Is the 2020 Sampson equation the best formula for LDL-C estimation?

More than 4 million deaths in Europe are caused by cardiovascular disease (CVD) each year. Low-density lipoprotein-cholesterol (LDLC) has been demonstrated to be one of the major eterminants of atherogenesis and CVD burden, resulting the most important modifiable risk factor for CVD prevention strategies. According to the last European Guidelines, both direct and indirect assessment of LDL-C can be used in clinical practice. However, the direct measurement techniques are time consuming, expensive, not fully standardized, and not worldwide available. Thus, the most used method for LDL-C quantification continues to be the 1972 old, landmark Friedewald formula (FF): LDL-C = Total cholesterol – High-Density Lipoprotein cholesterol (HDL-C) – riglycerides/5. FF is based on the two assumptions that, in chylomicron absence, most plasma TG are contained in triglyceride-rich Very-Low Density Lipoproteins (VLDL), and the ratio of TG mass to that of VLDL is relatively constant and roughly equal to 5:1 in normal subjects as well as patients with all types of hyperlipoproteinemia, excluding the rare Type III. FF results in reasonably approximated LDL-C estimations, however it suffers from some limitations: it is not applicable for patient with chylomicronemia, overestimates LDL-C values in patients with Type III ypercholesterolemia and leads to LDL-C underestimation in patients with plasma TG ≥ 400 mg/dl [3,4]. Moreover, LDL-C underestimation has also been reported for subjects with low TG levels [5]. For this reason, different research groups have developed new equations for LDL-C estimation during the last decades [6–8]. Although promising, the efficacy and potential clinical role of these new formulae have not been thoroughly validated and while one formula should be preferred to another is still being debatin