Plasma hydroxyanthranilic acid as a predictor of stress induced myocardial ischemia in non-obstructive coronary artery disease

Abstract Background The tryptophan catabolite hydroxyanthranilic acid (HAA) has potent immunomodulatory and vasoactive effects. HAA is also a precursor in the synthesis of nicotinamide adenine dinucleotide (NAD), a crucial cofactor in energy-metabolism. We have previously demonstrated that elevated plasma HAA predicted risk of myocardial infarction. Purpose To explore if plasma HAA is associated with stress induced myocardial ischemia in non-obstructive coronary artery disease (CAD). Methods In 132 patients with chest pain and non-obstructive CAD by coronary computed tomography angiography (CCTA), plasma HAA was analyzed by gas chromatography tandem mass spectrometry. All participants underwent myocardial contrast stress echocardiography. Myocardial ischemia was assessed as delayed contrast replenishment at peak dobutamine stress during real-time low mechanical index imaging and destruction replenishment. The extent of ischemia was defined as the number of segments with delayed contrast enhancement using a 17-segment left ventricular model. Associations of plasma HAA with myocardial ischemia was evaluated in a multivariate adjusted linear regression model. Results Mean (SD) age at inclusion was 63 (8) years and 56% were women. At CCTA, the median (25th, 75th percentile) coronary artery calcium (CAC) score was 42 (13–107) Agatston units, whereas the mean (SD) segment involvement score (SIS) was 2.6 (1.6). Myocardial ischemia was found in 52% of patients with on average 5 (3) ischemic segments per patient. Serum HAA did not correlate with the CAC score or SIS (p>0.29). After multivariate adjustment including age, sex, body mass index, systolic blood pressure, diabetes, current smoking, and LDL cholesterol, the odds ratio and 95% confidence interval for myocardial ischemia was 1.55 (1.04–2.32), P=0.03, per SD increment of plasma HAA levels (log transformed). Plasma HAA was also associated with the extent of myocardial ischemia with a multivariate adjusted β of 0.26, P=0.004. Conclusion Plasma HAA is associated with the extent of myocardial ischemia in non-obstructive CAD. Potential roles of this metabolite in atherogenesis, vascular dysfunction and as a predictor of myocardial ischemia should be further elucidated. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Western Norway Regional Health Authority