Fig. 19.1
Pathophysiologic mechanisms of stress on the development of atherosclerosis. Stress activates the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system and depresses the parasympathetic nervous system. This results in numerous adverse effects peripherally which promote a heightened physiologic response and increase the risk of cardiovascular related events (Adapted with permission from Rozanski et al. [15], figure 7)
There is a long established association between acute cardiovascular events such as myocardial infarction and unstable angina occurring in a circadian rhythm which is correlated with the rhythm of sympathetic nervous system activity [17]. Mental stress has been shown to increase heart rate, blood pressure, and myocardial oxygen demand. These effects are mediated at least in part by catecholamine secretion. Another study also has shown a link between psychosocial stress and plaque rupture in the setting of increased sympathetic nervous system activity with surges in heart rate, blood pressure, as well as weakening of the collagenous plaque cap from inflammatory processes, all of which may contribute to plaque instability [18]. Anger and other forms of mental stress were specified as triggers for myocardial infarction in a study that examined the behaviors leading up to left ventricular dysfunction and blood pressure elevation in coronary patients [19]. In addition to hemodynamic effects, mental stress also has been shown to increase platelet aggregability as well as coagulation [20].
The literature has demonstrated that during periods of stress that affect a whole population, the numbers of people presenting with heart attacks is increased. For example, the rate of admission for acute myocardial infarction increased significantly on the day England lost to Argentina in the 1998 World Cup [21]. Similarly, on the day of the Los Angeles Earthquake in 1994, there was a large increase in the number of sudden cardiac deaths from cardiac causes related to atherosclerotic cardiovascular disease [22]. Studies have also shown that women under a greater degree of stress have higher cortisol levels, which in turn, may influence eating behavior and lead to weight gain. High cortisol levels have been shown to accelerate aging, increase abdominal fat accumulation, and impair immune function [23]. It is clear that insulin resistance and diabetes brought on as a result of abdominal obesity, which may be the result of blunted sex hormones and hypercortisolemia, are particularly important cardiovascular risk factors in women [15].
There is a growing body of literature on the influence of stress on telomeres. A telomere is a repetitive sequence of nucleotides at the end of a chromosome which protects the chromosome from deterioration. As telomeres shorten, important genomic information is lost. Interestingly, one recent study demonstrated that there is a stress related shortening of telomeres in the cells of women taking care of chronically ill children and among women who were formerly abused [24, 25]. In contrast, exercise and meditation have been found to reduce stress, and some small studies have demonstrated that these two beneficial activities actually prevent shortening of telomeres [26]. Shorter telomeres are associated with many age related diseases and predict an increased incidence and poorer prognosis for cardiovascular disease. So called “resiliency factors” dampen the effects of stress on the heart. For example, regular exercise, consumption of fruits and vegetables, abstaining from alcohol and tobacco, significantly decrease a woman’s risk of developing heart disease [27]. Waist circumference has also been shown to correlate with future cardiovascular events in women [28]. Multiple studies support evidence that diets consisting mainly of fruits and vegetables offer significant protection against coronary heart disease, reduce levels of circulating inflammatory agents, and decrease insulin resistance [29–31]. Although behavior modifications are extremely effective, pharmacologic agents may also be used adjunctively to control co-morbidities associated with poor cardiovascular health, such as high blood pressure and diabetes.
Studies point to a link between acute psychological stress leading to acute MI and sudden cardiac death in certain susceptible individuals. Although gender differences in this link are not clear, there are cardiovascular conditions that are almost exclusive to women. The most notable example of this is Takotsubo cardiomyopathy. In this specific cardiomyopathy, sudden, unexpected emotional or physical stress causes a reversible cardiomyopathy with markedly elevated levels of plasma catecholamines [32]. The left ventricular chamber is predominantly affected with transient hypokinesis, akinesis, or dyskinesis of the apical and mid segments; regional wall motion abnormalities may extend beyond a single epicardial vascular distribution in the absence of obstructive coronary disease or angiographic evidence of acute plaque rupture. The prognosis of patients with Takotsubo cardiomyopathy is generally favorable and systolic function may recover with hemodynamic and pharmacologic support [33]. Takotsubo cardiomyopathy occurs predominantly in postmenopausal, older women, which is in concordance with the fact that the great majority of women who have established heart disease are older [34].
Depression and Anxiety
As stated already in this chapter, women encounter specific stressors and are vulnerable to certain illnesses which ultimately contribute to their risk of cardiovascular disease. In particular, women are more likely than men to experience depression, anxiety, and abuse, which in turn, influences their heart health. Studies have shown that women are twice as likely to suffer from major depression during their lifetime as men [1]. In addition, this condition leads to many negative lifestyle choices, including sedentary behavior and smoking, as well as a failure to adhere to medical treatment. As a result, women with depression may have as much as a 50 % increased risk of experiencing adverse cardiac events [35].
The immense responsibilities placed on women in our society often lead to excess stress which may trigger depression. Depressed mood and social isolation are associated with damaging health behaviors such as cigarette smoking, poor diet and lack of exercise which are well known risk factors for coronary heart disease (CHD). Also, studies have demonstrated that depression makes women less compliant in taking their cardiovascular medications [36]. It is important that all women with heart disease are evaluated for depressive symptoms so they can be referred for treatment if necessary [27]. Roughly one in every eight woman can expect to develop clinical depression during their lifetime [37], with several factors unique to women, including developmental, reproductive, hormonal, genetic, and biological differences (e.g. premenstrual syndrome, childbirth, infertility and menopause) all contributing to its development. Approximately 10–15 % of all new mothers experience postpartum depression [38]. There is also a strong relationship between eating disorders (anorexia and bulimia nervosa) and depression in women. Research shows that one out of three people with the condition also suffer from some form of substance abuse or dependence [38].
Unfortunately, depression in women is misdiagnosed approximately 30–50 % of the time and fewer than half of the women suffering from it actually seek care [39]. However, clinical depression is a treatable illness which can be managed successfully with medication, psychotherapy or a combination of both. According to a Mental Health America survey on public attitudes and beliefs about clinical depression: More than one-half of women believe it is “normal” for a woman to be depressed during menopause and that treatment is not necessary [38]. More than one-half of women believe it is a “normal part of aging” and that it is normal for a mother to feel depressed for at least 2 weeks after giving birth [38]. More than one-half of women cited denial as a barrier to treatment while 41 % of women surveyed cited embarrassment or shame as barriers to treatment. In general, over one-half of the women said they think they “know” more about depression than men do [38].
Depression and the other unique psychosocial risk factors mentioned already in this chapter make women more prone to develop heart disease [40]. Both in cases with and without known cardiovascular disease, clinical evidence points to depression as a significant and independent predictor of morbidity and mortality in such individuals. In fact, heart disease is the leading cause of death among American women [41]. It is also important to realize the outcomes of women with heart disease are worse than in men. For example, women are more likely to die from a heart attack than men and 1-year mortality after a heart attack is greater in women [42]. The INTERHEART study was undertaken to determine risk factors for acute myocardial infarction stratified by different populations. Specifically, it investigated the association of psychosocial risk factors with risk of acute myocardial infarction (MI) in 11,119 cases and 13,648 controls from 52 countries [4]. One of the most significant findings of the INTERHEART study was the correlation between stress and the risk of MI. Episodic stress in the workplace or at home increased MI risk by 45 %, while sustained permanent stress increased risk by 117 % [4]. It also demonstrated that smoking, high cholesterol, diabetes, obesity, diet, high blood pressure, physical inactivity, alcohol consumption, and psychosocial factors account for over 90 % of the risk of heart attack [4]. Additional studies support the direct dose response between weight and high blood pressure, which is an important risk factor for cardiovascular disease [43]. It has been shown that by getting just moderate exercise, like walking daily, a woman can lower her risk of heart disease by 50 % [44, 45]. In addition, when designing treatment plans for women with established heart disease, some consideration must be taken into account of the different psychosocial roles that they may be involved in, such as being caretakers of children, aging sick parents, and older ill spouses, in addition to their work responsibilities, and the sometime overlapping nature of these responsibilities [46].
Often times, it is believed that health conditions that lead to an increased risk of heart disease are more prevalent among men. However, among Americans, the prevalence of diabetes is roughly the same in both men and women [47]. The same misconception may be said for elevated blood pressure, but according to national statistics, the same number of American women have hypertension as their male counterparts [48]. Among Americans over the age of 60, the percentage of women living in the United States with obesity is slightly greater than number of men who are obese [49]. Therefore, there are a great proportion of American women with serious co-morbidities such as high blood pressure, obesity, and diabetes which ultimately places them at a higher risk for sub-optimal heart health.
Although genetic factors play a large role in the state of health of an individual, there are many other controllable factors that women can modify to positively influence their state of health. For example, women can adopt a holistic approach and address different parts of health – mind, body, and soul. One easily modifiable risk factor to reduce a woman’s chances of developing cardiovascular disease is cessation of smoking. An article from the American Journal of Public Health which looked at trends in mortality in U.S. women demonstrated that mortality disparities widened in review of recent data, in part, because of causes of death for which smoking is a major risk factor [50]. One of the major risk factors influencing death from heart disease is smoking. Therefore, by tirelessly encouraging smoking cessation, healthcare providers can hope to reduce the rates of cardiovascular disease among their female patients [27]. Adhering to a Mediterranean or low fat diet has also been shown to positively influence heart health [31, 51, 52]. Health interventions that target the common co-morbidities women have, such as high blood pressure or obesity, should also be initiated for secondary prevention.
Summary
The link between ischemic heart disease in women and psychosocial factors is gaining more and more support as a result of accumulating clinical evidence. Research suggests there to be a strong link between psychosocial stress and all recognized mechanisms underlying cardiac events (clustering of traditional cardiovascular risk factors, endothelial dysfunction, myocardial ischemia, plaque rupture, thrombosis, and malignant arrhythmias). General acceptance of psychosocial stress as a nontraditional risk factor is becoming more widespread [12]. Further, there is increasingly greater interest in targeting the evaluation and management of psychosocial stress in cardiac practice because psychosocial stressors have such an immense impact on cardiovascular health in women (Fig. 19.2).
Fig. 19.2
Six reasons that promote interest in the evaluation and management of psychosocial stress in cardiac practice (Adapted with permission from Rozanski et al. [15], figure 7)
It is clear that women are not only affected by psychosocial factors such as depression, but that the typical contemporary woman who is balancing career and family responsibilities experiences a unique kind of stress that might be described as female role overload. It is especially important to utilize current evidence to both identify those women who are at increased risk of coronary heart disease (CHD) as a result of depression or stress (associated with multiple roles, including responsibilities at work, home, caregiving responsibilities, lack of personal time, sleep deprivation, fatigue, etc.), and to create interventions that take these psychological factors into consideration in treatment options for both those with CHD and those at risk. It is important to keep in mind that adherence to treatment and prevention recommendations in women may be affected by these same female role overload factors.
We want to emphasize the importance of an early and a multidisciplinary approach to keep women healthy in order to prevent deleterious consequences in the future. It is of great importance for healthcare providers to identify which populations they should focus their attention on to promote cardiovascular health. For example, effort should be placed on identifying woman who are depressed [53]. We know that women are much more likely than men to suffer from depression and anxiety. We also know that women face a challenging set of both acute and chronic, negative and positive stressors over the span of their lifetime which ultimately shapes their heart health. Research has shown that at risk women over 45 years of age who are informed about their condition are more likely to be motivated to modify their cardiovascular risk factors [54]. Steps to ameliorate the effects of stress on a woman’s health should be taken by women and their healthcare providers for primary prevention. Integrative medicine and a holistic cardiac care approach in women must be employed. A recent study evaluating a holistic cardiac rehabilitation program in reducing biopsychosocial risk factors among patients with coronary heart disease demonstrated a reduction in perceived stress, depression, and cholesterol levels among patients cared for using a holistic approach [55]. In the future, it will be essential to focus on assisting women to increase their social support, address their spirituality, treat their depression, reduce the hostility they encounter at work, and boost their overall health status and life satisfaction.
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