Usefulness of Fetuin-A to Predict Risk for Cardiovascular Disease Among Patients With Obstructive Sleep Apnea

Abstract

Patients with obstructive sleep apnea (OSA) are at increased risk for cardiovascular diseases (CVDs). Fetuin-A, a novel hepatokine, has been associated with the metabolic syndrome (MetS), insulin resistance, and type 2 diabetes mellitus, all of which are highly prevalent in patients with OSA and associated with increased CVD risk. The goal of this study was to determine whether fetuin-A could be involved in the pathogenesis of CVD risk in patients with OSA, through relations of fetuin-A with MetS components and/or insulin resistance. Overweight or obese, nondiabetic volunteers (n = 120) were diagnosed with OSA by in-laboratory nocturnal polysomnography. Steady-state plasma glucose concentrations derived during the insulin suppression test were used to quantify insulin-mediated glucose uptake; higher steady-state plasma glucose concentrations indicated greater insulin resistance. Fasting plasma fetuin-A and lipoprotein concentrations were measured. Whereas neither the prevalence of MetS nor the number of MetS components was associated with tertiles of fetuin-A concentrations, the lipoprotein components of MetS, triglycerides and high-density lipoprotein cholesterol, increased (p <0.01) and decreased (p <0.05), respectively, across fetuin-A tertiles. Additionally, comprehensive lipoprotein analysis revealed that very low density lipoprotein (VLDL) particles and VLDL subfractions (VLDL1+2 and VLDL3) were increased across fetuin-A tertiles. In contrast, neither insulin resistance nor sleep measurements related to OSA were found to be modified by fetuin-A concentrations. In conclusion, abnormalities of lipoprotein metabolism, but not MetS or insulin resistance per se, may represent a mechanism by which fetuin-A contributes to increased CVD risk in patients with OSA.