Proprotein Convertase Subtilisin/Kexin Type 9 in the Inflammation-Related Dyslipidemia of Patients with Axial Spondyloarthritis is Related to Disease Activity.

Abstract

Introduction: 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 to cardiovascular risk. The purpose of the present study was to examine whether PCSK9 levels are related to both abnormalities in the lipid profile and the development of severe atherosclerosis that often occurs in patients with axial spondyloarthritis (axSpA). Methods: Cross-sectional study that encompassed 545 individuals; 299 patients with axSpA and 246 statin use-matched controls. PCSK9, lipoproteins serum concentrations and standard lipid profiles were analyzed in patients and controls. Carotid intima-media thickness (cIMT) and carotid plaques were assessed in patients. A multivariable analysis, adjusted for standard cardiovascular risk factors, was performed to evaluate the influence of PCSK9 on axSpA related dyslipidemia and subclinical carotid atherosclerosis.Results: Most lipid panel parameters (total cholesterol, HDL- and LDL-cholesterol, lipoprotein (a) and apoliprotein A1) were significantly lower in axSpA patients than controls. PCSK9 serum levels (beta coef. -44 [95%CI -60- -27] ng/dl, p=0.000) were also downregulated in axSpA patients after fully multivariate adjustment, including other lipid profile-related molecules modifications that the disease generates. Unadjusted higher levels of PCSK9 were associated with carotid plaque in axSpA patients (beta coef. 27 [95%CI 9-45], p=0.003). ASDAS-CRP was found to be independently and significantly related to PCSK9 (beta coef. 10 [95%CI 1-18] ng/dl, p=0.023) after analyzing fully adjusted models that took age, sex, and the rest of lipid profile molecules into account. Whereas patients taking prednisone showed higher serum levels of PCSK9 (55 [95%CI 24-8]) ng/ml, p=0.001), those under anti-TNF alpha therapies exhibited lower levels (beta coef. -26 [95%CI -43- -9], p=0.003).Conclusion: PCSK9 is downregulated in patients with axSpA. Disease activity is positive and significantly related to PSCK9. Anti-TNF-therapy yields reduction in PCSK9 serum levels.