Comparación de los métodos de Friedewald y Vujovic con la concentración de LDL calculada en un autoanalizador bioquímico / Comparison of the Friedewald and Vujovic methods with the calculated LDL concentration in a biochemical auto-analyzer

Objective To compare the concentration of Low-Density Lipoprotein (LDL-c) obtained using the Friedewald formula with those obtained directly with the RAYTO CHEMRAY 120 autoanalyzer. Methods Cross-sectional study. We evaluated outpatients with a medical request for a lipid profile study (total cholesterol, triglycerides, LDL, and HDL). The analyses were carried out in a RAYTO CHEMRAY 120 autoanalyzer under the principle of spectrophotometry. We obtained LDL-c using the Friedewald and Vujovic formulas. Results We evaluated 199 individuals whose direct LDL concentration averages were measured by the RAYTO CHEMRAY 120 equipment. Those calculated by the Friedewald and Vujovic formulas were 129.97 ± 32.66, 119.28 ± 30.44, and 127.01 ± 32.01, respectively, and in all cases, significant differences (P < 0.001) were observed with the RAYTO analyzer. In both cases a low positive bias was found with the RAYTO analyzer.. The Passing-Bablok and Deming's regressions showed a linear correlation between both methods (Friedewald and Vujovic) with the LDL values obtained with the Rayto autoanalyzer. Conclusions Our study found that the Friedewald and Vujovic methods are good predictors of LDL cholesterol levels and have a low level of bias. Therefore, they could be used as potential predictors.

Objetivo Comparar las concentraciones de Lipoproteínas de Baja Densidad (LDL-c) obtenidas mediante la fórmula de Friedewald con las obtenidas directamente con el autoanalizador RAYTO CHEMRAY 120. Métodos Estudio transversal. Se evaluaron pacientes ambulatorios con solicitud médica de perfil lipídico (colesterol total, triglicéridos, LDL y HDL). Los análisis se realizaron con un autoanalizador RAYTO CHEMRAY 120 bajo el principio de espectrofotometría. Obtuvimos el LDL-c usando las fórmulas de Friedewald y Vujovic. Resultados Se evaluaron 199 individuos cuyos promedios directos de concentración de LDL fueron medidos con el equipo RAYTO CHEMRAY 120. Las concentraciones calculadas por las fórmulas de Friedewald y Vujovic fueron de 129,97 ± 32,66, 119,28 ± 30,44, y de 127,01 ± 32,01, respectivamente, y en todos los casos se observaron diferencias significativas (P < 0,001) con el analizador RAYTO. En ambos casos se encontró un sesgo positivo bajo en el analizador RAYTO. Las regresiones de Passing-Bablok y Deming mostraron una correlación lineal entre ambos métodos (Friedewald y Vujovic) con los valores de LDL obtenidos con el autoanalizador Rayto. Conclusión Nuestro estudio encontro que los métodos de Friedewald y Vujovic son buenos predictores de los niveles de colesterol LDL y presentan un nivel de sesgo bajo. Por lo que podrían usarse como potenciales predictores.

Comparison of Friedewald’s formula, modified Friedewald’s formula and Anandaraja’s formula with direct homogenous serum LDL cholesterol method in CHD patients

Background: Elevated serum Low-Density Lipoprotein Cholesterol (LDL-C) concentration is a well-known atherogenic risk factor with a high predictive value for coronary heart disease. An important aspect of the assessment of coronary heart disease risk for a dyslipidemic subject is the estimation of serum Low-Density Lipoprotein Cholesterol (LDL-C). There are many homogenous assays currently available for the estimation of serum LDL-C. Most clinical laboratories determine LDL-C (mg/dl) by Friedewald’s formula (FF), LD-=(TC)-HDL-C)-(TG/5), Modified Friedewald’s formula (MFF), LDL-C=(TC)-(HDL-C)-(TG/6), Recently Anandaraja and colleagues have derived a new formula for calculating LDL-C, AR-LDL-C=0.9 TC-(0.9 TG/5)-28.Methods: It is cross-sectional study. Lipid profile data was collected from known of CHD patients, who had come for lipid profile investigation to the Central Biochemistry laboratory of ACPM Medical College and hospital. LDL-C estimation was done by direct homogenous assay and also calculated using the Friedewald’s Formula, Modified Friedewald’s Formula and Anandaraja’s Formula for assessing and validity of the LDL cholesterol.Results: From the present study, The LDL-FF, MFW and AR are increased with levels of TGL > 200 mg/dl and decreased level of TC < 200 mg/dl seem to interfere with the estimation of Direct LDL cholesterolConclusions: Authors conclude that, LDL-C by direct method is most reliable and sensitive in CHD patients compare with FF, MFW, and ARF.

Concordancia entre la medición directa y el valor estimado de colesterol de LDL en pacientes ambulatorios / Concordance between direct measurement and estimated LDL cholesterol in outpatients / Concordância entre medição direta e colesterol LDL estimado em pacientes ambulatoriais

Los laboratorios clínicos estiman la concentración del colesterol asociado a la lipoproteína de baja densidad (cLDL) mediante la ecuación de Friedewald; sin embargo, ésta presenta una notable desviación cuando la concentración sérica de triglicéridos se encuentra elevada. Se compararon 4.644 resultados de cLDL valorados en el laboratorio central del Hospital Edgardo Rebagliati Martins (Lima-Perú), mediante el ensayo directo homogéneo, con los valores estimados por las ecuaciones de Friedewald, Anandaraja, Chen, Vujovic, Córdova y de regresión múltiple. Además, se estratificaron los resultados en 5 grupos en función de las concentraciones de triglicéridos para determinar la influencia que ejerce el nivel de triglicéridos sobre dichas ecuaciones. En el total de las estimaciones, las ecuaciones de regresión y Vujovic mostraron los menores sesgos de -3,00 y -2,90 mg/dL, respectivamente. Asimismo, ambas ecuaciones presentaron un grado de acuerdo sustancial con la determinación directa y un menor error sistemático en los tres niveles de decisión clínica para el cLDL; sin embargo, la ecuación de regresión presentó una mejor performance para estimar el cLDL en concentraciones de triglicéridos ≥401 mg/dL. Se concluye que la ecuación de regresión presenta bajo error analítico, además de mostrar una buena concordancia con el método directo, incluso a concentraciones altas de triglicéridos.

Clinical laboratories estimate the concentration of low-density lipoprotein cholesterol (LDLc) associated with the Friedewald equation, but the latter shows a significant deviation when the serum triglyceride concentration is elevated. A total of 4644 LDLc values assessed at the central laboratory of the Edgardo Rebagliati Martins Lima-Perú Hospital were compared by means of the homogeneous direct assay with the values estimated by the Friedewald, Anandaraja, Chen, Vujovic, Córdova and multiple regression equations. Besides, the results were stratified into 5 groups based on triglyceride concentrations to determine the influence exerted by the triglyceride level on these equations. In the total of the estimates, the regression equations and Vujovic showed the lowest biases of -3.00 and -2.90 mg/dL respectively. Likewise, both equations presented a degree of substantial agreement with the direct determination and a smaller systematic error in the three levels of clinical decision for LDLc. However, the regression equation showed a better performance for estimating LDLc at triglyceride concentrations ≥401 mg/dL. It is concludeasdasdd that the regression equation presents low analytical error, besides showing a good concordance with the direct method even at high triglyceride concentrations.

Laboratórios clínicos calculam a concentração do colesterol associado à lipoproteína de baixa densidade (LDLc), utilizando a equação de Friedewald; no entanto ela apresenta um desvio significativo quando a concentração sérica de triglicerídeos está elevada. 4644 resultados de LDLc foram comparados avaliados no laboratório central do Hospital Edgardo Rebagliati Martins (Lima-Peru), por ensaio directo homogêneo, com os valores estimados pelas equações Friedewald, Anandaraja, Chen, Vujovic, Córdova e de regressão múltipla. Além disso, foram estratificados os resultados em cinco grupos com base nas concentrações de triglicerídeos para determinar a influência que exerce o nível de triglicerídeos sobre tais equações. No total das estimativas, as equações de regressão e Vujovic mostraram os menores vieses de -3,00 e -2,90 mg/DL, respectivamente. Também, ambas as equações apresentaram um grau substancial de acordo com a determinação direta e um menor erro sistemático nos três níveis de decisão clínica para o LDLc; contudo, a equação de regressão apresentou melhor desempenho para estimar o LDLc em concentrações de triglicerídeos ≥401 mg/dL. Conclui-se que a equação de regressão apresenta baixo erro analítico, além de mostrar boa concordância com o método direto, mesmo em altas concentrações de triglicerídeos.

Martin's Equation as the Most Suitable Method for Estimation of Low-Density Lipoprotein Cholesterol Levels in Korean Adults / 가정의학회지

BACKGROUND: Friedewald equation is the most widely used method for estimating low-density lipoprotein cholesterol (LDL-C) level. However, due to potential over- or underestimation, many studies have used a modified equation. This study aimed to compare estimates by 4 different equations to directly measured LDL-C concentrations in order to propose the most appropriate method for LDL-C estimation in the Korean population. METHODS: We studied data of 4,350 subjects that included total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and LDL-C concentrations that had been measured at one university hospital in Seoul. We investigated 4 equations: LDL-C by Friedewald's original equation (LDL-C(F)) and its 3 modifications. Pearson correlation analysis was performed to compare these estimates to the direct measurement. RESULTS: Pearson correlation analysis revealed a good correlation among all 4 estimated LDL-C values and the directly measured LDL-C value. The Pearson coefficients were 0.951 for LDL-C(F), 0.917 for LDL-C by Hatta equation (LDL-C(H)), 0.968 for LDL-C by Puavilai equation (LDL-C(P)), and 0.983 for LDL-C by Martin equation (LDL-C(M)). Martin equation (LDL-C(M)) resulted in the best approximation (mean difference from the direct measurement, 5.5 mg/dL; mean percentage difference from the direct measurement, 5.1%) and the best agreement with the direct measurement (86.1%). LDL-C(P) resulted in the second-best approximation (mean difference, 7.0 mg/dL; mean percentage difference, 6.2%; concordance, 82.5%). LDL-C(M) was found to be less influenced by TG and HDL-C levels than by LDL-C(F). CONCLUSION: Estimates by Martin equation had the best agreement with direct LDL-C concentrations and both Martin and Puavilai equations were superior to Friedewald equation for estimating LDL-C concentrations in Korean adults.

Valores de colesterol LDL en una población adulta de referencia / LDL cholesterol values in a reference mature population

Se llevó a cabo un estudio descriptivo de 205 usuarios del Laboratorio Central del Hospital Provincial Docente Clinicoquirúrgico "Saturnino Lora Torres" de Santiago de Cuba, desde diciembre del 2013 hasta igual periodo del 2014, a fin de determinar los niveles de referencia de colesterol LDL por el método enzimático e identificar variaciones en las estimaciones del analito según 2 metodologías. Se aplicó la prueba estadística paramétrica de Anderson Darling. Predominaron el sexo masculino, el adulto joven y los pacientes normopeso. Se establecieron los valores de referencia para el colesterol LDL por método directo de 1,37 a 4,89 mmol/L para la población general. Se obtuvo un coeficiente de correlación de Pearson de 0,82 entre el método directo y la fórmula de Friedewald. Los valores obtenidos no se encontraron contenidos en el rango clínico establecido para este analito y aunque ambas metodologías se asociaron, dichos valores fueron marcadamente inferiores para el método calculado.

A descriptive study of 205 users of the Central Laboratory of "Saturnino Lora Torres" Teaching Clinical Surgical Provincial Hospital in Santiago de Cuba was carried out from December, 2013 to the same period in 2014, in order to determine the reference levels of LDL cholesterol for the enzymatic method and identify estimates variations of analito according to 2 methodologies. Anderson Darling's parametric statistical test was applied. Male sex, young adult and the patients with normal weight prevailed. The reference values were established for LDL cholesterol by direct method from 1.37 to 4.89 mmol/L for the general population. A Pearson correlation coefficient of 0.82 was obtained between the direct method and the Friedewald formula. The obtained values were not contained in the established clinical range for this analito and although both methodologies were associated, such values were markedly inferior for the calculated method.

Comparison of Formulas for Calculating Low-density Lipoprotein Cholesterol in General Population and High-risk Patients with Cardiovascular Disease

BACKGROUND AND OBJECTIVES: Low-density lipoprotein cholesterol (LDL-C), an established cardiovascular risk factor, can be generally determined by calculation from total cholesterol, high-density lipoprotein cholesterol, and triglyceride concentrations. The aim of this study was to compare LDL-C estimations using various formulas with directly measured LDL-C in a community-based group and hospital-based group among the Korean population. SUBJECTS AND METHODS: A total of 1498 participants were classified into four groups according to triglyceride concentrations as follows: <100, 100–199, 200–299, and ≥300 mg/dL. LDL-C was calculated using the Friedewald, Chen, Vujovic, Hattori, de Cordova, and Anandaraja formulas and directly measured using a homogenous enzymatic method. Pearson's correlation coefficients, intraclass correlation coefficients (ICC), Passing & Bablok regression, and Bland-Altman plots were used to evaluate the performance of six formulas. RESULTS: The Friedewald formula had the highest accuracy (ICC=0.977; 95% confidence interval 0.974-0.979) of all the triglyceride ranges, while the Vujovic formula had the highest accuracy (ICC=0.876; 98.75% confidence interval 0.668–0.951) in people with triglycerides ≥300 mg/dL. The mean difference was the lowest for the Friedewald formula (0.5 mg/dL) and the percentage error was the lowest for the Vujovic formula (30.2%). However, underestimation of the LDL-C formulas increased with triglyceride concentrations. CONCLUSION: The accuracy of the LDL-C formulas varied considerably with differences in triglyceride concentrations. The Friedewald formula outperformed other formulas for estimating LDL-C against a direct measurement and the Vujovic formula was suitable for hypertriglyceridemic samples; it could be used as an alternative cost-effective tool to measure LDL-C when the direct measurement cannot be afforded.

DETERMINACIÓN DE LOS NIVELES DE COLESTEROL LDL COMPARANDO EL MÉTODO PRECIPITADO VS LA FÓRMULA DE FRIEDEWALD EN CANINOS / DETERMINATION OF LDL CHOLESTEROL LEVELS OF COMPARING THE PRECIPITATE METHOD VS THE FRIEDEWALD FORMULA CANINE

El objetivo del presente estudio fue comparar el método de precipitación con el método de fórmula de Friedewald para la determinación de colesterol LDL en caninos. Para ello, se tomaron muestras de sangre de 185 caninos adultos en estado de ayuno de diferente raza y sexo. Se determinaron los niveles de colesterol LDL mediante el método precipitado y posteriormente con el método de Friedewald. Los resultados fueron analizados estadísticamente mediante ANOVA de una vía. El método precipitado reportó valores en mg/dl de: 52,40 promedio; 2,66 mínimo; 132,67 máximo; 130,01 rango y 24,29 de desviación estándar. Por su parte, los valores del método de Friedewald en mg/dl fueron: 65,19 promedio; 4,55 mínimo; 184,20 máximo; 179,65 rango y 31,51 de desviación estándar. El valor de p en el test F fue menor a 0.05, indicando diferencia estadísticamente significativa entre los dos métodos analizados con un nivel de confianza del 95,0%. En conclusión se recomienda utilizar el método precipitado para la determinación de los niveles de colesterol LDL en caninos.

The objetive of this study was to compare the precipitation method with the method of Friedewald formula for the determination ofLDL cholesterol in dogs. For that, blood samples of 185 overnight fasted adult dogs of different breed and sex were obtained. Blood levels of LDL cholesterol were determined by the precipitation method and later by the Friedewald method. The results were analyzed using one way ANOVA. The precipitate method reported values in mg/dl of: 52.40 average, 2.66 minimum, 132.67 maximum, 130.01 range and 24.29 of standard deviation. For its part, the Friedewald equation values in mg/dl were: 65.19 average, 4.55 minimum, 184.20 maximum, 179.65 range and 31.51 of standard deviation. The p-value in the F test was less than 0.05, indicating statistically significant difference between the two methods analyzed with a confidence level of 95.0%. In conclusion it can be used the precipitated method for determining LDL cholesterol levels in dogs.

Evaluation of Recently Developed Regression Equation with Direct Measurement of Low-density Lipoprotein Cholesterol in a Bangladeshi Population.

Background: Meaningful underestimation of low-density lipoprotein (LDL) cholesterol is an important shortcoming of Friedewald’s formula (FF) at higher triglyceride (TG) levels. Recently a regression equation (RE) has been developed using lipid profiles in one setting and validated externally for the calculation of LDL cholesterol. This newly developed RE requires more studies in different settings. Objective: The aim of this study was to evaluate the performance of the regression equation against direct measurement. Materials and Methods: Lipid profiles of 600 subjects attending a tertiary healthcare center were included in this study. Specimens were collected and lipid profiles were measured by standard methods. Sixty two lipid profiles with TG above 400 mg/dL were excluded. Calculated LDL cholesterol values using FF and RE were compared with measured LDL cholesterol by Pearson’s correlation test, Passing & Bablok regression, accuracy within ±5% and ±12% of measured LDL cholesterol and two-tailed paired t test at various TG ranges. Results: The mean value of LDL cholesterol was 148.6 ± 37.2 mg/dL for direct measurement, 146.9 ± 42.4 mg/dL for FF and 148.6 ± 34.7 mg/dL for RE. The correlation coefficients of calculated LDL cholesterol values with measured LDL cholesterol were 0.949 (p<0.001) for FF and 0.959 (p<0.001) for RE. Passing & Bablok regression equation against measured LDL cholesterol was y = 0.897x + 16.2 for FF and y = 1.0842x – 13.1 for RE. Accuracy within ±5% of measured LDL cholesterol was 45% for FF, 57% for RE and within ±12% of measured LDL cholesterol was 84% for FF, 93% for RE. When calculated LDL cholesterol was compared with measured LDL cholesterol at different TG ranges, FF significantly underestimated LDL cholesterol at TG concentrations above 200 mg/dL whereas no significant difference was observed for RE. Conclusion: This study reveals that RE equation has similar performance to direct measurement for calculation of LDL cholesterol.

Evaluation of the Novel Method and the Regression Equation for Calculation of Low-Density Lipoprotein Cholesterol.

Background: Friedewald’s formula (FF) is used worldwide to calculate low-density lipoprotein cholesterol (LDL-chol). But it has several shortcomings: overestimation at lower triglyceride (TG) concentrations and underestimation at higher concentrations. In FF, TG to very low-density lipoprotein cholesterol (VLDL-chol) ratio (TG/VLDL-chol) is considered as constant, but practically it is not a fixed value. Recently, by analyzing lipid profiles in a large population, continuously adjustable values of TG/VLDL-chol were used to derive a novel method (NM) for the calculation of LDL-chol. Objective: The aim of this study was to evaluate the performance of the novel method compared with direct measurement and regression equation (RE) developed for Bangladeshi population. Materials and Methods: In this cross-sectional comparative study we used lipid profiles of 955 adult Bangladeshi subjects. Total cholesterol (TC), TG, HDL-chol and LDL-chol were measured by direct methods using automation. LDL-chol was also calculated by NM and RE. LDL-chol calculated by NM and RE were compared with measured LDL-chol by twotailed paired t test, Pearson’s correlation test, bias against measured LDL-chol by Bland-Altman test, accuracy within ±5% and ±12% of measured LDL-chol and by inter-rater agreements with measured LDL-chol at different cut-off values. Results: The mean values of LDL-chol were 110.7 ± 32.0 mg/dL for direct measurement, 111.9 ± 34.8 mg/dL for NM and 113.2 ± 31.7 mg/dL for RE. Mean values of calculated LDL-chol by both NM and RE differed from that of measured LDL-chol (p<0.01 for NM and p<0.0001 for RE). The correlation coefficients of calculated LDL-chol values with measured LDL-chol were 0.944 (p<0.0001) for NM and 0.945 (p<0.0001) for RE. Bland- Altman plots showed good agreement between calculated and measured LDL-chol. Accuracy within ±5% of measured LDL-chol was 49% for NM, 46% for RE and within ±12% of measured LDL-chol was 79% for both NM and RE. Inter-rater agreements (κ) between calculated and measured LDL-chol at LDL-chol <100 mg/dL, 100–130 mg/dL and >130 mg/dL were 0.816 vs 0.815, 0.637 vs 0.649 and 0.791 vs 0.791 for NM and RE respectively. Conclusion: This study reveals that NM and RE developed for Bangladeshi population have similar performance and can be used for the calculation of LDL-chol.

Measuring Low Density Lipoprotein Cholesterol: Comparison of Direct Measurement by HiSens Reagents and Friedewald Estimation / 가정의학회지

BACKGROUND: Directly measured low density lipoprotein cholesterol (DLDLC) has been reported to be more accurate than calculated low density lipoprotein cholesterol (CLDLC) using the Friedewald equation. However, some limitations of DLDLC have been reported. In this study, we evaluated differences between CLDLC and DLDLC measured using HiSens reagents. METHODS: Data were collected from 582 persons undergoing routine physical examinations at a general hospital. LDLC measurements were made directly or estimated using the Friedewald formula, and were classified according to the National Cholesterol Education Program's Adult Treatment Panel III guidelines. The relationship between these differences and other clinically relevant factors, such as triglyceride (TG) levels, were examined using multiple logistic regression analysis. RESULTS: The DLDLC and CLDLC were strongly correlated according to simple linear regression analysis (r=0.917, P0.5). CONCLUSION: Unlike other studies, DLDLC was significantly lower than CLDLC and the large differences in LDLC concentrations were not dependent on TG concentration. Our work suggests that verification of DLDLC accuracy is needed and differences in LDLC measurements should be accounted for in making clinical decisions.

Evaluation of Performance of the Newly Developed de Cordova's Formula for Calculation of Low-Density Lipoprotein Cholesterol without Use of Triglycerides.

Background: Various formulas are available to estimate serum low-density lipoprotein (LDL) cholesterol. All of these are serum triglycerides (TG) dependent. But very recently de Cordova et al developed a simple formula (CF) to calculate LDL cholesterol without using serum TG and claimed it to be more accurate than Friedewald.s formula (FF). Objective: The objective of the present study was to evaluate the performance of the CF for the calculation of LDL cholesterol in a Bangladeshi population. Materials and Methods: Three hundred and sixty adult Bangladeshi subjects were purposively included in this study. Serum total cholesterol (TC), TG, high-density lipoprotein (HDL) cholesterol and LDL cholesterol were measured by direct automated methods. LDL cholesterol was also calculated by CF and FF. Results were expressed in conventional unit as mean ± SD and compared by two-tailed paired t test, bias against measured LDL cholesterol, Pearson's correlation coefficient (r), Passing & Bablok regression and accuracy within ±10% of the measured LDL cholesterol. Results: The mean values of directly measured LDL cholesterol, LDL cholesterol calculated by CF and FF were 117.7 ± 31.0, 111.8 ± 31.0 and 108.9 ± 39.7 mg/dL respectively. Bias of calculated LDL cholesterol against measured LDL cholesterol was -5.2% for CF and -9.6% for FF. The correlation coefficients of measured LDL cholesterol were 0.9796 (p<0.001) for CF and 0.9525 (p<0.001) for FF. Passing & Bablok regression yielded the equation y = 0.9938x - 6.2 for CF and y = 1.2774x - 40.9 for FF. Accuracy within ±10% of measured LDL cholesterol was 81% for CF and 49% for FF. Conclusion: This study revealed better performance of the de Cordova's formula than Friedewald's formula for approximate calculation of LDL cholesterol without using serum triglycerides.

Colesterol -LDL: ¿determinación química, fórmula de Friedewald o análisis de Regresión ? / LDL cholesterol: Direct homogeneous assay, Friedewald formula, or regression analysis?

La elevación del colesterol de la lipoproteína de baja densidad (C-LDL) es una de las principales causas de riesgo cardiovascular. Pese a la existencia de métodos analíticos para medir la concentración de C-LDL, el uso de la fórmula de Friedewald permite estimar su valor a partir de los valores de colesterol, triglicéridos y colesterol de la lipoproteína de alta densidad (C-HDL). Nuestro objetivo fue el evaluar la validez de la utilización de la fórmula, comparándola con la medida directa del C-LDL y el análisis de regresión múltiple a partir de datos de muestras de pacientes pediátricos. Se realizo un análisis de regresión lineal múltiple. La ecuación de regresión obtenida fue: C-LDL= -1,5988 + (0,845168*CT)-(0,0966192*TG)-(0,80157*C-HDL)+ (1,13943*sexo). Este modelo resulta satisfactorio (p-valor < 0,00001) ya que explica el 95,43% del comportamiento de las C-LDL con un valor de R2 = 0,9543. Los valores de C-LDL predichos con la ecuación de regresión presentaron un valor 97,26 ± 35,57 mg/dl, no mostrando diferencias significativas (p-valor=0,981) con los valores hallados con el método homogéneo 97,47 ± 36,55 mg/dl lo que permitiría su aplicación en nuestro laboratorio (AU)

High low-density lipoprotein (LDL) cholesterol levels is one of the main causes of cardiovascular risk. Although different analytical methods exist, the Friedewald formula allows to estimate LDL based on total cholesterol, triglyceride, and high-density lipoprotein (HDL) cholesterol levels. Our aim was to evaluate the validity of the formula comparing it to direct LDL-cholesterol measurement using multiple linear regression analysis of the data of samples of pediatric patients. Performing multiple regression analysis, the regression equation obtained was: LDL cholesterol =-1.5988+(0.845168*CT)- (0.0966192*TG)-(0.80157*HDL cholesterol)+(1.13943*sex). The model proved to be satisfactory (p-value < 0.00001) as it confirmed 95.43% of the LDL cholesterol levels with an R2 value = 0.9543. The LDL cholesterol levels predicted by regression equation were 97.26 ± 35.57 mg/dl, not showing significant differences (p-value=0.981) compared with levels found using the homogeneous method (97.47 ± 36.55 mg/dl) allowing its use in our laboratory (AU)

Medida del colesterol de lipoproteínas de baja densidad utilizando tres metodologías / Measurement of cholesterol low-density lipoprotein using three methodologies / Medida do colesterol de lipoproteínas de baixa densidade utilizando tres metodologias

Tomando en cuenta que aún no existe una metodología estándar de rutina para la determinación del colesterol de lipoproteínas de baja densidad (LDL-c) se decidió evaluar su determinación analítica utilizando tres técnicas: determinación enzimática homogénea, precipitación con sulfato de polivinilo y fórmula de Friedewald. Fueron procesadas 98 muestras de suero a las cuales se les determinó triglicéridos (TG), colesterol total (CT), colesterol de lipoproteínas de alta densidad (HDL-c) y colesterol de lipoproteínas de baja densidad (LDL-c). Los valores promedio de CT fueron 194,46 ± 43,54 mg/dL, HDL-c 51,12 ± 12,36 mg/dL y TG 132,88 ± 76,93 mg/dL. Aun cuando el análisis de regresión mostró una buena correlación entre los valores de LDL-c, los resultados indicaron una diferencia estadísticamente significativa en los mismos cuando los niveles de TG superaron los 200 mg/dL. La misma se observó principalmente entre el método de precipitación y la fórmula de Friedewald, siendo los valores significativamente más bajos en esta última (LDL-c por precipitación: 141,3 ± 26,2 mg/dL; LDL-c por fórmula de Friedewald: 110,1 ± 35,4 mg/dL). De la misma manera se vio afectada la proporción de individuos clasificados según su riesgo coronario. Es necesario comparar las técnicas aplicadas en este estudio con la cuantificación beta para evaluar cuál tiene un mayor nivel de exactitud.

Considering that there is still no standard methodology for routine determination of low density lipoprotein (LDL-c) it was decided to evaluate their analytical determination using three techniques: homogeneous enzymatic determination, polyvinyl sulphate precipitation and Friedewald formula. Ninety-eight serum samples were processed; triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL-c) and LDL-c were determined. Mean total cholesterol was 194.46 ± 43.54 mg/dL, HDL-C was 51.12 ± 12.36 mg/dL and TG was 132.88 ± 76.93 mg/dL. Although regression analysis showed a good correlation between LDL-c, the results showed a statistically significative difference in them when TG levels exceeded 200 mg/dL. It was mainly observed in the precipitation method and the Friedewald formula, the latter values being significantly lower (LDL-C by precipitation: 141.3 ± 26.2 mg/dL, LDL-C by the Friedewald formula: 110, 1 ± 35.4 mg/dL). Moreover, this difference affected the proportion of individuals classified according to their coronary risk. It is necessary to compare the techniques applied in this study with beta quantification to assess which has a higher level of accuracy.

Levando em consideragao que ainda nao existe uma metodologia padrao de rotina para a determinagao do colesterol de lipoproteínas de baixa densidade (LDL-c) se decidiu avaliar sua determinagao analítica utilizando tres técnicas: determinagao enzimática homogénea, precipitagao com sulfato de polivinil e fórmula de Friedewald. Foram processadas 98 amostras de soro as quais lhes foi determinado triglicerídeos (TG), colesterol total (CT), colesterol de lipoproteínas de alta densidade (HDL-c) e colesterol de lipoproteínas de baixa densidade (LDL-c). Os valores médios de CT foram 194,46 ± 43,54 mg/dL, HDL-c 51,12 ± 12,36 mg/dL e TG 132,88 ± 76,93 mg/dL. Inclusive quando a análise de regressao mostrou uma boa correlagao entre os valores de LDL-c, os resultados indicaram uma diferenga estatisticamente significativa nos mesmos quando os niveis de TG superaram os 200 mg/dL. A mesma se observou principalmente entre o método de precipitagao e a fórmula de Friedewald, sendo os valores significativamente mais baixos nesta última (LDL-c por precipitagao: 141,3 ± 26,2 mg/dL; LDL-c por fórmula de Friedewald: 110,1 ± 35,4 mg/dL). Da mesma maneira se viu afetada a proporgao de indivíduos classificados conforme seu risco coronariano. É necessário comparar as técnicas aplicadas neste estudo com a quantificagao beta para avaliar qual é que tem maior nível de exatidao.

Optimal Range of Triglyceride Values to Estimate Serum Low Density Lipoprotein Cholesterol Concentration in Korean Adults: the Korea National Health and Nutrition Examination Survey, 2009

The aims of this study were to investigate the validity of Friedewald's formula and to propose a range of triglyceride values over which the formula can be used without significant error. This was a cross-sectional analysis of 1,929 subjects (946 males and 983 females) aged 20 yr and older using data of the Korea National Health and Nutrition Examination Survey in 2009. Estimated total number was considered to be 10,633,655 (5,846,384 males and 4,787,271 females). Calculated and directly-measured low density lipoprotein cholesterol (LDL-C) values were highly correlated (r = 0.96); however, significant differences were observed between the directly-measured and calculated LDL-C concentrations. Subjects in the underestimated group (10.5%) had higher dysmetabolic profiles than those in the overestimated group (11.4%). Although serum triglyceride level showed the greatest independent association with differences between the calculated and directly-measured LDL-C concentrations, no statistically significant differences were noted when triglyceride concentration was between 36 and 298 mg/dL (93.2%). In conclusion, Friedewald's formula accurately estimates directly-measured serum LDL-C concentration in Korean adults. However, the formula can be applied to subjects with serum triglyceride concentrations from 36 to 298 mg/dL without significant error.

Comparison of low-density lipoprotein obtained from the Friedewald formula and new formulae in a heterogeneous population / Comparación de lipoproteínas de baja densidad obtenidas por fórmula de Friedewald y nuevas fórmulas en una población heterogénea

Introduction: Although the levels of low-density lipoprotein (LDL-C) should ideally be determined by beta quantification or enzymatic methods, there are limitations in developing countries. The goal of this study is to compare LDL-C obtained through three formulae (LDL-Cnf) with LDL-C obtained through the Friedewald formula (LDL-Cf) using LDL-C through enzymatic methods as the most-accepted reference method in clinical practice (LDL-Cr). Methods: A concordance study was carried out in a reference laboratory in Cali, Colombia. The three formulae were (mg/dl): Men with triglycerides under 400 mg/dl: LDL-C = Total Cholesterol (TC) - triglycerides (TG) /6.5) - 45; men with triglycerides equal to or greater than 400 mg/dl: LDL-C = (TC - (TG / 7)) -50 and women: LDL-C = (TC-(TG /6.5)) - 70. Results: Three-hundred fifteen values were obtained of which 53% were for women. The mean age and LDL-Cr were 54 years (±15.8) and 112.1 mg/dl (±32.5), respectively. The median (interquartile range, mg/dl) of TC, high-density lipoprotein (HDL-C) and TG were 204 mg/dl (171-229), 51 mg/dl (41-61), and 156 mg/dl (99-237), respectively. There were no differences between mean values of LDL-Cr and LDL-Cnf (113.48 vs. 112.67 mg/dl; p=0.45). The intraclass correlation coefficient among LDL-Cr and LDL-Cf and LDL-Cnf were high (R=0.93 and 0.92, respectively). The correlation between LDL-Cf and LDL-Cnf was 0.95. There is no difference between the areas under the  receiver operating characteristic (ROC) curve with the level of LDL-Cr at 160 mg/dl for LDL-Cnf and LDL-Cf. (0.94 vs. 0.93; p=0.27). Conclusion: There is high concordance between LDL-Cf and LDL-Cnf. These formulae could be an alternative when there are limitations to determine LDL-C because of the lack of enzymatic methods or through Friedewald formula due to the absence of HDL-C.

Introducción: Aunque los niveles de colesterol de lipoproteínas de baja densidad (LDL-C) deben ser determinados idealmente por betacuantificación o métodos enzimáticos, hay limitaciones en países en vía de desarrollo. El objetivo de este estudio es comparar LDL-C obtenido a través de tres fórmulas (LDL-Cnf) con LDL-C obtenido a través de la fórmula de Friedewald (LDL-Cf) usando LDL-C (LDL-Cr) enzimático considerado como referente más aceptado clínicamente. Métodos: Se realizó un estudio de pruebas diagnósticas en un laboratorio de referencia en Cali, Colombia. Las tres fórmulas fueron (mg/dl): Hombres con triglicéridos menores de 400 mg/dl: LDL-C= Colesterol total (CT) - triglicéridos (TG)/6.5)- 45; hombres con triglicéridos iguales a o mayores de 400 mg/dl: LDL-C= (CT- (TG/7))- 50 y mujeres: LDL-C= (CT- (TG/6.5))- 70. Resultados: Se obtuvieron 315 valores de los cuales 53% eran mujeres. El promedio de edad y LDL-Cr fueron 54 años (±15.8) y 112.1 mg/dl (±32.5), respectivamente. La mediana (rango intercuartil) de CT, lipoproteínas de alta densidad (HDL-C) y TG fueron de 204 mg/dl (171-229), 51 mg/dl (41-61) y 156 mg/dl (99-237), respectivamente. No hubo diferencia en los valores promedio de LDL-Cr y LDL-Cnf (113.48 vs. 112.67 mg/dl; p=0.45). Los coeficientes de correlación intraclase entre LDL-Cr y LDL-Cf y LDL-Cnf fueron altos (r=0.93 y 0.92, respectivamente). La correlación entre LDL-Cf y LDL-Cnf fue de 0.95. No hubo diferencias en las áreas bajo la curvas de características operativas del receptor (COR) con niveles de LDL-Cr de 160 mg/dl (0.94 vs. 093; p=0.27). Conclusión: Existe una alta correlación entre LDL-Cf y LDL-Cnf. Estas formulas podrían ser una alternativa cuando existen limitaciones para determinar el LDL-C.

Factors Affecting the Difference between the Low-Density Lipoprotein Cholesterol Concentrations Measured Directly and Calculated Using the Friedewald Formula / 임상검사와정도관리

BACKGROUND: National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) is the guideline for detection evaluation, and treatment of high blood cholesterol in adults. The risk of coronary heart disease (CHD) is assessed by the presence of CHD risk equivalents and the number of risk factors. LDL-cholesterol is the goal of treatment for hyperlipidemia. Contents: The most common approach for determining LDL-cholesterol level in clinical laboratory is to calculate it based on Friedewald formula. For accurate risk assessment by the calculated LDL-cholesterol, good analytical performances of total cholesterol, HDL-cholesterol and triglyceride are prerequisite. Even if the analytical performance of these three analytes are within the acceptable criteria, pooled imprecision and bias of the calculated LDL-cholesterol could not meet the criteria for LDL-cholesterol. Even under conditions satisfying the requirements of Friedewald formula, the calculated LDL-cholesterol level was lower than the directly measured level and the difference was dependent on the level of triglyceride, LDL-cholesterol and total cholesterol. When evaluatingpatients with hyperlipidemia, Friedewald calculation may underestimate the risk for coronary heart disease which may lead to inappropriate treatment option. CONCLUSIONS: When evaluating patients with hyperlipidemia, direct measurement of LDL-cholesterol appears to be better than Friedewald calculation.

Comparação analítica de valores de LDL-colesterol utilizando a dosagem direta e o cálculo pela fórmula de Friedewald / Analytical comparison of values of LDL-cholesterol using the direct dosage and the calculation through the formula of Friedewald

A avaliação fidedigna do perfil lipídico dos pacientes é fator fundamental para acompanhamento e prevenção das patologias cardiovasculares. A proposta deste trabalho é avaliar o desempenho de dois métodos para dosagem do LDL-colesterol, um método direto e o método indireto pela fórmula de Friedewald, em uma população heterogênea. Para tal foram realizadas dosagens de triglicerídeos, colesterol total e HDL-colesterol através de métodos enzimáticos tradicionais. Para dosagens de LDL-colesterol foramutilizados os métodos: direto, sem precipitação e o indireto pela estimativa. Os pacientes foram divididos em cinco grupos, de acordocom o resultado das dosagens de triglicerídeos. A estimativa do LDL-colesterol tendeu a mostrar resultados ligeiramente diminuídosem comparação a dosagem pelo método homogêneo para valores de triglicérides inferiores a 70 mg/dL. Entretanto, a estimativa do LDL-colesterol tendeu a produzir resultados significativamente mais elevados, em comparação ao método direto de dosagem, para faixasde triglicérides de 181-290 mg/dL; 291-400 mg/dL e valores superiores a 400 mg/dL. Na faixa de triglicérides de 71-180 mg/dL não houve alteração significativa entre as metodologias empregadas. Este trabalho demonstrou que resultados de LDL-colesterol utilizando a fórmula de Friedewald e a medida direta não são idênticos com diferentes níveis de triglicerídeos.

A worthy evaluation over the lipidic profile of patients is a fundamental factor to the accompaniment and prevention of cardiovascular pathologies. The proposal of this research is to evaluate the performance of two methods of LDL-cholesterol dosage. One is the direct method, and the other is the indirect one which uses the Friedewald's equation, both methods were used on a heterogen population. To make the test there were necessary the dosage of triglycerides, total cholesterol and HDL-cholesterol through traditional enzymatic tests. To the dosage of LDL-cholesterol there were used: the direct method previously said, which is a method without precipitation and the indirect one, that is the method that uses the equation. The patients were divided by five groups, in accordance with their triglyceride dosage results. The indirect method tended to show results slightly diminished in comparison to the dosage through the homogen method to values of triglyceride less than 70 mg/dl. In the other hand the LDL-cholesterol estimative also tends to produce significant higher results in comparison with the direct method. For bands of triglyceride between 181-290mg/dl; 291-400 mg/dl and values greater than 400 mg/dl. In the bands of triglyceride between 71-180 mg/dl there was no significant difference among the two methods. This research showes tha the results of LDL-cholesterol reached through the Friedewald equation and the direct method, are not identical when comparing differents rates of triglyceride.

Comparación entre la determinación analítica del colesterol-LDL y su estimación por cálculo / Comparison between the analytical determination of LDL-cholesterol and its estimation by calculation

El colesterol­LDL (LDL.C) es uno de los principales marcadores de riesgo aterogénico y es utilizado para objetivos preventivos, su determinación por cálculo es frecuente en los laboratorios. Por lo tanto, el objetivo de este estudio fue comparar el método de Friedewal con un método analítico basado en la precipitación de las LDL con sulfato de polivinilo (PVS) descrito por Kerscher. El colesterol ligado a las mismas se determinó empleando el sistema enzimático con colorimetría de Trinder. Por diferencia entre el Colesterol total y el determinado en el sobrenadante, se obtuvo el colesterol unido a las LDL.(C.LDLa). Se comparó con el método por cálculo para la estimación de LDL.C (C.LDLc).Se eliminaron todos los valores de triglicéridos > o = a 400 mg/dl. En los pacientes normolipémicos el valor medio de C.LDLa fue 95 ±29 mg/dl y para C­LDL 99 ±26 mg/dl. El coeficiente de correlación fue r= 0.91 (p< 0.001). En pacientes hipercolesterolémicos, el valor medio de C­LDLa fue 170± 22 mg/dl y para C­LDLc 160 ± 21 mg/dl; el coeficiente de correlación fue r = 0.87 (p< 0.001). En los hipertrigliceridémicos, el valor medio de C­LDLa fue 122 ± 42 mg/dl y para C­LDLc 106 ± 41 mg/dl con coeficiente de correlación r = 0.92 (p< 0.001). En base a estos resultados podemos destacar que el método analítico es rápido, preciso y fácilmente utilizable en el laboratorio clínico y que ambos métodos son comparables entre sí hasta valores de triglicéridos menores a 400 mg/dl.

LDL­cholesterol(LDL­C) is one of the principal markers of atherogenic risk and is used for preventive aims. The determination of this marker by calculation is frequent in laboratories. Thus, the aim of this study was to compare Friedewald formula with an analytical method based on the precipitation of LDL with polyvinyl sulphate (PVS) described by Kerscher. The cholesterol linked to these proteins was determined using the enzymatic colorimetric system of Trinder. The cholesterol linked to LDL (LDL­Ca) was obtained by the difference between total cholesterol and the one determined in the supernatant. This result was compared with the method of calculation for LDL­C estimation. All values of triglycerids > or equal to 400 mg/dl were eliminated. In the normolipemic patients, the mean LDL­Cc was 95 ± 29 mg/dl and for LDL­Cc 99 ± 26 mg/dl. The correlation coefficient was r=0.91 (p <0.001). In hypercholesterolemic patients, mean LDL­Ca was 170 ± 22 mg/dl and for LDL­Cc 160 ± 21 mg/dl; the correlation coefficient was r=0.87 (p <0.001). In hypertriglyceridemic patients, mean LDL­Ca was 122 ± 42 mg/dl and LDL­Cc 106 ± 41 mg/dl with a correlation coefficient of r= 0.92 (p <0.001). Based in these results, we could emphasize that the analytical method is rapid, precise and easy to use in the clinical laboratory and that both methods are comparable for triglyceride values lower than 400 mg/dl.