Session Information
Title: Rheumatoid Arthritis - Clinical Aspects (ACR): Comorbidities, Treatment Outcomes and Mortality
Session Type: Abstract Submissions (ACR)
Background/Purpose
Proteinase K-like serine protease PCSK9 binds the low-density lipoprotein (LDL) receptor at the surface of hepatocytes, thereby preventing its recycling and enhancing its degradation in endosomes/lysosomes, resulting in reduced LDL-cholesterol clearance. Therefore, gain-of-function in PCSK9 lead to higher levels of LDL-cholesterol and increased risk of cardiovascular disease. The objective is to investigate how PCSK9, one of the molecules involved in the metabolism of LDL-cholesterol, is expressed in patients with rheumatoid arthritis (RA) and its potential relationship with the dyslipidemia and the endothelial dysfunction observed in these patients.
Methods
Plasma PCSK9 concentrations and brachial artery flow-mediated dilation (FMD) by ultrasound were measured in 115 patients with RA and 101 matched controls. A multivariable analysis adjusted for standard cardiovascular risk factors, disease activity and lipids, including LDL cholesterol, was performed to evaluate the relation of PCSK9 on RA dyslipidemia and endothelial dysfunction compared to controls.
Results
FMD was higher in controls when compared to RA patients (8.5 [95%CI 4.5-15.6] vs. 5.3 [0.0-9.2] mm, p=0.00). In the univariate analysis, RA patients tended to have lower levels of total cholesterol(p=0.08), LDL(p=0.18) and apolipoprotein A1(p=0.15), although statistical significance was not reached. PCSK9 levels were not different between patients and controls even adjusting for comorbidity or disease activity. PCSK9 tended to be correlated with LDL cholesterol in patients and controls, but statistical significance was not reached. Nevertheless PCSK9 was positively correlated with apolipoprotein B in RA patients (beta coef. 0.06 [0.02-0.09] x10 ng/ml, p=0.00) but not in controls. Disease activity score DAS28, both considering as continuous (766 [100-1432] ng/ml, p=0.03) or categorical -low, moderate, high and very high- (832 [82-1583] ng/ml, p=0.03) was correlated with PCSK9 levels. Therefore, higher DAS28 was associated with greater PCSK9 concentration. When RA patients were split in tertiles according to PCSK9 values we observed that patients which were more commonly included in the third tertile, showed the higher values of FMD. Therefore, in RA patients, as FMD increased we observed that the risk of having PCSK9 values included in the third tertile compared to that of being in the first tertile was statistically significant multiplied by OR 0.98 ([0.82-0.99],p=0.04). However, this association was not found in controls.
Conclusion
PCSK9 concentrations are associated with disease activity scores and endothelial dysfunction in RA patients. The role of PCSK9 in RA related dyslipidemia and cardiovascular risk needs further investigation.
Disclosure:
E. Delgado-Frias,
None;
I. Ferraz-Amaro,
None;
V. Hernandez-Hernandez,
None;
A. M. de Vera-Gonzalez,
None;
A. F. Gonzalez-Rivero,
None;
M. A. González-Gay,
None;
F. Diaz-Gonzalez,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/proteinase-k-like-serine-protease-pcsk9-influence-on-the-dyslipidemia-and-endothelial-dysfunction-observed-in-rheumatoid-arthritis-patients/