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抗TNF-α治疗对活动期类风湿关节炎患者血脂谱的影响。

Effects of anti-TNF-alpha treatment on lipid profile in patients with active rheumatoid arthritis.

作者信息

Seriolo Bruno, Paolino Sabrina, Sulli Alberto, Fasciolo Daniela, Cutolo Maurizio

机构信息

Division of Rheumatology, Department of Internal Medicine and Medical Specialities, University of Genova, Genova, Italy.

出版信息

Ann N Y Acad Sci. 2006 Jun;1069:414-9. doi: 10.1196/annals.1351.039.

Abstract

UNLABELLED

Cardiovascular morbidity and mortality appear to be increased in rheumatoid arthritis (RA), which might be due to increased prevalence of risk factors for cardiovascular disease, such as an accelerated progression of atherosclerosis. Patients with active RA frequently show an atherogenic lipid profile, which has been linked with the inflammatory reaction. Tumor necrosis factor-alpha (TNF-alpha), a pivotal proinflammatory cytokine implicated in the pathogenesis of atherosclerosis in RA, may be involved in the development of the altered lipid profile observed in active RA. Our aim was to investigate the effects of anti-TNF-alpha treatment in combination with methotrexate (MTX) and corticosteroid therapy on lipid profile in patients with active RA. In this prospective study 34 consecutive RA patients were included (all women, mean age 51.6 +/- 7.9 years, range 46-72 years) with active (defined as Disease Activity Index 28 joint score [DAS-28], of at least 3.2) and refractory RA, in stable treatment with MTX (7.5-10 mg/week) and prednisone (7.5-10 mg/day) for 3 months. All patients received TNF-alpha blockers (n = 16, etanercept 25 mg twice weekly; n = 14, infliximab 3 mg/kg on 0, 2, 6, and every 8 weeks thereafter; and finally, n = 4, adalimumab 40 mg every other week). Total cholesterol, high-density lipoprotein cholesterol (HDL cholesterol), triglycerides (TG) and lipoprotein (a) [Lp(a)] levels and the atherogenic index (ratio cholesterol/HDL cholesterol) were measured at base line, and at 16 and 24 weeks. Results were as follows: The DAS-28 was 6.9 +/- 2.1 at base line and decreased to 4.6 +/- 1.8 after 16 weeks, and further to 4.1 +/- 1.3 after 24 weeks (both, P < 0.01). Following anti-TNF-alpha treatment, the mean levels of total cholesterol were 168 +/- 24 mg/dL at base line and increased to 188 +/- 28 mg/dL at 16 weeks (P < 0.01), and 197 +/- 26 mg/dL at 24 weeks (P < 0.001). However, also the mean levels of HDL cholesterol were significantly higher than basal values after 16 and 24 weeks of treatment (34 +/- 12 mg/dL versus 36 +/- 18 mg/dL [P < 0.05] and 38 +/- 14 mg/dL [P < 0.01], respectively). TG and Lp(a) levels, as well as the atherogenic index were not significantly changed. Interestingly, variations in disease activity were significantly and inversely correlated with HDL cholesterol levels.

IN CONCLUSION

Short anti-TNF-alpha treatment was associated with a significant increase of both total cholesterol and HDL cholesterol levels, and correlated with decreased disease activity. The atherogenic index showed no changes during the study. Therefore, anti-TNF-alpha treatment might affect lipid profile in RA patients.

摘要

未标注

类风湿关节炎(RA)患者的心血管发病率和死亡率似乎有所增加,这可能是由于心血管疾病危险因素的患病率增加,如动脉粥样硬化加速进展。活动期RA患者常表现出致动脉粥样硬化的血脂谱,这与炎症反应有关。肿瘤坏死因子-α(TNF-α)是RA动脉粥样硬化发病机制中的关键促炎细胞因子,可能参与了活动期RA患者血脂谱改变的发生。我们的目的是研究抗TNF-α治疗联合甲氨蝶呤(MTX)和皮质类固醇疗法对活动期RA患者血脂谱的影响。在这项前瞻性研究中,纳入了34例连续的RA患者(均为女性,平均年龄51.6±7.9岁,范围46 - 72岁),患有活动期(定义为疾病活动指数28关节评分[DAS - 28]至少为3.2)和难治性RA,接受MTX(7.5 - 10mg/周)和泼尼松(7.5 - 10mg/天)稳定治疗3个月。所有患者接受TNF-α阻滞剂治疗(16例,依那西普25mg每周两次;14例,英夫利昔单抗3mg/kg在第0、2、6周及此后每8周一次;最后4例,阿达木单抗40mg每隔一周一次)。在基线、16周和24周时测量总胆固醇、高密度脂蛋白胆固醇(HDL胆固醇)、甘油三酯(TG)和脂蛋白(a)[Lp(a)]水平以及动脉粥样硬化指数(胆固醇/HDL胆固醇比值)。结果如下:基线时DAS - 28为6.9±2.1,16周后降至4.6±1.8,24周后进一步降至4.1±1.3(均P < 0.01)。抗TNF-α治疗后,总胆固醇平均水平在基线时为168±24mg/dL,16周时升至188±28mg/dL(P < 0.01),24周时为197±26mg/dL(P < 0.001)。然而,治疗16周和24周后HDL胆固醇平均水平也显著高于基线值(分别为34±12mg/dL对36±18mg/dL[P < 0.05]和38±14mg/dL[P < 0.01])。TG和Lp(a)水平以及动脉粥样硬化指数无显著变化。有趣的是,疾病活动度的变化与HDL胆固醇水平显著负相关。

结论

短期抗TNF-α治疗与总胆固醇和HDL胆固醇水平显著升高相关,并与疾病活动度降低相关。研究期间动脉粥样硬化指数无变化。因此,抗TNF-α治疗可能影响RA患者的血脂谱。

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