The association of Xylitol and incident cardiovascular events: the CLSA and EPIC-Norfolk cohort studies
T M Zheng, I D Stewart, U Makhmudova, Y Chen, M Piezner, U Landmesser, S Zhou, N Wareham, M WitkowskiAbstract
Background and aims
Artificial sweeteners are generally regarded as safe by regulatory agencies and incorporated into processed foods in large amounts. Recent studies found that the low-calorie sweetener xylitol is associated with cardiovascular outcomes in high-risk populations and enhances thrombosis potential in vivo. The association of xylitol with cardiovascular event risk in the general population is unknown.
Methods
Untargeted metabolomics data from two prospective observational studies across both North America and Europe (Canadian Longitudinal Study on Aging (CLSA), n=7,651; European Prospective Investigation into Cancer (EPIC)-Norfolk, n=10,059) were analyzed. Cox regression models adjusted for traditional cardiovascular risk factors were built to analyze the association between xylitol plasma concentrations and risk of incident major cardiovascular events (myocardial infarction, stroke or death, MACE).
Results
A total of 17,710 participants from the two cohorts with a mean age of 60.9 years were included. During the follow-up (6 years for CLSA und 30 years for EPIC-Norfolk), a total of 2,950 events occurred in CLSA, 5,670 events occurred in EPIC-Norfolk. Independent of traditional cardiovascular risk factors, circulating xylitol levels were associated with incident MACE risk: Q4 vs. Q1; adjusted hazard ratio(aHR) [95% confidence interval] 1.47 [1.15 - 1.86], P= 0.002 in CLSA and aHR 1.18 [1.09 – 1.27], P< 0.0001 in EPIC-Norfolk. Subgroup analyses showed a consistent significant increase in MACE risk across different subpopulations in both cohort studies irrespective of baseline characteristics and preexisting cardiometabolic factors.
Conclusions
Xylitol is independently associated with incident MACE risk in two large population-based cohorts and thus predicts residual cardiovascular event risk in primary prevention subjects. Based on the known pro-thrombotic properties, xylitol appears to promote event risk in the absence of overt cardiometabolic risk factors.