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

Abstract

OBJECTIVE Leucine-rich α-2 glycoprotein 1 (LRG1) is a circulating protein potentially involved in several pathways related to pathogenesis of heart failure (HF). We aimed to study whether plasma LRG1 is associated with risks of incident HF and hospitalization attributable to HF (HHF) in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 1,978 individuals with type 2 diabetes were followed for a median of 7.1 years (interquartile range 6.1–7.6). Association of LRG1 with HF was studied using cause-specific Cox regression models. RESULTS In follow-up, 191 incident HF and 119 HHF events were identified. As compared with quartile 1, participants with LRG1 in quartiles 3 and 4 had 3.60-fold (95% CI 1.63–7.99) and 5.99-fold (95% CI 2.21–16.20) increased risk of incident HF and 5.88-fold (95% CI 1.83–18.85) and 10.44-fold (95% CI 2.37–45.98) increased risk of HHF, respectively, after adjustment for multiple known cardiorenal risk factors. As a continuous variable, 1 SD increment in natural log-transformed LRG1 was associated with 1.78-fold (95% CI 1.33–2.38) adjusted risk of incident HF and 1.92-fold (95% CI 1.27–2.92) adjusted risk of HHF. Adding LRG1 to the clinical variable–based model improved risk discrimination for incident HF (area under the curve [AUC] 0.79–0.81; P = 0.02) and HHF (AUC 0.81–0.84; P = 0.02). Conclusions Plasma LRG1 is associated with risks of incident HF and HHF, suggesting that it may potentially be involved in pathogenesis of HF in individuals with type 2 diabetes. Additional studies are warranted to determine whether LRG1 is a novel biomarker for HF risk stratification.