Discordantly high apolipoprotein B despite normal LDL cholesterol across AHA PREVENT cardiometabolic risk strata...

Apolipoprotein B (ApoB) reflects the number of circulating atherogenic lipoprotein particles and may reveal residual lipid-related risk when LDL cholesterol (LDL-C) appears normal. Whether AHA PREVENT-estimated cardiovascular risk identifies LDL-C-normal adults with discordantly high ApoB remains unclear.

We analyzed NHANES 2005-2016 adults aged 30-79 years without prevalent cardiovascular disease. Discordantly high ApoB was defined as LDL-C < 100 mg/dL with ApoB ≥ 90 mg/dL. Survey-weighted analyses estimated ApoB-high prevalence across AHA PREVENT-estimated ASCVD, total CVD, and heart failure risk domains. Additional analyses examined alternative PREVENT thresholds, percentile-based ApoB-LDL-C discordance, discrimination using weighted AUC, and attenuation after accounting for shared cardiometabolic determinants.

Among 7659 adults in the final analytic sample, 2122 had LDL-C < 100 mg/dL. Within this LDL-C-normal subgroup, elevated PREVENT-estimated ASCVD risk was associated with higher ApoB-high prevalence than low risk (18.1% vs. 8.6%; crude OR 2.36, 95% CI 1.66-3.37). Similar patterns were observed for total CVD risk (16.6% vs. 7.7%; OR 2.39, 95% CI 1.67-3.41) and heart failure risk (15.8% vs. 9.1%; OR 1.87, 95% CI 1.24-2.81). Results were directionally consistent using alternative PREVENT thresholds and percentile-based ApoB-LDL-C discordance definitions. However, discrimination for ApoB ≥ 90 mg/dL was stronger for lipid-specific markers such as non-HDL-C and triglycerides than for PREVENT risk alone, and the PREVENT-ApoB association was substantially attenuated after adjustment for triglycerides and other shared metabolic determinants.

Elevated PREVENT-estimated risk identifies LDL-C-normal adults with higher prevalence of discordantly high ApoB, but this pattern largely reflects shared cardiometabolic determinants rather than independent prediction. PREVENT-based risk stratification may help identify higher-yield groups for ApoB assessment, while prospective outcome studies are needed to determine its clinical utility.

The online version contains supplementary material available at https://doi.org/10.1007/s40200-026-02091-3.