Background SLE patients are characterized by a lipid metabolism dysregulation. Proprotein convertase subtilisin/kexin type 9(PCSK9) regulates cholesterol metabolism through low-density-lipoprotein (LDL) receptor degradation. PCSK9 has been linked to cardiovascular risk(CVR) in general population. The purpose of this study is to examine whether PCSK9 levels are related to disease activity, damage and severity scores; abnormalities in the lipid profile; and the subclinical atherosclerosis that occur in SLE patients.
Methods Cross-sectional study that encompasses 195 SLE patients. PCSK9 and lipoproteins serum concentrations were assessed. Activity (SLEDAI), severity (Katz) and damage (SLICC) index scores, and carotid ultrasound sonography were evaluated. A multivariable analysis was performed to evaluate the association of PCSK9 with SLE related dyslipidemia, subclinical atherosclerosis and activity/damage status
Results In the univariate analysis, body mass index, waist circumference, traditional CVR factors and triglycerides were related with PSCK9 serum levels. On the contrary, HDL cholesterol and apolipoprotein A levels showed a negative association. LDL cholesterol exhibited a trend to a negative association (beta coeff. −0.30, 95% CI −0.67–0.07, p=0.11). Carotid plaques and cIMT were not associated with PCSK9 levels although a trend was observed. Patients with longer disease duration (beta coeff. 1.25, 95% CI 0.15–2.35, p=0.026) and higher C reactive protein levels (beta coeff. 1.42, 95% CI 0.61–2.22, p=0.00) disclosed higher PCSK9 levels. Prednisone intake was positively associated with PCSK9 (beta coeff. 35.48, 95% CI 14.29–56.6), p=0.001), and patients that were taking any DMARD or hydroxicloroquine disclosed significant lower levels of PCSK9 (beta coeff. −27.91, 95% CI −54.5–−1.32, p=0.040 and beta coeff. −39.21, 95% CI −62.21–−16.21, p=0.001 respectively). Higher values of SLICC (beta coeff. 9.66, 95% CI 4.47–14.84, p=0.000) and patients that were in the high/very high SLEDAI activity category (beta coeff. 62.98 95% CI 18.10–107.86, p=0.006) disclosed significant higher values of PCSK9. When multivariate analysis was performed these positive associations with both SLICC and SLEDAI and the use of prednisone were maintained, as well as negative associations with LDL levels and the use of hydroxychloroquine.
Conclusions PCSK9 serum levels are independently related to SLE activity and damage scores. This would imply that the mechanisms leading to lipid metabolism dysregulation in SLE patients may be mediated or be a consequence of PCSK9.
Funding Source(s): This work was supported by a grant to I.F-A. from the Spanish Ministry of Health, Subdirección General de Evaluación y Fomento de la Investigación, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016 and by Fondo Europeo de Desarrollo Regional - FEDER - (Fondo de Investigaciones Sanitarias, FIS PI14/00394, PI17/00083)
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