Dysfunctional antioxidant capacity of high‐density lipoprotein in rheumatoid arthritis

• Published in: European journal of clinical investigation Vol. 53; no. 8; pp. e13999 - n/a
• Main Authors: García‐Gómez, María Carmen, Padró, Teresa, Muñoz‐García, Natàlia, Bianchi, María, Álvarez, Lorenzo, Badimon, Lina, Corbella, Emili, Pintó, Xavier
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.08.2023
• Subjects: Antioxidants; Antioxidants - therapeutic use; Arteriosclerosis; Arthritis; Arthritis, Rheumatoid - complications; Assaying; Atherosclerosis; Atherosclerosis - complications; atherosclerotic plaque; Autoimmune diseases; Cardiovascular diseases; cardiovascular risk factors; Chemotherapy; Cholesterol; Cross-Sectional Studies; Density; Dienes; Drug therapy; Erythrocyte sedimentation rate; Fibrinogen; Glucocorticoids; HDL functionality; Health risks; High density lipoprotein; Humans; Inflammation; Inflammation - complications; lipids; Lipoproteins; Lipoproteins, HDL; Lipoproteins, LDL; Low density lipoprotein; Oxidants; Oxidation; Oxidation resistance; oxidized LDL; Oxidizing agents; Rheumatoid arthritis; Risk factors; HDL functionality; lipids; cardiovascular risk factors; oxidized LDL; atherosclerotic plaque; rheumatoid arthritis
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/eci.13999

Background High‐density lipoprotein (HDL) presents atheroprotective functions not readily reflected by plasma HDL‐cholesterol levels. The aim of this study was to investigate HDL antioxidant function in patients with rheumatoid arthritis (RA). Methods This pilot and cross‐sectional study included 50 RA patients and 50 controls matched by age, gender, cardiovascular risk factors and drug therapy. The antioxidant capacity of HDL was assessed by the total radical‐trapping antioxidative potential test (TRAP‐assay) and the susceptibility of low‐density lipoprotein (LDL) to oxidation by the Conjugated Dienes Assay (Dmax). A carotid ultrasound was performed in all participants to detect subclinical atherosclerosis. Results High‐density lipoprotein from RA patients showed lower antioxidant capacity than those from controls [oxidized‐LDL%: 35.8 (27–42) vs. 24.4 (20–32), p < .001] when analysed with the TRAP‐assay. In addition, the time to achieve 50% of maximal LDL oxidation (Lag‐time) was shorter in RA‐patients than in matched controls [57.2 (42–71) vs. 69.5 (55–75) minutes, (p = .003)]. RA patients showed a higher atherosclerotic burden than controls. The pro‐oxidant pattern in RA was irrespective of the presence of carotid atherosclerosis. On the contrary, there was a positive correlation between inflammatory parameters (erythrocyte sedimentation rate, ultrasensitive C‐reactive protein and fibrinogen) and the loss of HDL‐anti‐oxidant capacity measured by the TRAP‐assay (rho = .211, p = .035; rho = .231, p = .021 and rho = .206, p = .041, respectively). Furthermore, the glucocorticoid dose at recruitment was negatively associated with the Lag‐time in RA patients (rho = −.387, p = .026). Conclusion Rheumatoid arthritis patients present reduced HDL antioxidant capacity and a lower resistance of LDL particles to oxidation, mainly related to the degree of inflammation. Rheumatoid arthritis patients show impaired lipoprotein functionality, specifically a lower HDL antioxidant capacity and lower resistance of LDL particles to oxidation compared to control subjects, mainly related to the degree of inflammation. Another remarkable finding is that female RA patients presented a higher atherogenic burden in the carotid, at younger ages and after a short time of disease evolution. The predisposition of RA patients to develop atherosclerosis may be related to impairment in HDL antioxidant capacity and HDL susceptibility to oxidation.