Human immune system baseline activity exhibits remarkable inter-individual variation due to a complex interplay of heritable and non-heritable factors, while demonstrating notable stability within a single person over time [1]. Conversely, atherosclerosis is initiated by a series of intricate, interconnected immune responses engaging an interplay between pro-atherogenic and anti-atherogenic factors that contribute to the prolonged latency period [2,3]. Thus, to implement targeted preventive strategies that address risk factors for atherosclerotic cardiovascular disease (ASCVD), effective risk stratification is crucial. It is well-established that most of the risk for ASCVD is attributable to traditional risk factors [4]. Consequently, the currently widely accepted risk assessment models, such as European Society of Cardiology (ESC) Systematic Coronary Risk Evaluation 2 (SCORE2), include age, systolic blood pressure, non-high-density lipoprotein (HDL) cholesterol, and smoking [5]. Incorporating novel biomarkers may be useful, particularly in patients classified as having intermediate or high CV risk [[6], [7], [8]].

Although there are biomarkers available to evaluate immune system activity status, such as C-reactive protein (CRP), cytokines, or levels of antibodies [9], the impact of single biomarker measurements on clinical ASCVD risk assessment remains uncertain. We therefore aimed to explore the utility of various immune-related biochemical markers in predicting 20-year incidence of ASCVD events. Acknowledging the significant interaction between individual biomarkers and the risk of multicollinearity, we sought to develop a composite immune biomarker score. Therefore, our main objective was to assess the predictive accuracy of an immune biomarker score for 20-year ASCVD incidence in an apparently healthy adult population. Further, we sought to evaluate the incremental value of such a score when added to the HellenicSCORE II+, the Greek-calibrated version of the SCORE2 model for 10-year ASCVD risk assessment.