![]() 4Ĭoncluding Thoughts About the Need for More Rigorous Testing of Equation 2Įquation 2 is an interesting development and brings more attention to the clinically relevant issue of LDL-C accuracy. Also, using Friedewald errors as the comparator may not be appropriate, as the AHA/ACC/Multi-society Cholesterol Guidelines specifically note direct LDL-C assays should instead be used at higher TG levels. ![]() Whether such errors would be acceptable according to the National Cholesterol Education Program thresholds remains to be seen, but certainly such errors may have implications in high and very-high risk patients. Most patients will have LDL-C values falling in the middle of a guideline category, and therefore redistribution upwards or downwards by up to 30 mg/dL may easily reclassify a patient. However, this calls into question whether one should tolerate this level of error, as up to 30 mg/dL in absolute error represents one full strata difference in guideline LDL-C categories. The authors also state that errors of up to 30 mg/dL in VLDL-C (and hence in LDL-C) were tolerated in their equation with TGs ranging up to 800 mg/dL, noting similar absolute errors were present with Friedewald estimation at moderately elevated TG values. ![]() Second, the superimposing of all other shades over the light purple shade (TG 0-320 mg/dL) doesn't allow for a fair comparison between both equations at TG<400 mg/dL, where performance of Martin/Hopkins is similar as clearly demonstrated by MAD and reclassification analyses in Figures 3 and 4. Equation 2 at higher TG values sways the reader at first glance towards assuming that Equation 2 is more accurate. First, the fanning of the scatter plots of Martin/Hopkins equation vs. The color scheme in these two figures can be visually misleading for two reasons. Only one color, the light purple shade in the figures corresponding to TG values of 0-320 mg/dL, is directly applicable and comparable for Martin/Hopkins and Friedewald equations however, this represents a minority of the visually presented data. Low accuracy in non-fasting state, particularly at low LDL-C and high TG levels.īetter accuracy than Friedewald's in the non-fasting state across all LDL-C levels with significantly higher accuracy at very low LDL-C 2880 mg/dL. Less overestimation at high Non-HDL-C levels Tends to overestimate LDL-C at high Non-HDL-C levels Next, reclassification of LDL-C based on guideline LDL-C cutpoints was examined across the entire sample stratified by TG (100 mg/dLĪccuracy improves as Non-HDL-C levels increase MADs were also smaller overall across the range of TGs (0 to 3000 mg/dL) when compared to the Roche direct LDL-C assay. Mean absolute differences (MAD) were calculated between estimated LDL-C and β-quantification LDL-C values at various TG and non-HDL-C cutpoints, and the authors found overall lower MAD with Equation 2 (MAD 24.9 mg/dL) in patients with TG > 400 mg/dL compared to Friedewald (MAD 56.4 mg/dL) or Martin/Hopkins estimation (MAD 44.8 mg/dL). In fact, only 35 individuals in Friedewald's derivation sample had an LDL-C 2880 mg/dL) and LDL-C values (0-800 mg/dL), the authors found aggregate root mean square errors (RMSE) with Equation 2 (15.2) were significantly lower compared to Friedewald estimation (RMSE 32) or Martin/Hopkins estimation (RMSE 25.7). Lower LDL-C levels were not achievable or strongly recommended as statins and other modern pharmacotherapies were not available. In the era when the Friedewald equation was introduced, inaccuracies were tolerated because the VLDL-C estimate was a relatively small proportion of the equation. This results in marked underestimation of LDL-C. However, the equation is prone to inaccuracy at low LDL-C and/or high TG levels, where errors in estimating VLDL-C are magnified given its use of a fixed factor of 5 to describe the relationship between TG and VLDL-C. 1 Originally developed for research purposes from a sample of just 448 individuals, the Friedewald equation has been widely adopted in clinical practice for several decades. The Friedewald equation was developed in 1972 and estimates LDL-C as: total cholesterol (TC) minus high-density lipoprotein-cholesterol (HDL-C) minus triglycerides (TG)/5, with the latter term serving as an estimate for very low-density lipoprotein-cholesterol (VLDL-C). The gold standard of LDL-C measurement has been preparative ultracentrifugation, but given its time requirements and expenses, other methods have been developed as alternatives to estimate LDL-C. Low-density lipoprotein-cholesterol (LDL-C) remains of utmost clinical importance it is positioned in clinical trials as a treatment target and is emphasized in worldwide guidelines as the primary cholesterol target.
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