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ORIGINAL ARTICLE Korean J Clin Lab Sci. 2018;50(3):245-252 https://doi.org/10.15324/kjcls.2018.50.3.245 pissn 1738-3544 eissn 2288-1662 Korean J Clin Lab Sci. Vol. 50, No. 3, September 2018 245 Significance of Non HDL-cholesterol and Triglyceride to HDL-cholesterol Ratio as Predictors for Metabolic Syndrome among Korean Elderly Seung Bok Hong 1, Kyung-A Shin 2 1 Department of Clinical Laboratory Science, Chungbuk Health & Science University, Cheongju, Korea 2 Department of Clinical Laboratory Science, Shinsung University, Dangjin, Korea 한국노인의대사증후군예측인자로서혈중 Non HDL 콜레스테롤과중성지방 /HDL 콜레스테롤비의의의 홍승복 1, 신경아 2 1 충북보건과학대학교임상병리과, 2 신성대학교임상병리과 We evaluated the possible clinical application of Non HDL-cholesterol and triglyceride to HDL-cholesterol ratio as a metabolic syndrome predictor for the elderly in Korea. 1,543 elderly persons aged 65 years or older who visited the health examination center of Gyeonggi Regional General Hospital from January 2015 to December 2017 and had a health checkup were enrolled in this study. Metabolic syndrome was diagnosed based on the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) standards. Abdominal obesity was assessed by the Asia-Pacific standards presented at the World Health Organization (WHO) West Pacific Region. Non-HDL-cholesterol was calculated as the difference between total cholesterol and HDLcholesterol. The metabolic syndrome predictive power was higher for triglyceride to HDLcholesterol ratio than for Non HDL-cholesterol. After correcting for related factors, triglyceride to HDL-cholesterol ratio was higher in the 4 th quartile, which had a higher risk of developing metabolic syndrome, than in the 1 st quartile. The optimal cutoff value for the triglyceride to HDL-cholesterol ratio that predicts the onset of metabolic syndrome was 2.8. triglyceride to HDL-cholesterol ratio can be a simple and practical indicator of the risk of metabolic syndrome. Key words: Metabolic syndrome, Non HDL-cholesterol, Triglyceride to HDL-cholesterol ratio 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: August 29, 2018 Revised 1 st : September 5, 2018 Revised 2 nd : September 5, 2018 Accepted: September 6, 2018 서론대사증후군은고혈압, 내당능장애, 이상지질혈증, 복부비만의심혈관계위험요인들이군집되어나타나는현상으로공통된원인은인슐린저항성으로보고되고있다 [1]. 국민건강영양조사자료를바탕으로우리나라의대사증후군유병률은 1998년 남성 13.5%, 여성 15.0% 였으나, 2009년남성 28.3%, 여성 16.6% 로증가하는추세이다 [2]. 노인의대사증후군유병률은 2007년국민건강영양조사자료를통해남성 21.7%, 여성 46.7% 로남성보다여성에서연령증가와함께큰폭의증가를보이며 [3], 이러한국내노인의대사증후군유병률은유럽에비해높은실정이다 [4, 5].

246 Seung Bok Hong and Kyung-A Shin. Non HDL-cholesterol and Triglyceride to HDL-cholesterol Ratio 한편, 총콜레스테롤과고밀도지단백콜레스테롤 (high density lipoprotein cholesterol, HDL-콜레스테롤 ) 의차이로계산되는비고밀도지단백콜레스테롤 (non high density lipoprotein cholesterol, Non HDL-콜레스테롤 ) 은최근에심혈관질환의위험을평가하는새로운지표로제안되었다 [6-8]. 대사증후군진단기준중이상지질혈증을평가하는지표는중성지방과 HDL-콜레스테롤로구성되어있으며, Non HDL-콜레스테롤측정은지질대사이상을유발하는초저밀도지질단백질 (very low density lipoprotein, VLDL), 중간밀도지질단백질 (intermediate density lipoprotein, IDL), 저밀도지단백콜레스테롤 (low density lipoprotein cholesterol, LDL-콜레스테롤 ), 지질단백질 (a) (Lipoprotein (a)) 에존재하는콜레스테롤을확인할수있다는장점이있다 [6]. Keys 등 [9] 은 24년간의추적관찰을통해 Non HDL-콜레스테롤과관상동맥질환간의관련성이 HDL-콜레스테롤보다높다고보고하였다. 또한 Menotti 등 [10] 은 3,395명의남성을 10년간조사한결과에서 Non HDL-콜레스테롤이관상동맥질환에의한사망을예측하는지표라고보고하였다. 그러나대사증후군과 Non HDL-콜레스테롤간의관련성에대한연구는진단기준, 연령등의차이로단순비교는어려우나, Lee 등 [11] 은여성을대상으로 Non HDL-콜레스테롤이대사증후군의위험요인이기는하지만대사증후군을진단하는전통적인진단기준인 HDL-콜레스테롤이나중성지방보다예측력이좋은지표는아니라고보고하였다. 또한각각의지질지표를단독적으로측정하는것보다지질측정지표의조합에의한비율로이상지질혈증을평가하는것은심혈관질환의좋은예측지표로알려져있다 [12, 13]. 특히중성지방 /HDL-콜레스테롤비율 (triglyceride to high density lipoprotein cholesterol ratio, TG/HDL-C ratio) 은심혈관질환을예측하는유용한지표이다 [12-14]. 대사증후군의주요원인인인슐린저항성을예측하는지표로중성지방 /HDL-콜레스테롤비율이주목받고있으며 [12], HDL-콜레스테롤과중성지방간에는역상관관계가존재해두가지지표를복합적으로평가하는것이제안된다 [15]. 그러나이지표들은쉽게적용가능한지표이기는하나국가와인종, 성별, 연령등의차이에따라일관되게임상에적용하는데어려움이있다. 현재까지관상동맥질환에의한사망의예측지표로서 Non HDL-콜레스테롤과중성지방 /HDL-콜레스테롤비율을평가한연구가일부보고되고는있으나, 국내에서는노인을대상으로 Non HDL-콜레스테롤과중성지방 /HDL- 콜레스테롤비율의유용성을평가한연구는부족한실정이다. 이에본연구에서는한국노인을대상으로대사증후군예측인 자로서혈중 Non HDL-콜레스테롤과중성지방 /HDL-콜레스테롤비율의임상적용가능성을평가하기위해발병예측능과적정기준값을제시하고자하였다. 대상및방법 1. 연구대상 2015년 1월부터 2017년 12월까지경기지역종합병원의건강검진센터를내원하여건강검진을실시한 65세이상노인을대상으로하였다. 건강검진문진표의과거병력을바탕으로간질환이나신장질환, 갑상선질환의병력자, 혈중지질수치에영향을미치는약물을복용하거나, 결측값을포함하는경우를제외한최종대상자는 1,543명 ( 남성 956명, 여성 587명 ) 이었다. 본연구는경기지역종합병원에서생명윤리심의위원회의심의를거쳐승인을받은후실시하였다 (IRB No: SP-2018-14- 012-058). 2. 연구방법 1) 신체측정및혈액검사혈압측정은아네로이드혈압계 (Medisave UK Ltd., Weymouth, UK) 를사용하여안정상태에서 2회반복측정후평균값을제시하였으며, 신장및체중은자동화된체성분분석기 Inbody 720 (Biospace Co., Seoul, Korea) 로측정하였다. 체중 (kg) 을키 (m) 의제곱으로나누어체질량지수 (body mass index, BMI) 를계산하였다. 허리둘레측정은양발을벌리고가볍게숨을내쉰상태에서최하위늑골하부와골반장골능과의중간지점을줄자로측정하였다. 혈액분석을위해 8시간이상공복상태에서오전에전주정맥 (antecubital vein) 에서채혈을실시하였다. 총콜레스테롤, 중성지방, HDL-C, LDL-C, 공복혈당, 요산, 고감도 C-반응성단백 (high sensitivity C-reactive protein, hs- CRP) 은 TBA-200FR NEO (Toshiba, Tokyo, Japan) 생화학장비로측정하였다. 당화혈색소 (hemoglobin A1c, HbA1c, GHb) 는 Variant II (Bio Rad, CA, USA) 로분석하였으며, 인슐린은 Roche Modular Analytics E170 (Roche, Mannheim, Germany) 로분석하였다. Non HDL-콜레스테롤은총콜레스테롤과 HDL-콜레스테롤의차이로계산하였다 [7, 8]. 2) 대사증후군진단기준대사증후군은 2005년미국심장학회에서발표한 American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) 기준에따라 5가지지표중 3가지항목이상만족

Korean J Clin Lab Sci. Vol. 50, No. 3, September 2018 247 하는경우진단하였다. 또한 AHA/NHLBI 의기준중복부비만은 World Health Organization (WHO) West Pacific Region 에서제시하는아시아-태평양인의기준을적용하였다 [16, 17]. 구체적인진단기준은다음과같다. 1 허리둘레 : 남성 90 cm, 여성 80 cm 2 공복혈당 : 100 mg/dl 3 중성지방 : 150 mg/dl 4 HDL-C: 남성 <40 mg/dl, 여성 <50 mg/dl 5 혈압 : 수축기혈압 130 mmhg 또는이완기혈압 85 mmhg 이며, 고혈압이나당뇨병약제를투여하고있는대상자는해당진단기준에속하는것으로간주하였다. 3. 통계분석이연구의통계분석은 IBM SPSS Statistics 24.0 (IBM, NY, USA) 를이용하여처리하였으며, 연구결과는평균 ± 표준편차로제시되었다. 한국노인의성별, 대사증후군진단유무에따른집단간임상적특성의차이를확인하기위해독립표본 t-test (independent sample t-test) 를실시하였다. 또한대사증후군위험요인항목수에따른혈중 Non HDL-콜레스테롤과중성지방 /HDL-콜레스테롤비율의차이를확인하기위해일원변량분석 (one way analysis of variance, one-way ANOVA) 을통해결과를얻었으며, Scheffe의사후검정을통해유의성을검증하였다. 대사증후군위험요인과 Non HDL-콜레스테롤및중성지방 /HDL-콜레스테롤비율간에연관성에대해서는상관관계 (Correlation, correlation coefficient) 를분석하였으며, ROC (receiver operating characteristic) 곡선을통해민감도와특이도를구하여대사증후군예측력과적정기준값을구하였다. Non HDL-콜레스테롤과중성지방 /HDL-콜레스테롤비율의사분위수를바탕으로대사증후군발병률을예측하기위해연령, 허리둘레, 혈압, 공복혈당을보정한후로지스틱회귀분석 (logistic regression) 을적용하였다. 통계적유의성의판정은유의확률값이 0.05 미만인경우로하였다. 결과 1. 성별및대사증후군진단유무에따른대상자의임상적특성 65세이상노인의성별에따른대상자의임상적특성은 Table 1에제시한바와같다. 신장, 체중, 허리둘레는여성보다남성이높았으며, BMI는남성보다여성이높았다 ( 모두 P< 0.001). 총콜레스테롤, HDL-콜레스테롤, LDL-콜레스테롤, Non HDL-콜레스테롤은여성이남성보다높았으며 ( 모두 P< 0.001), 공복혈당, 요산, hs-crp는여성보다남성이높게나타났다 ( 모두 P<0.001). 그러나연령, 수축기와이완기혈압, 중성지방, 중성지방 /HDL- 콜레스테롤비율, HbA1c, 인슐린은성별에따른차이가없었다. 대사증후군진단유무에따른대상자의임상적특징으로연령은대사증후군진단군이높았으며 Table 1. Characteristics of the study participants according to gender and presence of metabolic syndrome Variables Women (N=587) Men (N=956) P-value Without MetS (N=1,232) With MetS (N=311) P-value Age (years) 70.38±4.58 70.67±4.84 0.244 70.43±4.66 71.09±5.02 0.028 Height (cm) 152.28±5.52 165.09±6.11 <0.001 160.42±8.39 159.42±9.18 0.082 Weight (kg) 57.31±7.62 65.96±9.33 <0.001 61.61±9.39 66.86±9.68 <0.001 BMI (kg/m 2 ) 24.71±2.95 24.17±2.97 <0.001 23.90±2.93 26.26±2.33 <0.001 WC (cm) 81.02±7.44 85.07±8.03 <0.001 82.16±7.77 88.96±6.75 <0.001 SBP (mmhg) 119.50±16.59 119.05±14.71 0.584 117.04±14.62 127.86±15.61 <0.001 DBP (mmhg) 74.33±9.88 74.48±9.17 0.763 73.36±9.17 78.61±9.36 <0.001 TC (mg/dl) 200.35±37.12 185.67±32.67 <0.001 190.54±34.47 194.07±37.65 0.114 HDL-C (mg/dl) 55.87±13.32 52.76±13.96 <0.001 56.08±13.66 45.49±10.80 <0.001 LDL-C (mg/dl) 125.80±33.76 113.92±29.13 <0.001 117.39±30.97 122.91±33.32 0.008 TG (mg/dl) 124.96±70.53 121.40±67.68 0.324 108.38±56.61 179.69±82.05 <0.001 Non-HDL-C (mg/dl) 144.48±36.90 132.90±32.11 <0.001 134.46±33.63 148.58±35.46 <0.001 TG to HDL-C ratio (mg/dl) 2.49±1.93 2.57±1.79 0.406 2.11±1.40 4.23±2.36 <0.001 Glucose (mg/dl) 95.39±17.99 99.65±24.01 <0.001 95.08±20.63 109.72±23.40 <0.001 HbA1c (%) 5.99±0.72 6.04±0.93 0.314 5.92±0.80 6.45±0.95 <0.001 Insulin (µu/ml) 5.53±3.89 4.98±3.80 0.133 4.50±3.18 7.71±4.77 <0.001 Uric acid (mg/dl) 4.45±1.18 5.55±1.33 <0.001 5.09±1.34 5.28±1.52 0.028 hs-crp (mg/dl) 0.16±0.26 0.26±0.65 <0.001 0.21±0.54 0.25±0.50 0.227 Values are presented as means±standard deviations. Abbreviations: MetS, metabolic syndrome; BMI, body mass index; WC, waist circumference; SBP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; TG, triglyceride; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; HbA1c, hemoglobin A1c; hs-crp, high sensitivity C-reactive protein.

248 Seung Bok Hong and Kyung-A Shin. Non HDL-cholesterol and Triglyceride to HDL-cholesterol Ratio (P=0.028), 체중, BMI, 허리둘레, 수축기와이완기혈압또한대사증후군비진단군보다대사증후군진단군에서높게나타났다 ( 모두 P<0.001). LDL-콜레스테롤 (P=0.008), 중성지방, Non HDL-콜레스테롤, 중성지방 /HDL-콜레스테롤비율, 공복혈당, HbA1c, 인슐린, 요산은대사증후군진단군에서높았으며 ( 모두 P<0.001), HDL-콜레스테롤은대사증후군진단군보다대사증후군비진단군에서높게나타났다 (P<0.001). 그러나대사증후군진단유무에따른신장, 총콜레스테롤, hs-crp는집단간차이가없었다 (Table 1). 2. 대사증후군위험요인항목수에따른 Non HDL- 콜레스테롤과중성지방 /HDL- 콜레스테롤비율의차이남성의대사증후군위험요인항목수에따른 Non HDL-콜레스테롤의차이는대사증후군위험요인이없는군보다대사증후군위험요인이 2개, 3개인군에서 Non HDL-콜레스테롤이높았으며, 대사증후군위험요인이 1개인군보다대사증후군위험요인이 3개인군에서 Non HDL-콜레스테롤이높았다 (P< 0.05). 여성의경우대사증후군위험요인이없는군, 1개, 2개인군보다대사증후군위험요인이 4개이상인군에서 Non HDL- 콜레스테롤이높았으며, 대사증후군위험요인이 3개인군은대사증후군위험요인이 1개인군보다 Non HDL-콜레스테롤이높았다 (Figure 1). 대사증후군위험요인항목수에따른남성의중성지방 /HDL-콜레스테롤비율의차이는대사증후군위험요인항목수가증가할수록중성지방 /HDL-콜레스테롤비가비례하여증가하였으며, 여성의경우대사증후군위험요인이 2개이상인군에서대사증후군위험요인항목수가증가할수록중성지방 /HDL-콜레스테롤비가비례적으로증가하였다 (Figure 1). 3. 대사증후군위험요인과 Non HDL-콜레스테롤및중성지방 /HDL- 콜레스테롤비율간의상관관계대사증후군위험요인과 Non HDL-콜레스테롤및중성지방 / HDL-콜레스테롤비율간의상관관계를확인한결과는 Table 2 에제시하였다. 모든성별에서 Non HDL-콜레스테롤은허리둘레 (r=0.080), 수축기 (r=0.069) 와이완기혈압 (r=0.065), 중성지방 (r=0.373) 과양의상관관계를보였으며, HDL-콜레스테롤 (r= 0.150) 과는음의상관관계를나타냈다. 여성의경우 Non HDL-콜레스테롤은공복혈당을제외한대사증후군위험요인과상관관계를보였으며, 남성에서는허리둘레 (r=0.143), 중성지방 (r=0.385) 과양의상관관계를, HDL-콜레스테롤 (r= 0.177) 과는음의상관성을보였다. 모든성별에서중성지방 / HDL-콜레스테롤비율은허리둘레 (r=0.214), 수축기 (r=0.064) 와이완기혈압 (r=0.079), 중성지방 (r=0.936), 공복혈당 (r=0.085) 과양의상관관계를보였으며, HDL-콜레스테롤 (r= 0.568) 과는음의상관관계를나타냈다. 여성의경우중성지방 /HDL-콜 Table 2. Correlations between the Non-HDL-C, TG to HDL-C ratio and metabolic syndrome components Non-HDL-C TG to HDL-C ratio Overall WC (cm) 0.080** 0.214** SBP (mmhg) 0.069** 0.064* DBP (mmhg) 0.065* 0.079** TG (mg/dl) 0.373** 0.936** HDL-C (mg/dl) 0.150** 0.568** Glucose (mg/dl) 0.019 0.085** Women WC (cm) 0.100* 0.188** SBP (mmhg) 0.130** 0.139** DBP (mmhg) 0.110** 0.163** TG (mg/dl) 0.359** 0.940** HDL-C (mg/dl) 0.164** 0.560** Glucose (mg/dl) 0.006 0.031 Men WC (cm) 0.143** 0.233** SBP (mmhg) 0.018 0.008 DBP (mmhg) 0.035 0.019 TG (mg/dl) 0.385** 0.936** HDL-C (mg/dl) 0.177** 0.577** Glucose (mg/dl) 0.009 0.111** *P<0.05, **P<0.001. Abbreviations: See Table 1. Figure 1. Differences in Non HDL-C and TG to HDL-C ratio according to the number of risk factors for metabolic syndrome. Abbreviations: See Table 1. a, significantly different from the MetS score 0 at P<0.05; b, significantly different from the MetS score 1 at P< 0.05; c, significantly different from the MetS score 2 at P<0.05; d, significantly different from the MetS score 3 at P<0.05.

Korean J Clin Lab Sci. Vol. 50, No. 3, September 2018 249 레스테롤비율은공복혈당을제외한대사증후군위험요인과상관관계를나타냈으며, 남성은허리둘레 (r=0.233), 중성지방 (r=0.936), 공복혈당 (r=0.111) 과는양의상관관계를, HDL-콜레스테롤 (r= 0.577) 과는음의상관성을나타냈다 (Table 2). 4. Non HDL-콜레스테롤및중성지방 /HDL- 콜레스테롤비율의대사증후군예측력대사증후군예측을위한 Non HDL-콜레스테롤및중성지방 / HDL-콜레스테롤비의 AUC (95% CI) 는 Table 3에제시한바와같다. Non HDL-콜레스테롤의 AUC 값은 0.616, 0.588, 0.624 ( 전체대상자, 남성, 여성 ) 로나타났다. ROC 곡선을통한대사증후군예측을위한 Non HDL 콜레스테롤의적정기준값은전체대상자및여성에서 141.50, 남성에서 131.50 이었다. 중성지방 /HDL-콜레스테롤비율의 AUC값은 0.825, 0.847, 0.819 ( 전체대상자, 여성, 남성 ) 로나타났다. ROC 곡선을통한대사증후군예측을위한 Non HDL-콜레스테롤의적정기준값은전체대상자에서는 2.78, 여성은 2.79, 남성은 2.77 이었다 (Table 3). 5. Non HDL-콜레스테롤및중성지방 /HDL- 콜레스테롤비율의사분위수에따른대사증후군발병률 Non HDL-콜레스테롤사분위수에따른대사증후군발병가능성은남녀모두에서연령, 허리둘레, 혈압, 공복혈당을보정한경우와보정하지않은경우모두에서유의한차이가없었다 (Table 4). 남성에서중성지방 /HDL-콜레스테롤비사분위수에따른대사증후군발병가능성은보정하지않은경우 1사분위수의위험도를 1로보았을때 3사분위수에서대사증후군발병위험도는 2.9, 4사분위수의대사증후군발병위험도는 17로나타났다. 반면, 연령, 허리둘레, 혈압, 공복혈당을보정한경우 1사분위수와비교하여 4사분위수에서대사증후군발병위험도는 27로나타났다. 여성에서중성지방 /HDL-콜레스테롤비사분위수에따른대사증후군발병가능성은보정하지않은경우 1사분위수와비교하여 3사분위수에서대사증후군발병위험도는 9.5, 4사분위수에서대사증후군발병위험도는 29로나타났다. 반면, 연령, 허리둘레, 혈압, 공복혈당을보정한경우 1사분위수와비교하여 4사분위수에서의대사증후군발병위험도는 29 이었다 (Table 5). Table 3. Non-HDL-C and TG to HDL-C ratio quartile to predict of metabolic syndrome Cutoff value AUC (95% CI) Sensitivity Specificity Overall Non-HDL-C 131.50 0.616 (0.582 0.650) 0.717 0.483 TG to HDL-C ratio 2.78 0.825 (0.799 0.851) 0.778 0.783 Women Non-HDL-C 141.50 0.624 (0.575 0.674) 0.693 0.526 TG to HDL-C ratio 2.79 0.847 (0.810 0.885) 0.733 0.851 Men Non-HDL-C 131.50 0.588 (0.540 0.636) 0.665 0.514 TG to HDL-C ratio 2.77 0.819 (0.783 0.856) 0.820 0.746 Abbreviations: See Table 1; AUC, area under the curve; CI, confidence interval. Table 4. Unadjusted and adjusted odds ratios of the Non-HDL-C associated with metabolic syndrome Odds ratio for Men Unadjusted (95% CI) P-value Adjusted (95% CI) P-value 1 st Quartile 1 1 2 nd Quartile 0.744 (0.408 1.360) 0.337 1.504 (0.531 4.256) 0.442 3 rd Quartile 1.039 (0.592 1.822) 0.895 1.751 (0.473 6.486) 0.402 4 th Quartile 0.746 (0.407 1.366) 0.343 2.793 (0.413 18.879) 0.292 Odds ratio for Women 1 st Quartile 1 1 2 nd Quartile 1.390 (0.603 3.206) 0.440 1.652 (0.454 6.009) 0.446 3 rd Quartile 1.296 (0.588 2.860) 0.520 0.925 (0.202 4.241) 0.920 4 th Quartile 1.138 (0.524 2.470) 0.744 0.511 (0.069 3.779) 0.511 Adjusted odds ratios for age, waist circumference, blood pressure, and fasting glucose. Abbreviations: See Table 3.

250 Seung Bok Hong and Kyung-A Shin. Non HDL-cholesterol and Triglyceride to HDL-cholesterol Ratio Table 5. Unadjusted and adjusted odds ratios of the TG to HDL-C ratio associated with metabolic syndrome Odds ratio for Men Unadjusted (95% CI) P-value Adjusted (95% CI) P-value 1 st Quartile 1 1 2 nd Quartile 0.785 (0.287 2.147) 0.637 0.408 (0.100 1.673) 0.213 3 rd Quartile 2.857 (1.257 6.495) 0.012 1.814 (0.562 5.854) 0.319 4 th Quartile 17.025 (7.789 37.213) <0.001 27.114 (17.279 37.997) <0.001 Odds ratio for Women 1 st Quartile 1 1 2 nd Quartile 3.435 (0.950 12.425) 0.060 0.652 (0.130 3.267) 0.603 3 rd Quartile 9.459 (2.824 21.683) <0.001 2.272 (0.486 10.627) 0.297 4 th Quartile 29.190 (10.22 33.53) <0.001 28.624 (10.460 31.135) <0.001 Adjusted odds ratios for age, waist circumference, blood pressure, and fasting glucose. Abbreviations: See Table 3. 고찰본연구결과대사증후군예측력은 Non HDL-콜레스테롤보다중성지방 /HDL-콜레스테롤비율이높게나타났으며, 대사증후군발병을예측하는중성지방 /HDL-콜레스테롤비율의적정기준값은 2.8이었다. 또한연령, 허리둘레, 혈압, 공복혈당을보정한후중성지방 /HDL-콜레스테롤비율은 1사분위수보다 4 사분위수의대사증후군발병위험이유의하게높았다. 전세계적으로심혈관질환은가장많은사망원인중하나이며, 인슐린저항성이나대사증후군은심혈관계질환과밀접한관련이있다 [18, 19]. LDL-콜레스테롤은심혈관질환을예측할수있으며, 약물에의한 LDL-콜레스테롤의감소는심혈관질환에긍정적인효과를가져오는것으로알려져있다 [20, 21]. 따라서수년간의지질강하지침에서 LDL-콜레스테롤을치료의주요대상으로추천하고있다 [22]. 그러나 LDL-콜레스테롤은대사증후군기본구성요소에포함되어있지않으며, 이를보완하기위해 LDL-콜레스테롤의정보를포함한 Non HDL-콜레스테롤을계산하여제공하는것이유용하다고보고된다 [23]. 중요한것은 Non HDL-콜레스테롤이 LDL-콜레스테롤뿐만아니라아포지질단백 B보다심혈관사건의위험과더밀접하게관련되어있다고보고된점이다 [24]. 또한 68세이상의노인을대상으로남성에서 Non HDL-콜레스테롤은동맥경화발생의위험요인으로제안되며, LDL-콜레스테롤보다도상대위험도가높았다 [6]. 대사증후군과관련하여 Lee 등 [11] 은 Non HDL-콜레스테롤이대사증후군발병에독립적인위험요인이지만, 중성지방 /HDL-콜레스테롤비율, 중성지방, 아포지질단백 B/ 아포지질단백 A1 비율, 총콜레스테롤 /HDL-콜레스테롤비율등보다상대위험도가낮다고보고하였다. 노인을대상으로한본연구 에서도 Non HDL-콜레스테롤은중성지방 /HDL-콜레스테롤비율보다대사증후군예측력이낮았으며, 대사증후군발병에유의미한영향을미치지못하는것으로나타났다. 혈중중성지방증가와 HDL-콜레스테롤저하는인슐린저항성의특징적대사이상이다 [25]. 따라서, 10년동안 Framingham 방정식으로평가한결과중성지방 /HDL-콜레스테롤비율이증가할수록관상동맥질환위험도는높아진다 [26]. 또한높은중성지방 /HDL-콜레스테롤비율은작고조밀한저밀도지단백질입자 (small, dense low density lipoprotein particles) 의존재를예측하는지표이며 [27], 인슐린저항성및대사증후군발병을진단하는데유용하다 [28]. 미국및유럽인을대상으로높은중성지방 /HDL-콜레스테롤비율은당뇨병발병을암시하지만, 중성지방 /HDL-콜레스테롤비율과인슐린저항성의관계는인종, 민족, 성별에따라다양한결과를보인다 [12, 29]. 본연구결과중성지방 /HDL-콜레스테롤비율은대사증후군발병에영향을미치며, 관련요인을보정한후남녀모두에서중성지방 / HDL-콜레스테롤비율은 1사분위수보다 4사분위수의대사증후군발병위험이남녀각각 27배, 29배유의하게높았다. 이는비용효율적인중성지방 /HDL-콜레스테롤비율이대사증후군을확인하기위한대안적이고간단한방법이될수있음을의미하는결과이다. 또한중성지방 /HDL-콜레스테롤비율은내장지방수치와높은상관관계가있는것으로보고되며 [30], 본연구에서는중성지방과 HDL-콜레스테롤을제외하면허리둘레와상관관계가상대적으로높게나타났다. 이전의연구에서중성지방 /HDL-콜레스테롤비율과인슐린저항성사이의관계는성별에따라다른결과를나타낸다. 다낭성난소증후군으로진단된한국여성을대상으로중성지방 / HDL-콜레스테롤비율의진단기준값은 2.5로보고된다 [31].

Korean J Clin Lab Sci. Vol. 50, No. 3, September 2018 251 백인을대상으로인슐린저항성을예측하기위한중성지방 / HDL-콜레스테롤비율의최적기준값은남성과여성을포함하여수행된연구에서 3.5이었으며 [27], 과체중과인슐린저항성의지표로서제시되는중성지방 /HDL-콜레스테롤비율의적정기준값은 3.0으로보고된다 [26]. 또다른연구는유럽과멕시코인에서중성지방 /HDL-콜레스테롤비율이각각 2.5와 3.5를초과하는여성과남성에서인슐린저항성이더높았다 [12, 32]. 노인을대상으로한본연구결과대사증후군발병을예측하는중성지방 /HDL-콜레스테롤비율의적정기준값은남녀모두 2.8 이었다. 이러한결과는기저질환이나연령뿐만아니라인종에따라서도다양하게나타나는데, Eckel 등 [33] 은그기전으로지단백분해효소 (lipoprotein lipase, LPL) 활성에대한인종간의차이를제안하였다. 지단백분해효소는혈중중성지방이풍부한지질단백질을제거하는역할을하는데, 아프리카계인종이코카서스인종보다지단백분해효소가높게나타나중성지방을낮추는원인이된다 [34]. 따라서노인을대상으로중성지방 / HDL-콜레스테롤비율 2.8을기준으로낮은군과높은군의차이를전향적으로평가할수있는후속연구가요구된다. 결론적으로노인에서 Non HDL-콜레스테롤보다중성지방 / HDL-콜레스테롤비율이대사증후군진단을위해임상적으로적용가능성이더높았다. 또한중성지방 /HDL-콜레스테롤비율은대사증후군위험을평가하는간단하고실용적인지표가될수있겠다. 요약한국노인을대상으로대사증후군예측인자로서혈중 Non HDL-콜레스테롤과중성지방 /HDL-콜레스테롤비율의임상적용가능성을평가하고자하였다. 2015년 1월부터 2017년 12 월까지경기지역종합병원의건강검진센터를내원하여건강검진을실시한 65세이상노인을 1,543명을대상으로하였다. 대사증후군은 American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) 기준에따라진단하였다. 복부비만은 World Health Organization (WHO) West Pacific Region 에서제시하는아시아-태평양인의기준을적용하였다. Non HDL-콜레스테롤은총콜레스테롤과 HDL-콜레스테롤의차이로계산하였다. 대사증후군예측력은 Non HDL- 콜레스테롤보다중성지방 /HDL-콜레스테롤비율이높게나타났다. 관련요인을보정한후중성지방 /HDL-콜레스테롤비율은 1사분위수보다 4사분위수의대사증후군발병위험이높았다. 또한대사증후군발병을예측하는중성지방 /HDL-콜레스 테롤비율의적정기준값은 2.8이었다. 중성지방 /HDL-콜레스테롤비율은대사증후군위험을평가하는간단하고실용적인지표가될수있겠다. Acknowledgements: None Conflict of interest: None REFERENCES 1. Reaven GM. Role of insulin resistance in human disease (syndrome X): an expanded definition. Annu Rev Med. 1993; 44:121-131. 2. Park HS, Lee SY, Kim SM, Han JH, Kim DJ. Prevalence of the metabolic syndrome among Korean adults according to the criteria of the International Diabetes Federation. Diabetes Care. 2006;29:933-934. 3. Lim JW, Kim SY, Ke SS, Cho BL. The prevalence of obesity, abdominal obesity and metabolic syndrome among elderly in general population. Korean J Fam Med. 2011;32:128-134. https://doi.org/10.4082/2011;32:128. 4. Guize L, Thomas F, Pannier B, Bean K, Danchin N, Bénétos A. Metabolic syndrome: prevalence, risk factors and mortality in a French population of 62,000 subjects. Bull Acad Natl Med. 2006;190:685-697. 5. Miccoli R, Bianchi C, Odoguardi L, Penno G, Caricato F, Giovannitti MG, et al. Prevalence of the metabolic syndrome among Italian adults according to ATP III definition. Nutr Metab Cardiovasc Dis. 2005;15:250-254. 6. Kawamoto R, Oka Y, Tomita H, Kodama A. Non-HDL cholesterol as a predictor of carotid atherosclerosis in the elderly. J Atheroscler Thromb. 2005;12:143-148. 7. Cui Y, Blumenthal RS, Flaws JA, Whiteman MK, Langenberg P, Bachorik PS, et al. Non-high-density lipoprotein cholesterol level as a predictor of cardiovascular disease mortality. Arch Intern Med. 2001;161:1413-1419. 8. Lu W, Resnick HE, Jablonski KA, Jones KL, Jain AK, Howard WJ, et al. Non-HDL cholesterol as a predictor of cardiovascular disease in type 2 diabetes: the strong heart study. Diabetes Care. 2003;26:16-23. 9. Keys A, Karvonen MJ, Punsar S, Menotti A, Fidanza F, Farchi G. HDL serum cholesterol and 24-year mortality of men in Finland. Int J Epidemiol. 1984;13:428-435. 10. Menotti A, Spagnolo A, Scanga M, Dima F. Multivariate prediction of coronary deaths in a 10 year follow-up of an Italian occupational male cohort. Acta Cardiol. 1992;47:311-320. 11. Lee KH, Son JC, Kim BT, Choi BH, Hye JS, Cha CK, et al. Non-HDL Cholesterol as a risk factor of metabolic syndrome in Korean women. Korean J Obes. 2007;16:102-110. 12. Salazar MR, Carbajal HA, Espeche WG, Leiva Sisnieguez CE, Balbín E, Dulbecco CA, et al. Relation among the plasma triglyceride/high-density lipoprotein cholesterol concentration ratio, insulin resistance, and associated cardio-metabolic risk factors in men and women. Am J Cardiol. 2012;109:1749-1753.

252 Seung Bok Hong and Kyung-A Shin. Non HDL-cholesterol and Triglyceride to HDL-cholesterol Ratio 13. Salazar MR, Carbajal HA, Espeche WG, Aizpurúa M, Leiva Sisnieguez CE, Leiva Sisnieguez BC, et al. Use of the plasma triglyceride/high-density lipoprotein cholesterol ratio to identify cardiovascular disease in hypertensive subjects. J Am Soc Hypertens. 2014;8:724-731. 14. Jeppesen J, Hein HO, Suadicani P, Gyntelberg F. High triglycerides/low high-density lipoprotein cholesterol, ischemic electrocardiogram changes, and risk of ischemic heart disease. Am Heart J. 2003;145:103-108. 15. Burchfiel CM, Laws A, Benfante R, Goldberg RJ, Hwang LJ, Chiu D, et al. Combined effects of HDL cholesterol, triglyceride, and total cholesterol concentrations on 18-year risk of atherosclerotic disease. Circulation. 1995;92:1430-1436. 16. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112:2735-2752. 17. World Health Organization. The Asia-Pacific Perspective: redefining obesity and its treatment. Sydney, Australia: Health communications Australia; 2000. p19-20. 18. Lee SW, Kim HC, Lee HS, Suh I. Thirty-year trends in mortality from cerebrovascular diseases in Korea. Korean Circ J. 2016;46:507-514. 19. Tsay YC, Chen CH, Pan WH. Ages at onset of 5 cardiometabolic diseases adjusting for nonsusceptibility: implications for the pathogenesis of metabolic syndrome. Am J Epidemiol. 2016;184:366-377. 20. Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97:1837-1847. 21. Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670-1681. 22. Preiss D, Neely D. Biochemistry laboratories should routinely report non-hdl-cholesterol. Ann Clin Biochem. 2015;52(Pt 6):629-631. 23. Khan SH, Asif N, Ijaz A, Manzoor SM, Niazi NK, Fazal N. Status of non-hdl-cholesterol and LDL-cholesterol among subjects with and without metabolic syndrome. J Pak Med Assoc. 2018;68:554-558. 24. Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302:1993-2000. 25. Ginsberg HN, Zhang YL, Hernandez-Ono A. Regulation of plasma triglycerides in insulin resistance and diabetes. Arch Med Res. 2005;36:232-240. 26. Marotta T, Russo BF, Ferrara LA. Triglyceride-to-HDL-cholesterol ratio and metabolic syndrome as contributors to cardiovascular risk in overweight patients. Obesity (Silver Spring). 2010;18:1608-1613. 27. McLaughlin T, Reaven G, Abbasi F, Lamendola C, Saad M, Waters D, et al. Is there a simple way to identify insulin-resistant individuals at increased risk of cardiovascular disease? Am J Cardiol. 2005;96:399-404. 28. Kannel WB, Vasan RS, Keyes MJ, Sullivan LM, Robins SJ. Usefulness of the triglyceride-high-density lipoprotein versus the cholesterol-high-density lipoprotein ratio for predicting insulin resistance and cardiometabolic risk (from the Framingham Offspring Cohort). Am J Cardiol. 2008;101:497-501. 29. Kim-Dorner SJ, Deuster PA, Zeno SA, Remaley AT, Poth M. Should triglycerides and the triglycerides to high-density lipoprotein cholesterol ratio be used as surrogates for insulin resistance? Metabolism. 2010;59:299-304. 30. Salazar MR, Carbajal HA, Espeche WG, Aizpurúa M, Maciel PM, Reaven GM. Identification of cardiometabolic risk: visceral adiposity index versus triglyceride/hdl cholesterol ratio. Am J Med. 2014;127:152-157. 31. Song DK, Lee H, Sung YA, Oh JY. Triglycerides to high-density lipoprotein cholesterol ratio can predict impaired glucose tolerance in young women with polycystic ovary syndrome. Yonsei Med J. 2016;57:1404-1411. 32. Murguía-Romero M, Jiménez-Flores JR, Sigrist-Flores SC, Espinoza-Camacho MA, Jiménez-Morales M, Piña E, Méndez- Cruz AR, et al. Plasma triglyceride/hdl-cholesterol ratio, insulin resistance, and cardiometabolic risk in young adults. J Lipid Res. 2013;54:2795-2799. 33. Eckel RH, Yost TJ, Jensen DR. Alterations in lipoprotein lipase in insulin resistance. Int J Obes Relat Metab Disord. 1995;19(Suppl 1):S16-21. 34. Grundy SM. Hypertriglyceridemia, atherogenic dyslipidemia, and the metabolic syndrome. Am J Cardiol. 1998;81:18-25.