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

## TL;DR

Higher levels of the protein sVCAM-1 are linked to increased risk of atrial fibrillation and heart failure, with a stronger effect when combined with genetic risk.

## Contribution

This study demonstrates that sVCAM-1 is a strong biomarker for AF and HF risk, especially when combined with genetic risk scores.

## Key findings

- Higher sVCAM-1 levels were associated with a 72% increased risk of AF and 104% increased risk of HF.
- The highest sVCAM-1 tertile showed 6.44% 10-year AF and 3.01% 10-year HF incidence.
- sVCAM-1 was linked to reduced left atrial emptying fraction in imaging data.

## Abstract

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.

Participants were included from 2006 to 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. Among 48 495 included individuals, 54.6% were women. Median age at enrollment was 58 (50–63) years. During follow-up, 3484 were diagnosed with AF and 1937 with clinically diagnosed HF. Increasing sVCAM-1 levels were associated with rates of AF [HR: 1.72, 95% confidence interval (CI): 1.54–1.91] and HF (HR: 2.04, 95% CI: 1.78–2.34). In the highest sVCAM-1 tertile, 10-year cumulative incidence for AF and HF were 6.44% (95% CI: 6.05–6.82) 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).

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 with risk of AF.

Graphical AbstractAF, atrial fibrillation; BMI, body mass index; CAD, coronary artery disease; CI, confidence interval; cMRI, cardiac magnetic resonance imaging; HF, heart failure; HR, hazard ratio; IL-6, interleukin-6; LAEF, left atrial emptying fraction; LAVi, left atrial volume index; LVEF, left ventricular ejection fraction; LVESV, left ventricular end-systolic volume; LVGCS, left ventricular global circumferential strain; sVCAM-1, soluble vascular cell adhesion molecule 1; TNF, tumour necrosis factor. Created in BioRender. Baadsgaard, J. (2025)  https://BioRender.com/eomk29v.

AF, atrial fibrillation; BMI, body mass index; CAD, coronary artery disease; CI, confidence interval; cMRI, cardiac magnetic resonance imaging; HF, heart failure; HR, hazard ratio; IL-6, interleukin-6; LAEF, left atrial emptying fraction; LAVi, left atrial volume index; LVEF, left ventricular ejection fraction; LVESV, left ventricular end-systolic volume; LVGCS, left ventricular global circumferential strain; sVCAM-1, soluble vascular cell adhesion molecule 1; TNF, tumour necrosis factor. Created in BioRender. Baadsgaard, J. (2025)  https://BioRender.com/eomk29v.