Mental stress-induced ischaemia in patients with stable coronary heart disease is associated with an elevated risk of adverse cardiovascular events.

The finding comes from a pooled analysis of two prospective cohort studies, in which mental stress was provoked with a public speaking test and measured using myocardial perfusion testing.

The primary outcome was a composite of cardiovascular death or first or recurrent nonfatal myocardial infarction over a follow up period of 5-6 years.

The study found the pooled event rate was 6.9 per 100 patient-years in patients with mental stress–induced ischaemia compared to 2.6 per 100 patient-years in those without (adjusted HR 2.5).

“When examined separately, mental stress–induced ischaemia alone but not conventional stress ischaemia alone was significantly associated with an increased risk.”

“The known association of conventional stress ischaemia with outcomes in patients with CHD may be in part explained by its co-occurrence with mental stress–induced ischaemia,” the study said.

The secondary end point of hospitalisations for heart failure was observed in 12.6 per 100 patient-years for patients with mental stress–induced ischaemia and 5.6 per 100 patient-years for those without mental stress–induced ischaemia (adjusted HR, 2.0 (95% CI, 1.5-2.5).

The study, published in JAMA, said the association was stronger among men than women.

“As a whole, this evidence suggests that the value of stress and mental health factors for CHD risk stratification should be investigated, given that they are amenable to medical and lifestyle intervention, including aerobic exercise and stress management training, antidepressants, and β-blockers and antianginal drugs.”

“Although these findings may provide insights into mechanisms of myocardial ischaemia, further research is needed to assess whether testing for mental stress–induced ischaemia has clinical value.”

An editorial in the journal said there was sufficient evidence now that mental stress can trigger myocardial infarction, reversible cardiomyopathy, and sudden cardiac death in susceptible individuals.

“The link between mental stress and CHD was first described over a century ago and has become an important topic of research over the past 40 years.”

It said the present study confirmed prior observations and extended the findings to women, Black and younger individuals with stable CHD.

“In addition, this study reports for the first time the complex interplay that seems to exist between inducible ischaemia by mental stress and conventional stress testing, which can result in distinct ischaemia phenotypes that may have different risk profiles.”

“In particular, it is remarkable that mental stress ischaemia (without conventional stress ischaemia) appears to be a stronger risk factor than conventional stress ischaemia (without concomitant mental stress ischaemia) for cardiovascular death, nonfatal myocardial infarction, or heart failure hospital admission.”

The authors said several questions remained:

• To what extent is mental stress ischaemia therapeutically modifiable?
• Can screening for and treatment of mental stress ischaemia lead to improved outcomes?
• Is mental stress testing reproducible and feasible in clinical practice?
• Are there additional at-risk populations in whom mental stress ischaemia testing should be considered?