Circulating Apolipoprotein E concentration and incident cardiovascular diseases: evidence from an electronic health record-based cohort

BACKGROUND: Circulating Apolipoprotein E (ApoE) plays key roles in lipoprotein metabolism, but its clinical utility in cardiovascular risk assessment and its relationship with incident heart failure remain unclear. This study aims to evaluate the association of serum ApoE concentration with incident cardiovascular outcomes. METHODS: This retrospective cohort study used electronic health records from a multi-specialty outpatient population in Shenzhen, China. Adults who had serum ApoE measured and did not have prior ischemic heart disease, stroke, or heart failure were included (N=14,852). The outcomes were incident major adverse cardiovascular events (MACE), ischemic heart disease, stroke, and heart failure. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. RESULTS: During a median follow-up of 4.0 years, we observed 491 MACE, 515 ischemic heart disease, 293 stroke, and 181 heart failure incident events. Higher ApoE concentrations were significantly associated with increased risks of incident MACE (HR[95%CI] per 1mg/dL increment: 1.09[1.04-1.15]), ischemic heart disease (1.07[1.02-1.13]), and heart failure (1.14[1.07-1.22]), but not stroke (1.03[0.96-1.11]). These associations were independent of low-density lipoprotein cholesterol (LDL-C), small and dense LDL-C, high-density lipoprotein cholesterol, and neutrophil-to-lymphocyte ratio. However, adjustment for triglycerides attenuated the associations. Individuals with elevations in both ApoE and triglycerides had disproportionately higher risks of cardiovascular events. CONCLUSIONS: Elevated circulating ApoE concentrations are risk factors for incident MACE, ischemic heart disease, and heart failure, and may signal the residual risk of cardiovascular disease beyond cholesterol markers. Concurrent elevation in ApoE and triglycerides may represent a high-risk clinical phenotype, suggesting the joint assessment of ApoE and triglycerides may improve risk stratification for hypertriglyceridemic individuals.