Is the Commitment to LDL-C Eternal?

Low-density lipoprotein cholesterol (LDL-C) has been the cornerstone of cardiovascular risk assessment and therapy since 1988. Every guideline group and consensus report has repeated and reinforced this commitment. Yet in 2019, the European Society of Cardiology/European Atherosclerosis Society Lipid Guidelines declared that (1) apolipoprotein B (apoB) was a more accurate marker of cardiovascular risk than LDL-C or non-high-density lipoprotein cholesterol (HDL-C); (2) that apoB was a more accurate marker of the adequacy of therapy to lower cardiovascular risk than LDL-C or non-HDL-C; (3) that apoB was essential to diagnose disorders such as type III hyperlipoproteinemia and familial combined hyperlipidemia; and (4) that apoB could be measured more accurately, particularly at low concentrations, than LDL-C or non-HDL-C. Yet LDL-C remained the dominant metric for clinical care in their recommendations, and in the 7 years since, there has been minimal organized teaching about apoB in either Europe or the United States. In 2026, the American College of Cardiology/American Heart Association/Multisociety dyslipidemia guideline followed virtually the same course. Based on the evidence, apoB was ranked above both LDL-C and HDL-C for assessment of risk and the effectiveness of therapy. However, the actual recommendations ranked apoB below both and, as written, make it unlikely that apoB will be commonly used in clinical care for either purpose.

How can this be, and what can we learn? LDL-C transformed cardiovascular care, and the effort to teach patients and doctors about LDL-C is unprecedented. How much of the resistance to apoB is the concern that it is too late to change? How many who write the guidelines have routinely used apoB in their clinical care? I believe that an unreasonable commitment to continuity of message and too closed a process of deliberation and review have produced this unprecedented contradiction between the guideline recommendations and the evidence. This article outlines the critical need to re-evaluate the framework and procedural standards governing our current guidelines.