Apolipoprotein B/A1 Ratio Improves Discrimination of Severe Atherosclerosis Beyond Conventional Lipid Markers in High-Risk Statin-Naive Patients

Background/Objectives: The apolipoprotein B to apolipoprotein A1 (ApoB/A1) ratio has been proposed as a marker of cardiovascular risk, but its value for assessing extracranial and intracranial atherosclerosis beyond conventional lipid markers remains uncertain. We evaluated whether the ApoB/A1 ratio improves discrimination of severe atherosclerosis in high-risk statin-naive patients. Methods: We retrospectively included 3416 statin-naive patients who underwent lipid profiling and carotid duplex ultrasonography and/or cerebrovascular imaging between 2014 and 2023. The primary outcome was stenosis severity, categorized as normal, mild (<50% stenosis), or severe (≥50% stenosis, including occlusion), based on clinical imaging reports. Secondary outcomes were carotid plaque score and the number of stenotic intracranial vessels. Associations were assessed using multivariable ordinal logistic regression with 1-SD–standardized lipid markers. Results: The ApoB/A1 ratio was independently associated with greater stenosis severity (adjusted odds ratio 1.24 per 1-SD increase, 95% CI 1.15–1.35; p < 0.0001). Adding ApoB/A1 to a model including clinical covariates, LDL-C, and HDL-C significantly improved discrimination of severe stenosis on every metric examined (continuous NRI +0.142, 95% CI 0.053–0.227; IDI +0.0058, 0.0026–0.0088; likelihood ratio p = 0.0004), although the absolute increase in AUC was modest (0.660 to 0.668; ΔAUC +0.008; DeLong p = 0.026). Associations were consistent for carotid plaque score and intracranial vessel-count outcomes. Conclusions: In high-risk statin-naive patients undergoing carotid or cerebrovascular evaluation, the ApoB/A1 ratio was independently associated with atherosclerosis severity and provided modest incremental discrimination beyond conventional lipid markers. Apolipoprotein assessment may help refine risk stratification in this population.