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Published on: May 31, 2016
Epidemiological and Translational Study of Calprotectin and Atherosclerotic Cardiovascular Disease
Yu Zuo1, Somanathapura K NaveenKumar1, Sherwin Navaz1
1Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor.
Insights
Higher calprotectin levels indicate increased risk for atherosclerotic cardiovascular disease (ASCVD) events. This neutrophil activation biomarker shows potential for predicting ASCVD, independent of other risk factors.
Area of Science:
- Immunology
- Cardiovascular Medicine
- Biomarker Discovery
Background:
- Innate immunity and neutrophil activation are implicated in atherosclerotic cardiovascular disease (ASCVD) pathogenesis.
- Calprotectin, a marker of neutrophil activation, requires further investigation as a potential ASCVD biomarker in diverse populations.
Purpose of the Study:
- To assess the association between circulating calprotectin and ASCVD risk in a multiethnic cohort.
- To explore the in vitro mechanistic role of calprotectin in ASCVD.
Main Methods:
- Plasma calprotectin levels were measured in 2412 participants from the Dallas Heart Study.
- Prospective associations with ASCVD events were analyzed using Cox models, adjusting for risk factors and other biomarkers.
- In vitro studies investigated calprotectin's effects on endothelial cells.
Main Results:
- Elevated calprotectin correlated with traditional ASCVD risk factors and poorer lipid profiles.
- Higher calprotectin levels were independently associated with an increased risk of ASCVD events over 8 years (HR, 1.43 after full adjustment).
- In vitro, calprotectin impaired endothelial integrity and function, suggesting mechanisms for ASCVD progression.
Conclusions:
- Calprotectin may serve as a mechanistically informed biomarker for ASCVD, beyond traditional risk factors and established biomarkers.
- Further evaluation is needed to determine the clinical utility of calprotectin in ASCVD risk assessment.
Importance:
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.
Objective:
To examine the prospective association between circulating calprotectin and ASCVD in a diverse, population-based cohort while also exploring calprotectin's mechanistic contributions to ASCVD in vitro.
Design, Setting, And Participants:
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.
Main Outcomes And Measures:
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-brain natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT).
Results:
Higher calprotectin levels were associated with older age, male sex, Black race, hypertension, diabetes, and smoking history. Individuals with higher calprotectin had higher hemoglobin A1c, 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 (P < .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.
Conclusions And Relevance:
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.
