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|Title:||Diastolic Left Ventricular Function in Relation to Circulating Metabolic Biomarkers in a General Population||Authors:||Zhang, Zhen-Yu
Marrachelli, Vannina G.
Staessen, Jan A.
|Issue Date:||2016||Publisher:||WILEY-BLACKWELL||Source:||JOURNAL OF THE AMERICAN HEART ASSOCIATION, 5(3)||Abstract:||Background-The metabolic signature associated with subclinical diastolic left ventricular (LV) dysfunction in the population remains ill defined. Methods and Results-In 711 randomly recruited Flemish (50.8% women; mean age, 50.8 years), we assessed echocardiographic Doppler indexes of diastolic LV function in relation to 44 circulating metabolites determined by nuclear magnetic resonance spectroscopy. In multivariable-adjusted regression analysis with Bonferroni correction of significance levels applied, peak a' decreased (P <= 0.048) and e'/a' increased (P <= 0.044) with circulating tyrosine, high-density lipoprotein apolipoproteins, glucose+glutamine, and an unidentified molecule. Effect sizes expressed per 1-SD increment in the metabolite ranged from -0.277 to -0.203 cm/s for peak a' and from +0.047 to +0.054 for e'/a'. In addition, peak a' decreased (P <= 0.031) with glucose+2-aminobutyrate (-0.261 cm/s) and glucose+2-phosphoglycerate (-0.209 cm/s). In partial least square discriminant analysis (PLS-DA), metabolites associated with normal diastolic LV function (n=538) included glucose+glutamine, glucose+2-aminobutyrate, and glucose+2-phosphoglycerate, whereas those siding with abnormal function encompassed 4-aminobutyrate, 4-hydroxybutyrate, creatinine, and phosphocholine. In receiver operating characteristics plots, adding 3 latent factors identified by PLS-DA to prohormone brain natriuretic peptide increased (P<0.0001) the area under the curve from 0.64 (95% CI, 0.58-0.68) to 0.73 (0.68-0.78). Conclusions-In a general population, circulating metabolites indicative of energy substrate utilization and protection against oxidative stress differentiated normal from abnormal diastolic LV function. These findings improve our understanding of the pathophysiology underlying deterioration of diastolic LV function and potentially point to new targets for prevention and treatment of this condition.||Notes:||[Zhang, Zhen-Yu; Thijs, Lutgarde; Yang, Wen-Yi; Wei, Fang-Fei; Jacobs, Lotte; Kuznetsova, Tatiana; Staessen, Jan A.] Univ Leuven, KU Leuven, Dept Cardiovasc Sci, Studies Coordinating Ctr,Res Unit Hypertens & Car, Campus Sint Rafael,Kapucijnenvoer 35,Box 7001, BE-7001 Leuven, Belgium. [Verhamme, Peter] Univ Leuven, KU Leuven, Dept Cardiovasc Sci, Ctr Mol & Vasc Biol, Leuven, Belgium. [Voigt, Jens-Uwe] Univ Leuven, KU Leuven, Dept Cardiovasc Sci, Res Unit Cardiol, Leuven, Belgium. [Marrachelli, Vannina G.; Monleon, Daniel; Redon, Josep] Fdn Invest Clin Valencia INCLI, Metabol & Mol Image Lab, Valencia, Spain. [Nawrot, Tim] Univ Hasselt, Ctr Environm Sci, Diepenbeek, Belgium. [Nawrot, Tim] Univ Leuven, KU Leuven, Dept Publ Hlth & Primary Care, Res Unit Environm & Hlth, Leuven, Belgium. [Redon, Josep] Univ Valencia, Hosp Clin, Hypertens Unit, Div Internal Med, E-46003 Valencia, Spain. [Redon, Josep] Ctr Invest Biomed Fisiopatol Obesidad & Nutr CIBE, Madrid, Spain. [Staessen, Jan A.] Maastricht Univ, R&D Grp VitaK, Maastricht, Netherlands.||Keywords:||biomarker; diastolic left ventricular function; metabolomics; nuclear magnetic resonance spectroscopy; population science;biomarker; diastolic left ventricular function; metabolomics; nuclear magnetic resonance spectroscopy; population science||Document URI:||http://hdl.handle.net/1942/22741||ISSN:||2047-9980||e-ISSN:||2047-9980||DOI:||10.1161/JAHA.115.002681||ISI #:||000385312200013||Rights:||© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.||Category:||A1||Type:||Journal Contribution||Validations:||ecoom 2017|
|Appears in Collections:||Research publications|
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