Association of Plasma Leucine-Rich α-2 Glycoprotein 1, a Modulator of Transforming Growth Factor-β Signaling Pathway, With Incident Heart Failure in Individuals With Type 2 Diabetes

<b>Objective: </b>Leucine-rich alpha-2 glycoprotein 1 (LRG1) is a circulating protein which potentially involves in several pathways related with pathogenesis of heart failure (HF). We aim to study whether plasma LRG1 is associated with risk of incident HF and hospitalization attributable to HF (HHF) in individuals with type 2 diabetes. <p><b>Design and Methods</b>: 1978 individuals with type 2 diabetes were followed for a median of 7.1 (IQR 6.1-7.6) years. Association of LRG1 with HF was studied by cause-specific Cox regression models. </p> <p><b>Results</b>: 191 incident HF and 119 HHF events were identified in follow-up. As compared to quartile 1, participants with LRG1 in quartile 3 and 4 had 3.60 (95% CI 1.63- 7.99) and 5.99 (95% CI 2.21-16.20) folds increased risk for incident HF, and 5.88 (95% CI 1.83-18.85) and 10.44 (95% CI 2.37- 45.98) folds increased risk for HHF after adjustment for multiple known cardio-renal risk factors. As a continuous variable, 1- SD increment in natural log-transformed LRG1 was associated with 1.78 (95% CI 1.33-2.38) folds adjusted risk for incident HF and 1.92 (95% CI 1.27- 2.92) folds adjusted risk for HHF. Adding LRG1 onto clinical variable- based model improved risk discrimination for incident HF (AUC 0.79 to 0.81, P=0.02) and HHF (AUC 0.81 to 0.84, P=0.02).</p> <p><b>Conclusion</b>: Plasma LRG1 is associated with risk of incident HF and HHF, suggesting that it may potentially involve in pathogenesis of HF in individuals with type 2 diabetes. Further studies are warranted to determine whether LRG1 may be a novel biomarker for HF risk-stratification.</p>