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

Abstract Objectives To validate the prognostic accuracy of anti-apolipoprotein A-1 IgG (AAA1) for incident major adverse cardiovascular (CV) events (MACE) in rheumatoid arthritis (RA) and study their associations with the lipid paradox at a multicentric scale. Methods Baseline AAA1 -, lipid profile, atherogenic indexes, and cardiac biomarkers were measured on the serum of 1472 RA patients 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 nonfatal stroke, or myocardial infarction (MI), while elective coronary revascularisation (ECR) was the secondary endpoint. Discriminant accuracy, and incidence rate ratios (IRR) were respectively assessed by C-statistics and Poisson regression models. Results During follow-up, 2.4% (35/1472) patients experienced MACE, consisting in 6 CV deaths, 11 MI and 18 strokes. ECR occurred in 2.1% (31/1472) of patients. C-statistics indicated that AAA1 had a significant discriminant accuracy for incident MACE (C-statistics: 0.60, 95% confidence intervals [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) and without predicting incident ECR. IRR indicated that for every unit increase in AAA1, incident CV death rate increased by 5-fold (95%CI:3.6-7.3), independently of various models’ adjustments. At the predefined and validated cut-off, AAA1 displayed negative predictive values above 97% for the MACE components. AAA1 inversely correlated with total, and HDL cholesterol, but not with atherogenic indexes. Conclusions AAA1 independently predict CV deaths in RA. Whether AAA1 could improve CV risk stratification by identifying in particular low CV risk patients remains to be demonstrated.