Trimethyllysine, trimethylamine N-oxide, and long-term risk of stroke: the western norway coronary angiography cohort

Abstract Background Trimethyllysine (TML) is a precursor of the gut-microbiota derived metabolite trimethylamine N-oxide (TMAO), and both biomarkers are associated with adverse cardiovascular outcomes. Whether circulating levels of TML or TMAO predict long-term risk of stroke is uncertain. Purpose To examine prospective associations of plasma TML and TMAO with long-term risk of total and ischemic stroke. Methods By Cox regression analyses, risk-associations were examined among 4132 patients undergoing elective coronary angiography for suspected stable coronary heart disease. Endpoints were obtained from the Cardiovascular Disease in Norway project. Results Median levels of TML and TMAO were 0.67 and 5.7 µmol/L, respectively. Median age was 62 years and 28.1% of the participants were female. During a median follow up of 7.4 years, 240 (5.8%) patients experienced a stroke, of which 193 were ischemic strokes. After multivariable adjustments for cardiovascular risk factors, the hazard ratios (95% confidence intervals) per 1 standard deviation increase in log-transformed plasma TML were 1.05 (0.92-1.19, p=0.49) for total stroke and 0.99 (0.86-1.15, p=0.92) for ischemic stroke. Corresponding risk estimates were 0.99 (0.86-1.13, p=0.83) and 0.95 (0.82-1.12, p=0.55) per 1 standard deviation increase in log-transformed plasma TMAO. Conclusion In this large prospective cohort of patients with suspected coronary heart disease, neither plasma TML nor plasma TMAO predicted long-term (∼7 years) risk of stroke.