대한폐경학회지제 16 권제 2 호 2010 Vol. 16, No. 2, August. 2010 폐경전후여성에서상완 - 발목맥파속도에영향을미치는요인의비교 연세대학교의과대학세브란스병원산부인과학교실 1, 강남세브란스병원산부인과학교실 2 정찬경 1 ㆍ윤보현 1 ㆍ서석교 1 ㆍ임경진 1 ㆍ전영은 2 ㆍ양효인 1 ㆍ이경은 2 ㆍ조시현 2 ㆍ최영식 1 ㆍ이병석 2 =Abstract= Comparison of Factors Which Influence the Brachial-Ankle Pulse Wave Velocity in Pre- and Postmenopausal Women Chan Kyung Chung, M.D. 1, Bo Hyon Yun, M.D. 1, Seok Kyo Seo, M.D. 1, Kyung Jin Lim, M.D. 1, Young Eun Jeon, M.D. 2, Hyo In Yang, M.D. 1, Kyung Eun Lee, M.D. 2, SiHyun Cho, M.D. 2, Young Sik Choi, M.D. 1, Byung Seok Lee, M.D. 2 Department of Obstetrics and Gynecology, 1 Severance Hospital, 2 Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea Objectives: The aim of this study was to compare the factors which influence the brachial-ankle pulse wave velocity (bapwv) in pre- and post-menopausal women. We also investigated the association of menopause with arterial stiffness measured by bapwv. Methods: We performed a retrospective review of 241 postmenopausal women who attended the health promotion center for a routine checkup. Simple and multiple regression analyses were performed to determine the parameters influencing bapwv in preand postmenopausal women. Multiple logistic regression analysis was performed to identify the independent parameters related to increased of arterial stiffness. Results: Multiple regression analysis showed that diastolic blood pressure (DBP; β = 0.402, P = 0.009) was identified as an independent determinant for bapwv in premenopausal women, and DBP (β = 0.329, P = 0.021) and the neutrophil-to-lymphocyte ratio (NLR; β = 0.210, P = 0.016) were identified as independent determinants for bapwv in postmenopausal women. The odds ratio (95% CI) of menopause for a high bapwv was 2.666 (1.025 6.937). Conclusion: The NLR is associated with arterial stiffness in postmenopausal women. Consequently, inflammation is thought to play a crucial role in increased arterial stiffness in postmenopausal women. Menopause is associated with a high bapwv, suggesting that changes in the concentrations of sex hormones during the menopausal transition may influence arterial stiffness in clinically healthy women. (J Korean Soc Menopause 2010;16:86-92) Key Words: Arterial stiffness, Brachial-ankle pulse wave velocity, Premenopausal women, Postmenopausal women 수축기혈압, 이완기혈압, 맥압 ( 수축기혈압과이완기혈압의차이 ) 등은나이가들어감에따라변화하는데, 수축기혈압과맥압은큰동맥경직도 (arterial stiffness) 에의하여더영향을받으며나이가많아짐에따라증가한다. 1 수축기혈압은 60 세이상의노인에서관상동맥질환의발생을예측하는데이완기혈압보다더우수한것으로알려져있으며, 최근에는상승되어있는수축기혈압보다증가된맥압이더욱중요한위험인 자라는것이보고되고있으므로, 맥압의결정에중요한역할을하는동맥경직도의중요성이강조되고있다. 2 따라서심혈관질환의위험도를측정하기위하여동맥의경직도를평가하는것이임상적으로유용하며, 아직까지명확하게알려져있지않으나동맥의경직도를호전시키는것이심혈관질환의위험도를감소시킬것으로기대된다. 혈관손상이일어나면동맥의신전성과경직도가변화하게 접수일 : 2010 년 6 월 30 일, 심사일 : 2010 년 7 월 13 일, 게재확정일 : 2010 년 7 월 13 일주관책임자 : 이병석, 우 ) 135-720 서울시강남구도곡동 146-92, 연세대학교의과대학강남세브란스병원산부인과학교실 Tel: (02) 2019-3435, Fax: (02) 2019-8209, e-mail: dr222@yuhs.ac -86-
정찬경외 되는데맥파속도 (pulse wave velocity, PWV) 는이변화를반영하는지표이다. 3 맥파속도의증가는동맥의경직도를증가시키고, 이는심실에부담을주어심박출량을감소시키고심근의산소요구량을증가시키며동맥경화증을촉진시킨다. 4 고전적인방법으로는경동맥-대퇴동맥맥파속도 (carotid-femoral PWV, cfpwv) 가많이쓰이지만이는경동맥과대퇴동맥에탐촉자 (transducer) 를정확하게고정하여야하기때문에측정시간이많이걸리며, 침습적이고재현성 (reproducibility) 이낮다. 이러한문제점을보완한검사방법으로상완- 발목맥파속도 (brachia-lankle PWV, bapwv) 를측정하는방법이개발되었으며, 측정방법이상대적으로용이하고비교적짧은시간에측정할수있으므로대규모선별검사에보다적합한것으로알려지고있다. 또한상완-발목맥파속도의측정이타당성 (validity) 과재현성이높으며혈관손상을반영하는지표로적합하다고보고되기도하였다. 3 관상동맥질환은폐경기여성에서주된사망원인으로알려져있으며, 5 폐경이되면심혈관질환의위험성이 2 3배로증가된다. 6,7 또한폐경이전에양측난소절제술을받은여성에서도관상동맥질환의발병위험이증가된다. 8 따라서폐경기여성에서심혈관질환의발생을예방하고고위험군을선별, 관리하기위해서는동맥경직도와관련된요인들을파악하고폐경전여성과의비교분석이중요할것으로사료된다. 이에저자들은 45 56세사이의폐경전후여성을대상으로상완-발목맥파속도에영향을미치는요인을비교분석하고자하였다. 또한폐경이동맥경직도의증가에독립적인영향을미치는인자인지파악하고자하였다. 연구대상및방법 1. 연구대상 2008년 1월부터 2009년 6월까지강남세브란스병원건강증진센터에내원하여건강검진을받은여성중 45세이상이고 56세미만이면서상완- 발목맥파속도를측정한수검자를대상으로하였으며의무기록을바탕으로후향적으로연구하였다. 모든대상자는자기기입설문지를통하여흡연및음주상태, 과거병력, 현재병력, 복용약물등을기록하였으며신체계측으로는신장과체중을측정하였고, 체질량지수 (body mass index, BMI) 는체중 (kg) 을신장제곱 (m 2 ) 으로나누어계산하였다. 혈압은대상자가최소 10분이상안정을하도록한후, 앉은자세에서자동혈압측정기를이용하여두번측정하였고, 측정한혈압의평균값을취하였다. 폐경은마지막생리후 1년이상경과하였고혈청난포자극호르몬 (follicular stimulating hormone, FSH) 의농도가 40 miu/ml 이상인경우로정의하였다. 모든연구대상자들은비흡연자였고최근 6개월이내에호르몬치료를받은과거력이없었다. 고혈압, 당뇨, 고지혈증, 갑상선질환등상완- 발목맥파속도에영향을줄수있는질병으로치료받고있는여성들은제외하였다. 2. 혈액검사혈액검사를위한채혈은검사전최소 12시간이상금식을하도록한후, 검사당일오전에전주정맥 (antecubital vein) 에서시행하였다. 백혈구감별검사 (white blood cell differential count) 는자동혈구분석기 (ADIVA R 120 Hematology System [Bayer Coporation, Terrytown, NY, USA]) 를이용하여측정하였고, 호중구-림프구비 (neutrophil to lymphocyte ratio, NLR) 는절대호중구수를절대림프구수로나눈값으로정의하였다. 공복혈당, 총콜레스테롤 (total cholesterol), 고밀도지단백콜레스테롤 (high density lipoprotein cholesterol, HDL-C), 저밀도지단백콜레스테롤 (low density lipoprotein cholesterol, LDL-C), 중성지방 (triglyceride, TG), 요산 (uric acid) 등은 7600-110 Chemistry Autoanalyzer (Hitachi, Tokyo, Japan) 을사용하여측정하였다. 3. 상완-발목맥파속도측정상완- 발목맥파속도는누운자세로최소 10분이상안정후자동파형분석기 (model BP-203RPE; [Colin, Komaki, Japan]) 를사용하여측정하였다. 맥파속도를결정하는시간간격 ( T) 은상완과발목의맥파가컴퓨터에의해자동으로해석된후두지점간의시간차가측정되었고, 흉골하패임 (substernal notch) 에서상완의길이 (Lb = 0.2195 대상자의키 ) 와흉골하패임에서발목까지의거리 (La = 0.8129 대상자의키 ) 는대상자의키 (cm) 를근거로하여자동으로계산되었다. 상완- 발목맥파속도는맥파가진행한거리 (La Lb) 를맥파의전파시간 ( T) 으로나누어산출하였으며, 우측상완-발목맥파속도와좌측상완- 발목맥파속도의평균값을취하였다. 4. 통계분석폐경전후여성의일반적특성은평균표준편차로표시하였고, 이들특성의차이는 T-검정을이용하여분석하였다. 폐경전후여성에서상완- 발목맥파속도와다른변수들간의관련성을알아보기위해단순회귀분석과다중회귀분석을시행하였다. 폐경이상완- 발목맥파속도의증가에미치는영향을알아보기위하여로지스틱회귀분석을시행하였다. 분석에사용한프로그램은 SPSS 15.0 (SPSS Inc., Chicago, IL, USA) 이었고, 통계적유의수준은 0.05 미만으로하였다. -87-
폐경전후여성에서상완 - 발목맥파속도 결 과 3. 폐경후여성에서상완-발목맥파속도에영향을미치는요인분석 1. 대상자의일반적인특성전체대상자 241명중, 폐경전여성이 100명 (41.5%), 폐경여성은 141명 (58.5%) 으로, 이들의평균연령은각각 48.07 ± 2.33세와 51.90 ± 2.58세이었다. 폐경여성은폐경전여성에비해체질량지수, 백혈구수, 호중구 -림프구비, 총콜레스테롤, 저밀도지단백콜레스테롤, 중성지방, 요산, alkaline phosphatase (ALP), Gamma-glutamyltransferase (r-gt), 상완-발목맥파속도등의수치가유의하게높았다 (Table 1). 2. 폐경전여성에서상완-발목맥파속도에영향을미치는요인분석단순회귀분석에서는체질량지수, 수축기혈압, 이완기혈압, 백혈구수, 호중구-림프구비, C-reactive protein (CRP), 공복혈당, 중성지방, ALP 등이상완- 발목맥파속도와통계적으로유의한연관성이있었으며, 중회귀분석에서는이완기혈압이상완-발목맥파속도와통계적으로유의한연관성이있었다 (Table 2). 단순회귀분석에서는수축기혈압, 이완기혈압, 백혈구수, 호중구- 림프구비, CRP, 공복혈당, 총콜레스테롤, 요산, r-gt 등이상완 -발목맥파속도와통계적으로유의한연관성이있었으며, 중회귀분석에서는이완기혈압과호중구-림프구비가상완-발목맥파속도와통계적으로유의한연관성이있었다 (Table 3). 4. 폐경이상완-발목맥파속도의증가에미치는영향분석로지스틱회귀분석에서이완기혈압 (OR = 1.112; 95% CI 1.034 1.197), 공복혈당 (OR = 1.034; 95% CI 1.000 1.069), 폐경 (OR = 2.666; 95% CI 1.025 6.937) 이증가된상완- 발목맥파속도 (bapwv > 1,300 cm/s) 와통계학적으로유의한연관성을보였다 (Table 4). 고찰본연구는폐경전후여성에서상완- 발목맥파속도에영향을미치는요인이다르다는것을보여주었으며, 특히염증지표로사용한호중구-림프구비가폐경후여성에서상완-발목맥 Table 1. General characteristics of the study participants Pre-menopausal women (n = 100) Post-menopausal women (n = 141) Total (n = 241) Age (y)* 48.07 ± 2.33 51.90 ± 2.58 50.31 ± 3.11 BMI (kg/m 2 )* 21.71 ± 2.25 22.18 ± 2.40 21.99 ± 2.35 SBP (mmhg) 112.65 ± 13.64 116.04 ± 16.88 114.63 ± 15.68 DBP (mmhg) 70.53 ± 9.08 72.41 ± 10.21 71.63 ± 9.78 WBC count (10 3 /μl)* 5.46 ± 1.72 4.99 ± 1.43 5.18 ± 1.57 NLR* 1.83 ± 0.75 2.22 ± 1.07 1.99 ± 0.92 CRP (mg/l) 1.08 ± 2.13 1.35 ± 2.45 1.24 ± 2.32 Glucose (mg/dl) 87.50 ± 13.61 90.39 ± 10.92 89.19 ± 12.17 Total cholesterol (mg/dl)* 189.42 ± 29.38 208.94 ± 31.27 200.84 ± 31.93 HDL-cholesterol (mg/dl) 60.38 ± 11.86 58.63 ± 12.68 59.35 ± 12.36 LDL-cholesterol (mg/dl)* 117.37 ± 28.87 133.64 ± 30.62 126.89 ± 30.91 Triglycerides (mg/dl)* 81.97 ± 41.81 95.18 ± 51.50 89.70 ± 48.07 Uric acid (mg/dl)* 4.12 ± 0.77 4.46 ± 0.92 4.32 ± 0.88 ALP (IU/L)* 47.44 ± 13.18 67.29 ± 22.14 59.05 ± 21.30 r-gt (IU/L)* 17.95 ± 12.99 31.63 ± 79.22 25.95 ± 61.45 bapwv (cm/s)* 1,253.08 ± 128.75 1,313.59 ± 155.04 1,288.48 ± 147.48 *P < 0.05, Data are expressed as the mean ± standard deviation, BMI: body mass index, SBP: systolic blood pressure, DBP: diastolic blood pressure, WBC: white blood cell, NLR: neutrophil-to-lymphocyte ratio, CRP: C-reactive protein, HDL: high-density lipoprotein, LDL: low-density lipoprotein, ALP: alkaline phosphatase, r-gt: gamma-glutamyl transpeptidase, bapwv: brachial-ankle pulse wave velocity -88-
정찬경외 Table 2. Simple and multiple regression analysis for bapwv in pre-menopausal women Simple regression Multiple regression β P value β P value Age (y) 0.145 0.150 BMI (kg/m 2 ) 0.203 0.043 0.078 0.370 SBP (mmhg) 0.630 < 0.001 0.209 0.199 DBP (mmhg) 0.640 < 0.001 0.402 0.009 WBC count (10 3 /μl) 0.325 0.001 0.149 0.206 NLR 0.234 0.019 0.067 0.557 CRP (mg/l) 0.262 0.008 0.013 0.883 Glucose (mg/dl) 0.284 0.004 0.082 0.359 Total cholesterol (mg/dl) 0.147 0.145 HDL-cholesterol (mg/dl) 0.191 0.057 LDL-cholesterol (mg/dl) 0.156 0.121 Triglycerides (mg/dl) 0.349 < 0.001 0.065 0.534 Uric acid (mg/dl) 0.026 0.795 ALP (IU/L) 0.200 0.046 0.081 0.314 r-gt (IU/L) 0.136 0.179 R square = 0.503 in multiple regression analysis, BMI: body mass index, SBP: systolic blood pressure, DBP: diastolic blood pressure, WBC: white blood cell, NLR: neutrophil-to-lymphocyte ratio, CRP: C-reactive protein, HDL: high-density lipoprotein, LDL: low-density lipoprotein, ALP: alkaline phosphatase, r-gt: gamma-glutamyl transpeptidase, bapwv: brachial-ankle pulse wave velocity Table 3. Simple and multiple regression analysis for bapwv in post-menopausal women Simple regression Multiple regression β P value β P value Age (y) 0.130 0.125 BMI (kg/m 2 ) 0.033 0.698 SBP (mmhg) 0.541 < 0.001 0.183 0.206 DBP (mmhg) 0.556 < 0.001 0.329 0.021 WBC count (10 3 /μl) 0.236 0.005 0.020 0.821 NLR 0.269 0.001 0.210 0.016 CRP (mg/l) 0.216 0.010 0.063 0.408 Glucose (mg/dl) 0.332 < 0.001 0.092 0.237 Total cholesterol (mg/dl) 0.168 0.047 0.095 0.174 HDL-cholesterol (mg/dl) 0.065 0.447 LDL-cholesterol (mg/dl) 0.163 0.053 Triglycerides (mg/dl) 0.129 0.126 Uric acid (mg/dl) 0.227 0.007 0.098 0.174 ALP (IU/L) 0.116 0.171 r-gt (IU/L) 0.181 0.031 0.022 0.776 R square = 0.429 in multiple regression analysis, BMI: body mass index, SBP: systolic blood pressure, DBP: diastolic blood pressure, WBC: white blood cell, NLR: neutrophil-to-lymphocyte ratio, CRP: C-reactive protein, HDL: high-density lipoprotein, LDL: low-density lipoprotein, ALP: alkaline phosphatase, r-gt: gamma-glutamyl transpeptidase, bapwv: brachial-ankle pulse wave velocity 파속도와양의상관관계가있음을보여주었다. 또한폐경이상완-발목맥파속도의증가에독립적인영향을미치는것을증명하였는데이는폐경과심혈관질환이밀접한관련이있음을 시사한다. 맥파속도와심혈관질환과의관련성에관한많은연구들은대부분중심대동맥의맥파속도, 특히경동맥-대퇴동맥맥파속 -89-
폐경전후여성에서상완 - 발목맥파속도 Table 4. Multiple logistic regression analysis for prediction of high pulse-wave velocity (bapwv > 1,300 cm/s) OR 95% CI P value Age (y) 0.967 0.843 1.110 0.636 SBP (mmhg) 1.007 0.963 1.053 0.746 DBP (mmhg) 1.112 1.034 1.197 0.004 WBC count (10 3 /μl) 1.000 1.000 1.001 0.060 NLR 1.200 0.743 1.939 0.457 CRP (mg/l) 1.046 0.898 1.218 0.566 Glucose (mg/dl) 1.034 1.000 1.069 0.047 HDL-cholesterol (mg/dl) 1.001 0.971 1.033 0.938 Triglycerides (mg/dl) 1.001 0.992 1.010 0.851 Uric acid (mg/dl) 1.338 0.875 2.044 0.179 ALP (IU/L) 1.012 0.994 1.030 0.190 Menopause 2.666 1.025 6.937 0.044 SBP: systolic blood pressure, DBP: diastolic blood pressure, WBC: white blood cell, NLR: neutrophil-to-lymphocyte ratio, CRP: C-reactive protein, HDL: high-density lipoprotein, ALP: alkaline phosphatase 도를측정하여이루어졌다. 그러나경동맥- 대퇴동맥맥파속도는일반인구집단에서선별검사로이용하는것은제한이있다. 이는계측이번거롭고기술이요구되며측정의재현성이낮다. 또한맥파속도의측정값에큰영향을주는혈압을동시에측정하지못하는단점이있다. 본연구에서사용된상완- 발목맥파속도는이를보완하기위하여최근널리보급되고있는방법으로말초혈관도포함하여계측하기때문에경동맥- 대퇴동맥맥파속도와병태생리학적의의가다를가능성도있지만측정의재현성이좋으며관혈적으로측정한대동맥맥파속도의측정과도상관관계가높아서동맥경직도의지표로많이사용되고있다. 3 동맥경직도는나이뿐만아니라비만, 고혈압, 대사증후군, 당뇨, 고콜레스테롤혈증등기타다른심혈관계위험인자와독립적으로연관이되어있다는것이알려져있다. 9,10 Tomiyama 등은 CRP의증가가동맥경직도의증가와연관성이있음을보고하였고이등은백혈구수 (white blood cell count, WBC count) 의증가가동맥경직도의증가와연관성이있음을보고하였는데이는동맥경직도의증가에염증반응이관여함을의미한다. 11,12 하지만이두연구모두동맥경직도와염증지표사이에통계학적으로유의한상관관계가있음을보여주지는못했다. 본연구의경우염증지표로백혈구수, CRP, 호중구- 림프구비를사용하였는데단순회귀분석에서는폐경전후여성에서모든염증지표가동맥경직도와통계학적으로유의한상관관계를보였으며, 중회귀분석에서는폐경여성에서만호중구- 림프구비가동맥경직도와통계학적으로유의한상관관계를보였다. 이러한결과는동맥경직도와염증반응의관련성 을의미하며, 특히폐경후여성에서염증반응이동맥경직도의증가에보다중요한역할을할것으로추측할수있다. 호중구-림프구비는이미혈관의염증반응을반영하는지표로알려져있으며, 최근연구에의하면심혈관질환의발생과사망률의유용한예측인자로보고되고있다. 13,14 또한호중구 -림프구비는통상적으로시행하는백혈구수측정시쉽게얻을수있으며저렴하다는장점이있다. 따라서폐경여성에서동맥경직도와함께호중구- 림프구비를측정하는것은심혈관질환을예측하는평가도구로써유용할것으로사료된다. 한편 40세이상의전체폐경여성을대상으로한이전연구에서는호중구-림프구비뿐만아니라나이도동맥경직도와통계학적으로유의한상관관계를보였지만, 15 45 56세를대상으로한본연구에서는나이와동맥경직도사이에는뚜렷한상관관계를보이지않았다. 일반적으로노화 (aging) 는탄성섬유 (elastic fiber) 의변성을일으키며결과적으로점진적인동맥의경직을일으키게되며, 이렇게증가된동맥경직도는나이와연관된맥파속도의증가와밀접하게연관된다. 16 여성호르몬의항죽종형성효과는혈관에대한직접적인효과가주된작용을하고, 부가적으로혈액응고와혈전용해기전, 항산화기전, 혈관활성화물질 (vasoactive molecules), 전구염증성사이토카인 (proinflammatotory cytokines) 등이관련된다고알려져있는데, 폐경주변기에여성호르몬이감소하면서이러한효과가소실되고나이보다동맥경직도에더많은영향을미치기때문에본연구와같은결과가나타난것으로추측된다. 죽상동맥경화증 (atherosclerosis) 은혈관벽손상에대한일련의염증반응으로, 조직학적으로는혈관벽내에지방선조 (fatty streak) 로시작해서지질및괴사조직으로이루어진핵 (core of lipid and necrotic tissue) 과이를덮는섬유성모자 (fibrous cap) 를갖는동맥경화반 (atherosclerotic plaque) 을형성하게되며, 혈관경직도가증가하고맥파속도도증가한다. 따라서염증반응이죽상동맥경화증의진행과동맥경직도의증가에중요한역할을한다고볼수있다. Booth 등은염증반응이증가함에따라혈관내피세포의기능부전이증가하고혈관내피세포에서분비되는산화질소 (nitric oxide) 가감소하여동맥경직도를증가시킨다고보고하였는데, 이는염증반응이동맥경직도를증가시키는가설을뒷받침하는연구로볼수있다. 17 또한만성염증성질환인류마티스관절염과전신홍반루푸스환자에서동맥경직도가증가한다는연구가보고되었는데, 이또한염증반응과동맥경직도의연관성을뒷받침하는증거라할수있다. 맥파속도의상승은동맥경화의진전, 혈관의노화를나타내며심혈관질환이나총사망률의예측인자로알려져있는데, 심혈관질환의고위험군에서동맥맥파속도를측정하는것은동맥경화를조기에판별할수있는새로운지표로유용하 -90-
정찬경외 다. 18,19 Yamashina 등은상완-발목맥파속도 (bapwv) 값이 1,400 cm/s 이상인경우 Framingham score에의한심혈관위험도예측에서독립적인예측인자로보고하였으며, 20 Boutouyire 등은상완 -발목맥파속도값이 1,300 cm/s 이상이면관상동맥질환의위험이약 40% 증가한다고언급하였다. 21 관상동맥질환에는여러가지위험인자가관여하고있으나폐경은여성에서만의독특한위험인자로폐경여성의경우관상동맥질환의위험성은 3배이상증가한다. 본연구에서도폐경이상완-발목맥파속도의증가 (bapwv > 1,300 cm/s) 에독립적인영향인자임을보여주었으며이러한결과는폐경이관상동맥질환의위험인자임을간접적으로증명한다고볼수있다. 또한비침습적인방법으로측정되는상완-발목맥파속도가선별검사에서초기단계의죽상동맥경화증을찾아내는데유용할수있음을시사한다. 실제로본연구진은폐경여성에서상완- 발목맥파속도의증가 (bapwv > 1,500 cm/s) 가죽상동맥경화증의선별검사로유용할수있음을보고한바가있다. 15 본연구는종합병원에건강검진을받으러온여성들을대상으로하였기때문에이번연구에포함된여성을폐경전후여성들의특징으로일반화시키기에는제한이있으며, 후향적단면연구로인과관계를정확히파악할수없기때문에향후전향적연구가필요할것으로생각된다. 또한동맥경직도와연관성이있다고알려진운동과같은생활습관에대한고려가이루어지지않았다는단점이있다. 그럼에도불구하고본연구는폐경전후여성을대상으로심혈관질환의발생이나사망률과연관성이있다고알려진상완-발목맥파속도에미치는요인을비교분석한최초의연구이며, 폐경여성에서염증반응이동맥경직도의증가와관련성이있음을증명하였다. 또한폐경이동맥경직도의증가에영향을미치는독립적인인자라는결과도도출하였다. 따라서폐경여성의경우에스트로겐의결핍으로인하여염증반응이증가하고동맥경직도가증가하는데이러한현상이심혈관질환의위험도를높이는하나의원인이될수있다고추측할수있다. 향후호르몬치료가염증반응과동맥경직도에미치는영향에대한전향적연구가필요할것으로생각되며, 이러한연구가폐경여성의삶의질과건강의향상에도움이될것으로생각된다. 참고문헌 1. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. The Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 2003; 289: 2560-72. 2. Franklin SS, Larson MG, Khan SA, Wong ND, Leip EP, Kannel WB, et al. Does the relation of blood pressure to coronary heart disease risk change with aging? The Framingham Heart Study. Circulation 2001; 103: 1245-9. 3. Yamashina A, Tomiyama H, Takeda K, Tsuda H, Arai T, Hirose K, et al. Validity, reproducibility, and clinical significance of noninvasive brachial-ankle pulse wave velocity measurement. Hypertens Res 2002; 25: 359-64. 4. London GM, Guerin AP, Marchais SJ, Pannier B, Safar ME, Day M, et al. Cardiac and arterial interactions in end-stage renal disease. Kidney Int 1996; 50: 600-8. 5. Johansson S, Vedin A, Wilhelmsson C. Myocardial infarction in women. Epidemiol Rev 1983; 5: 67-95. 6. Kannel WB, Hjortland MC, McNamara PM, Gordon T. Menopause and risk of cardiovascular disease: the Framingham study. Ann Intern Med 1976; 85: 447-52. 7. Colditz GA, Willett WC, Stampfer MJ, Rosner B, Speizer FE, Hennekens CH. Menopause and the risk of coronary heart disease in women. N Engl J Med 1987; 316: 1105-10. 8. Stampfer MJ, Colditz GA, Willett WC. Menopause and heart disease. A review. Ann N Y Acad Sci 1990; 592: 193-203. 9. Nakamura U, Iwase M, Nohara S, Kanai H, Ichikawa K, Iida M. Usefulness of brachial-ankle pulse wave velocity measurement: correlation with abdominal aortic calcification. Hypertens Res 2003; 26: 163-7. 10. Suzuki E, Kashiwagi A, Nishio Y, Egawa K, Shimizu S, Maegawa H, et al. Increased arterial wall stiffness limits flow volume in the lower extremities in type 2 diabetic patients. Diabetes Care 2001; 24: 2107-14. 11. Tomiyama H, Arai T, Koji Y, Yambe M, Hirayama Y, Yamamoto Y, et al. The relationship between high-sensitive C-reactive protein and pulse wave velocity in healthy Japanese men. Atherosclerosis 2004; 174: 373-7. 12. Lee YJ, Lee JW, Kim JK, Lee JH, Kim JH, Kwon KY, et al. Elevated white blood cell count is associated with arterial stiffness. Nutr Metab Cardiovasc Dis 2009; 19: 3-7. 13. Margolis KL, Manson JE, Greenland P, Rodabough RJ, Bray PF, Safford M, et al. Leukocyte count as a predictor of cardiovascular events and mortality in postmenopausal women: the Women's Health Initiative Observational Study. Arch Intern Med 2005; 165: 500-8. 14. Tamhane UU, Aneja S, Montgomery D, Rogers EK, Eagle KA, Gurm HS. Association between admission neutrophil to lym- -91-
폐경전후여성에서상완 - 발목맥파속도 phocyte ratio and outcomes in patients with acute coronary syndrome. Am J Cardiol 2008; 102: 653-7. 15. Seo SK, Cho S, Kim HY, Choi YS, Park KH, Cho DJ, et al. Bone mineral density, arterial stiffness, and coronary atherosclerosis in healthy postmenopausal women. Menopause 2009; 16: 937-43. 16. Asmar R, Benetos A, London G, Hugue C, Weiss Y, Topouchian J, et al. Aortic distensibility in normotensive, untreated and treated hypertensive patients. Blood Press 1995; 4: 48-54. 17. Booth AD, Wallace S, McEniery CM, Yasmin, Brown J, Jayne DR, et al. Inflammation and arterial stiffness in systemic vasculitis: a model of vascular inflammation. Arthritis Rheum 2004; 50: 581-8. 18. Amar J, Ruidavets JB, Chamontin B, Drouet L, Ferrieres J. Arterial stiffness and cardiovascular risk factors in a population-based study. J Hypertens 2001; 19: 381-7. 19. van Popele NM, Grobbee DE, Bots ML, Asmar R, Topouchian J, Reneman RS, et al. Association between arterial stiffness and atherosclerosis: the Rotterdam Study. Stroke 2001; 32: 454-60. 20. Yamashina A, Tomiyama H, Arai T, Hirose K, Koji Y, Hirayama Y, et al. Brachial-ankle pulse wave velocity as a marker of atherosclerotic vascular damage and cardiovascular risk. Hypertens Res 2003; 26: 615-22. 21. Boutouyrie P, Tropeano AI, Asmar R, Gautier I, Benetos A, Lacolley P, et al. Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: a longitudinal study. Hypertension 2002; 39: 10-5. = 국문초록 = 연구목적 : 본연구는 45 56세사이의폐경전후여성을대상으로상완- 발목맥파속도에영향을미치는요인을비교분석하고자하였다. 또한폐경과동맥경직도와의연관성을알아보고자하였다. 연구재료및방법 : 2008년 1월부터 2009년 6월까지강남세브란스병원건강증진센터에내원하여건강검진을받은여성중 45세이상이고 56세미만이면서상완- 발목맥파속도를측정한수검자를대상으로하였으며의무기록을바탕으로후향적으로연구하였다. 폐경전후여성에서상완- 발목맥파속도와다른변수들간의관련성을알아보기위해단순회귀분석과다중회귀분석을시행하였으며, 폐경이상완-발목맥파속도의증가에미치는영향을알아보기위하여로지스틱회귀분석을시행하였다. 결과 : 단순회귀분석및다중회귀분석에서폐경전여성의경우이완기혈압 (β = 0.402, P = 0.009) 이통계학적으로유의한연관성을보였으며, 폐경여성의경우이완기혈압 (β = 0.329, P = 0.021) 과호중구- 림프구비 (β = 0.210, P = 0.016) 가통계학적으로유의한연관성을보였다. 이완기혈압 (OR = 1.112; 95% CI 1.034 1.197), 공복혈당 (OR = 1.034; 95% CI 1.000 1.069), 폐경 (OR = 2.666; 95% CI 1.025 6.937) 이증가된상완- 발목맥파속도 (bapwv > 1,300 cm/s) 와통계학적으로유의한연관성을보였다. 결론 : 폐경전후여성에서상완 -발목맥파속도에영향을미치는요인이다르며, 특히폐경여성의경우염증반응이상완-발목맥파속도와뚜렷한연관성이있었다. 또한폐경이상완-발목맥파속도를증가시키는독립적인인자였으며, 이는폐경이행기의호르몬변화가상완- 발목맥파속도에영향을미치는것으로생각된다. 중심단어 : 동맥경직도, 상완 - 발목맥파속도, 폐경전여성, 폐경후여성 -92-