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

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

Author information

1
1 Research Unit Hypertension and Cardiovascular Epidemiology, University of Leuven, Belgium.
2
2 Department of Cardiology, Shanghai General Hospital, China.
3
3 Metabolomic and Molecular Image Laboratory, Fundación Investigatión Clínico de Valencia (INCLIVA), Spain.
4
4 Department of Physiology, University of Valencia, Valencia, Spain.
5
5 Research Unit Cardiology, University of Leuven, Belgium.
6
6 Centre for Molecular and Vascular Biology, University of Leuven, Belgium.
7
7 Hypertension Unit, University of Valencia, Spain.
8
8 Centro de Investigación Biomédica de la Fisiopatología de la Obesidad y la Nutrición (CIBERObn), Ministerio de Ciencia e Innovación, Spain.
9
9 Instituto de Salud Carlos III, Spain.
10
10 Cardiovascular Research Institute (CARIM), Maastricht University, The Netherlands.

Abstract

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

PMID:
30196724
DOI:
10.1177/2047487318797395

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