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A noninvasive clinically useful predictor for mental stress-induced ischemia.

Acute psychological stress is a nontraditional risk factor for adverse outcomes in patients with coronary artery disease (CAD). Several observational studies have demonstrated the adverse effects of acute psychological stress on patients with CAD in settings of natural disasters and terrorist attacks (1–3). From laboratory studies it is now clear that acute psychological stress can induce transient myocardial ischemia in 30% to 60% of patients with CAD (4). The PIMI (Psychological Investigation of Myocardial Ischemia) study showed that this phenomenon of mental stress-induced myocardial ischemia confers a threefold increased risk of death at 5 years after controlling for traditional risk factors (5). Thus the detection and treatment of this phenomenon is clinically relevant and may translate into important clinical benefits for the large CAD population in the United States and around the world. Mental stress-induced myocardial ischemia is a welldefined clinical phenotype. However, it is challenging to detect clinically given that it is almost always asymptomatic and is rarely associated with the classic electrocardiographic changes observed with other ischemic syndromes (4). Laboratory studies have demonstrated that mental stress-induced myocardial ischemia occurs via several unique mechanisms, with the most consistently reported one seeming to be a widespread peripheral systemic vasoconstriction with consequent rapid rise in systemic vascular resistance and myocardial supply-demand related ischemia (6). In this issue of the journal, Burg and colleagues (7) demonstrate that this peripheral vasoconstrictive response to psychological stress provides a unique opportunity for the detection of mental stress ischemia. They report the utility of a novel peripheral arterial tonometry (PAT) technique for the detection of mental stress ischemia. They used the PAT device to measure finger-pulse wave amplitude during rest and psychological stress. The stress to rest PAT ratio was found to have modest accuracy for the detection of mental stress ischemia with a sensitivity of 0.62 and a specificity of 0.63. Furthermore, among patients taking angiotensin converter enzyme (ACE) inhibitors, the sensitivity and specificity of the test increased to 0.86 and 0.73, respectively. This study provides further insights into potential mechanisms underlying the development of mental stress-induced ischemia. One possibility is that the exaggerated peripheral vascular constriction during mental stress imposes increased demand on the myocardium, or alternatively, the excessive peripheral vasoconstriction reflects similar changes in the coronary circulation, including the microcirculation, that limits blood flow increase and thus precipitates myocardial ischemia. The findings of this study have potential practical clinical application. Given that the development of myocardial ischemia during laboratory mental stress testing confers increased risk for morbidity and mortality independent of traditional risk factors, it is reasonable to assume that identifying patients at risk for this phenomenon is clinically useful. Studies are currently under way to develop effective behavioral and pharmacologic therapeutic intervention for this phenomenon. Although it is not yet used in clinical settings, we believe that laboratory mental stress testing will become applicable once an effective therapeutic strategy becomes available for mental stress ischemia. The findings of this study will be useful in that regard. Although the predictive accuracy of this technique is imperfect, it is equivalent to the accuracy of exercise testing in the detection of exercise-induced ischemia. It is possible that future studies might identify better prediction tools by combining this technique with other stress response markers. We have recently published data suggesting that patients with a specific genetic marker related to adrenergic receptor polymorphisms are at significantly increased risk for developing mental stress ischemia (8). The use of the PAT approach with genetic markers or other clinical signals of ischemia may improve the accuracy of this technique. Another equally important area to investigate is the accuracy of this approach in predicting clinical outcomes such as death and other cardiac events.