Circulating TMAO was independently associated with major adverse cardiac and cerebrovascular events and provided complementary prognostic information beyond clinical variables and CT-FFR, particularly among patients without functionally significant ischemia.
Event rates were similar between patients with functionally significant ischemia and those without, based on CT-FFR.
Higher TMAO levels were independently associated with major adverse cardiac and cerebrovascular events (MACCE) after adjustment for clinical covariates and CT-FFR.
Adding TMAO improved discrimination for MACCE beyond clinical variables and CT-FFR, although absolute discrimination remained modest.
Among patients with preserved CT-FFR, elevated TMAO identified a subgroup with higher event rates, whereas those with preserved CT-FFR and low TMAO had the most favorable prognosis.
Serum TMAO was measured from cryopreserved biobank samples in a retrospective biobank-linked cohort.
The authors conclude that physiological assessment and clinical outcomes are not synonymous and that integrating systemic biomarkers with coronary physiology may improve individualized risk evaluation.
Heart scans called coronary CT angiography, combined with a computed measure of blood flow (CT-FFR), help doctors find narrowings in heart arteries that limit blood flow. But heart attacks, strokes and other serious events still occur in people whose scans show no significant flow limitation. This study asked whether a blood marker made partly by gut bacteria, called TMAO, could help identify who is at higher risk. Researchers followed 3978 patients who had these scans for about 3 years. Event rates were nearly the same in people with and without flow-limiting narrowing (10.6% vs 10.0%). Patients with higher TMAO had about 1.8 times the risk of major cardiac and cerebrovascular events, even after accounting for other clinical factors and CT-FFR. Among people with normal CT-FFR, those with high TMAO had more events, while those with normal CT-FFR and low TMAO fared best. This research suggests TMAO may add useful information to imaging-based risk assessment. However, the improvement in the model's ability to separate higher- from lower-risk patients was modest (C-index 0.552 to 0.591), and this was a retrospective study, so it shows association rather than proof that lowering TMAO would reduce events. Further research would be needed to determine how such a marker might be used in practice.
Shao B, Zhang R, Guo J, Li X, Liu G, Liu F. (2026). Residual Cardiovascular Risk Beyond Coronary Physiology: Complementary Prognostic Value of Trimethylamine N-Oxide in Patients Undergoing Coronary Computed Tomography Angiography With Computed Tomography-Derived Fractional Flow Reserve.. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.126.050221