Associations between plasma tryptophan and indole-3-propionic acid levels and mortality in patients with coronary artery disease

Abstract

Indole-3-propionic acid (IPA), a microbiota-produced tryptophan metabolite, has been shown to exhibit cardioprotective effects in animal models. However, the relation of IPA with cardiovascular risk in humans is currently unknown. This prospective study aimed to investigate whether plasma tryptophan and IPA levels are associated with decreased risks of mortality. Ultra-HPLC-MS/MS was used to measure plasma tryptophan and IPA levels in 1829 patients with coronary artery disease (CAD). Cox proportional hazards regression models were used to estimate the associations between tryptophan and IPA levels and the risks of cardiovascular and all-cause mortality. During the median 9.2-year follow-up, 424 all-cause deaths occurred, of which 272 were cardiovascular deaths. Plasma tryptophan and IPA levels were significantly associated with reduced risks of cardiovascular and all-cause mortality. Patients with CAD with the highest quartiles of tryptophan and IPA levels had multivariable-adjusted HRs of 0.62 (95% CI, 0.43-0.89) and 0.71 (95% CI, 0.50-0.99), respectively, for cardiovascular mortality and 0.67 (95% CI, 0.50-0.90) and 0.75 (95% CI, 0.57-0.99), respectively, for all-cause mortality compared with those in patients with CAD in the lowest quartile. After multivariable adjustments, 1-SD increases in the continuous plasma tryptophan and IPA levels were associated with 16% and 14% decreases, respectively, in the risks of cardiovascular mortality and with 13% and 14% decreases, respectively, in the risks of all-cause mortality. Restricted cubic splines displayed linear associations between plasma tryptophan and IPA levels and cardiovascular and all-cause mortality among patients with CAD. Our findings suggest that plasma tryptophan and IPA levels are significantly associated with decreased risks of cardiovascular and all-cause mortality in patients with CAD. Further studies are needed to determine the clinical diagnostic and therapeutic values of tryptophan and IPA levels on the risks of mortality among patients with CAD.