Abstract 10: Enhanced Benefits of the Life's Essential 8 in APOE Epsilon 4 Carriers

Background: Adherence to the American Heart Association's Life’s Essential 8 (LE8) reduces the risk of cardiovascular disease. While the epsilon (ε) 4 variants within the APOE gene have been extensively investigated as a risk factor for dementia and stroke, APOE ε4 carriers have not been thoroughly studied as an at-risk population. We hypothesized that, compared to non-carriers, APOE ε4 carriers derive additional neuro- and cardiovascular health benefits from LE8 optimization.

Methods: We used longitudinal data from the UK Biobank (UKB), a large, prospective study undertaken in the UK. Participants with prior stroke, transient ischemic attack (TIA) or myocardial infarction (MI) were excluded. The independent variable or “exposure” was the LE8 score, which was based on data on blood pressure, blood glucose and cholesterol, body mass index, smoking, physical activity, sleep duration and diet. Our outcome was a composite of stroke, TIA or MI. Multivariable logistic regression models with product terms were used to test for interaction between APOE ε4 status and LE8 score.

Results: Of the 317,174 UKB participants (mean age 56 years, 54% female) with available genetic and LE8 data, 81,877 (26%) were APOE ε4 carriers (1 or 2 alleles), including 74,384 (91%) heterozygous and 7,493 (9%) homozygous. Among all participants, a 1 SD increase in the LE8 score correlated with a 28% risk reduction for incident stroke, TIA, or MI (OR 0.72, 95%CI 0.71-0.73; p<0.001). APOE ε4 status significantly modified the association between the LE8 score and the composite risk of stroke, TIA, or MI (interaction p=0.008): while APOE ε4 carriers had a 30% risk reduction (OR 0.70, 95%CI 0.68-0.72; p<0.001) per 1 SD increase in the LE8 score, APOE ε4 non-carriers had a 27% risk reduction (OR 0.73, 95%CI 0.72-0.74; p<0.001). Thus, APOE-e4 carriers experienced an 11% increase in benefit.

Conclusion: Compared to non-carriers, middle-aged APOE ε4 carriers without a history of vascular events derive greater benefit from LE8 optimization. Now that direct-to-consumer genotyping companies are routinely returning APOE data to millions of Americans, our findings provide important information to educate this population on proven strategies that improve long-term neuro- and cardiovascular outcomes.