Mangoni Arduino A, Baghdadi Leena R, Shanahan E Michael, Wiese Michael D, Tommasi Sara, Elliot David, Woodman Richard J
Department of Clinical Pharmacology, School of Medicine, Flinders University and Flinders Medical Centre, Bedford Park, SA 5042, Australia.
Department of Clinical Pharmacology, School of Medicine, Flinders University and Flinders Medical Centre, Adelaide, Australia.
Ther Adv Musculoskelet Dis. 2017 Sep;9(9):213-229. doi: 10.1177/1759720X17719850. Epub 2017 Aug 1.
Methotrexate (MTX) treatment in rheumatoid arthritis (RA) has been associated with lower cardiovascular risk compared to other disease-modifying antirheumatic drugs (DMARDs). We sought to identify whether the MTX-associated cardioprotection involves changes in blood pressure (BP) and/or arterial function.
Clinic and 24-hour peripheral and central systolic and diastolic BP (SBP and DBP), augmentation index (AIx), pulse wave velocity (PWV) and plasma asymmetric dimethylarginine (ADMA) were assessed in RA patients on stable treatment with either MTX ± other DMARDs (MTX group, = 56, age 61 ± 13 years, 70% females) or other DMARDs (non-MTX group, = 30, age 63 ± 12 years, 76% females). Measurements were performed at baseline and after 8 months.
After adjusting for visit, age, gender, body mass index, folic acid use and 28-joint disease activity score, the MTX group had significantly lower clinic peripheral SBP (-7.7 mmHg, 95% CI -13.2 to -2.3, = 0.006) and DBP (-6.1 mmHg, 95% CI -9.8 to -2.4, = 0.001) and clinic central SBP (-7.8 mmHg, 95% CI -13.1 to -2.6, = 0.003) and DBP (-5.4 mmHg, 95% CI -9.1 to -1.6, = 0.005) the non-MTX group. Furthermore, the MTX group had significantly lower 24-hour peripheral and central SBP and DBP and PWV the non-MTX group ( < 0.01 for all comparisons). By contrast, there were no significant between-group differences in AIx and ADMA.
RA patients on MTX treatment had significantly lower clinic and 24-hour peripheral and central BP compared to those who did not take MTX. The lower BP with MTX may be related to differences in PWV, but not in AIx or ADMA concentrations. Further longitudinal studies including randomized controlled trials are warranted to confirm these findings, to identify other possible mechanisms responsible for the effects of MTX on BP and PWV, and to establish whether these effects might account for the reduced cardiovascular risk with MTX.
与其他改善病情抗风湿药物（DMARDs）相比，类风湿关节炎（RA）患者使用甲氨蝶呤（MTX）治疗与较低的心血管风险相关。我们试图确定MTX相关的心脏保护作用是否涉及血压（BP）和/或动脉功能的变化。
对稳定接受MTX±其他DMARDs治疗的RA患者（MTX组，n = 56，年龄61±13岁，70%为女性）或其他DMARDs治疗的患者（非MTX组，n = 30，年龄63±12岁，76%为女性）进行临床及24小时外周和中心收缩压及舒张压（SBP和DBP）、增强指数（AIx）、脉搏波速度（PWV）和血浆不对称二甲基精氨酸（ADMA）评估。在基线和8个月后进行测量。
在对就诊、年龄、性别、体重指数、叶酸使用情况和28关节疾病活动评分进行校正后，MTX组的临床外周SBP（-7.7 mmHg，95%CI -13.2至-2.3，P = 0.006）和DBP（-6.1 mmHg，95%CI -9.8至-2.4，P = 0.001）以及临床中心SBP（-7.8 mmHg，95%CI -13.1至-2.6，P = 0.003）和DBP（-5.4 mmHg，95%CI -9.1至-1.6，P = 0.005）均显著低于非MTX组。此外，MTX组的24小时外周和中心SBP、DBP和PWV均显著低于非MTX组（所有比较P < 0.01）。相比之下，AIx和ADMA在组间无显著差异。
与未服用MTX的患者相比，接受MTX治疗的RA患者的临床及24小时外周和中心血压显著更低。MTX导致的较低血压可能与PWV的差异有关，而与AIx或ADMA浓度无关。需要进一步的纵向研究，包括随机对照试验，以证实这些发现，确定MTX对血压和PWV影响的其他可能机制，并确定这些影响是否可能解释MTX降低的心血管风险。
