Association Between Oxidation-Modified Lipoproteins and Coronary Plaque in Psoriasis : An Observational Cohort Study

Abstract

<div class="section"> <a class="named-anchor" id="S1"> <!-- named anchor --> </a> <h5 class="section-title" id="d634274e252">Rationale:</h5> <p id="P1">Psoriasis (PSO) is a systemic inflammatory skin disease associated with cardiovascular disease (CVD) and lipid dysfunction. However, traditional lipid parameters have limited prognostic value whereas assessing oxidation-modified lipids (OMLs) in this inflammatory driven condition may capture additional risk. Recently, a study showed that PSO was associated with increased lipid rich coronary plaques, therefore, investigating potential relationships with OMLs may speed understanding of increased CVD in PSO. </p> </div><div class="section"> <a class="named-anchor" id="S2"> <!-- named anchor --> </a> <h5 class="section-title" id="d634274e257">Objective:</h5> <p id="P2">To understand whether OMLs associate with traditional lipid phenotypes, cardiometabolic disease biomarkers and total coronary plaque, with focus on non-calcified burden (NCB) by CCTA in psoriasis. </p> </div><div class="section"> <a class="named-anchor" id="S3"> <!-- named anchor --> </a> <h5 class="section-title" id="d634274e262">Methods and Results:</h5> <p id="P3">PSO subjects and controls (n=252) had profiling for oxidation-modified LDL, HDL, Lp(a), cholesterol efflux capacity (CEC), lipoprotein particle size and number by NMR spectroscopy and paraoxonase (PON1) activity. Blinded CCTA coronary artery disease characterization included total burden (TB), NCB and dense-calcified burden (DCB). Compared to healthy volunteers (HV), PSO subjects were older (mean age=50.1), had increased BMI and HOMA-IR. PSO subjects had increase in oxLp(a), Lp(a) and oxHDL (p&lt;0.05 for all) with significant association of oxLDL (β=0.10, p=0.020) and oxHDL (β=−0.11, p=0.007) with NCB. Moreover, PSO subjects expressed significantly higher PON1 (kU/μl) activity compared to HV (8.55 ± 3.21 vs. 6.24 ± 3.82, p=0.01). Finally, PSO treatment was associated with a reduction in oxHDL (U/ml) (203.79 ± 88.40 vs. 116.36 ± 85.03, p&lt;0.001) and with a concomitant decrease in NCB at one year (1.04 ± 0.44 vs. 0.95 ± 0.32, p=0.03). </p> </div><div class="section"> <a class="named-anchor" id="S4"> <!-- named anchor --> </a> <h5 class="section-title" id="d634274e267">Conclusions:</h5> <p id="P4">Traditional lipids did not capture risk of lipid rich plaque as assessed by NCB, whereas assaying oxidation-modification of lipids revealed significant association with oxLDL and oxHDL. The PON-1 activity was increased in PSO suggesting possible compensatory anti-oxidative effect. Psoriasis treatment was associated with a reduction in oxHDL. These findings support performance of larger studies to understand oxidation-modified lipids in inflammatory states. </p> </div>