Additional information and tables for: Association of circulating metabolites in plasma or serum and risk of stroke: Meta-analysis from seven prospective cohorts

Objective: To conduct a comprehensive analysis of circulating metabolites
and incident stroke in large prospective population-based settings.
Methods: We investigated the association of metabolites with risk of
stroke in seven prospective cohort studies including 1,791 incident stroke
events among 38,797 participants in whom circulating metabolites were
measured by Nuclear Magnetic Resonance (1H-NMR) technology. The
relationship between metabolites and stroke was assessed using Cox
proportional hazards regression models. The analyses were performed
considering all incident stroke events and ischemic and hemorrhagic events
separately. Results: The analyses revealed ten significant metabolite
associations. Amino acid histidine (hazard ratio (HR) per standard
deviation (SD) = 0.90, 95% confidence interval (CI): 0.85, 0.94; P =
4.45×10-5), glycolysis-related metabolite pyruvate (HR per SD = 1.09, 95%
CI: 1.04, 1.14; P = 7.45×10-4), acute phase reaction marker glycoprotein
acetyls (HR per SD = 1.09, 95% CI: 1.03, 1.15; P = 1.27×10-3), cholesterol
in high-density lipoprotein (HDL) 2 and several other lipoprotein
particles were associated with risk of stroke. When focusing on incident
ischemic stroke, a significant association was observed with phenylalanine
(HR per SD = 1.12, 95% CI: 1.05, 1.19; P = 4.13×10-4) and total and free
cholesterol in large HDL particles. Conclusions: We found association of
amino acids, glycolysis-related metabolites, acute phase reaction markers,
and several lipoprotein subfractions with the risk of stroke. These
findings support the potential of metabolomics to provide new insights
into the metabolic changes preceding stroke.