Abstract
Mental stress induced left ventricular dysfunction (LVD) has been associated with a greater risk of adverse events in coronary heart disease (CHD) patients independent of conventional risk indicators. The underlying biochemical mechanisms of this cardiovascular condition are poorly understood. Our objective was to use metabolomics technology to identify biochemical changes that co-occur with mental stress-induced LVD in patients with clinically stable CHD. Participants were adult CHD patients who were recruited for mental stress-induced myocardial ischemia screening. For this study, we randomly selected 30 patients representing the extremes of the mental stress-induced left ventricular ejection fraction (LVEF) change distribution; 15 who showed LVD (i.e. LVEF reduction ≥5) and 15 who showed a normal left ventricular response (NLVR; i.e. a LVEF increase of ≥5) to three mental stressors. An electrochemistry based metabolomics platform was used to profile pre- and post-stress serum samples yielding data for 22 known compounds, primarily within the tyrosine, tryptophan, purine and methionine pathways. There were significant stress-induced changes in several compounds. A comparison between the NLVR and LVD groups showed significant effects for kynurenine (p = .036, N-acetylserotonin (p = .054), uric acid (p = .015), tyrosine (p = .019) and a trend for methionine (p = .065); the NLVR group showed a significantly greater stress-induced reduction in all of those compounds compared to the LVD group. Many of these biochemicals have been implicated in other stress-related phenomena and are plausible candidates for mechanisms underlying LVD in response to mental stress.
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Acknowledgments
The authors would also like to thank Ye Zhang, MA, Kevin Prybol, MPH, and Kaitlyn Weinberg for their contributions to the creation of figures and tables for this paper and their assistance in editing the manuscript. The study was funded by National Heart, Lung, and Blood Institute, grant number R01HL085704.
Conflict of interest
Dr. Redford B. Williams reports holding a U.S. patent on the 5HTTLPR L allele for use as a marker of increased cardiovascular risk in stressed persons and is a founder and major stockholder of Williams LifeSkills, Inc. Dr. Velazquez reports receiving research grants from Abbott Laboratories, Evalve, and Ikaria, and consulting fees from Boehringer Ingelheim, Gilead, and Novartis. Dr. O’Connor reports receiving funding from the following: Actelion Pharmaceuticals Ltd., Amgen, Inc., Biscardia, LLC, Cardiology Consulting Associates, Faculty Connection, GE Healthcare, Ikaria, Neurotronik/Interventional Autonomics Corporation, Novella Clinical, Inc., Pfizer Inc., Pozen, and Roche Diagnostics. Dr. Wayne R. Matson is currently Chief Scientist at Counterpoint Health Solutions and is involved in developing patens in disease risk factors based on metabolomics.
Funding Source
The REMIT study was funded by the National Heart Lung and Blood Institute (NHLBI, R01HL085704), Bethesda, Maryland.
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Boyle, S.H., Matson, W.R., Velazquez, E.J. et al. Metabolomics analysis reveals insights into biochemical mechanisms of mental stress-induced left ventricular dysfunction. Metabolomics 11, 571–582 (2015). https://doi.org/10.1007/s11306-014-0718-y
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DOI: https://doi.org/10.1007/s11306-014-0718-y