The Importance of Sex in the Stress–Heart Disease Relationship and the Potential Contribution of Gender to Future Research

Abstract

We now have numerous studies that have linked increased levels of negative emotions and stress with the development and progression of cardiovascular disease-a relationship that seems to be sex specific in its pattern of outcomes. 1,2 However, the mechanisms of these relationships are still a source of much debate. One of the strongest potential pathways linking acute psychological stress with worse outcomes is through mental stress-induced myocardial ischemia (MSIMI).3 Though there is a large overlap (ca. 70%) in individuals who demonstrate both MSIMI and more common (ie, exercise or pharmacological) stress-induced ischemia, 4 these seem to be distinctly different entities. Firstly, it would seem that more individuals are likely to have MSIMI only than exercise/pharmacological stress-induced ischemia only (20% versus 10%).5 Furthermore, the profiles and potential mechanistic factors of those at risk for MSIMI compared with exercise/pharmacological stress-induced ischemia are different. For example, those individuals who exhibit MSIMI are more likely to be women, have greater microvascular disease, have poorer left ventricular dysfunction, and display endothelial dysfunction, whereas exercise/pharmacological stress-induced ischemia is generally associated with men and those with larger and more diffuse coronary artery plaque. [4][5][6] Though there are sex differences in the rates of presentations of both MSIMI and exercise/pharmacological stress-induced ischemia, both men and women do exhibit both of these forms of ischemia. However, we do not know if the mechanistic factors that underlie these stress-induced ischemia differ by sex; for example, does MSIMI in women differ from MSIMI in men? Understanding these processes can ultimately help in the development of better tailored diagnostic procedures and interventions to treat cardiovascular disease. See accompanying article on page 473The article by Sullivan et al 7 provides some important initial insights into sex differences in the potential mechanisms driving MSIMI. This secondary analysis of 678 (25% women) patients in the MIPS study (Mental Stress Ischemia Mechanisms and Prognosis) evaluated mental stress (public speaking)-induced vascular and hemodynamic responses. The authors found that MSIMI was generally driven by peripheral vasoconstriction in women compared with increased hemodynamic workload in men, results that were independent of exercise/pharmacological stress-induced ischemia. These results suggest that men with MSIMI are effectively cardiac stress reactors, with increased myocardial oxygen demands, and women with MSIMI are more likely to be vascular reactors, with greater endothelial driven increases in vascular resistance (which leads to increased left ventricular afterload and dysfunction).8 However, the article by Sullivan et al does only provide initial insights, and there is a great deal of further information that we need. For example, building a more complex map of MSIMI, to include additional measures of the autonomic nervous system, the...

The Health Externalities of Downsizing

“…the estimated coefficients appear small at face value (4 quarters after the ML, the effect on cardiac events is 0.05 percentage points), compared to the sample mean this corresponds to an increase of 58 percent. This partly explains why females have more hospital days after the ML, and is consistent with the recent medical literature suggesting that women are more susceptible to heart problems following stressful events than men (Bacon 2018). In fact, women's risk to develop stress-induced myocardial ischemia is twice as high than men's, and this difference cannot be explained by psychosocial or clinical risk factors (Vaccarino et al 2018).…”

“…Females are particularly prone to stress-induced ischemia, which are episodes of reduced blood flow to the heart (Bacon 2018, Vaccarino et al 2018. Ischemia is associated with increased risk of heart attack.…”

Sex Effect on Cardiac Damage in Mice With Experimental Autoimmune Encephalomyelitis

“…(Dutra et al, 2013) There was gender difference in the rate of stress-heart disease, mental stress-induced myocardial ischemia was more likely to be woman, while exercise/pharmacological stress-induced ischemia was more likely to be man. (Bacon, 2018) The change of mitochondrial deacetylases Sirt3 (Sirtuin 3) expression may result in vascular dysfunction such as endothelial dysfunction, vascular hypertrophy and inflammation. (Dikalova et al, 2020) Difference of mitochondrial biology may result in cardiovascular disease gender difference.…”