Association between anti-apolipoprotein A-1 antibodies and cardiovascular disease in the general population

Abstract

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.

Anti-Apolipoprotein A-1 IgG Predict All-Cause Mortality and Are Associated with Fc Receptor-Like 3 Polymorphisms

“…Our results extend previous findings (19, 22, 25, 26) and suggest that preclinical autoimmunity against apoA-1/HDL—which affects up to one-fifth of the general population—may identify individuals at increased risk of death. Our findings raise the possibility that presence of anti-apoA-1 IgG leads to pathophysiological events affecting not only CV prognosis, but also survival in the long term.…”

“…Moreover, similar to what has been reported with other autoantibodies (7), our group recently demonstrated that elevated anti-apoA-1 IgG levels were present in up to 20% of individuals in the general population and associated with prevalent CVD independently of traditional CV risk factors (25). Nevertheless, the association of anti-apoA-1 IgG with all-cause mortality in the general population has not yet been studied.…”

“…Our findings raise the possibility that presence of anti-apoA-1 IgG leads to pathophysiological events affecting not only CV prognosis, but also survival in the long term. Based upon previous studies, such events could be related to a chronic low-grade inflammatory state through sustained activation of the TLR2/TLR4/CD14 complex and production of pro-inflammatory cytokines (14, 18, 21, 24, 38), associations with elevated high-sensitivity C-reactive protein and uric acid levels (23, 25), impairment of HDL function (10–13, 16, 17), interference with basal heart rate regulation (22, 24, 25) or B-cell epitope spreading (39). Other pathophysiological mechanisms, other than those currently ascribed to anti-apoA-1 IgG could also be involved, in the same way that multiple molecular pathways underlie the associations of other autoantibodies with all-cause mortality in the community (7, 9, 40, 41).…”

“…The fact that the distribution of anti-apoA-1 IgG values is positively skewed (25) and that low CV risk participants are known to present lower levels of anti-apoA-1 IgG than high CV risk subjects (19, 22, 25) could explain these relatively low anti-apoA-1 IgG values in the general population, despite significant differences between survivors and non-survivors. Finally, the observed anti-apoA-1 IgG values translates in a 19.9% anti-apoA-1 IgG positivity in the sample, which is similar to the reported prevalence of other IgG autoantibodies in the community (7).…”

“…Recently, due to these pro-inflammatory and pro-atherogenic properties, anti-apoA-1 IgG gained interest as independent biomarkers for incident cardiovascular (CV) disease (CVD) and mortality, as well as potential therapeutic targets for immune-modulating interventions, in high CV risk populations (16, 19, 20, 22, 25–28). Moreover, similar to what has been reported with other autoantibodies (7), our group recently demonstrated that elevated anti-apoA-1 IgG levels were present in up to 20% of individuals in the general population and associated with prevalent CVD independently of traditional CV risk factors (25).…”