Anti-apoA-1 IgG are independent predictors of nonfatal incident CAD in the general population. The strength of this association is dependent on a functional polymorphism of the CD14 receptor gene, a finding suggesting a gene-autoantibody interaction for the development of CAD.

BackgroundAutoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) have emerged as an independent biomarker for cardiovascular disease and mortality. However, their association with all-cause mortality in the community, as well as their genetic determinants, have not been studied.ObjectiveTo determine whether anti-apoA-1 IgG: (a) predict all-cause mortality in the general population and (b) are associated with single-nucleotide polymorphisms (SNPs) in a genome-wide association study (GWAS).MethodsClinical, biological, and genetic data were obtained from the population-based, prospective CoLaus study, including 5,220 participants (mean age 52.6 years, 47.3% men) followed over a median duration of 5.6 years. The primary study outcome was all-cause mortality.ResultsAfter multivariate adjustment, anti-apoA-1 IgG positivity independently predicted all-cause mortality: hazard ratio (HR) = 1.54, 95% confidence interval (95% CI): 1.11–2.13, P = 0.01. A dose–effect relationship was also observed, each SD of logarithmically transformed anti-apoA-1 IgG being associated with a 15% increase in mortality risk: HR = 1.15, 95% CI: 1.02–1.28, P = 0.028. The GWAS yielded nine SNPs belonging to the Fc receptor-like 3 (FCRL3) gene, which were significantly associated with anti-apoA-1 IgG levels, with the lead SNP (rs6427397, P = 1.54 × 10−9) explaining 0.67% of anti-apoA-1 IgG level variation.ConclusionAnti-apoA-1 IgG levels (a) independently predict all-cause mortality in the general population and (b) are linked to FCRL3, a susceptibility gene for numerous autoimmune diseases. Our findings indicate that preclinical autoimmunity to anti-apoA-1 IgG may represent a novel mortality risk factor.

Autoantibodies against apolipoprotein A-I (anti-apoA-I IgGs) are prevalent in atherosclerosis-related conditions. It remains elusive whether they improve the prognostic accuracy of the Global Registry of Acute Coronary Events (GRACE) score 2.0 (GS) in acute coronary syndromes (ACS). In this prospective multicenter registry, 1713 ACS patients were included and followed for 1 year. The primary endpoint (major adverse cardiovascular events (MACE)) was defined as the composite of myocardial infarction, stroke (including transient ischemic attack), or cardiovascular (CV) death with individual events independently adjudicated. Plasma levels of anti-apoA-I IgGs upon study inclusion were assessed using ELISA. The association between anti-apoA-I IgGs and incident MACE was assessed using Cox models with splines and C-statistics. One-year MACE incidence was 8.4% (144/1713). Anti-apoA-I IgG levels were associated with MACE with a non-linear relationship (p = 0.01), which remained unchanged after adjusting for the GS (p = 0.04). The hazard increased progressively across the two first anti-apoA-I IgG quartiles before decreasing thereafter. Anti-apoA-I IgGs marginally improved the prognostic accuracy of the GS (c-statistics increased from 0.68 to 0.70). In this multicenter study, anti-apoA-I IgGs were predictive of incident MACE in ACS independently of the GS but in a nonlinear manner. The practical implications of these findings remain to be defined.