Calprotectin Emerges as Predictor of ASCVD in Diverse US Cohort

Emerging evidence from the Dallas Heart Study suggests that circulating calprotectin, a marker of neutrophil activation and innate immune activity, may be a promising biomarker for atherosclerotic cardiovascular disease (ASCVD), independent of both traditional and contemporary risk factors.

The results were published in JAMA Cardiology.

Plasma calprotectin levels were assessed in 2,412 participants from phase 2 of this multiethnic, population-based cohort study, with a median follow-up period of 8 years after sample collection.

Cox proportional hazards models were used to evaluate associations between calprotectin levels and future ASCVD events, including first nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or cardiovascular death. Analyses were adjusted for established cardiovascular risk factors, such as high-sensitivity C-reactive protein (hs-CRP), N-terminal pro–brain natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT).

Elevated calprotectin levels were more commonly observed in individuals who were older; male; of Black race; and those with hypertension, diabetes, or a history of smoking. Higher calprotectin concentrations were also associated with adverse metabolic profiles, including increased HbA1c, very-low-density lipoprotein cholesterol, and triglycerides, along with reduced high-density lipoprotein cholesterol and diminished cholesterol efflux capacity.

Log-transformed calprotectin levels were significantly associated with an increased risk for ASCVD events over an 8-year period (hazard ratio [HR], 1.98 per log increase; 95% CI, 1.54-2.53). This association persisted after adjustment for prior ASCVD and conventional risk factors (HR, 1.61; 95% CI, 1.22-2.13) and remained significant even after further adjustment for hs-CRP, NT-proBNP, and hs-cTnT (HR, 1.43; 95% CI, 1.04-1.96). In addition, elevated calprotectin levels were significantly correlated with higher coronary artery calcium scores (P<0.001), reinforcing its potential link to subclinical atherosclerosis.

Mechanistic in vitro analyses further demonstrated that calprotectin compromises coronary endothelial integrity, reduces nitric oxide production, and promotes endothelial to mesenchymal transition, key potential processes in the development and progression of ASCVD.

Reference

Zuo Y, et al. JAMA Cardiol. 2025:e250945. doi:10.1001/jamacardio.2025.0945