Increase in Peripheral Arterial Tone Predicts Myocardial Ischemia Induced by Mental Stress

INCREASE IN PERIPHERAL ARTERIAL TONE PREDICTS MYOCARDIAL ISCHEMIA INDUCED BY MENTAL STRESS Brendon Graeber, B.A., Matthew M. Burg, Ph.D., Aseem Vashist, M.D., Christine Earley, M.A., Joyce Liu, B.A., and Robert Soufer, M.D. Department of Internal Medicine, Yale University School of Medicine, New Haven, CT Mental stress ischemia (MSI) is associated with poor prognosis for coronary artery disease (CAD) and is amenable to treatment, yet no easily administered test exists to diagnose it. Given the known increase in systemic vascular tone in response to stress, we studied the ability of peripheral arterial tonometry (PAT), a noninvasive functional measure of arterial tone, to predict those vulnerable to MSI. Seventy-seven patients with chronic stable CAD were subjected to mental stress with concomitant assessment of myocardial perfusion and pulse wave amplitude. Nuclear perfusion imaging was used to document MSI, and PAT was used to measure pulse wave and microarterial tone. A ratio of PAT measurements during stress to those before stress was used to characterize vascular responses. Serum catecholamines and endothelin-1 (ET-1) were simultaneously measured. Subjects who experienced MSI had a lower average PAT ratio than those who did not (0.76 ± 0.04 vs. 0.91 ± 0.05, P = 0.03). A receiver operating characteristics curve for PAT ratio predicting MSI had an area under the curve of 0.613 (standard error, 0.065, one-sided P = 0.04). Maxima of sensitivity and specificity were observed at a threshold of 0.78 to define an abnormal PAT ratio. Cross-tabulation of groups above and below this threshold with groups of subjects with and without MSI showed a significant predictive relationship between PAT ratio and MSI (P = 0.03). Subjects at or below this threshold (≤0.78) displayed a significant increase in norepinephrine levels during mental stress (235 pg/ml at baseline, 259 pg/ml during mental stress, P = 0.007). Subjects above this threshold (>0.78) displayed a significant decline in their ET-1 levels 24 hours after mental stress (1.15 pg/ml after mental stress, 0.93 pg/ml 24 hours later, P = 0.01), while those at or below threshold had a continued increase. PAT ratio is a complex functional measure of peripheral arterial tone that significantly predicts the occurrence of MSI. It may have clinical value as an easily administered screening test for MSI. ACKNOWLEDGEMENTS I would like to acknowledge the generous guidance and assistance of the following individuals and groups in completing this research project: Dr. Robert Soufer, Dr. Matthew Burg, and the physicians and staff of the Neurocardiac Research Lab Dr. George Tellides, Dr. Hooman Ranjbaran, Dr. Amy Gallo, and the researchers of the Tellides Lab Dr. Liana Fraenkel Ralph Jacob and the staff of the Yale General Clinical Research Center Dr. John Forrest and the Office of Student Research This work was supported by a Clinical Research Fellowship from the Doris Duke Charitable Foundation, by an NIH Predoctoral Clinical Research Training Fellowship, and by the James G. Hirsch, M.D., Endowed Medical Student Research Fellowship.