Low-density Lipoprotein Cholesterol Assay Research Articles

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.

Analytical Validation of Familial Hypercholesterolemia Biomarkers in Dried Blood Spots.

Heterozygous familial hypercholesterolemia (HeFH) is a common, treatable genetic disorder characterized by premature atherosclerosis and cardiovascular disease, yet the majority of affected individuals remain undiagnosed. Newborn screening could play a role in identification of at-risk individuals and provide an opportunity for early intervention, prior to the onset of symptoms. The objective of this study was to develop and validate assays for quantification of candidate HeFH biomarkers in dried blood spots (DBS). Commercially available enzyme assay kits for quantification of serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) were modified for high-throughput analysis of DBS. Apolipoprotein B (ApoB) concentrations in DBS were measured using an immunoassay with modifications from published studies. All three assays were validated according to the College of American Pathologists guidelines for clinical laboratories. The performance of TC, LDL-C, and ApoB assays was assessed by precision, recovery, limit of quantification (LOQ) and linearity. Precision studies yielded coefficients of variation (CV) of less than 15%, with recovery greater than 75% for all three assays. The determined LOQ and linearity were comparable to serum-based assays. In a direct comparison between serum and DBS concentrations, positive correlations were demonstrated for TC, LDL-C, and ApoB. Additionally, the initial evaluation of the three biomarker concentrations within the unaffected population was similar to values obtained in previous published studies. This study reports on methods for quantification of TC, LDL-C, and ApoB in DBS. Assay validation results were within acceptable limits for newborn screening. This is an important first step toward the identification of newborns with HeFH.

Comparison of Methods to Estimate Low-Density Lipoprotein Cholesterol in Patients With High Triglyceride Levels

Low-density lipoprotein cholesterol (LDL-C) is typically estimated with the Friedewald or Martin/Hopkins equation; however, if triglyceride levels are 400 mg/dL or greater, laboratories reflexively perform direct LDL-C (dLDL-C) measurement. The use of direct chemical LDL-C assays and estimation of LDL-C via the National Institutes of Health Sampson equation are not well validated, and data on the accuracy of LDL-C estimation at higher triglyceride levels are limited. To compare an extended Martin/Hopkins equation for triglyceride values of 400 to 799 mg/dL with the Friedewald and Sampson equations. This cross-sectional study evaluated consecutive patients at clinical sites across the US with patient lipid distributions representative of the US population in the Very Large Database of Lipids from January 1, 2006, to December 31, 2015, with triglyceride levels of 400 to 799 mg/dL. Data analysis was performed from November 9, 2020, to March 23, 2021. Accuracy in LDL-C classification according to guideline-based categories and absolute errors between estimated LDL-C and dLDL-C levels. Patients were randomly assigned 2:1 to derivation and validation data sets. Levels of dLDL-C were measured by vertical spin-density gradient ultracentrifugation. The LDL-C levels were estimated using the Friedewald method, with a fixed ratio of triglycerides to very low-density lipoprotein cholesterol (VLDL-C ratio of 5:1), extended Martin/Hopkins equation with a flexible ratio, and Sampson equation with VLDL-C estimation by multiple least-squares regression. A total of 111 939 patients (mean [SD] age, 52 [13] years; 65.0% male) with triglyceride levels of 400 to 799 mg/dL were included, representing 2.2% of 5 081 680 patients in the database. Across all individual guideline LDL-C classes (<40, 40-69, 70-99, 100-129, 130-159, 160-189, and ≥190), estimation of LDL-C by the extended Martin/Hopkins equation was most accurate (62.1%) compared with the Friedewald (19.3%) and Sampson (40.4%) equations. In classifying LDL-C levels less than 70 mg/dL across all triglyceride strata, the extended Martin/Hopkins equation was most accurate (67.3%) compared with Friedewald (5.1%) and Sampson (26.4%) equations. In addition, for classifying LDL-C levels less than 40 mg/dL across all triglyceride strata, the extended Martin/Hopkins equation was most accurate (57.2%) compared with the Friedewald (4.3%) and Sampson (14.4%) equations. However, considerable underclassification of LDL-C occurred. The magnitude of error between the Martin/Hopkins equation estimation and dLDL-C was also smaller: at LDL-C levels less than 40 mg/dL, 2.7% of patients had 30 mg/dL or greater differences between dLDL-C and estimated LDL-C using the Martin/Hopkins equation compared with the Friedewald (92.5%) and Sampson (38.7%) equations. In this cross-sectional study, the extended Martin/Hopkins equation offered greater LDL-C accuracy compared with the Friedewald and Sampson equations in patients with triglyceride levels of 400 to 799 mg/dL. However, regardless of method used, caution is advised with LDL-C estimation in this triglyceride range.

A Tale of Two Approaches.

To summarize and assess the literature on the performances of methods beyond the Friedewald formula (FF) used in routine practice to determine low-density lipoprotein cholesterol (LDL-C). A literature review was performed by searching the PubMed database. Many peer-reviewed articles were assessed. The examined methods included direct homogeneous LDL-C assays, the FF, mathematical equations derived from the FF, the Martin-Hopkins equation (MHE), and the Sampson equation. Direct homogeneous assays perform inconsistently across manufacturers and disease status, whereas most FF-derived methods exhibit variable levels of performance across populations. The MHE consistently outperforms the FF but cannot be applied in the setting of severe hypertriglyceridemia. The Sampson equation shows promise against both the FF and MHE, especially in severe hypertriglyceridemia, but data are still limited on its validation in various settings, including disease and therapeutic states. There is still no consensus on a universal best method to estimate LDL-C in routine practice. Further studies are needed to assess the performance of the Sampson equation.

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.

Accuracy evaluation of five analytical systems for high- and low-density lipoprotein cholesterol assays in Korea

Accuracy evaluation of five analytical systems for high- and low-density lipoprotein cholesterol assays in Korea

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.

Differences in reaction specificity toward lipoprotein X and abnormal LDL among 6 homogeneous assays for LDL-cholesterol

BackgroundWe investigated the reaction specificity toward cholesterol in lipoprotein X (Lp-X) and abnormal LDL among 6 homogeneous assays for low-density lipoprotein cholesterol (LDL-C) based on different measurement principles. MethodsThe homogeneous LDL-C assays used were based on the liquid selective detergent, selective solubilization, elimination, enzyme-selective protection, calixarene complex, and phosphate complex inhibition methods. The fraction with a density of 1.006–1.063kg/l was isolated from cholestatic sera, and the reactivity of cholesterol in the lipoprotein fractions by gel filtration for each homogeneous LDL-C assay was determined. ResultsThe liquid selective detergent and elimination methods showed increased cholesterol reactivity in the Lp-X fraction in a concentration-dependent manner, while the selective solubilization and phosphate complex inhibition methods were less reactive toward Lp-X cholesterol. Meanwhile, the homogeneous LDL-C assays showed decreased reactivity against cholesterol in abnormal LDL, with increased ratios of phospholipids and triglycerides against cholesterol. ConclusionThe homogeneous LDL-C assays showed differential reactivity toward Lp-X and abnormal LDL. Our findings enable accurate interpretation of the LDL-C values in these homogeneous assays, and suggest that these methods should be improved to distinguish between normal LDL and abnormal LDL or Lp-X.

Reliability of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B measurement

There is little understanding of the reliability of laboratory measurements among clinicians. Low-density lipoprotein cholesterol (LDL-C) measurement is the cornerstone of cardiovascular risk assessment and prevention, but it is fraught with error. Therefore, we have reviewed issues related to accuracy and precision for the measurement of LDL-C and the related markers non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B. Despite the widespread belief that LDL-C is standardized and reproducible, available data suggest that results can vary significantly as the result of methods from different manufacturers. Similar problems with direct HDL-C assays raise concerns about the reliability of non-HDL-C measurement. The root cause of method-specific bias relates to the ambiguity in the definition of both LDL and HDL, and the heterogeneity of LDL and HDL particle size and composition. Apolipoprotein B appears to provide a more reliable alternative, but assays for it have not been as rigorously tested as direct LDL-C and HDL-C assays.

Multiple lipoprotein and electrolyte laboratory artifacts caused by lipoprotein X in obstructive biliary cholestasis secondary to pancreatic cancer

Lipoprotein X (Lp-X) is an abnormal lipoprotein which may form in patients with intra- and extra-hepatic cholestasis. The presence of very high levels of Lp-X has been shown to be a rare cause of pseudohyponatremia. We present a patient with severe obstructive cholestasis secondary to pancreatic cancer leading to very high Lp-X concentrations resulting in pseudohyponatremia, pseudohypokalemia, pseudohypochloremia and interference with the selective micellary solubilization direct low density lipoprotein cholesterol assay. These spurious laboratory anomalies impeded the initial clinical management of the patient including the attempted correction of the electrolyte abnormalities. After relief of obstruction following biliary stent placement, the patient's lipid levels normalized. Clinicians must be wary of laboratory artifacts and remember to correlate the laboratory values with the clinical presentation of the patient. Assays employing direct ion-selective electrodes such as those in blood gas analyzers are not subject to the interference of high concentrations of lipids or proteins, and maybe useful in situations where such interference is suspected. Furthermore the Vertical Auto Profile (VAP®) ultracentrifugation assay may be useful to detect lipoprotein X and low density lipoprotein cholesterol levels when the selective micellary solubilization technique fails to detect or quantify these lipid moieties.

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.

Letter by Lund et al Regarding Article, “Fasting Compared With Nonfasting Lipids and Apolipoproteins for Predicting Incident Cardiovascular Events”

To the Editor: We are delighted about the report from Mora et al showing a lack of predictive value for future cardiovascular disease (CVD) of nonfasting low-density lipoprotein cholesterol (LDL-C) contrasting with the well-known predictive value of fasting LDL-C.1 In our opinion, the applied methodology has some pitfalls: 1. Measurement by a direct assay (Genzyme or Roche) in frozen samples might not produce reliable LDL-C estimates compared with fresh samples. 2. The evidence for using direct LDL-C assays in nonfasting samples (fresh or frozen) with respect to the agreement with the method recommended by the Centers for Disease Control and Prevention for measurement of LDL-C (ie, the β quantification) is sparse. 3. In daily …

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.

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.