Discordance of LDL Cholesterol with Alternative LDL-Related Measures and Future Coronary Events

This prospective study of 27,533 initially healthy women directly quantified the prevalence and consequences of discordance between LDL cholesterol and alternative lipid measures — apoB, LDL particle number, and non-HDL cholesterol — and examined which measure tracked with actual coronary event risk.

Discordance was common: 11.6 to 24 percent of women had discordant LDL-C versus alternative measures depending on the pairing. When discordance was present, risk tracked with the alternative measure rather than LDL-C. Women with low LDL-C but discordantly high apoB had 2.5-fold higher coronary risk than those with concordantly low values. Women with high LDL-C but low apoB had significantly lower risk (HR 0.34) — below even the average for women with concordant high levels.

The asymmetry is the key finding. Discordantly high apoB with low LDL-C produces higher risk than the LDL-C suggests; discordantly low apoB with high LDL-C produces lower risk. This is the mathematical signature of what particle-number proponents have long argued: cholesterol filling per particle is variable, and when it’s high (large buoyant LDL), LDL-C overstates risk. When it’s low (small dense LDL), it understates it.

We rate the evidence strong, with high clinical significance. A definitive prospective cohort study establishing that in discordant patients, apoB is the more accurate predictor of coronary risk — with direct implications for risk stratification in patients with metabolic syndrome, diabetes, or hypertriglyceridemia.