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Anti-apolipoprotein A-1 IgG, incident cardiovascular events, and lipid paradox in rheumatoid arthritis
Denis Mongin1, Sabrina Pagano2, Celine Lamacchia1
1Division of Rheumatology, Geneva University Hospital and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Insights
Anti-apolipoprotein A-1 IgG (AAA1) independently predicts cardiovascular deaths in rheumatoid arthritis (RA) patients. AAA1 may help identify RA patients at low cardiovascular risk.
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.
Objective:
To validate the prognostic accuracy of anti-apolipoprotein A-1 (AAA1) IgG for incident major adverse cardiovascular (CV) events (MACE) in rheumatoid arthritis (RA) and study their associations with the lipid paradox at a multicentric scale.
Method:
Baseline AAA1 IgG, lipid profile, atherogenic indexes, and cardiac biomarkers were measured on the serum of 1,472 patients with RA included in the prospective Swiss Clinical Quality Management registry with a median follow-up duration of 4.4 years. MACE was the primary endpoint defined as CV death, incident fatal or non-fatal stroke, or myocardial infarction (MI), while elective coronary revascularization (ECR) was the secondary endpoint. Discriminant accuracy and incidence rate ratios (IRR) were respectively assessed using C-statistics and Poisson regression models.
Results:
During follow-up, 2.4% (35/1,472) of patients had a MACE, consisting of 6 CV deaths, 11 MIs, and 18 strokes; ECR occurred in 2.1% (31/1,472) of patients. C-statistics indicated that AAA1 had a significant discriminant accuracy for incident MACE [C-statistics: 0.60, 95% confidence interval (95% CI): 0.57-0.98, p = 0.03], mostly driven by CV deaths (C-statistics: 0.77; 95% CI: 0.57-0.98, p = 0.01). IRR indicated that each unit of AAA1 IgG increase was associated with a fivefold incident CV death rate, independent of models' adjustments. At the predefined and validated cut-off, AAA1 displayed negative predictive values above 97% for MACE. AAA1 inversely correlated with total and HDL cholesterol.
Conclusions:
AAA1 independently predicts CV deaths, and marginally MACE in RA. Further investigations are requested to ascertain whether AAA1 could enhance CV risk stratification by identifying patients with RA at low CV risk.
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