Background The
cysteine protease legumain is increased in patients with
atherosclerosis, but its causal role in
atherogenesis and
cardiovascular disease is still unclear. The aim of the study was to investigate the association of
legumain with clinical outcome in a large cohort of patients with
acute coronary syndrome. Methods and Results Serum levels of
legumain were analyzed in 4883 patients with
acute coronary syndrome from a substudy of the PLATO (Platelet Inhibition and Patient Outcomes) trial. Levels were analyzed at admission and after 1 month follow-up. Associations between
legumain and a composite of cardiovascular death, spontaneous
myocardial infarction or
stroke, and its individual components were assessed by multivariable Cox regression analyses. At baseline, a 50% increase in
legumain level was associated with a hazard ratio (HR) of 1.13 (95% CI, 1.04-1.21), P=0.0018, for the primary composite end point, adjusted for randomized treatment. The association remained significant after adjustment for important clinical and demographic variables (HR, 1.10; 95% CI, 1.02-1.19; P=0.013) but not in the fully adjusted model.
Legumain levels at 1 month were not associated with the composite end point but were negatively associated with
stroke (HR, 0.62; 95% CI, 0.44-0.88; P=0.0069), including in the fully adjusted model (HR, 0.57; 95% CI, 0.37-0.88; P=0.0114). Conclusions Baseline
legumain was associated with the primary outcome in patients with
acute coronary syndrome, but not in the fully adjusted model. The association between high levels of
legumain at 1 month and decreased occurrence of
stroke could be of interest from a mechanistic point of view, illustrating the potential dual role of
legumain during
atherogenesis and
acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00391872.