基于UK Biobank的C-反应蛋白-甘油三酯-葡萄糖指数与腹主动脉瘤发病风险的前瞻性队列研究

Association of the C-reactive protein-triglyceride-glucose index with incident abdominal aortic aneurysm: a prospective cohort study from the UK Biobank

摘要:

背景与目的 腹主动脉瘤（AAA）是一种高致死性的血管疾病，其发生发展与慢性炎症和胰岛素抵抗（IR）密切相关。C-反应蛋白-甘油三酯-葡萄糖指数（CTI）是一种整合炎症与IR状态的新型指标，但其与AAA发病风险之间的关系尚不明确。本研究基于英国生物样本库（UK Biobank）队列，探讨CTI与AAA发病风险的关联。方法 纳入UK Biobank中315 003名基线无主动脉瘤且CTI资料完整的参与者。以随访期间新发AAA为研究终点。采用Kaplan-Meier法评估不同CTI水平人群AAA累积发病率，采用多变量回归模型评估CTI与AAA发病风险的关联，并利用限制性立方样条（RCS）分析剂量-反应关系。进一步进行亚组分析和敏感性分析验证结果稳健性。结果 中位随访时间16.37年，其间共发生AAA 1 343例（0.43%）。Kaplan-Meier曲线显示，AAA累积发病率随CTI水平升高而逐渐增加。在完全调整模型中，CTI每升高1个标准差，AAA发病风险增加39%（HR=1.39，95% CI=1.30~1.48）。与最低四分位组（Q1）相比，最高四分位组（Q4）AAA发病风险显著升高（HR=2.15，95% CI=1.73~2.66；P_趋势<0.001）。RCS分析显示CTI与AAA发病风险存在显著非线性关联（P_非线性=0.008）。亚组分析显示，该关联在吸烟者或既往吸烟者、HbA1c<48 mmol/mol、无高血压、无糖尿病、无冠心病及未使用降脂药物人群中更为显著（均P_交互<0.05）。敏感性分析结果与主分析一致。结论 CTI升高与AAA发病风险增加独立相关，并呈明显剂量-反应关系。CTI作为同时反映炎症和IR状态的复合指标，可能成为AAA早期风险识别和风险分层的潜在生物标志物。

Abstract:

Background and Aims Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease closely associated with chronic inflammation and insulin resistance (IR). The C-reactive protein-triglyceride-glucose index (CTI), a novel composite biomarker integrating inflammatory and metabolic status, has shown prognostic value in cardiovascular diseases. However, its association with AAA risk remains unclear. This study aimed to investigate the relationship between CTI and incident AAA using data from the UK Biobank.Methods A total of 315 003 participants free of aneurysmal disease at baseline with available CTI data were included from the UK Biobank cohort. Incident AAA was defined as the primary outcome. Kaplan-Meier analysis was used to estimate the cumulative incidence of AAA across CTI levels, while multivariable regression models and restricted cubic spline (RCS) analysis were employed to evaluate the association between CTI and incident AAA risk and to assess the dose-response relationship. Subgroup and sensitivity analyses were conducted to assess the robustness of the findings.Results During a median follow-up of 16.37 years, 1 343 participants developed AAA. Kaplan-Meier curves demonstrated a progressive increase in cumulative AAA incidence across CTI quartiles. In the fully adjusted model, each standard deviation increase in CTI was associated with a 39% higher risk of AAA (HR=1.39, 95% CI=1.30-1.48). Compared with the lowest CTI quartile, participants in the highest quartile had a significantly elevated risk of AAA (HR=2.15, 95% CI=1.73-2.66; P_trend<0.001). RCS analysis revealed a significant nonlinear association between CTI and AAA risk (P_non-linear=0.008). The association was more pronounced among current or former smokers, participants with HbA1c<48 mmol/mol, and those without hypertension, diabetes, coronary heart disease, or lipid-lowering medication use (all P_interaction<0.05). Sensitivity analyses yielded consistent results.Conclusion Elevated CTI was independently associated with an increased risk of incident AAA in a dose-dependent manner. CTI may serve as a readily available biomarker for early risk identification and risk stratification of AAA.