Are heart rate and blood pressure responses to mental stress predictive of clinical cardiovascular events? The answer varies by coronary artery disease syndrome☆
Article Outline
The investigators of the Post Coronary Artery Bypass Graft biobehavioral study are to be congratulated for performing a difficult study within a multicenter trial of a group of patients after coronary artery bypass grafting.1 The objective of the study was to assess the predictive value of heart rate and blood pressure responses to mental stress testing after surgery for detecting subsequent clinical events among patients who have undergone recent coronary artery bypass surgery. The authors studied 521 patients (351 men and 170 women) from the cohort of 759 patients in the Post-Coronary Artery Bypass Graft biobehavioral study. They used 2 mental stressors, a mirror tracing test and a speech task, and performed them at 6 months postoperative. Medical status was then ascertained for as long as 3 years after surgery from questionnaires and medical records. The investigators observed that greater heart rate and blood pressure responses to mental stress were linked to a lower risk for clinical events in this population. This finding differs dramatically from patterns previously reported either for other categories of patients with coronary artery disease2, 3 or for adult male patients in a population-based study4; thus the article adds valuable data to the literature relating to the importance of behavioral responses in patients with various types of coronary artery disease syndromes. The investigators were able to perform a detailed laboratory mental stress protocol in a multicenter trial format and were able to produce blood pressure and heart rate responses similar to those obtained in previous studies from single centers. Therefore, an additional contribution of the study lies in demonstrating the feasibility of performing behavioral stress testing in the context of a multicenter clinical trial. Another strength of the study was that the investigators enrolled a large number of women, which is commendable, and were thus able to show that the responses in women are very similar to those in men.
The design of the study did have some limitations that decreased the ability to generalize the results to the population of patients who are post-bypass graft surgery, and the authors acknowledged most of these limitations. First, the mental stress testing was performed 6 months after bypass grafting, a time after many of the clinical events had already occurred. Second, and perhaps more important, the testing was not performed in all the cohort; the sickest patients were excluded. Patients who were excluded included 20 patients (3%) who died between coronary artery bypass surgery and the 6-month follow-up, 19% who refused participation, 10% who were unable to participate because of blood pressure >160/105 mm Hg, anginal episodes more than once per week, acute myocardial infarction since surgery, cardiac arrhythmias requiring hospitalization or anti-arrhythmic medications, or refusal by the patient’s physician. Patients who did not participate in the mental stress testing had twice the mortality rate as those who participated. In addition, the patients who reported treatment with cardiovascular drugs, including β-blocking agents, diuretic drugs, calcium channel drugs, and other drugs to control blood pressure, had an increased mortality rate during follow-up (6.9% vs 1.9% P = .006). Also, it is impossible to determine the degree to which the hemodynamic responses to mental stress testing independently predicted events over and above other known risk factors for adverse outcomes. The investigators state in the Methods section that the primary analysis was a time-to-event analysis with covariates including ejection fraction, age, sex, and prior myocardial infarction. However, little information is given subsequently about the effect of ejection fraction in their modeling. Presumably, the ejection fraction measurement was the preoperative ejection fraction, and the important information for this study would have been the postoperative ejection fraction measurement. It would be interesting to know what the correlation was between heart rate and blood pressure responses to mental stress and left ventricular function either at rest or during stress. It may have been (as the authors indicated in the Discussion section) that patients who have the lowest heart rate and blood pressure change with mental stress have the poorest ventricular function, and the change in hemodynamics was simply a reflection of poor ventricular function.
Despite these limitations, these findings are provocative and suggest that the hemodynamic responses to mental stress testing in patients after bypass grafting do not have the same implications as in most previously studied populations with coronary disease. Most of the previous investigations of mental stress testing in patients with coronary artery disease have been done in groups of patients with documented coronary artery disease and exercise induced ischemia (ie, entry criteria for participation in these prior studies was positive exercise test results). Therefore, those patients differ from the general population of patients after bypass grafting, most of whom we would presume to be less likely to have exercise-induced ischemia in the early post-bypass graft time frame.
Previous studies of patients with exercise-induced ischemia and coronary disease have reported that men with coronary heart disease who had clinical cardiac events responded to psychophysiologic test procedures with greater increases in systolic blood pressure than patients without subsequent events.2, 3 Furthermore, the Psychophysiological Interventions in Myocardial Ischemia (PIMI) study reported that patients with higher hemodynamic responses to stress were more likely to have myocardial ischemia detected with radionuclide techniques during the stressor.5 However, in the PIMI follow-up study, only a specific marker of ischemia during the stressor (ie, wall motion abnormalities) was predictive of subsequent death.6 This is probably because ischemia produced during mental stress may reflect not only increases in myocardial oxygen demand—as indicated by change in heart rate and blood pressure—but also by decreases in supply caused by epicardial coronary constriction, microvascular changes, or both.7 Therefore, as the authors point out in their discussion, an exaggerated blood pressure response to mental stress testing may constitute a risk factor for cardiovascular events only when the higher response is associated with myocardial ischemia.
It would be interesting to know whether heart rate variability measurements taken during the mental stressor might have provided further diagnostic power. The authors conclude their discussion by stating that patients in the biobehavioral study may have had heart rate and blood pressure responses to mental stress testing that were determined more by left ventricular ability to respond than myocardial ischemia.
What lessons can be learned from the results of this study? First, the predictive value of hemodynamic responses to mental stress testing has to be assessed in the context of the patient population being tested. Results obtained in patients with exercise-induced ischemia who have not had previous bypass graft surgery cannot be extrapolated to the post-bypass graft population. This is not surprising, because it is also well known that other tests such as treadmill testing are not very helpful in patients who are post-bypass grafting.8 However, this does not deny that mental stress testing using different types of diagnostic measurements (perhaps of myocardial perfusion during mental stress) might be useful in predicting future events even in the post-bypass graft population. Whether this would turn out to be incrementally predictive to exercise or chemical-induced perfusion abnormalities in that population remains to be determined.
References
- Heart rate and blood pressure responses to mental stress and clinical cardiovascular events in men and women after coronary artery bypass grafting (the Post Coronary Artery Bypass Graft (Post-CABG) biobehavioral study). Am Heart J. 2003;146:273
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- Stress-induced blood pressure reactivity and incident stroke in middle-aged men. Stroke. 2001;32:1263–1270
- Ischemic, hemodynamic, and neurohormonal responses to mental and exercise stress (experience from the Psychophysiological Investigations of Myocardial Ischemia Study (PIMI)). Circulation. 1996;94:2402–2409
- Mental stress ischemia and all-cause mortality in patients with coronary artery disease (results from the Psychophysiological Investigations of Myocardial Ischemia Study (PIMI)). Circulation. 2002;105:1780–1784
- Myocardial blood-flow response during mental stress in patients with coronary artery disease. Lancet. 2000;356:310–311
- . Use of the exercise test to predict prognosis after coronary artery bypass grafting. Am J Cardiol. 1989;63:530–533
☆ Reprints not available from the authors.
PII: S0002-8703(03)00183-2
doi:10.1016/S0002-8703(03)00183-2
© 2003 Mosby, Inc. All rights reserved.
