To appropriately address gender inequities in cardiovascular health, cardiologists should recognize that psychosocial stress negatively affects cardiovascular health and is unequally distributed between men and women, a new review reports. The state-of-the-art review, published in online Monday and in the July 16 issue of the Journal of the American College of Cardiology, noted that despite advances in treatment and prevention, cardiovascular disease (CVD) remains the leading cause of death in women - warning that although age-adjusted death rates for CVD in the United States decreased from 1980 to 2010, “There has been an upward trend in recent years.” Led by Imo A. Ebong, MD, MS, from the Department of Internal Medicine at University of California Davis, Sacramento, the team added that young and midlife women have shown worse trends than other demographic groups - both in the incidence and case-fatality of coronary heart disease (CHD). “Compared with men, younger women continue to have worse morbidity, mortality, and quality of life after an acute myocardial infarction (MI), a difference that is not explained by traditional risk factors, comorbidities, disease severity, or treatment,” noted the authors. They added that evidence has consistently linked stressful exposures and mental health conditions— consequent to traumatic stress, such as mood and anxiety disorders and posttraumatic stress disorders (PTSDs)—to adverse CVD outcomes in both healthy individuals and those with pre-existing CVD. “Stress is ubiquitous in our society, but its timing and duration, as well as individual susceptibility and physiologic responses, are implicated in its subsequent impact on health and disease,” said the authors. “Women face unique propensity toward the cardiovascular consequences of psychosocial stress,” they said, noting that women have a distinctive burden of psychosocial adversities, especially at young ages and in midlife, as well as stress-related mood and anxiety disorders. “Not only do women have a higher prevalence of these conditions than do men, but they are also more susceptible to adverse cardiovascular sequelae from these exposures.” Linking psychosocial stress with CVD Ebong and colleagues noted that psychosocial stress contributes to cardiovascular disease through multiple pathways - adding that young and midlife women, and especially those from marginalized groups, are particularly vulnerable to the adverse effects of psychosocial stress. They noted that stress is “inherently complex” because it is experienced at multiple levels—social, psychological and biological—with multiple definitions and assessment methods at each level. “A distinction is often made between acute and chronic stress,” they said, noting that because of the short but intense nature of acute stressors, they can trigger cardiovascular events in individuals at high risk, such as those with underlying coronary atherosclerosis. “Chronic stressors on the other hand, are negative experiences that can persist over an extended period, such as months or years, and can be continuous or recurring,” they said. “Because of their persistent and cumulative nature, chronic stressors are thought to facilitate the development and progression of diseases, including CVD.” Furthermore, they said that the distinction between acute and chronic stressors is not absolute, noting that the repetition of acute stressors can lead to cumulative chronic effects, and that stressful experience (whether acute or chronic), can have enduring consequences and result in biological maladaptation affecting the risk of CVD or disease progression - especially if traumatic and with onset in early life. “Certain stressors, such as socioeconomic disadvantage, childhood adversity, intimate partner violence and caregiving stress, are especially common among women,” said the authors, noting that the consequences of stress begin at a young age and persist throughout the life course. Stress mechanisms The biological effects of such psychosocial stress that are implicated in cardiovascular sequelae among women include dysregulation of the neuroendocrine axis and autonomic nervous system, and their effects on immune function, inflammation and vascular function, the authors added. “Not only is psychosocial adversity prevalent in women, but it could have more pronounced consequences for cardiovascular risk among women than among men,” they said. “These differential effects could reside in sex differences in responses to stress, combined with women’s propensity toward vasomotor reactivity, microvascular dysfunction and inflammation,” they said. Indeed, Ebong and colleagues noted that when stressors become recurrent or chronic, or after traumatic exposures, repeated activation of neuroendocrine stress response systems - the hypothalamic-pituitary-adrenal (HPA) axis, with release of cortisol from the adrenal cortex, and the sympathetic-adrenal-medullary system, with release of noradrenaline from peripheral nerves and adrenaline from the adrenal medulla - can lead to alterations of normal physiology, including immune function, blood pressure, vascular function, visceral fat deposition, coagulation and metabolic effects. “Whereas normal men show greater cortisol responses to achievement challenges, women manifest increased cortisol responses to social rejection,” noted the authors, adding that because women tend to experience more daily psychosocial stressors than men, they could have more long-term adverse consequences of HPA activation. It has also long been documented that acute mental stress results in an inflammatory cytokine surge through sympathetic nervous system activation, they said, adding that the HPA axis also modulates immune system responses through the glucocorticoid receptor. “Women have a more pronounced inflammatory response to acute mental stress than men of similar age and CHD status, particularly interleukin-6,” noted the team. “Furthermore, women manifest decreased glucocorticoid sensitivity after an acute stressor compared with men, leading to more protracted inflammation, and heightened platelet aggregation both at rest and with mental stress.” Such responses can contribute to the risk of subsequent CVD events, the authors warned, adding that women with CHD, including ischemia and nonobstructive coronary artery disease (INOCA), exhibit enhanced peripheral vasoconstriction with mental stress, while coronary microvascular dysfunction in women likely contributes to mental stress–induced myocardial ischemia (MSIMI), and is also a feature of stress-induced cardiomyopathy - which is typically triggered by strong emotions. “Notably, similarly to inflammation, microvascular changes with mental stress have been linked to adverse cardiac events in women but not in men,” they said. Future perspectives Ebong and colleagues concluded that psychosocial stress is a key modifiable risk factor for women, especially for young and midlife women and those in underrepresented groups - warning that consideration of the psychosocial milieu is essential to improve cardiovascular health in women and decrease their future risk. “To appropriately address gender inequities in cardiovascular health, cardiologists should recognize that psychosocial stress negatively affects cardiovascular health and is unequally distributed between men and women,” they said, noting that addressing psychosocial stress could help to mitigate CVD risk among women. “Programs and policies should focus on structural and environmental conditions that affect psychosocial health,” they said, noting that clinical trials should explore the benefits of targeting psychosocial stress to improve women’s cardiovascular health and that strategies specific for women should be tested. “For maximum impact, psychosocial adversity must be considered using a multipronged approach that addresses various sources of stress at the individual and community levels,” they said. Source: Ebong IA, Quesada Q, Fonkoue IT, et al. The Role of Psychosocial Stress on Cardiovascular Disease in Women: JACC State-of-the-Art Review. J Am Coll Cardiol 2024;84:298-314. Image Credit: pixardi – stock.adobe.com