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.

We aimed to determine the association between autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) and prevalent cardiovascular (CV) disease (CVD) as well as markers of CV risk in the general population. Cross-sectional data were obtained from 6649 subjects (age 52.6 ± 10.7 years, 47.4 % male) of the population-based CoLaus study. CVD was defined as myocardial infarction, angina pectoris, percutaneous revascularisation or bypass grafting for ischaemic heart disease stroke or transient ischaemic attack, and was assessed according to standardised medical records. Anti-apoA-1 IgG and biological markers were measured by ELISA and conventional automated techniques, respectively. Prevalence of high anti-apoA-1 IgG levels in the general population was 19.9 %. Presence of anti-apoA-1 IgG was significantly associated with CVD [odds ratio 1.34, 95 % confidence interval (1.05-1.70), p=0.018], independently of established CV risk factors (CVRFs) including age, sex, hypertension, smoking, diabetes, low and high-density lipoprotein cholesterol levels. The n=455 (6.8 %) study participants with a history of CVD (secondary prevention subgroup) presented higher median anti-ApoA-1 IgG values compared with subjects without CVD (p=0.029). Among patients in the secondary prevention subgroup, those with positive anti-apoA-1 IgG levels had lower HDL (p=0.002) and magnesium (p=0.001) levels, but increased uric acid and high-sensitivity C-reactive protein levels (p=0.022, and p<0.001, respectively) compared to patients with negative anti-apoA-1 IgG levels. In conclusion, anti-apoA-1 IgG levels are independently associated with CVD in the general population and also related to CV biomarkers in secondary prevention. These findings indicate that anti-apoA-1 IgG may represent a novel CVRF and need further study in prospective cohorts.

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