Date: Sunday, October 21, 2018
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Cardiovascular disease is one of the major causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). SLE patients are characterized by a lipid metabolism dysregulation. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that 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. If this were shown to be the case, PCSK9 would be a link between the disease and the lipid metabolism dysregulation that occurs 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, adjusted for standard CVR factors, 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 (BMI), waist circumference, traditional CVR factors and triglycerides were strongly 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 coef. -0.30, 95% CI -0.67-0.069, p=0.11). The presence of carotid plaques and cIMT were not associated with PCSK9 levels although a trend was observed (beta coeff. 20.21, 95% CI -2.47 – 42.72, p=0.081 and beta coeff. 71.19, 95% CI -18.38 – 160.76, p=0.12 respectively).
Regarding SLE data, patients with longer disease duration (beta coeff. 1.25, 95% CI 0.15-2.35, p=0.026) and higher C reactive protein (CRP) 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 levels (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 index (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 (adjusted by BMI, waist circumference, gender, hypertension, dyslipidemia, CRP levels and atherogenic index) these positive associations with both SLICC index and SLEDAI activity and the use of prednisone were maintained, as well as negative associations with LDL levels and the use of hydroxychloroquine.
Conclusion: 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.
To cite this abstract in AMA style:Sanchez-Perez H, Quevedo JC, Rua-Figueroa I, Tejera-Segura B, AM DVG, Gonzalez-Delgado A, Díaz-González F, Ferraz-Amaro I. Association of PCSK9 Serum Levels with Lipid Metabolism Dysregulation, Activity/Damage Scores and Subclinical Atherosclerosis in SLE Patients [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/association-of-pcsk9-serum-levels-with-lipid-metabolism-dysregulation-activity-damage-scores-and-subclinical-atherosclerosis-in-sle-patients/. Accessed October 25, 2020.
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