Response by Vaccarino et al to Letter Regarding Article, “Mental Stress-Induced-Myocardial Ischemia in Young Patients With Recent Myocardial Infarction: Sex Differences and Mechanisms”

We thank Drs. Singh and Mian for their interest in our recently published paper.¹ We are aware that reproductive hormone status could be an important correlate of vascular response to stress in women. However, menopausal status had little influence on such responses in our study. As mentioned in a footnote to Table 5 in our published paper, adding menopausal status to the model for women did not materially change the results.

In our data, while the prevalence of ever smoking was slightly lower in female controls compared with male controls (25% vs 30%), it was slightly higher among women who had survived a myocardial infarction (MI) than among their male counterparts (61% vs. 56%). Drs. Singh and Mian are correct in pointing out that the prevalence of ever smoking in our post-MI female sample was quite high, and much higher than in the general population of women. However, this is not surprising given that our study is based on a young post-MI sample, and smoking is a stronger risk factor for MI at younger age² and a stronger risk factors among women than men.³ We chose to use ever smoking as our main smoking exposure variable in consideration of the fact that patients may change their smoking habits after an acute MI. In addition, in our sample there was no difference in current smoking status between post-MI women (23%) and post-MI men (24%), and current smoking among controls was quite rare in both sexes (5% in women and 4% in men).

While we agree with Drs. Singh and Mian that depression has been previously associated with endothelial dysfunction and mental stress-induced myocardial ischemia, depression was not associated with vascular function changes with mental stress in our sample of post-MI patients, and, as shown in Table 5 of our published paper, neither psychosocial factors (including depression) nor use of antidepressants meaningfully explained the sex difference in myocardial ischemia with mental stress.

We did not perform myocardial perfusion imaging among controls because this test would not be informative in a low risk, asymptomatic population. We respectfully disagree with Drs. Singh and Mian that such testing could be of value in patients with risk factors but without a history of coronary artery disease if they are asymptomatic and have no indications for this test, as shown, for example, in patients with diabetes mellitus.⁴ Furthermore, it would expose such individuals to unnecessary radiation.