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1 대사증후군을동반한고혈압환자의임상적특성및표적장기손상 성영준 1,5 김상현 2,5 김현진 1,5 이향림 3,5 김상희 2 변경옥 2 서명기 2,5 서재빈 2,5 박경우 1,5 정우영 2,5 채인호 4,5 조주희 2,5 김명아 2,5 최동주 4,5 김효수 1,5 김철호 4,5 손대원 1,5 오병희 1,5 박영배 1,5 서울대학교병원내과 1, 보라매병원내과 2, 서울북부병원내과 3, 분당서울대학교병원내과 4, 서울대학교의과대학내과학교실 5 Clinical Characteristics and Target-Organ Damage in Hypertensive Patients with Metabolic Syndrome Young-Jun Sung 1,5, Sang-Hyun Kim 2,5, Hyun-Jin Kim 1,5, Hyang-Lim Lee 3,5, Sang-Hee Kim 2, Kyung-Ock Byun 2, Myung-Gi Seo 2,5, Jae-Bin Seo 2,5, Kyung-Woo Park 1,5, Woung-Young Chung 2,5, In-Ho Chae 4,5, Joo-Hee Zo 2,5, Myung-A Kim 2,5, Dong-Ju Choi 4,5, Hyosoo Kim 1,5, Cheol-Ho Kim 4,5, Dae-Won Sohn 1,5, Byung-Hee Oh 1,5 Young-Bae Park 1,5 Division of Cardiology, Department of Internal Medicine, Seoul National University Hopital 1, Boramae Medical Center 2, Seoul Bukbu Hospital 3, Bundang Seoul National University Hospital 4, Seoul National University College of Medicine 5, Seoul, Korea Abstract Objective: The metabolic syndrome consists of abdominal obesity, insulin resistance, glucose intolerance, hypertension, and dyslipidemia. The prevalence of metabolic syndrome (MS) in Korea is continuously increasing. Hypertension is a component of metabolic syndrome and has intimate relations with pathophysiology and clinical importance. The aim of this study is to evaluate clinical and chemical characters in hypertensive patients with MS. Methods: We reviewed medical records of patients with hypertension in BORAMAE Medical center. Only the patients with metabolic syndrome were included. Anti-hypertension medications were classified according to their action mechanism. The prevalence of target-organ damage was evaluated, including left ventricular hypertrophy, heart failure, coronary artery disease, albuminuria, renal failure, carotid atheroma, arterial stiffness, cerebrovascular disease. Results: Of 155 patients with MS, 66% was obese, 46% had high triglyceride, 61% had low HDL-cholsterol, 62% was glucose intolerance. ACE inhibitor and ARB was used in 86 patients, BB in 34 patients, CCB in 86 논문접수일 : , 수정논문접수일 : , 심사완료일 : 책임저자 : 김상현서울시동작구신대방 2 동 425 보라매병원내과 Tel: , Fax: , shkimmd@snu.ac.kr

2 성영준등 : 대사증후군을동반한고혈압환자의임상적특성및표적장기손상 patients, diuretics in 25 patients. The prevalence of disease related with target-organ was 31, 28, 15, 16 events respectively for heart, kidney, peripheral vessels, brain. Conclusion: The hypertensive patients with MS showed multiple target-organ damage and need proper management on hypertension, diabetes, dyslipidemia, obesity. ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ Key Words: ACE (Angiotensin Converting Enzyme), ARB (Angiotensin II receptor blocker), BB (Beta blocker), CCB (Calcium channel blocker) 배 경 대상및방법 대사증후군은심혈관질환과제2형당뇨병의위험을증가시키는복부비만, 인슐린저항성, 고혈압, 이상지질혈증이군집성으로존재하는상태를말한다. 1,2 식생활변화및신체활동량의감소로인한비만인구의증가와이와관련된대사증후군환자증가는중요한건강문제로제기되고있다. 국내국민건강영양조사에의하면 20세이상연령보정대사증후군의유병률은 1998년 24.9% 에서 2001년 29.2% 로증가하였고 2007년조사에서는 31.3% 로꾸준한증가세를보였다. 3 향후심혈관질환및당뇨병발병의위험이더욱증가할수있음을예견할수있고이에대한적절한관리가요구된다. 고혈압은대사증후군의구성요소이면서병인및임상적중요성에서밀접한관련을가지고있다. 대사증후군환자의인슐린저항성과관련하여여러기전으로고혈압을일으키고, 대사증후군이동반된고혈압환자는심혈관질환의발생위험성및표적장기손상도증가하는것으로알려져있다. 4-7 이전에여러연구에서국내의대사증후군환자의유병률, 특성, 비만기준등에대한조사를하였으나이번연구에서는고혈압환자중대사증후군이동반된환자들만을대상으로각질환별유병률, 고혈압약의종류별사용빈도, 관련혈액검사수치, 표적장기손상비율을알아보았다. 1. 연구대상서울특별시보라매병원에내원한본태성고혈압환자들중에서 2008년 1월부터 2010년 8월까지환자들중무작위추출하여자료를분석하였다. 이들의의무기록및검사결과를검토하여대사증후군진단기준을만족하고이차성고혈압은배제를한후분석을시행하였다. 2. 연구방법본연구는본태성고혈압환자의의무기록을이용하는후향적단면분석연구이다. 의무기록을통해나이, 성별, 체중, 신장, 허리둘레, 복용중인고혈압약제, 동반질환, 각종검사실검사결과를분석하였다. 환자들중일부는심초음파, 뇌영상 (brain MRI/CT), 경동맥초음파검사, 맥파전파속도 (PWV; Pulse wave velocity), 발목상완지수 (ABI; Ankle brachial index) 를시행하였고이들에대해서는검사결과를같이분석하였다. 심초음파 (Vivid E9, GE, USA) 는경흉부 (transthoracic) 에서검사하였고, 경동맥초음파는양쪽총경동맥부터내경동맥까지이상소견을관찰하였다. 맥파전파속도와발목상완지수는 VP-2000 (Colin, Japan) 을통해측정하였으며맥파전파속도는상완동맥과발목동맥사이의거리를맥파전달시간으로나누어구하고, 발목상완지수는발목수축기혈압을상완수축기혈압으로나누어구

3 Korean J Lipidol 2011;21:86-93 Table 1. Definitions of Metabolic Syndrome according to ATP III Criteria Definition Obesity BMI>25 kg/m 2 Hypertension 130/85 mmhg or anti-hypertensive medication Triglyceride 150 mg/dl HDL-Cholesterol <40 mg/dl in male, <50 mg/dl in female or treated dyslipidemia Fasting glucose 100 mg/dl or DM medication ATP III, Adult treatment panel III; BMI, Body mass index; HDL, High density lipoprotein; DM, Diabetes mellitus. Table 2. Target-Organ Damage Definition LVH Electrocardiography: S V1+R V5 or V6>35 mm Echocardiography: LVMI 125 g/m 2 in male, 110 g/m 2 in female Heart failure EF<55%, diagnosis of HF CAD Angina, myocardial infarction, coronary stenosis Microalbuminuria >1+ in dipstick test urine albumin/creatinine ratio>30 mg/g CRF MDRD GFR<60 ml/min/1.73m 2 Carotid atheroma plaque in carotid sonogram PWV >12 m/sec ABI <0.9 CVA transient ischemic attack, ischemic stroke, cerebral hemorrhage LVH, Left ventricular hypertrophy; LVMI, Left ventricular mass index; EF, Ejection fraction; HF, Heart failure; CAD, Coronary artery disease; CRF, Chronic renal failure; PWV, Pulse wave velocity; ABI, Ankle brachial index; CVA, Cerebrovascular accident. 하였다. 대사증후군의정의는 ATP III 진단기준을적용하여 5가지항목중 3가지이상의위험인자를가지고있으면대사증후군으로진단하였다. 허리둘레에따른비만판정이서양인을기준으로하였으며, 이에비하여동양인에게서표적장기손상이증가하는비만의기준 (cut-off value) 이낮다는보고는이미잘알려져있다. 또한외래를다니는환자중허리둘레를측정한경우가적고허리둘레와체질량지수 (BMI; Body mass index) 의밀접한연관성을고려하여허리둘레를대신하여 BMI를비만위험인자로인정하였다 (Table 1). 8 표적장기손상은 2007년 ESH-ESC 고혈압치료지침을참조하여정의및분류를하였다. 9 좌심실비대는심전도에서 Sokolow-Lyon 진단기준 10을만족하거나심초음파를통해좌심실질량 지수 (LVMI; left ventricular mass index) 를측정하여남자 125 g/m 2, 여자 110 g/m 2 이상인경우로하였다. 심부전은심박출량이 55% 미만이거나진단받았을때, 관상동맥질환은협심증 / 심근경색의진단이나관상동맥조영술상협착소견을보일때를의미한다. 단백뇨는시험지 (dipstick) 검사에서 1+ 이상이거나 albumin/creatinine ratio 30 mg/g 이상, 만성신부전은 Modification of Diet in Renal Disease formula로계산한신사구체여과율 (GRF; Glomerular filtration rate) 60 ml/min/1.73m 2 미만인경우로하였다. 경동맥죽상경화는죽상판 (plaque) 여부로, 말초혈관질환은맥파전파속도 12 m/sec 이상또는발목상완지수 0.9 미만으로정의하였다. 뇌혈관질환은일과성허혈발작및뇌출혈 / 뇌경색을포함한다 (Table 2)

4 성영준등 : 대사증후군을동반한고혈압환자의임상적특성및표적장기손상 3. 통계조사된자료는평균 ± 표준편차로표시하였으며빈도는퍼센트 (%) 로계산하여분석하였다. 모든통계분석에는 IBM SPSS Statistics v19를사용하였다. 결과 초기선별결과총 317명의고혈압환자들을대상으로선정되었다. 이들의의무기록을통해특성및검사결과를확인하였다. 그중대사증후군진단을만족하는 155명의환자들이분석에포함되었다. 1. 환자특성평균연령은 62세로측정이되었고여자는 85 명, 남자는 70명이포함되었다. 55세미만은여자는 14명, 45세미만남자는 14명이었다. 당뇨병 진단받은환자는 21% 였고, 이상지질혈증진단은환자는 80% 였다. 평균 BMI는 26 kg/m 2 으로측정되어높은것을알수있다. 대사증후군각구성요소별로비율을살펴보면, 복부비만은 BMI를측정한 110명의환자중 72명 (66%), 높은중성지방은 145명중 66명 (46%), 낮은 HDL-콜레스테롤은 145명중 88명 (61%), 인슐린저항성은 151명중 117명 (77%) 이포함되었다. 고혈압은모든환자가진단받았다. 총콜레스테롤은평균 179 mg/dl, 중성지방은 159 mg/dl, HDL-콜레스테롤은 44 mg/dl, LDL- 콜레스테롤은 109 mg/dl, 공복혈당은 124 mg/dl, 당화혈색소는 5.7%, Creatinine은 0.9 mg/dl로측정이되었다. 여자의평균 HDL-콜레스테롤은 48 mg/dl, 남자는 39 mg/dl로대사증후군진단기준보다낮았다 (Table 3). 2. 고혈압약제전체 155명중 130명이고혈압에대한약을복용하고있었으며평균개수는 1.5개이다. ACE 저 Table 3. Characteristics for clinical and chemical parameters Clinical Age (years) 62±12 Sex (Femal/Male) BMI (kg/m 2 ) DM (%) Dyslipidemia (%) Obesity (%) High TG (%) Low HDL (%) Glucose intolerance 85/70 26±3 31 (21%) 123 (80%) 72/110 (66%) 66/145 (46%) 88/145 (61%) 117/151 (77%) Chemical Total cholesterol (mg/dl) Tirglyceried (mg/dl) HDL (mg/dl) LDL (mg/dl) Fasting glucse (mg/dl) HbA1c (%) Creatinine (mg/dl) ±36 159±89 44±13 109±33 124±92 5.7± ±0.5 BMI, Body mass index; DM, Diabetes mellitus; HDL, High density lipoprotein; LDL, Low density lipoprotein.

Korean J Lipidol 2011;21:86-93 해제 (ACE inhibitor; Angiotensin converting enzyme inhibitor) 는 13명, 안지오텐신수용체차단제 (ARB; Angiotensin II receptor blocker) 는 73명, 베타차단제 (BB; Beta blocker) 는 34명, 칼슘채널차단제

5 Korean J Lipidol 2011;21:86-93 해제 (ACE inhibitor; Angiotensin converting enzyme inhibitor) 는 13명, 안지오텐신수용체차단제 (ARB; Angiotensin II receptor blocker) 는 73명, 베타차단제 (BB; Beta blocker) 는 34명, 칼슘채널차단제 (CCB; Calcium channel blocker) 는 86명, 이뇨제는 25명이복용하고있었다. 단일제제로는칼슘채널차단제가가장사용빈도가높았다 (Fig. 1). 3. 표적장기손상 1) 심장좌심실비대는 9명 (6%) 에서확인이되었으며, 심전도진단기준을만족하여 8명이포함되었고심초음파에서좌심실질량지수가기준치를넘는환자는 1명이었다. 심부전과관상동맥질환은각각 7명 (5%), 15명 (10%) 이진단되었고, 진단이되지않은환자들을정상환자로분류하였다. 질환의숫자를합하면 31개이며중복질환을고려하면환자수는 29명이다. 2) 신장소변검사에서미세단백뇨진단기준만족한환자는 10명 (9%) 이었고, 가장높은단백뇨수치는 3.2 g이었다. 신사구체여과율이감소되어있는환자는 18명 (14%) 이었고, GFR이 14.5로감소한환자가가장낮았다. 총질환의합은 28개이며환자수는 27명이다. 3) 말초혈관경동맥죽상경화를보인환자는 4명 (57%) 이었고, PWV는검사한모든환자에게서상승하였으며 ABI는 1명 (8%) 이감소한소견을보였다. ABI 가감소한환자는우측 0.78, 좌측 0.93으로양쪽이차이를보였고 PWV는 13~14 m/s 측정되었다. 심장질환은진단이되지않으면정상으로분류하였지만혈관질환은검사를하지않은환자들에게서도이상소견을보일수있기때문에비율을산정할때전체환자를분모로하지않고검사횟수를기준으로하였다. 총질환의합은 15 개이며환자수는 14명이다. Fig. 1. The number of patients taking anti-hypertension medication. This figure shows the number of patients who were taking anti-hypertension medication regularly. Of medications, CCB was the most frequently used type. ACEi, Angiotensin Converting Enzyme inhibitor; ARB, Angiotensin II receptor blocker; BB, Beta blocker; CCB, Calcium channel blocker

성영준등 : 대사증후군을동반한고혈압환자의임상적특성및표적장기손상 Fig. 2-1. Target-Organ Damage (Event Number). The target-organ damages were classified into 9 categories. Overall cardiac events were 31 including LVH, HF and CAD.

6 성영준등 : 대사증후군을동반한고혈압환자의임상적특성및표적장기손상 Fig Target-Organ Damage (Event Number). The target-organ damages were classified into 9 categories. Overall cardiac events were 31 including LVH, HF and CAD. Renal events were 28 including microalbuminura and CRF. Peripheral artery disease was determined by carotid atheroma, PWV and ABI. Cerebrovascular diseases were represented in single category CVA. LVH, Left ventricular hypertrophy; HF, Heart failure; CAD, Coronary artery disease; MA, Microalbuminuria; CRF, Chronic renal failure; Carotid, Carotid atheroma; PWV, Pulse wave velocity; ABI, Ankle brachial index; CVA, Cerebrovascular accident. 4) 뇌혈관컴퓨터단층촬영또는자기공명영상을통해출혈, 경색소견을보인환자는 14명이었고, 이전진단병력으로 2명이포함되었다. 심장질환과마찬가지로영상소견이나이전에진단이되지않으면정상으로간주하였다. 뇌혈관질환이있는환자는총 16명이었다 (Fig. 2-1, 2-2). 고찰및결론 이번연구는대사증후군을동반한고혈압환자의각위험요인별구성비율과고혈압의치료약제종류, 이로인한표적장기손상의빈도에대해살펴보고자하는연구이다. 대사증후군환자에게서복부비만, 높은중성지방, 낮은 HDL-콜레스테롤, 높은혈당은 46~77% 정도의비율로존재함을확인할수있었다. 이를지질대사이상을총체적으로의미하는이상지질 혈증진단을기준으로분류를하면무려 80% 의환자가관련이있다. 이는고혈압, 당뇨병뿐만아니라지질대사조절또한중요한사항임을간접적으로확인할수있는단서를제공한다. 고혈압약제복용현황을살펴보면 RAS 억제제 (Renin-angiotensin-aldosteron system inhibitor; ACE inhibitor, ARB) 와칼슘채널차단제가각각 86명으로가장많이사용되고있는것을알수있다. 2007년 ESH-ESC 고혈압치료지침을따르면대사증후군환자에게는 RAS 억제제를먼저사용할것으로권장하고있으며추가로칼슘채널차단제, 이뇨제를사용하도록권고하고있다. 9 현재의치료가이러한사항과크게다르지않음을확인할수있겠다. 표적장기손상의빈도확인을위해 9가지의항목으로조사를하였고, 이를장기별로통합하여발생빈도를확인하였다. 심장질환에포함된좌심실비대, 심부전, 관상동맥질환의단순합산횟수는 31개의질환을확인할수있다. 신장질환

Korean J Lipidol 2011;21:86-93 Fig. 2-2. Target-Organ Damage (Proportion). The proportions to each categories of target-organ damage were shown.

7 Korean J Lipidol 2011;21:86-93 Fig Target-Organ Damage (Proportion). The proportions to each categories of target-organ damage were shown. Almost every category demonstrated similar proportion except carotid atheroma and PWV. Since carotid sonogram and PWV were examined in few patients, their proportions were higher than the others. LVH, Left ventricular hypertrophy; HF, Heart failure; CAD, Coronary artery disease; CRF, Chronic renal failure; PWV, Pulse wave velocity; ABI, Ankle brachial index; CVA, Cerebrovascular accident. 에해당하는단백뇨, 만성신부전의합산횟수는 28개이고말초혈관질환에해당하는경동맥죽상경화, PWV 증가, ABI 감소의합은 15개이다. 뇌혈관질환도 16개확인되었다. 말초혈관질환과뇌혈관질환은다른검사에비해시행횟수가낮은점을감안하면대사증후군으로인해특정표적장기의위험성이더커지는것이아님을예상해볼수있다. 오히려말초혈관질환의경우 PWV는시행한모두에게서증가되어있는것은표적장기손상에앞서동맥경직도가증가함을 추측할수있다. 실제로동맥경직도와관상동맥질환과의관련성은여러연구에서도확인되고있다. 11,12 이번연구는제한점으로는다음과같다. 첫번째, 포함된환자의숫자가통계적으로분석을하기에는적고, 그나마포함된환자에게서각종검사결과를완벽하게조사할수없었다. 두번째, 대조군을설정하여위험율, 상관관계등의통계적분석이필요하나그렇지못하였다. 세번째, 비만의기준을복부둘레가아니라체질량지수

8 성영준등 : 대사증후군을동반한고혈압환자의임상적특성및표적장기손상 를적용하여분류및분석하였다. 네번째, 표적장기손상을관찰하기에는추적관찰기간이짧다. 결론적으로, 대사증후군을동반한고혈압환자는심장, 신장, 말초혈관, 뇌혈관에걸친다양한표적장기손상을동반하고있어고혈압및당뇨병, 지질대사, 비만에걸친총체적인치료가중요하겠다. 참고문헌 1. Timar O, Sestier F, Levy E. Metabolic syndrome X: a review. Can J Cardiol 2000;16: Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004;109: Soo Lim et al: Increasing Prevalence of Metabolic Syndrome in Korea: The Korean National Health and Nutrition Examination Survey for Diabetes Care April 19, Mule G, Cerasola G. The metabolic syndrome and its relationship to hypertensive target organ damage. J Clin Hypertens 2006;8: Schillaci G, Pirro M, Vaudo G, Gemelli F, Marchesi S, Porcellati C,Mannarino E. Prognostic value of the metabolic syndrome in essential hypertension. J Am Coll Cardiol 2004;43: Onat A, Hergenc G, Sari I, Turkmen S, Can G, Sansoy V. Dyslipidemic hypertension: distinctive features and cardiovascular risk in a prospective population-based study. Am J Hypertens 2005; 18: Dekker JM, Girman C, Rhodes T, Nijpels G, Stehouwer CD, Bouter LM, Heine RJ. Metabolic syndrome and 10-year cardiovascular disease risk in the Hoorn Study. Circulation 2005;112: International Obesity Task Force (on behalf of the Steering Committee). The Asia-Pacific Perspective: Redefining Obesity and Its Treatment. Western Pacific Region. Sydney, Australia: Health Communications Australia Pty Limited; ESH-ESC Practice Guidelines for the Management of Arterial Hypertension. Journal of Hypertension 2007;25: R L Antikainen, T Grodzicki, D G Beevers, J Webster, J J Jokelainen and C J Bulpitt. Left ventricular hypertrophy by Sokolow-Lyon voltage criterion predicts mortality in overweight hypertensive subjectslvh and the risk of mortality in overweight subjects. Journal of Human Hypertension 23, (January 2009). 11. Hirai T, Sasayama S, Kawasaki T, Yagi S. Stiffness of systemic arteries in patients with myocardial infarction: a noninvasive method to predict severity of coronary atherosclerosis. Circulation 1989;80: Waddell TK, Dart AM, Medley TL, Cameron JD, Kingwell BA. Carotid pressure is a better predictor of coronary artery disease severity than brachial pressure. Hypertension 2001;38:

Risk of Developing Hypertension by Daily Intake of Alcohol

Risk of Developing Hypertension by Daily Intake of Alcohol JNC 7 ESH/ESC (Guidelines) Guidelines 2003. 5 JNC 7 Guidelines ; The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure JAMA. 2003;289:2560-2572.