Abstract 1132: Levels of Serum Soluble Lectin-like Oxidized LDL Receptor (sLOX-1) Predict Adverse Cardiovascular Outcomes in Patients With Stable Coronary Artery Disease
Background: Oxidized LDL (oxLDL) has been proposed as an independent biomarker of risk for adverse cardiovascular (CV) outcomes. Lectin-like oxLDL receptor-1 (LOX-1) is expressed in advanced plaques and activated platelets and may play a role in plaque rupture; a soluble form (sLOX-1) can be measured in serum. We aimed to define the prognostic value of these biomarkers in patients with stable coronary artery disease (CAD).
Methods: Levels of sLOX-1 and oxLDL [the latter using 2 different ELISAs: competitive (oxLDLc) and sandwich (oxLDLs)] were measured on baseline samples in 3791 patients enrolled in PEACE, a placebo-controlled trial of trandolapril vs placebo in patients w/stable CAD followed for 4.8 y for clinical outcomes. Multivariable Cox regression (limited access dataset, NHLBI) was used to adjust for age, sex, CV risk factors, lipid profile (apoB, apoA), lipid-lowering therapy, and treatment group.
Results: The incidence of the composite of CV death, MI or stroke significantly increased across quartiles of each of the three biomarkers (Table⇓). Both oxLDLc and oxLDLs levels were strongly correlated with apoB levels (r=0.64 and 0.53, respectively), whereas sLOX-1 was not (r=0.06). After adjustment for clinical factors, only sLOX-1 remained a significant predictor of CV death, MI or stroke (P=0.026 for trend; adj HR 1.41, 95% CI 1.03–1.94, P=0.015 for Q4 vs Q1). sLOX-1 was not strongly correlated with either high-sensitivity C-reactive protein (hs-CRP) or lipoprotein-associated phospholipase A2 (Lp-PLA2) (r=0.14 and r=0.05, respectively). After further adjustment for hs-CRP and Lp-PLA2, sLOX-1 remained a significant predictor of CV death, MI or stroke (P=0.038 for trend, adj HR 1.39, 95% CI 1.01–1.92, P=0.04 for Q4 vs Q1).
Conclusion: In stable CAD, an elevated level of sLOX-1 predicts CV death, MI or stroke independent of clinical risk factors and other inflammatory biomarkers. Further studies are needed to determine the clinical utility of measuring sLOX-1.