Paradoxical Long-Term Impact Between Serum Apolipoprotein E and High-Density Lipoprotein Cholesterol in Patients Undergoing Percutaneous Coronary Intervention

Aim: Apolipoprotein E (ApoE) strongly affects arteriosclerosis but has atheroprotective effects in combination with high-density lipoprotein cholesterol (HDL-C). The impact of the quantitative relationship between serum ApoE and HDL-C levels in patients with coronary artery disease (CAD) remains unclear. Methods: A total of 3632 consecutive patients who underwent their first intervention between 2000 and 2016 were included. They were categorized into normal and abnormal HDL-C groups based on the normal HDL-C value, and each group was subdivided into high and low ApoE subgroups based on the group-specific median ApoE value. We evaluated the incidence of major adverse cardiac and cerebrovascular events (MACCE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and all-cause death Results: During a 6.4-year follow-up, 419 patients developed MACCE and 570 patients died. The interaction term between ApoE levels and HDL-C status in MACCE and all-cause death proved to be statistically significant. Kaplan–Meier analysis revealed that the cumulative incidence of MACCE was significantly higher for elevated pre-procedural ApoE levels than for reduced preprocedural ApoE levels in the normal HDL-C group. Conversely, the cumulative incidence of MACCE was significantly higher for reduced pre-procedural ApoE levels than for elevated pre-procedural ApoE levels in the abnormal HDL-C group. After adjustment for important covariates, multivariable Cox hazard analysis revealed that the serum ApoE level was a strongly independent predictor of MACCE; this was inversely related in both groups. Conclusions: Serum ApoE levels may have a paradoxical impact on the future cardiovascular risk depending on the HDL-C status in patients with CAD.