Metabolomics approach reveals effects of antihypertensives and lipid-lowering drugs on the human metabolism

Elisabeth Altmaier, Gisela Fobo, Margit Heier, Barbara Thorand, Christine Meisinger, Werner Römisch-Margl, Melanie Waldenberger, Christian Gieger, Thomas Illig, Jerzy Adamski, Karsten Suhre, Gabi Kastenmüller

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The mechanism of antihypertensive and lipid-lowering drugs on the human organism is still not fully understood. New insights on the drugs' action can be provided by a metabolomics-driven approach, which offers a detailed view of the physiological state of an organism. Here, we report a metabolome-wide association study with 295 metabolites in human serum from 1,762 participants of the KORA F4 (Cooperative Health Research in the Region of Augsburg) study population. Our intent was to find variations of metabolite concentrations related to the intake of various drug classes and-based on the associations found-to generate new hypotheses about on-target as well as off-target effects of these drugs. In total, we found 41 significant associations for the drug classes investigated: For beta-blockers (11 associations), angiotensin- converting enzyme (ACE) inhibitors (four assoc.), diuretics (seven assoc.), statins (ten assoc.), and fibrates (nine assoc.) the top hits were pyroglutamine, phenylalanylphenylalanine, pseudouridine, 1- arachidonoylglycerophosphocholine, and 2-hydroxyisobutyrate, respectively. For beta-blockers we observed significant associations with metabolite concentrations that are indicative of drug side-effects, such as increased serotonin and decreased free fatty acid levels. Intake of ACE inhibitors and statins associated with metabolites that provide insight into the action of the drug itself on its target, such as an association of ACE inhibitors with des-Arg(9)-bradykinin and aspartylphenylalanine, a substrate and a product of the drug-inhibited ACE. The intake of statins which reduce blood cholesterol levels, resulted in changes in the concentration of metabolites of the biosynthesis as well as of the degradation of cholesterol. Fibrates showed the strongest association with 2-hydroxyisobutyrate which might be a breakdown product of fenofibrate and, thus, a possible marker for the degradation of this drug in the human organism. The analysis of diuretics showed a heterogeneous picture that is difficult to interpret. Taken together, our results provide a basis for a deeper functional understanding of the action and side-effects of antihypertensive and lipid-lowering drugs in the general population.

Original languageEnglish
Pages (from-to)325-336
Number of pages12
JournalEuropean Journal of Epidemiology
Volume29
Issue number5
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Metabolomics
Antihypertensive Agents
Lipids
Pharmaceutical Preparations
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Angiotensin-Converting Enzyme Inhibitors
Fibric Acids
Diuretics
aspartyl-phenylalanine
phenylalanylphenylalanine
Pseudouridine
Cholesterol
Fenofibrate
Metabolome
Peptidyl-Dipeptidase A
Drug-Related Side Effects and Adverse Reactions
Nonesterified Fatty Acids
Population
Serotonin
Health

Keywords

  • Angiotensin-converting enzyme inhibitors
  • Beta-blockers
  • Diuretics
  • Fibrates
  • Metabolomics
  • Statins

ASJC Scopus subject areas

  • Epidemiology

Cite this

Altmaier, E., Fobo, G., Heier, M., Thorand, B., Meisinger, C., Römisch-Margl, W., ... Kastenmüller, G. (2014). Metabolomics approach reveals effects of antihypertensives and lipid-lowering drugs on the human metabolism. European Journal of Epidemiology, 29(5), 325-336. https://doi.org/10.1007/s10654-014-9910-7

Metabolomics approach reveals effects of antihypertensives and lipid-lowering drugs on the human metabolism. / Altmaier, Elisabeth; Fobo, Gisela; Heier, Margit; Thorand, Barbara; Meisinger, Christine; Römisch-Margl, Werner; Waldenberger, Melanie; Gieger, Christian; Illig, Thomas; Adamski, Jerzy; Suhre, Karsten; Kastenmüller, Gabi.

In: European Journal of Epidemiology, Vol. 29, No. 5, 2014, p. 325-336.

Research output: Contribution to journalArticle

Altmaier, E, Fobo, G, Heier, M, Thorand, B, Meisinger, C, Römisch-Margl, W, Waldenberger, M, Gieger, C, Illig, T, Adamski, J, Suhre, K & Kastenmüller, G 2014, 'Metabolomics approach reveals effects of antihypertensives and lipid-lowering drugs on the human metabolism', European Journal of Epidemiology, vol. 29, no. 5, pp. 325-336. https://doi.org/10.1007/s10654-014-9910-7
Altmaier, Elisabeth ; Fobo, Gisela ; Heier, Margit ; Thorand, Barbara ; Meisinger, Christine ; Römisch-Margl, Werner ; Waldenberger, Melanie ; Gieger, Christian ; Illig, Thomas ; Adamski, Jerzy ; Suhre, Karsten ; Kastenmüller, Gabi. / Metabolomics approach reveals effects of antihypertensives and lipid-lowering drugs on the human metabolism. In: European Journal of Epidemiology. 2014 ; Vol. 29, No. 5. pp. 325-336.
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