Sex Differences in Mental Stress-Induced Myocardial Ischemia in Patients With Coronary Heart Disease

Abstract

Background: Emerging data suggest that young women with coronary heart disease (CHD) are disproportionally vulnerable to the adverse cardiovascular effects of psychological stress. We hypothesized that younger, but not older, women with stable CHD are more likely than their male peers to develop mental stress-induced myocardial ischemia (MSIMI).

Methods and results: We studied 686 patients (191 women) with stable coronary heart disease (CHD). Patients underwent (99m)Tc-sestamibi myocardial perfusion imaging at rest and with both mental (speech task) and conventional (exercise/pharmacological) stress testing. We compared quantitative (by automated software) and visual parameters of inducible ischemia between women and men and assessed age as an effect modifier. Women had a more-adverse psychosocial profile than men whereas there were few differences in medical history and CHD risk factors. Both quantitative and visual indicators of ischemia with mental stress were disproportionally larger in younger women. For each 10 years of decreasing age, the total reversibility severity score with mental stress was 9.6 incremental points higher (interaction, P<0.001) and the incidence of MSIMI was 82.6% higher (interaction, P=0.004) in women than in men. Incidence of MSIMI in women ≤50 years was almost 4-fold higher than in men of similar age and older patients. These results persisted when adjusting for sociodemographic and medical risk factors, psychosocial factors, and medications. There were no significant sex differences in inducible ischemia with conventional stress.

Conclusions: Young women with stable CHD are susceptible to MSIMI, which could play a role in the prognosis of this group.

Keywords: ischemia; ischemic heart disease; sex differences; stress; women.

Figure 1

Diagram of patient selection for the main analysis (n=686) and additional analyses in the study. Slightly different numbers were included in subgroup analyses because of missing values. CHD indicates coronary heart disease; SPECT, single‐photon emission computed tomography.

Figure 2

Inducible myocardial ischemia with mental stress according to sex and age as a continuous variable. Ischemia was expressed as percent of ischemic myocardium derived by automated quantitative analysis. LV indicates left ventricle.

Figure 3

Inducible myocardial ischemia with mental stress according to sex and age group. Young women (≤50 years) showed more ischemia with mental stress than any of the other groups. Ischemia was expressed as percent of ischemic myocardium and was derived with 2 separate methods: automated quantitative analysis (A) and visual analysis (B). In both analyses, the interaction between sex and age was highly significant (P<0.001), and the comparison between women and men in the group ≤50 was also highly significant (P<0.0001). Error bars indicate confidence intervals.