Non-HDL Cholesterol and Apolipoprotein B in the Prediction of Coronary Heart Disease in Men

This nested case-control study from the Health Professionals Follow-Up Study compared the predictive value of apolipoprotein B (ApoB), non-HDL cholesterol (non-HDL-C), and LDL-C for coronary heart disease in 798 men (399 cases, 399 controls matched for age, smoking, and time of blood draw).

ApoB was the strongest predictor: comparing the highest to lowest quintiles, the relative risk was 3.01 for ApoB, 2.76 for non-HDL-C, and only 1.81 for LDL-C. The critical finding came from mutual adjustment: when all three measures were entered simultaneously, ApoB remained highly and significantly predictive (RR 4.18), while non-HDL-C lost statistical significance (RR 0.70). This mutual adjustment result indicates that ApoB captures the atherogenic information in non-HDL-C, but the reverse is not true — non-HDL-C does not fully capture the information in ApoB.

The mechanistic interpretation is consistent with particle biology. LDL-C and non-HDL-C measure cholesterol mass in atherogenic particles; ApoB counts the particles themselves. When two particles have the same total cholesterol content but different numbers, it is the number that determines arterial wall encounter rate and plaque-forming potential.

This study was foundational in establishing ApoB as the superior atherogenic marker in direct comparisons with non-HDL-C — a hierarchy that Mendelian randomization studies have since confirmed.

We rate the evidence moderate. A rigorous nested case-control analysis providing important evidence that ApoB is the superior atherogenic marker when compared with LDL-C and non-HDL-C in mutual adjustment.