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

Abstract Background As 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. Methods In 191,333 individuals with Friedewald LDL-C  Results Friedewald 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  Conclusions Estimation 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.