Anti-apolipoprotein A-1 IgG, incident cardiovascular events, and lipid paradox in rheumatoid arthritis

Area of Science:

• Cardiovascular Medicine
• Rheumatology
• Immunology

Background:

• Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease (CVD).
• The lipid paradox in RA refers to dyslipidemia despite adequate lipid-lowering therapy, complicating CVD risk assessment.
• Novel biomarkers are needed to improve CVD risk stratification in RA patients.

Purpose of the Study:

• To validate the prognostic accuracy of anti-apolipoprotein A-1 (AAA1) IgG for incident major adverse cardiovascular (CV) events (MACE) in RA.
• To investigate the association between AAA1 IgG and the lipid paradox in RA.
• To assess AAA1 IgG's utility in CV risk stratification for RA patients.

Main Methods:

• A multicentric, prospective study of 1,472 RA patients from the Swiss Clinical Quality Management registry.
• Measurement of baseline AAA1 IgG, lipid profiles, atherogenic indexes, and cardiac biomarkers.
• Follow-up for a median of 4.4 years to ascertain MACE (CV death, stroke, myocardial infarction) and elective coronary revascularization (ECR).
• Statistical analysis using C-statistics for discriminant accuracy and Poisson regression for incidence rate ratios (IRR).

Main Results:

• MACE occurred in 2.4% and ECR in 2.1% of patients during follow-up.
• AAA1 IgG demonstrated significant discriminant accuracy for incident MACE (C-statistic: 0.60, p=0.03), primarily driven by CV deaths (C-statistic: 0.77, p=0.01).
• Each unit increase in AAA1 IgG was associated with a fivefold increased rate of CV death (IRR), independent of adjustments.
• AAA1 IgG showed negative predictive values >97% for MACE and inversely correlated with total and HDL cholesterol.

Conclusions:

• AAA1 IgG independently predicts cardiovascular deaths and marginally MACE in RA patients.
• AAA1 IgG may contribute to improved CV risk stratification in RA.
• Further research is warranted to confirm AAA1 IgG's role in identifying low CV risk RA patients.