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136 Kyung-A Shin. Rate Pressure Product Prevent Metabolic Syndrome ORIGINAL ARTICLE Korean J Clin Lab Sci. 2018;50(2):136-143 https://doi.org/10.15324/kjcls.2018.50.2.136 pissn 1738-3544 eissn 2288-1662 Optimal Cutoff Points of Rate Pressure Product in Each Stage of Treadmill Exercise Test According to the Degree of Metabolic Syndrome in Korean Adults Kyung-A Shin Department of Clinical Laboratory Science, Shinsung University, Dangjin, Korea 한국성인의대사증후군예방을위한운동부하검사시각단계별심근부담률의적정임계점 신경아 신성대학교임상병리과 The rate pressure product (RPP) is expressed as a product of the heart rate and systolic blood pressure as an index indirectly measuring the myocardial oxygen consumption, and it indicates the burden on the myocardium. The aim of this study was to determine the optimal level of RPP for preventing metabolic syndrome in a treadmill exercise test in Korean adults. Metabolic syndrome was the diagnosis of the third executive summary report on the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. According to the criteria, the metabolic syndrome diagnosis group (MetS, N=25), pre-metabolic syndrome group (Pre-MetS, N=106), and non-risk factor group (Non-MetS, N=65) were classified. The exercise stress test was performed based on the Bruce protocol. The RPP was calculated as (heart rate systolic blood pressure) 1,000. The results showed that the maximum systolic blood pressure was high despite the low daily dose reached in the diagnostic group of metabolic syndrome. The optimal threshold of the RPP at the time of the exercise treadmill test for a metabolic syndrome prediction was 12.56 mmhg beats/min 10-3 in the first stage of the exercise stress test. The second stage of the exercise test was 16.94 mmhg beats/min 10-3, and at the third stage of the exercise test was 21.11 mmhg beats/min 10-3. Key words: Cutoff points, Metabolic syndrome, Rate pressure product, Treadmill Corresponding author: Kyung-A Shin Department of Clinical Laboratory Science, Shinsung University, 1 Daehak-ro, Jeongmi-myeon, Dangjin 31801, Korea Tel: 82-41-350-1408 Fax: 82-41-350-1355 E-mail: mobitz2@hanmail.net This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright 2018 The Korean Society for Clinical Laboratory Science. All rights reserved. Received: March 1, 2018 Revised 1 st : March 14, 2018 Revised 2 nd : March 26, 2018 Revised 3 rd : April 2, 2018 Accepted: April 3, 2018 서론운동시심혈관계반응의영향력을알아보는다양한지표중심근산소소비량 (myocardial oxygen uptake, MVO 2 ) 은심장에가해지는부담정도를측정하는지표이다 [1]. 심근산소소비량의주요결정요인은관상동맥혈류량, 심실수축기압력, 심 실용적, 질량, 수축력및심박수등이다 [2-5]. 심근산소소비량을직접측정하기는어렵지만, 심박수에수축기혈압의곱으로심근이받는부담을나타내는심근부담률 (RPP, rate pressure product) 은심근산소소비량과강한상관관계를보이고있어심장근육의산소소비량, 즉관상동맥순환반응을간접적으로측정하는지표로이용된다 [6, 7]. 심근부담률이증가할수록심

Korean J Clin Lab Sci. Vol. 50, No. 2, June 2018 137 근의에너지효율이떨어짐을의미하는데, 혈압및심박수의지나친상승을조절하여심근의부담을덜어주는것은심혈관계질환을예방하기위해중요하다 [8,9]. 관상동맥질환자의새벽허혈성심장질환발생은심근부담률상승과밀접한관련이있으며, 운동시만성적혈압상승에의해유도되는높은심근부담률은부정맥및심근허혈을일으킬수있다 [10-12]. 근육의산소소비량은운동에의해증가하게되는데, 이에따라심근의동정맥산소차가증가하므로운동중에는심근이요구하는산소공급을충족시키기위해관상동맥혈류량역시증가한다 [2]. 운동시혈압반응은안정시혈압보다고혈압유병률이나심혈관사건발생을예측하는데더유용한지표이며, 허리둘레와엉덩이둘레같은비만지표는운동부하검사시혈압상승률에영향을미치는위험요인으로보고되었다 [13, 14]. 운동부하검사중심근부담률의증가는협심증환자에서심근허혈의원인이된다는보고되며, 심부전환자에서운동능력저하에의해낮은심근부담률을보이는경우사망률이증가하는부정적인요인이된다 [11, 12, 15]. 이와같이운동중혈압이상승함에따라심근부담률이증가하는것은고혈압이나심혈관위험요인을보유한질환자에게중요한임상적문제를야기할수있으나이에대한논의는이루어지지않고있다. 한편, 대사증후군은고혈압, 고혈당, 고지혈증, 복부비만이한개인에게동시에발생하는질환군으로서대사증후군을유발하는원인으로인슐린저항성이핵심역할을하는것으로알려져있다 [16]. 또한대사증후군은혈액응고, 혈관내피세포기능이상등혈관성질환을유발하여당뇨병및심혈관질환의위험을증가시키는것으로알려져있다 [16, 17]. 대사증후군위험요인은안정시심박수증가및고혈압발병과관련이있으며, 대사증후군으로진단받은경우높은심박수와고혈압을동반하는경우가많은것으로알려진다 [18, 19]. 이와같이대사증후군이심혈관합병증의위험을증가시키는것으로알려져있으나, 그기전에관해서는아직명확히밝혀진바가없다. 특히안정시높은심박수와혈압반응을보이는대사증후군에서는운동에의해높은심근부담률을보일수있기때문에심혈관위험이내제되어있는대사증후군질환자에게운동부하검사를통한심근부담률의평가는중요한의미가있다 [20]. 그러므로대사증후군에서운동부하검사시심근부담률의적정임계치를제시하는것은궁극적으로당뇨병이나심혈관질환의위험을예측하기위한지침을설정하는데근거가될수있으리라생각되지만, 대사증후군에서심근부담률의효율성을제시한연구는전무하다. 본연구에서는한국성인을대상으로트레드밀운동부하검사시대사증후군에서심근부담률의적정수준을제시함으로써 대사증후군정도에따른심근부담률의목표치를설정하여그기준을제시하고자하였다. 대상및방법 1. 연구대상이연구는 2017년 1월부터 2017년 12월까지일개종합병원건강증진센터에서종합건강검진을실시한 20세이상성인남녀중운동부하검사를받은피험자를대상으로하였다. 전체대상자인 252명중고혈압, 당뇨병, 고지혈증으로진단받아약물치료를받고있는경우, 심박수를조절하는약물복용자, 심장질환자, 운동부하검사를중단하였거나연구자료에결측치를포함하는경우에해당하는 56명을제외한최종연구대상자는 196명이었다. 최종대상자중남성 139명, 여성 57명이었다. 진단병력및약물치료유무에관한자료는자기기입식설문지를통해조사하였으며, 본연구는기관생명윤리위원회 (institutional review board, IRB) 의심의를받아승인후연구를수행하였다 (IRB No: SP-2017-11-009-004). 2. 연구방법 1) 신체계측및혈압측정체성분분석기 Inbody 720 (Biospace Co., Seoul, Korea) 으로신장과체중을측정하였으며, 체질량지수 (body mass index, BMI) 는체중 (kg) 을신장 (m) 의제곱으로나눈수치로적용하였다. 허리둘레측정은직립자세에서줄자로 WHO의권고방법인갈비뼈가장아래부분과골반의가장높은부분의중간부위를수평으로호기말에측정하였다. 수축기와이완기혈압은 5분간안정상태에서 1 2 분간격으로 2회측정하여평균값을사용하였으며, 보정된아네로이드혈압계로측정하였다. 2) 대사증후군진단기준및혈액분석대사증후군진단은 2001년 US National Cholesterol. Education Program (NCEP) 의 Adult Treatment Panel (ATP) III 에서제시한지침에따라 1 허리둘레 ; 남성 >102 cm, 여성 >88 cm 2 고중성지방혈증 ; 중성지방 150 mg/dl 3 저 HDL-콜레스테롤혈증 ; 남성 <40 mg/dl, 여성 <50 mg/dl 4 고혈압 ; 수축기혈압 130 mmhg 또는이완기혈압 85 mmhg 5 고혈당 ; 공복혈당 110 mg/dl의 5가지진단기준중 3개이상충족하는경우대사증후군진단군 (MetS) 으로정의하였다 [21]. 또한 1 2 개의기준에해당하는경우를대사증후군전단계군 (Pre-MetS), 5개의진단기준에해당하지않는경우

138 Kyung-A Shin. Rate Pressure Product Prevent Metabolic Syndrome 는대사증후군위험요인이없는군 (Non-MetS) 으로분류하였다. 본연구에서는 NCEP-ATP III에서제시한허리둘레기준대신 WHO 아시아 / 태평양지역에서제시한허리둘레기준인남성 >90 cm, 여성>80 cm를적용하여대사증후군의복부비만을진단하였다 [22]. 혈액분석은 12시간이상금식후상완정중주정맥 (median cubital vein) 에서채혈하여분석하였다. 총콜레스테롤, 중성지방, HDL (high density lipoprotein)-콜레스테롤, LDL (low density lipoprotein)- 콜레스테롤, 공복혈당, 요산, 고감도 C- 반응단백 (high sensitivity C-reactive protein, hs-crp) 항목은혈청분리관 (serum separate tube, SST) 에채혈후혈청분리하여 TBA-200FR NEO (Toshiba, Tokyo, Japan) 로측정하였다. 당화혈색소 (hemoglobin A1c, HbA1c) 는 EDTA (ethylene diamine tetra acetic acid, EDTA) tube에채혈후전혈검체로고속액체크로마토그래피법 (high performance liquid chromatography, HPLC) 의원리에따라 Variant II (Bio Rad, CA, USA) 로측정하였다. 인슐린은전기화학발광면역측정법 (electrochemiluminescence immunoassay, ECLIA) 의측정원리로 Roche Modular Analytics E170 (Roche, Mannheim, Germany) 로검사하였다. 3) 운동부하검사운동부하검사는운동부하검사용트레드밀장비 (Medtrack ST 55, Quinton Instrument Co., Boston, USA) 를이용하여 3 분간격으로각단계 (stage) 마다회전속도와경사도를증가시키는 Bruce 프로토콜을적용하여시행하였다 [23]. 운동부하검사 stage 1은회전속도 1.7 mile/h, 경사도 10%, stage 2는회전속도 2.5 mile/h, 경사도 12%, stage 3은 3.4 mile/h, 경사도 14% 로운동부하검사를실시하였다. 심전도는운동직전과운동중 1분간격으로기록하였으며, 2분간격으로심박수와혈압을측정하였다. 정확한혈압측정을위해상완동맥부위에마이크로폰이내장된커프를감고정확한심장박동음을듣고혈압을측정하였으며, 회복기반응을확인하기위해운동부하검사후 1 분대에심전도, 심박수, 혈압을측정하였다. 운동부하검사중심박수와심전도는실시간 12채널 Quinton stress test system (Q4500, Quinton Instrument Co., Boston, USA) 을이용하여측정하였으며, 운동부하검사는최대심박수인 [220-연령] 의 85% 이상도달하는시점까지시행하였다. 또한대사당량 (metabolic equivalent, MET) 은 treadmill 의회전속도와경사도를이용하여다음의공식으로구하였다. MET=[(Speed 0.1)+(Grade/100 1.8 Speed)+3.5]/3.5 이다. 운동부하검 사후회복기는운동을마친후경사도를 0% 로고정하고속도를 1.3 mph로하여 30 40 초간트레드밀을걷고, 트레드밀이완전히멈춘후침대에누워 5분동안심전도, 심박수, 혈압반응을확인하였다. 심근부담률 (rate pressure product, RPP) 은측정된심박수와수축기혈압을통해 ( 심박수 수축기혈압 ) 1,000으로도출하였다 [7]. 운동부하검사안정시, 운동중, 회복기각단계별심근부담률의변화율은 Δ RPP로나타냈으며, 운동부하검사전안정시심근부담률값을 100으로하였을때운동부하검사각단계별심근부담률값의변화를백분율로제시하였다. 3. 통계분석이연구결과에서얻어진자료는 IBM SPSS Statistics 24.0 (IBM, NY, USA) 통계프로그램을사용하여통계처리하였다. 모든측정형자료는평균과표준편차의기술통계치로표시하였으며, 범주형및명목형자료는 % 로나타냈다. 범주형및명목형자료의대사증후군정도에따른집단간차이는카이제곱검정 (chi-square test) 을시행하였다. 대사증후군정도에따른대상자의임상적특성, 운동부하검사단계별혈역학적반응및심근부담률의차이를파악하기위해일원변량분석 (one way analysis of variance, one-way ANOVA) 을실시하였으며, 일원변량분석결과유의한차이가나타난경우 bonferroni 검증방법을이용하여사후검증 (post-hoc test, multiple comparison) 을실시하였다. 또한대사증후군을예측하기위한심근부담률의적정분별점 (cutoff points) 을제시하기위해 ROC 곡선 (receiver operating characteristic curve, ROC curve) 분석을실시하였다. ROC 분석을통해곡선아래의면적 (area under the curve, AUC), 민감도 (sensitivity) 와특이도 (specificity) 를평가하였으며, 민감도와특이도의합이최대인지점을적정임계점으로선정하였다. 이연구의모든통계적유의수준은 P<0.05 로설정하였다. 결과 1. 대사증후군정도에따른연구대상자의임상적특성대사증후군정도에따른연구대상자의임상적특징을확인한결과 Table 1과같다. 대사증후군정도에따른성별은집단간차이가없었다. 연령과체중은대사증후군전단계군과대사증후군진단군이대사증후군위험요인이없는군보다높았다 ( 각각 P=0.004, P<0.001). 체질량지수, 허리둘레, 수축기와이완기혈압은대사증후군위험요인이없는군보다대사증후군전

Korean J Clin Lab Sci. Vol. 50, No. 2, June 2018 139 Table 1. Clinical characteristics of the subject according to metabolic syndrome status Variable Non-MetS (N=65) Pre-MetS (N=106) MetS (N=25) P-value Men, n (%) 45 (69.2) 77 (72.6) 17 (68.0) 0.841 Age (yr) 44.84±10.22 48.76±10.13* 52.12±8.66* 0.004 Height (cm) 166.31±8.05 166.26±9.25 164.81±9.20 0.742 Weight (kg) 62.56±9.25 68.81±12.21* 72.94±13.78* <0.001 BMI (kg/m 2 ) 22.53±2.39 24.74±2.98* 26.64±3.58*, <0.001 Waist circumference (cm) 76.31±6.74 83.70±7.46* 88.60±8.33*, <0.001 Systolic BP (mmhg) 105.76±9.96 116.55±14.66* 126.40±17.53*, <0.001 Diastolic BP (mmhg) 68.84±8.32 75.81±10.30* 83.60±11.94*, <0.001 Total cholesterol (mg/dl) 196.75±31.74 203.36±35.43 203.00±31.66 0.444 HDL-C (mg/dl) 60.66±13.10 49.03±10.64* 43.16±10.61* <0.001 LDL-C (mg/dl) 122.15±30.52 132.69±31.13 127.56±31.31 0.098 Triglyceride (mg/dl) 87.69±32.36 141.92±76.66* 234.08±125.23*, <0.001 Fasting glucose (mg/dl) 88.81±7.99 95.66±17.73* 110.28±22.49*, <0.001 HbA1c (%) 5.49±0.30 5.86±0.66* 6.32±0.77*, <0.001 Insulin (uu/ml) 4.63±2.92 6.65±3.70* 8.89±5.56*, <0.001 Uric acid (mg/dl) 5.23±1.43 5.60±1.38 5.63±1.44 0.215 hs-crp (mg/dl) 0.23±0.64 0.20±0.62 0.21±0.20 0.957 Calculated by one-way ANOVA and chi-square test. Values are presented as mean±sd and number(%). *Significantly different from the Non-MetS at P<0.05, Significantly different from Pre-MetS at P<0.05. Abbreviations: MetS, metabolic syndrome; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; HbA1c, hemoglobin A1c; hs-crp, high sensitivity C-reactive protein. Table 2. Comparison of the hemodynamic response during treadmill exercise test by metabolic syndrome status Variable Non-MetS (N=65) Pre-MetS (N=106) MetS (N=25) P-value Supine HR (beats/min) 62.10±9.95 62.83±10.68 65.60±10.44 0.360 Supine SBP (mmhg) 114.29±13.19 121.04±14.68* 131.04±17.74*, <0.001 Supine DBP (mmhg) 70.38±9.13 76.76±11.53* 84.28±12.87*, <0.001 Stage 1 HR (beats/min) 100.24±12.18 105.27±15.83 106.80±10.87 0.054 Stage 1 SBP (mmhg) 127.66±16.29 135.66±21.80* 143.04±22.12* 0.003 Stage 1 DBP (mmhg) 71.44±10.02 78.96±13.19* 84.00±15.74* <0.001 Stage 2 HR (beats/min) 119.78±16.07 120.74±15.01 123.68±11.29 0.543 Stage 2 SBP (mmhg) 137.24±16.53 145.50±21.35* 156.04±23.20* <0.001 Stage 2 DBP (mmhg) 71.24±9.65 78.66±12.66* 85.76±15.93*, <0.001 Stage 3 HR (beats/min) 142.01±18.30 141.99±17.86 142.54±13.48 0.990 Stage 3 SBP (mmhg) 148.54±17.01 156.60±23.10 169.66±22.13*, <0.001 Stage 3 DBP (mmhg) 74.32±10.55 79.75±11.49* 85.62±14.03* <0.001 Max HR (beats/min) 165.92±12.54 159.12±17.69* 153.68±12.84* 0.002 Max SBP (mmhg) 159.68±18.47 166.72±21.98 176.96±22.53* 0.002 Max DBP (mmhg) 77.09±9.81 82.10±11.85* 87.56±14.59* <0.001 Recovery 1 min HR (beats/min) 130.00±16.36 127.06±19.32 127.20±14.11 0.561 Recovery 1 min SBP(mmHg) 133.62±25.32 152.38±24.56* 151.11±24.58* <0.001 Recovery 1 min DBP(mmHg) 69.72±12.70 77.85±14.58* 80.00±14.05* 0.002 Exercise duration (min) 10.30±1.42 9.53±1.96* 8.67±1.74* <0.001 Exercise capacity (MET) 12.33±1.69 11.54±2.11* 10.50±1.99* <0.001 Calculated by one-way ANOVA. Values are presented as mean±sd. *Significantly different from the Non-MetS at P<0.05, Significantly different from Pre-MetS at P<0.05. Abbreviations: MetS, metabolic syndrome; HR, heat rate; SBP, systolic blood pressure; DBP, diastolic blood pressure; MET, metabolic equivalent.

140 Kyung-A Shin. Rate Pressure Product Prevent Metabolic Syndrome 단계군과대사증후군진단군이높았으며, 대사증후군진단군은대사증후군전단계군보다높았다 ( 각각 P<0.001). 혈액학적변인중 HDL-콜레스테롤은대사증후군위험요인이없는군보다대사증후군전단계군과대사증후군진단군에서낮게나타났다 (P<0.001). 중성지방, 공복혈당, HbA1c, 인슐린은대사증후군전단계군과대사증후군진단군에서대사증후군위험요인이없는군보다높게나타났으며, 대사증후군진단군은대사증후군전단계군보다높았다 ( 각각 P<0.001). 그러나 LDL-콜레스테롤, 요산, hs-crp는대사증후군정도에따른집단간차이는없었다. 2. 대사증후군정도에따른운동부하검사단계별혈역학적반응의차이대사증후군정도에따른운동부하검사각단계별혈역학적반응의차이를확인한결과 Table 2에제시된바와같다. 대사증후군정도에따른안정시심박수, 운동부하검사 1단계심박수, 운동부하검사 2단계심박수및운동부하검사 3단계심박수는집단간차이가없었다. 안정시수축기와이완기혈압은대사증후군진단군과대사증후군전단계군이대사증후군위험요인이없는군보다높았으며, 대사증후군진단군은대사증후군전단계군보다높았다 ( 각각 P<0.001). 운동부하검사 1단계에서의수축기와이완기혈압은대사증후군위험요인이없는군보다대사증후군전단계군과대사증후군진단군이높았다 ( 각각 P=0.003, P<0.001). 운동부하검사 2단계에서의수축기와이완기혈압은대사증후군위험요인이없는군보다대사증후군전단계군과대사증후군진단군에서높았으며, 이완기혈압은대사증후군진단군이대사증후군전단계군보다도높았다 ( 각각 P<0.001). 운동부하검사최대심박수와최대이완기혈압은대사증후군전단계군과대사증후군진단군이대사증후군위험 요인이없는군보다높았다 ( 각각 P=0.002, P<0.001). 또한운동부하검사최대수축기혈압은대사증후군위험요인이없는군과대사증후군전단계군보다대사증후군진단군에서높았다 (P=0.002). 운동부하검사후 1분대의수축기와이완기혈압은대사증후군위험요인이없는군보다대사증후군전단계군과대사증후군진단군이높았으며 ( 각각 P<0.001, P=0.002), 운동부하검사후회복기 1분대의심박수는집단간차이가없었다. 운동능력을나타내는운동시간과대사당량은대사증후군위험요인이없는군보다대사증후군전단계군과대사증후군진단군에서낮게나타났다 ( 각각 P<0.001). 3. 대사증후군정도에따른운동부하검사단계별심근부담률의차이대사증후군정도에따른운동부하검사각단계별심근부담률의차이를확인한결과안정시심근부담률은대사증후군위험요인이없는군보다대사증후군진단군이높았으며, 대사증후군진단군은대사증후군전단계군보다도높았다 (P<0.001). 운동부하검사 1단계에서의심근부담률은대사증후군위험요인이없는군보다대사증후군전단계군과대사증후군진단군에서높았다 (P=0.001). 운동부하검사 2단계와 3단계에서의심근부담률은대사증후군진단군에서대사증후군위험요인이없는군과대사증후군전단계군보다높게나타났다 ( 각각 P=0.002, P=0.010). 그러나최대운동시심근부담률은대사증후군정도에따라차이가없었다. 또한운동부하검사각단계별심근부담률의변화율은대사증후군정도에따른집단간차이가없었다 (Table 3). Table 3. Comparison of the RPP response during treadmill exercise test by metabolic syndrome status Variable Non-MetS (N=65) Pre-MetS (N=106) MetS (N=25) P-Value Supine RPP (mmhg beats/min 10-3 ) 7.08±1.29 7.62±1.69 8.65±2.12*, <0.001 Stage 1 RPP (mmhg beats/min 10-3 ) 12.79±2.29 14.38±3.72* 15.40±3.51* 0.001 Stage 2 RPP (mmhg beats/min 10-3 ) 16.46±3.10 17.64±3.81 19.41±4.12* 0.002 Stage 3 RPP (mmhg beats/min 10-3 ) 21.10±3.63 22.32±4.73 24.30±4.90* 0.010 Max RPP (mmhg beats/min 10-3 ) 26.49±4.07 26.47±4.12 27.25±4.69 0.692 Δ stage 1 RPP (%) 183.41±31.15 191.54±42.42 182.13±37.39 0.304 Δ stage 2 RPP (%) 235.91±42.69 238.26±53.86 231.58±54.15 0.830 Δ stage 3 RPP (%) 302.64±53.34 302.72±75.66 295.48±72.36 0.891 Δ Max RPP (%) 383.91±73.82 359.75±82.88 329.65±83.85* 0.013 Calculated by one-way ANOVA. Values are presented as mean±sd. *Significantly different from the Non-MetS at P<0.05, Significantly different from Pre-MetS at P<0.05. Abbreviations: RPP, rate pressure products; MetS, metabolic syndrome.

Korean J Clin Lab Sci. Vol. 50, No. 2, June 2018 141 Table 4. Cutoff points of RPP response during treadmill exercise test with metabolic syndrome Variable Cutoff points Sensitivity Specificity AUC (95% confidence interval) P-value Supine RPP 8.47 45.8% 83.0% 0.668 (0.556 0.779) 0.008 Stage 1 RPP 12.56 83.3% 47.3% 0.663 (0.546 0.781) 0.010 Stage 2 RPP 16.94 75.0% 58.2% 0.668 (0.562 0.775) 0.008 Stage 3 RPP 21.11 79.2% 49.7% 0.648 (0.546 0.751) 0.019 Abbreviations: AUC, area under the curve; RPP, rate pressure. 4. 대사증후군을예측하기위한운동부하검사단계별적정심근부담률 ROC 분석으로대사증후군예측을위한운동부하검사각단계별적정심근부담률은 Table 4에제시된바와같다. 대사증후군예측을위한안정시심근부담률의 AUC 값은 0.668, 운동부하검사 1단계에서의심근부담률의 AUC 값은 0.663, 운동부하검사 2단계의심근부담률의 AUC 값은 0.668, 운동부하검사 3 단계의심근부담률의 AUC 값은 0.648로나타났다. 또한대사증후군예측을위한안정시심근부담률의적정임계점은 8.47 mmhg beats/min 10-3, 민감도는 45.8%, 특이도는 83.0% 으로나타났다 (P=0.008). 대사증후군예측을위한운동부하검사 1단계의심근부담률의적정임계점은 12.56 mmhg beats/min 10-3, 민감도는 83.3%, 특이도는 47.3% 였다 (P=0.010). 대사증후군예측을위한운동부하검사 2단계의심근부담률의적정임계점은 16.94 mmhg beats/min 10-3, 민감도는 75.0%, 특이도는 58.2% 였다 (P=0.008). 또한대사증후군예측을위한운동부하검사 3단계에서의심근부담률의적정임계점은 21.11 mmhg beats/min 10-3 이며, 민감도는 79.2%, 특이도는 49.7% 로나타났다 (P=0.019). 고찰본연구는운동부하검사시각단계별대사증후군에따른심근부담률의적정임계점을제시하고자하였다. 심근산소소비량 (MVO 2) 은증가된심근산소요구량에대한관상동맥순환반응의좋은지표이다 [24]. 일상적으로임상에서심근산소소비량의직접측정이어렵지만박출작업량 (stroke work), 용질확산법칙 (Fick principle), 장력시간계수 (tension time index) 및심근부담률 (rate pressure product, RPP) 과같은간접적인방법으로산출가능하다 [25]. 특히심박수와수축기혈압의곱으로쉽게측정할수있는지표인심근부담률은심근산소소비량의직접측정법과높은상관성을보이며심근대사요구에대한관상동맥순환반응과더불어혈류량증가를잘정 의하고있다 [7, 26]. 심박수와수축기혈압은모두안정시와운동중에심근산소소비의변화를결정하는가장중요한변수이며, 심근부담률은운동중활동심근에적절한혈액을공급하기위해심장의작업부하와교감신경유출 (sympathetic nerve discharge) 증가로운동시증가한다 [27]. 일반적으로운동부하검사시미국심장협회에서제시한 [220-연령] 의 85% 이상도달하는시점으로최대심박수또는최대운동강도를예측하는데사용하고있으나 [28], 이는심박수만을고려한경우로심박수에영향을미치는베타차단제와같은약물복용자에게적용이어려워심박수와더불어수축기혈압상승을고려한심근부담률을활용할필요성이있겠다 [29]. 협심증환자의경우심박수와수축기혈압상승에따른심근부담률의상승은심근허혈을일으키는원인이며, 베타차단제와같은약물에의해심박수와수축기혈압을낮추게되면협심증예방에도움이되는것으로알려져있다 [11, 12, 30]. 본연구결과에서대사증후군진단군은도달한일량이낮음에도불구하고최대수축기혈압이높은것으로나타났으며, 이러한요인은말초동맥의확장기능장애로인한후부하상승으로다른집단보다과도한혈압상승을보이기때문으로생각된다. 따라서대사증후군진단군에서운동시운동강도를설정할때대사증후군위험요인이없는집단보다운동에의해높은혈압상승을보이므로수축기혈압상승을고려하여야하겠다. 심근부담률은운동이진행됨에따라점진적으로증가하는데관상동맥질환을동반한폐경전여성에서최대심근부담률은 27±1.0 mmhg beats/min 10-3 이며, 폐경기여성은 25± 1.0 mmhg beats/min 10-3 으로관상동맥질환을동반한폐경기여성에서낮은심근부담률을보였다 [24]. 최대심근부담률은심장의심근산소요구량과심장의부하를정확하게반영하는지표이며, 허혈성심질환자에게서심근부담률이 25 mmhg beats/min 10-3 를초과하는경우는드문것으로보고된다 [24]. 본연구에서는성인을대상으로운동부하검사시대사증후군예방을위한적정심근부담률의임계점은운동부하검사 1단계에서 12.56 mmhg beats/min 10-3, 운동부하검사 2단계는 16.94 mmhg beats/min 10-3, 운동부하검사 3단계에서

142 Kyung-A Shin. Rate Pressure Product Prevent Metabolic Syndrome 는 21.11 mmhg beats/min 10-3 로나타났다. 심박수의변화없이혈압의증가는혈압의증가와함께심박수가증가하는경우보다심근산소화 (myocardial oxygenation) 에더유익한것으로보고된다 [26]. 심근부담률의임계치에대한선행연구중 Fornitano 와 Godoy [31] 의연구에따르면최대운동시 30 mmhg beats/min 10-3 이상의심근부담률을나타내는경우폐쇄성관상동맥질환을예측하는유용한도구가될수있음을입증하였다. 안정시심근부담률은 7-9 mmhg beats/ min 10-3 정도이며, 심근부담률이 10 mmhg beats/min 10-3 이상이면심장질환의위험이증가하는명확한지표라는결과가제시된다 [25, 32]. 그러나운동에의한심근부담률이 22 mmhg beats/min 10-3 이상이면심근허혈과협심증의위험이증가하는것으로간주된다 [32]. 그러므로 White [6] 에의하면건강인에서심박수가 60 120 bpm이고수축기혈압이 100 140 mmhg, 심근부담률은 12 mmhg beats/min 10-3 이하이면심혈관합병증위험이없는것으로간주된다고보고하였다. 대사증후군예측을위한심근부담률의적정기준치를확인한선행연구가없어비교는어려우나, 운동부하검사시각단계별로본연구에서정량화하여제시한심근부담률의임계치를적용하는것은심혈관계위험요인들이군집해서나타나는대사증후군의예방을위한지침을설정하는데기준이될수있을것으로생각된다. 심근부담률에대한선행연구에따르면, 비만정도가심해질수록안정시, 운동시, 회복기심근부담률이증가하며, 유산소운동은심근부담률을감소시키는효과가있었다 [33, 34]. 또한만성안정형협심증환자에게서지속적인유산소운동을통해같은운동강도에서심근부담률을감소시켰으며, 이로인해협심증발생을낮추는효과를확인하였다 [35]. 관상동맥질환자의경우심근부담률이증가할수록허혈발생가능성이증가하는반면, 체력적으로매우허약한심혈관질환자에게서지속적인운동으로최대심근부담률이증가하였다면이는심근이부하된운동량을견디면서일할수있는능력이향상되었다는긍정적인결과로해석된다 [11, 12, 36]. 본연구는운동부하검사시대사증후군에따른각단계별심근부담률의적정임계점을추정하여제시하고자하였으나, 일부민감도와특이도가가낮아진단적선별검사의기준으로서제한점이있다. 또한대사증후군정도에따른집단간연령에차이를보이고있으나이를통제하지않은점에서결과해석에주의를요한다. 그럼에도불구하고이연구는한국의성인남녀를대상으로대사증후군에따른운동부하검사시심근부담률의목표치를제시하였다는데의미가있을것으로판단되며, 향후다 양한연령별, 성별에따른심근부담률의임계치를제시하는연구가필요하리라생각된다. 요약 심근부담률은심근산소소비량을간접적으로측정하는지표로심박수와수축기혈압의곱으로나타내며, 심근이받는부담을나타낸다. 본연구는한국성인을대상으로트레드밀운동부하검사시대사증후군에따른심근부담률의적정수준을제시함으로써대사증후군유병률을낮추기위한심근부담률의목표치를설정하여그기준을제시하고자하였다. 대사증후군진단은 National Cholesterol Education Program (NCEP) 의 Adult Treatment Panel (ATP) III에서제시한 5가지진단기준중 3개이상충족하는경우대사증후군진단군 (MetS, N=25), 1 2 개의기준에해당하는경우를대사증후군전단계군 (Pre-MetS, N=106), 5개의진단기준에해당하지않는경우는대사증후군위험요인이없는군 (Non-MetS, N=65) 으로분류하였다. 운동부하검사는 Bruce 프로토콜에따라시행하였다. 심근부담률은 ( 심박수 수축기혈압 ) 1,000으로구하였다. 본연구결과대사증후군진단군에서도달한일량이낮음에도불구하고최대수축기혈압이높은것으로나타났다. 또한대사증후군에따른운동부하검사시심근부담률의최적임계점은운동부하검사 1단계에서는 12.56 mmhg beats/min 10-3, 운동부하검사 2단계는 16.94 mmhg beats/min 10-3, 운동부하검사 3단계에서는 21.11 mmhg beats/min 10-3 로나타났다. Acknowledgements: None Conflict of interest: None REFERENCES 1. Jin SM, Shin SY, Kim WJ. The effects of 12-weeks' intermittent high-intensity exercise on the myocardial oxygen uptake and pulse wave velocity. Journal of Wellness. 2017;12:689-698. 2. Cheitlin MD, Sokolow M. Clinical cardiology. Norwalk: Appleton and Lange; 1993. p1-38. 3. Detollenaere M, Duprez D, De Buyzere M, Vandekerckhove H, De Cock N, De Backer G. Myocardial oxygen demands of job activities in post-myocardial infarct patients. Eur Heart J. 1993;14:373-376. 4. Meyer K, Samek L, Pinchas A, Baier M, Betz P, Roskamm H. Relationship between ventilatory threshold and onset of ischaemia in ECG during stress testing. Eur Heart J. 1995; 16:623-630. 5. Ridocci F, Velasco JA, Echánove I, Soriano G, Cruz Torregrosa

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