Cardiovascular events are not associated with MTHFR polymorphisms, but are associated with methotrexate use and traditional risk factors in US veterans with rheumatoid arthritis

Lisa A. Davis, Grant W. Cannon, Lauren F. Pointer, Leah M. Haverhals, Roger K. Wolff, Ted R. Mikuls, Andreas M. Reimold, Gail S. Kerr, J. Steuart Richards, Dannette S. Johnson, Robert Valuck, Allan Prochazka, Liron Caplan

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Objective. C677T and A1298C polymorphisms in the enzyme methylenetetrahydrofolate reductase (MTHFR) have been associated with increased cardiovascular (CV) events in non-rheumatoid arthritis (RA) populations. We investigated potential associations of MTHFR polymorphisms and use of methotrexate (MTX) with time-to-CV event in data from the Veterans Affairs Rheumatoid Arthritis (VARA) registry. Methods. VARA participants were genotyped for MTHFR polymorphisms. Variables included demographic information, baseline comorbidities, RA duration, autoantibody status, and disease activity. Patients' comorbidities and outcome variables were defined using International Classification of Diseases-9 and Current Procedural Terminology codes. The combined CV event outcome included myocardial infarction (MI), percutaneous coronary intervention, coronary artery bypass graft surgery, and stroke. Cox proportional hazards regression was used to model the time-to-CV event. Results. Data were available for 1047 subjects. Post-enrollment CV events occurred in 97 patients (9.26%). Although there was a trend toward reduced risk of CV events, MTHFR polymorphisms were not significantly associated with time-to-CV event. Time-to-CV event was associated with prior stroke (HR 2.01, 95% CI 1.03-3.90), prior MI (HR 1.70, 95% CI 1.06-2.71), hyperlipidemia (HR 1.57, 95% CI 1.01-2.43), and increased modified Charlson-Deyo index (HR 1.23, 95% CI 1.13-1.34). MTX use (HR 0.66, 95% CI 0.44-0.99) and increasing education (HR 0.87, 95% CI 0.80-0.95) were associated with a lower risk for CV events. Conclusion. Although MTHFR polymorphisms were previously associated with CV events in non-RA populations, we found only a trend toward decreased association with CV events in RA. Traditional risk factors conferred substantial CV risk, while MTX use and increasing years of education were protective.

Original languageEnglish (US)
Pages (from-to)809-817
Number of pages9
JournalJournal of Rheumatology
Volume40
Issue number6
DOIs
StatePublished - Jun 1 2013

Keywords

  • Cardiovascular Diseases
  • Methotrexate
  • Methylenetetrahydrofolate Reductase
  • Rheumatoid Arthritis
  • Single-Nucleotide Polymorphism

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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    Davis, L. A., Cannon, G. W., Pointer, L. F., Haverhals, L. M., Wolff, R. K., Mikuls, T. R., Reimold, A. M., Kerr, G. S., Richards, J. S., Johnson, D. S., Valuck, R., Prochazka, A., & Caplan, L. (2013). Cardiovascular events are not associated with MTHFR polymorphisms, but are associated with methotrexate use and traditional risk factors in US veterans with rheumatoid arthritis. Journal of Rheumatology, 40(6), 809-817. https://doi.org/10.3899/jrheum.121012