Using Immune Markers to Predict Future Heart Disease Risk

Recent research highlights the significant role of the immune system in the development of atherosclerotic cardiovascular disease, a condition characterized by the gradual buildup of fatty plaques within the arteries. This arterial narrowing impairs blood flow to vital organs, increasing the likelihood of heart attacks and strokes. The process begins with damage to the artery lining, which triggers an immune response involving neutrophils and other immune cells. While these cells help combat injury or infection, excessive activity can lead to persistent inflammation, accelerating plaque growth and disease progression. Often, these processes occur silently over years, making early detection challenging due to the scarcity of reliable markers.

A promising biomarker in this context is calprotectin, a protein released by activated neutrophils. Elevated calprotectin levels indicate heightened neutrophil activity and the formation of neutrophil extracellular traps, structures that promote inflammation and contribute to plaque formation. Previously, calprotectin has been studied in inflammatory disorders such as antiphospholipid syndrome and COVID-19, but recent findings suggest its potential as a predictor for atherosclerosis in the general population.

A study led by researchers from the University of Michigan and UT Southwestern used samples from the Dallas Heart Study, a large diverse cohort, to investigate the relationship between calprotectin levels and future cardiovascular disease (CVD). Measuring calprotectin in blood samples from 2,412 participants, the researchers found that higher levels of this protein predicted the development of atherosclerotic heart disease within eight years, independent of traditional risk factors like age, sex, race, smoking, blood pressure, cholesterol, and kidney health. Participants with elevated calprotectin also showed increased coronary artery calcium scores, an indicator of early plaque buildup.

Further laboratory experiments revealed that calprotectin adversely affects blood vessel health by reducing nitric oxide production, which is essential for artery flexibility, and possibly promotes vascular scarring. These insights suggest that calprotectin not only serves as a early biomarker but might also play a direct role in the pathogenesis of atherosclerosis.

The implications of this research are substantial, as measuring calprotectin levels could help identify at-risk individuals before symptoms appear, potentially guiding early intervention strategies. Dr. Ray Zuo, one of the lead scientists, emphasizes that targeting calprotectin might offer new therapeutic avenues in preventing cardiovascular disease. The study underscores the importance of immune activity in heart disease development and highlights the potential of immune-based biomarkers to improve early detection and prevention methods.

This work was supported by the ongoing efforts of the Dallas Heart Study, a longitudinal project tracking diverse populations’ health. As heart disease remains the leading cause of death worldwide, these advancements represent a promising step toward better risk assessment and timely treatment, ultimately saving lives.