title: Metabolomics analysis reveals insights into biochemical mechanisms of mental stress-induced left ventricular dysfunction.
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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 3366, Durham, NC 27710, USA.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Boyle
authors.affiliation: Department of Systems Biochemistry, Counterpoint Health Solutions Inc, Bedford, MA, USA.
authors.forename: Wayne R
authors.initials: WR
authors.lastname: Matson
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Velazquez
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Zainab
authors.initials: Z
authors.lastname: Samad
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 3366, Durham, NC 27710, USA.
authors.forename: Redford B
authors.initials: RB
authors.lastname: Williams
authors.affiliation: Department of Systems Biochemistry, Counterpoint Health Solutions Inc, Bedford, MA, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Systems Biochemistry, Counterpoint Health Solutions Inc, Bedford, MA, USA.
authors.forename: Beena
authors.initials: B
authors.lastname: Thomas
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 3366, Durham, NC 27710, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Wilson
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: O'Connor
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 3366, Durham, NC 27710, USA, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
keywords: Left ventricular dysfunction; Mental stress; Metabolomics