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1 ORIGINAL ARTICLE Korean J Clin Lab Sci. 2016, 48(3): pissn eissn Korean J Clin Lab Sci. Vol. 48, No. 3, September The Association of Urine Microalbumin and Pulse Pressure in Korean Adults Mee Young Gee 1, Hyun Yoon 2 1 Department of Nursing, Christian College of Nursing, Gwangju 61662, Korea 2 Department of Biomedical Laboratory Science, Hanlyo University, Gwangyang 57764, Korea 한국성인에서뇨중 Microalbumin 과맥압의관련성 기미영 1, 윤현 2 1 광주기독간호대학교간호학과, 2 한려대학교임상병리학과 The aim of this study was to assess the association between microalbumin and pulse pressure (PP) in Korean adults. The study subjects were Korean adults 20 years or older (n=4,948) who participated in the Korea National Health and Nutrition Examination Survey The urine microalbumin level (M±SE) was significantly higher (p=0.047) in the high PP group (PP>60.0 mmhg) [33.02±4.93 g/ml (95% confidence interval (CI), )] than the normal PP group (PP 60.0 mmhg) [22.57±1.63 g/ml (95% CI, )], after adjusting for age, gender, smoking, drinking, regular exercising, WM, BMI, TC, TG, HDL-C, FBG, BUN, creatinine, and urine creatinine. In conclusion, pulse pressure was associated with the microalbumin level in Korean adults. Key words: Microalbumin, Pulse pressure Corresponding author: Hyun Yoon Department of Biomedical Laboratory Science, Hanlyo University, 94-13, Hallyeodae-gil, Gwangyang-eup, Gwangyang 57764, Korea Tel: Fax: yh9074@yahoo.co.kr This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright 2016 The Korean Society for Clinical Laboratory Science. All rights reserved. Received: July 20, 2016 Revised 1 st : August 7, 2016 Revised 2 nd : August 18, 2016 Revised 3 rd : August 23, 2016 Revised 4 th : August 25, 2016 Accepted: August 25, 2016 서론미세알부민뇨 (microalbuminuria) 는단백뇨 (proteinuria) 가배설되기전에미세한양의알부민이배설되는것으로 [1], 향후단백뇨를동반한당뇨병성신증을예측하는지표가될수있다 [2,3]. 맥압 (Pulse pressure, PP) 은수축기혈압 (systolic blood pressure, SBP) 과이완기혈압 (diastolic blood pressure, DBP) 의차이로정의되며, 동맥의탄성과파장반사로결정되기때문에동맥경직도가증가할수록증가한다 [4]. 동맥경직도증가의위험인자로는연령, 당뇨, 고혈압, 대사증후군및죽상경화증등이있다 [5-7]. 특히, 맥압은만성신질환의진행과관련이있으며 [8], 당뇨의발생에있어서강력한예측인자로각광을받고있다 [9]. 그러나, 이와같은만성 신질환의진행및당뇨발생의예측인자인맥압과당뇨병성신증의예측인자인뇨중 microalbumin 의관련성에대한연구는거의없다. 따라서본연구는제 5기국민건강영양조사자료를이용하여대한민국성인에서뇨중 microalbumin과맥압의관련성에대하여알아보고자하였다. 재료및방법 1. 연구대상본연구는질병관리본부주관으로시행된국민건강영양조사 (2012년) 의자료를이용하였다. 조사참여자수는 8,058명이었고, 이중에서 20세이상성인은 6,221명이었다. 본연구대상자는

2 184 Mee Young Gee and Hyun Yoon. Microalbumin and Pulse Pressure 6,221명중건강설문에서불충분한응답 (362명) 과혈압, 혈액및뇨중 microalbumin 등의검사결과가누락 (911명) 이되어있는대상자 1,273명을제외한총 4,948명을최종분석대상자로하였다. 제 5기 3차년도국민건강영양조사자료는질병관리본부연구윤리심의위원회의심의및승인을받았다 ( 승인번호 ; EXP-01-2C). 2. 자료수집본연구는 2012년도부터 1월부터 12월까지 12개월동안시행된제 5기국민건강영양조사자료를이용하였다. 조사항목으로는대상자들의성별, 연령, WM, BMI, 안정시혈압및맥압, 아침공복시의혈액검사, 뇨중 creatinine 과 microalbumin 등이었다. 추가적으로 FBG, creatinine, 요중 creatinine 을보정하였다. 모든통계량의유의수준은 p<0.05 로판정하였다. 결과 1. 연구대상자의일반적특성연구대상자의일반적특성은 Table 1과같다. 본연구의총연구대상자는 4,948명이었고, 남성은 2,174명 (43.9%), 여성은 2,754명 (56.1%) 이었다. 전체대상자중, High PP에해당되는대상자는 543 명 (11.0%) 이었고, 뇨중 microalbumin의평균값은 23.71± g/ml 이었다. 3. 대상자의특성 1) 일반적특성및혈액화학검사대상자중연령은평균값으로, 성별은남녀로구분하였다. 신체계측은체질량지수 (body mass index, BMI), 허리둘레 (waist measurement, WM), SBP, DBP의측정값을사용하였다. 혈액화학검사는총콜레스테롤 (total cholesterol, TC), 중성지방 (triglyceride, TG), 고밀도콜레스테롤 (HDL-cholesterol, HDL-C), 공복시혈당 (fasting blood glucose, FBG), 혈중요소질소 (blood urea nitrogen, BUN) 및 creatinine 의측정값을사용하였고, 뇨중 creatinine 과 microalbumin 의측정값을사용하였다. 2) 맥압및 microalbumin 맥압은 SBP에서 DBP를차감하여계산하였고, PP 60.0 mmhg를 Normal PP로, PP>60.0 mmhg를 High PP로구분하였다 [10]. 뇨중 microalbumin 의사분위는 1사분위 (<2.60 g/ml), 2사분위 ( g/ml), 3사분위 ( g/ml), 4사분위 ( g/ml) 로구분하였다. 4. 자료처리및분석자료의통계처리는 SPSS WIN version 18.0 (SPSS Inc., Chicago, IL, USA) 통계프로그램을이용하였다. 대상자의특성에대한분포는빈도와백분율로나타내었고연속형자료는평균과표준편차로표시하였다. 뇨중 microalbumin의사분위에따른특성은교차분석과 ANOVA test를이용하여분석하였고, ANCOVA test에서네가지의 Model을실시하여 PP가뇨중 microalbumin 에독립적으로영향을주는지를알아보았다. Model 1은연령과성별을보정하였고, Model 2는 Model 1에추가적으로흡연, 음주, 규칙적인운동을보정하였다. Model 3은 Model 2에추가적으로 WM, BMI, TC, TG, HDL-C를보정하였고, Model 4는 Model 3에 2. 뇨중 microalbumin 의사분위에따른대상자들의임상적특성 뇨중 microalbumin 의사분위에따른대상자들의임상적특성은 Table 2와같다. 뇨중 microalbumin의사분위에서유의한차이를보이는변수는연령 (p<0.001), SBP (p<0.001), DBP (p<0.001), PP (p<0.001), BMI (p<0.001), WM (p<0.001), TG (p<0.001), HDL-C (p<0.001), FBG (p<0.001), BUN (p<0.001), creatinine (p<0.001) 및뇨중 creatinine (p<0.001) 등이었고, 성별 (p=0.093), 흡연습관 (p=0.175), 음주습관 (p=0.227), 운동습관 (p=0.075), TC (p=0.715) 등은유의한차이를보이지않았다. Table 1. General characteristics of research subjects (n=4,948) Variables Category n (%), M±SD Age (year) 51.88±16.02 Gender Males 2,174 (43.9) Smoking Current smoker 1,020 (20.6) Drinking Yes 2,495 (50.4) Regular exercising Yes 628 (12.7) BMI (kg/m 2 ) 23.84±3.34 WM (cm) 81.50±9.58 SBP (mmhg) ±16.98 DBP (mmhg) 75.91±10.49 PP (mmhg) 44.18±13.80 High PP PP 60.0 mmhg 543 (11.0) TC (mg/dl) ±36.11 TG (mg/dl) ±87.19 HDL-C (mg/dl) 51.52±12.63 FBG (mg/dl) 98.92±21.78 BUN (mg/dl) 14.65±4.49 Creatinine (mg/dl) 0.84±0.23 Urine creatinine (mg/dl) ±84.99 Microalbumin ( g/ml) 23.71± Abbreviation: BMI, body mass index; WM, waist measurement; SBP, systolic blood pressure; DBP, diastolic blood pressure; PP, pulse pressure; TC, total Cholesterol; TG, triglyceride; HDL-C, High density lipoprotein cholesterol; FBG, fasting blood glucose; BUN, blood urea nitrogen.

3 Korean J Clin Lab Sci. Vol. 48, No. 3, September Table 2. Clinical characteristics of subjects in relation for microalbumin quartile Variables Quartile 1 (n=1,235) (<2.60 g/ml) Quartile 2 (n=1,218) ( g/ml) Quartile 3 (n=1,250) ( g/ml) Quartile 4 (n=1,245) ( g/ml) p-value Age (years) 50.94± ± ± ±16.89 <0.001 Gender (Males) 505 (40.9) 553 (45.4) 556 (44.5) 560 (45.0) Current smoker 247 (20.0) 254 (20.9) 250 (20.0) 269 (21.6) Drinker 618 (50.0) 643 (52.8) 628 (50.2) 606 (48.7) Regular exerciser 183 (14.9) 142 (11.7) 152 (12.2) 151 (12.2) SBP (mmhg) ± ± ± ±18.70 <0.001 DBP (mmhg) 74.38± ± ± ±11.98 <0.001 PP (mmhg) 42.45± ± ± ±16.17 <0.001 BMI (kg/m 2 ) 23.56± ± ± ±3.68 <0.001 WM (cm) 80.45± ± ± ±10.23 <0.001 TC (mg/dl) ± ± ± ± TG (mg/dl) ± ± ± ± <0.001 HDL-C (mg/dl) 52.73± ± ± ±12.36 <0.001 FBG (mg/dl) 95.62± ± ± ±60.49 <0.001 BUN (mg/dl) 13.94± ± ± ±5.61 <0.001 Creatinine (mg/dl) 0.82± ± ± ±0.36 <0.001 Urine creatinine (mg/dl) 88.39± ± ± ± <0.001 n (%), M±SD, (n=4,948). Table 3. Multiple linear regression analysis evaluating the independent determinants of microalbumin (n=4,948) B SE p-value Microalbumin ( g/ml) Intercept <0.001 Age Males <0.001 Current smoker Drinker Regular exerciser BMI WM SBP <0.001 DBP TC TG HDL-C FBG <0.001 BUN Creatinine <0.001 Urine creatinine 뇨중 microalbuminn 에영향을미치는요인 뇨중 microalbumin 에영향을미치는요인은 Table 3과같다. 뇨중 microalbumin 의평균값에독립적으로영향을미치는변수는성별 (p<0.001), SBP (p<0.001), TG (p=0.001), FBG (p<0.001), BUN (p=0.001), creatinine (p<0.001) 및뇨중 creatinine (p=0.014) 등이었고, 연령 (p=0.060), 흡연습관 (p=0.847), 음주습관 (p=0.313), 운동습관 (p=0.101), BMI (p=0.557), WM (p=0.581), DBP (p=0.669), TC (p=0.211), HDL-C (p=0.211) 등은독립적으로유의한변수가아니었다. 4. PP에따른뇨중 microalbumin 의평균값비교 PP에따른뇨중 microalbumin 의평균값비교는 Table 4와같다. PP를 Normal PP와 High PP로나누었을때, 연령, 성별, 흡연습관, 음주습관, 운동습관, WM, BMI, TC, TG, HDL-C, FBG, BUN, creatinine 및뇨중 creatinine 등을보정한후의결과에서 High PP의뇨중 microalbumin평균값 (M±SE) 은 33.02±4.93 g/ml ( ), Normal PP의뇨중 microalbumin 평균값 (M±SE) 은 22.57±1.63 g/ml ( ) 로 High PP에서유의하게높았다 (p=0.047). 고찰본연구는 2012년도에시행된국민건강영양조사제 5기 3차년도자료를이용하여실시한뇨중 microalbumin 과맥압의관련성에대한연구이다. 본연구의주요결과는뇨중 microalbumin와관련된변수를보정한후에 High PP의뇨중 microalbumin 평균값이 Normal PP의뇨중 microalbumin평균값보다높았다. PP는단순히 SBP과 DBP의차로환산된수치지만, PP의증가는동맥경화, 고지혈증, 당뇨, 죽상경화및이로인한심ㆍ뇌혈관질환등을예측하는중요인자로알려져있다 [9,11-13]. 맥압이증가하는경우는첫째, DBP가 SBP보다상대적으로많이감소하는경우로

4 186 Mee Young Gee and Hyun Yoon. Microalbumin and Pulse Pressure Table 4. Comparisons of serum microalbumin levels for PP (n=4,948) Variables Normal PP (PP <60.0 mmhg) High PP (PP 60.0 mmhg) p-value Microalbumin ( g/ml) Model ±1.72 ( ) 37.62±5.17 ( ) Model ±1.72 ( ) 37.94±5.17 ( ) Model ±1.72 ( ) 37.28±5.18 ( ) Model ±1.63 ( ) 33.02±4.93 ( ) Model 1 [M±SE (95% CI)]: adjusted for age and gender. Model 2 [M±SE (95% CI)]: adjusted for age, gender, smoking, drinking, and regular exercising. Model 3 [M±SE (95% CI)]: adjusted for age, gender, smoking, drinking, regular exercising, WM, BMI, TC, TG, and HDL-C. Model 4 [M±SE (95% CI)]: adjusted for age, gender, smoking, drinking, regular exercising, WM, BMI, TC, TG, HDL-C, FBG, BUN, creatinine, and urine creatinine. 큰동맥의경직도가증가함으로써발생한다고알려져있다 [14]. 둘째, SBP가 DBP보다상대적으로많이증가하는경우로 1회심박출량또는심실박출률 (ventricular ejection rate) 이증가하여심장기능에상당한부담으로작용할수있다 [15]. Franklin 등은 PP가 10 mmhg 상승하면 22%, SBP가 10 mmhg 상승하면 16%, DBP가 10 mmhg 상승하면 14% 정도관상동맥질환이증가한다고하였고, SBP의상승에의한관상동맥질환환자중에서 DBP가낮을수록, PP가높을수록사망률이높아진다고하였다 [16]. 또한, Staessen 등은 SBP가 160 mmhg 이상인대상자중에서 SBP가 10 mmhg 증가했을때사망률은 1.22 (p<0.05) 배, 뇌졸중은 1.22 (p<0.05) 배증가하고, SBP의증가로인한고혈압의합병증에서도 SBP의증가에대하여 DBP가높으면합병증도낮아진다는연구결과로고혈압환자에서는 SBP와 DBP수치도중요하지만, PP수치가더욱중요하다고기술하였다 [17]. 뇨중 microalbumin 의증가는당뇨병성신증의예측인자이며 [2,3], 심ㆍ뇌혈관질환및고혈압에영향을미치는주요한영향인자이다 [18,19]. Yudkin 등은심혈관질환이없는대상자중뇨중 microalbumin가증가된대상자에서동맥의경직도가증가하였기때문에뇨중 microalbumin 의증가는동맥경화의위험인자라고하였다 [20]. 현재, 뇨중 microalbumin과 PP의관련성에대한연구는거의없다. Pedrinelli 등은 211명의이탈리아인을대상으로실시한연구에서 microalbuminuria (urine microalbumin 15 g/ml) 는심혈관질환의강력한위험인자이며, 특히 PP의증가와관련이있다고하였다 (p<0.001) [21]. 또한, Cirillo 등은 1,567명 ( 남성, 677 명 ; 여성, 890명 ) 의이탈리아인을대상으로실시한연구에서 microalbuminuria (urine microalbumin 20 g/ml) 의위험비 (Odds ratios) 가 PP가 15 mmhg증가할수록 1.71배 ( ) 가증가한다고하였다 [22]. 본연구의선형회귀분석결과에서 SBP, TG 및 FBG는뇨중 microalbumin 의평균값을증가시키는유의한변수였지만, DBP는유의한변수가아니었다. TG와 FBG는 PP를 증가시키는강력한위험인자이며 [23], PP는 SBP에서 DBP를차감한수치이기때문에 PP의증가가일어나는첫번째경우인 SBP의증가로인한 PP가증가하였기때문으로사료된다. 결론적으로, 대한민국성인에서 PP의증가는뇨중 microalbumin 의증가와유의한관련성이있었다. 뇨중 microalbumin과 SBP 및 DBP는인종마다다르기때문에 [24], 뇨중 microalbumin 과 PP의관련성도인종과나라마다다를수있다. 또한, 본연구는단면연구이기때문에 PP의증가가뇨중 microalbumin의증가에영향을주는지, 아니면뇨중 microalbumin 의증가가 PP의증가에영향을주는지는알수없다. 따라서이에대한코호트연구를시행할수있다면정확한인과관계를확인하기위한더욱더정확한결과를얻을수있을것으로기대된다. 요약본연구는국가자료인 2012년도국민건강영양조사자료를이용하여 20세이상성인 (n=4,948) 에서뇨중 microalbumin 과맥압 (Pulse pressure, PP) 의관련성을평가하고자실시하였다. 연구결과에서연령, 성별, 흡연습관, 음주습관, 운동습관, WM, BMI, TC, TG, HDL-C, FBG, BUN, creatinine, 및요중 creatinine 등을보정하였을때, 뇨중 microalbumin 평균값에서, High PP (PP>60.0 mmhg) [33.02±4.93 g/ml (95% confidence interval (CI), )] 가 Normal PP (PP 60.0 mmhg) [22.57±1.63 g/ml (95% CI, )] 에비하여유의하게높았다 (p=0.047). 결론적으로대한민국성인에서 PP의증가는뇨중 microalbumin 의증가와유의한관련성이있었다. Acknowledgements: None Funding: None Conflict of interest: None

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