BACKGROUND AND AIMS: Triglyceride-rich lipoproteins are causally associated with high risk of ischemic heart disease (IHD), and apolipoprotein E (apoE) has a central role in their plasma clearance. While both quantitative and qualitative changes of apoE are established causes of rare dyslipidemia syndromes, it remains unclear whether plasma levels of apoE are associated with risk of IHD in the general population.

METHODS: We tested whether plasma levels of apoE at enrollment were associated with future risk of IHD and myocardial infarction (MI) in 91,695 individuals from the general population.

RESULTS: Multifactorially adjusted hazard ratios (HRs) for highest versus lowest apoE tertile were 1.15 (1.04-1.27) for IHD and 1.16 (1.00-1.36) for MI in men, and 0.94 (0.84-1.05) and 1.04 (0.85-1.26) in women. These associations were attenuated by adjustments for triglyceride levels. Corresponding HRs for highest versus lowest apoE tertile in ε33 carriers were 1.18 (1.03-1.36) for IHD and 1.21 (0.98-1.49) for MI in men, and 0.91 (0.78-1.06) and 0.93 (0.71-1.21) in women. Thus, the present associations were independent of APOE genotype.

CONCLUSION: These findings suggest that high plasma levels of apoE are associated with IHD in men but not in women. Triglyceride-rich lipoproteins may partly explain these associations.