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

Circ Cardiovasc Genet. 2016 Dec;9(6):487-494. doi: 10.1161/CIRCGENETICS.116.001444. Epub 2016 Oct 26.


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-based cohort 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 used for 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.

Keywords: acylcarnitines; amino acids; cardiovascular disease; lifestyle; lipids; metabolomics.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alcohol Drinking / adverse effects
  • Alcohol Drinking / blood
  • Amino Acids / blood*
  • Biomarkers / blood
  • Body Mass Index
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / epidemiology
  • Carnitine / analogs & derivatives*
  • Carnitine / blood
  • Cross-Sectional Studies
  • Female
  • Germany / epidemiology
  • Hexoses / blood*
  • Humans
  • Linear Models
  • Lipids / blood*
  • Longitudinal Studies
  • Male
  • Metabolomics / methods
  • Middle Aged
  • Multivariate Analysis
  • Obesity / blood
  • Obesity / epidemiology
  • Risk Assessment
  • Risk Factors
  • Sex Factors
  • Smoking / adverse effects
  • Smoking / blood
  • Time Factors


  • Amino Acids
  • Biomarkers
  • Hexoses
  • Lipids
  • acylcarnitine
  • Carnitine