Clinical significance of measuring soluble LR11, a circulating marker of atherosclerosis and HbA1c in familial hypercholesterolemia

Abstract

ObjectivesThe LDL receptor relative with 11 ligand-binding repeats (LR11) is closely related to atherosclerotic disease or diabetes. The aim of the study was to clarify how soluble LR11 was related to Achilles' tendon thickness (ATT) and HbA1c in familial hypercholesterolemia. Design and methodsThe present study is a cross-sectional case-control study. We enrolled twenty-four patients with heterozygous FH (age 51.0±20.0year; male, 50%; 20 cases with LDL receptor mutation, 1 case with proprotein convertase subtilisin/kexin type 9 (PCSK9) E32K and 3 cases without confirmed mutations). Soluble LR11 (sLR11) was measured using a sandwich enzyme-linked immunosorbent assay method. ResultsUnivariate regression analysis showed that sLR11 had positive correlations with age and HbA1c, and inverse correlations with apoA1 in FH. There were also positive correlations of sLR11 with apoE, IDL-C and average ATT. Multivariate regression analysis showed that there were positive correlations of sLR11 to IDL-C and HbA1c independent of age and BMI. In another multivariate regression analysis on the relationships of average ATT as a dependent variable with age, BMI and sLR11 (IDL-C and HbA1c) as independent variables, sLR11 had a positive correlation with average ATT, independent of age and BMI. However, this independency did not persist after adding IDL-C and HbA1c as confounding factors. Of special note is that HbA1c showed a significant correlation with average ATT, independent of other parameters including sLR11. ConclusionIt is crucial to intervene in the existence of remnant lipoprotein as well as hypercholesterolemia from an early stage and conduct glycemic control to prevent the progression of atherosclerotic disease in FH.