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Gustav Smith

Associate professor

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Pharmacometabolomic Profiling Of The General Population: Relation Of Active Metabolite Levels To Cardiovascular Risk Factor Control And Manifest Atherosclerosis

Author

  • Madeleine Johansson
  • Nilanjan Ghosh
  • Carl Lejonberg
  • Tomasz Czuba
  • Maya Landenhed Smith
  • Tove Fall
  • Gunnar Engström
  • Gustav Smith

Summary, in English

Introduction: The use of medications in the general population has increased over time. Information on active metabolite concentrations for common drugs in the general population is limited. Recent advances in metabolomic technologies have made high-throughput profiling of many active metabolites in large epidemiological cohorts increasingly feasible.

Aim: 1. Prospective assessment of the proportion of measurable active metabolite levels of major drugs in the general population using mass spectrometry. 2. Relation of cardiovascular (CV) drugs with inadequate risk factor control and CV disease.

Methods: Assessment of CV risk factors by coronary CT angiography and carotid ultrasound imaging in a large prospective cohort of 6,251 individuals randomly selected from the general population in Malmö, Sweden (age 50-64 years). Untargeted metabolomic profiling of fasting plasma was performed by Metabolon, USA in a random subset of 3,986 subjects.

Results: Intake of at least one prescribed drug was reported in 1840 subjects (46%). Combination drugs were reported in 249 subjects (6%). The most common drug classes reported were lipid-lowering (n=369, 9% of which most were statins), beta blockers (n=307, 8%), ARB (n=272, 7%), and ACE inhibitors (268, 7%), followed by levothyroxine, CCB, antidepressants, glucocorticoids, PPI, antidiabetic, bronchodilators and diuretics. For major CV drugs, detectable active metabolite levels ranged from 54% (atorvastatin and enalapril) to 96% (metoprolol and metformin). Non-detectable levels of lipid-lowering, antihypertensive, and antidiabetic drugs were associated with higher LDL, cholesterol, BP and glucose, although only antidiabetic drugs were significant (p<0.05). Non-detectable levels of lipid-lowering and antihypertensive drugs were also non-significantly associated with increased coronary calcium and carotid plaque.

Conclusion: Our study provides an overview of the distribution of common drugs with detectable levels in a contemporary Swedish population. Pharmacometabolomic profiling revealed that non-measurable levels of common CV drugs were associated with lower risk factor control and non-significant trends towards more atherosclerotic disease by imaging in a substantial number of subjects.

Department/s

  • Cardiovascular Research - Hypertension
  • Molecular Epidemiology and Cardiology
  • Cardiology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Artificial Intelligence in CardioThoracic Sciences (AICTS)
  • Thoracic Surgery
  • Cardiovascular Research - Epidemiology
  • EpiHealth: Epidemiology for Health
  • WCMM-Wallenberg Centre for Molecular Medicine
  • Heart Failure and Mechanical Support
  • Cardiovascular Epigenetics

Publishing year

2021-11-08

Language

English

Publication/Series

Circulation

Volume

144

Issue

suppl_1

Document type

Conference paper: abstract

Publisher

Lippincott Williams & Wilkins

Topic

  • Clinical Medicine
  • Cardiac and Cardiovascular Systems

Keywords

  • Cardiology
  • Metabolomics
  • EPIDEMIOLOGY
  • Atherosclerosis
  • Cardiovascular risk factors

Conference name

American Heart Association (AHA), Scientific Session 2021

Conference date

2021-11-13 - 2021-11-15

Conference place

Boston, United States

Status

Published

Research group

  • Cardiovascular Research - Hypertension
  • Molecular Epidemiology and Cardiology
  • Artificial Intelligence in CardioThoracic Sciences (AICTS)
  • Cardiovascular Research - Epidemiology
  • Heart Failure and Mechanical Support
  • Cardiovascular Epigenetics

ISBN/ISSN/Other

  • ISSN: 1524-4539