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

Abstract

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. To assess if non-HDL cholesterol provides information on ASCVD beyond apoB, and vice versa. 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. 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. 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. 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). 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.