Excess apolipoprotein B improves risk assessment of all-cause and cardiovascular mortality in patients with aortic stenosis: insights from the ARISTOTLE study

Abstract Aim Discordance analysis suggests that apolipoprotein B (apoB), a marker of atherogenic particle number, may capture residual lipid-related risk beyond low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). However, the prognostic relevance of apoB-cholesterol discordance in patients with established aortic stenosis (AS) remains unclear. Methods Patients with moderate-to-severe AS ( n = 467) from the ARISTOTLE study were included. Excess apoB was defined as measured apoB minus expected apoB for a given LDL-C or non-HDL-C level. Associations of excess apoB with all-cause and cardiovascular mortality were assessed using Cox regression. Model performance was evaluated using C-index, 2-year survival net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results ApoB was strongly correlated with LDL-C ( r = 0.92) and non-HDL-C ( r = 0.93). In fully adjusted Cox models, each 10 mg/dL increase in LDL-C-based excess apoB was associated with higher all-cause mortality (HR 1.179, 95% CI 1.004–1.385) and cardiovascular mortality (HR 1.305, 95% CI 1.059–1.609). Compared with the lowest quartile, the highest quartile of LDL-C-based excess apoB was associated with all-cause mortality (HR 1.815, 95% CI 1.123–2.936) and cardiovascular mortality (HR 2.676, 95% CI 1.333–5.374). Similar associations were observed for non-HDL-C-based excess apoB. Model performance analysis showed modest improvements in discrimination and significant 2-year reclassification improvement after adding excess apoB to the clinical model. Conclusions Excess apoB was associated with increased risks of all-cause and cardiovascular mortality in patients with moderate-to-severe AS. Trial registration : ARISTOTLE (Aortic Valve Diseases Risk Factor Assessment and Prognosis Model Construction) study was a multicenter real-world study involving hospitalized patients with AS to assess valve disease and analyze the risk factors influencing prognosis, retrospectively registered in the Chinese Clinical Trials Registry (registration number: NCT06069232).