suPAR Identifies Treatment-Resistant Inflammatory Risk Beyond hs-CRP in Type 2 Diabetes With Coronary Artery Disease: An Ancillary Analysis of BARI 2D.

research_design_and_methods

In this ancillary analysis of Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D), we measured plasma suPAR and hs-CRP at baseline (n = 2,277) and 1 year (landmark cohort, n = 1,978).

在这项Bypass Angioplasty Revascularization Investigation 2 Diabetes（BARI 2D）的辅助分析中，我们在基线时（n = 2,277）和1年后（里程碑队列，n = 1,978）测量了血浆suPAR和hs-CRP。

The primary outcome was all-cause death, nonfatal myocardial infarction, or nonfatal stroke.

主要结果是全因死亡、非致命性心肌梗死或非致命性中风。

Associations were assessed using sequentially adjusted Cox models.

使用顺序调整的Cox模型评估关联。

Results

Over 1 year, suPAR was not reduced by diabetes (insulin sensitizing vs. insulin provision) or cardiac (revascularization vs. medical therapy) treatment strategies (median 2.96-3.15 ng/mL; all-treatment arm P ≥ 0.75), while hs-CRP declined substantially (median 2.07-1.30 mg/L). suPAR independently predicted the composite outcome (adjusted hazard ratio[HR] 1.40 per SD; 95% CI 1.27-1.55), unattenuated after hs-CRP adjustment.

在1年内，suPAR并未因糖尿病（胰岛素敏感化与胰岛素提供）或心脏（再血管化与药物治疗）治疗策略而降低（中位数2.96-3.15 ng/mL；所有治疗组P ≥ 0.75），而hs-CRP显著下降（中位数2.07-1.30 mg/L）。suPAR独立预测了复合结果（调整后的风险比[HR] 1.40每SD；95% CI 1.27-1.55），在调整hs-CRP后未减弱。

In an exploratory analysis, suPAR modified the diabetes treatment effect (P-interaction = 0.005), with insulin provision associated with worse outcomes in the highest suPAR tertile (HR 1.33; 95% CI 1.03-1.72).

在一项探索性分析中，suPAR改变了糖尿病治疗效果（P-交互作用 = 0.005），在最高suPAR三分位数中，胰岛素提供与更差的结果相关（HR 1.33；95% CI 1.03-1.72）。

Baseline suPAR predicted risk in participants whose hs-CRP normalized (HR 1.45; 95% CI 1.04-2.03).

基线时的suPAR预测了hs-CRP正常化的参与者的风险（HR 1.45；95% CI 1.04-2.03）。

Joint classification revealed a threefold gradient in event rates (7.1% to 21.6%), with elevated suPAR conferring excess risk even after hs-CRP normalization.

联合分类揭示了事件率的三倍梯度（7.1%至21.6%），即使在hs-CRP正常化后，升高的suPAR也带来了额外的风险。

Conclusions

Over 1 year, suPAR was unmodified by diabetes or revascularization strategies in BARI 2D despite intensive guideline-directed medical optimization, in contrast to hs-CRP, which declined substantially.

在BARI 2D研究中，尽管进行了密集的指南导向的药物优化治疗，但超过1年的时间内，糖尿病或血管重建策略并未改变suPAR水平，与之形成对比的是，hs-CRP显著下降。

Combined suPAR and hs-CRP classification produced a graded risk hierarchy that hs-CRP normalization alone did not resolve.

结合suPAR和hs-CRP的分类产生了一个分级风险层次结构，仅hs-CRP正常化无法解决。