Circulating leucine-rich α-2 glycoprotein 1 and its prognostic significance in established heart failure

Leucine-rich α-2 glycoprotein 1 (LRG1) is a secreted glycoprotein involved in key pathophysiological processes, including inflammation, fibrosis, and neo-angiogenesis, likely contributing to the development and progression of cardiovascular disease and heart failure (HF). However, its prognostic value in patients with established HF is unclear. This prospective cohort study included 314 patients with a confirmed diagnosis of HF. All-cause mortality and a composite endpoint of HF hospitalization and cardiac death were assessed over a 5-year follow-up period. LRG1 levels were measured using an enzyme-linked immunosorbent assay. During follow-up, 147 patients died, and the composite cardiac endpoint occurred in 142 patients. In Cox regression analyses, each doubling of LRG1 was significantly associated with an increased risk of all-cause mortality (HR = 2.09, 95% CI: 1.59–2.75; p < 0.001) and the composite cardiac endpoint (HR = 1.73, 95% CI: 1.30–2.29; p < 0.001). These associations remained significant after adjustment for established clinical risk factors, including NT-proBNP, and medication use. The addition of LRG1 provided incremental prognostic information beyond established clinical risk factors and NT-proBNP, although improvements varied across performance measures. In conclusion, elevated circulating LRG1 concentrations are independently associated with adverse outcomes in patients with established HF and may provide complementary prognostic information beyond established risk markers.