Background There is increasing evidence that oxidatively modified form of low-density lipoprotein cholesterol (LDL) is more important than native LDL in atherogenesis and vascular damage. The accelerated development of atherosclerosis has been recognized in patients with autoimmune rheumatic diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Recent studies reported about the oxidation ratio of LDL that can be more significant in the premature development of coronary artery disease.
Objectives To estimate the oxidated forms of LDL and their involvement in atherosclerotic lesions of the vessel wall in female-patients with autoimmune rheumatic diseases (ARD).
Methods The study included 77 female-patients with ARD (RA (n=37), mean age 45,0 (33,0; 51,0) years old, disease duration 9,0 (3,0; 14,0) years, disease activity (DAS28=5,37 (4,69; 5,86) points) and SLE (n=40), mean age 33,5 (27,5; 44,5) years old, disease duration 8,0 (5,0; 14,5) years, disease activity SLEDAI-2K 7,0 (4,0; 11,5) points). Twenty-two women with the history of myocardial infarction (MI) (i.e. clinical manifestation of atherosclerosis) formed the control group.
The levels of OxLDL, high sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor - α (TNF-α) were determined with ELISA according to the instruction of manufacturer. The oxidation ratio of LDL (Ox-LDL/TC, Ox-LDL/HDL-C, Ox-LDL/LDL-C) was calculated. The presence of carotid atherosclerotic alterations (intima-media thickness and the presence of atherosclerotic plaques) was revealed ultrasonographically according to the described ESH/ESC Guidelines for the management of arterial hypertension.
Results The levels of OxLDL, hs-CRP, IL-6, TNF-α, Ox-LDL/HDL-C were significantly higher in ARD patients than in the control group, what may indicate the disease activity. The presence of subclinical atherosclerosis was observed in 54,55% patients with ARD. When we compared the values of investigated parameters in patients with subclinical and clinical atherosclerosis, we revealed that only inflammatory markers (hs-CRP, IL-6, TNF-α) were significantly higher in ARD patients with atherosclerosis. However those without atherosclerosis had significantly higher values of OxLDL, hs-CRP, IL-6, Ox-LDL/TC, Ox-LDL/HDL-C, Ox-LDL/LDL-C than the control group. The positive association between hs-CRP, IL-6 and oxidation ratio Ox-LDL/TC was found in patients with subclinical atherosclerosis (p=0,0003 and p=0,007, respectively), between TNF-α and Ox-LDL/LDL-C in patients without atherosclerosis (p=0,002). The negative association between TNF-α and Ox-LDL/TC was found in patients with MI that can explain because of the lower levels of OxLDL in this group of patient considering that statins can inhibit oxidative stress.
Conclusions More than half of patients with ARD had subclinical atherosclerosis. We demonstrated the elevated levels of OxLDL and inflammatory markers (hs-CRP, IL-6, TNF-α) in patients with ARD. The presence of OxLDL, especially when used in combination with TC, is better than only OxLDL for estimation of association with inflammation in patients with clinical and subclinical atherosclerosis. Thus we suggest that inflammation can influence to oxidative modification of LDL in patients with RA and SLE and during this process induce endothelial dysfunction and early development of atherosclerosis as its result.
Disclosure of Interest None declared