Background/Purpose: High plasma homocysteine is an independent risk factor for arterial ischemic events. The objective of this study is to evaluate plasma homocysteine levels in patients with Takayasu arteritis (TA) and in controls, and to analyze the association between homocysteine levels and paraoxonase 1 (PON1) activity, methotrexate and folate use, disease activity, extension of arterial involvement and with ischemic arterial events in TA.

Methods: A cross-sectional study was performed with 29 TA patients and 30 control subjects. Plasma homocysteine levels were determined by high performance liquid chromatography using fluorimetric detection and isocratic elution. PON1 activity was evaluated by spectrophotometry using paraoxon as substrate with 1M sodium chloride. Disease activity was ascertained by the National Institutes of Healthy criteria and the extension of arterial involvement by the angiographic classification of the International TA conference in Tokyo 1994.

Results: Active disease was observed in 9 (31.0%) and previous arterial ischemic events in 10 (34.5%) TA patients. Nine (31.0%) TA patients were on methotrexate therapy with a mean dose of 20.5 ± 3.9 mg/week and it was associated to folic acid in 8 cases. Median homocysteine levels were significantly higher in TA patients in comparison to control subjects [10.9 (8.5-24.7) vs. 6.9 µmol/L (2.8-15.1); P < 0.001]. TA patients with active disease presented lower homocysteine (10.4 ± 2.1 vs. 13.1 ± 4.2 µmol/L; P = 0.034) when compared to patients in remission. Median homocysteine levels were higher in patients with previous ischemic events [13.2 (9.6-24.4) vs. 9.8 (8.5-17.9) µmol/L; P = 0.027]. In a multivariate model that included age, disease duration and homocysteine levels, age (OR: 1.13; 95% CI: 1.01-1.25; P = 0.022) and 1 µmol/L increase in homocysteine plasma levels (OR: 1.31; 95% CI: 1.01-1.71; P = 0.041) were independently associated with ischemic events in TA. Mean homocysteine levels were similar in TA patients on methotrexate and in those being treated with other immunosuppressive agents (12.8 ± 5.3 vs. 12.1 ± 3.2 µmol/L; P = 0.662) and regarding the extension of arterial involvement, no differences in homocysteine levels were found in TA patients with angiographic type V in comparison to other angiographic types (12.7 ± 4.2 vs. 11.0 ± 2.6 µmol/L; P = 0.342). No differences in PON1 activity were found in TA patients with active disease in than those in remission (386.7 ± 251.2 vs. 323.7 ± 264.1 U/mL; P = 0.552) and between TA patients with and without previous ischemic events (411.4 ± 232.3 vs. 307.4 ± 268.6 U/mL; P = 0.310). No correlation was found between plasma homocysteine and PON1 activity (ρ = 0.214; P = 0.265).

Conclusion: Patients with TA presented higher homocysteine levels than control subjects and homocysteine levels were independently associated with acute arterial ischemic events in TA. Higher homocysteine levels were not observed in TA patients with active disease or with extensive vascular involvement and folate use associated to methotrexate seemed to prevent higher homocysteine levels in TA. No associations were found between PON1 activity with homocysteine levels, active disease or ischemic events.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/higher-homocysteine-levels-are-associated-with-ischemic-arterial-events-rather-than-disease-activity-and-the-extension-of-arterial-involvement-in-takayasu-arteritis/