{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:08:35Z","timestamp":1791065315479,"version":"4.1.0"},"reference-count":45,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:sec id=\"ab-hoi250019-4\"><jats:title>Importance<\/jats:title><jats:p>Innate immunity, particularly neutrophil activation, plays a crucial role in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). The potential of calprotectin, a biomarker of neutrophil activation, as a mechanistically informed biomarker for ASCVD in an ethnically diverse population requires further investigation.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi250019-5\"><jats:title>Objective<\/jats:title><jats:p>To examine the prospective association between circulating calprotectin and ASCVD in a diverse, population-based cohort while also exploring calprotectin\u2019s mechanistic contributions to ASCVD in vitro.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi250019-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>Circulating calprotectin was measured in plasma collected from 2412 participants during phase 2 of the Dallas Heart Study, a multiethnic, population-based cohort study. The median follow-up after plasma collection was 8 years.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi250019-7\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Associations with future ASCVD events (defined as first nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or death from a cardiovascular cause) were assessed using Cox proportional hazards models, adjusted for known cardiovascular disease risk factors as well as high-sensitivity C-reactive protein (hs-CRP), N-terminal pro\u2013brain natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT).<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi250019-8\"><jats:title>Results<\/jats:title><jats:p>Higher calprotectin levels were associated with older age, male sex, Black race, hypertension, diabetes, and smoking history. Individuals with higher calprotectin had higher hemoglobin A<jats:sub>1c<\/jats:sub>, very low-density lipoprotein cholesterol, and triglycerides, and lower high-density lipoprotein cholesterol and cholesterol efflux capacity. Log-transformed calprotectin levels were associated with an increased risk of ASCVD events over 8 years (hazard ratio [HR], 1.98 per log increase [95% CI, 1.54-2.53]). This association remained statistically significant after adjusting for prior ASCVD and traditional risk factors (HR, 1.61 [95% CI, 1.22-2.13]) and hs-CRP, NT-proBNP, and hs-cTnT (HR, 1.43 [95% CI, 1.04-1.96]). Higher calprotectin also correlated with higher coronary artery calcium scores (<jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001). In vitro studies revealed that calprotectin impaired coronary endothelial integrity, diminished nitric oxide production, and fostered endothelial to mesenchymal transition, providing potential mechanisms for ASCVD progression.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi250019-9\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>The findings suggest that calprotectin may serve as a mechanistically informed biomarker for ASCVD, independent of traditional and contemporary cardiovascular risk factors and biomarkers. However, its clinical utility warrants further evaluation.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamacardio.2025.0945","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T11:47:57Z","timestamp":1746618477000},"page":"718","source":"Crossref","is-referenced-by-count":8,"title":["Epidemiological and Translational Study of Calprotectin and Atherosclerotic Cardiovascular Disease"],"prefix":"10.1001","volume":"10","author":[{"given":"Yu","family":"Zuo","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somanathapura K.","family":"NaveenKumar","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann 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