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Serum glypican-4 is associated with the 10-year clinical outcome of patients with peripheral artery disease

      Highlights

      • GPC4 is linked with age, low kidney function, and C-reactive protein
      • High GPC4 increases risk of future cardiac events and mortality
      • GPC4 is associated with worse outcome independently from traditional risk factors

      Abstract

      Background

      Patients with peripheral artery disease (PAD) are at increased risk of cardiovascular events and mortality compared with non-PAD populations. Blood based biomarkers may improve clinical risk assessment. Recently, we found significant associations of serum glypican-4 (GPC4) with cardiovascular events and mortality in coronary angiography patients. The impact of serum GPC4 on the clinical outcome in PAD patients is unknown and has been addressed in a prospective cohort study.

      Methods

      We measured GPC4 levels using an enzyme-linked immunosorbent assay in 295 PAD patients. The primary endpoint was major adverse cardiovascular events (MACE); we further investigated vascular mortality and all-cause mortality over 10 years of follow-up.

      Results

      Serum GPC4 levels were positively linked with age, low kidney function, C-reactive protein (CRP), and the use of cardiovascular medications. During the 10-year follow-up period, MACE, vascular mortality, and all-cause mortality occurred in 43.1%, 33.4%, and 45.4%, respectively, of the patients. High serum GPC4 was significantly associated with all three endpoints (each log-rank P-value <0.001). In Cox regression analysis serum GPC4 significantly predicted MACE, vascular mortality, and all-cause mortality independently from traditional risk factors including age, sex, T2DM, hypertension, low kidney function, severity of PAD, smoking, and CRP, with adjusted hazard ratios [95% confidence interval] for one standard deviation change of serum GPC4 of 1.38 [1.06–1.80], 1.84 [1.28–2.64], and 1.94 [1.51–2.51], respectively.

      Conclusion

      We conclude that serum GPC4 is a predictor of the 10-year clinical outcome in patients with PAD.

      Keywords

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