ApoB and Non-HDL Cholesterol as Discordant Predictors of Coronary Artery Disease: INTERHEART Secondary Analysis

This secondary analysis of the INTERHEART study — a global case-control study of 21,465 subjects across 52 countries — examined the degree to which ApoB and non-HDL-C were discordant predictors of first acute myocardial infarction, and which marker was superior when they disagreed.

When ApoB and non-HDL-C were concordant, their associations with MI risk were similar. When discordant, the pattern was consistent: participants whose ApoB indicated higher risk than non-HDL-C had significantly elevated MI risk, while those with elevated non-HDL-C but lower ApoB did not. ApoB dominated the predictive relationship. This held across geographic regions, sexes, and lipid-lowering treatment status.

The INTERHEART study’s strength — 52 countries and 21,465 subjects — makes it one of the most geographically diverse cardiovascular risk datasets available. The finding that ApoB captures MI risk beyond what non-HDL-C measures, and that non-HDL-C does not capture independent risk beyond ApoB, directly addresses the practical clinical question: when these two measures disagree, which one should guide treatment?

The answer from INTERHEART is ApoB. Non-HDL-C provides a reasonable approximation when ApoB is unavailable, but in discordant patients — where the decision actually matters — ApoB is the more accurate predictor of who will have a heart attack.

We rate the evidence strong. A large multinational secondary analysis of the INTERHEART study demonstrating ApoB’s superiority over non-HDL-C in discordant cases — one of the most powerful geographically diverse datasets supporting ApoB as the preferred atherogenic particle marker.