Dey, Amit K, Gaddipati, Ranjitha, Aksentijevich, Milena, Choi, Harry, Elnabawi, Youssef, Ongstad, Emily, Scott, Colin, Khalil, Noor O, Rodante, Justin, Anzenberg, Paula, Al Najafi, Mina, Reddy, Aarthi, Teague, Heather, Argueta-Amaya, Jenis, Sorokin, Alexander, Joshi, Aditya A, Playford, Martin, Chen, Marcus, Karathanasis, Sotirios, Gelfand, Joel, Gupta, Ruchi, and Mehta, Nehal N
Introduction:Psoriasis, a chronic inflammatory skin disease, is associated with HDL dysfunction assessed as cholesterol efflux capacity (CEC), and increased high-risk coronary plaque (HRP) by coronary computed tomography angiography (CCTA). Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a scavenger receptor for oxidized low-density lipoprotein, is critical to the development of HDL dysfunction, and lipid-rich high-risk atherosclerotic plaques. We aimed to understand the relationships of soluble LOX-1 (sLOX-1) with CEC, and HRP in psoriasis.Methods:Consecutive psoriasis patients (n=175) underwent CCTA scans and ELISA to identify HRP (Medis, Netherlands) and measure sLOX-1 (Medimmune, USA) respectively. HRP was characterized as a low attenuation plaque or a positively remodeled plaque or both. CEC was measured in duplicate using a validated cell-based ex vivo assay.Results:Psoriasis patients were middle-aged, predominantly male, with low CV risk by Framingham risk and had moderate-severe psoriasis severity (Table 1). sLOX-1 negatively associated with CEC in unadjusted (?=-0.17, p=0.03) as well as when adjusted for Framingham risk score, body mass index, hs-CRP, statin use, and biologic psoriasis treatment (?=-0.19, p=0.02). Moreover, patients with higher sLOX-1 (dichotomized based on mean sLOX-1 levels in psoriasis) were at significantly higher odds of prevalent high-risk plaque in adjusted analyses [odds ratio (OR): 3.47; 95% confidence interval (CI): 1.110-10.819, p=0.03] with positive remodeling in the coronary artery, associating with circulating sLOX-1 in fully adjusted models (?=0.10, p=0.04).Conclusions:sLOX-1 was significantly associated with CEC and HRP in psoriasis, demonstrating the potential role of sLOX-1 in HDL dysfunction and subclinical cardiovascular disease in psoriasis. Our findings support further studies evaluating sLOX-1 in chronic inflammation associated cardiometabolic disease.