Direct Low-density Lipoprotein Cholesterol Assay Research Articles

Descriptive Evaluation in Outpatient Follow-up of Direct LDL-C in Patient with Elevated Triglycerides and Diabetes

Introduction. An annual fasting lipid panel (FLP) is recommended for patients with diabetes, and more frequent testing is advised when escalating cholesterol-lowering therapy. However, the calculated low-density lipoprotein cholesterol (LDL-C) using the Friedewald equation may be inaccurate when triglycerides (TG) are ≥400 mg/dL. In such cases, providers are required to order a separate direct LDL-C assay to confirm results, which increases the risk of overlooking the need for therapy intensification. Methods. The authors conducted a retrospective chart review across 13 outpatient clinics within a single health system over a five-year period. Patients aged 40-75 years, diagnosed with diabetes, and having at least one invalid LDL-C result were included. The primary outcome assessed the frequency of ordering a direct LDL-C assay within 7 days following an invalid LDL-C. Results. Among 1364 unique cases with invalid FLPs, 97 (7.1%) met the primary outcome. No significant association was identified between provider type and the likelihood of ordering a direct LDL-C. Therapy escalation was not significantly impacted by a direct LDL-C (14.1% direct vs 16.3% indirect) (p=0.6269) or provider type (16% MD/DO, 14.9% PA, 20.4% APRN) (p=0.6871). Conclusions: Our findings indicate that the current practice of manually verifying invalid LDL-C results at this institution may overlook necessary therapeutic intensification to meet guideline-based goals. The addition of a reflex direct LDL-C assay may enhance this process.

A-215 Calculated LDL-cholesterol: Comparability of the extended Martin-Hopkins,Sampson-NIH, Friedewald and four other equations in South African patients

Abstract Background Ultracentrifugation for LDL-C (low-density lipoprotein cholesterol) measurement is the gold standard, but it is unsuitable for routine use. Direct LDL-C assays and predictive equations such as the Friedewald equation are thus used as alternatives. The Friedewald equation is known to be error-prone in hypertriglyceridaemic patients, as well as in LDL-C levels < 1.8 mmol/L (70 mg/dL) which has become increasingly attainable with the use of pro-protein convertase subtilisin/kexin type 9 inhibitors. This study evaluates the comparability of the Friedewald, extended Martin/Hopkins, Sampson/NIH and four other equations to a direct LDL-C assay to establish a suitable alternative to the Friedewald equation. Methods We analysed 44 194 lipid profiles from a mixed South African population. The Friedewald, extended Martin/Hopkins and Sampson/NIH LDL-C and four other predictive equations (Vujovic, Puavilai, Delong, Anandaraja) were compared to the Beckman Coulter direct LDL-C assay. Non-parametric statistics were used to analyse the data. Results The extended Martin/Hopkins equation displayed the best correlation with direct LDL-C, having the most values fall within the desirable bias (59%) and total allowable error (89%) specifications. In patients with TG values between 4.5 mmol (400 mg/dL) and 9.0 mmol/L (800 mg/dL), the extended Martin/Hopkins equation was more likely to overestimate LDL-C levels, showing a positive median bias of 7.3%, while Friedewald (−21.2%) and Sampson/NIH (−9.8%) showed larger negative median biases as compared to the direct LDL-C assay. The direct LDL-C assay classified 13.9% of patients in the low LDL-C (1.0–1.8 mmol/L) (39–70 mg/dL) category, in comparison to the Martin/Hopkins equation (13.4%), the Sampson equation (14.6%) and the Friedewald equation (16.0%). The extended Martin/Hopkins equation performed better than Sampson/NIH equation in the cohort. Conclusion We suggest the extended Martin/Hopkins equation as an alternative to Friedewald’s equation and direct LDL-C assay. Careful consideration is advised as the choice of analyser platform for the lipid profile used in the equations may influence their performance.

Calculated LDL-cholesterol: comparability of the extended Martin/Hopkins, Sampson/NIH, Friedewald and four other equations in South African patients

AimsThe reference method for low-density lipoprotein-cholesterol (LDL-C) is ultracentrifugation. However, this is unsuitable for routine use and therefore direct LDL-C assays and predictive equations are used. In this study, we...

Evaluation of equations for calculating LDL-cholesterol in patients with concomitant hypertriglyceridemia and low LDL-cholesterol: is there a preferred equation?

It is critical to reliably estimate Low Density Lipoprotein Cholesterol (LDL-C) in patients with concomitant hypertriglyceridemia and low LDL-C. We retrospectively compared the performances of the Friedewald (LDL-F), Martin-Hopkins (LDL-MH) and Sampson (LDL-SA) equations against a direct homogeneous LDL-C assay (dLDL-C) on observations presenting mild hypertriglyceridemia (triglycerides between 1.69 and 3.9 mmol/L) and low LDL-C (< 2.58 mmol/L). Observations were stratified according to their LDL-C. Agreement of the equations with dLDL-C was assessed using Intraclass Correlation Coefficients (ICC) with an agreement cut-off of 0.9, and analysis of Bland-Altman plots. Independently of the LDL-C stratum evaluated, the three equations failed to meet the 0.9 ICC cut-off, although their agreement with dLDL-C improves as LDL-C increases. Analysis of Bland-Altman plots shows a downwards discordance of LDL-F with dLDL-C, and an upwards discordance of LDL-MH and LDL-SA with direct LDL-C. LDL-MH resulted in the least observations outside the Bland-Altman limits of agreement. While no equation can be deemed satisfactory enough to replace direct assays in patients with low LDL-C and concomitant hypertriglyceridemia, LDL-MH seems to perform better than the other equations in estimating LDL-C in these patients.

Prospective Validation of a Machine Learning Model for Low-Density Lipoprotein Cholesterol Estimation.

We aim to prospectively validate a previously developed machine learning algorithm for low-density lipoprotein cholesterol (LDL-C) estimation. We retrospectively and prospectively evaluated a machine learning algorithm based on k-nearest neighbors (KNN) according to age, sex, healthcare setting, and triglyceridemia against a direct LDL-C assay. The agreement of low-density lipoprotein-k-nearest neighbors (LDL-KNN) with the direct measurement was assessed using intraclass correlation coefficient (ICC). The analysis comprised 31,853 retrospective and 6599 prospective observations, with a mean age of 54.2 ± 17.2 years. LDL-KNN exhibited an ICC greater than 0.9 independently of age, sex, and disease status. LDL-KNN was in satisfactory agreement with direct LDL-C in observations with normal triglyceridemia and mild hypertriglyceridemia but displayed an ICC slightly below 0.9 in severely hypertriglyceridemic patients and lower in very low LDL-C observations. LDL-KNN performs robustly across ages, genders, healthcare settings, and triglyceridemia. Further algorithm development is needed for very low LDL-C observations.

Is Machine Learning-derived Low-Density Lipoprotein Cholesterol estimation more reliable than standard closed form equations? Insights from a laboratory database by comparison with a direct homogeneous assay

BackgroundThere is no consensus on the best method to estimate Low Density Lipoprotein-Cholesterol (LDL-C) in routine laboratories. MethodsWe conducted a retrospective study to compare the performances of a Machine Learning (ML) algorithm using the K-Nearest Neighbors (LDL-KNN) method with that of the Friedewald formula (LDL-F), the Martin-Hopkins equation (LDL-NF), the de Cordova equation (LDL-CO) and the Sampson equation (LDL-SA) against direct homogeneous LDL-C assay (LDL-D) in patients who presented to the Laboratories of Hôtel Dieu de France university hospital in Beirut, Lebanon, from September 2017 to July 2020. Agreements between methods were analyzed using Intraclass Correlation Coefficients (ICC) and the Bland-Altman method of agreement. Results31,922 observations from 19,279 subjects were included, with a mean age of 52 ± 18 years and 10,075 (52.3%) females. All methods except LDL-F and LDL-CO exhibited an overall ICC beyond the 0.9 cut-off. LDL-SA, LDL-NF and LDL-KNN were less susceptible to triglyceridemia than LDL-F and LDL-CO, with LDL-KNN resulting in the lesser fraction of points beyond the Bland-Altman limits of agreement. ConclusionAn ML algorithm using LDL-KNN is promising for the estimation of LDL-C as it agrees better with LDL-D than closed form equations, especially in mild and severe hypertriglyceridemia.

A comparative analysis of direct LDL-C assay and Friedewald’s formula in subjects of ischemic heart disease &amp; stroke in a tertiary care centre

Introduction: Among the various risk factors for the development of Ischemic heart diseases (IHD) as well as stroke is elevated low density lipoprotein cholesterol (LDL-C) levels. This makes accurate reporting of LDL-C crucial in the management of IHD. On one hand estimation of LDL-C by direct method is available, but it is expensive and on the other hand the Friedewald’s formula is most commonly employed but a method with limitations. Aim: Therefore the aim of this study is to evaluate the correlation between calculated LDL-C with direct LDL-C method and analyse their appropriateness. Materials and Methods: This study was a hospital based cross-sectional study. LDL-C was measured by both Friedewald’s formula (FF) and direct LDL method in 501 participants between the age group of 30–70 years. Paired t-test was used to test the difference in LDL concentration obtained by a direct method and Friedewald’s formula. The level of significance was taken as P Results: The mean and standard deviation (SD) of LDL-C estimated by both direct assay and FF showed a significant difference (p0.05) at TG range >400 mg/dL. There was a discrepancy of 37 out of 501participants (7.38%) classified as cardiac risk groups by the two methods used. A significant correlation between LDL-C levels obtained by FF and direct methods, (p value Conclusion: The study concludes that both methods can be employed depending on TG levels. Direct LDL estimation appears to be unreliable at TG concentrations >400 mg/dL but useful when sample is collected from a non-fasting participants. Keywords: Low density lipoprotein, Ischemic heart disease, Stroke.

Abstract MP72: Using Non-HDL-C/Triglyceride Ratio To Screen For Direct LDL-C Testing: Improving LDL-C Estimates At A Cost

Introduction: Despite more accurate low-density lipoprotein cholesterol (LDL-C) estimates by the Martin (mLDL-C) method, most laboratories still use the Friedewald (fLDL-C) equation. Low non-high density lipoprotein (non-HDL-C) and high triglycerides (TG) drive inaccuracy in LDL-C estimation. We compared a strategy of identifying errors in fLDL-C using non-HDL-C/TG ratios with subsequent reflex direct LDL-C testing to a strategy of using mLDL-C. Methods: We included 4,939,542 individuals (2/3 derivation, 1/3 validation dataset) with TG &lt;400 mg/dL with lipid profiles directly measured via Vertical Auto Profile from the Very Large Database of Lipids. We compared directly measured LDL-C with estimated fLDL-C and mLDL-C. The direct LDL-C assay has an allowable error of 12% which was used as the threshold for accuracy assessment. LDL-C estimates above and below non-HDL-C/TG cutpoints (range 0-2.0) were evaluated for accuracy from the derivation dataset and the 4 best performing ratios were tested in the validation set. Individuals with non-HDL-C/TG ratios below the cutpoints were assumed to require direct LDL-C measurement. Medicare costs ($17 lipid panel; $12 direct LDL-C) were used to estimate added costs of direct LDL-C measurement. Results: Nearly 8% of fLDL-C results deviated &gt;12% from direct LDL-C compared with only 2.5% of mLDL-C results in the entire population. Non-HDL-C/TG ratios of 0.6-0.9 performed best in the derivation dataset. In the validation dataset, a non-HDL-C/TG ratio of 0.7 had the highest area under the curve for identifying &gt;12% error in fLDL-C estimates (Table). At this ratio, 14.5% of fLDL-C samples would need direct LDL-C measurement at an increase in costs of lipid testing by 10%. Conclusions: Use of non-HDL-C/TG ratio &lt;0.7 as screening for direct LDL-C measurement can improve the accuracy of LDL-C estimates in labs using the Friedewald equation. However, such an approach is significantly costlier than using mLDL-C.

Evaluation of Martin's equation for LDL-C estimation in type 2 diabetes mellitus Egyptian patients

IntroductionType 2 Diabetes Mellitus has characteristic dyslipidemia. Low-density lipoprotein cholesterol (LDL-C) measurement plays a role in cardiovascular risk assessment and management. Friedewald equation (FE) has several limitations. This study aims to evaluate the effectiveness of Martin equation (ME) in Egyptian patients, especially those with type 2 diabetes. MethodsA cross-sectional study was conducted on 454 diabetic and non-diabetic patients who were referred to the internal medicine outpatient clinic. Lipid profile was assessed by Cobas 8000 Modular Analyzer. ResultsThe LDL-C was estimated by both FE and ME. In diabetic patients, LDL-C estimated by FE was underestimated with a bias of −3.9 ± 5.3 mg/dL (p = .04). But LDL-C estimated by ME was not significantly different compared to directly measured LDL-C. FE underestimate LDL-C with a bias of −4.6 ± 6.4 mg/dL (p = .042) in uncontrolled diabetic patients. A non-significant difference in both uncontrolled patients and controlled ones was detected by ME. FE had lower sensitivity and specificity (80% and 88.9 respectively) compared to the ME (95.9% sensitivity, and 95.6% specificity). ME was not influenced by triglyceride levels (p = .34). ConclusionThe ME improves concordance of calculated LDL-C with a direct LDL-C assay in Egyptian diabetic patients.

Underestimation of Low Density Lipoprotein-Cholesterol With the Friedewald Equation Versus a Direct Homogenous Low Density Lipoprotein-Cholesterol Assay.

Low-density lipoprotein cholesterol (LDL-C) concentrations are the primary therapeutic target in patients with atherosclerotic cardiovascular disease (ASCVD). However, at low LDL-C concentrations, there is a significant underestimation using the Friedewald equation compared with ultracentrifugation. In this pilot study, we compared LDL-C concentrations obtained using the Friedewald equation (LDL-F) vs those concentrations from a direct LDL-C (LDL-D) assay in 152 consecutive specimens from patients with triglyceride levels between 200-399 mg/dL and LDL-F <100 mg/dL. Also, we compared LDL-F and LDL-D results to the novel formula (LDL-N). The LDL-F value was significantly lower than that of LDL-D when LDL concentrations were 70-99 mg/dL (P <.001, 14% negative bias), and this decrease was accentuated in specimens with LDL <70 mg/dL, (P <.001, 27% negative bias). When compared with the LDL-N value, LDL-F and LDL-D values showed a 17% and 2% negative bias for specimens with LDL-C values of 70-99 mg/dL and 36% and 1% negative bias, respectively, at LDL-C <70 mg/dL (P <.001 for comparisons of LDL-F and LDL-N values). To provide accurate LDL-C levels in patients at high risk for ASCVD, if beta quantification by ultracentrifugation is unavailable and if LDL-C is <100 mg/dL and triglycerides are 200-399 mg/dL, laboratories should revert to direct LDL-C measurements or use the novel formula. Although LDL-N is more cost-effective, LDL-D can be run on most platforms, does not require a specimen from a fasting individual, is standardized, and has the advantage of being validated in large trials such as the Heart Protection Study.

A Simple Economical Method for Assay of Atherogenic Small Dense Low-Density Lipoprotein-Cholesterol (sdLDL-C)

In the present study, we report a simple and economical precipitation method for the quantitative determination of small, dense LDL-cholesterol (sdLDL-C) in serum that is considered to be an emerging risk factor for cardiovascular disease. This method consisted of precipitation of lipoproteins of density <1.044g/ml using heparin-MnCl(2) and quantification of cholesterol existed in the supernatant using reagents for routine cholesterol assay instead of the costly direct low density lipoprotein-cholesterol assay kit. The supernatant contained sdLDL and high-density lipoprotein (HDL) that was confirmed by polyacrylamide gel electrophoresis. sdLDL-C concentration can be calculated by subtracting the HDL-C value from the total cholesterol concentration of the supernatant. sdLDL-C values obtained by this modified method were similar to those obtained by direct assay of sdLDL-C and there was significant correlation between the two methods. In conclusion, this method is highly economical, do not require special equipments and is useful to evaluate atherogenic risk.

Comparison of low-density lipoprotein cholesterol concentrations measured by a direct homogeneous assay and by the Friedewald formula in a large community population

Background We compare the direct homogeneous low-density lipoprotein cholesterol (LDL-C) assay with the Friedewald formula (FF) for determination of LDL-C in a large community-dwelling population. Methods A total of 21,194 apparently healthy subjects aged 40 to 79 years with triglyceride (TG) concentrations < 4.52 mmol/l were enrolled. LDL-C were directly measured by the enzymatic homogeneous assay (LDL-C (D)) and also estimated by the FF (LDL-C (F)). Paired t-test, Pearson's correlation coefficient and linear regression analysis were performed and the concordances of the National Cholesterol Education Program (NCEP) risk category were estimated. Results Both in fasting (n = 3270) and nonfasting samples (n = 17,924), LDL-C (D) highly correlated with LDL-C (F): r = 0.971 and 0.955, respectively. Concordant results for NCEP categories were 84.8% for fasting samples and 80.1% for nonfasting samples. However, the bias between the 2 measurements increased in samples with TG concentrations > 1.69 mmol/l, especially in nonfasting samples. Conclusions The results showing less variability of the direct LDL-C assay than that of the FF in nonfasting samples suggest that epidemiological studies can use LDL-C measured by the direct assay both in fasting and nonfasting samples.

Nonfasting Low-Density Lipoprotein Testing: Utility for Cholesterol Screening in Pediatric Primary Care

This prospective study assessed the clinical application of a nonfasting low-density lipoprotein cholesterol measure in a pediatric primary care population. A homogenous direct low-density lipoprotein cholesterol assay was tested in healthy children, aged 4 to 12 years, at risk for hyperlipidemia, as defined by American Academy of Pediatrics, and including patients with incomplete family histories. This nonfasting homogeneous assay was comparable to modified beta quantification, the gold standard reference method of measuring low-density lipoprotein cholesterol, and the current recommended screening method, total cholesterol. Results from the study suggest that this nonfasting assay can provide more direct low-density lipoprotein cholesterol measurements for healthy children, with improved clinical utility and greater overall patient convenience in testing for important cholesterol abnormalities.

Low-density lipoprotein cholesterol estimation by a new formula in Indian population

Background Estimation of low-density lipoprotein cholesterol is crucial in the management of ischemic heart disease patients. Low-density lipoprotein cholesterol is routinely calculated in laboratories world over by applying Friedewald formula for logistic reasons. We derived a new formula based on multiple regression approach. Methods Lipid profiles were done on blood samples of 2008 patients. In initial 1000 patients, low-density lipoprotein cholesterol was estimated by a direct method and also by Friedewald formula. By applying linear regression methods on the data of direct estimation method, a new formula was obtained and the accuracy of this new formula was validated in the next 1008 patients. Results The mean low-density lipoprotein cholesterol was 116±41.5 mg/dl (3.02±1.08 mmol/l) measured by direct low-density lipoprotein cholesterol assay and that calculated by Friedewald formula was 119±46 mg/dl (3.09±1.2 mmol/l) for the initial 1000 patients. Low-density lipoprotein cholesterol measured by direct low-density lipoprotein cholesterol assay and calculated from Friedewald formula showed good correlation ( r=0.88), however, there was minimal overestimation by the Friedewald formula. The correlation improved between direct low-density lipoprotein cholesterol and calculated low-density lipoprotein cholesterol after excluding the patients with triglycerides more than 350 mg/dl ( r=0.92). The mean low-density lipoprotein cholesterol measured by the direct assay and by new formula in the next 1008 patients was 117±40 mg/dl (3.04±1.04 mmol/l) and 113.7±37 mg/dl (2.96±0.96 mmol/l), respectively with very good correlation ( r=0.97) between them. Conclusions The new formula derived from multiple linear regression analysis appears to be more accurate than Friedewald formula in Indian population.

Validity of the Conventional Indirect Methods Including Friedewald Method for Determining Serum Low‐Density Lipoprotein Cholesterol Level: Comparison with the Direct Homogeneous Enzymatic Analysis

Validity of the Conventional Indirect Methods Including Friedewald Method for Determining Serum Low‐Density Lipoprotein Cholesterol Level: Comparison with the Direct Homogeneous Enzymatic Analysis: Noriyuki Nakanishi, et al. Department of Social and Environmental Medicine, Course of Social Medicine, Osaka University Graduate School of Medicine F2—Low‐density lipoprotein cholesterol (LDLC) concentrations are most commonly estimated by the Friedewald formula [LDLC=total cholesterol (TC) ‐ high‐density lipoprotein cholesterol ‐ triglycerides (TG)/5]. To assess the validity of the conventional indirect methods including Friedewald method for determining serum LDLC level, we analyzed 1953 serum samples from Japanese male office workers and compared the measured (the direct N‐geneous assay) serum LDLC concentrations with calculated values, by using several terms for TG (i.e., TG/4, TG/4.5, TG/5, TG/5.5, TG/6, TG/7, and TG/8) in the Friedewald formula. Linear regression analyses showed the highest correlation for the estimated LDLC by the original Friedewald formula, with the term TG/5, with the measured LDLC (r=0.958). The mean LDLC estimated by means of the original Friedewald formula was 1.4 mg/d/ higher than the mean measured LDLC (p&lt;0.001), but the difference between the mean estimated LDLC and the mean measured LDLC was the smallest for estimation by means of the original Friedewald formula. As for the accuracy of calculation methods, TG/5 agreed best with the direct assay for TG concentrations ≤99 mg/d/and TG/4.5 was best for TG concentrations of 100‐249 mg/d/. For TG concentrations ≥250 mg/d/, TG/5 most closely matched the measured LDLC and gave the smallest mean percent errors, but with increasingly large estimation errors as TG increased. As for the accuracy of calculation methods according to lipidemic type, TG/5 was the best estimating term for normolipidemics (TC ≤219 mg/d/ and TG ≤149 mg/d/) and hypertriglyceridemics (TC ≤ 219 mg/d/and TG ≥ 150 mg/ 61), but the percentages of samples correctly estimated decreased with increasing TG concentrations. These results suggest that the original Friedewald formula, with the term TG/5, is reasonably well classified at TG concentrations ≤99 mg/d/ or in normolipidemics, but the potential for significant estimation errors steadily increases with increasing TG concentrations. We conclude that direct LDLC assay such as the N‐geneous method is a useful tool in the diagnosis and management of hypercholesterolemics, especially for those with increased TG.

Direct Method for the Measurement of Low-Density Lipoprotein Cholesterol Levels in Patients with Chronic Renal Disease: A Comparative Assessment

Background/Aim: This study was performed to comparatively evaluate the results obtained for low-density lipoprotein (LDL) cholesterol concentrations by either a newly described direct method or the Friedewald equation in subjects with and without chronic renal disease. Methods: Fasting plasma was obtained from a total of 169 subjects, 105 with normal renal function (including 53 hyperlipidaemic) and 64 with chronic renal disease (nephrotic syndrome and/or chronic renal failure; including 40 hyperlipidaemic patients), and analyzed for LDL cholesterol using the Friedewald equation and a direct LDL assay method. Results: The Friedewald equation and the direct LDL cholesterol assay correlated well with each other (r = 0.79–0.90 in all subjects with plasma triglyceride, TG, levels greater than or less than 4.0 mmol/l and with and without chronic renal disease and/or hyperlipidaemia, all p < 0.0001). The values for LDL cholesterol, however, tended to be higher with the direct measurement. This mean difference was trivial in hyperlipidaemic subjects with (8.5%) and without (7.1%) normal renal function (both p < 0.05), but could be clinically significant in those with TG >4.0 mmol/l (mean difference 18%, p < 0.001). Indeed, bias plots confirmed this observation of wider negative bias for Friedewald estimation in these moderately hypertriglyceridaemic subjects. Conclusion: For most routine laboratories the options immediately available for assessment of lipid levels are the Friedewald equation or the direct measurement. The Friedewald equation and the direct assay method for LDL cholesterol are about equally good for assessment of the LDL status in patients with chronic renal disease and plasma TG <4.0 mmol/l. Where there are restraints on laboratory budgets, it would appear appropriate that the more expensive direct assay method be restricted to cases in whom plasma TG >4.0 mmol/l or to patients who, for whatever reason, are unable to produce fasting samples.

Evaluation and Clinical Application of a Direct Low-Density Lipoprotein Cholesterol Assay in Normolipidemic and Hyperlipidemic Adults

This study examines the performance and clinical use of a commercial immunoseparation assay for low-density lipoprotein (LDL) cholesterol in a sample population of normolipidemic and hyperlipidemic adult volunteers. Using paired fasting and nonfasting samples, we compared the direct LDL assay with the β quantification method and the Friedewald calculation. Overall, the direct LDL assay correctly classified 82% and 60% of fasting and nonfasting subjects, respectively, into National Cholesterol Education Program risk groups. The Friedewald method correctly classified 84% of subjects. The fasting direct LDL assay has comparable positive and negative predictive values to the Friedewald method, except at an LDL cholesterol of 100 mg/dl. The nonfasting direct LDL assay demonstrates unacceptable positive predictive values when LDL cholesterol decreases to the 130 to 159 and ≥160 mg/dl categories. Overall, direct LDL assay demonstrates limitations in the nonfasting state and at the LDL cholesterol level of 100 mg/dl used for patients with established coronary heart disease.

A More Valid Measurement of Low-Density Lipoprotein Cholesterol in Diabetic Patients

PURPOSE: This study was conducted to determine if the direct low-density lipoprotein (LDL) cholesterol assay would provide a more valid measure of LDL cholesterol in diabetic patients compared with the Friedewald equation.PATIENTS AND METHODS: Fasting plasma from 148 diabetic patients, 40 with insulin-dependent diabetes (IDDM) and 108 with non-insulin-dependent diabetes (NIDDM) with triglyceride levels <400 mg/dL, were analyzed for LDL cholesterol using the Friedewald equation, the direct LDL assay, and beta-quantification. Forty-six diabetic patients with triglyceride levels ≥400 mg/dL were also studied to determine the validity of the direct LDL cholesterol assay with hypertriglyceridemia.RESULTS: The Friedewald equation and the direct LDL cholesterol assay correlated well with beta-quantification (r = 0.969 and r = 0.971, respectively) for LDL cholesterol determination in diabetic patients. Although the Friedewald equation in comparison with beta-quantification underestimated (8%) LDL cholesterol values in diabetic patients, the direct LDL cholesterol assay had a mean bias of <1%. Also, the underestimation by the Friedewald equation exceeded 10% for the triglyceride subgroup of 200 to 400 mg/dL. Furthermore, the accuracy of the direct LDL cholesterol assay was superior to the Friedewald equation since LDL cholesterol levels determined by the two methods coincided within ±10% of beta-quantification in 85% and 68% of diabetic patients, respectively (P = 0.0005). Similar results for both the Friedewald equation and the direct LDL cholesterol assay in comparison with beta-quantification were seen when diabetic patients were subgrouped into IDDM and NIDDM. Also, the direct LDL cholesterol assay appeared to provide a reliable estimate in patients with triglycerides ≥400 mg/dL.CONCLUSION: The results of our studies indicate that the direct LDL cholesterol assay is a more reliable and accurate method than the Friedewald formula for LDL cholesterol determination in diabetic patients and is more rapid and cost effective than the reference method.

Analytical performance and clinical utility of a direct LDL-cholesterol assay in a hyperlipidemic pediatric population

This study compares a new latex immunoseparation method for the direct determination of plasma low-density lipoprotein cholesterol (LDL-C) with the reference procedure for LDL-C (beta-quantification) in a pediatric hyperlipidemic population. The direct LDL-C assay has a mean bias of -98 mg/L in a fasting group (n = 96) of patients (mean triglycerides 1057 +/- 720 mg/L) and a bias of +177 mg/L in a nonfasting group (n = 42, mean triglycerides 4854 +/- 5457 mg/L). The mean total analytical error calculated from our data is 13.8%. The direct LDL-C assay and the commonly used Friedewald calculation respectively classified 81% and 84% of fasting patients correctly, according to the cutoffs of 1100 and 1300 mg/L for LDL-C set by the National Cholesterol Education Program for pediatric patients. Of combined fasting and nonfasting patients, 80% were correctly classified by the direct LDL-C assay. Therefore, despite several analytical shortcomings, the direct LDL-C assay may be useful in managing hyperlipidemic children without the need for a fasting specimen.

Variability in cholesterol measurements: comparison of calculated and direct LDL cholesterol determinations

Calculated low-density lipoprotein cholesterol (LDL-C) concentrations determined from the Friedewald equation have a large intraindividual CV, in part because the calculation incorporates the variability of cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglyceride measurements. We studied whether a new assay that measures LDL-C directly will reduce this variability and reduce the need for averaging serial specimens. Four blood samples were obtained 1 week apart from 35 mildly hypercholesterolemic subjects and analyzed for total cholesterol, triglycerides, and HDL-C. LDL-C was calculated by the Friedewald equation, and was also measured directly with a commercially available direct LDL-C assay. The intraindividual CV for the direct and calculated LDL-C assays were similar [CV of direct LDL-C assay (mean +/- SE): 6.8 +/- 0.5% vs calculated LDL-C: 7.3 +/- 0.6%; difference 0.44%, 95% confidence interval: -0.7-1.5%]. For both assays, at least two blood tests were required from each subject to reduce total variability of LDL-C to less than or equal to 5%. We conclude that the direct LDL-C assay did not reduce the variability in LDL-C compared with the conventional LDL-C calculation. However, it may have a specific role in lipid disorder evaluation and (or) monitoring when triglycerides are increased or the LDL-C value alone is needed.