Apolipoprotein B improves risk assessment of future coronary heart disease in the Framingham heart study beyond LDL-C and non-HDL-C

Aims: Analyses using conventional statistical methodologies have yielded conflicting results as to whether low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) or apolipoprotein B (apoB) is the best marker of the apoB-associated risk of coronary heart disease. The aim of this study was to determine the additional value of apoB beyond LDL-C or non-HDL-C as a predictor of coronary heart disease. Methods and results: For each patient from the Framingham Offspring Cohort aged 40-75 years (n=2966), we calculated the extent to which the observed apoB differed from the expected apoB based on their LDL-C or non-HDL-C. We added this difference to a Cox model predicting new onset coronary heart disease over a maximum of 20 years adjusting for standard risk factors plus LDL-C or non-HDL. The difference between observed and expected apoB over LDL-C or non-HDL-C was highly prognostic of future coronary heart disease events: adjusted hazard ratios 1.26 (95% confidence interval: 1.15, 1.37) and 1.20 (1.11, 1.29), respectively, for each standard deviation increase beyond expected apoB levels. When this difference between observed and expected apoB was added to standard coronary heart disease prediction models including LDL-C or non-HDL-C, prediction improved significantly (likelihood ratio test p-values <0.0001) and discrimination c-statistics increased from 0.72 to 0.73. The corresponding relative integrated discrimination improvements were 11% and 8%, respectively. Conclusions: apoB improves risk assessment of future coronary heart disease events over and beyond LDL-C or non-HDL-C, which is consistent with coronary risk being more closely related to the number of atherogenic apoB particles than to the mass of cholesterol within them.