Apolipoprotein B is a better target for therapy than LDL cholesterol

This is, in a sense, where the modern ApoB argument begins — an early, forceful manifesto from the field’s most persistent advocate that we are measuring the wrong thing.

Sniderman’s case is physiological. LDL cholesterol measures cholesterol mass; ApoB counts atherogenic particles — and since each particle carries one ApoB, ApoB is the truer measure of how many disease-causing particles a person has. The two diverge most in metabolic syndrome and diabetes, where small, cholesterol-poor LDL particles mean a “normal” LDL-C masks a high particle count. In those discordant patients, he argues, treating to LDL-C leaves dangerous residual risk on the table.

The practical takeaway, well ahead of its time in 2008: measure ApoB in metabolically high-risk patients and treat to ApoB targets even when LDL-C looks fine. The resistance was the entirely LDL-centric guidelines of the era, plus testing cost and clinical inertia.

We rate the evidence low as a document — a narrative opinion piece without new data, from an avowed advocate. But its clinical significance is high in hindsight: the “discordance” concept it pressed became central to understanding residual risk in the diabetes and obesity era, and the argument has steadily worked its way into guidelines. A foundational opinion more than a proof.