Evaluation of alternative calculation methods for determining low-density lipoprotein cholesterol in hemodialysis patients

OBJECTIVES: To evaluate alternative equations for the estimation of low-density lipoprotein cholesterol (LDL-C) than the Friedewald equation in hemodialysis patients. DESIGN AND METHODS: The equations LDL-C = 0.41TC - 0.14TG + 0.66ApoB - 10.43 and LDL-C = 0.94TC - 0.94HDL-C - 0.19TG were evaluated in 86 patients and compared with the Friedewald equation and the ultracentrifugation procedure. RESULTS: The alternative equations yield significantly lower bias than the Friedewald equation and are less affected by increased triglycerides (TG) levels. CONCLUSION: The alternative equations for LDL-C yield slightly better results than the Friedewald equation especially in hypertriglyceridemia.     

Comparing a novel equation for calculating low-density lipoprotein cholesterol with the Friedewald equation: A VOYAGER analysis

Treating elevated low-density lipoprotein cholesterol (LDL-C) to risk-stratified target levels is recommended in several guidelines. Thus, accurate estimation of LDL-C is required. LDL-C is typically calculated using the Friedewald equation: (total cholesterol) – (non-high-density lipoprotein cholesterol [non-HDL-C]) – (triglycerides [TGs]/5). As the equation uses a fixed value equal to 5 as a divisor for TGs, it does not account for inter-individual variability, often resulting in underestimation of risk and potentially undertreatment. It is specifically inapplicable in patients with fasting triglycerides ≥400 mg/dL. A novel method of LDL-C calculation was derived and validated by Martin et al.: (non-HDL-C) – (triglycerides/adjustable factor). This equation uses an adjustable factor, the median TG:very-low-density lipoprotein cholesterol ratio in strata defined by levels of TG and non-HDLC, as divisor for TGs, and the adjustable factor ranging from 3 to 12 has been shown to provide more accurate estimates of LDL-C compared with the Friedewald equation using a direct assay as the gold standard.We used 70,209 baseline and on-treatment lipid values from the VOYAGER meta-analysis database to determine the difference in calculated LDL-C values using the Friedewald and novel equations. In patients with TGs <400 mg/dL, LDL-C values calculated using the novel equation were plotted against those calculated using the Friedewald equation. The novel equation generally resulted in LDL-C values greater than the Friedewald calculation, with differences increasing with decreasing LDL-C levels; 23% of individuals who reached a LDL-C target of 70 mg/dL with the Friedewald equation did not achieve this target when the novel equation was used to calculate LDL-C; these figures were 8% and 2% for <100 mg/dL and < 130 mg/dL targets, respectively. In patients with triglycerides ≥400 mg/dL, in whom the Friedewald equation is not valid, lipid values calculated using the novel equation were compared with those obtained by β-quantification. Values calculated with the novel equation did not appear to be closely related with those calculated by β-quantification in these patients. In conclusion, the novel equation provides a higher estimation of exact LDL-C values than the Friedewald equation, particularly in patients with low LDL-C levels, which may result in undertreatment of some patients whose LDL-C was calculated using the Friedewald method. However, neither may be suitable for patients with TG ≥400 mg/dL.     

Direct measurement of LDL-C in children: performance of two surfactant-based methods in a general pediatric population

OBJECTIVES: Several pediatric advisory groups have recommended selective screening for dyslipidemia in children. Low-density lipoprotein cholesterol (LDL-C) is measured clinically with the Friedewald calculation in fasting samples. Nonfasting measurement of LDL-C would be clinically useful in children. DESIGN AND METHODS: In the present study, we examine the performance of two surfactant-based direct LDL-C assays in paired samples, fasting and nonfasting, from 100 children. RESULTS: LDL-C in the fasting state was significantly lower with the Friedewald estimation: 2.43 +/- 0. 61 mmol/L, N-geneous (Genzyme Corp.) direct LDL-C: 2.30 +/- 0.59 mmol/L, and Roche (Roche Diagnostics) direct LDL-C: 2.32 +/- 0.57 mmol/L than with ultracentrifugation-dextran-sulfate-Mg(2+) precipitation (UC-DS): 2.47 +/- 0.64 mmol/L. Moreover, there was increased negative bias using nonfasting samples with N-geneous: 2. 25 +/- 0.56 mmol/L and Roche: 2.26 +/- 0.56 mmol/L compared with fasting UC-DS. Correlation with US-DS was highest for Friedewald (r = 0.974) and fasting N-geneous (r = 0.973), and lowest with nonfasting N-geneous (r = 0.849) and Roche in fasting (r = 0.891) and nonfasting samples (r = 0.747). The sensitivity at LDL-C concentration of 2.85 mmol/L for the two direct methods when either fasting or nonfasting samples were used, was lower than that obtained with Friedewald. CONCLUSION: Overall, these direct LDL-C assays demonstrated limited utility in screening children but may be useful in the management of lipid disorders.     

血脂相关指标测定方法的比较研究

目的对比研究肝素抗凝、方法选择等因素对血脂指标测定值的影响。方法⑴随机抽样体检者130人,采血后离心分离血浆(肝素抗凝)和血清。按试剂盒方法(直接法),分别测定两组的甘油三酯(TG),总胆固醇(TC),低密度脂蛋白胆固醇(LDL-C),高密度脂蛋白胆固醇(HDL-C),载脂蛋白A(ApoA),载脂蛋白B(ApoB)等指标,并对两组差异进行统计性分析。⑵随机抽样心血管患者320人,按直接法测定血清TG,TC,LDL-C,HDLC,ApoA,ApoB等指标。将患者分为TG<1.5mmol/L(n=170),1.5≤TG<2.5mmol/L(n=96),2.5≤TG<3.5mmol/L(n=29),3.5≤TG<4.5mmol/L(n=10),TG≥4.5mmol/L(n=15)等5组,根据Friedewald、Planella公式,分别计算两组的LDL-C值,并与直接法比较统计学差异。结果⑴血浆、血清测定指标中,TG分别为2.63±2.03mmol/L,2.56±2.06mmol/L,P<0.05;TC,LDL-C,HDLC,ApoA,ApoB相互比较,P>0.05。⑵Friedewald公式所得的5组LDL-C值与直接法比较,P<0.01;Planella公式所得的5组LDL-C值与直接法比较,P>0.1,P<0.01,P<0.002,P<0.01,P>0.05。结论直接法测定TC,LDL-C,HDLC,ApoA,ApoB时,可用肝素抗凝的血浆替代血清,但直接法测定TG及公式法计算LDL-C时不能替代;Friedewald、Planella公式计算LDL-C误差较大,TG<1.5mmol/L时可采用Planella公式,TG>1.5mmol/L时建议采用直接法。     

Impact of the Martin/Hopkins modified equation for estimating LDL-C on lipid target attainment in a high risk patient population

ObjectiveTo evaluate the Martin/Hopkins equation for estimating LDL-C as target in a population composed of high cardiac risk patients.MethodsLipid profile data from patients with TG ≤ 4.52 mmol/L (<400 mg/dl) were used. The high cardiac risk group (N 4150) consisted of patients over 40 years of age that had an A1C level of 6.5% or above and patients with a history of atherosclerotic cardiovascular disease (ASCVD). Comparisons were made between the Martin/Hopkins formula (MH-LDL-C), the Friedewald formula (F-LDL-C), Non-HDL-C and ApoB.ResultsHigher LDL-C values (0.15 mmol/L or 7.3%) were obtained using MH-LDL-C compared to the F-LDL-C. The % within target (%WT) values for F-LDL-C, MH-LDL-C, Non-HDL-C and ApoB were similar when TG levels were ≤ 1.5 mmol/L with a high degree of concordance as measured by the kappa statistic. When compared to F-LDL-C, Non-HDL-C and ApoB showed a profound decrease in the WT value as TG levels increased from normal (67.7%) to intermediate (39.1%) and high levels (20.8%). MH-LDL-C showed an attenuated decrease in the WT value as TG increased from normal (61.4%) intermediate (43.4%) and high levels (32.7%). Concordance with the alternate target parameters was higher for MH-LDL-C than for F-LDL-C when triglycerides levels were increased.ConclusionThe Martin/Hopkins modified equation for estimating LDL-C is a significant improvement on the decade’s old Friedewald formula; however it remains an imperfect tool to estimate the atherogenic load in patients with high TG levels.     

Validation of the Friedewald formula for the determination of low-density lipoprotein cholesterol compared with beta-quantification in a large population

Lipoprotein data from 9477 subjects, covering a wide range of total plasma cholesterol levels, were used to examine the validity of the Friedewald formula for estimating plasma concentrations of low-density lipoprotein cholesterol (LDL-C) using high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) concentrations. Values of LDL-C obtained from the Friedewald formula were compared with values of LDL-C derived from preparative ultracentrifugation used as a reference method. We found that the bias associated with the Friedewald formula was not related to plasma LDL-C levels and was smaller than −4.0% even for plasma LDL-C values <3.0 mmol/l. Moreover, in the subgroup of individuals with plasma TG levels ≤4.5 mmol/l, the Friedewald formula underestimated LDL-C levels with a bias between −3.1% and −1.9% according to TG quartiles. Interestingly, the Friedewald formula showed no significant bias in patients with plasma TG levels between 4.51 and 8.82 mmol/l, suggesting that the calculated LDL-C are reliable and could be clinically useful in patients with plasma TG levels higher than 4.5 mmol/l which is the reference cut-point value used by most clinical laboratories. Finally, multiple regression analyses showed that the very low-density lipoprotein cholesterol (VLDL-C)/TG ratio represented nearly 63% (P < 0.0001) of the variance of the bias associated with the Friedewald formula. We concluded that the Friedewald formula may be reliable at low LDL-C levels and at TG levels up to 9 mmol/l but may be used with caution when the VLDL-C/TG ratio is high as observed in patients with type III dysbetalipoproteinemia.     

Calculated low density lipoprotein cholesterol levels frequently underestimate directly measured low density lipoprotein cholesterol determinations in patients with serum triglyceride levels < or =4.52 mmol/l: an analysis comparing the LipiDirect magnetic LDL assay with the Friedewald calculation

BACKGROUND: Increased low density lipoprotein cholesterol (LDL-C) is an established risk factor for the development of coronary artery disease (CAD). Recent guidelines detail specific LDL-C cutpoints for therapeutic goals. In practice, LDL-C is usually derived from the Friedewald formula (FF). This calculation is known to be inaccurate with serum triglyceride (TG) concentrations >4.52 mmol/l, however, its accuracy among relatively healthy patient cohorts with TG concentrations < or =4.52 mmol/l is less well studied. METHODS: We studied 661 ambulatory adults with TG concentrations < or =4.52 mmol/l and no overt CAD. Fasting venous lipid panels were obtained. LDL-C was calculated from the FF and also directly measured with the LipiDirect Magnetic LDL assay. Linear regression and paired t-test analyses were performed. RESULTS: Calculated and directly measured LDL-C concentrations were significantly different (4.26+/-0.88 vs. 4.83+/-1.06 mmol/l respectively, p<0.0001). In 93% of measurements directly measured LDL-C exceeded calculated LDL-C. Although calculated and directly measured LDL-C concentrations were related (R=0.90), the discrepancy between them increased linearly with increasing TG concentrations (R=0.67) and clinically important differences existed at normal or slightly increased TG concentrations. Concordant results for NCEP ATP-III risk categories were present for only 48.1% of samples. CONCLUSIONS: Significant differences between calculated and directly measured LDL-C using the LipiDirect Magnetic LDL assay exist in healthy subjects with TG < or =4.52 mmol/l. These differences are linearly related to TG concentrations and occur frequently at relatively low TG concentrations.     

Effects of total cholesterol and triglyceride on the percentage difference between the low-density lipoprotein cholesterol concentration measured directly and calculated using the Friedewald formula.

BACKGROUND: We elucidate how the triglyceride (TG) and total cholesterol (TC) concentrations affect the percentage difference (%DeltaLDL) between the low-density lipoprotein cholesterol (LDL-C) concentration evaluated by direct measurement (DLDL-C) and calculated using the Friedewald formula (FLDL-C), under conditions allowing the calculation. METHODS: Serum concentrations of TC, TG, high-density lipoprotein cholesterol (HDL-C), and DLDL-C were measured and the FLDL-C and %DeltaLDL were calculated for 38,243 Koreans who had TG values <4.52 mmol/L. The DLDL-C was measured using the homogeneous Kyowa Medex assay (Kyowa, Tokyo, Japan). The %DeltaLDL was calculated using the equation: [(FLDL-C-DLDL-C)/DLDL-C]x100. RESULTS: The mean %DeltaLDL-C was -9.1+/-6.4%. The %DeltaLDL differed by more than +/-5% in 75.4% of the subjects, and the FLDL-C was lower than the DLDL-C in 96.3%. The mean %DeltaLDL-C for the group with the highest TG and lowest TC was 11.8-fold that for the group with the lowest TG and highest TC. CONCLUSIONS: Under conditions satisfying the requirements of the Friedewald formula, the DLDL-C and FLDL-C differed significantly over the concentration ranges of both TC and TG. In an evaluation of patients with hyperlipidemia, the Friedewald calculation may underestimate the risk for coronary heart disease.     

Estimation of LDL cholesterol based on the Friedewald formula and on apo B levels

OBJECTIVES: The plasma apolipoprotein B (apo B) concentrations have been considered to be a more accurate representation of atherogenic particles and it has been proposed that the formula LDL-C (mmol/L) = 0.41TC - 0.32TG + 1.70apo B - 0.27 is reliable for the estimation of LDL-C (Clin Chem 1997; 43: 808-15). We undertook the present study to investigate the reliability of this formula in a large number of hyperlipidemic patients. DESIGN AND METHODS: 1) The Friedewald formula (LDL-F) and the apo B-based formula (LDL-B) were compared with the beta-quantification reference procedure in 130 individuals with a wide range of total cholesterol (TC) and triglyceride (TG) levels, and 2) the LDL-C levels obtained by the Friedewald formula were compared with those calculated by the apo B-based formula in 1010 individuals attending our outpatient lipid clinic. RESULTS: The LDL-F and the LDL-B formulae for LDL-C estimation were found to be in good agreement with the beta-quantification (r = 0.96 and 0.97, respectively). The bias of each method plotted as a function of TG (up to 4.52 mmol/L) was found positive for the LDL-F, whereas the LDL-B was independent of the concentrations of TG. When a large number of individuals were examined, a good correlation between the two equations was found (n = 1010, r = 0.98). The difference between the two methods was not correlated with serum TG levels. However, it was correlated to serum TC, and apo B levels. CONCLUSIONS: The LDL-B formula is a more reliable and accurate method than the LDL-F formula, especially at TG levels >2.26 mmol/L, although it underestimates LDL-C concentrations. Furthermore, this equation can be used in hypertriglyceridemic patients (TG >4.52 mmol/L) in whom the Friedewald equation is inaccurate.     

Analytical performance and clinical efficacy of three routine procedures for LDL cholesterol measurement compared with the ultracentrifugation-dextran sulfate-Mg(2+) method

The diagnosis and management of adults with hypercholesterolemia in the US are largely based on low-density lipoprotein cholesterol (LDL-C) concentration. In order to classify someone correctly into the National Cholesterol Education Program cut-points, LDL-C must be measured with a total error of 相似文献   

Validation of the Friedewald Equation for Evaluation of Plasma LDL-Cholesterol

In most clinical laboratories, low density lipoprotein (LDL) cholesterol is usually estimated indirectly with the Friedewald equation or directly with the N-geneous assay. We assessed LDL-cholesterol values obtained by both methods to find an appropriate fasting period and to assess the influence of the energy content of the last meal. Blood samples were taken from 28 healthy volunteers who had consumed a standard meal (107 g of carbohydrate, 658 kcal) followed by a fasting period of 12 and 18 h, or a high-energy meal (190 g of carbohydrate, 1011 kcal) with a fasting period of 12 h. Prolongation of the fasting period from 12 h to 18 h decreased glucose level, but did not decrease triacylglycerol, total cholesterol, or high density lipoprotein (HDL) cholesterol. LDL-cholesterol levels measured with the N-geneous assay did not change (94.0 +/- 21.5 to 96.3 +/- 19.1 mg/dl). LDL-cholesterol levels calculated with the Friedewald equation were also similar after fasting periods of 12 h (98.5 +/- 21.4 mg/dl) and 18 h (99.7 +/- 20.2 mg/dl). The high-energy meal did not change the level of LDL-cholesterol measured with the N-geneous assay (96.1 +/- 21.2 mg/dl), or the glucose, triacylglycerol, total cholesterol, or HDL-cholesterol level, but LDL-cholesterol levels evaluated from the Friedewald equation (92.6 +/- 20.3 mg/dl) became significantly lower. A fasting time longer than 12 h is not necessary to obtain reasonable blood lipid levels. The Friedewald equation gave higher LDL-cholesterol levels than N-geneous assay in young Japanese females who had eaten a low-energy meal, and lower values when they had eaten a high-energy meal. Thus, it may be necessary to pay attention to energy of nigh meal prior to blood withdrawal.     

Influence of intermediate-density lipoproteins on the accuracy of the Friedewald formula

Values of low-density lipoprotein (LDL) cholesterol (C) according to the Friedewald formula (Clin Chem 1972;18:499-502) were compared with those obtained by lipoprotein fractionation in 98 healthy subjects (control group), 135 specimens from patients with peripheral vascular and cerebrovascular disease (atherosclerotic group), and 45 with chronic renal failure on hemodialysis (CRF group). All had concentrations of total cholesterol between 3.23 and 7.76 mmol/L (1.25-3.00 g/L) and triglycerides less than 3.39 mmol/L (less than 3.00 g/L). The percentage error of calculated LDL-C was 4% in controls with a cholesterol/triglycerides (C/TG) ratio for very-low-density lipoprotein (VLDL) of 0.20, but greater than 60% in those with a (C/TG)VLDL ratio of 0.40. The percentage of error in sera of patients with atherosclerosis and chronic renal failure was higher than in controls with a similar mean (C/TG)VLDL ratio. The percentage of error of calculated LDL-C increases progressively with the increase in the C/TG intermediate-density lipoprotein (IDL) ratio, both in controls and in the atherosclerotic and CRF groups. Similar findings are observed when the mean percentage of error of measured LDL-C is evaluated. The percentage of error from calculated LDL-C in the atherosclerotic and CRF groups is significantly lower than that obtained by comparison of LDL-C separated by ultracentrifugation when the "broad cut" LDL (IDL plus LDL, both by ultracentrifugation) was used. The high percentage of errors found in the groups of patients studied underlines the need for caution when assessing the reliability of the Friedewald formula, particularly in cases in which disturbances in IDL composition are suspected.     

低密度脂蛋白胆固醇保护性试剂匀相测定法的临床评价

目的 对低密度脂蛋白胆固醇(LDT-C)保护性试剂匀相测定法进行临床评价。 方法 分析了保护性试剂匀相测定法的精密度、准确性、特异性和干扰因素.并随机选取了219份病人血清标本,比较分析用保护性试剂匀相测定法直接测定与Friedewald公式和Planella公式计算的LDL—C结果。 结果 保护性试剂匀相测定法具有较好的精密度(批内、批间CV和总CV均小于3％)。线性范围至10.4mmol/L,最低检测浓度为0.08mmol/L,平均同收率为101.2％:基本不受极低密度脂蛋白(VLDL)、高密度脂蛋白(HDL)和血红蛋白的影响。在TG<4.52mmol/L时,用匀相测定法与Friedewald公式和Planella公式的计算法结果之间相关性良好,两种公式计算法结果之间的也有较好相关性;而在TG>4.52mmoL/L时,匀相测定法与两种计算法之间的相关性差。结论 保护性试剂匀相测定法简便、快速、结果准确,易于自动分析,适合在临床实验室常规检测应用。     

Marked effects of extreme levels of lipoprotein(a) on estimation of low-density lipoprotein cholesterol

Background

Low-density lipoprotein cholesterol (LDL-C) is usually calculated using the Friedewald equation. However, this calculation method does not account for the cholesterol associated with lipoprotein(a) [Lp(a)]. Using the Dahlen equation, Li et al. have shown a strong positive correlation between serum Lp(a) levels and overestimation of LDL-C levels.

Objective

To determine how the extreme levels of Lp(a) influence the LDL-C calculation.

Methods

We performed a retrospective chart review of the lipid profile and Lp(a) of 223 patients (men and women). LDL-C was calculated using the Friedewald equation. Lp(a) concentrations were measured by an ELISA. Other serum lipids were measured enzymatically by standard methodology. Corrected LDL-C was calculated using the Dahlen equation.

Results

We found that this overestimation is very significant in individuals with extreme levels of Lp(a) (mean overestimation of 40% at Lp(a) > 1200 mg/L).

Conclusions

Calculated LDL-C is markedly overestimated in patients with extreme levels of Lp(a).     

直接法和公式法检测血清LDL-C含量的偏差和分析

目的:观察和分析直接法测定血清低密度脂蛋白胆固醇(LDL-C)的含量与Friedewald公式换算值之间的关系。方法:采集1330例送检者的血脂水平,其血清三酰甘油均低于400mg.dL-1(4.52mmol·L-1)。测定LDL-C采用选择性水解法和根据Friedewald公式换算。结果:两种方法检测LDL-C值随非高密度脂蛋白胆固醇(non-HDL-C)水平的线性变化而波动,其偏差超过直接法检测值10%以上的占所有血样的40.76%。结论:直接法和Friedewald公式法检测血清LDL-C含量存在明显的偏差,可能与两种方法的系统误差有关。     

Low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol and apolipoprotein B: relationships among the different measurements

Serum low-density lipoprotein cholesterol (LDLC) value is a recognized target for atherosclerotic risk management, and is generally calculated using the "Friedewald formula". Alternative risk markers include directly measured LDLC, non-high-density lipoprotein cholesterol (non-HDLC) and apolipoprotein B (ApoB). The relationships among such various measured or calculated quantities in medium-sized sets of patient results were investigated. Results from two sets of patients were retrieved from our laboratory information systems. One group (n=8436) included results of cholesterol, HDLC, triglyceride (TG) and glucose measurements. A second group (n = 902) included, in addition, results of ApoB measurement. The results confirmed the unreliability of the Friedewald formula at TG >350 mg/dL (3.96 mmol/L), but also indicated TG-linked underestimation of LDLC below such a TG level. By contrast, non-HDLC values were shown to be independent of TG, and better correlated to ApoB than LDLC values. Mathematically, the difference between non-HDLC and LDLC is TG x 0.458 (values in mmol/L): therefore, the latter cannot be compared to (or converted into) the former by simply adding a constant amount. The ratio LDLC/ApoB was shown continuously to decrease with increasing TG concentrations, while the ratio non-HDLC/ApoB did not. The TG-dependent underestimation of LDLC may be the reason for the reported better cardiovascular risk predictivity of non-HDLC in diseases associated with TG increase, such as in diabetes. Non-HDLC values are not influenced by TG levels, and are better correlated with ApoB.     

血脂代谢紊乱与中青年脑梗死危险因素的相关性分析

目的探讨血脂与中青年人脑梗死的关系. 方法检测了 111例中青年人脑梗死患者及 80例对照者的三酰甘油、总胆固醇、高密度脂蛋白胆固醇 (High density lipoprotein cholesterol, HDL-C)、低密度脂蛋白胆固醇 (Low density lipoprotein cholesterol,LDL-C)、载脂蛋白 A-I(apolipoproteinA-I,ApoA-I)、载脂蛋白 B100(apolipoprotein B100, ApoB100)和脂蛋白 (a)血清含量. 结果脑梗死组三酰甘油 [(1.92± 1.33)mmol/L],总胆固醇 [(5.21± 1.08)mmol/L],LDL-C[(3.13± 0.96)]mmol/L,ApoB100[(1.10± 0.29)g/L]及脂蛋白 (a)[(0.23± 0.18)]g/L水平高于对照组 (t=2.523～ 3.796,P< 0.05),总胆固醇与年龄呈正相关 [青年 (4.96± 1.14)mmol/L,中年 (5.27± 1.06)mmol/L], HDL-C与年龄呈负相关 [青年 (1.39± 0.43)mmol/L,中年 (1.26± 0.35)mmol/L].亚组分析发现青年人脑梗死亚组的脂蛋白 (a)水平和中年人脑梗死亚组的三酰甘油、总胆固醇、 LDL-C、 ApoB100及脂蛋白 (a)水平均显著高于相应的对照组 (t=2.571～ 4.107,P< 0.05);皮层支动脉闭塞亚组脂蛋白 (a)水平显著高于穿通支动脉闭塞亚组 (t=5.414,P< 0.01);首发脑梗死亚组与复发脑梗死亚组之间的血脂水平无显著差异. 结论血脂代谢紊乱是中青年人脑梗死的危险因素.     

Analytical performance of a direct assay for LDL-cholesterol.

We evaluated a direct assay for the determination of LDL-cholesterol (LDL-C) L-Type assay, Wako Pure Chemicals in two laboratories. This assay is applicable to most random access clinical chemistry analyzers, allowing full automation. Between-run coefficient of variation (NCCLS EP5) varied between 1.29% and 3.13% and thus met the National Cholesterol Education Program (NCEP) goal. The assay was considered linear over a physiologically relevant range of LDL-C, 2.22 to 7.04 mmol/l (NCCLS EP6). Method comparison yielded identical results at both evaluation sites for LDL-C when assayed with the direct method. LDL-C results obtained with the homogeneous method under investigation (y) differed significantly from values from density-gradient ultracentrifugation (x) according to Chung (y = 0.87x + 0.43 mmol/l, s(yx) = 0.38 mmol/l, r = 0.91). With the latter method as a reference method, mean bias was 3.16% meeting the NCEP criteria. Diagnostic performance was excellent at a clinically relevant cut-off level of 3.37 mmol/l. Results of the direct method (y) and the commonly used Friedewald formula (x) were highly correlated (s(yx) = 0.22 mmol/l, r = 0.97), but both slope and intercept differed significantly from one and zero respectively (y = 0.90x + 0.37 mmol/l). Bilirubin, hemolysis and ascorbate did not interfere; triglycerides did not cause clinically relevant interference below 11.3 mmol/l. The direct method we investigated is user-friendly and provides an improvement in the determination of LDL-C in routine laboratories.     

甘孜县藏族成年人群脂代谢指标参考区间及血脂异常分析

目的初步调查甘孜县藏族成年人血脂代谢指标的参考区间及该人群血脂异常情况。方法采集甘孜县661名健康体检者血清,测定总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白A1(ApoA1)和载脂蛋白B(ApoB)水平。依据美国临床实验室标准化协会(CLSI)C28-A3文件及国际临床化学和检验医学联合会(IFCC)的相关要求制定的参考区间的合理方法和可靠依据,建立上述脂代谢指标的参考区间。参照2007年《中国成人血脂异常防治指南》,分析该人群中的血脂异常情况。结果该人群中,男性血清中TG、LDL-C和ApoB较女性高,而HDL-C、ApoA1较女性低,差异均具有统计学意义(P0.05)。TC、LDL-C和TG水平随年龄变化趋势明显,HDL-C、ApoA1和ApoB水平随年龄变化不明显。该人群中,TC、LDL-C和ApoB参考区间分别为2.75~6.82、1.36~4.3、0.24~1.38 mmol/L;男性人群中TG、HDL-C和ApoA1参考区间分别为0.5~2.36、0.9~1.93、0.82~1.87mmol/L;女性人群中TG、HDL-C和ApoA1参考区间分别为0.47~3.19、0.96~2.19、0.94~2.02mmol/L。该区藏族成人血脂紊乱异常发生率高,高胆固醇血症、高三酰甘油血症、混合型高脂血症和低高密度脂蛋白血症发生率分别为32.07%、21.18%、12.86%和6.51%。结论初步建立了甘孜县藏族成人血脂代谢指标的参考区间,分析了该人群高脂血症临床分型的发生率,为甘孜地区藏族人群高脂血症患者的临床干预治疗提供了参考数据,有助于指导该地区血脂异常防治工作的开展。     

Comparison of a new method for the direct and simultaneous assessment of LDL- and HDL-cholesterol with ultracentrifugation and established methods

BACKGROUND: Automated electrophoresis combined with enzymatic cholesterol staining might improve routine assessment of LDL- and HDL-cholesterol (LDLC and HDLC), as an alternative to the Friedewald equation and precipitation. A new method (Hydrasys; SEBIA) that adapts the cholesterol esterase/cholesterol oxidase reaction within urea-free gels was evaluated. METHODS: Fresh sera from 725 subjects (512 dyslipidemics) were analyzed by electrophoresis, in parallel with sequential ultracentrifugation, beta-quantification, calculation, and precipitation. RESULTS: Electrophoresis was linear up to 4 g/L cholesterol, with a detection limit of 0.042 g/L cholesterol/band. Within-run, between-run, between-batch, and between-operator imprecision (CVs) were 1.6%, 2.0%, 1.5%, and 2.7% for LDLC, and 3.9%, 4.3%, 5.5%, and 4.9% for HDLC, and remained unchanged up to 6.3 g/L plasma triglycerides (TGs). Precision decreased with very low HDLC (<0.25 g/L). Serum storage for 3-7 days at +4 or -80 degrees C did not interfere significantly with the assay. Agreement with beta-quantification was stable for LDLC up to 5.07 g/L (r = 0.94), even at TG concentrations >4 g/L (r = 0.91). Bias (2.88% +/- 12%) and total error (7.84%) were unchanged at TG concentrations up to 18.5 g/L. Electrophoresis predicted National Cholesterol Education Program cut-points with <0.04 g/L error, exactly and appropriately classified 79% and 96% of the subjects, and divided by 2.4 (all subjects) and 5.8 (TGs >1.5 g/L) the percentage of subjects underestimated by calculation. One-half of the patients with TGs >4 g/L had LDLC >1.30 g/L. For HDLC, correlation was better with precipitation (r = 0.87) than ultracentrifugation (r = 0.76). Error (-0.10% +/- 26%) increased when HDLC decreased (<0.35 g/L). Direct assessment of the LDLC/HDLC ratio detected 45% more high-risk subjects than the calculation/precipitation combination. CONCLUSIONS: Electrophoresis provides reliable quantification of LDLC, improving precision, accuracy, and concordance over calculation, particularly with increasing plasma TGs. Implementation of methods to detect low cholesterol concentrations could extend the applications for HDLC assessment.