Abstract 1461: ApoE Modulates the Impact of ApoCIII Containing Lipoproteins on Coronary Heart Disease
Objectives ApoCIII containing lipoproteins are positively associated with risk of coronary heart disease (CHD). ApoE is a physiological antagonist of apoCIII in lipid metabolism. We explored whether the apoE content of lipoproteins with apoCIII influences their association with CHD.
Methods We followed CHD-free participants, 18,225 men from the Health Professionals Follow-up Study (HPFS) for 10 years, and 32,826 women from the Nurses’ Health Study (NHS) for 14 years; and selected 731 patients who had a fatal or non-fatal myocardial infarction (cases, 317 from NHS and 414 from HPFS). Using risk set sampling, cases were matched 1:1 to controls of the same age, date of blood collection and smoking status. In cases and controls, we isolated VLDL with apoCIII (VLDL-CIII) and LDL with apoCIII (LDL-CIII) from baseline plasma and measured their apoB and apoE content.
Results The concentrations of VLDL-CIII and LDL-CIII (reflected by their apoB) were strong risk factors for CHD. However, a high concentration of apoE in LDL-CIII partially attenuated the risk conferred by these particles. For participants whose concentrations of apoE in LDL-CIII were in the lowest tertile, the relative risk for the highest versus lowest tertile of LDL-CIII was 3.46 (95% CI: 1.98 – 6.06); while for participants in the highest tertile of apoE in LDL-CIII this relative risk was 2.33 (95% CI: 1.54 –3.51). This tendency persisted even after extensive multivariate adjustment including LDL and HDL cholesterol (Figure⇓). A similar but less pronounced pattern was found for apoE in VLDL-CIII.
Conclusions The apoE content of LDL with apoCIII was associated with attenuation of its atherogenicity.