만인사람에비해 160 mg/dl 이상인경우남자에서 관상동맥질환발생위험은약 2.3 배, 여자에서 1.4배증가하였으며, HDL 콜레스테롤이 mg/dl인사람에비해 35 mg/dl 미만인경우관상동맥질환발생위험은남자에서약 1.7배증가하였다. 11 이상지질혈증의유병률 국민건강영양조사에의하면우리나라 30세이상성인에서고콜레스테롤혈증유병률은남자에서 2005년 7.2%, 2014년 13.9%, 여자에서 2005년 8.4%, 2014년 15.0% 로, 남녀모두약 2배가량증가하였고, 고중성지방혈증유병률또한 1998년 10.2% 에서 2014년 17.9% 로약 2배가량증가하였다. 12 한국지질 동맥경화학회의이상지질혈증통계자료 (Dyslipidemia Fact Sheet 2015) 에의하면 2013년우리나라 30세이상성인에서이상지질혈증유병률은 47.8% 이며, 남자가 57.6% 로여자 38.3% 에비해높았다. 연령대가증가할수록유병률도증가하는데 (30대, 34.4%; 40대, 43.5%; 50대, 55.4%; 60대, 58.8%; 70세이상, 58.9%), 남자의경우 50대까지증가하다 60대이후감소하는경향을보이며, 여자에서는 50대이후급증하는경향을보인다 (Fig. 1). 13 이상지질혈증세부유형별로는고LDL콜레스테롤혈증이 15.5%, 고중성지방혈증이 18.6%, 그리고저HDL콜레스테롤혈증이 28.4% 였다 (Fig. 2). 13 과거우리나라의경우일반적으로 94

3 Kyoung Hwa Ha, et al.: Epidemiologic Characteristics of Dyslipidemia in Korea Fig. 2. Prevalence of each lipid abnormalities of dyslipidemia in the Korea National Health and Nutrition Examination Survey (KNHANES) The definitions of lipid abnormalities of dyslipidemia were made according the following criteria: hyper-low density lipoprotein (LDL) cholesterolemia (LDL cholesterol 160 mg/dl or use of lipid-lowering drugs); hypertriglyceridemia (triglyceride 200 mg/dl); and hypo-high density lipoprotein (HDL) cholesterolemia (HDL cholesterol <40 mg/dl in both sexes). Fig. 3. Mean values of serum lipids by gender. HDL; high density lipoprotein, LDL; low density lipoprotein. 고중성지방혈증과저HDL콜레스테롤혈증의유병률이높고고 LDL콜레스테롤혈증유병률이낮은특성을갖고있었으나식습관의서구화등으로고LDL콜레스테롤혈증유병률또한지속적으로증가하고있다. 이는고LDL콜레스테롤혈증, 고중성지방혈증, 저 HDL콜레스테롤혈증이동시에나타나는죽상동맥경화증호발성이상지질혈증 (atherogenic dyslipidemia) 환자가증가하고있다고볼수있다. 우리나라 30세이상성인의혈청지질의평균은남자에서총콜레스테롤 189 mg/dl, 중성지방 172 mg/dl, HDL 콜레스테롤 45 mg/dl, LDL 콜레스테롤 114 mg/dl이며, 여자에서총콜레스테롤 192 mg/dl, 중성지방 121 mg/dl, HDL 콜레스테롤 50 mg/dl, LDL 콜레스테롤 118 mg/dl이다 (Fig. 3). 13 중성지방을제외한나머지혈청지질에서여자가남자보다높기때문에고LDL 콜레스테롤혈증유병률은여자에서더높으며 ( 남자, 13.4%; 여자, 17.4%), 고중성지방혈증과저HDL콜레스테롤혈증유병률은남자에서 25.5%, 37.9% 이며, 여자에서 11.8%, 18.9% 로여자가더낮다. 13 HDL 콜레스테롤농도의남녀별차이는 5 mg/dl로, 미국 National Health and Nutrition Examination Surveys (NHANES) 에서보고한남녀별차이에비해크지않다. 14 하지만우리나라의기존연구들은 National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) 에서제시한 95

4 J Lipid Atheroscler 2015;4(2):93-99 JOURNAL OF LIPID AND ATHEROSCLEROSIS Fig. 4. Distribution of dyslipidemia in obese patients in the Korea National Health and Nutrition Examination Survey (KNHANES) General obesity was defined as a body mass index (BMI) categories: underweight (BMI<18.5 kg/m 2 ), normal (18.5 BMI<23 kg/m 2 ), overweight (23 BMI<25 kg/m 2 ), and obese (BMI 25 kg/m 2 ). Abdominal obesity was defined as a waist circumference of 90 cm or greater for men and 85 cm or greater for women. 진단기준 ( 남자, <40 mg/dl; 여자, <50 mg/dl) 을적용하여여자의저HDL콜레스테롤혈증및대사증후군의유병률이과도하게추정되었다고볼수있다. 산화된 LDL입자 (oxidized LDL) 가내피세포에서 pro-oxidant 로작용하여죽상동맥경화를일으키면서심혈관계질환발생에독립적인위험요인으로작용한다는것은잘알려진사실이다. 15 이와반대로 HDL 콜레스테롤은콜레스테롤역수송 (Reverse Cholesterol Transport) 에의해동맥혈관조직내의콜레스테롤을감소시키고, foam cell 의형성을억제하여총콜레스테롤양의항상성을유지하여동맥경화발생을저해한다. 16 고중성지방혈증과심혈관계질환관련성에대하여논란이있으나일반적으로중성지방은혈관에작용하여내피세포와혈관평활근세포의손상과 foam cell의형성을통해산화스트레스를증가시키며, 중성지방이풍부한지단백 (Triglyceride-rich lipoprotein, TRL) 이죽상경화를촉진한다고알려져있다. 특히, 중성지방이증가하면서 HDL 콜레스테롤은간리파제 (hepatic lipase) 로인해쉽게대사되어신장으로배설되면서혈중농도가감소하며, LDL 콜레스테롤은중성지방을통해 small dense LDL로변화되어심혈관계질환위험을높이는것으로알려져있다. 17,18 폐경과이상지질혈증 여성에서이상지질혈증유병률은연령이증가할수록증가하며 (30대, 18.8%; 40대, 29.5%; 50대, 45.0%; 60대, 56.7%; 70세이상, 61.3%), 특히 50대이후에급격하게증가하고있다. 또한, 대사증후군유병률은폐경전후로 11.8% 에서 47.6% 로 약 4배증가하였다. 13 여성에서 50세이후에이상지질혈증의유병률이급격히높아지는것은폐경에따른호르몬의변화로설명할수있다. 에스트로겐은 LDL 수용체의활성화를통해 LDL 대사에영향을미치며, 간의 apolipoprotein A1 증가를통하여 HDL 콜레스테롤합성을증가시킨다. 19 에스트로겐은초경의시작과함께증가하다폐경이되는 50세경에감소되는데, 이로인해폐경후 LDL 콜레스테롤증가및 HDL 콜레스테롤감소를초래하며, 특히, HDL 콜레스테롤중 cardio-protective로여겨지는 HDL 2 콜레스테롤의감소와혈관내피세포등의부착력이높은 small dense LDL 입자의증가로심혈관계질환위험이급격히증가한다. 20 비만과이상지질혈증 우리나라비만유병률은 2001년 29.2% 에서 2013년 31.8% 로증가하였으며, 이상지질혈증약물을복용하는사람또한 2003 년 2.8% 에서 2013 년 12.9% 로증가하고있다. 한국지질 동맥경화학회의이상지질혈증통계자료 (Dyslipidemia Fact Sheet 2015) 에의하면비만도에따른이상지질혈증유병률은저체중에서 16.4%, 정상에서 33.7%, 과체중에서 52.4% 비만에서 62.2% 로, 비만도가증가할수록이상지질혈증유병률도증가하였다 (Fig. 4). 13,21 비만이이상지질혈증에관여하는기전은명확하게밝혀지지않았다. 비만으로인하여간으로유입되는유리지방산 (free fatty acid) 이증가되면간내 very low density lipoproteins (VLDL) 이증가하여혈액내 LDL, intermediate-density lipoprotein (IDL) 96

5 Kyoung Hwa Ha, et al.: Epidemiologic Characteristics of Dyslipidemia in Korea 수치가올라감과 HDL 콜레스테롤혈중농도의저하및입자의기능장애를초래한다고알려져있다. 22 특히, 내장비만은간리파제의활성을증가시켜 HDL 2 콜레스테롤의감소와 small dense LDL 콜레스테롤을증가시키는데, 폐경전비만여성을대상으로한연구에서는피하지방보다내장지방이 HDL 2 콜레스테롤의농도저하에더강력한연관성을보였다 이상지질혈증은대사증후군과당뇨병에서흔히볼수있는지질대사이상으로, 우리나라 30세이상성인의이상지질혈증유병률은저HDL 콜레스테롤혈증 28.4%, 고중성지방혈증 18.6%, 고LDL콜레스테롤혈증 15.5% 순으로저HDL콜레스테롤혈증과고중성지방혈증의유병률이높다. 특히, 만 30세이상에서고중성지방혈증의경우 1998년 10.2% 에서 2014년 17.9% 로증가하였는데, 저HDL콜레스테롤혈증과고중성지방혈증을반영하는대사증후군또한이상지질혈증유병률의증가와함께급격히증가되고있다. 26 또한, 한국지질 동맥경화학회의이상지질혈증통계자료 (Dyslipidemia Fact Sheet 2015) 에의하면우리나라당뇨병환자의 73.1% 가이상지질혈증을갖고있으며, 국민건강보험공단자료를통해국제질병분류 (International Classification of Diseases- 10, ICD-10) 의질병분류코드에근거하여 E78로진단을받고고지혈증약물을복용하는경우를이상지질혈증으로정의할경우, 제2형당뇨병에서이상지질혈증으로치료받고있는환자수는 2006년 27.8% 에서 2013년 49.5% 로증가하였으며, 당뇨병이아닌사람에비해 5배높았다. 13,27 하지만당뇨병환자중본인의이상지질혈증을인지하고있는경우는 34.6% 였으며, 치료율도 23.6% 로낮았다. 또한 NCEP-ATP III의이상지질혈증치료지침기준 [LDL 콜레스테롤 <100 mg/dl, 중성지방 <150 mg/dl, HDL 콜레스테롤 >40 mg/dl( 남자 ), >50 mg/dl( 여자 )] 에맞추어이상지질혈증을조절하고있는경우는 17.4% 였다. 28 대사증후군과당뇨병에서의지질이상은고중성지방혈증, 저 HDL콜레스테롤혈증, small dense LDL 콜레스테롤분획의증가를동반하는경우가많은데, 인슐린신호전달과정에서의이상이 sterol regulatory element binding protein (SREBP) 1c의활성을증가시켜 VLDL과 LDL의주요구성성분인 apolipoprotein B의합성을증가시키며, 지질단백지질분해효소 (lipoprotein lipase, LPL) 의활성을감소시키면서고중성지방혈증을초래한다. 또한, cholesteryl ester transfer protein (CETP) 에의해 LDL 콜레스테롤이 small dense LDL 콜레스테롤로변형되며, HDL 콜레스테롤이감소된다. 29,30 소아청소년과이상지질혈증 제 2 형당뇨병및대사증후군과이상지질혈증 소아청소년에서의이상지질혈증은비만, 고혈압과함께성인기심혈관계질환의주요위험인자로보고되고있다. 31 특히, 아동기에서의혈중지질농도는성인기에지속적으로영향을주기때문에소아청소년기에서부터의조기진단및치료를권고하고있다. 32,33 한국지질 동맥경화학회의이상지질혈증치료지침진단기준에의하면소아청소년에서고콜레스테롤혈증은 200 mg/dl 이상인경우, 고중성지방혈증은 0-9세인경우 100 mg/dl 이상, 10-19세인경우 130 mg/dl 이상인경우, 고LDL콜레스테롤혈증은 130 mg/dl 이상인경우, 저HDL콜레스테롤혈증은 40 mg/dl 미만인경우로정의된다. 5 소아청소년의비만이증가함에따라이상지질혈증의유병률도동시에증가되고있는데, 우리나라 2-18세소아청소년의비만유병률은 1997년 5.8% 에서 2005년 9.7% 로증가하였으며, 10-19세소아청소년의저HDL콜레스테롤혈증은남자의경우 1998년 5.4% 에서 2005년 14.0% 로증가하였으나, 여자의경우 1998년 16.6% 에서 2005년 16.3% 로유병률에차이가없었다. 34,35 대사증후군도남자에서 1998년 1.4% 에서 2005년 2.0% 로증가하였으나, 여자에서 1998년 3.0% 에서 2005년 1.6% 로감소하는경향을보인다. 35 결론 미국을비롯한세계여러나라에서이상지질혈증의개선을통해심혈관계질환을예방하기위한치료지침들을발표하고있다. 또한, 약 80% 가심혈관계질환으로사망하는제2형당뇨병환자의경우, 이상지질혈증, 비만등심혈관계질환의위험인자가동반되므로개개의위험인자에대한적극적인관리가필요하다. 하지만우리나라의경우아직까지다른만성질환에비해이상지질혈증에대한인지도및치료율이낮다. 따라서이상지질혈증에대한위험성을알리고, 적정체중을유지하기위한식사및운동요법, 금연과절주등의일차적예방과이상지질혈증조기발견 97

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한국성인에서초기황반변성질환과 연관된위험요인연구

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