Background: Recent studies identify trimethylamine N-oxide (TMAO) as a gut microbiota-generated proatherogenic and prothrombotic metabolite that contributes to the development and progression of cardiovascular diseases (CVDs). The association between TMAO and subclinical myocardial dysfunction and/or necrosis in stable subjects at risk for CVD is unclear.
Hypothesis: We hypothesize that elevated TMAO is associated with increased risk of underlying subclinical myocardial dysfunction and/or necrosis.
Methods: We analyzed NT-proBNP, hs-cTnT, and TMAO levels in 3,943 sequential consenting subjects who underwent elective cardiac catheterization without acute coronary syndrome. We defined subclinical myocardial dysfunction as NT-proBNP >125 pg/mL and subclinical myocardial necrosis as hs-cTnT >0.01 ng/mL.
Results: In our study cohort (mean age 64±11 years, 68% male, 37% diabetes, 73% hypertension, median TMAO levels 3.63 [IQR 2.42-6.07] uM), 67% had evidence of subclinical myocardial dysfunction and 58% had subclinical myocardial necrosis. Elevated TMAO levels (>6.07 uM, quartile 4) had a 1.96-fold increased risk for SMD (95%CI 1.63-2.35, p<0.001), 2.66-fold increased risk for SMN (95%CI 2.19-3.24, p<0.001) and a 2.48-fold increased risk for either or both SMD or SMN occurring (95%CI 2.09-2.94, p<0.001). After adjusting for traditional cardiac risk factors, the associations of TMAO with SMD (adjusted OR 1.62, 95%CI 1.31-2.00,p<0.001) and SMN (adjusted OR 1.29, 95%CI 1.06-1.57, p<0.05), and/or both (adjusted OR 1.52, 95%CI 1.27-1.82, p<0.001) remained significant (see Figure).
Conclusion: Elevated levels of the gut microbiota metabolite TMAO is associated with increased risk of underlying subclinical myocardial dysfunction and/or necrosis in stable cardiac patients even after adjusting for traditional cardiac risk factors.