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Variation of homocysteine levels in rheumatoid arthritis patients: relationship to inflammation, cardiovascular risk factors, and methotrexate

Unterschiede der Homocysteinwerte bei Patienten mit rheumatoider Arthritis: Zusammenhang mit Entzündung, kardiovaskulären Risikofaktoren und Methotrexat

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Abstract

Background

The aim of this study was to evaluate the variation of homocysteine (Hcy) levels in patients with rheumatoid arthritis (RA) and to analyze the relationship to inflammatory parameters, cardiovascular risk, and methotrexate (MTX).

Methods

This cross-sectional study assessed disease activity and treatment in RA patients. The European League Against Rheumatism (EULAR) 2015 HeartSCORE was performed for cardiovascular (CV) risk estimation and levels of plasma Hcy, serum folate concentrations, vitamin B12, and erythrocyte sedimentation rate (ESR) were measured.

Results

A total of 103 participants with mean age 53 ± 10 years and mean disease duration 10.55 ± 7.34 years were included. Patients were treated with MTX in 69.9% of cases and corticosteroid in 80.5% of cases. Of all patients, 13% had a cardiovascular inheritance, 25% were hypertensive, and 18% had diabetes. The EULAR 2015 HeartSCORE was high and very high (≥5%) in 35% of cases. Mean Hcy level was 12.54 ± 4.2 µmol/L [6.89–32.92] and hyperhomocysteinemia was noted in 20.4% of patients. Analytic study demonstrated that hyperhomocysteinemia was associated with male gender (p = 0.01), MTX use (p = 0.01), smoking (p = 0.008), renal failure (p = 0.04), and high disease activity (p = 0.05), but there was no association with the HeartSCORE (p = 0.23). Hcy level was negatively correlated with folate (p = 0.009) and vitamin B12 level (p = 0.02) and positively with age (p = 0.01), C‑reactive protein (CRP; p = 0.05), and Simplified Disease Activity Index (SDAI; p = 0.03). In multivariate logistic regression analysis, current MTX use, levels of vitamin B12 and creatine, and Clinical Disease Activity Index (CDAI) appeared to be independent factors associated with hyperhomocysteinemia.

Conclusion

MTX use, CDAI, and the levels of vitamin B12 and creatine are independent factors associated with hyperhomocysteinemia.

Zusammenfassung

Hintergrund

Ziel der vorliegenden Studie war es, Unterschiede in den Werten für Homocystein (Hcy) bei Patienten mit rheumatoider Arthritis (RA) und den Zusammenhang mit Entzündungsparametern, Herz-Kreislauf-Risiko und Methotrexat (MTX) zu untersuchen.

Methoden

In dieser Querschnittstudie wurden Krankheitsaktivität und Therapie von RA-Patienten analysiert. Zur Abschätzung des kardiovaskulären Risikos wurde The European League Against Rheumatism (EULAR) 2015 HeartSCORE eingesetzt und die Werte für Plasma-Hcy, Folsäurekonzentration im Serum, Vitamin B12 und Blutsenkungsgeschwindigkeit (BSG) bestimmt.

Ergebnisse

Es wurden 103 Teilnehmer mit einem mittleren Alter von 53 ± 10 Jahren und einer mittleren Krankheitsdauer von 10,55 ± 7,34 Jahren in die Studie einbezogen. In 69,9% der Fälle wurden die Patienten mit MTX und in 80,5% mit Kortikosteroiden behandelt. Bei 13% der Patienten bestanden familiär kardiovaskuläre Erkrankungen, bei 25% Hypertonie und bei 18% Diabetes mellitus. In 35% der Fälle war der EULAR 2015 HeartSCORE hoch oder sehr hoch (>5%). Im Mittel betrug der Hcy-Wert 12,54 ± 4,2 µmol/l [6,89–32,92], und eine Hyperhomocysteinämie lag bei 20,4% der Patienten vor. Die Auswertung ergab, dass eine Hyperhomocysteinämie mit männlichem Geschlecht (p = 0,01), MTX-Therapie (p = 0,01), Rauchen (p = 0,008), Niereninsuffizienz (p = 0,04) und hoher Krankheitsaktivität (p = 0,05) assoziiert war, aber es gab keinen Zusammenhang mit dem HeartSCORE (p = 0,23). Der Hcy-Wert war negativ mit den Werten für Folsäure (p = 0,009) und Vitamin B12 (p = 0,02) korreliert und positiv mit dem Alter (p = 0,01), C‑reaktivem Protein (CRP; p = 0,05) und dem Simplified Disease Activity Index (SDAI; p = 0,03). In der multivariaten logistischen Regressionsanalyse schienen eine derzeitige MTX-Therapie, Werte für Vitamin B12 und Kreatin sowie der Clinical Disease Activity Index (CDAI) unabhängige Faktoren zu sein, die mit Hyperhomocysteinämie assoziiert waren.

Schlussfolgerung

MTX-Therapie, CDAI und die Werte für Vitamin B12 und Kreatin sind unabhängige, mit Hyperhomocysteinämie assoziierte Faktoren.

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Acknowledgements

We thank the departments of rheumatology and cardiology for assistance, access to patients, and for comments that greatly improved the manuscript. We would also like to show our gratitude to the department of biochemistry for facilitating the blood collection and fast results during this research

Funding

No specific funding was received to carry out the work described in this article from any bodies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Medicine University Tunis EL Manar, Tunis, Tunisia

    Rawdha Tekaya, Leila Rouached MD, Habib Ben Ahmed, Aicha Ben Tekaya, Selma Bouden, Olfa Saidane, Kahena Bouzid, Ines Mahmoud & Leila Abdelmoula

  2. Department of rheumatology, Charles Nicolle Hospital, Tunis, Tunisia

    Rawdha Tekaya, Leila Rouached MD, Aicha Ben Tekaya, Selma Bouden, Olfa Saidane, Ines Mahmoud & Leila Abdelmoula

  3. Department of biochemistry, Charles Nicolle Hospital, Tunis, Tunisia

    Kahena Bouzid

  4. Department of cardiology, Charles Nicolle Hospital, Tunis, Tunisia

    Habib Ben Ahmed

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  1. Rawdha Tekaya
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  2. Leila Rouached MD
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Correspondence to Leila Rouached MD.

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Conflict of interest

R. Tekaya, L. Rouached, H. Ben Ahmed, A. Ben Tekaya, S. Bouden, O. Saidane, K. Bouzid, I. Mahmoud, and L. Abdelmoula declare that they have no competing interests.

This study complies with the Declaration of Helsinki. The locally appointed ethics committee of Charles Nicolle Hospital approved the research protocol and the study, and informed consent was obtained from the subjects (in French).

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Ulf Müller-Ladner, Bad Nauheim

Uwe Lange, Bad Nauheim

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Tekaya, R., Rouached, L., Ben Ahmed, H. et al. Variation of homocysteine levels in rheumatoid arthritis patients: relationship to inflammation, cardiovascular risk factors, and methotrexate. Z Rheumatol 82 (Suppl 1), 38–43 (2023). https://doi.org/10.1007/s00393-021-01092-2

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