Methotrexate, blood pressure and markers of arterial function in patients with rheumatoid arthritis: a repeated cross-sectional study

Abstract

Background: 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. Methods: 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, n = 56, age 61 ± 13 years, 70% females) or other DMARDs (non-MTX group, n = 30, age 63 ± 12 years, 76% females). Measurements were performed at baseline and after 8 months. Results: 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, p = 0.006) and DBP (−6.1 mmHg, 95% CI −9.8 to −2.4, p = 0.001) and clinic central SBP (−7.8 mmHg, 95% CI −13.1 to −2.6, p = 0.003) and DBP (−5.4 mmHg, 95% CI −9.1 to −1.6, p = 0.005) versus the non-MTX group. Furthermore, the MTX group had significantly lower 24-hour peripheral and central SBP and DBP and PWV versus the non-MTX group (p < 0.01 for all comparisons). By contrast, there were no significant between-group differences in AIx and ADMA. Conclusions: 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.

Methotrexate and Vasculoprotection: Mechanistic Insights and Potential Therapeutic Applications in Old Age

“…In a study in patients with rheumatoid arthritis, methotrexate treatment did not reduce arterial stiffness [102]. By contrast, in a repeated cross-sectional study of patients with rheumatoid arthritis, methotrexate treatment was independently associated with reduced pulse-wave velocity, a marker of arterial stiffness, measured over 24 hours, after adjusting for age, gender, body mass index, rheumatoid arthritis disease severity and use of folic acid [103].…”

“…Observational cross-sectional and prospective studies in rheumatoid arthritis have also shown that methotrexate use is associated with lower systolic and diastolic blood pressure and reduced incidence of hypertension, when compared to other DMARDs or no treatment [103][104][105][106][107][108]. In one of these studies, the associations between methotrexate treatment and lower blood pressure were also observed for 24-hr measures of peripheral and central blood pressure [103]. Twenty-four-hour averages of systolic and diastolic blood pressure are significantly superior to clinical blood pressure in terms of cardiovascular risk stratification [109].…”

Chronic Heart Failure in Rheumatoid Arthritis Patients (Part III): Effects of Antirheumatic Drugs

“…При использовании метотрексата шанс достижения целевых значений АД был выше на 9%. Также продемонстрирована ассоциация между приемом метотрексата и более низкими значениями скорости пульсовой волны, центрального, систолического и диастолического АД при офисном измерении и суточном мониторировании у больных РА [21].…”

Cardiovascular Safety of Anti-TNF and Non-TNF Biological Therapy in Patients with Rheumatoid Arthritis

“…Furthermore, methotrexate, the drug of choice as first-line treatment, is associated with a consistent reduction in mortality (70%), a decline in the rate of total cardiovascular events (around 28%), and up to 18% lower risk of myocardial infarction in patients with RA [31]. Unlike the anti-TNF agents, methotrexate is not related to a significant decrease in strokes and major adverse cardiac events; nevertheless, it seems that the risk of heart failure is also decreased [1,2,31,32].…”