Abstract Details

Title Enhanced Benefits of the Life’s Essential 8 in APOE Epsilon 4 Carriers

Topic Cerebrovascular Disease and Interventional Neurology

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 5-014

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.

Objective To test the hypothesis that, compared to non-carriers, APOE ε4 carriers derive additional neuro- and cardiovascular health benefits from LE8 optimization.

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.

Authors/Disclosures
Santiago Clocchiatti-Tuozzo (Yale University, Department of Neurology) PRESENTER	Mr. Clocchiatti-Tuozzo has nothing to disclose.
Cyprien Rivier, MD (Yale University)	Dr. Rivier has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pyxis Partners.
Daniela B. Renedo, MD (Yale University)	Dr. Renedo has nothing to disclose.
Shufan Huo, MD, PhD (Yale University)	Dr. Huo has nothing to disclose.
Victor M. Torres-Lopez, MA (Yale University)	Mr. Torres-Lopez has nothing to disclose.
Adam De Havenon, MD, FAAN (Yale University)	Dr. De Havenon has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novo Nordisk. Dr. De Havenon has stock in Certus. Dr. De Havenon has stock in TitinKM. The institution of Dr. De Havenon has received research support from NIH/NINDS. Dr. De Havenon has received publishing royalties from a publication relating to health care.
Kevin N. Sheth, MD, FAAN (Yale UniversityDivision of Neuro and Critical Care)	Dr. Sheth has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ceribell. Dr. Sheth has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Zoll. Dr. Sheth has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NControl. Dr. Sheth has received stock or an ownership interest from Astrocyte. Dr. Sheth has received stock or an ownership interest from Alva. The institution of Dr. Sheth has received research support from Biogen. The institution of Dr. Sheth has received research support from Novartis. The institution of Dr. Sheth has received research support from Bard. The institution of Dr. Sheth has received research support from Hyperfine. Dr. Sheth has received intellectual property interests from a discovery or technology relating to health care.
Thomas Gill	No disclosure on file
Guido J. Falcone, MD (Yale School of Medicine)	The institution of Dr. Falcone has received research support from NIH. The institution of Dr. Falcone has received research support from AHA.