Abstract Details

Title Genetic Risk Loci for Cholesterol Levels are Associated with Risk of Spontaneous Intracerebral Hemorrhage

Topic Neuro Trauma, Critical Care, and Sports Neurology

Presentation(s) S2 - Neurocritical Care (1:11 PM-1:22 PM)

Poster/Presentation
Number 002

Background Observational studies found an inverse correlation between cholesterol levels and risk of spontaneous ICH. We investigated whether the cumulative burden of known genetic risk loci for cholesterol levels influences the risk of ICH.

Objective To determine if the cumulative burden of lipid-related risk loci is associated with risk of intracerebral hemorrhage (ICH).

Design/Methods We utilized genetic risk scores (GRSs) to model the cumulative burden of cholesterol-related common genetic variants (CGVs). GRSs were constructed using an approach that combines summary statistics from CGVs known to influence the exposure (cholesterol levels) and outcome (ICH) of interest. Summary statistics were identified using the Cerebrovascular Disease Knowledge Portal. For cholesterol levels (derivation dataset), we abstracted summary statistics for independent CGVs associated with cholesterol levels at p<5x10^-5 from a meta-analysis of data from Kaiser Permanente, UK Biobank, and Global Lipids Genetics Consortium. For ICH (testing dataset), we abstracted summary statistics from a meta-analysis of five genetic studies.

Results

We identified 711 CGVs associated with cholesterol levels in the derivation dataset (study population 76,627, mean age 56 [SD 9], female sex 44,856 [59%]). Summary statistics were available for 468 of these CGVs in the ICH testing dataset (study population 3,026, mean age 67 [SD 10], female sex 1,362 [45%]). The GRSs for total cholesterol (OR 0.87, 95%CI 0.73-1.01; p=0.04), LDL (OR 0.78, 95%CI 0.65-0.91; p=0.0002) and triglycerides (OR 1.18, 95%CI 1.04-1.32; p=0.02) were associated with risk of all ICH. After stratifying by location, deep ICH was strongly associated with total cholesterol (OR 0.77, 95%CI 0.61-0.93; p=0.001) and LDL (OR 0.70, 95%CI 0.55-0.85; p=8x10^-6). Only the triglycerides-based GRS was associated with lobar ICH (OR 1.26, 95%CI 1.08-1.44; p=0.01).

Conclusions

The cumulative burden of cholesterol-related mutations, specifically total cholesterol and LDL, is inversely associated with risk of ICH. These associations are stronger for deep ICH.

Authors/Disclosures
Elayna Kirsch PRESENTER	No disclosure on file
Audrey Leasure	Ms. Leasure has nothing to disclose.
Rommell Noche	Mr. Noche has nothing to disclose.
Charles Matouk	Charles Matouk has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Silk Road Medical. Charles Matouk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Microvention. Charles Matouk has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Navigantis.
Lauren H. Sansing, MD	Dr. Sansing has nothing to disclose.
	No disclosure on file
Christina Kourkoulis	No disclosure on file
Daniel Woo, MD, FAAN (University at Buffalo)	The institution of Dr. Woo has received research support from NIH.
Jonathan Rosand, MD (Massachusetts General Hospital)	Dr. Rosand has received personal compensation for serving as an employee of Massachusetts General Hospital. Dr. Rosand has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly and Co. Dr. Rosand has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Rosand has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for National Football League. The institution of Dr. Rosand has received research support from NIH. The institution of Dr. Rosand has received research support from American Heart Association. Dr. Rosand has received personal compensation in the range of $0-$499 for serving as a Peer reviewer with National Institutes of Health. Dr. Rosand has a non-compensated relationship as a Trustee with Columbia University that is relevant to AAN interests or activities.
Christopher D. Anderson, MD, PhD, FAAN (Brigham and Women's Hospital)	The institution of Dr. Anderson has received research support from Bayer AG. The institution of Dr. Anderson has received research support from American Heart Association. The institution of Dr. Anderson has received research support from National Institutes of Health. An immediate family member of Dr. Anderson 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.
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.

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