Severe atherosclerosis in rheumatoid arthritis and hyperhomocysteinemia: is there a link?

Area of Science:

• Cardiology
• Rheumatology
• Genetics

Background:

• Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular morbidity and mortality.
• Accelerated atheroma is a major complication of RA, with hyperhomocysteinemia implicated as a contributing factor.
• Elevated homocysteine levels are a known risk factor for both arterial and venous diseases.

Observation:

• A 46-year-old female patient with RA presented with severe arterial and venous disease.
• She lacked conventional cardiovascular risk factors and rheumatoid vasculitis but had elevated serum homocysteine (20.9 micromol/L).
• Genetic analysis revealed a homozygous C667T mutation in the methylenetetrahydrofolate (MTHFR) gene, alongside a positive circulating anticoagulant.

Findings:

• Hyperhomocysteinemia, defined as homocysteine >15 micromol/L, is prevalent in 20%-42% of RA patients.
• Common causes of hyperhomocysteinemia in RA include methotrexate therapy, MTHFR gene mutations, vitamin B12 deficiency, renal failure, and smoking.
• This patient's elevated homocysteine was linked to MTHFR gene mutation, not vitamin deficiencies or methotrexate.

Implications:

• Hyperhomocysteinemia is a significant, often treatable, risk factor for cardiovascular complications in rheumatoid arthritis patients.
• Identifying and managing hyperhomocysteinemia, particularly in RA patients with MTHFR mutations, is crucial for preventing atheroma and thrombosis.
• Folic acid supplementation is an effective strategy to normalize homocysteine levels and reduce cardiovascular risk in affected individuals.