Leucine-rich α-2 glycoprotein 1 is associated with increased mortality risk in patients with peripheral artery...

Leucine-rich α-2 glycoprotein 1 (LRG1) is a pro-inflammatory protein involved in pathogenic neovascularization and is considered a predictor of poor clinical outcomes in specific patient populations. The prospective value of LRG1 for predicting clinical outcomes in patients with established peripheral artery disease (PAD) is unclear and was investigated in the present study. The study included a total of 295 patients with sonographically confirmed PAD, who were followed for a period of 10 years. Primary endpoints were all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE). LRG1 was significantly associated with increased risk across all primary endpoints. Hazard ratios (HR) from univariate Cox regression analysis were 3.12 [95% CI: 2.20-4.42]; P < 0.001 for all-cause mortality, 2.58 [95% CI: 1.56-4.26]; P < 0.001 for cardiovascular mortality, and 1.69 [95% CI: 1.18-2.42], P = 0.004 for MACE. In multivariable Cox regression analysis adjusting for traditional cardiovascular risk factors, the association of LRG1 with all-cause mortality and cardiovascular mortality remained significant (P < 0.001 and P = 0.011, respectively), but not with MACE. The inclusion of LRG1 in a conventional clinical risk model significantly enhanced the model's discriminatory ability between individuals who died and those who survived. Subgroup analysis revealed sex-related differences in the prognostic value of LRG1, with a stronger association observed in males compared to females. In conclusion, LRG1 was a strong and independent predictor of 10-year mortality among PAD patients. Further studies are warranted to validate these findings in other, more diverse cohorts. KEY MESSAGES: LRG1 predicts 10-year mortality in patients with peripheral artery disease. LRG1 predicts both cardiovascular and non-cardiovascular mortality. LRG1 is linked to outcome independently of traditional risk factors. LRG1 improves prediction beyond conventional risk factors for all-cause mortality. Subgroup analysis revealed sex-related differences in the prognostic value of LRG1.