Vascular cell adhesion molecule 1: a marker for atrial fibrillation and heart failure risk

Background and aims The plasma protein soluble vascular cell adhesion molecule 1 (sVCAM-1) has been suggested as a biomarker for atrial fibrillation (AF). This study aimed to evaluate sVCAM-1 as a marker of AF and heart failure (HF) risk in the UK Biobank, incorporating genetic risk. Methods Participants were included from 2006-2010. End of follow-up was 2023. Outcomes were incident AF and HF. Hazard ratios (HRs) per standard deviation increase in sVCAM-1 were assessed using Cox proportional hazard regression models. In sub-analyses, the cohort was stratified by tertiles of polygenic risk score (PRS) of AF and sVCAM-1. Associations between sVCAM-1 and cardiac magnetic resonance imaging measures were assessed in a sub-cohort. Results 48,495 individuals (54.6% women, median age 58 [50-63] years) were included. During follow-up, 3,484 were diagnosed with AF and 1,937 with clinically diagnosed HF. Increasing sVCAM-1 levels were associated with rates of AF (HR: 1.72, 95% confidence interval [CI]: 1.54 to 1.91) and HF (HR: 2.04, 95% CI: 1.78 to 2.34). In the highest sVCAM-1 tertile, 10-year cumulative incidence for AF and HF were 6.44% (95% CI: 6.05 to 6.82) and 3.01% (95% CI: 2.74-3.29), respectively. Stratified by tertiles of AF PRS and sVCAM-1 levels, a dose-response-like relationship emerged. In the imaging sub-cohort (n=933), higher sVCAM-1 levels were associated with a reduced LAEF (β: -2.51, 95% CI: -4.33 to -0.70). Conclusion Higher sVCAM-1 levels were associated with AF and HF, and lower LAEF. Integration of an AF PRS with sVCAM-1 levels identified a dose-response-like relationship of the risk.