VEGF as a predictor of major adverse events in patients with peripheral arterial disease - an exploratory study

Peripheral arterial disease (PAD) is an atherosclerotic disease caused by the narrowing of peripheral arteries due to atheromatous plaque build-up. Angiogenesis can be beneficial in patients with PAD however it may contribute to negative long-term cardiovascular outcomes. Vascular endothelial growth factor-A (VEGF/VEGF-A) has been associated with PAD. This study investigated the association between VEGF and major adverse cardiovascular events (MACE), and major adverse limb events (MALE) in patient with PAD. Plasma levels of VEGF were quantified in 300 patients with PAD (ABI < 0.9). Patients were monitored for MACE, defined as the composite of myocardial infarction, stroke, and cardiovascular-related death and MALE, defined as composite of progression to chronic limb threatening ischemia, need for surgical intervention, graft/stent re-occlusion, and need for minor or major limb amputation. Multivariable Cox proportional hazards regression was used to assess associations between VEGF levels and the risk of MACE and MALE, reported as hazard ratios with 95% confidence intervals. A Bonferroni correction was applied to address multiple hypothesis testing with p < 0.025 considered as significant. VEGF was independently associated with an increased risk of MACE (HR 1.26, 95% CI: 1.14-1.40, p < 0.001) and MALE (HR 1.176, 95% CI: 1.066-1.297, p = 0.001) after adjusting for cardiovascular risk factors. VEGF demonstrated a strong association with MACE and MALE events with each unit increase in VEGF being associated with a 26.0% increase in the risk of MACE and 17.6% increase in the risk of MALE, supporting its potential utility in risk stratification in patients with PAD.