Chemical Metrology Division, Applied Sciences Group, Health Sciences Authority, Singapore.
Department of Laboratory Medicine, National University Hospital, Singapore.
Clin Chem Lab Med. 2023 Apr 4;61(10):1808-1819. doi: 10.1515/cclm-2022-1301. Print 2023 Sep 26.
Low-density lipoprotein cholesterol (LDLC) is the primary cholesterol target for the diagnosis and treatment of cardiovascular disease (CVD). Although beta-quantitation (BQ) is the gold standard to determine LDLC levels accurately, many clinical laboratories apply the Friedewald equation to calculate LDLC. As LDLC is an important risk factor for CVD, we evaluated the accuracy of Friedewald and alternative equations (Martin/Hopkins and Sampson) for LDLC.
We calculated LDLC based on three equations (Friedewald, Martin/Hopkins and Sampson) using the total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDLC) in commutable serum samples measured by clinical laboratories participating in the Health Sciences Authority (HSA) external quality assessment (EQA) programme over a 5 years period (number of datasets, n=345). LDLC calculated from the equations were comparatively evaluated against the reference values, determined from BQ-isotope dilution mass spectrometry (IDMS) with traceability to the International System of Units (SI).
Among the three equations, Martin/Hopkins equation derived LDLC had the best linearity against direct measured (y=1.141x - 14.403; R=0.8626) and traceable LDLC (y=1.1692x - 22.137; R=0.9638). Martin/Hopkins equation (R=0.9638) had the strongest R in association with traceable LDLC compared with the Friedewald (R=0.9262) and Sampson (R=0.9447) equation. The discordance with traceable LDLC was the lowest in Martin/Hopkins (median=-0.725%, IQR=6.914%) as compared to Friedewald (median=-4.094%, IQR=10.305%) and Sampson equation (median=-1.389%, IQR=9.972%). Martin/Hopkins was found to result in the lowest number of misclassifications, whereas Friedewald had the most numbers of misclassification. Samples with high TG, low HDLC and high LDLC had no misclassification by Martin/Hopkins equation, but Friedewald equation resulted in ∼50% misclassification in these samples.
The Martin/Hopkins equation was found to achieve better agreement with the LDLC reference values as compared to Friedewald and Sampson equations, especially in samples with high TG and low HDLC. Martin/Hopkins derived LDLC also enabled a more accurate classification of LDLC levels.
低密度脂蛋白胆固醇（LDLC）是诊断和治疗心血管疾病（CVD）的主要胆固醇靶标。尽管β定量（BQ）是准确确定 LDLC 水平的金标准，但许多临床实验室应用 Friedewald 方程来计算 LDLC。由于 LDLC 是 CVD 的重要危险因素，我们评估了 Friedewald 及其替代方程（Martin/Hopkins 和 Sampson）对 LDLC 的准确性。
我们使用临床实验室参加卫生科学局（HSA）外部质量评估（EQA）计划 5 年来测量的可互换血清样本中的总胆固醇（TC）、甘油三酯（TG）和高密度脂蛋白胆固醇（HDLC），根据三个方程（Friedewald、Martin/Hopkins 和 Sampson）计算 LDLC（数据集数量，n=345）。比较了从方程计算出的 LDLC 与通过同位素稀释质谱法（IDMS）直接测量的参考值，IDMS 具有与国际单位制（SI）的可追溯性。
在这三个方程中，Martin/Hopkins 方程得出的 LDLC 与直接测量的 LDLC 具有最佳的线性关系（y=1.141x-14.403；R=0.8626）和可追溯的 LDLC（y=1.1692x-22.137；R=0.9638）。与 Friedewald（R=0.9262）和 Sampson（R=0.9447）方程相比，Martin/Hopkins 方程与可追溯 LDLC 的关联具有最强的 R（R=0.9638）。与 Friedewald（中位数=-4.094%，IQR=10.305%）和 Sampson 方程（中位数=-1.389%，IQR=9.972%）相比，Martin/Hopkins 方程的差异最小（中位数=-0.725%，IQR=6.914%）。Martin/Hopkins 方程导致的错误分类数量最少，而 Friedewald 方程导致的错误分类数量最多。高 TG、低 HDLC 和高 LDLC 的样本用 Martin/Hopkins 方程没有错误分类，但 Friedewald 方程在这些样本中导致了约 50%的错误分类。
与 Friedewald 和 Sampson 方程相比，Martin/Hopkins 方程与 LDLC 参考值的一致性更好，特别是在高 TG 和低 HDLC 的样本中。Martin/Hopkins 衍生的 LDLC 还能够更准确地分类 LDLC 水平。
