DPP3 as a Biomarker in Patients with Cardiovascular Critical Illness

Dipeptidyl peptidase 3 (DPP3) exerts vasodilatory and myocardial depressant effects in preclinical models and is a potential therapeutic target in cardiogenic shock (CS).

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.

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).

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.