Cardiovascular Risk Factors Associated with Blood Metabolite Concentrations and Their Alterations during a 4-Year Period in a Population-Based Cohort

Title
Cardiovascular Risk Factors Associated with Blood Metabolite Concentrations and Their Alterations during a 4-Year Period in a Population-Based Cohort
Publication type
Journal Article
Year of Publication
2016
Journal
Circulation: Cardiovascular Genetics
Volume
9
Issue
6
Pagination
487 - 494
Date published
2016
Keywords
Abstract

Abstract

Background-The effects of lifestyle risk factors considered collectively on the human metabolism are to date unknown. We aim to investigate the association of these risk factors with metabolites and their changes during 4 years. Methods and Results-One hundred and sixty-three metabolites were measured in serum samples with the AbsoluteIDQ kit p150 (Biocrates) following a targeted metabolomics approach, in a population-basedcohort of 1030 individuals, aged 45 to 83 years at baseline. We evaluated associations between metabolite concentrations (28 acylcarnitines, 14 amino acids, 9 lysophosphocholines, 72 phosphocholines, 10 sphingomyelins and sum of hexoses) and 5 lifestyle risk factors (body mass index [BMI], alcohol consumption, smoking, diet, and exercise). Multilevel or simple linear regression modeling adjusted for relevant covariates was usedfor the evaluation of cross-sectional or longitudinal associations, respectively; multiple testing correction was based on false discovery rate. BMI,alcohol consumption, 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.