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Abstract Details

Adipokines May Partly Mediate the Favorable Effect of Gluteofemoral Adipose Tissue Distribution on Cardiovascular Risk: A Mediation Mendelian Randomization Analysis
Cerebrovascular Disease and Interventional Neurology
P1 - Poster Session 1 (8:00 AM-9:00 AM)
5-030
Recent evidence suggests that body fat distribution is associated with cardiovascular risk. Previously, we have shown that GFAT is associated with a favorable stroke risk profile, mainly driven by reduced large artery (LAS) and small vessel (SVS) stroke risk.
To explore the role of gluteofemoral adipose tissue (GFAT) distribution in relevant vascular phenotypes and investigate the mediatory role of cardiovascular, inflammatory, glycemic, and adipose-specific factors underlying these associations.
Utilizing data from Genome-Wide Association Studies (GWAS) of MRI-derived GFAT (n= 37,750), we selected genome-wide, independent, BMI- and height-adjusted single nucleotide polymorphisms (SNPs). We performed univariable Mendelian Randomization (MR) of genetically proxied GFAT on ischemic stroke (IS) (n=62,100), LAS (n=6,399), SVS (n=6,811), coronary artery disease (CAD) (n=181,522), lacunar stroke (n=6,030), and carotid intima media thickness (cIMT) (n=45,185). We then explored the mediatory effect of common cardiovascular (systolic blood pressure (SBP), diabetes (T2DM), LDL), insulin resistance (fasting insulin), inflammatory (C-reactive protein (CRP)), and adipose tissue-specific (adiponectin, leptin) factors by performing two-step mediation MR analyses. Factors that showed significant univariable MR associations with both GFAT and the vascular phenotypes were considered candidate mediators.
Genetically proxied GFAT was associated with decreased risk of IS (p=0.006), LAS (p=0.016), SVS (p<0.001), CAD (p<0.001), and lacunar stroke (p=0.001), and lower mean cIMT (p=0.001)While common vascular risk factors were predominant mediators across outcomes, neither CRP nor insulin resistance were significant mediators. Both adiponectin (15% (2-57%) in IS, 4% (1-14%) in CAD) and leptin were mediators or candidate mediators, respectively.
In the setting of an unhealthy body fat distribution, targeting adipose-tissue specific pathways may provide additional benefit to reducing vascular risk, beyond addressing traditional risk factors.
Authors/Disclosures
Evangelos Pavlos Myserlis, MD (Department of Neurology)
PRESENTER
The institution of Dr. Myserlis has received research support from American Academy of Neurology.
No disclosure on file
No disclosure on file
Ernst Mayerhofer, MD Dr. Mayerhofer has nothing to disclose.
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.