Abstract 10334: The Association of Trimethylamine N-oxide (TMAO) with Findings of Vascular Brain Injury on Magnetic Resonance Imaging in the Cardiovascular Health Study (CHS)

Abstract

Introduction: Findings on MRI of vascular brain injury, such as brain infarcts and white matter hyperintensities, are chronic manifestation of atherosclerosis. A gut-microbiome-generated metabolite, trimethylamine N-oxide (TMAO), is an independent predictor of clinical cardiovascular events. However, no study has examined associations between TMAO and subclinical vascular brain injury in the general population. Hypothesis: TMAO levels are positively associated with evidence of progressive subclinical vascular brain injury on serial MRI scans with incident brain infarcts and white matter worsening. Methods: The Cardiovascular Health Study (CHS) is a community-based prospective cohort study in adults aged >65 years. Plasma TMAO was measured using mass spectrometry from samples collected in 1992-1993 and 1996-1997. Brain MRI was performed at 1991-1994 and again at 1997-1999. White matter was graded on a 10-point scale, higher being worse, and white matter worsening (WMW) was defined by an increase of least one point comparing initial and follow up scans. In these analyses, participants with prior TIA or stroke were excluded. Those with serum TMAO and both MRI scans were included: n=1196 for incident brain infarct and n=1553 for white matter worsening. Logistic regression was used for the association of baseline TMAO levels and incident brain infarcts, and Poisson regression, for the change in TMAO levels and WMW. Models were adjusted for age, sex, race, alcohol use, intake of meat and vegetable, and vascular risk factors. Results: Between the two MRI scans, 191(15.9%) participants had subclinical incident brain infarcts, and 423 (27.2%) participants had WMW. Comparing the highest vs. lowest quartile, the first TMAO were not significantly associated with incident brain infarcts: odds ratio 0.78 (95% CI: 0.49 to 1.25). Again comparing the highest vs. lowest quartile, changes in TMAO were not associated with WMW: 1.08 (0.77 to 1.51). Conclusions: Baseline and changes in plasma TMAO levels were not associated with findings of subclinical vascular brain injury on MRI in older US adults. The associations of TMAO with the adverse clinical events seen in prior clinical samples of patients were not seen at the subclinical level in our population-based study.