대한내과학회지 : 제 91 권제 2 호 2016 http://dx.doi.org/10.3904/kjm.2016.91.2.158 한국인중년여성급성심근경색증환자의임상경과에대한나이의영향-55세를기준으로 1 전남대학교병원심장센터, 2 보건복지부지정심장질환특성화연구센터, 3 전남대학교의과대학예방의학교실, 4 전남대학교간호대학 오미숙 1,2 정명호 1,2 이승헌 1,2 이정애 3 최진수 3 박인혜 4 김청 1,2 김은정 1,2 국현이 1,2 이기홍 1,2 심두선 1,2 김계훈 1,2 홍영준 1,2 박형욱 1,2 김주한 1,2 안영근 1,2 조정관 1,2 박종춘 1,2 김상형 1,2 Impact of Age on Clinical Outcomes in Middle-aged Korean Female Patients with Acute Myocardial Infarction - Based on a Cut-off Age of 55 Years Mi Sook Oh 1,2, Myung Ho Jeong 1,2, Seung Hun Lee 1,2, Jung Ae Rhee 3, Jin Su Choi 3, In Hyae Park 4, Chung Kim 1,2, Eun Jung Kim 1,2, Hyun Yi Kook 1,2, Ki Hong Lee 1,2, Doo Sun Sim 1,2, Kye Hun Kim 1,2, Young Joon Hong 1,2, Hyung Wook Park 1,2, Ju Han Kim 1,2, Young keun Ahn 1,2, Jeong Gwan Cho 1,2, Jong Chun Park 1,2, and Sang Hyung Kim 1,2 1 The Heart Center of Chonnam National University Hospital, 2 The Heart Research Center Designated by Korea Ministry of Health and Welfare, 3 Department of Preventive Medicine, Chonnam National University Medical School, 4 Chonnam National University College of Nursing, Gwangju, Korea Background/Aims: It is well known that the menopause is related to interference in lipid metabolism, obesity, and a hypercoagulable state. The aim of the present study was to examine the impact of the menopause in middle-aged Korean females with acute myocardial infarction (AMI). Methods: A total of 1,781 middle-aged females (aged < 65 years) in the Korean Acute Myocardial Infarction registry were enrolled into this study between November 2005 and December 2013. The patients were divided into two groups; the pre-menopause group ( 55 years old) and the menopause group (56-64 years old). Major adverse cardiac events (MACE) were analyzed over a one-year follow-up period. Results: The pre-menopause and menopause groups comprised 669 patients (mean age, 49.1 ± 5.6 years) and 1,112 patients (mean age, 60.6 ± 2.6 years), respectively. The incidence of hypertension (42.2% vs. 59.4%, p < 0.001), diabetes mellitus (DM) (27.4% vs. 35.7%, p < 0.001), and dyslipidemia (12.9% vs. 17.7%, p = 0.008) were more frequent in menopausal patients. Additionally, the Received: 2015. 10. 26 Revised: 2016. 5. 9 Accepted: 2016. 8. 2 Correspondence to Myung Ho Jeong, M.D., Ph.D., FACC, FAHA, FESC, FSCAI, FAPSIC The Heart Research Center of Chonnam National University Hospital, 42 Jaebong-ro, Dong-gu, Gwangju 61469, Korea Tel: +82-62-220-6243, Fax: +82-62-228-7174, E-mail: myungho@chollian.net, mhjeong@chonnam.ac.kr * This study was supported by grant of The Korean Health Technology R&D Project, Ministry of Health & Welfare (HI13C1527), Korea. Copyright c 2016 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution - 158 - Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Mi Sook Oh, et al. Menopause in acute myocardial infarction - rates of smoking (20% vs. 12.7%, p < 0.001) and familial history (12% vs. 6.8%, p < 0.001) were higher in the pre-menopause group. The cumulative rates of MACE did not show any differences between the two groups. A history of atrial fibrillation, previous AMI and DM, higher Killip class, and multi-vessel disease were independent risk factors for predicting one-year MACE. Conclusions: The survival analysis demonstrated that there was no significant difference in MACE rates between the pre-menopause and menopause groups during the one-year follow-up. Therefore, middle-aged pre-menopausal women should be treated more intensively, regardless of whether they are menopausal. (Korean J Med 2016;91:158-165) Keywords: Menopause; Myocardial infarction; Prognosis 서론오늘날현대인들의생활수준이향상되면서활동량은줄어들고영양섭취량은많아지면서질병양상이급성질환에서고혈압, 당뇨병, 고지혈증등만성질환의증가로변화하였다 [1]. 한국인에서사망의원인도변화하고있다. 악성신생물이높은순위를차지하고있지만단일기관으로인한사망률로볼때는심뇌혈관질환이빠른속도로증가하고있다 [2]. 심혈관질환의유병률은여성보다남성의유병률이대체로높지만중년이후에서는여성의유병률이높아지고있다 [3]. 2013년고혈압학회에서발표한질병관리본부의조사내용에서는고혈압유병률이현저하게중년이후여성에서높아지는것을볼수있다 [1]. 한국인급성심근경색증등록사업 (Korea Acute Myocardial Infarction Registry, KAMIR) 에등록된데이터를분석한결과 6년동안한국여성의급성심근경색증의발생률은남성에비해서나이가들어갈수록증가되었으며, 그증가율이중년이후부터빠른속도로증가되는것을알수있었고 70대에가장높은것으로나타났다 [4]. 중년이후여성들의심혈관질환이증가하는데는폐경기를거치면서난소에서의에스트로겐의분비감소가원인이라는여러연구에서보고되었다 [5,6]. 대표적인연구결과로는난소에서분비되는에스트로겐호르몬은혈관에존재하는난포호르몬수용체를통해혈관내피세포와혈관의평활근세포에작용하여혈관을확장시키므로폐경후의에스트로겐분비감소는혈압상승의원인이된다 [7]. 그리고폐경후에는총콜레스테롤과저밀도지단백콜레스테롤이증가되면서고지혈증의발생으로동맥경화증이진행이급속히되고혈액응고인자인섬유소원의농도가증가되면서혈전증에대한위험이높아지고심혈관질환의이환율이높아지게된다 [8,9]. 여성들은폐경에의해서같은나이의남성보다심혈관질환의위험이증가하는데, 이는폐경여성의체질량지수 (body mass index, BMI), 체지방량, 지방분포의변화와에스트로겐호르몬의감소로기초대사량이감소하면서체중의증가로심혈관질환의위험을증가시킨다 [10]. 이연구의목적은폐경을기준으로폐경전심근경색증이발생한환자와폐경후심근경색증이발생한환자의임상적특징및예후를파악해보고폐경전후발생한심근경색증환자의치료및관리에중요한자료를제공하고자본연구를시행하였다. 대상및방법연구대상 2005년 11월부터 2013년도 12월까지 KAMIR 에등록된 30-64 세까지의 4,128명중심근경색증발생후 1년추적조사가된 1,781명중년여성으로폐경전여성 699명 (I군, 55세, 49.1 ± 5.6세 ) 과폐경후여성 1,112명 (II군, 56-64 세, 60.6 ± 2.6세 ) 을대상으로두군간의임상경과를비교분석하였다. 연구방법한국심장학회 50주년기념연구사업으로진행되었던 KAMIR 의환자정보기록를이용하였다 [11]. 전남대학병원생명윤리위원회의심의 (CNUH 05-49) 를통과하여모든환자의동의서취득후이루어졌다. 일반적특성으로는연령, 신장, 몸무게, BMI, 체중, 혈압, 맥박, Killip Class, 심방세동, 고혈압, 당뇨병, 이상지질혈증, 흡연, 가족력, 심근경색증기왕력, 심혈관사건, 최종진단명, 주요심장사건에대해조사하였다. 임상적특징으로는헤모글로빈, 혈당, 크레아티닌, creatine kinase (CK), CK-MB, Troponin-I, 총콜레스테롤, 중성지 - 159 -
- 대한내과학회지 : 제 91 권제 2 호통권제 672 호 2016 - 방, 고밀도지단백콜레스테롤, 저밀도지단백콜레스테롤, high sensitivity C-reactive protein (hs-crp), N-terminal brain natriuretic peptide (NT pro-bnp), glycated hemoglobin 등을조사하였다. 본연구에서는주요심혈관사건으로는 1개월, 6개월, 12개월째의생존분석을심장사망, 비심인성사망 으로조사하였다. 통계분석방법수집된자료는 SPSS ver. 21.0 for window (SPSS Inc., Chicago, IL, USA) 를이용하여대상자의일반적특성과질병 Table 1. Baseline clinical characteristics of the subjects Variables Group I (n = 699) Group II (n = 1,112) p value Age, yrs 49.1 ± 5.6 60.6 ± 2.6 < 0.001 Height, cm 157.7 ± 5.6 155.9 ± 5.7 < 0.001 Weight, kg 60.5 ± 10.2 59.6 ± 8.8 0.087 Body mass index 24.2 ± 3.2 24.6 ± 3.3 0.048 Waist circumference, cm 90.3 ± 9.4 92.0 ± 9.5 0.005 Vital signs on admission SBP, mm/hg 129.7 ± 27.9 131.1 ± 29.2 0.338 DBP, mm/hg 78.8 ± 17.3 79.0 ± 16.8 0.014 HR, times/min 78.7 ± 17.9 76.6 ± 17.7 0.014 Final diagnosis 0.064 NSTMI 376 (56.6) 589 (53.5) STMI 288 (43.4) 512 (46.5) Killip class 0.017 I 533 (81.6) 825 (77.0) II 60 (9.2) 131 (12.2) III 35 (5.4) 86 (8.0) IV 25 (3.8) 29 (2.7) Risk factors Smoking 18 (2.7) 21 (1.9) < 0.001 Atrial fibrillation 3 (0.4) 8 (0.7) 0.693 Hypertension 282 (42.2) 661 (59.4) < 0.001 Diabetes mellitus 183 (27.4) 397 (35.7) < 0.001 Dyslipidemia 86 (12.9) 197 (17.7) 0.008 Prior MI 69 (10.3) 135 (12.1) 0.273 Family history 80 (12.0) 75 ( 6.8) < 0.001 Laboratory findings Hemoglobin, g/dl 13.0 ± 1.8 12.8 ± 1.7 0.243 Glucose, mg/dl 189.1 ± 94.6 197.5 ± 90.4 0.065 Total cholesterol, mg/dl 185.5 ± 48.1 194.5 ± 47.6 < 0.001 Triglyceride, mg/dl 131.3 ± 97.0 131.6 ± 101.3 0.955 HDL-cholesterol, mg/dl 47.4 ± 13.6 48.0 ± 30.2 0.580 LDL-cholesterol, mg/dl 116.1 ± 40.8 125.8 ± 47.9 < 0.001 NT-proBNP, pg/ml 2271.6 ± 5835.5 2556.5 ± 6128.6 0.429 hs-crp, mg/dl 2.6 ± 6.5 3.0 ± 7.1 0.213 HbA1c, % 6.9 ± 2.0 7.0 ± 1.8 0.379 Creatinine, mg/dl 1.1 ± 1.7 1.0 ± 1.2 0.491 Creatine kinase, U/L 847.8 ± 1329.0 911.8 ± 1380.2 0.394 CK-MB, ng/ml 91.8 ± 145.8 108.4 ± 261.8 0.093 TnI, ng/ml 28.7 ± 51.2 31.9 ± 53.4 0.271 Values are presented as mean ± SD or n (%). SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; NSTEMI, non-st-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction; MI, myocardial infarction; HDL, high-density lipoprotein; LDL, low-density lipoprotein; NT-proBNP, N-terminal brain natriuretic peptide; hs-crp, high-sensitivity C-reactive protein; HbA1C, glycosylated hemoglobin; CK-MB, creatin kinase myoglobin; TnI, troponin-i. - 160 -
- 오미숙외 18 인. 폐경기심근경색증 - 관련특성은빈도와백분율, 평균과표준편차로, 폐경전후에따른심근경색증의특징과예후는 t-test로, 대상자의일반적특성과질병관련특성에따른폐경전후의심근경색증특징과예후의차이는 Chi-Square test로분석하였다. 주요심혈관사건의발생유무의독립적인예측요인을분석을위해서는단변량회귀분석결과 p값이의미있는변수들로다중회귀분석을하여분석하였다. 결과폐경전후의일반적특성및임상적특징폐경전여성의평균연령은 49.1 ± 5.6세였고폐경후여성의평균연령은 60.6 ± 2.6세였다. BMI 는 I군에서 24.2 ± 3.2 kg/m 2 였고 II군은 24.6 ± 3.3 kg/m 2 로 II군에서통계적으로유의한차이를보였다. 체중과활력징후에서수축기혈압은두군간에유의한차이는없었으며, 이완기혈압 (I군, 78.8 ± 17.3 mmhg vs. II군, 79.0 ± 16.8 mmhg; p = 0.014), 맥박 (I군, 78.7 ± 17.9 rate/min vs. II군, 76.6 ± 17.7 rate/min; p = 0.014) 은 II군에서유의하게높았다. 입원시최종진단은두군간유의한차이가없었다. Killip class는 II군 (p = 0.017) 에서높았다. 심혈관질환의위험요인중에서는고혈압 (I군, 42.2% vs. II군, 59.4%; p < 0.001), 당뇨병 (I군, 27.4% vs. II군, 35.7%; p < 0.001), 이상지질혈증 (I군, 12.9% vs. II군, 17.7%; p = 0.008) 은 II군에서유의하게높았으며, 흡연 (I군, 2.7% vs. II군, 1.9%; p < 0.001) 과가족력 (I군, 12.0% vs. II군, 6.8%; p < 0.001) 은 I군에서유의하게높았다. 심방세동 (I군, 3명 [0.4%] vs. II군, 8명 [0.7%]; p = 0.693) 은유의하지않았다 (Table 1). 내원시에시행한혈액검사에서혈당과당화혈색소는두군간에유의한차이는없었다. 혈청지질검사는총콜레스테롤 (I군, 185.5 ± 48.1 mg/dl vs. II군, 194.5 ± 47.6 mg/dl; p < 0.001) 과저밀도지단백콜레스테롤 (I군, 116.1 ± 40.8 mg/dl vs. II군, 125.8 ± 47.9 mg/dl; p < 0.001) 은 II군에서높게나타났으며, 중성지방과고밀도지단백콜레스테롤은두군간차이가없었다. NT-proBNP, hs-crp, creatinine, creatin kinase, CK-MB, troponin I은두군간통계적으로유의한차이를보이지않았다 (Table 1). 심근경색증발생후치료약물은 aspirin, cilostazol, statin, angiotensin converting enzyme inhibitor, angiotensin receptor blocker, calcium channel blocker는두군간에차이가없었으 며, clopidogrel은 II군 (p = 0.045) 에서유의하게많이사용되었다. 관상동맥중재술시사용되었던약물용출스텐트와금속스텐트는두군간에차이가없었다 (Table 2). 1 년간임상적추적관찰 1년임상적추적관찰결과주요심장사건은 I군 51건 (7.6%), II군 95건 (8.5%) 으로서 (p = 0.551) 두군간유의하지않았다. 심장사망 (I군, 5명 [0.7%] vs. II군, 14명 [1.3%]; p = 0.436), 비심인성사망 (I군, 2명 [0.3%] vs. II군, 11명 [1.0%]; p = 0.171), 심근경색증 (I군, 6명 [0.9%] vs. II군, 8명 [0.7%]; p = 0.894), 재관상동맥중재술 (I군, 15명 [2.2%] vs. II군, 37명 [3.3%]; p = 0.241), 뇌졸중 (I군, 1명 [0.1%] vs. II군, 4명 [0.4%]; p = 0.727), 심부전으로인한입원 (I군, 3명 [0.4%] vs. II군, 4명 [0.4%]; p = 1.000) 등은두군간에차이가없었다 (Table 3). Table 2. Therapeutic modalities for myocardial infarction Variables Group I Group II (n = 699) (n = 1,112) p value Aspirin 689 (98.6) 1,067 (98.7) 1.000 Clopidogrel 630 (90.2) 1,043 (93.8) 0.045 Cilostazol 189 (27.0) 339 (30.5) 0.339 Statin 578 (82.7) 934 (84.0) 0.649 ARB 176 (25.2) 340 (30.6) 0.063 ACE I 403 (57.6) 647 (58.2) 0.891 CCB 127 (18.1) 97 (13.8) 0.068 STENT DES BMS 28 (4.0) 404 (57.8) 52 (4.7) 796 (71.6) 0.447 Values are presented as n (%). ARB, angiotensin II receptor blocker; ACE, angiotensin converting enzyme inhibitor; CCB, calcium channel blocker; DES, drug eluting stent; BMS, bare metal stent. Table 3. One-year clinical outcomes Variables Group I (n = 699) Group II (n = 1,112) p value MACE 51 (7.6) 95 (8.5) 0.551 Cardiac death 5 (0.7) 14 (1.3) 0.436 Non-cardiac death 2 (0.3) 11 (1.0) 0.171 MI 6 (0.9) 8 (0.7) 0.894 repci 15 (2.2) 37 (3.3) 0.241 Stroke 1 (0.1) 4 (0.4) 0.727 Hospitalization.HF 3 (0.4) 4 (0.4) 1.000 Values are presented as n (%). MACE, major adverse cardiac events; MI, myocardial infarction; PCI, percutaneous coronary intervention; HF, heart failure. - 161 -
- The Korean Journal of Medicine: Vol. 91, No. 2, 2016 - 생존과주요심혈관사건에영향을미치는인자에대한다변량회귀분석 단변량분석결과중의미있는값을다변량분석을한결과, 당뇨병 (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.16-2.45, p = 0.006), 심방세동 (HR 5.95, 95% CI 1.44-21.29, p = 0.007), 심근경색증기왕력 (HR 1.86, 95% CI 1.15-2.94, p=0.009), 다혈관질환 (HR 1.54, 95% CI 1.05-2.22, p = 0.025), Killip class (HR 1.26, 95% CI 1.02-1.54, p = 0.028), 가족력 (HR 1.78, 95% CI 0.99-3.03, p = 0.042) 은 1년주요심혈관사건을예측하는독립적인위험요인이었다 (Table 4 and 5). Kaplan-Meier법을이용한생존분석결과에서생존율도두군간사이에유의한차이는없었다 (Fig. 1). Table 4. Results of univariate logistic regression Variables HR 95% CI p value Group 1.13 0.80-1.62 0.493 Age 1.01 0.98-1.04 0.483 Obesity 0.89 0.62-1.28 0.543 SBP 1.00 0.99-1.00 0.649 DBP 1.00 0.99-1.01 0.909 HR 1.00 0.99-1.01 0.595 Killip classification 1.37 1.12-1.64 0.001 Atrial Fibrillation 6.55 1.70-21.96 0.003 Waist circumference 1.01 0.98-1.03 0.542 Hypertension 1.34 0.95-1.90 0.094 Diabetic mellitus 1.97 1.40-2.77 <0.001 Dyslipidemia 0.88 0.53-1.39 0.604 Smoking 0.78 0.49-1.18 0.269 Family history 1.53 0.88-2.53 0.110 Pre MI 2.17 1.39-3.30 0.000 Multi vessel disease 0.60 0.42-0.85 0.004 HR, heart rate; CI, confidence interval; SBP, systolic blood pressure; DBP, diastolic blood pressure, MI, myocardial infarction. Table 5. Multiple logistic regression analysis for the independent predictors of major adverse cardiac events Variables HR 95% CI p value DM 1.69 1.16-2.45 0.006 AF 5.95 1.44-21.29 0.007 Pre MI 1.86 1.15-2.94 0.009 Multi vessel disease 1.54 1.05-2.22 0.025 Killip class 1.26 1.02-1.54 0.028 FHx 1.78 0.99-3.03 0.042 HR, hazard ratio; CI, confidence interval; DM, diabetic mellitus; AF, atrial fibrillation; MI, myocardial infarction; FHx, family history. Figure 1. Kaplan-Meier curve of major adverse cardiac events (MACE)-free survival in menopausal (dotted black line) and pre-menopausal women (solid black line) at the one-year follow-up. HR, hazard ratio; CI, confidence interval. 고 폐경은심혈관질환의위험인자로알려져있는지질대사, 혈전형성촉진그리고비만과관련이있다고추정되고있어, 본연구에서는한국중년여성에서폐경과급성심근경색증발생후임상경과를알아보고자하였다. 그결과폐경전과폐경후의일반적인특성및임상적경과는유의한차이는없었으나, 폐경후여성에서당뇨병과고혈압, 이상지혈증이심근경색증발생의주요한위험인자였으며, 폐경전여성에서는흡연과가족력이위험인자였다. 최근우리나라사망원인통계에의하면심혈관질환으로인한사망이전체사망의 2위를차지하고있다 [2]. 심장질환으로인한사망률이인구십만명당 2003년 35.3명, 2013년 50.2명으로 10년간 42.2% 의증가를보이고있다 [2]. 심혈관질환은심장과혈관에발생하는질환을말하며심혈관질환을이루는고혈압성질환, 허혈성심장질환, 뇌혈관질환을의미한다. 급성심근경색증은세계적으로사망률및장기적기능부전의주요한요인으로서 [12], 증상은전흉부또는후흉부로발생하는흉통으로서짓누르는, 타는듯한, 바늘로찌르는듯한다양한양상으로나타나는데, 이전연구에서남성은흉통증상이전형적인데비여성은비전형적인것으로보고되었다 [3,5]. 발병연령을비교한결과대상자의평균나이는남성보다여성이 10년더늦게발병하였고 [13], 집단별연령분포에서남성은 50세이하가많았고여성은 70세이상이많 찰 - 162 -
- Mi Sook Oh, et al. Menopause in acute myocardial infarction - 았다 [3]. 특히여성은폐경을시작으로생리적, 생물학적변화가생기며관상동맥질환유병률이높아졌으며 [14], 폐경전에는관상동맥질환발생이매우드물었다 [15]. 같은연령군을비교해보았을때폐경이전여성보다폐경여성에서관상동맥질환발생위험이 4배에달하였다 [16]. 본연구에서또한중년여성에서폐경후여성이폐경전여성에비해심근경색증발생률이 3배정도높았다. 폐경발생에대한연령은연구마다차이가나타나고, 해마다증가하는양상을보였다. 1994년보고되었던한국여성의폐경연령은평균 48세였고 [17], 2001년보고에서는폐경연령이 49.2세로다소높아지는추세였다 [18]. 국외 cohort 연구에서폐경평균연령은 51.4세였으며 [19], 다민족을대상으로한 Study of Women s Health Across the Nation' 연구에서는폐경평균연령이 51.4 세였다. 특이한양상은일본여성이백인여성보다폐경평균연령이 51.8세로가장높았다 [20]. 2005-2012년까지 KAMIR에등록된환자의폐경전여성의평균연령은 50.4세로나타났다. 이결과를바탕으로 KAMIR 데이터의폐경연령은 50.4세보다더높아질것으로추정되어본연구에서는폐경연령을 55세기준으로정하였으며향후폐경연령에대한연구가더필요하다고생각된다. 여성은폐경기가되면에스트로겐호르몬이감소하고체력이급격히떨어지며여러가지생리적인변화가나타난다. 폐경이전의여성은항동맥경화증인자인고밀도지단백콜레스테롤의수치가남성보다높고, 저밀도지단백콜레스테롤의수치가낮게나타나지만, 폐경이후에는난포호르몬결핍에의한난소기능의저하로에스트로겐자극과저밀도지단백수용체활동의감소가이루어져저밀도지단백콜레스테롤이증가하고고밀도지단백콜레스테롤의수준이낮아져서 [21,22], 폐경기여성들의심혈관질환의유병률을증가시키는원인이된다 [23,24]. 폐경이후감소하는에스트로겐은관상동맥에서혈관을보호하는기전인저밀도지단백산화의억제, 콜레스테롤의혈관벽내유입억제, 혈관벽으로부터콜레스테롤유출증가, 혈관평활근세포및 myoinitial cell 의증식억제, collagen과 elastin 생성을억제, 혈소판의응집억제, prostacyclin의생성을증가시켜죽상동맥경화증의형성을억제할수있다 [25-27]. 폐경전여성에서도에스트로겐의수치가낮은여성은심혈관질환위험도가더높아짐을볼수있다. 본연구에서도폐경후군에서저밀도지단백콜레스테롤이높았다. 폐경여성에서에스트로겐호르몬치료를통해심혈관질 환발생이감소됨을볼수있었던결과 [28] 와폐경전여성에서도에스트로겐의수치가낮은여성은심혈관질환위험도가더높아짐을볼수있다 [29]. 그러나본연구에서는폐경전후두군간에급성심근경색증발생후일년간주요심혈관사건에는크게차이가없었다. 일반적으로폐경전후여성들은체중이점차증가하게되며, 체질량지수가증가하면혈압이증가하고체질량지수가 25 이상일때는콜레스테롤이높아지며저밀도지단백 / 고밀도지단백의비가증가되었다 [22]. 이러한변화는관상동맥질환의위험인자에해당이되므로과체중비만여성들에게는관리가중요하다 [22]. 본연구에서는폐경전과후에비만도는큰차이가없었으나폐경후여성에서는이상지혈증이더증가되는것을볼수있었으며, 이완기혈압은의미있게폐경후군에서높았다. 흡연과심혈관질환은밀접한관련이있으며, 흡연은폐경연령을앞당긴다는결과들이있다 [8]. 본연구에서도폐경전여성에서는흡연이급성심근경색증발생위험인자로써의미있는결과로분석되었다. 기존연구에서도폐경으로인한에스트로겐의부족, 흡연, 비만, 지단백의변화, 운동부족등은심혈관질환위험도를증가시키고심혈관질환으로인한사망과밀접한관련이있다는것을볼수있었다 [23,24]. 한국인젊은심근경색증환자중 40세전후양군을대상으로주요심장사건및 1년간무사건생존율을비교하였을때양군간의유의한통계적차이는없었으며 [30], 심근경색증으로내원한 75세이상의노인환자들을대상으로젊은대조군과주요심혈관사건의차이를 1년간추적한결과양군의유의한차이를보이지않았다 [31]. 본연구에서도폐경이급성심근경색증발생에영향을미치고발생후주요심혈관사건에서도폐경후중년여성에서더높을것이라고예측하였지만, 위의연구결과와같이양군간의유의한차이가없었다. 예측하건대의학의발달로다양한좋은치료약들과스텐트, 식이요법과운동에대한교육으로발생후관리가잘되고있는것으로보여진다. 하지만폐경전중년여성들의건강관리가부족한것으로보여지므로폐경전여성들에대한집중적인관리가필요하며, 장기간추적관찰의필요성이요구된다. 본연구의제한점은후향적이며폐경전그룹의표본수가폐경후군에비해적었다. 또한 KAMIR 에등록된다기관의대규모데이터를활용하여폐경의정확한연령을알수없었다는점이다. 여러가지문헌고찰을통해폐경으로인한에 - 163 -
- 대한내과학회지 : 제 91 권제 2 호통권제 672 호 2016 - 스트로겐분비의감소가체중증가, 당뇨, 고혈압, 저밀도지단백콜레스테롤의증가등의여러가지변화를오게하는요인으로보여지고, 또한심혈관질환의위험요인들과밀접한관련이있는것으로사료된다. 그러나본연구는후향적연구로써폐경후여성호르몬요법등의치료여부에대한조사가되어있지않아서여성호르몬치료전후의차이를알수없었다, 향후폐경후여성의호르몬치료에대한자료를추가하여연구가더필요할거라생각된다. 본연구에서의제한점을보완하여장기간의임상적관찰을통해중년여성의심근경색증환자의효과적인치료와관리를위한기초자료를마련하고폐경전중년여성심근경색증환자의집중적인관리로예후를향상시킬수있는기초자료를마련하고자한다. 은두군간차이를나타내지않았다. 또한생존율과생존분석도두군간에유의한차이가없었다. 다변량분석을한결과당뇨병 (HR 1.69, 95% CI 1.16-2.45, p = 0.006), 심방세동 (HR 5.95, 95% CI 1.44-21.29, p = 0.007), 심근경색증기왕력 (HR 1.86, 95% CI 1.15-2.94, p = 0.009), 다혈관질환 (HR 1.54, 95% CI 1.05-2.22, p = 0.025) 그리고 Killip class (HR 1.26, 95% CI 1.02-1.54, p = 0.028), 가족력 (HR 1.78, 95% CI 0.99-3.03, p = 0.042) 은 1년주요심혈관사건을예측하는독립적인위험요인이었다. 결론 : 한국인중년여성심근경색증환자에서 1년간추적관찰결과생존분석과주요심혈관사건은폐경전후유의한차이가없었다. 따라서폐경전중년여성심근경색증환자도집중관리가필요할것으로생각된다. 요 약 중심단어 : 폐경 ; 심근경색증 ; 예후 목적 : 폐경은지질대사장애, 비만그리고혈전형성촉진과관련이있는것으로알려져있다. 본연구에서는한국중년여성에서폐경과급성심근경색증환자의임상경과를알아보고자하였다. 대상및방법 : 2005년 11월부터 2013년 12월까지한국인급성심근경색증등록사업에등록된 1,781명의 65세미만중년여성을대상으로폐경전그룹 (I군, 55세, 669 명 ) 과폐경후그룹 (II군, 56-64 세, 1,112명 ) 으로나누어서 1년후주요심혈관사건을비교분석하였다. 결과 : 폐경전여성은 669명 (I군 49.1 ± 5.6세 ) 이며폐경후여성은 1,112명 (II군 60.6 ± 2.6세 ) 이었다. 체질량지수 (I군 24.2 ± 3.2 kg/m 2 vs. II군 24.6±3.3kg/m 2 ; p = 0.048) 와복부둘레 (I군 90.3 ± 9.4 cm vs. II군 92 ± 9.5 cm; p = 0.005) 는 II군에서유의하게높았다. 고혈압 (I군 42.2% vs. II군 59.4%; p < 0.001), 당뇨병 (I군 27.4% vs. II군 35.7%; p < 0.001), 이상지질혈증 (I군 12.9% vs. II군 17.7%; p = 0.008) 은 II군에서유의하게더높았다. 흡연 (I군 2.7% vs. II군 1.9%; p < 0.001) 과가족력 (I군 12% vs. II군 6.8%; p < 0.001) 은 I군에서높게나타났다. 총콜레스테롤 (I군 185.5 ± 48.1 mg/dl vs. II군 194.5 ± 47.6 mg/dl; p < 0.001) 과저밀도지단백콜레스테롤 (I군 116.1 ± 40.8 mg/dl vs. II군 125.8 ± 47.9 mg/dl; p < 0.001) 은 II군에서유의하게높았다. 주요심혈관사건에있어서 1개월 (I군 1.7% vs. II군 2.5%; p = 0.481), 6개월 (I군 4.9% vs. II군 4.6%; p = 0.911), 12개월 (I군 7.6% vs. II군 8.5%; p = 0.551) 발생률 REFERENCES 1. Center for Disease Control & Prevention. Korea National Health and Nutrition Examination Survey in 2013 [Internet]. Ceongju (KR): Center for Disease Control & Prevention, c2015 [cited 2015 Jan 20]. Available from: http://stat.mohw.go.kr/front/statdata/publicationview.jsp? menuid=47&bbsseq=13&nttseq=21549&searchkey=&sea rchword=&npage=1&topselect=. 2. Korean Statistical Information Service. Cause of Death Statistics [Internet]. Daejeon (KR): Korean Statistical Information Service, c2014 [cited 2014 Sep 23]. Available from: http: //kostat.go.kr/portal/korea/kor_nw/2/1/index.board?bmode =read&aseq=330181. 3. Milner KA, Vaccarino V, Arnold AL, Funk M, Goldberg RJ. Gender and age differences in chief complaints of acute myocardial infarction (Worcestor Heart Attack Study). Am J Cardiol 2004;93:606-608. 4. Health Insurance Review & Assessment Service. Evaluation result of Acute Myocardial Infarction in 2013 [Internet]. Wonju (KR): Health Insurance Review & Assessment Service, c2013 [cited 2013 Dec 12]. Available from: http://www. hira.or.kr/dummy.do?pgmid=hiraa020041000000&cmsurl=/cms/inform/02/1322009_27116.html&subject=%ec% 8b%ac%ed%8f%89%ec%9b%90+%ea%b8%89%ec%84% b1%ec%8b%ac%ea%b7%bc%ea%b2%bd%ec%83%89% ec%a6%9d+%ed%8f%89%ea%b0%80+%ea%b2%b0% ea%b3%bc%2c+%ec%b9%98%eb%a3%8c%eb%8a%94 +%ec%84%b8%ea%b3%84%ec%a0%81+%ec%88%98%e c%a4%80. - 164 -
- 오미숙외 18 인. 폐경기심근경색증 - 5. Isaksso RM, Holmgren L, Lundblad D, Brulin C, Eliasson M. Time trends in symptoms and prehospital delay time in women vs. men with myocardial infarction over a 15-year period. The Northern Sweden MONICA study. Eur J Cardiovasc Nurs 2008;7:152-158. 6. van der Schouw YT, van der Graaf Y, Steyerberg EW, Eijkemans JC, Banga JD. Age at menopause as a risk factor for cardiovascular mortality. Lancet 1996;347:714-718. 7. Yeoum SG. The investigation on the risk factors of cardiovascular disease for postmenopausal women over 50 years. J Menopausal Med 2003;9:3. 8. Crawford SL, Johannes CB. The epidemiology of cardiovascular disease in postmenopausal women. J Clin Endocrinol Metab 1999;84:1803-1806. 9. Gaspard UJ, Gottal JM, van den Brûle FA. Postmenopausal changes of lipid and glucose metabolism: a review of their main aspects. Maturitas 1995;21:171-178. 10. Stemfeld B, Bhat AK, Wang H, Sharp T, Quesenberry CP Jr. Menopause, physical activity, and body composition/fat distribution in midlife women. Med Sci Sports Exerc 2005;37: 1195-1202. 11. Jeong MH. Can time delay be shortened in the treatment of acute myocardial Infarction?: Experience from Korea acute myocardial Infarction registry. Korean J Med 2010;78:582-585. 12. Moshki M, Zareie M, Hashemizadeh H. Sex difference in acute myocardial infarction. Nurs Midwifery Stud 2015;4:e22395. 13. Lloyd-Jones D, Adams R, Carnethon M, et al. Heart disease and stroke statistics--2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009;119:e21-e181. 14. Tackett AH, Bailey AL, Foody JM, et al. Hormone replacement therapy among postmenopausal women presenting with acute myocardial infarction: insights from the GUSTO-III trial. Am Heart J 2010;160:678-684. 15. Jneid H, Thacker HL. Coronary artery disease in women: different often undertreated. Cleve Clin J Med 2001;68:441-448. 16. Rosengren A, Spetz CL, Köster M, Hammar N, Alfredsson L, Rosén M. Sex differences in survival after myocardial infarction in Sweden; data from the Swedish National Acute Myocardial Infarction Register. Eur Heart J 2001;22:314-322. 17. The Korean society of Menopause, Lee JY, Koo BS, et al. Management of menopausal women. 1st ed. Seoul: Kalbinseojeok, 1994. 18. Park YJ, Koo BS, Kang HC, Chun SH, Yoon JW. The menopausal age and climacteric symptoms and the related factors of Korean women. Korean J Women Health Nurs 2001;7:473-485. 19. Henderson KD, Bernstein L, Henderson B, Kolonel L, Pike MC. Predictor of timing of natural menopause in the multiethnic cohort study. Am J Epidemiol 2008;167:1287-1294. 20. Gold EB, Bromberger J, Crawford S, et al. Factors associated with age at natural menopause in a multiethnic sample of midlife women. Am J of Epidemiol 2001;153:865-874. 21. Grundy SM. Cholesterol and coronary heart disease. Future directions. JAMA 1990;264:3053-3059. 22. Brown CD, Higgins M, Donato KA, et al. Body mass index and the prevalence of hypertension and dyslipidemia. Obes Res 2000;8:605-619. 23. Kuller LH, Gutai JP, Meilahn E, Matthews KA, Plantinga P. Relationship of endogenous sex steroid hormones to lipids and apoproteins in postmenopausal women. Arteriosclerosis 1990;10:1058-1066. 24. Frost PH, Davis BR, Burlando AJ, et al. Coronary heart disease risk factors in men and women aged 60 years and older: findings from the Systolic Hypertension in the Elderly Program. Circulation 1996;94:26-34. 25. Ford ES, DeStefano F. Risk factors for mortality from all causes and from coronary heart disease among persons with diabetes. Findings from the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study. Am J Epidemiol 1991;133:1220-1230. 26. Singh AT, Rainwater DL, Haffner SM, et al. Effect of diabetes on lipoprotein size. Arterioscler Thromb Vasc Biol 1995;15:1805-1811. 27. Vogel RA. Coronary risk factors, endothelial function, and artherosclerosis: a review. Clin Cardiol 1997;20:426-432. 28. Glasser SP, Selwyn AP, Ganz P. Atherosclerosis: risk factors and the vascular endothelium. Am Heart J 1996;131:379-384. 29. Tannen RL, Weiner MG, Xie D, Barnhart K. Estrogen affects post-menopausal women differently than estrogen plus progestin replacement therapy. Hum Reprod 2007;22:1769-1777. 30. Cho JY, Jeong MH, Ahn Y, et al. Predictive factors of major adverse cardiac events and clinical outcomes of acute myocardial infarction in young Korean patients. Korean Circ J 2008;38:161-169. 31. Lim SY, Jeong MH, Yang BR, et al. Long-term clinical outcomes after primary percutaneous coronary intervention in patients with acute myocardial infarction older than 75 years. Korean Circ J 2005;35:613-619. - 165 -