Department of Systemic Rheumatic Diseases, V.A. Nasonova Research Institute of Rheumatology, Kashirskoe Shosse, 115522 Moscow, Russia.
Chair of Organization and Economy of Pharmacy, Institute of Pharmacy, A.P. Nelyubina, I.M. Sechenov First Moscow State Medical University (Sechenov University), 96k1 Ave. Vernadsky, 119526 Moscow, Russia.
Int J Mol Sci. 2024 Nov 19;25(22):12425. doi: 10.3390/ijms252212425.
In recent years, many atherogenesis researchers have focused on the role of inflammatory cytokines in the development of cardiovascular disease (CVD). Interleukin-6 (IL-6) cytokine is independently associated with higher CVD risk in patients with rheumatoid arthritis (RA). The effect of IL-6 inhibitors on the cardiovascular system in RA patients remains poorly understood, especially with its long-term use. This study investigates the effect of therapy with IL-6 receptor blocker tocilizumab (TCZ) on the dynamics of cardiovascular risk (CVR), modifiable risk factors (RFs), carotid artery (CA) structural changes, and the incidence of cardiovascular complications (CVCs) in RA patients during a 265-week follow-up period. Forty-five patients with active RA (DAS28-ESR 6.2 (5.5;6.8) with ineffectiveness and/or intolerance to disease-modifying antirheumatic drugs (DMARDs) were included in this study. During long-term therapy with TCZ in RA patients, no increase in CVR and no significant structural changes in CA were observed. No significant changes in the blood lipid spectrum were observed in patients without statin therapy. In the group of patients receiving statins, there was a 43% increase in high-density lipoprotein cholesterol (HDL-C), a 15% reduction in total cholesterol levels, and a 56% decrease in the atherogenicity index ( < 0.01 in all cases). Associations were found between ∆ total cholesterol and ∆ C-reactive protein (CRP) (R = 0.36, = 0.04), ∆ low-density lipoprotein cholesterol (LDL-C), and ∆-CRP (R = 0.42, = 0.03) in RA patients receiving statins. Initially, the thickness of the intima-media complex of carotid arteries (cIMT) positively moderately correlated with age (R = 0.7; < 0.01), BMI (R = 0.37; < 0.01), and systolic blood pressure (R = 0.64; < 0.01); however, it weakly correlated with the lipid spectrum parameters: total cholesterol (R = 0.29; < 0.01) and LDL-C (R = 0.33; < 0.01). No new associations of cIMT by the end of the follow-up period, as well as the relationship of cIMT value with RA activity and therapy, were revealed. Patients with carotid ASPs showed an oppositely directed relationship between total cholesterol and sVCAM-1 at baseline (R = -0.25, = 0.01) and at the end of this study (R = 0.29, < 0.01). The incidence of cardiovascular events was 0.53 per 100 patient-years during the 265-week period of TCZ therapy.
近年来，许多动脉粥样硬化发生机制的研究人员都聚焦于炎症细胞因子在心血管疾病（CVD）发展中的作用。白细胞介素 6（IL-6）细胞因子与类风湿关节炎（RA）患者更高的 CVD 风险独立相关。IL-6 抑制剂对 RA 患者心血管系统的影响仍知之甚少，尤其是在长期使用的情况下。本研究旨在探讨白细胞介素 6 受体阻滞剂托珠单抗（TCZ）治疗对 RA 患者心血管风险（CVR）、可改变的危险因素（RFs）、颈动脉（CA）结构变化以及心血管并发症（CVCs）发生率的影响，共对 45 例接受 TCZ 治疗 265 周的活动性 RA 患者进行了随访。在这项研究中，患者的疾病活动度用 DAS28-ESR 评估（6.2（5.5；6.8），且对疾病修正抗风湿药物（DMARDs）治疗无效和/或不耐受）。在 RA 患者的长期 TCZ 治疗期间，未观察到 CVR 增加，也未观察到 CA 结构的显著变化。未接受他汀类药物治疗的患者血脂谱无明显变化。在接受他汀类药物治疗的患者中，高密度脂蛋白胆固醇（HDL-C）增加 43%，总胆固醇水平降低 15%，致动脉粥样硬化指数降低 56%（所有情况均 < 0.01）。在接受他汀类药物治疗的 RA 患者中，总胆固醇（CRP）（R = 0.36， = 0.04）和 LDL-C（CRP）（R = 0.42， = 0.03）的变化与 CRP 的变化呈正相关。在接受他汀类药物治疗的 RA 患者中，颈动脉内-中膜厚度（cIMT）的初始厚度与年龄（R = 0.7； < 0.01）、BMI（R = 0.37； < 0.01）和收缩压（R = 0.64； < 0.01）呈中度正相关；然而，cIMT 与血脂谱参数呈弱相关：总胆固醇（R = 0.29； < 0.01）和 LDL-C（R = 0.33； < 0.01）。在随访结束时，cIMT 没有新的相关性，cIMT 值与 RA 活动度和治疗的关系也没有揭示。颈动脉有粥样斑块的患者在基线时（R = -0.25， = 0.01）和研究结束时（R = 0.29， < 0.01）总胆固醇和 sVCAM-1 之间呈反向关系。在接受 TCZ 治疗的 265 周期间，心血管事件的发生率为 0.53/100 患者-年。
