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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/22741

Title: Diastolic Left Ventricular Function in Relation to Circulating Metabolic Biomarkers in a General Population
Authors: Zhang, Zhen-Yu
Marrachelli, Vannina G.
Thijs, Lutgarde
Yang, Wen-Yi
Wei, Fang-Fei
Monleon, Daniel
Jacobs, Lotte
Nawrot, Tim
Verhamme, Peter
Voigt, Jens-Uwe
Kuznetsova, Tatiana
Redon, Josep
Staessen, Jan A.
Issue Date: 2016
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.
URI: http://hdl.handle.net/1942/22741
DOI: 10.1161/JAHA.115.002681
ISI #: 000385312200013
ISSN: 2047-9980
Category: A1
Type: Journal Contribution
Validation: ecoom, 2017
Appears in Collections: Research publications

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