Accuracy of low-density lipoprotein cholesterol estimation at very low levels

Abstract

BackgroundAs the approach to low-density lipoprotein cholesterol (LDL-C) lowering becomes increasingly intensive, accurate assessment of LDL-C at very low levels warrants closer attention in individualized clinical efficacy and safety evaluation. We aimed to assess the accuracy of LDL-C estimation at very low levels by the Friedewald equation, the de facto clinical standard, and compare its accuracy with a novel, big data-derived LDL-C estimate.MethodsIn 191,333 individuals with Friedewald LDL-C < 70 mg/dL, we compared the accuracy of Friedewald and novel LDL-C values in relation to direct measurements by Vertical Auto Profile ultracentrifugation. We examined differences (estimate minus ultracentrifugation) and classification according to levels initiating additional safety precautions per clinical practice guidelines.ResultsFriedewald values were less than ultracentrifugation measurement, with a median difference (25th to 75th percentile) of –2.4 (–7.4 to 0.6) at 50–69 mg/dL, –7.0 (–16.2 to –1.2) at 25–39 mg/dL, and –29.0 (–37.4 to –19.6) at < 15 mg/dL. The respective values by novel estimation were –0.1 (–1.5 to 1.3), –1.1 (–2.5 to 0.3), and –2.7 (–4.9 to 0.0) mg/dL. Among those with Friedewald LDL–C < 15, 15 to < 25, and 25 to < 40 mg/dL, the classification was discordantly low in 94.9%, 82.6%, and 59.9% of individuals as compared with 48.3%, 42.4%, and 22.4% by novel estimation.ConclusionsEstimation of even lower LDL-C values (by Friedewald and novel methods) is even more inaccurate. More often than not, a Friedewald value < 40 mg/dL is underestimated, which translates into unnecessary safety alarms that could be reduced in half by estimation using our novel method.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0852-2) contains supplementary material, which is available to authorized users.

Validity of a Novel Method for Estimating Low-Density Lipoprotein Cholesterol Levels in Cardiovascular Disease Patients Treated with Statins

“…Martin et al reported that among general subjects in the United States, LDL-C(M) showed good concordance with directly measured LDL-C at LDL-C level < 70 mg/dL compared with LDL-C(F) [LDL-C(M); 94.1%, LDL-C(F); 77.2%] 14 ) . Quisepe et al have also demonstrated that in patients with an LDL-C(F) level of 50–69 mg/dL, 29% of patients show LDL-C(D) level ≥ 70 mg/dL 16 ) . Furthermore, Meeusen et al pointed out that the discordance between LDL-C(F) and LDL-C( β Q), which is measured by β quantification and is considered the gold-standard method for determining LDL-C, was increased for LDL-C level < 70 mg/dL 15 ) .…”

“…Furthermore, Meeusen et al reported that LDL-C(F) underestimated LDL-C measured by β quantification [LDL-C( β Q)], which is considered the gold standard of LDL-C measurement, particularly in patients with LDL-C( β Q) < 70 mg/dL 15 ) . A recent study also demonstrated that LDL-C(M) by the Martin method correlated strongly with directly measured LDL-C(D), compared with LDL-C(F) at LDL-C < 40 mg/dL 16 ) . The validity of LDL-C(M) in different races and in patients with CVD, particularly with low LDL-C levels resulting from statin therapy, has not been elucidated.…”

Managing dyslipidaemia for the primary prevention of cardiovascular disease

“…However, this calculation is not valid for those with high triglycerides or very low LDLc 11. A novel estimate of LDL has been developed that shows good correlation with ultra-centrifugation and more precision than Friedwald across different ranges of triglycerides but also at very low LDL.…”

Comparing a novel machine learning method to the Friedewald formula and Martin-Hopkins equation for low-density lipoprotein estimation

“…This novel method has helped recategorize patients who were previously undertreated and is currently the method used for LDL-C estimation at multiple clinical laboratories [21]. However, the Martin-Hopkins equation was developed based on traditional linear regression analysis, and although it outperforms the Friedewald formula, there remain inaccuracies, especially at lower LDL-C estimates [22]. The accepted reference method for lipoprotein fraction measurement is the beta-quantification (BQ) method, which is possible in a limited setting but not suitable for mass screening due to its cost and labor-intensive nature.…”