Diastolic left ventricular function in relation to circulating metabolic biomarkers in a population study

Eur J Prev Cardiol. 2019 Jan;26(1):22-32. doi: 10.1177/2047487318797395. Epub 2018 Sep 10.


Aims: We studied the association of circulating metabolic biomarkers with asymptomatic left ventricular diastolic dysfunction, a risk-carrying condition that affects 25% of the population.

Methods and results: In 570 randomly recruited people, we assessed in 2005-2010 and in 2009-2013 the multivariable-adjusted correlations of e' (early left ventricular relaxation) and E/e' (left ventricular filling pressure) measured by Doppler echocardiography with 43 serum metabolites, quantified by magnetic resonance spectroscopy. In 2009-2013, e' cross-sectionally increased (Bonferroni corrected p ≤ 0.016) with the branched-chain amino acid valine (per one standard deviation increment, +0.274 cm/s (95% confidence interval, 0.057-0.491)) and glucose+the amino acid (AA) taurine (+0.258 cm/s (0.067-0.481)), while E/e' decreased ( p ≤ 0.017) with valine (-0.264 (-0.496- -0.031)). The risk of developing left ventricular diastolic dysfunction over follow-up (9.4%) was inversely associated ( p ≤ 0.0059) with baseline glucose+amino acid taurine (odds ratio, 0.64 (0.44-0.94). In partial least squares analyses of all the baseline and follow-up data, markers consistently associated with better diastolic left ventricular function included the amino acids 2-aminobutyrate and 4-hydroxybutyrate and the branched-chain amino acids leucine and valine, and those consistently associated with worse diastolic left ventricular function glucose+amino acid glutamine and fatty acid pentanoate. Branched-chain amino acid metabolism (-log10 p = 12.6) and aminoacyl-tRNA biosynthesis (9.9) were among the top metabolic pathways associated with left ventricular diastolic dysfunction.

Conclusion: The associations of left ventricular diastolic dysfunction with circulating amino acids and branched-chain amino acids were consistent over a five-year interval and suggested a key role of branched-chain amino acid metabolism and aminoacyl-tRNA biosynthesis in maintaining diastolic left ventricular function.

Keywords: Biomarker; branched-chain amino acids; diastolic left ventricular dysfunction; metabolomics; population science.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acids, Branched-Chain / blood*
  • Asymptomatic Diseases
  • Belgium / epidemiology
  • Biomarkers / blood
  • Diastole
  • Echocardiography, Doppler
  • Female
  • Humans
  • Incidence
  • Magnetic Resonance Spectroscopy
  • Male
  • Metabolomics
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • RNA, Transfer, Amino Acid-Specific / blood*
  • Time Factors
  • Transfer RNA Aminoacylation
  • Ventricular Dysfunction, Left / blood*
  • Ventricular Dysfunction, Left / diagnostic imaging
  • Ventricular Dysfunction, Left / epidemiology
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Function, Left*


  • Amino Acids, Branched-Chain
  • Biomarkers
  • RNA, Transfer, Amino Acid-Specific