Myocardial Ischemia and Mental Stress: Mechanisms Differ in Women and Men

An investigation into mechanisms underpinning mental stress-induced myocardial ischemia in men and women suggests distinct cardiovascular responses between the sexes, with ischemia in women mostly influenced by changes in the microvasculature.

By contrast, mental-stress induced myocardial ischemia in men is mostly a response to hemodynamic changes, including increased blood pressure and heart rate.

“This means that men and women potentially differ in their vulnerability, in terms of mechanisms, to mental stress-induced ischemia,” senior investigator Viola Vaccarino, MD, PhD (Emory University, Atlanta, GA), told TCTMD. “In the past, it’s already been shown that women have a greater propensity toward microvascular disease, meaning their microcirculation is more likely to be impaired even if they don’t have obvious narrowing in the large coronary arteries. . . . We think that’s what we’re picking up here.”

The results, published today in Arteriosclerosis, Thrombosis, and Vascular Biology, support a more prominent microvascular role for women in the development of myocardial ischemia induced by mental and/or emotional stress, say researchers.  

Stressful Public Speaking (to ‘White-Coated’ Audience)

Speaking with TCTMD, Vaccarino said several decades ago researchers showed that psychological stress can induce myocardial ischemia in individuals with coronary artery disease. Emotional stress and stress-induced physiological changes have also been shown to negatively affect cardiovascular risk and to predict future adverse events.

Acute sympathetic nervous system activation caused by mental/emotional stress results in an increase in blood pressure and heart rate as well arterial vasoconstriction, particularly in the microvasculature. These changes can increase the cardiac workload. Vaccarino noted that vasoconstriction caused by stress can also occur in the coronary arteries. Among those who develop mental stress-induced ischemia, there is an approximately twofold increase in risk of cardiac events and mortality, said Vaccarino.

“The problem with those previous studies was that they included primarily male subjects,” she said. “Up until now, we have known very little about [this] phenomenon among women.”

With that in mind, the researchers assessed sex-specific mechanisms that might explain the differential responses to mental or emotional stress in the Mental Stress Ischemia Mechanisms and Prognosis Study (MIPS).

In total, 678 subjects, including 186 women, were asked to imagine a stressful situation (a close relative mistreated in a nursing home) and then speak for 3 minutes in front of a camera and an audience wearing white coats. Myocardial perfusion imaging with single-photon emission computed tomography was performed 30 to 60 minutes after the stressful public speaking task. Blood pressure and heart rate, which was used to calculate the rate pressure product (RPP), a measure of hemodynamic stress, were recorded during the 30-minute resting phase preceding the task and at 1-minute intervals during the public speaking task.

Compared to women without stress-induced ischemia, those with reduced myocardial blood flow had significantly higher heart rates throughout (including rest, during the speaking task, and recovery) but no significant differences in hemodynamic workload, including the RPP. Women with stress-induced ischemia did have a significantly lower peripheral arterial tonometry ratio—which is a marker of greater vasoconstriction—when compared with women without stress-induced ischemia.

Men with stress-induced ischemia, on the other hand, had larger increases in multiple hemodynamic markers, including a higher RPP, during the speaking assignment compared with men without ischemia. There was no difference in the peripheral arterial tonometry ratio among men with and without emotional stress-induced myocardial ischemia.

“Peripheral vasoconstriction in women is a much stronger predictor of ischemia from mental stress than in men,” said Vaccarino. “Women who had this pronounced peripheral response to stress were much more likely to develop myocardial ischemia. For men, we did not find this. It was the other pathway, the increase in heart rate and blood pressure, that made them much more vulnerable to mental stress.”    

In the present study, the researchers were unable to link stress-induced ischemia to adverse cardiovascular outcomes. For that reason, it is difficult to determine the clinical meaningfulness of the sex-specific differences in response to psychological stress. In studies with men, stress-induced ischemia was associated with adverse clinical outcomes, “so we assume that these women will be at higher risk, too,” said Vaccarino.