LDL Cholesterol 또는 Total Cholesterol의 적용에 따른 Framingham Risk Score와 10년 내 심혈관질환 발생 위험도 평가

권세영 ( Se Young Kwon ),나영악 ( Young Ak Na ) 대한임상검사과학회 2016 대한임상검사과학회지(KJCLS) Vol.48 No.2

증가하고 있는 심혈관질환을 예방하기 위한 연구와 함께 심혈관질환 위험도를 예측할 수 있는 평가도구에 대한 연구도 꾸준히 진행되고 있다. 가장 널리 알려져 있는 Framingham risk score (FRS)는 여러 선행 연구에서 그 타당성이 검증되었다. 본 연구에서는 연구 대상자들의 LDL 콜레스테롤과 총 콜레스테롤의 적용에 따른 FRS의 점수 차이를 살펴보고, 두 변수의 선택 적용에 따른 10년 내심혈관질환 발생 위험도의 판정에 대한 일치도를 평가해 보고자 하였다. 2011 국민건강영양조사 데이터 중 심혈관질환 진단을 받은 자를 제외한 1,530명(남성 755명, 여성 775명)의 자료를 이용하였다. LDL 콜레스테롤 또는 총 콜레스테롤 중에 어떤 항목을 적용하느냐에 따라 FRS와 심혈관질환의 10년 예측위험도는 차이가 있었다. 남녀 모두 FRS는 LDL 콜레스테롤 적용 점수 보다 총콜레스테롤적용 점수가 더 높았다. 위험도 10% 미만의 저위험군, 10∼19%의 중등도 위험군, 20% 이상의 고위험군 분류에서 남성 106명, 여성26명의 판정이 일치하지 않았다. 코헨의 카파 계수는 남성의 경우 0.718, 여성의 경우 0.884로 나타나 여성의 경우 더 높은 일치성을 보였다. 심혈관질환의 10년 예측위험도와의 관련성에서도 LDL 콜레스테롤을 포함한 회귀식 보다 총 콜레스테롤을 포함한 회귀식에서 남녀 모두 설명력이 더 높아 총 콜레스테롤을 반영한 FRS 산출과 10년 예측 위험도의 평가가 더 상관성이 더 높고, 더불어 남성 보다는 여성에서 더 일치하는 결과가 나타남을 알 수 있었다. Studies on assessment tools for predicting cardiovascular disease risk (CDR), along with the studies to prevent CDR have been consistently reported. The validity of the Framingham risk score (FRS), a commonly known tool, has been verified through the precedent studies. In this study, we examined the differences of FRS according to the application of categories of LDL cholesterol (LDL-C) or Total cholesterol (TC), and attempted to evaluate the agreement of 10 yr CHD risk judgment based on the above-mentioned application. Excluding those diagnosed as cardiovascular diseases, data on subjects (755 men and 775 women) from the 2011 Korean National Health and Nutrition Examination Survey were used. We found differences of FRS and 10 yr CHD risk depending on the application of categories of LDL cholesterol (LDL-C) or Total cholesterol (TC). FRS of TC points were higher than those of LDL-C in both men and women. In classification of low risk (<10%), intermediate risk (10∼19%), and high risk (≥20%), there were disagreements for 106 men and 26 women. Women showed almost perfect agreement from Coefficient of Cohen’s Kappa (0.718 in men, and 0.884 in women). In assessment of 10 yr CHD risk, R-squared value from regression including TC was higher than that of LDC-C in both men and women (0.972 vs 0.885). From this result, we can draw a conclusion that correlation coefficients of FRS and CHD risk including TC were higher than those of LDC-C, and women showed a greater degree of agreement than men.

Comparison of LDL-Cholesterol direct measurement with the estimate using various formula

( Se Young Kwon ),( Young-ak Na ) 대한임상검사과학회 2012 대한임상검사과학회지(KJCLS) Vol.44 No.3

Low-Density Lipoprotein cholesterol (LDLC) is the most important marker for the treatment of hyperlipidemiain NCEP-ATP III(National Cholesterol Education Program-Adult Treatment Panel III) guideline. Therefore, LDL cholesterol is pathologically meaningful, accurate measurement should be a top priority. Currently, LDLC is directly measured in most cases, but, the estimate is still used in mass health examination or screening test. This study is about the comparison of LDL-Cholesterol direct measurement with the estimate using various formula (Friedewald: [LDL-F=TC-HDL-TG/5], Nakajima: [LDL-N=TCHDL- TG/4], Hattori: [LDL-H =0.94TC -0.94HDL-0.19TG], Puavilai: [LDL-P=TC-HDL-TG/6], Carvalho: [LDL-C=3(TC-HDL)/4]) for calculating more accurate value. We analyzed total cholesterol (TC), tryglyceride (TG), high-density lipoprotein cholesterol (HDLC), and LDLC levels of 210 subjects between June and November in 2011. Until now, the Friedewald formula is the most commonly used estimate for the LDLC. When Friedewald formula was applied, the correlation coefficient (r) was 0.940, showing high correlation. But, the result of the direct method was significantly different, compared with those of the Friedewald formula in triglyceride levels≥400 mg/dL(p<0.05). There was the highest correlation when we used LDL-P formula(r=0.947) in triglyceride levels <400 mg/dl. Also there was the lowest mean difference regardless of triglyceride level. Therefore, the study showed that TG/6 is more precise means of calculation than TG/5. On the other hand, the calculation of LDL-Cholesterol was underestimated, compared with direct measurement. It is necessary to have more data and modified Friedewald formula should be used for the accurate calculation.

LDL-콜레스테롤의 추정: Friedewald 공식과 Martin 방법의 비교

장성옥,손희정,이종석 통계청 2015 통계연구 Vol.20 No.2

Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for cardio-cerebrovascular disease such as myocardial infarction and stoke. While its accurate assessment is important, It is typically calculated using the Friedewald formula as a cost-effective method. In the Korea National Health Screening Program, LDL-C is calculated for subjects accounting for nearly 98% of its total participants when triglycerides are lower than 400 mg/dL. However, previous studies have suggested that the formula underestimates LDL-C, particularly at high triglyceride levels. In a recent study, the Martin Method as an alternative to the Friedewald formula was proposed to improve estimation of LDL-C. The aim of this study was to compare the performance of the Martin method and the Friedewald equation using a sample of 5,665 Korean adults with LDL-C measured by an enzymatic homogeneous assay (LDL-CD). The Friedewald LDL-C (LDL-CF) tended to underestimate LDL-C for subjects with triglycerides of ≥ 100 mg/dL and HDL-cholesterol levels of < 50 mg/dL. Based on the N strata of triglyceride and non-HDL- cholesterol and triglyceride levels, we generated the Martin LDL-C (LDL-CN) estimates including LDL-C5, LDL-C10, LDL-C20, LDL-C25, and LDL-C50. Compared with LDL-CF, each of LDL-CN estimates more closely approximated LDL-CD and exhibited a significantly higher overall concordance in the guideline risk classification with LDL-CD (p < 0.001 for each comparison). Overall concordance was 82.9% for LDL-CF, 85.5% for LDL-C5, and 85.8% for LDL-C25. The Martin method achieved the greatest improvement in concordance with LDL-CD at triglyceride levels of 200-399 mg/dL. In this triglyceride category, concordance was 70.4% for LDL-CF versus 80.0% for LDL-C5. Our findings suggest that the Martin method significantly improves LDL-C estimation when compared to the Friedewald formula. However, the new method requires validation in various populations to evaluate whether improvements over the Friedewald calculation are compelling enough to justify its adoption. LDL-콜레스테롤은 심근경색이나 뇌졸중 같은 심뇌혈관질환의 주된 위험인자로서, 그 정확한 측정값을 임상에 적용하는 것이 중요하다. 하지만 이의 측정은 실측값이 아닌 Friedewald 공식에의한 추정값이 널리 이용되고 있다. Friedewald 공식은 비용-효과적인 장점을 가지지만, 중성지방이 높은 수준에서 LDL-콜레스테롤을 과소평가한다는 문제점이 제기되어 왔다. 본 연구의 목적은 Friedewald 공식의 대안으로서 최근에 제시된 Martin 방법의 성과를 평가하는 것이다. 이를위해 국민건강영양조사 3개년(2009-2011) 자료를 이용하여 20세 이상의 성인 5,665명을 대상으로, 중성지방 농도 400 mg/dL 미만에서 두 가지 추정 방법의 정확도를 비교하였다. Friedewald 공식은 중성지방 농도 100 mg/dL 이상과 HDL-콜레스테롤 농도 50 mg/dL 미만에서 LDL-콜레스테롤을 과소평가하는 경향이 있었다. Friedewald 추정값과 비교했을 때, Martin 추정값들은 LDL- 콜레스테롤 실측값에 더 근접했다(p < 0.001). Friedewald 추정값의 LDL-콜레스테롤 위험수준 분류 일치도는 82.9%인 반면, Martin 추정값들의 일치도는 85.5% 수준이었다(p < 0.001). 특히 중성지방 농도가 200-399 mg/dL일 때 일치도를 크게 향상시켰는데, Friedewald 추정값은 70.4%인반면 Martin 추정값들은 80% 수준이었다. 이러한 결과는 Friedewald 공식과 비교했을 때, Martin 방법이 LDL-콜레스테롤 추정을 유의하게 개선한다는 것을 제시한다. 우리나라 국가건강검진에서 중성지방 농도 400 mg/dL 미만인 사람들에 대해서 Friedewald 추정값을 사용하는데, 이는 전체 수검자의 98% 정도에 해당한다. 향후 Friedewald 공식을 대체할 만큼 Martin 방법이탁월한지에 대한 다양한 표본을 이용한 타당성 평가를 통해, 국가건강검진의 LDL-콜레스테롤 추정에 있어 새로운 방법의 채택을 고려해볼 필요가 있다.

오히려 LDL 콜레스테롤 보다 비 HDL 콜레스테롤을 사용하는 것의 타당성

권세영,나영악 대한임상검사과학회 2013 대한임상검사과학회지(KJCLS) Vol.45 No.2

NonHDL cholesterol values have been suggested as a risk marker for cardiovascular disease. NonHDL cholesterol values were calculated, using a very simple measurement [nonHDL cholesterol =serum total cholesterol-HDL cholesterol]. This formula is very useful as a screening tool for identifying dyslipoproteinemias, risk assessment, and assessing the results of hypolipidemic therapy. The data from the 2009 Korean National Health and Nutrition Examination Survey were used. Analysis was done for 1,992 subjects with lipid panels (Cholesterol, HDL, LDLdirect and Triglycerides) results. We studied the relationship between nonHDL cholesterol and LDL cholesterol. As a result, nonHDL cholesterol values were plotted against the LDL direct and calculated values. The linear regression equation for nonHDL cholesterol and direct LDL cholesterol was nonHDLchol=23.60+1.03×LDLdirect (p<0.0001, r2=0.80) in all subjects. The subjects were classified into triglyceride values. When triglycerides are below 400 mg/dL, the linear fit to LDL direct is found to be [nonHDLchol=17.34+1.07×LDLdirect] (p<0.0001, r2=0.88) and to the Friedewald LDL calculation is [nonHDLchol=23.10+1.02×LDLcalc] (p<0.0001, r2=0.82). For triglycerides above 400 mg/dL, the linear fit equation is [nonHDLchol=87.57+0.92×LDLdirect] (p <0.0001, r2=0.50) and to the LDL calculated, it is [nonHDLchol=142.70+0.50×LDLcalc] (p <0.0001, r2=0.32). This study provides examples of the utility of nonHDL cholesterol concentrations in clinical medicine.

Validity for Use of Non-HDL Cholesterol Rather than LDL Cholesterol

Kwon, Se-Young,Na, Young-Ak 대한임상검사과학회 2013 대한임상검사과학회지(KJCLS) Vol.45 No.2

NonHDL cholesterol values have been suggested as a risk marker for cardiovascular disease. NonHDL cholesterol values were calculated, using a very simple measurement [nonHDL cholesterol=serum total cholesterol-HDL cholesterol]. This formula is very useful as a screening tool for identifying dyslipoproteinemias, risk assessment, and assessing the results of hypolipidemic therapy. The data from the 2009 Korean National Health and Nutrition Examination Survey were used. Analysis was done for 1,992 subjects with lipid panels (Cholesterol, HDL, LDLdirect and Triglycerides) results. We studied the relationship between nonHDL cholesterol and LDL cholesterol. As a result, nonHDL cholesterol values were plotted against the LDL direct and calculated values. The linear regression equation for nonHDL cholesterol and direct LDL cholesterol was $nonHDLchol=23.60+1.03{\times}LDLdirect$ (p<0.0001, $r^2=0.80$) in all subjects. The subjects were classified into triglyceride values. When triglycerides are below 400 mg/dL, the linear fit to LDL direct is found to be $[nonHDLchol=17.34+1.07{\times}LDLdirect]$ (p<0.0001, $r^2=0.88$) and to the Friedewald LDL calculation is $[nonHDLchol=23.10+1.02{\times}LDLcalc]$ (p<0.0001, $r^2=0.82$). For triglycerides above 400 mg/dL, the linear fit equation is $[nonHDLchol=87.57+0.92{\times}LDLdirect]$ (p<0.0001, $r^2=0.50$) and to the LDL calculated, it is $[nonHDLchol=142.70+0.50{\times}LDLcalc]$ (p<0.0001, $r^2=0.32$). This study provides examples of the utility of nonHDL cholesterol concentrations in clinical medicine.

Validity for Use of Non-HDL Cholesterol Rather than LDL Cholesterol

( Se-young Kwon ),( Young-ak Na ) 대한임상검사과학회 2013 대한임상검사과학회지(KJCLS) Vol.45 No.2

NonHDL cholesterol values have been suggested as a risk marker for cardiovascular disease. NonHDL cholesterol values were calculated, using a very simple measurement [nonHDL cholesterol =serum total cholesterol-HDL cholesterol]. This formula is very useful as a screening tool for identifying dyslipoproteinemias, risk assessment, and assessing the results of hypolipidemic therapy. The data from the 2009 Korean National Health and Nutrition Examination Survey were used. Analysis was done for 1,992 subjects with lipid panels (Cholesterol, HDL, LDLdirect and Triglycerides) results. We studied the relationship between nonHDL cholesterol and LDL cholesterol. As a result, nonHDL cholesterol values were plotted against the LDL direct and calculated values. The linear regression equation for nonHDL cholesterol and direct LDL cholesterol was nonHDLchol=23.60+1.03×LDLdirect (p<0.0001, r2=0.80) in all subjects. The subjects were classified into triglyceride values. When triglycerides are below 400 mg/dL, the linear fit to LDL direct is found to be [nonHDLchol=17.34+1.07×LDLdirect] (p<0.0001, r2=0.88) and to the Friedewald LDL calculation is [nonHDLchol=23.10+1.02×LDLcalc] (p<0.0001, r2=0.82). For triglycerides above 400 mg/dL, the linear fit equation is [nonHDLchol=87.57+0.92×LDLdirect] (p <0.0001, r2=0.50) and to the LDL calculated, it is [nonHDLchol=142.70+0.50×LDLcalc] (p <0.0001, r2=0.32). This study provides examples of the utility of nonHDL cholesterol concentrations in clinical medicine.

12주간 수중운동이 노인여성의 체중, 체지방율, 혈당 및 혈중지질에 미치는 영향

이명천(MyungChunLee),장유정(YouJungJang) 한국체육학회 2009 한국체육학회지 Vol.48 No.5

본 연구는 수중운동이 LDL-콜레스테롤이 ‘경계성높음(130mn/dl)’ 이상이고 체지방율이 30% 이상인 63세 이상의 노인여성에서 비만과 혈중지질의 개선에 어느 정도의 효과를 나타내는지 확인하고자 시행되었다. 수중운동프로그램은 12주간 주 3회 50분 동안 실시하였고 피험자의 수가 적어 비모수적 검정 방법(Kruskal-Wallis, Wilcoxon's signed rank test)을 사용하여 실험 전·후 체중, 체지방율, 혈당 및 혈중지질(총 콜레스테롤, 중성지방, HDL-콜레스테롤, LDL-콜레스테롤)의 변화를 비교하였다. 연구결과 총 콜레스테롤(P=0.031)과 LDL-콜레스테롤(P=0.031)은 감소하였지만 중성지방은 증가하였다(P=0.031). 체지방율, 혈당, HDL-콜레스테롤은 운동 후 감소하였으나 통계적 의미는 없었다(P=0.063). 결론적으로 12주간의 수중운동이 LDL-콜레스테롤이 높은 여성노인에서도 다른 약물이나 식이요법의 병행 없이도 LDL-콜레스테롤을 낮출 수 있음을 보여주었으며 식이를 조절하지 못하게 될 경우 운동만으로는 중성지방을 감소시킬 수 없음을 알 수 있었다. This study was designed to confirm whether aquatic exercise has positive effect on obesity and serum lipid levels on elderly women, especially whose LDL-cholesterol level was already high. The subjects were 63 years-old or older, whose percent body fat (PBF) was 30% or higher, and whose LDL-cholesterol was 130mg/dl or higher (borderline high). The exercise program was 12-week course with 50 minutes work-out, three times a week. Weight, PBF, serum glucose, and serum lipid (total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol) levels were measured before and after 12-week exercise and nonparametric test (Kruskal-Wallis, Wilcoxon's signed rank test) was used for statistical analysis. Total cholesterol (P=0.031) and LDL-cholesterol (P=0.031) level decreased but triglyceride level increased (P=0.031). PBF, serum glucose, and HDL-cholesterol level decreased but with no statistical significance. This study showed that 12-week aquatic exercise alone normalizes LDL-cholesterol levels without any medication or diet modification on elderly women whose LDL-cholesterol was high. It also showed that exercise alone cannot reduce triglyceride level suggesting the need of diet modification.

Comparison of LDL-Cholesterol direct measurement with the estimate using various formula

Kwon, Se Young,Na, Young-Ak 대한임상검사과학회 2012 대한임상검사과학회지(KJCLS) Vol.44 No.3

Low-Density Lipoprotein cholesterol (LDLC) is the most important marker for the treatment of hyperlipidemia in NCEP-ATP III(National Cholesterol Education Program-Adult Treatment Panel III) guideline. Therefore, LDL cholesterol is pathologically meaningful, accurate measurement should be a top priority. Currently, LDLC is directly measured in most cases, but, the estimate is still used in mass health examination or screening test. This study is about the comparison of LDL-Cholesterol direct measurement with the estimate using various formula (Friedewald: [LDL-F=TC-HDL-TG/5], Nakajima: [LDL-N=TC-HDL-TG/4], Hattori: [LDL-H =0.94TC-0.94HDL-0.19TG], Puavilai: [LDL-P=TC-HDL-TG/6], Carvalho: [LDL-C=3(TC-HDL)/4]) for calculating more accurate value. We analyzed total cholesterol (TC), try-glyceride (TG), high-density lipoprotein cholesterol (HDLC), and LDLC levels of 210 subjects between June and November in 2011. Until now, the Friedewald formula is the most commonly used estimate for the LDLC. When Friedewald formula was applied, the correlation coefficient (r) was 0.940, showing high correlation. But, the result of the direct method was significantly different, compared with those of the Friedewald formula in triglyceride levels ${\geq}400mg/dL$(p<0.05). There was the highest correlation when we used LDL-P formula(r=0.947) in triglyceride levels <400 mg/dl. Also there was the lowest mean difference regardless of triglyceride level. Therefore, the study showed that TG/6 is more precise means of calculation than TG/5. On the other hand, the calculation of LDL-Cholesterol was underestimated, compared with direct measurement. It is necessary to have more data and modified Friedewald formula should be used for the accurate calculation.

LDL 콜레스테롤 직접 측정법과 다양한 공식을 사용한 추정의 비교

권세영,나영악 대한임상검사과학회 2012 대한임상검사과학회지(KJCLS) Vol.44 No.3

Low-Density Lipoprotein cholesterol (LDLC) is the most important marker for the treatment of hyperlipidemia in NCEP-ATP III(National Cholesterol Education Program-Adult Treatment Panel III) guideline. Therefore, LDL cholesterol is pathologically meaningful, accurate measurement should be a top priority. Currently, LDLC is directly measured in most cases, but, the estimate is still used in mass health examination or screening test. This study is about the comparison of LDL-Cholesterol direct measurement with the estimate using various formula (Friedewald: [LDL-F=TC-HDL-TG/5], Nakajima: [LDL-N=TCHDL- TG/4], Hattori: [LDL-H =0.94TC -0.94HDL-0.19TG], Puavilai: [LDL-P=TC-HDL-TG/6], Carvalho: [LDL-C=3(TC-HDL)/4]) for calculating more accurate value. We analyzed total cholesterol (TC), tryglyceride (TG), high-density lipoprotein cholesterol (HDLC), and LDLC levels of 210 subjects between June and November in 2011. Until now, the Friedewald formula is the most commonly used estimate for the LDLC. When Friedewald formula was applied, the correlation coefficient (r) was 0.940, showing high correlation. But, the result of the direct method was significantly different, compared with those of the Friedewald formula in triglyceride levels≥400 mg/dL(p<0.05). There was the highest correlation when we used LDL-P formula(r=0.947) in triglyceride levels <400 mg/dl. Also there was the lowest mean difference regardless of triglyceride level. Therefore, the study showed that TG/6 is more precise means of calculation than TG/5. On the other hand, the calculation of LDL-Cholesterol was underestimated, compared with direct measurement. It is necessary to have more data and modified Friedewald formula should be used for the accurate calculation. .

Synthetic High-Density Lipoprotein-Like Nanocarrier Improved Cellular Transport of Lysosomal Cholesterol in Human Sterol Carrier Protein-Deficient Fibroblasts

남다은,김옥경,박유경,이정민 한국식품영양과학회 2016 Journal of medicinal food Vol.19 No.1

Sterol carrier protein-2 (SCP-2), which is not found in tissues of people with Zellweger syndrome, facilitates the movement of cholesterol within cells, resulting in abnormal accumulation of cholesterol in SCP-2-deficient cells. This study investigated whether synthetic high-density lipoprotein-like nanocarrier (sHDL-NC) improves the cellular transport of lysosomal cholesterol to plasma membrane in SCP-2-deficient fibroblasts. Human SCP-2-deficient fibroblasts were incubated with [3H-cholesterol]LDL as a source of cholesterol and sHDL-NC. The cells were fractionated by centrifugation permit tracking of [3H]-cholesterol from lysosome into plasma membrane. Furthermore, cellular content of cholesteryl ester as a storage form and mRNA expression of low-density lipoprotein (LDL) receptor were measured to support the cholesterol transport to plasma membrane. Incubation with sHDL-NC for 8 h significantly increased uptake of [3H]-cholesterol to lysosome by 53% and further enhanced the transport of [3H]-cholesterol to plasma membrane by 32%. Treatment with sHDLNC significantly reduced cellular content of cholesteryl ester and increased mRNA expression of LDL receptor (LDL-R). In conclusion, sHDL-NC enables increased transport of lysosomal cholesterol to plasma membrane. In addition, these data were indirectly supported by decreased cellular content of cholesteryl ester and increased gene expression of LDL-R. Therefore, sHDL-NC may be a useful vehicle for transporting cholesterol, which may help to prevent accumulation of cholesterol in SCP-2-deficient fibroblasts.