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ABSTRACT & COMMENTARY
By Harold L. Karpman, MD, FACC, FACP
Clinical Professor of Medicine, UCLA School of Medicine
Dr. Karpman reports no financial relationships relevant to this field of study.
SYNOPSIS: In a systematic review and meta-analysis of prospective studies examining the association between mental stress-induced myocardial ischemia (MSIMI) and adverse outcome events in patients with stable CAD, all existing investigations point to an approximate doubling of cardiovascular risk in patients with MSIMI.
SOURCE: Wei J, et al. Meta-analysis of mental stress-induced myocardial ischemia and subsequent cardiac events in patients with coronary artery disease. Am J Cardiol 2014;114:187-192.
It has been reported that one-third to one-half of patients with coronary artery disease (CAD) develop myocardial ischemia in response to mental stress.1 Mental stress-induced myocardial ischemia (MSIMI) differs from physical exercise or pharmacologic stress-induced myocardial ischemia in that it is less likely to result in chest pain and/or electrocardiographic changes and is not always related to the severity of the coronary atherosclerosis that is present.2,3
Because the prognostic significance of MSIMI has not been previously clarified and because the effects of the various treatment modalities are emerging,4,5 Wei and colleagues performed a systematic review and meta-analysis of the subject with the primary objective of summarizing the existing evidence of the association between MSIMI and adverse outcomes in patients with CAD. Only five studies each with a sample size of less than 200 patients and with fewer than 50 outcome events met the inclusion criteria. The results demonstrated that MSIMI was associated with a two-fold increased risk of a combined endpoint of cardiac events or total mortality.
Despite a systematic review of the literature, Wei et al were only able to find five prospective studies that had investigated MSIMI as a prognostic factor in patients with CAD. Their pooled analysis confirmed a strong association between MSIMI and adverse outcome events in patients with CAD. However, it should be carefully noted that there were only five prospective studies, all of which were relatively small in number and were mostly based on selected small samples with only a few female and minority participants. In addition, most of the studies were incompletely adjusted for potential confounding factors such as medication use and history of other chronic illnesses. Also, since these studies were mostly concerned with patients who were enrolled many years previously, none of the studies used myocardial perfusion imaging, which is believed to be more accurate for the detection of MSIMI than other diagnostic testing methods, based solely on changes in left ventricular function.6
Although several other studies have examined the subject,1,7 the current meta-analysis by Wei et al was the first study to summarize the existing literature on the prospective association between MSIMI and adverse outcomes in patients with CAD. In addition, the precise mechanisms for the association between MSIMI and adverse outcomes are unclear; one possibility is that mental stress causes both coronary artery vasoconstriction and increased heart rate and/or blood pressure, thereby resulting in a myocardial oxygen supply/demand mismatch.6,8 Mental stress has been linked to impaired endothelial function,9 exaggerated peripheral microvascular tone,3,10 and vasoconstriction of normal coronary artery segments.11 Finally, mental stress has also been associated with induced cardiac electrical instability, possibly resulting in cardiac arrhythmias and even sudden cardiac death.12-14
Physicians should be aware of the possible untoward effects of MSIMI and, although more data are needed, MSIMI recognition and management may provide a novel therapeutic approach that may improve patient outcomes over and above the outcomes expected when using only the standard treatments of CAD complications.