Fig 1.

Untargeted metabolomics reveals that p-cresol is associated with overall mortality. (A) Comparison of electron ionization spectra of the compound detected in plasma and an authentic standard of the trimethylsilyl derivative of p-cresol. (B) Relative plasma levels of p-cresol in sequential stable subjects undergoing elective diagnostic cardiac evaluation. Subjects (n = 1,149; discovery cohort) were divided into groups as indicated based on whether or not they died during the 5-year follow-up. In the box-whisker plot, the upper and lower boundaries of the box represent the 25th and 75th percentiles, the median is marked by a horizontal line inside the box, and the whiskers represent 10% and 90% measured values. (C) Kaplan-Meier estimates of the risk of incident death by quartile of relative amounts of p-cresol from the untargeted analysis. (D) Forest plots showing overall mortality within 5 years among test subjects according to the quartiles for the relative level of p-cresol (black), or a multivariable Cox model for hazard ratio that includes adjustments for age, sex, current smoking, high-density lipoprotein, low-density lipoprotein, triglyceride level, systolic blood pressure, diabetes mellitus, and high-sensitivity C-reactive protein (adjusted, red). Symbols represent hazard ratios and the 95% CIs are indicated by the line length.