SAT0383 ENHANCED PERFORMANCE OF THE ASAS CLASSIFICATION CRITERIA BY DELETION OF NON-DISCRIMINATORY CLINICAL ITEMS: DATA FROM THE SCREENING IN AXIAL SPONDYLOARTHRITIS IN PSORIASIS, IRITIS, AND COLITIS COHORT

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism through low-density lipoprotein receptor degradation and that has been linked with cardiovascular (CV) risk. Patients with spondyloarthritis (SpA) are prone to an increased and premature prevalence of atherosclerosis that has been linked to an atherogenic lipid profile among these individuals. Objectives: The purpose of the present study was to examine whether PCSK9 levels are related to both abnormalities in the lipid profile and the severe atherosclerosis that occur in patients with SpA. Methods: Cross-sectional study that encompassed 545 individuals; 299 patients with SpA and 246 statins intake-matched controls. PCSK9 and lipoproteins serum concentrations, standard lipid profile and carotid intima-media thickness and carotid plaques were assessed in patients and controls. A multivariable analysis, adjusted for standard CV risk factors, was performed to evaluate the influence of PCSK9 on SpA related dyslipidemia, disease related data, and subclinical carotid atherosclerosis. Results: Lipid profiles showed that most lipid panel parameters (total cholesterol, HDL- and LDL-cholesterol, lipoprotein A and apoliprotein A1) were lower in SpA patients compared to controls. Contrary, Apo B:Apo A1 and LDL:HDL cholesterol ratios were higher in SpA. The mean PCSK9 serum levels were significantly lower in SpA patients compared to controls (249 ± 105 vs. 199 ± 74, ng/ml, p=0.000) in the univariate analysis. An additional multivariable analysis adjusting for demographics and CV risk factors plus all the lipid-related molecules (that were found to be different between patients and controls) disclosed that PCSK9 (beta coef. -44 [95%CI -60- -27] % mg/dl, p=0.000) conserved its downregulation in SpA patients. Traditional CV risk factors were not related to PCSK9 in controls and patients. Concerning lipid profile, some correlations were found between lipid-related molecules and PCSK9. In this sense, triglycerides were positively associated with PCSK9 in both patients and controls; total cholesterol and apolipoprotein A1 serum levels were associated with PCSK9 in patients but not in controls and; Lipoprotein (a) was related to PCSK9 only in controls (Table 1). Regarding disease-related data, disease duration (log beta coef. 10 [0-20], p=0.043), and ASDAS-CRP (12 [95%CI 4-20], p=0.004) and BASFI (log beta coef. 12 [95%CI 0-25], p=0.049) scores,were positively related to PCSK9. Moreover, patients in the very high disease activity ASDAS-CRP category disclosed higher serum levels of PCSK9 compared to those in the remission category (32 [95%CI 2-63], p=0.038). Remarkably, while patients on current prednisone showed higher serum levels of PCSK9 (55 [95%CI 24-8]) ng/ml, p=0.001), patients under anti-TNF alpha therapies exhibited inferior levels (beta coef. -26 [95%CI -43- -9], p=0.003). PCSK9 in SPA patients with carotid plaque was higher compared to patients without plaque, however, this difference was lost after multivariable analysis. Conclusion: PCSK9 is downregulated in SpA patients independently of other inflammation-related lipid profile modifications that occur in the disease. Disease activity is positively associated with PCSK9 serum levels. PCSK9 is univariately related to the presence of carotid plaque. Disclosure of Interests: Juan Carlos Quevedo-Abeledo Speakers bureau: Abbvie, Laura de Armas-Rillo: None declared, Vanessa Hernandez-Hernandez Speakers bureau: Pfizer, Abbvie, MSD, delgado frias esmeralda Speakers bureau: Pfizer, Abbvie, MSD, Antonia de Vera-Gonzalez: None declared, Alejandra Delgado-Gonzalez: None declared, Jose Antonio Garcia-Dopico: None declared, Ivan Ferraz-Amaro Grant/research support from: Pfizer, Abbvie, Speakers bureau: Pfizer, Abbvie, MSD.