Non-HDL Cholesterol and Apolipoprotein B Measures and Risk of Atherosclerotic Cardiovascular Disease

Importance: Non-high-density-lipoprotein (non-HDL) cholesterol and apolipoprotein B (apoB) are better markers of atherosclerotic cardiovascular disease (ASCVD) risk than low-density-lipoprotein cholesterol, but whether non-HDL cholesterol or apoB is superior to the other is less clear. Objective: To assess if non-HDL cholesterol provides information on ASCVD beyond apoB, and vice versa. Design, Setting, and Participants: The Copenhagen General Population Study, a population-based contemporary cohort study in Danish individuals recruited in 2003-2015 with a median of 13.2 (IQR, 10.3-15.8) years of follow-up, included women and men not taking lipid-lowering medication and with non-HDL cholesterol and apoB measurements at baseline. Data were analyzed from January 3 through June 23, 2025. Exposures: Continuous non-HDL cholesterol and apoB assessed as absolute levels and SDs as well as categories of concordance/discordance between non-HDL cholesterol and apoB defined by medians-(1) concordant low: non-HDL cholesterol and apoB less than the median; (2) discordant high apoB: non-HDL cholesterol less than the median and apoB greater than the median; (3) discordant high non-HDL cholesterol: non-HDL cholesterol greater than the median and apoB less than the median; and (4) concordant high: non-HDL cholesterol and apoB greater than median values. Main Outcomes and Measures: Myocardial infarction and ASCVD events estimated by Cox proportional hazards regressions using age as 19 years the underlying time scale and delayed entry (left truncation) at baseline. Results: This cohort study in 94 398 individuals (53 042 women [56%]) with a total of 2462 first myocardial infarction (MI) and 5723 first ASCVD events found that any higher levels of non-HDL cholesterol or apoB on continuous scales were associated with similar increased risk of MI and ASCVD; for 1-SD higher levels, the multivariable-adjusted hazard ratio (HR) for ASCVD was 1.16 (95% CI, 1.13-1.19) for non-HDL cholesterol (39 mg/dL) and 1.14 (95% CI, 1.12-1.17) for apoB (30 mg/dL). Further adjusting for non-HDL cholesterol in the apoB model, and vice versa, attenuated the HRs, although the findings were still significant. Compared with concordant low non-HDL cholesterol and apoB, the HR for MI was 1.32 (95% CI, 1.10-1.59) for discordant high apoB, 1.30 (95% CI, 1.05-1.60) for discordant high non-HDL cholesterol, and 1.69 (95% CI, 1.53-1.85) for concordant high non-HDL cholesterol and apoB; corresponding values for ASCVD were 1.14 (95% CI, 1.01-1.29), 1.21 (95% CI, 1.06-1.38), and 1.36 (95% CI, 1.28-1.44). Conclusions and Relevance: In this study, in individuals not taking lipid-lowering medication, non-HDL cholesterol provides information on ASCVD risk beyond apoB, and vice versa, indicating that both cholesterol content and particle number are important for risk.