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.     

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.     

Five methods for determining low-density lipoprotein cholesterol compared

We evaluated three precipitation methods for determination of low-density lipoprotein cholesterol in serum and an indirect method involving the Friedewald formula (Clin Chem 18: 499-502, 1972) by comparison with results by ultracentrifugation. The results of all methods for 83 sera, including 59 hyperlipidemic type IIA, IIB, and IV sera agreed very well, at least for concentrations of serum triglycerides below 8 mmol/L. The accuracy of the Friedewald formula was confirmed in 285 other sera, including 66 sera with triglycerides content between 4.52 and 8.0 mmol/L. For type III sera, the precipitation methods produced similar values to those obtained with the Friedewald formula, all being much higher than the ultracentrifugation values. Density-gradient ultracentrifugation showed that the very-low-density lipoprotein remnants in type III sera almost completely coprecipitated with the low-density lipoproteins. The precipitation methods are not only accurate but also very precise (CV less than 5%); they can therefore be used in clinical laboratories to measure atherogenic low-density lipoproteins plus the remnants of very-low-density lipoproteins. However, when serum triglycerides and high-density lipoprotein cholesterol also are determined, the Friedewald formula is a reliable alternative.     

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.     

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.     

Calculation of low-density lipoprotein cholesterol with use of triglyceride/cholesterol ratios in lipoproteins compared with other calculation methods

Low-density lipoprotein cholesterol was calculated with a formula that utilizes the triglyceride/cholesterol ratios in the different lipoprotein fractions, and also with different modifications of the Friedewald formula. Results of the former calculation correlated well with the ultracentrifugation-derived values and performed better than the other calculations at different lipid concentrations.     

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。     

Evaluation of five methods for determining low-density lipoprotein cholesterol (LDL-C) in hemodialysis patients(1)

Objectives: Current recommendations for the management of dyslipidemia are largely based on the concentration of LDL-C. Most clinical laboratories estimate the concentration of LDL-C by the recommended routine method, the equation of Friedewald, in specimens from fasting subjects and with TG concentrations < 4.52 mmol/L. Because of the limitations of the Friedewald calculation, direct methods for an accurate quantification of LDL-C are needed.

Design and Methods: In the present study we evaluated the accuracy of the following 5 different procedures for LDL-C in 98 patients on hemodialysis: the Friedewald equation, where LDL-C is calculated from HDL-C, measured either by the precipitation procedure with dextran sulfate-Mg²⁺ (Method 1), or by a direct HDL-C assay (Method 2), the Direct LDL™ assay (Method 3), the homogeneous N-geneous™ LDL assay (Method 4) and the calculated LDL-C values deriving from the ApoB based equation: 0.41TC - 0.32TG + 1.70ApoB - 0.27, (Clin Chem 1997;43:808–815) (Method 5).

Results: All five LDL-C methods were found to be in good agreement with ultracentrifugation/dextran sulfate-Mg²⁺ precipitation with the coefficients of correlation of the assays to ranging between 0.93–0.95. However, significant differences in the mean values and biases vs. the reference method were observed. The Friedewald equation and the Direct assay were less affected by high LDL-C levels, and they presented higher sensitivity and higher negative predictive value. The N-geneous assay and the ApoB derived calculation were less affected by high triglyceride levels, and they presented higher specificity and higher positive predictive value. At the diagnostic LDL-C level of 3.37 mmol/L, both Friedewald calculations correctly classified 82/92 patients; Direct assay 86/98; N-geneous assay 88/98; and ApoB derived calculation 88/98. At the diagnostic LDL-C level of 2.98 mmol/L, Friedewald calculations (Method 1 and Method 2) correctly classified 82/92 and 81/92 patients, respectively; Direct assay (LDL-3) 87/98; N-geneous assay (LDL-4) 91/98; and ApoB derived calculation (LDL-5) 91/98.

Conclusions: Among hemodialysis patients, who commonly present “average” LDL-C concentrations and high TG levels, the N-geneous assay and the apoB derived calculation seem to yield more acceptable results for the estimation of LDL-C.     

血脂与动脉粥样硬化发展阶段的相关性

目的通过检测动脉粥样硬化(As)不同发展阶段的各种血脂相关指标,来探讨各种检测值与As各个发展阶段的相关性。方法随机选择健康体检者60例[As(-)组]、脑As无并发症患者24例[As(+)组]、As性脑梗死患者67例[As(++)组],酶化学法测定血清三酰甘油(TG)、总胆固醇(TC),直接法测定低密度脂蛋白胆固醇(LDLC)、高密度脂蛋白胆固醇(HDLC),免疫透射比浊法测定载脂蛋白A1(ApoA1)、载脂蛋白B100(ApoB100)、脂蛋白(a)[LP(a)],并对三组的检测值进行统计分析。结果As(+)组与As(-)组比较,TG、TC、LDLC、ApoB100、LP(a)、ApoB100/ApoA1增高(P<0.05),HDLC、ApoA1降低(P<0.05)。As(++)组与As(+)组比较,ApoB100、LP(a)、ApoB100/ApoA1增高(P<0.05)。As(++)组与As(-)组比较,ApoB100、LP(a)、ApoB100/ApoA1显著增高(P<0.01)。结论TG、TC、LDLC、HDLC、ApoA1、ApoB100、LP(a)、ApoB100/ApoA1水平与As的早期发展阶段相关,而且ApoB100、LP(a)、ApoB100/ApoA1水平与As的晚期发展阶段相关。     

Estimation of cardiovascular risk: total cholesterol versus lipoprotein profile

Summary The complete lipoprotein profile is thought to give more information about the individual risk of coronary heart disease than total cholesterol alone. Although total cholesterol has a low sensitivity in the correct assessment of the risk of coronary heart disease, it may be of value in screening programs because of its low cost. In this study of 5,335 subjects, total cholesterol gave a different assessment of coronary heart disease risk (United States National Cholesterol Education Program guidelines) in 25% of subjects than the complete lipoprotein profile. Differences in risk assignment were mainly accounted for by high- and low-density lipoprotein-cholesterol (Friedewald equation). The calculated low-density lipoprotein-cholesterol was highly correlated with the value measured with a mixed ultracentrifugation and precipitation procedure. However, calculated values gave estimates of coronary heart disease risk which were 20% different from those from measure values. In 200 subjects in whom the lipoprotein profile was assessed three times in 1 year, the total cholesterol low-density lipoprotein-cholesterol varied by more than 30 mg/dl (0.78 mmol/l) in 52% and 50%, respectively, triglycerides by more than 30 mg/dl (0.34 mmol/l) in 75%, and high-density lipoprotein-cholesterol by more than 15 mg/dl (0.39 mmol/l) in 34%. Compared with the mean of the measurements, the single measurement of total cholesterol misclassified 48% of subjects, low-density lipoprotein-cholesterol 60%, high-density lipoprotein-cholesterol 12%, and 28%. We conclude that total cholesterol alone may be misleading in the assignment of coronary heart disease risk. Calculation of low-density lipoprotein-cholesterol, although less accurate than desirable, is the only way of evaluating this in clinical practice. Finally, repeated lipid measurements are required to assess coronary heart disease risk accurately.     

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。     

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.     

高脂血对不同方法测定血清高密度脂蛋白胆固醇的影响

目的　观察不同浓度血清三酰甘油 (TG)对高密度脂蛋白胆固醇 (HDL C)测定的影响 ,在临床实验室内寻找可靠的HDL -C测定方法以满足临床诊治需求。方法　采用全自动生化分析仪检测血清TG、TC、HDL C以及LDL C并与沉淀法和电泳法测定HDL C进行分组比较。结果　当血清TG <1.6 9mmol/L时 ,3种方法测定值之间无差异 ;当血清TG为 1.6 9～ 4 .0mmol/L范围时 ,各方法测定HDL -C有显著差异 ,但相关性良好。当TG >4 .0mmol/L ,各方法之间的差异程度不一致。结论　对高TG标本HDL C的测定电泳法、沉淀法和直接法之间有显著差异 ,有条件的实验室应尽可能采用电泳法测定高TG标本HDL C。     

The Friedewald formula underestimates LDL cholesterol at low concentrations.

Due to recent advances in the treatment of hypercholesterolemia, low density lipoprotein (LDL) cholesterol concentrations below 2.6 mmol/l have become attainable. In general, LDL cholesterol is determined indirectly according to Friedewald. We examined the performance of the Friedewald formula at low concentrations of LDL cholesterol in comparison with a beta-quantification method. We analyzed 176 samples from individuals treated by LDL apheresis with a mean LDL cholesterol concentration of 3.07 mmol/l and found that the Friedewald formula underestimated LDL cholesterol with a bias of -18.5%, -14.5%, -7.3%, and -3.8% at mean LDL cholesterol levels of 1.58, 2.4, 3.49, and 4.67 mmol/l, respectively. Thus, the lower the LDL cholesterol concentration was, the greater the negative bias. We conclude that the Friedewald formula may not be reliable at low LDL cholesterol concentrations produced by LDL apheresis. This finding may also be of relevance to the monitoring of patients being treated with lipid lowering drugs.     

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.     

Correlation between the ratio of serum low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with that of serum apolipoproteins B and A-I

Summary Phosphowolframate/magnesium chloride, a commonly used precipitation method for the determination of high-density lipoprotein cholesterol in human serum, yields a supernatant containing almost all of the lipoproteins apo A-I and apo A-II but no lipoprotein apo B. The correlation between high-density lipoprotein cholesterol and apo A-I was very high (r=0.94), as well as that between the precipitation method and ultracentrifugal analysis (r>0.95,P<0.001). In contrast, detergent precipitation (for the determination of low-density lipoprotein cholesterol in human serum) produced sediments which contained the major proportion of apo B and only minor amounts of apo A-I and apo A-II. The precipitation method for low-density lipoprotein cholesterol showed very good agreement with ultracentrifugal analysis (r=0.99). Yields of 80.2% were obtained for apo B with both methods. Results obtained using the precipitation methods showed excellent agreement with those obtained using the Friedewald formula (r>0.99). Results were also very similar when hypertriglyceridemic serum samples were briefly centrifuged before analysis of cholesterol, high-density lipoprotein cholesterol and triglyceride values. The present study shows highly significant correlations between cholesterol/high-density lipoprotein cholesterol or low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and apo B/apo A-I ratios (P<0.001). Apo B and apo A-I levels could be used in addition to low- and high-density lipoprotein cholesterol values when assessing the risk of cardiovascular disease, if the methods for determining serum apolipoproteins have been properly standardized.     

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.     

LDL cholesterol estimation using the Anandaraja's and Friedewald's formulas in schizophrenic patients treated with antipsychotic drugs

Objectives

The use of new antipsychotic drugs is associated with an increased risk of diabetes and metabolic syndrome, and the routine monitoring of blood lipids during treatment has been recommended. Recently, a new formula for the estimation of low-density lipoprotein (LDL) cholesterol from total cholesterol and triglycerides has been proposed by Anandaraja et al. (Int J Cardiol 2005; 102: 117), and the aim of our study was its evaluation in schizophrenic patients treated with antipsychotic drugs.

Materials and methods

In 487 serum samples from schizophrenic patients treated with clozapine in polytherapy, the concentrations of LDL cholesterol were determined by agar gel electrophoresis and the formula of Friedewald et al. (Clin Chem 1972; 18: 499), and compared with the results of the Anandaraja's formula.

Results

A higher correlation and lower error of the estimate of the electrophoresis results was found with those of Friedewald (r = 0.940, ma68 = 0.17 mmol/L) than those of Anandaraja (r = 0.811, ma68 = 0.31 mmol/L). Similar results were obtained on making a dichotomy of the patients with and without metabolic syndrome lipid profile. A highly significant correlation was found between the high-density lipoprotein (HDL) cholesterol levels and the Anandaraja/Electrophoresis (r = 0.817, p < 0.001) and Anandaraja/Friedewald (r = 0.977, p < 0.001) ratios.

Conclusions

According to our data, Anandaraja's formula tends towards an overestimation or underestimation of LDL cholesterol levels, depending on whether the HDL cholesterol levels are high or low, which may be clinically significant. These results do not support the proposed better accuracy of the Anandaraja's than the Friedewald's formula.     

Calculated values for low-density lipoprotein cholesterol in the assessment of lipid abnormalities and coronary disease risk

Low-density lipoprotein (LDL) cholesterol concentrations are most commonly estimated by the formula LDL cholesterol = total cholesterol - [triglycerides (TG)/5 + high-density lipoprotein cholesterol], although alternative factors such as TG/6 have also been used. Using standardized, automated, enzymatic lipid assays, we analyzed 4797 plasma samples from normal and dyslipidemic adults, to compare LDL cholesterol concentrations obtained after ultracentrifugation with those calculated by several such methods (i.e., TG/4-TG/8). or TG concentrations less than or equal to 0.50 g/L, TG/4 agreed best with the direct assay; for TG of 0.51-2.00 g/L, TG/4.5 was best; and for TG of 2.01-4.00 g/L, TG/5 was best. Differences in estimated values were generally small, however. At TG greater than 4.00 g/L, none of the factors tested allowed a reliable estimate of LDL cholesterol. When TG were less than or equal to 4.00 g/L, 86% of estimated LDL cholesterol values were properly classified according to National Cholesterol Education Program cutpoints when the factor TG/5 was used. We conclude that a convenient direct method for measuring LDL cholesterol is needed but, until one is available, use of the factor TG/5 will assure that most individuals with TG less than or equal to 4.00 g/L, as measured in a standardized laboratory, can be reasonably well classified for risk of coronary artery disease.     

Comparison of ultracentrifugation and a precipitation method for high-density lipoprotein cholesterol quantitation in insulin-dependent diabetic patients

We compared sodium phosphotungstic acid and magnesium chloride precipitation method for high-density lipoprotein (HDL) cholesterol quantitation with the ultracentrifugation method in 64 insulin-dependent diabetic patients with plasma triglyceride less than 3 mmol/l. The cholesterol content of HDL after precipitation of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) was 86% +/- 3% of the cholesterol content of HDL (q greater than 1.063) determined after ultracentrifugation at q = 1.063 (1.33 +/- 0.05 mmol/l vs 1.55 +/- 0.06 mmol/l; p less than 0.001). HDL cholesterol determined after precipitation closely correlated to HDL cholesterol determined after ultracentrifugation (r = 0.97; p less than 0.001). The absolute difference between the HDL cholesterol values obtained by the two methods was correlated to HDL cholesterol (ultracentrifugation) (r = 0.75; p less than 0.001), but it was not correlated to VLDL cholesterol, LDL cholesterol, triglyceride, HbA1c, blood glucose or serum albumin. LDL cholesterol calculated by use of Friedewald's formula was 108% +/- 4% of the cholesterol content of LDL (q = 1.019 to 1.063), determined after ultracentrifugation, but the calculated and the ultracentrifugally determined LDL cholesterol values were closely correlated (r = 0.98; p less than 0.001). These results suggest that during sodium phosphotungstic acid and magnesium chloride precipitation of plasma from diabetic patients, a constant fraction of HDL cholesterol is co-precipitated, resulting in a systematic difference in HDL cholesterol quantitation when compared with the ultracentrifugation method.