부산대학교 도서관

Introduction: Randomized controlled trials indicate that a Mediterranean-style Diet (MSD) reduces the risk of recurrent CVD, protects against adverse cardiovascular events, and improves biomarkers of CVD risk. However, the precise molecular mechanisms accounting for CVD protection are unknown.Methods: Untargeted metabolomic profiling assays, representing >10,000 spectral features, were conducted on sera from ~4,000 men and women ages 45-90, who were free from overt CVD. Diet was measured using a self-report food frequency questionnaire, and a MSD score was constructed based on median population splits for the following intakes: vegetables, legumes, fruit, nuts, whole grains, fish, and saturated to unsaturated fat ratio (positively scored), and red meat and high-fat dairy (negatively scored). A point was added for intake of one alcoholic drink per day on average. Incident CVD was assessed yearly via in-person clinic visits or telephone interview for 10 years after diet measures and serum sampling. Models which controlled for age, gender, ethnicity, data collection site and daily caloric intake were run between MSD, metabolomic information and incident CVD.Results: MSD score was associated with CVD incidence over a 10-year follow up period (HR=.95; P=.02). 288 spectral features were significantly associated with MSD score, at a metabolome-wide threshold of P<1.8*10. The sentinel metabolomic hit showed an inverse association with both MSD (β = -0.12; p=2.50*10), and incident CVD (OR=1.34; P=6.36*10). This molecule was identified as 1,5-anhydrosorbitol. When both 1,5-anhydrosorbitol and MSD were included in the same model, MSD was no longer associated with CVD (P=.11), while the association of 1,5-anhydrosorbitol with CVD remained significant (OR=1.34; P=2.08*10).Conclusions: These preliminary data suggest that 1,5-anhydrosorbitol may be a marker of both diet and incident CVD, and may partially account for the association between a MSD and CVD protection. These results hold promise for starting to identify the underlying pathways by which a MSD conveys CVD-protection.