DPP3 as a Biomarker in Patients with Cardiovascular Critical Illness

BACKGROUND: Dipeptidyl peptidase 3 (DPP3) exerts vasodilatory and myocardial depressant effects in preclinical models and is a potential therapeutic target in cardiogenic shock (CS). METHODS: Patients admitted to the CICU at Brigham and Women's Hospital were enrolled in a biorepository with samples collected at CICU admission. Using samples from 2017-2023, DPP3 was measured using an immunoluminometric assay (4TEEN4). Shock, defined by hypotension and end-organ hypoperfusion, was adjudicated as CS (classic or vasodilatory) or distributive (DS). Controls were CICU patients without shock. Models were adjusted for age, sex, eGFR, and SOFA score. RESULTS: Of 1082 CICU patients, 381 (35.2%) had CS, 70 (6.5%) had DS, and 618 (57.2%) were non-shock controls. DPP3 values were higher in CS (median, 42.7 [Q1-Q3, 25.6-84.3] ng/mL) than in non-shock controls (31.8 [20.2-57.2] ng/mL; p<0.001) but, nevertheless, were elevated (>30 ng/mL) in 53.6% of non-shock controls. CICU patients with DPP3 >30 ng/mL had higher in-hospital mortality (19.9% vs. 8.4%; OR 2.7 [95% CI 1.8-4.0]; p<0.001), with a consistent pattern across CS, DS, and non-shock patients (p-interaction=0.72) and across CS etiologic subgroups (p-interaction=0.18). In adjusted analyses including both shock and non-shock patients, DPP3 showed a graded association with mortality across quartiles (adj-OR Q4 vs. Q1: 3.0 [1.6-6.1]; p<0.001), and at a 30 ng/mL threshold (adj-OR: 2.1 [1.4-3.4]; p=0.001). CONCLUSION: Among critically ill CICU patients, DPP3 was elevated in shock and non-shock states and was associated with in-hospital mortality. These findings support a potential role for DPP3 as a biomarker for risk stratification and a possible target for therapy.