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Available online 3 December 2025
Direct versus calculated LDL cholesterol: Insights from the Friedewald, Martin–Hopkins, and Sampson approaches in the Indian population
Colesterol LDL directo frente a calculado: perspectivas desde los enfoques de Friedewald, Martin-Hopkins y Sampson en la población india
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Roshan Kumar Mahata, Suchismita Pandab,
Corresponding author
dr.suchismitapanda17@gmail.com

Corresponding author.
, Gautam Pandac
a Department of Biochemistry, Teerthanker Mahaveer Medical College & Research Centre, Teerthanker Mahaveer University, Moradabad, India
b Department of Biochemistry, Dharanidhar Medical College and Hospital, Keonjhar, India
c Department of Ophthalmology, Kalinga Hospital, Bhubaneswar, India
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Received 29 July 2025. Accepted 30 October 2025
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Table 1. Baseline characteristics of studied participants.
Tables
Table 2. Comparison of direct LDL-C with calculated LDL-C by Friedewald, Martin–Hopkins, and Sampson equations: bias, limits of agreement, and concordance.
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Table 3. Stratification of patients into therapeutic LDL-C categories by direct measurement and calculated formulas (Friedewald, Martin–Hopkins, Sampson) according to 2019 ESC/EAS guidelines.
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Abstract
Introduction and objectives

Low-density lipoprotein cholesterol (LDL-C) is a crucial biomarker for cardiovascular disease (CVD) risk assessment and management. Direct LDL-C measurement (D-LDL-C) is preferred but not always feasible, necessitating the use of estimation formulas. The Friedewald equation is the most widely used but is less reliable in cases of high triglycerides (TG). The Martin–Hopkins and Sampson equations offer improved accuracy, yet their performance in the Indian population remains underexplored. This study evaluates and compares these formulas against D-LDL-C in an Indian cohort.

Methods

A retrospective study was conducted on 4368 lipid profile samples collected between 2019 and 2024 at a tertiary care center in India. LDL-C was estimated using the Friedewald, Martin–Hopkins, and Sampson equations and compared with D-LDL-C across TG categories: <100mg/dL, 100–199mg/dL, 200–299mg/dL, 300–399mg/dL and ≥400mg/dL. Agreement and accuracy were evaluated using Pearson correlation, Lin&apos;s concordance correlation coefficient (CCC), and Bland–Altman plots.

Results

The Martin–Hopkins equation demonstrated the best concordance with D-LDL-C (CCC=0.9121; mean bias=−5.37mg/dL), followed by the Sampson (CCC=0.8710; bias=−11.61mg/dL) and Friedewald (CCC=0.7914; bias=−18.3mg/dL) formulas. Across TG categories, Sampson performed best in low TG (<200mg/dL; CCC=0.9442), but the Martin–Hopkins formula consistently demonstrated superior accuracy and the narrowest limits of agreement in TG ≥200mg/dL. At very-high TG (≥800mg/dL), Martin–Hopkins nearly matched D-LDL-C bias=0.32mg/dL; P=.674), while both Sampson and Friedewald showed significant underestimation.

Conclusions

The Martin–Hopkins equation outperforms the Friedewald and Sampson formulas for LDL-C estimation in the Indian population, especially in patients with elevated TG levels. Adoption of the Martin–Hopkins equation may improve cardiovascular disease risk stratification and guide more accurate therapeutic decisions in clinical practice.

Keywords:
Low-density lipoprotein cholesterol
Cardiovascular disease
Direct LDL-C
Martin–Hopkins equation
Sampson equation
Resumen
Introducción y objetivos

El colesterol unido a lipoproteínas de baja densidad (cLDL) es un biomarcador crucial para la evaluación y el control del riesgo de enfermedad cardiovascular. La medición directa del cLDL (D-cLDL) es el método preferido, pero no siempre es factible, lo que hace necesario el uso de fórmulas de estimación. La ecuación de Friedewald es la más utilizada, aunque resulta menos fiable en casos con triglicéridos (TG) elevados. Las ecuaciones de Martin-Hopkins y Sampson ofrecen mayor precisión, pero su rendimiento en la población india aún no ha sido ampliamente estudiado. Este trabajo evalúa y compara estas fórmulas frente al D-cLDL en una cohorte india.

Métodos

Se realizó un estudio retrospectivo con 4.368 muestras de perfil lipídico recogidas entre 2019 y 2024 en un centro de atención terciaria en India. El cLDL se estimó utilizando las ecuaciones de Friedewald, Martin-Hopkins y Sampson, y se comparó con el D-cLDL en distintas categorías de TG: <100mg/dl, 100-199mg/dl, 200-299mg/dl, 300-399mg/dl y ≥400mg/dl. La concordancia y la precisión se evaluaron mediante la correlación de Pearson, el coeficiente de correlación concordante de Lin (CCC) y gráficos de Bland-Altman.

Resultados

La ecuación de Martin-Hopkins mostró la mejor concordancia con el D-cLDL (CCC=0,9121; sesgo medio=−5,37mg/dl), seguida por la ecuación de Sampson (CCC=0,8710; sesgo=−11,61mg/dl) y la de Friedewald (CCC=0,7914; sesgo=−18,3mg/dl). En las diferentes categorías de TG, la ecuación de Sampson tuvo el mejor desempeño con TG bajos (<200mg/dl; CCC=0,9442), pero la ecuación de Martin-Hopkins mostró de manera consistente una mayor precisión y los límites de concordancia más estrechos en TG200mg/dl. En niveles muy altos de TG (≥800mg/dl) la ecuación de Martin-Hopkins prácticamente igualó al D-cLDL (sesgo=0,32mg/dl; p=0,674), mientras que las ecuaciones de Sampson y Friedewald mostraron una subestimación significativa.

Conclusiones

La ecuación de Martin-Hopkins supera a las fórmulas de Friedewald y Sampson para la estimación del cLDL en la población india, especialmente en pacientes con niveles elevados de TG. La adopción de la ecuación de Martin-Hopkins podría mejorar la estratificación del riesgo cardiovascular y favorecer decisiones terapéuticas más precisas en la práctica clínica.

Palabras clave:
Colesterol unido a lipoproteínas de baja densidad
Enfermedad cardiovascular
cLDL directo
Ecuación de Martin-Hopkins
Ecuación de Sampson

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