Calprotectin may be a biomarker for atherosclerotic cardiovascular disease (ASCVD), a new study shows. Yu Zuo, MD, MSCS, from the University of Michigan, Ann Arbor, and colleagues, reported these data in a manuscript published Wednesday online in the Journal of the American Medical Association. Calprotectin demonstrates neutrophil activation, which plays a critical role in the development of ASCVD. However, calprotectin has not formerly been independently evaluated as a biomarker in a diverse population. The investigators in this study sought to understand the relationship between circulating calprotectin and ASCVD, as well as examine the mechanisms behind calprotectin in its contribution to ASCVD in vitro. During phase 2 of the Dallas Heart Study, plasma was collected from 2,412 patients, and this plasma was used to measure circulating calprotectin in the present study. The median follow-up time post-plasm collection was 8 years. Future ASCVD events — first nonfatal myocardial infarction (MI), nonfatal stroke, coronary revascularization or cardiovascular-related death — were the main outcomes in this study. Cox proportional hazard models assessed for the main outcomes. The outcomes were adjusted for known cardiovascular disease risk factors, high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin (hs-cTnT). Patients who were older, male or Black had higher calprotectin levels. Additionally, patients who had hypertension, diabetes and a history of smoking were associated with higher levels of calprotectin. Higher hemoglobin A1C, but lower lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol and cholesterol efflux capacity were all present in patients who had higher levels of calprotectin. Over 8-years follow-up, calprotectin levels were associated with an increased risk of events related to ASCVD (hazard ratio [HR]=1.98 per log increase, 95% confidence interval [CI]=1.54-2.53). After adjusting for prior ASCVD and cardiovascular risk factors, the association stayed the same (HR=1.61, 95% CI=1.22-2.13). This remained true when adjustments were made for hs-CRP, NT-proBNP and hs-cTnT (HR=1.43, 95% CI=1.04-1.96). Higher levels of calprotectin were also associated with higher coronary calcium (p<0.001). The in vitro component of this study showed that calprotectin damaged coronary endothelial integrity, reduced nitric oxide production and encouraged the transition from endothelial to mesenchymal. These are potential mechanisms for ASCVD progression. Overall, the investigators concluded that calprotectin levels may be an important factor in the development of ASCVD, but these results warrant further investigation into the mechanisms and clinical utility of calprotectin. Source: Zuo Y, NaveenKumar SK, Navaz S. Epidemiological and translational study of calprotectin and atherosclerotic cardiovascular disease. JAMA. 2025 May 7 (Article in press). Image Credit: mojo_cp – stock.adobe.com