Abstract Background Cardiovascular disease (CVD) remains a leading cause of mortality worldwide, with inflammation playing a pivotal role in its pathogenesis. Despite advancements in risk prediction models like China-PAR and the Pooled Cohort Equations (PCE), there is a need for more accurate stratification, particularly in intermediate-risk groups. CCL17, a pro-inflammatory chemokine, has emerged as a potential biomarker for cardiovascular risk. This study aims to explore the association between CCL17 levels and major adverse cardiovascular events (MACEs) in multi-center cohorts. Methods We conducted a prospective analysis using data from the Shunyi Cohort in China (n=706) and the UK Biobank (n=36167). CCL17 levels were measured at baseline, and participants were followed for up to 10 years. MACEs, including all-cause mortality, myocardial infarction (MI), heart failure (HF), and stroke, were recorded. Multivariate Cox regression models were used to assess the association between CCL17 levels and MACEs. The predictive value of adding CCL17 to existing risk models (China-PAR and PCE) was evaluated using C-statistics, net reclassification improvement (NRI), and integrated discrimination index (IDI). Findings: In the Shunyi Cohort, participants with higher CCL17 levels had a significantly increased risk of MACEs (hazard ratio per 1 SD 2.28; 95% confidence interval 1.74–3.02). Similar findings were observed in the UK Biobank, where elevated CCL17 levels were associated with higher risks of MI, stroke, and all-cause mortality (hazard ratio per 1 SD 1.19; 95% confidence interval 1.16-1.23). Incorporating CCL17 into the China-PAR and PCE models improved risk stratification, with significant improvements in C-statistics (7.2% in the Shunyi Cohort; 0.4% in the UK Biobank) and NRI (15.1% in the Shunyi Cohort; 3.0% in the UK Biobank). Particularly, individuals in the intermediate clinical risk group with high CCL17 surpass the threshold for high clinical risk of MACEs with certain clinical decision for intervention. Interpretation: Elevated CCL17 levels are independently associated with an increased risk of MACEs in dual-verification prospective cohorts. The addition of CCL17 to existing risk prediction models enhances their discriminatory ability, particularly for intermediate-risk individuals. These findings suggest that CCL17 could serve as a valuable biomarker for refining cardiovascular risk assessment and guiding targeted interventions.Figure 1A Figure 1B
Wang et al. (Sat,) studied this question.