Circulating glypican-4 is a new predictor of all-cause mortality in patients with heart failure

Background: Heart failure confers a high burden of morbidity and mortality. However, risk prediction in heart failure patients still is limited. Blood-based biomarkers hold promise to improve clinical risk assessment. Recently we have identified circulating glypican-4 (GPC4) as a significant predictor of mortality in coronary angiography patients and patients with peripheral artery disease. The impact of serum GPC4 on mortality in patients with heart failure is unknown and is addressed in this prospective cohort study.Methods: We prospectively recorded all-cause mortality in 288 patients with heart failure. GPC4 levels were measured using an enzyme-linked immunosorbent assay at baseline.Results: During the 24-month follow-up period, 28.1% (n = 81) of the patients died. Serum GPC4 significantly predicted all-cause mortality (hazard ratio (HR) per doubling of GPC4 = 3.57 [2.31-5.53]; P < 0.001). Subgroup analysis showed that GPC4 was significantly associated with all-cause mortality in patients with reduced ejection fraction (HR per doubling = 3.25 [1.75-6.04]; P < 0.001) as well as in those with preserved ejection fraction (HR per doubling = 3.07 [1.22-7.70]; P = 0.017). The association between serum GPC4 and all-cause mortality remained significant in multivariable Cox regression analysis correcting for traditional risk factors (P = 0.035). Results from C-statistics indicated an additional prognostic value of GPC4 relative to NT-proBNP for the pre-diction of two-year all-cause mortality (P = 0.030).Conclusion: Circulating GPC4 independently predicts all-cause mortality in patients with heart failure.