Santiago Clocchiatti-Tuozzo1, Cyprien Rivier2, Daniela Renedo2, Shufan Huo3, Victor Torres-Lopez2, Adam De Havenon2, Kevin Sheth4, Thomas Gill3, Guido Falcone3
1Yale University, Department of Neurology, 2Yale University, 3Yale School of Medicine, 4Yale UniversityDivision of Neuro and Critical Care
Objective:
To test the hypothesis that, compared to non-carriers, APOE ε4 carriers derive additional neuro- and cardiovascular health benefits from LE8 optimization.
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, little is known about the APOE-ε4 carriers as an at-risk population.
Design/Methods:
We used longitudinal data from the UK Biobank (UKB), a large, prospective, population study. Participants with prior stroke, transient ischemic attack (TIA) or myocardial infarction (MI) were excluded. Our exposure was the LE8 score, which captures eight components (blood pressure, glucose and cholesterol, body mass index, smoking, physical activity, sleep, 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 data, 81,877 (26%) were APOE-ε4 carriers (1 or 2 alleles), including 74,384 (91%) heterozygous and 7,493 (9%) homozygous. Across all participants, a 1 SD LE8 score rise correlated with a 28% risk reduction for the composite outcome (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 outcome risk (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.
Conclusions:
Compared to non-carriers, middle-aged APOE-ε4 carriers without a history of vascular events derive greater benefit from LE8 optimization. These findings provide information to educate millions of newly genotyped Americans about proven strategies to improve long term neuro- and cardiovascular outcomes.