Bergström Ulf, Jovinge Stefan, Persson Jerker, Jacobsson Lennart T H, Turesson Carl
Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden.
Department of Rheumatology, Skåne University Hospital, Malmö, Sweden.
Curr Ther Res Clin Exp. 2018 Jul 23;89:1-6. doi: 10.1016/j.curtheres.2018.07.001. eCollection 2018.
Treatment with tumor necrosis factor inhibitors for rheumatoid arthritis has been associated with a decreased risk of cardiovascular disease in observational studies. There are conflicting data on the influence of tumor necrosis factor inhibitors on lipid levels.
To evaluate the effect of treatment with adalimumab on blood lipid levels, lipoproteins, and atherosclerosis of the carotid artery.
Fourteen patients with active rheumatoid arthritis (11 women and 3 men; mean age 63.7 years; median disease duration 9.0 years; and 78% rheumatoid factor positive) were treated with adalimumab 40 mg subcutaneously every 2 weeks and followed for 3 months. The patients had not been treated with adalimumab previously and had not received other tumor necrosis factor inhibitors within the past 3 months or moderate/high dose corticosteroids within the past 2 weeks. The intima-media thickness of the common carotid artery was assessed using B mode ultrasonography. Triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol levels were analyzed in fresh fasting blood samples, whereas apolipoprotein B and apolipoprotein A1 (apoA1) levels were determined in thawed plasma samples using standard turbidimetric immunoassays.
Total cholesterol (mean = 5.36 vs 5.96 mmol/L; = 0.005), LDL cholesterol (mean = 3.33 vs 3.77 mmol/L; = .005), HDL cholesterol (mean = 1.43 vs 1.55 mmol/L; = 0.048), apolipoprotein B (mean = 1.04 vs 1.13 g/L; = .012), and apoA1 (mean = 1.42 vs 1.58 g/L; = 0.005) all increased, but there were no major changes in the LDL to HDL cholesterol ratio (median = 2.56 vs 2.35; = 0.27) or the apolipoprotein B to apoA1 ratio (mean = 0.76 vs 0.74; = 0.46). There was no change in triglyceride levels ( = 0.55). Disease activity decreased significantly from baseline to the 3-month evaluation (disease activity score based on 28 joints mean = 5.6 vs 4.1; = 0.007). An increase in apoA1 correlated with decreases in the patient global assessment of disease severity ( = 0.79; = 0.001) and C-reactive protein level ( = 0.74; = 0.003). Changes in the apoliprotein B to apoA1 ratio correlated with changes in erythrocyte sedimentation rate ( = 0.54; = 0.046). There was no major change in the common carotid artery intima-media thickness (mean = 0.78 vs 0.80 mm; = 0.48).
Although these results suggest that control of inflammation could have a beneficial effect on the lipid profile through an increase in HDL cholesterol levels, the observed protective effect on cardiovascular disease events by tumor necrosis factor blockers is likely to be explained by other mechanisms than changes in lipid levels or short-term effects on atherosclerosis of the carotid artery.
在观察性研究中，使用肿瘤坏死因子抑制剂治疗类风湿关节炎与心血管疾病风险降低相关。关于肿瘤坏死因子抑制剂对血脂水平的影响，存在相互矛盾的数据。
评估阿达木单抗治疗对血脂水平、脂蛋白及颈动脉粥样硬化的影响。
14例活动期类风湿关节炎患者（11例女性，3例男性；平均年龄63.7岁；疾病中位病程9.0年；78%类风湿因子阳性），每2周皮下注射40mg阿达木单抗，随访3个月。患者此前未接受过阿达木单抗治疗，且在过去3个月内未使用过其他肿瘤坏死因子抑制剂，过去2周内未使用过中/高剂量皮质类固醇。使用B型超声评估颈总动脉内膜中层厚度。在新鲜空腹血样中分析甘油三酯、总胆固醇、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇水平，而载脂蛋白B和载脂蛋白A1（apoA1）水平则在解冻的血浆样本中使用标准比浊免疫测定法测定。
总胆固醇（均值=5.36 vs 5.96 mmol/L；P=0.005）、低密度脂蛋白胆固醇（均值=3.33 vs 3.77 mmol/L；P=0.005）、高密度脂蛋白胆固醇（均值=1.43 vs 1.55 mmol/L；P=0.048）、载脂蛋白B（均值=1.04 vs 1.13 g/L；P=0.012）和apoA1（均值=1.42 vs 1.58 g/L；P=0.005）均升高，但低密度脂蛋白与高密度脂蛋白胆固醇比值（中位数=2.56 vs 2.35；P=0.27）或载脂蛋白B与apoA1比值（均值=0.76 vs 0.74；P=0.46）无重大变化。甘油三酯水平无变化（P=0.55）。从基线到3个月评估时疾病活动度显著降低（基于28个关节的疾病活动评分均值=5.6 vs 4.1；P=0.007）。apoA1升高与患者对疾病严重程度的整体评估降低相关（r=0.79；P=0.001）以及C反应蛋白水平降低相关（r=0.74；P=0.003）。载脂蛋白B与apoA1比值的变化与红细胞沉降率的变化相关（r=0.54；P=0.046）。颈总动脉内膜中层厚度无重大变化（均值=0.78 vs 0.80 mm；P=0.48）。
尽管这些结果表明炎症控制可能通过升高高密度脂蛋白胆固醇水平对血脂谱产生有益影响，但观察到的肿瘤坏死因子阻滞剂对心血管疾病事件的保护作用可能由血脂水平变化以外的其他机制或对颈动脉粥样硬化的短期影响来解释。
