Why Should We Measure Low-Density Lipoprotein Cholesterol Directly? Comparison of Low-Density Lipoprotein Cholesterol Assessment by Friedewald Estimation, and Direct Measurement

Intorduction: Plasma levels of low-density lipoprotein cholesterol (LDL-C) are an important biomarker for coronary artery disease. In clinical and research settings worldwide, levels LDL-C are often not measured and are estimated using the Friedewald equation (total cholesterol - HDL cholesterol - triglycerides)/5). Bias of either over or underestimation of LDL-C can be corrected by direct measurement of LDL-C. We assessed the precision of the Friedewald equation in a heterogonous patients population within a wide range of lipid levels. Methods: A sample of consecutive fasting lipid profiles was obtained from ambulatory and hospitalized patients at the Chaim Sheba Medical Center, Tel-Hashomer. LDL-C concentrations were directly measured (dir LDL-C) (Olympus, Ireland) and correspondingly calculated at by the Friedewald equation (calc LDL-C). Results: 32,245 samples were analyzed. In 93% of the samples, underestimation of plasma levels of LDL-C was observed using the Friedewald equation. In 11,054 patients (34.3%), the difference between dir LDL and calc LDL were over 10mg/dl. In 7,693 patients (23.8%), the difference between dir LDL and calc LDL were over 20mg/dl. The difference between dir LDL and calc LDL correlated with plasma TG levels, including TG levels within the normal range. The difference between cal LDL and dir LDL levels is inversely correlated to cholesterol plasma levels. Conclusions: Direct measurement of LDL-C is more precise than Friedewald’s formula and overcomes the inaccurateness, due to elevated TG levels or relatively low LDL-C levels, in the setting of a heterogeneous Israeli population. In the era of extremely low LDL-C treatment goals, our findings require consideration due to their clinical importance and direct measurement of plasma LDL-C should be implemented as underestimation of LDL levels may lead to inappropriate therapeutic decisions.