suPAR Identifies Treatment-Resistant Inflammatory Risk Beyond hs-CRP in Type 2 Diabetes With Coronary Artery Disease: An Ancillary Analysis of BARI 2D
Abstract
Objective: To determine whether soluble urokinase plasminogen activator receptor (suPAR) is modified by randomized diabetes and revascularization strategies in patients with type 2 diabetes and coronary artery disease and whether combined suPAR and hs-CRP classification refines residual cardiovascular risk stratification.
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). The primary outcome was all-cause death, nonfatal myocardial infarction, or nonfatal stroke. Associations were assessed using sequentially adjusted Cox models.
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. 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). Baseline suPAR predicted risk in participants whose hs-CRP normalized (HR 1.45; 95% CI 1.04-2.03). Joint classification revealed a…
How strong is the evidence?
Evidence Hub reads this as a secondary / pooled analysis, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 2,277 participants or records.
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