Abstract Details

Title Oral Health as a Risk Factor for Spontaneous Intracerebral Hemorrhage: A Mendelian Randomization Analysis

Topic Cerebrovascular Disease and Interventional Neurology

Presentation(s) S34 - Stroke Risk Factors and Preventative Strategies (3:30 PM-3:42 PM)

Poster/Presentation
Number 001

Background Poor oral health is a highly prevalent and modifiable risk factor that is associated with higher risk of cardiovascular disease, including ischemic stroke. However, the relationship between oral health and spontaneous intracerebral hemorrhage (ICH) has not been studied.

Objective We hypothesize that genetically-determined poor oral health increases the risk of ICH.

Design/Methods We conducted a two-sample Mendelian Randomization (MR) study using summary statistics from the largest genome-wide associations studies of oral health and ICH conducted to date. As genetic instruments (e.g., genetic risk variants for oral health), we identified 105 independent single nucleotide polymorphisms known to be associated with higher risk of caries, dentures and missing teeth at genome wide levels (p<5x10^-8). The primary analysis employed summary statistics-based MR to assess the relationship between poor oral health and risk of ICH in any brain location. Secondary analyses evaluated deep and lobar ICH separately.

Results The primary analysis using the inverse variance-weighted MR method showed that genetically-increased risk of poor oral health was associated with a higher risk of ICH (OR 2.34, [1.08-5.06], p=0.029). Secondary analyses indicated a more potent association with deep ICH (OR 3.20 [1.34-7.6], p=0.008), whereas the link with lobar ICH was not statistically significant (OR 1.32 [0.53-3.27], p=0.543). Sensitivity analyses detected no horizontal pleiotropy in our findings (MR-PRESSO global test p-values >0.05).

Conclusions Genetically-determined poor oral health is associated with an increased risk of ICH, particularly in the case of deep ICH. Because gene-disease associations are less prone to confounding, our results suggest that this association is causal. However, further analyses are needed to validate these results and identify the mediating mechanisms. Because oral health is an easily modifiable process, it may be a promising target for very early interventions focused on mitigating the risk of hemorrhagic stroke.

Authors/Disclosures
Cyprien Rivier, MD (Yale University) PRESENTER	Dr. Rivier has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pyxis Partners.
Santiago Clocchiatti-Tuozzo (Yale University, Department of Neurology)	Mr. Clocchiatti-Tuozzo has nothing to disclose.
Shufan Huo, MD, PhD (Yale University)	Dr. Huo has nothing to disclose.
Daniela B. Renedo, MD (Yale University)	Dr. Renedo has nothing to disclose.
Maximiliano A. Hawkes, MD (Mayo Clinic)	Dr. Hawkes has nothing to disclose.
N. Abimbola Sunmonu, MD, PhD (Yale Neurology)	Dr. Sunmonu has nothing to disclose.
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.