October 20, 2023Atherosclerosis46 citationsOpen Access
Tryptophan metabolites and incident cardiovascular disease: The EPIC-Norfolk prospective population study
Key Result
Higher levels of kynurenine were associated with increased incident cardiovascular disease (HR 1.33; 95% CI 1.19-1.49), while higher tryptophan levels were inversely associated with fatal CVD.
Study Design
Type
Cohort (n=11,972)
Structured PICO
Are tryptophan metabolites associated with incident cardiovascular disease in apparently healthy adults?
P
Population
11,972 apparently healthy subjects from the community-based EPIC-Norfolk cohort, mean age 59.8 ± 9.0, 46.3% men.
O
Outcome
Incident development of cardiovascular disease (CVD)hard clinical
Higher levels of tryptophan metabolites, particularly kynurenine, are associated with an increased risk of incident cardiovascular disease in a healthy population.
Main Result
Effect estimate: HR 1.33 (95% CI 1.19-1.49)
Abstract
BACKGROUND AND AIMS: Cardiovascular disease (CVD) remains the largest cause of death globally due to various risk factors. One novel potential contributor to CVD might be the metabolism of the essential amino acid tryptophan (Trp), which through many pathways can produce immunomodulatory metabolites such as kynurenine, indole-3-propionate and serotonin. We aim to identify the metabolites with the strongest association with cardiovascular disease, utilizing a substantial and diverse cohort of individuals. In our pursuit of this aim, our primary focus is to validate and reinforce the findings from previous cross-sectional studies. METHODS: We used the community-based EPIC-Norfolk cohort (46.3 % men, age 59.8 ± 9.0) with a median follow-up of 22.1 (17.6-23.3) years to study associations between the relative levels of Trp metabolites measured with untargeted metabolomics and incident development of CVD. Serum from n = 11,972 apparently healthy subjects was analysed, of which 6982 individuals had developed CVD at the end of follow-up. Cox proportional hazard models were used to study associations, adjusted for sex, age, conventional cardiovascular risk factors and CRP. All metabolites were Ln-normalised prior to analysis. RESULTS: Higher levels of Trp were inversely associated with mortality (HR 0.73; CI 0.64-0.83) and fatal CVD (HR 0.76; CI 0.59-0.99). Higher levels of kynurenine (HR 1.33; CI 1.19-1.49) and the Kynurenine/Tryptophan-ratio (HR 1.24; CI 1.14-1.35) were associated with a higher incident development of CVD. Serotonin was not associated with overall CVD, but we did find associations for myocardial infarction and stroke. Adjustment for CRP did not yield any discernible differences in effect size. CONCLUSIONS: Tryptophan levels were inversely correlated with CVD, while several of its major metabolites (especially kynurenine and serotonin) were positively correlated. These findings indicate that mechanistic studies are required to understand the role of Trp metabolism in CVD with the goal to identify new therapeutic targets.
Cite This Study
Teunis et al. (Fri,) conducted a cohort in Cardiovascular disease (n=11,972). Tryptophan metabolites (kynurenine, serotonin, tryptophan) was evaluated on Incident development of CVD (HR 1.33, 95% CI 1.19-1.49). Higher levels of kynurenine were associated with increased incident cardiovascular disease (HR 1.33; 95% CI 1.19-1.49), while higher tryptophan levels were inversely associated with fatal CVD.