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Aim <p>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.</p> Methods <p>Patients with moderate-to-severe AS (<i>n</i> = 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).</p> Results <p>ApoB was strongly correlated with LDL-C (<i>r</i> = 0.92) and non-HDL-C (<i>r</i> = 0.93). In fully adjusted Cox models, each 10&#xa0;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.</p> Conclusions <p>Excess apoB was associated with increased risks of all-cause and cardiovascular mortality in patients with moderate-to-severe AS.</p> <p><i>Trial registration</i>: 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).</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月25日

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  • Mengjie Xie,
  • Zhenyu Xiong,
  • Zhen Guo,
  • Ruijie Li,
  • Shaozhao Zhang,
  • Guanzhong Chen,
  • Lixiang He,
  • Wenjing Zhang,
  • Menghui Liu,
  • Jiaying Li,
  • Xinxue Liao,
  • Xiaodong Zhuang

摘要

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).

Graphical Abstract