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1 Korean J Fam Pract. 2012;2: 동맥경직도와 QTc 간격과의관계 Original Article 박성원, 최지호, 손유나, 박광식, 이지원 * 연세대학교의과대학세브란스병원가정의학교실 Relationship between Arterial Stiffness and QTc Interval Sung-Won Park, Ji-Ho Choi, You-Na Son, Kwang-Shik Park, Ji-Won Lee* Department of Family Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea Background: Arterial stiffness is an efficient tool for early diagnosis of atherosclerosis and prediction of cardiovascular disease, and it has been known recently that the electrocardiogram QT interval is related to many cardiovascular diseases. In this study, we analyzed the relationship between arterial stiffness and corrected QT (QTc) interval in adults with no cardiovascular diseases who had visited family medicine clinics. Methods: Questionnaires, physical measurements, blood pressure measurements, and lab tests were carried out in 603 adults (39.28±11.59 years). Brachial-ankle pulse wave velocity was measured, and QTc interval was measured by a standard 12-lead electrocardiogram. Results: Pearson correlation showed a statistically positive correlation with age (r=0.222, P<0.001), body mass index (r=0.097, P=0.02), waist-hip circumference ratio (r=0.215, P<0.001), fasting plasma glucose (r=0.179, P<0.001), and fasting insulin (r=0.091, P=0.03) from QTc interval. Brachial-ankle pulse wave velocity showed a positive correlation with QTc interval (r=0.196, P<0.001). Multiple regression analysis after adjusting for age, sex, body mass index, systolic blood pressure, total cholesterol, high density lipoprotein, triglyceride, fasting plasma glucose, fasting insulin, and C-reactive protein showed a significant positive relationship with the QTc interval independent from brachial-ankle pulse wave velocity (P<0.01). Conclusion: There is a significant relationship between arterial stiffness and QTc interval, and QTc interval tends to increase as arterial stiffness increases. Therefore, those in primary care with increased QTc interval should be evaluated for risks of cardiovascular diseases as a primary prevention against cardiovascular diseases. Keywords: Arterial Stiffness; QTc Interval; Echocardiogram 서론 최근우리나라에서는식생활의서구화와생활양식의변화로인해심혈관질환으로인한사망률은최근 10년간 2배이 Received: August 17, 2010, Accepted: April 17, 2012 *Corresponding Author: Ji-Won Lee Tel: , Fax: indi5645@yuhs.ac Korean Journal of Family Practice Copyright 2012 by The Korean Academy of Family Medicine 상으로증가하여국내전체사망원인의 27.6% 로 1위를차지하고있으며동맥경화와관련있는허혈성심장병등이빠르게증가추세에있다. 1) 심혈관질환으로인한사망의 80% 는적절한관리를통해예방이가능하므로심혈관질환을조기에예측할수있는예측인자의중요성은더욱강조되고있는실정이다. 동맥경직도는동맥의죽상화와함께동맥경화의중요한인자로동맥경직도증가시좌심실후부하와관상동맥관류의감소로심근의산소요구량을증가시키고동맥벽에스트레스를가하여동맥경화를일으킨다고알려져있다. 2) 최근조기에동맥경직도와혈관손상의심각도를진단하는방법으로 148 Vol. 2, No. 2 Jun 2012 Korean J Fam Pract

2 박성원외 : 동맥경직도와 QTc 간격과의관계 맥파속도 (pulse wave velocity) 가사용되고있으며재현성이높으면서 3,4) 외래에서간단하고비침습적으로쉽게측정할수있어 5) 이는동맥경화조기판별과심혈관질환예측의유용한도구로널리이용되고있다. 6-8) 심전도상 QT 간격은 QRS군의시작부터 T파의끝까지의간격으로심실의탈분극 (depolarization) 의시작시점과심실재분극 (repolarization) 완료시점사이의시간간격을의미한다. 9) QT 간격은심박동수와반비례로변동하므로 Bazett 공식을이용하여심박동수 60회를기준으로교정한 QT (corrected QT, QTc) 간격을구하여사용한다. QTc 간격은연령이증가할수록증가하며정상치는남자에서 420 ms 이하, 여자에서 440 ms 이하로알려져있다. 심전도상 QTc 간격의연장은심실빈맥, 심실세동, 다형성심실빈맥 (torsades de pointes) 등치명적인부정맥을유발할수있으며 10) 허혈성심장질환과급사까지도초래할수있다. 11,12) QTc 간격을연장시키는원인으로는저칼륨혈증, 저체온증, 뇌지주막하출혈, 심근염, 급성심근경색, 선천성 QT 간격연장증후군등의질환이있으며약물로는 procainamide, quinidine, amiodarone, digitalis, diisopyramide, 삼환계항우울제등이유발하는것으로알려져있다. 13,14) 심혈관질환의초기단계평가인자로서동맥경직도와 QT 간격연장각각에대해서는여러연구들이보고되고왔지만아직까지평가인자로서동맥경직도와심전도상의 QTc 간격연장과의상호관련성에대해서는그중요성에비해잘알려져있지않다. 외국의경우 Maebuchi 등 15) 이 2,666명을대상으로시행한동맥경직도와 QTc 간격연장과의유의한관련성을밝힌연구가유일하였고국내에서는아직까지이에대한연구가없는실정이다. 따라서본연구에서는가정의학과를내원한한국성인남녀를대상으로동맥경직도와 QTc 간격과의관련성을알아보고자하였다. 방법 1. 연구대상 2004년 4월부터 2009년 12월까지세브란스병원가정의학과에내원한 20-70세의성인남녀중상완-발목맥파속도 (brachial-ankle pulse wave velocity) 를측정한 936명을대상으로시행하였다. 이가운데심전도를시행하지않은경우, 암, 심장질환, 말초혈관질환, 뇌혈관질환, 갑상선질환, 최근 6개월간급성심근경색의과거력이있는경우, 심전도상에서심방심실전도장애가있는경우, 항고혈압제를제외한심혈관약물을복용중인경우, QTc 간격을연장시킬수있는항히스타민제, 항우울제, 경구피임제를복용중인경우를연구대상에서 제외하여최종분석대상은 603명 ( 남자 146명, 여자 457명, 연령 20-70세 ) 이었으며, 본연구는해당병원의료윤리위원회 (institutional review board) 의승인을받았다. 2. 연구방법 1) 문진검사전설문지를통해대상자의현병력, 과거력, 약물복용력, 흡연및음주습관, 여성의경우폐경유무에대해조사하였다. 흡연은현재흡연을하는사람으로, 음주는일주일에한번이상음주를하는사람으로정의하였다. 2) 신체계측신장과체중은가벼운옷을입은상태로전자저울과전자신장계측기를이용하여각각킬로그램과센티미터단위로소수점한자리까지측정하였으며, 체질량지수 (body mass index) 는체중 (kg)/ 키 (m) 2 으로계산하였다. 허리둘레는직립자세에서양쪽엉덩뼈능선 (iliac crest) 3 cm 상방을중심으로, 엉덩이둘레는양측대퇴골대전자의가장넓은부위를중심으로소수점한자리까지측정하였으며, 허리엉덩이둘레비 (waist-tohip ratio) 는허리둘레 (cm) 를엉덩이둘레 (cm) 로나누어계산하였다. 혈압측정은 10분이상안정후에의자에서앉은상태로전자식혈압계로숙련된간호사가우측팔에서 1회측정하였으며정상이아닌경우에는 10분간재안정후재측정하였다. 3) 상완-발목맥파속도대상자는맥파속도측정전에적어도 5분이상안정을취한후수평침대에누운자세에서 Form/ABI 장치 (Nihon Colin, Komaki, Japan) 를이용하여측정하였다. 파형데이터는양쪽상완과발목에감긴측정띠의반도체센서를이용하여기록되었으며, 우측상완-발목맥파속도와좌측상완-발목맥파속도가측정되었다. 우측과좌측의상완-발목맥파속도는유의하게양의상관성이있으므로본연구에서는평균상완-발목맥파속도를사용하였다. 4) Corrected QT 간격심전도는표준 12-유도자동심전도기인 Marquette MAC 12 (General Electric Medical System Inc., Milwaukee, WI, USA) 를이용하여기록하였다. 심박동수와 QTc 간격은자동심전도분석프로그램 (12SL electrocardiogram [ECG] analysis program; GE- Marquette Medical Systems, Milwaukee, WI, USA) 에의해계산되었다. QTc 간격이심박동수와반비례로변동하므로가장널 가정의학 Vol. 2, No. 2 Jun

3 Sung-Won Park, et al: Relationship between Arterial Stiffness and QTc Interval 리사용되는 Bazett 공식 (QT 간격 /RR 간격 1/2 ) 에의해 QT 간격을계산하였으며, 16) QTc 간격연장은남자에서 420 ms, 여자에서 440 ms를초과하는경우로정의하였다. 13) 측정된심전도결과는모두가정의학과의사 1인에의해검토를받아 left bundle branch block, right bundle branch block, significant Q wave 소견이보이는지확인하였다. 2. QTc 간격과상완-발목맥파속도및심혈관위험인자들간의상관성 QTc 간격과상완-발목맥파속도및심혈관위험인자들간의상관성을알아보기위해피어슨상관분석을하였을때나이 (r=0.222, P<0.001), 체질량지수 (r=0.097, P=0.02), 허리엉덩이둘레비 (r=0.215, P<0.001), 공복혈당 (r=0.179, P<0.001), 공복인 5) 혈액검사대상자의혈액은검사전 8시간공복후아침에안정상태에서전주동맥에서채혈하였다. 총콜레스테롤 (total cholesterol), 고밀도지단백 (high density lipoprotein) 콜레스테롤, 중성지방 (triglyceride), 공복혈당은비색법 (colorimetry) 을이용한 ADVIA 1650 전자동임상화학분석기 (Bayer, Tarrytown, NY, USA) 를사용하여분석하였고, 저밀도지단백 (low density lipoptotein) 콜레스테롤은 ( 총콜레스테롤-[ 고밀도지단백콜레스테롤 + 중성지방 /5]) 로계산하였다. 3. 통계분석모든통계학적분석은 SPSS ver (SPSS Inc., Chicago, IL, USA) 통계패키지를이용하였다. QTc 간격을사분위로나누어신체계측치, 체성분구성, 혈액검사의평균값의차이가있는지알아보기위해일원배치분산분석 (one-way analysis of variance) 을이용하였고다중검정을위해 Tukey test를시행하였다. QTc 간격과상완-발목맥파속도및심혈관위험인자와의연관성을분석하기위해피어슨상관분석을실시하였다. 상완-발목맥파속도와 QTc 간격간의독립적인관련성을파악하기위해혼란변수인나이, 성별, 체질량지수, 허리엉덩이둘레, 수축기혈압, 총콜레스테롤, 고밀도지단백콜레스테롤, 중성지방, 공복혈당, 공복인슐린, C 반응단백을포함하여다중회귀분석을실시하였다. 통계학적인유의수준은 P값 0.05 미만으로하였다. 결과 1. 대상자의임상적특징연구대상자들은총 603명 (20-70세) 으로 Table 1은연구대상자들의일반적인특성, 신체계측및심혈관위험인자의차이를나타낸표이다. 성별은남자가 146명 (24.2%), 여자가 457 명 (75.8%) 이었고평균나이는 39.28±11.59세였다. 체질량지수는 24.27±4.71 kg/m 2 이었다. 평균맥파속도는 1,264.15± 이었고, QTc 간격의평균은 ±24.37 ms이었다. Table 1. Clinical characteristics. Value (n=603) Age (y) 39.28±11.59 Sex (male) (n, %) 146 (24.2) Anthropometry BMI (kg/m 2 ) 24.47±4.71 WHR 0.90±0.07 Waist circumference (cm) 92.34±12.14 Muscle mass (g) 25.75±6.03 Fat percent (%) 34.46±6.51 Metabolic variables SBP (mm Hg) ±15.18 DBP (mm Hg) 75.80±10.54 Total cholesterol (mg/dl) ±35.70 HDL-cholesterol (mg/dl) 51.62±12.88 Triglyceride (mg/dl) (16-647) Fasting glucose (mg/dl) 94.34±15.69 Fasting insulin (µiu/ml) 10.51±8.78 Hs-CRP (mg/l) 0.95 ( ) Life style Hypertension (n, %) 74 (13.4) Diabetes (n, %) 22 (3.6) Dyslipidemia (n, %) 32 (5.7) Smoking (n, %) 30 (5.9) Alcohol drinking (n, %) 75 (14.8) Mean pulse wave velocity* 1,264.15± QTc (ms) ±24.37 Values are presented as mean±sd or median (range). BMI: body mass index, WHR: waist-to-hip ratio, SBP: systolic blood pressure, DBP: diastolic blood pressure, HDL: high density lipoprotein, Hs-CRP: high-sensitivity C-reactive protein, QTc: corrected QT. *The mean index of arterial stiffness. Intervals were calculated from Bazett formula (QTc=QT/RR 1/2 ). 150 Vol. 2, No. 2 Jun 2012 Korean J Fam Pract

4 박성원외 : 동맥경직도와 QTc 간격과의관계 Table 2. Correlation between QTc interval and cardiovascular risk factors. QTc interval r P-value Age (y) <0.001 Anthropometry BMI (kg/m 2 ) WHR <0.001 Waist circumference (cm) Metabolic variables SBP (mm Hg) DBP (mm Hg) Total cholesterol (mg/dl) HDL-cholesterol (mg/dl) Triglyceride (mg/dl) Fasting glucose (mg/dl) <0.001 Fasting insulin (µiu/ml) Hs-CRP (mg/l) Mean pulse wave velocity* <0.001 Coefficients (r) and P-values are calculated by Pearson correlation model. QTc: corrected QT, BMI: body mass index, WHR: waist-to-hip ratio, SBP: systolic blood pressure, DBP: diastolic blood pressure, HDL: high density lipoprotein, Hs-CRP: high-sensitivity C-reactive protein. *The mean index of arterial stiffness. Table 3. Multiple regression analysis according to QTc interval. QTc interval β SE P-values* Age (y) Sex <0.001 BMI (kg/m 2 ) SBP (mm Hg) Total cholesterol (mg/dl) HDL-cholesterol (mg/dl) Triglyceride (mg/dl) Fasting glucose (mg/dl) Fasting insulin (µiu/ml) Hs-CRP (mg/l) Mean pulse wave velocity R 2 = QTc: corrected QT, BMI: body mass index, SBP: systolic blood pressure, HDL: high density lipoprotein, Hs-CRP: high-sensitivity C-reactive protein. *Calculated by multiple regression model using QTc interval as the dependent variable. Variables significantly associated with for QT interval (P<0.05) are shown in the table. The mean index of arterial stiffness. 슐린 (r=0.091, P=0.03) 과통계적으로유의한양의상관관계를나타내었다 (Table 2). 또한상완-발목맥파속도와 QTc 간격은유의한양의상관관계를나타냈다 (r=0.196, P<0.001) (Figure 1). 3. 상완-발목맥파속도와 QTc 간격과의독립적인연관성상완-발목맥파속도와 QTc 간격과의고유한관계를알아보기위하여나이, 성별, 체질량지수, 허리엉덩이둘레비, 수축기혈압, 총콜레스테롤, 고밀도지단백콜레스테롤, 중성지방, 공복혈당, 공복인슐린, C 반응단백을보정한후다중회귀분석을실시하였다. 혼란변수를보정한후에도 QTc 간격은상완- 발목맥파속도와독립적으로유의한양의연관성이있었다 (R 2 =0.154, P<0.01) (Table 3). 고찰 Figure 1. Correlation between QT interval and mean pulse wave velocity (PWV) (r=0.196, P<0.001). 본연구에서는세브란스병원가정의학과를내원한성인남녀를대상으로하였을때 QTc 간격은상완-발목맥파속도와독립적인양의상관관계가있었다. 즉심혈관질환과밀접 가정의학 Vol. 2, No. 2 Jun

5 Sung-Won Park, et al: Relationship between Arterial Stiffness and QTc Interval 한관련이있는동맥경직도가 7,8) 증가할수록 QTc 간격이증가하였고이는기존의연구결과와일치하는결과이다. 15) 최근무증상동맥질환의예측지표와 QTc 간격의연관성에대한관심이증가하고있는데 15,17-19) Maebuchi 등 15) 이심혈관질환이없는 2,666명을대상으로시행한 Hisayama Study에서는동맥경직도와 QTc 간격연장사이에양의상관관계가있으며독립적으로유의한양의연관성이있음을보고하였고 Festa 등 17) 은관상동맥질환이없는비당뇨인 912명을대상으로시행한 Insulin Resistance Atherosclerosis Study에서경동맥내막두께와 QTc 간격의밀접한관련성을보이며 QTc 간격이무증상동맥경화의예측인자임을보고하였다. Strohmer 등 18) 은 1,199명의건강한성인을대상으로 Salzburg Atherosclerosis Prevention Program 시행시남성에서경동맥내막두께와 QTc 간격간에독립적연관성이있음을보고하였다. QTc 간격의연장은건강한성인에서도기존역학조사및선행연구에서심혈관위험인자와밀접한관련이있으며 20) 심혈관질환의발생및사망위험을증가시킨다고알려져있다. 21,22) QTc 간격연장이심혈관질환의선행요인으로간주되는기전에대해서명확히알려져있지않지만지금까지의연구를살펴보면좌측교감신경활성도의우위성에의하거나심근막기능의결함에의한심실의전기적불안정성에기인한것이라는보고가있다. 23,24) 이처럼 QTc 간격은부정맥질환의선행현상으로많은연구들에서심인성급사의위험을증가시킨다고보고하고있다. 11,25) 상완-발목맥파속도는동맥경직도를대변하며혈관손상을반영하는표지자로최근에는상완-발목맥파속도가심혈관질환의이환률및사망률의강력한예측인자로알려져있다. 7) 또한상완-발목맥파속도가심혈관질환의초기단계평가인자로서유용하게사용될수있음이여러연구를통해알려졌는데, 8) 이러한상완-발목맥파속도와 QTc 간격의독립적인관련성은심전도를이용하여비교적일차진료에서측정이용이한 QTc 간격이증가할수록심혈관질환에대한주의를더욱기울여야함을의미한다. 동맥경직도가 QTc 간격을연장시키는기전에대해서는명확히밝혀져있지는않지만현재받아들여지는기전은무증상의동맥질환에서동맥경직도증가시심실의부하가증가되며이것이결과적으로심근의전기생리적리모델링을촉진하여 QTc 간격의연장을초래하는것과 26,27) 전신적인동맥질환과강한연관이있는관상동맥내진행된미세혈관동맥경화증이심내막하허혈로진행되어 QTc 간격이연장된다는이론이받아들여지고있다. 28) 본연구의제한점으로는첫째, 단면연구이기에동맥경직 도와 QTc 간격간의인과관계를정확히알수없고다른혼란변수를배제하지못하였을가능성이있다. 이에대해앞으로전향적인연구가필요하며, 병태생리학적기전을밝힐연구가필요할것으로생각된다. 둘째, 대상자의선정에있어세브란스병원가정의학과를내원한사람을대상으로하였기에선택편견이있을수있고한국성인으로일반화하기어려운점이있다. 셋째, QTc 간격에영향을주는칼륨, 나트륨, 마그네슘과같은혈중전해질농도를측정하지않았으나본연구대상자들의과거력조사시전해질이상을초래할질병을앓고있는대상자는없었다. 결론적으로본연구에서세브란스병원가정의학과를내원한성인남녀에서동맥경직도와 QTc 간격은유의한관련이있었으며동맥경직도가증가함에따라 QTc 간격도증가하는경향을보였다. 따라서심혈관질환의일차예방을위한효과적인전략으로향후일차진료에서 QTc 간격이연장된대상자는심혈관위험에대한고려가필요할것으로생각된다. 요약 연구배경 : 동맥경직도는동맥경화조기판별과심혈관질환예측의유용한도구로이용되며최근심전도상 corrected QT (QTc) 간격은여러심장질환과관련이있다고알려져있다. 본연구에서는세브란스병원가정의학과를내원하였으며심혈관질환이없는성인남녀를대상으로동맥경직도와 QTc 간격과의관련성을알아보고자하였다. 방법 : 성인남녀 603명 (39.28±11.59세) 을대상으로설문조사, 신체계측, 혈압측정및혈액검사를시행하였으며, 상완-발목맥파속도를측정하였고, QTc 간격은표준 12-유도심전도로부터측정되었다. 결과 : 피어슨상관분석을하였을때나이 (r=0.222, P<0.001), 체질량지수 (r=0.097, P=0.02), 허리엉덩이둘레비 (r=0.215, P<0.001), 공복혈당 (r=0.179, P<0.001), 공복인슐린 (r=0.091, P=0.03) 은 QTc 간격과통계적으로유의한양의상관관계를나타내었다. 상완-발목맥파속도와 QTc 간격은유의한양의상관관계를나타냈다 (r=0.196, P<0.001). 나이, 성별, 체질량지수, 수축기혈압, 총콜레스테롤, 고밀도지단백콜레스테롤, 중성지방, 공복혈당, 공복인슐린, C 반응단백을보정한후다중회귀분석을하였을때 QTc 간격은상완-발목맥파속도와독립적으로유의한양의연관성이있었다 (P<0.01). 결론 : 동맥경직도와 QTc 간격은유의한관련성이있었으며동맥경직도가증가함에따라 QTc 간격도연장되는경향을보였다. 심혈관질환의일차예방을위한효과적인전략으로향 152 Vol. 2, No. 2 Jun 2012 Korean J Fam Pract

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