Estimation of the Concentration of Low-Density Lipoprotein Cholesterol in Plasma, Without Use of the Preparative Ultracentrifuge¶
Why this mattered¶
Friedewald, Levy, and Fredrickson’s paper mattered because it turned LDL cholesterol from a specialized research measurement into a practical clinical variable. Before this, estimating the cholesterol content of the LDL fraction generally depended on preparative ultracentrifugation, a costly and technically demanding procedure unsuitable for routine population screening. The paper showed that, in fasting plasma, LDL cholesterol could be closely approximated from total cholesterol, HDL cholesterol, and triglycerides, using the relation now known as the Friedewald equation: LDL-C = total cholesterol - HDL-C - triglycerides/5 in mg/dL. That substitution made LDL-C available to ordinary clinical laboratories.
The shift was not merely technical convenience. It helped make LDL-C a central quantitative target in cardiovascular medicine. Once LDL could be estimated at scale, epidemiologic studies, risk stratification, preventive guidelines, and lipid-lowering trials could use LDL-C as a routine endpoint rather than a specialized laboratory result. This supported the later clinical framing of LDL as the principal modifiable atherogenic cholesterol measure, especially as statin trials and treatment guidelines increasingly organized prevention around LDL-C thresholds and reductions.
The paper also illustrates how a simple approximation can reshape a field while retaining clear boundaries. The method depended on fasting samples and on the empirical assumption that very-low-density lipoprotein cholesterol could be estimated from triglycerides; it is less reliable in marked hypertriglyceridemia and some dyslipidemic states. Even so, its practical effect was enormous: it standardized LDL-C estimation for decades and made possible the routine lipid panel as a tool of mass cardiovascular risk assessment.
Abstract¶
Abstract A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf0-20) is presented. The method involves measurements of fasting plasma total cholesterol, triglyceride, and high-density lipoprotein cholesterol concentrations, none of which requires the use of the preparative ultracentrifuge. Comparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded correlation coefficients of .94 to .99, depending on the patient population compared.