Dataset Information

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

ABSTRACT: 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.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.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.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.

SUBMITTER: Davis LA

PROVIDER: S-EPMC4097095 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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

Davis Lisa A LA Cannon Grant W GW Pointer Lauren F LF Haverhals Leah M LM Wolff Roger K RK Mikuls Ted R TR Reimold Andreas M AM Kerr Gail S GS Richards J Steuart JS Johnson Dannette S DS Valuck Robert R Prochazka Allan A Caplan Liron L

The Journal of rheumatology 20130401 6

<h4>Objective</h4>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.<h4>Methods</h4>VARA participants were genotyped for MTHFR polymorphisms. Variables included demogr ...[more]

PMID: 23547211

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Project description:BackgroundCardiovascular disease (CVD) is the leading cause of death in rheumatoid arthritis (RA) patients. This study is the first to report the association of hydroxychloroquine (an antirheumatic medication that has been associated with decreased risk of diabetes, a less atherogenic lipid profile, and antithrombotic properties) with CVD in RA.Methods and resultsA retrospective incident RA cohort from January 1, 2001, to October 31, 2013, excluding patients with CVD prior to RA diagnosis, was constructed. Patients were categorized as hydroxychloroquine users versus nonusers and were allowed to contribute time to either group according to hydroxychloroquine exposure. The primary outcome was adjudicated incident CVD defined as a composite of coronary artery disease, stroke, transient ischemic attack, sudden cardiac death, and peripheral artery disease with arterial revascularization procedure. The secondary outcome was a composite of incident coronary artery disease, stroke, and transient ischemic attack. Cox time-varying regression models were used to estimate the association between hydroxychloroquine exposure and development of CVD, after adjusting for propensity score and relevant confounders, including demographics, CVD-related comorbidities, RA severity, and activity indicators and medications. We included 1266 RA patients, 547 hydroxychloroquine users, and 719 nonusers. During the observation period, 102 CVD events occurred, 3 in hydroxychloroquine users and 99 in nonusers. The fully adjusted Cox model showed a hazard ratio of 0.28 (95% CI 0.12-0.63, P=0.002) for incident CVD and 0.30 (95% CI 0.13-0.68, P=0.004) for incident composite coronary artery disease, stroke, and transient ischemic attack for hydroxychloroquine users versus nonusers, respectively.ConclusionIn this hypothesis-generating study, hydroxychloroquine use was associated with a 72% decrease in the risk of incident CVD in RA patients. If these preliminary results are confirmed in larger studies, our findings may be used as a rationale for a randomized study of hydroxychloroquine use for primary prevention of CVD in RA or nonrheumatic high-risk patients.

Dataset Information

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

Publications

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

Similar Datasets

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