Discordance among apoB, non–high-density lipoprotein cholesterol, and triglycerides: implications for cardiovascular prevention

Abstract

Background and Aims Despite growing evidence that apolipoprotein B (apoB) is the most accurate marker of atherosclerotic cardiovascular disease (ASCVD) risk, its adoption in clinical practice has been low. This investigation sought to determine whether low-density lipoprotein cholesterol (LDL-C), non–high-density lipoprotein cholesterol (HDL-C), and triglycerides are sufficient for routine cardiovascular care. Methods A sample of 293 876 UK Biobank adults (age: 40–73 years, 42% men), free of cardiovascular disease, with a median follow-up for new-onset ASCVD of 11 years was included. Distribution of apoB at pre-specified levels of LDL-C, non-HDL-C, and triglycerides was examined graphically, and 10-year ASCVD event rates were compared for high vs. low apoB. Residuals of apoB were constructed after regressing apoB on LDL-C, non-HDL-C, and log-transformed triglycerides and used as predictors in a proportional hazards regression model for new-onset ASCVD adjusted for standard risk factors, including HDL-C. Results ApoB was highly correlated with LDL-C and non-HDL-C (Pearson’s r = .96, P < .001 for both) but less so with log triglycerides (r = .42, P < .001). With 19 982 new-onset ASCVD events on follow-up, in the adjusted model, residual apoB remained statistically significant after accounting for LDL-C and HDL-C (hazard ratio 1.06, 95% confidence interval 1.0–1.07), after accounting for non-HDL-C and HDL-C (hazard ratio 1.04, 95% confidence interval 1.03–1.06), and after accounting for triglycerides and HDL-C (hazard ratio 1.13, 95% confidence interval 1.12–1.15). None of the residuals of LDL-C, non-HDL-C, or of log triglycerides remained significant when apoB was included in the model. Conclusions High variability of apoB at individual levels of LDL-C, non-HDL-C, and triglycerides coupled with meaningful differences in 10-year ASCVD rates and significant residual information contained in apoB for prediction of new-onset ASCVD events demonstrate that LDL-C, non-HDL-C, and triglycerides are not adequate proxies for apoB in clinical care.