Associations of plasma TMAO and its precursors with stroke risk in the general population: A nested case‐control study

Abstract

Background. Trimethylamine N-oxide (TMAO) is a gut-derived atherogenic metabolite. However, the role of TMAO and its precursors in the development of stroke remains unclear. We aimed to examine the associations between metabolites in TMAO biosynthesis and stroke risk. Methods.A nested case-control study was performed in a community-based cohort (2013-2018, n = 16,113). We included 412 identified stroke cases and 412 controls matched by age and sex. Plasma carnitine, choline, betaine, trimethyl lysine (TML), and TMAO were measured by ultrahigh performance liquid chromatographytandem mass spectrometry. Conditional logistic regression analyses were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs) between these biomarkers and stroke risk.Results. After adjustment for body mass index, smoking, hypertension, educational attainment, and estimated glomerular filtration rate, the corresponding OR for the highest versus lowest quartile was 1.74 (95% CI: 1.16-2.61, P trend = 0.006) for total stroke and 1.81 (95% CI: 1.14-2.86, P trend = 0.020) for ischemic stroke in an essentially linear dose-response fashion. A significant association between TMAO and nonischemic stroke was shown as a J-shape with OR for the highest versus second quartile of 5.75 (95% CI: 1.73-19.1). No meaningful significant risk association was found among plasma carnitine, choline, betaine, and TML with stroke risk.Conclusions. Increased TMAO was associated with higher stroke risk in the community-based population, whereas the TMAO precursors carnitine, choline, betaine, and TML were not associated. Further studies are warranted to confirm these findings and to further elucidate the role of TMAO in the development of stroke.

The Tryptophan Index Is Associated with Risk of Ischemic Stroke: A Community-Based Nested Case–Control Study

“…Details of the Prospective Follow-up Study on Cardiovascular Morbidity and Mortality in China (PFS-CMMC), including study strategy and enrollment, have been previously described [ 16 , 17 ]. In summary, after excluding individuals with severe cancer, severe disability, and/or severe psychiatric disturbance, a total of 16,457 residents aged 35 to 74 years in Changshu (Jiangsu province, China) were recruited in 2013.…”

Dietary choline intake and health outcomes in U.S. adults: exploring the impact on cardiovascular disease, cancer prevalence, and all-cause mortality

“…Research has not conclusively established a clear link between choline intake and the risk of CVD [ 6 ], and persistent adherence to a high-choline diet may lower CVD-related mortality by addressing inflammation and associated risk factors [ 7 ]. Elevated plasma choline levels are also associated with increased susceptibility to major adverse cardiac events [ 8 ], and heightened trimethylamine N-oxide (TMAO), a choline metabolite, has been identified as a potential risk factor for stroke [ 9 ]. In the field of oncology, a meta-analysis of eleven scholarly articles indicated a possible inverse correlation between increased choline intake and overall cancer risk [ 10 ].…”

Cardiovascular effects of TMAO and other toxic metabolites of the intestinal microbiome

“…In this issue of the Journal of Internal Medicine , Liu et al. [1] report that plasma levels of trimethylamine N‐oxide (TMAO)—but not plasma levels of its metabolic precursors choline, carnitine, betaine, and trimethyl lysine—were associated with the risk of stroke. From a community‐based cohort of 16,113 persons recruited from 2013 to 2018, the authors identified 412 cases of first stroke (321 ischemic and 91 non‐ischemic) over a median follow‐up of 5.3 years and compared them with 412 controls matched for age and sex.…”

“…The role of the intestinal microbiome in the findings of Liu et al. [1] is revealed by their finding that high levels of plasma TMAO, but not of its metabolic precursors, were associated with stroke risk.…”

“…One lesson from the study of Liu et al. [1] is that people with renal impairment—including the elderly—should avoid red meat and egg yolk, and limit their intake of animal flesh [10].…”