Relationship between HDL Cholesterol Efflux Capacity, Calcium Coronary Artery Content, and Antibodies against ApolipoproteinA-1 in Obese and Healthy Subjects.

Aims: To explore the associations between cholesterol efflux capacity (CEC), coronary artery calcium (CAC) score, Framingham risk score (FRS), and antibodies against apolipoproteinA-1 (anti-apoA-1 IgG) in healthy and obese subjects (OS).

Methods And Results: ABCA1-, ABCG1-, passive diffusion (PD)-CEC and anti-apoA-1 IgG were measured in sera from 34 controls and 35 OS who underwent CAC score determination by chest computed tomography. Anti-apoA-1 IgG ability to modulate CEC and macrophage cholesterol content (MCC) was tested in vitro. Controls and OS displayed similar ABCG1-, ABCA1-, PD-CEC, CAC and FRS scores. Logistic regression analyses indicated that FRS was the only significant predictor of CAC lesion. Overall, anti-apoA-1 IgG were significantly correlated with ABCA1-CEC ( = 0.48, < 0.0001), PD-CEC ( = -0.33, = 0.004), and the CAC score ( = 0.37, = 0.03). ABCA1-CEC was correlated with CAC score ( = 0.47, = 0.004) and FRS ( = 0.18, = 0.29), while PD-CEC was inversely associated with the same parameters (CAC: = -0.46, = 0.006; FRS: score = -0.40, = 0.01). None of these associations was replicated in healthy controls or after excluding anti-apoA-1 IgG seropositive subjects. In vitro, anti-apoA-1 IgG inhibited PD-CEC ( < 0.0001), increased ABCA1-CEC ( < 0.0001), and increased MCC ( < 0.0001).

Conclusions: We report a paradoxical positive association between ABCA1-CEC and the CAC score, with the latter being inversely associated with PD in OS. Corroborating our clinical observations, anti-apoA-1 IgG enhanced ABCA1 while repressing PD-CEC, leading to MCC increase in vitro. These results indicate that anti-apoA-1 IgG have the potential to interfere with CEC and macrophage lipid metabolism, and may underpin paradoxical associations between ABCA1-CEC and cardiovascular risk.