Erythritol, Erythronate, and Cardiovascular Outcomes in Older Adults in the ARIC Study

BACKGROUND: Circulating erythritol, an endogenously produced metabolite and an artificial sweetener, is associated with cardiovascular outcomes. OBJECTIVES: The authors assessed associations of erythritol and its downstream metabolite, erythronate, with cardiovascular risk factors and events in older adults in the ARIC (Atherosclerosis Risk In Communities) study (visit 5, 2011-2013). METHODS: We included 4,006 participants without prevalent cardiovascular disease and with metabolomic profiling. Erythritol and erythronate were measured by mass spectrometry. We analyzed associations of log-transformed erythritol and erythronate with cardiovascular risk factors and events using Cox proportional hazard models. RESULTS: Participants in the highest tertiles of erythritol or erythronate were older, more likely to have diabetes, hypertension, hyperlipidemia, or microalbuminuria, and had higher body mass index and cardiac biomarkers and lower estimated glomerular filtration rate (P < 0.001). Over median follow-up of 8.41 (7.62, 8.93) years, higher erythritol and erythronate concentrations were significantly associated with heart failure (HF) hospitalization, HF with preserved ejection fraction, cardiovascular death, and total mortality after adjustment for demographics and traditional cardiovascular risk factors. Erythronate was additionally significantly associated with coronary heart disease (HR: 1.30 [95% CI: 1.04-1.61], P = 0.02), stroke (1.40 [95% CI: 1.08-1.83], P = 0.012), and HF with reduced ejection fraction (1.38 [95% CI: 1.09-1.74], P = 0.007). Diabetes status did not modify any of these associations (P for interaction >0.20). CONCLUSIONS: Circulating erythritol and erythronate levels are markers of cardiometabolic health and cardiovascular outcomes in an older adult population. In particular, erythronate is associated with all cardiovascular outcomes assessed. Future studies should assess the role of erythronate and its related pathways in cardiovascular disease.