Cardiovascular risk factors associated with blood metabolite concentrations and their alterations over a 4-year period in a population-based cohort.

BACKGROUND: -The effects of lifestyle risk-factors considered collectively on the human metabolism are so far unknown. We aim to investigate the association of these risk-factors with metabolites and their changes over 4 years. METHODS AND RESULTS: -163 metabolites were measured in serum samples with the AbsoluteIDQ kit p150 (Biocrates) following a targeted metabolomics approach, in a population-based cohort of 1030 individuals, aged 45-83 at baseline. We evaluated associations between metabolite concentrations (28 acylcarnitines, 14 amino acids, 9 lyso-phosphocholines, 72 phosphocholines, 10 sphingomyelins and sum of hexoses) and 5 lifestyle risk factors (BMI, alcohol consumption, smoking, diet and exercise). Multilevel or simple linear regression modelling adjusted for relevant covariates was used for the evaluation of cross-sectional and longitudinal associations respectively, multiple testing correction was based on false discovery rate. BMI, alcohol and smoking were associated with lipid metabolism (reduced lyso- and acyl-alkyl-phosphatidylcholines and increased diacylphosphatidylcholines concentrations). Smoking showed positive associations with acylcarnitines and BMI correlated inversely with nonessential amino acids. Fewer metabolites showed relative changes that were associated with baseline risk-factors: increases in 5 different acyl-alkyl phosphatidylcholines were associated with lower alcohol consumption and BMI, and with a healthier diet. Increased levels of tyrosine were associated with BMI. Sex-specific effects of smoking and BMI were found specifically related to acylcarnitine metabolism: in women higher BMI and in men more pack-years were associated with increases in acylcarnitines. CONCLUSIONS: -This study showed sex-specific effects of lifestyle risks factors on human metabolism and highlighted their long-term metabolic consequences.