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 Table of Contents  
REVIEW ARTICLE
Year : 2017  |  Volume : 1  |  Issue : 2  |  Page : 71-77

Advances in discovering the interrelationship between mental disorders and heart diseases


Medical Research Center of Guangdong General Hospital, Guangdong Provincial Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, China

Date of Web Publication16-Nov-2017

Correspondence Address:
Qingshan Geng
Guangdong Academy of Medical Sciences, Guangdong General Hospital, 102 Zhongshan Road, Guangzhou, Guangdong
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/hm.hm_14_17

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  Abstract 


In clinical practise physical illnesses are often accompanied by mental abnormality. Actually due to the development of our modern medical system, the underlying mental abnormality has been increasingly discovered, which in turn not only surprises researchers with the unexpected high morbidity, but also arouse the intense debate whether there is an interaction between mental disorders and physical illnesses. The attempt trying to figure out the mystery of mind and body can date back to the ancient time. It was not until 1818, the German psychiatrist Heinroth proposed the concept of mind-body disease for the first time. Later, William Osler successfully proved the close interaction between coronary heart disease and mental illness by dissecting cadaver of a patient with “angina” finding the coronary perfectly healthy. Owing to the importance of the cardiovascular system and the high sensitivity to the autonomic nervous system which is strongly influenced by the emotion, the intersection of cardiology and psychology gradually became the central issue in studying the physical and mental illness and eventually formed a new branch called “psycho-cardiology”.

Keywords: Cardiovascular diseases, mental disorders, psychological stress


How to cite this article:
Yin H, Geng Q. Advances in discovering the interrelationship between mental disorders and heart diseases. Heart Mind 2017;1:71-7

How to cite this URL:
Yin H, Geng Q. Advances in discovering the interrelationship between mental disorders and heart diseases. Heart Mind [serial online] 2017 [cited 2018 May 24];1:71-7. Available from: http://www.heartmindjournal.org/text.asp?2017/1/2/71/218517




  Introduction Top


In clinical practice, physical illnesses are often accompanied by mental abnormality. In fact, due to the development of our modern medical system, the underlying mental abnormality has been increasingly discovered, which in turn not only surprises researchers with the unexpected high morbidity, but also arises the intense debate whether there is an interaction between mental disorders and physical illnesses. The attempt trying to figure out the mystery of mind and body can date back to the ancient time. It was not until 1818, the German psychiatrist Heinroth proposed the concept of mind–body disease for the first time. Later, William Osler successfully proved the close interaction between coronary heart disease (CHD) and mental illness by dissecting the cadaver of a patient with “angina,” finding the coronary perfectly healthy. Owing to the importance of the cardiovascular system and the high sensitivity to the autonomic nervous system which is strongly influenced by the emotion, the intersection of cardiology and psychology gradually became the central issue in studying the physical and mental illnesses and eventually formed a new branch called “psycho-cardiology.”

With untiring efforts made by the researchers for decades, concrete evidences have been collected revealing that both mental abnormality and heart disease could exert a negative impact on each other. Furthermore, these two happen to be the most concerning issues along with the development of the modern society. This article aims to sum up the advances in the recent years in discovering the interrelationship between mental abnormalities and heart diseases, to depict the latest development of psycho-cardiology and to push the understanding of the interaction to a new height.

The most common mental abnormalities studied in psycho-cardiology are depression and anxiety. Yet the complete definition of mental disorder covers not only the comparatively mid- and short-term abnormalities such as adjustment disorder, depressive state, and anxious state, but also the severe and long-term disorders including major depression disorder (MDD), generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), and schizophrenia. Although several different criteria have been created for classifying the various mental abnormalities, the consensus that an accurate diagnosis of mental disorders comprises psychological, somatic, and behavioral symptoms has never been doubted. Therefore, to systematically review the complicated interaction between mental disorders and physical illnesses, we need to trace back to the source that causes or induces the mental abnormality and to summarize the interrelationship at the level of mind, body, and behavior so as to understand how the mind–body diseases origin, develop, and where they lead [Figure 1]. As a result, this article will elucidate the latest research progress in the following four aspects:
Figure 1: The interaction between psychological stress and somatopathy

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  1. The impact of psychological stress on cardiovascular system
  2. The interaction between mental disorders and heart diseases
  3. The effect of behavioral change
  4. The treatment for physical and mental illnesses.



  The Impact Of Psychological Stress On Cardiovascular System Top


Psychological stress as a potential and modifiable risk factor has been gaining much attention in the recent years. The impact of stress on cardiovascular system is mainly manifested in the following four stages of disease process:[1] (1) stress-related exposure to cardiovascular risk factors (e.g., smoking, reduction in physical activity), (2) long-term existence in accelerating the atherosclerosis, (3) acute triggering of adverse cardiovascular events, and (4) impact on the recovery and quality of life. However, the current studies about the impact of psychological stress on cardiovascular system mainly focus on the three topics: external stress, perceived stress, and mental stress.

External stress

External stress includes job strain, unfortunate experiences, marital problems, economic hardship, and social isolation. It seems not surprising that we all have experienced these stresses more or less, but according to the newest researches, the impact of these may not be ignored any longer.

Work pressure

Kivimäki et al.[2] made a systematic meta-analysis of 13 European cohort studies and found that, after adjusting for gender, age, and other factors, there is a great risk for an individual under working stress compared with no stress to have the CHD. The hazard ratio (HR) is 1.23 (95% confidence interval [CI]: 1.10–1.37). Further eliminating the interference of socioeconomic state, lifestyle, and traditional risk factors, the work pressure still lead to an increase of 3%–4% in morbidity.

From 1992 to 2010, Dupre et al.[3] conducted a prospective cohort study of 13,451 individuals aged from 51 to 75. It is found in this complex long-lasting research that the risk of acute myocardial infarction (AMI) is significantly higher in the unemployed (HR: 1.35 [95% CI, 1.10–1.66]), and meanwhile it positively correlates with the accumulative times of lay-off (one-time HR: 1.22 [1.04–1.42]), four or more times (HR: 1.63 [1.29–2.07]).

Unfortunate experiences

Su et al.[4] studied 213 African-Americans and 181 European-Americans in the past 23 years revealing that it is the diastolic blood pressure instead of mean blood pressure that presents a significant correlation with the unfortunate experience in childhood, and an individual who suffers multiple bad experiences at a younger age would exhibit a more rapid ascent in blood pressure after 30 years.

Similar conclusion was also presented by Sumner et al.[5] In their research, 49,978 females were included to explore the interrelationship between PTSD and cardiovascular disease. These results confirm that, compared with women without psychological trauma history, the one who experiences trauma and shows four or more PTSD symptoms is at a higher risk of having cardiovascular disease (HR: 1.60 [95% CI, 1.20–2.13]). However, even for those who do not exhibit any PTSD symptoms, the HR still remains at 1.45 (95% CI, 1.15–1.83).

Sick partner

Fosbøl et al.[6] conducted a detailed study exploring the impact of a sick partner on an individual. The outcome indicates that to the participant whose partner suffers AMI, no matter fatal or nonfatal, the risk of getting psychological abnormalities all the same increases. What is more, in this circumstance, male participants appear to be more vulnerable to depression.

Perceived stress

In comparison to external stress, perceived stress may be more precise when depicting the real feeling toward pressure.

The meta-analysis aimed at studying the relationship between job stress and the incidence of CHD from Virtanen et al.[7] brought 13 cohort studies covering 17,443 individuals into the final statistical analysis. The conclusion is that the employees with self-perceived highly unstable job are at a higher risk for CHD compared with those with self-perceived steady job (HR: 1.32 [95% CI, 1.09–1.59]). Even after taking demographic and some other factors into consideration, the risk still exists (HR: 1.19 [95% CI, 1.00–1.42]).

Richardson et al.[8] screened out six articles in completing the meta-analysis about the correlation between perceived stress and CHD. They discovered that participants who feel a high degree of stress are more likely to suffer CHD when compared with the control group (RR: 1.27 [95%CI,1.12-1.45]).

Similarly, Nabi et al.[9] summarized the results from an 18-year-long prospective research and found that, after revision of the sociodemographic characteristics, the risk of myocardial infarction or myocardial ischemia is significantly increased to 2.12 folds (95% CI, 1.52–2.98) in the participants who report to feel the pressure versus those feeling relaxed. A further adjustment for biological, behavioral, and other psychological factors fails to eliminate this impact (relative risk [RR]: 1.49 [95% CI, 1.01–2.22]).

Mental stress

Mental stress-induced myocardial ischemia

The phenomenon that mental stress-induced myocardial ischemia (MSIMI) is even more prevalent than exercise-induced myocardial ischemia (ESIMI) was discovered by Jiang et al.[10] in the REMIT study which included 400 participants with a recorded history of CHD. In comparison with ESIMI, the unique characteristics of MSIMI lie in the following aspects: (1) MSIMI occurs when the patient is at a lower heart rate, higher diastolic blood pressure, and lower product of systolic blood pressure and heart rate (2) MSIMI rarely exhibits an ischemic change on the electrocardiogram (3) peripheral vascular resistance increases significantly in MSIMI but decreases in ESIMI.[11]

Gender difference in mental stress-induced myocardial ischemia

Gender difference has already been noticed by Jiang in the REMIT study; she found that females (odds ratio [OR]: 1.88) and solitaries (OR: 2.24) are more likely to experience MSIMI.[10] Samad et al.[12] made a deeper exploration on the basis of Jiang and discovered that the platelet in women presents a high reactivity to collagen, serotonin, and adrenaline. Women also undergo more negative emotions and MSIMI (57% vs. 41%, respectively; P < 0.04), while in men, physical parameters such as blood pressure (P < 0.05) or product of systolic blood pressure and heart rate are more often seen to be altered.


  The Interaction Between Mental Disorders And Heart Diseases Top


The impact of mental disorder on cardiovascular system

Depression and cardiovascular disease

Cardiovascular disease and depression are the most common diseases that lead to the loss of social function. Both of them not only seriously compromise the quality of patient's life, but also take up much medical resources and increase the treatment costs.[13] Although it is a normal or even protective reaction to be depressive after the encounter of some misfortune, once the patient loses the initiative in struggling with the depressive mood, the evasive behavior and pessimistic attitude will undoubtedly exert negative influence on the health.

Due to the diverse diagnostic criteria, psychological rating scales, and the lack of guidance from psychiatric specialists, the comorbidity rate drawn from different researches may not be the same. However, one thing for sure is that the cardiovascular disease patients suffer a higher risk for depression and depressive patients are comparatively more likely to develop cardiovascular diseases. Researchers further confirm that the severity of depression determines the prognosis, indicating more serious depressive symptom heralds the worse outcomes.[13] In fact, according to another research, even the mildest depression can be one of the most dangerous risk factors for the relapse of cardiovascular disease and all-cause mortality.[14]

In 2014, the American Heart Association announced that depression is ascertained to be the risk factor for acute coronary syndrome in an elaborate systematic analysis.[15] Then in 2015, another scientific announcement declared that the youth with MDD or bipolar disorder possess an accelerated speed in atherosclerosis and are more likely to meet cardiovascular problem at a much younger age.[16] Similar findings have also been discovered in cerebral vessels. It is said that the risk for stroke doubles in the individuals aged 50 and above with persistent depressive symptoms.[17] Even though there have already been some theories (e.g., the inflammation theory) trying to elucidate the link between mental disorder and vascular lesions, a convincing and systematic explanation still lacks.

Anxiety and cardiovascular diseases

In the prospective cohort study of 185 inpatients carried out by Einvik et al.,[18] researchers noticed that anxiety is in fact widespread in hospitalized patients with an incidence of around 30% regardless of whether accompanied by heart failure or not. After adjustment for the relevant variables, anxiety still accounts for the increased mortality in patients with acute heart failure (RR: 2.0 [95% CI, 1.1–3.5]).

Another detailed large-scale clinical research by Gustad et al.[19] was designed to study the relationship between depression, anxiety symptoms, and the risk of AMI. The results came out just as expected, showing that there is a significant association between mental abnormalities and the increased risk of AMI (patients with depression: HR: 1.31 [95% CI, 1.03–1.66]; patients with anxiety: HR: 1.25 [95% CI, 0.99–1.57]; and patients with anxiety and depression: HR: 1.52 [95% CI, 1.11–2.08]). According to a recent study, whatever kind of cardiovascular disease (myocardial ischemia, arrhythmia, heart failure, valvular disease, or even comorbidities) the patients have, the existence of depression and anxiety would lead to the rise in 1-year mortality.[20]

Gender difference is also an important aspect that cannot be ignored when talking about the impact of mental disorder on cardiovascular system. In clinical practice, women with CHD seem to have a worse prognosis. Hence, to testify and explore the underlying mechanism behind this phenomenon, Paine et al.[21] carried out a study on 2342 participants. The conclusion drawn from this study is that women without a history of CHD share a higher risk for myocardial ischemia when accompanied by anxiety symptoms. Yet in men or patients with recorded CHD history, this correlation no longer exists. Interestingly, the gender difference disappears in the research made by Mathews et al.[22] They conducted a delicate analysis to understand the association between self-perceived psychological factors such as stress, anxiety, depression, and the indicators of cardiovascular health and realized that, despite the extensive correlation between adverse psychological stress and the lesion on cardiovascular system among different races, a significant diversity between men and women is actually failed to be found.

Psychological factor and heart diseases

By means of a modern technique to record the mind state in different periods of time of a day, Lampert et al.[23] obtained the records of dynamic electrocardiogram and emotional status in 95 patients with consecutive or paroxysmal atrial fibrillation and discovered that, even after correction of influence factors, negative emotions such as sorrow, anxiety, and anger are still significantly associated with atrial fibrillation. The risk of atrial fibrillation almost doubles if the mind state in the day before was summarized by patient as stressful or anxious.

Another study exploring the correlation between psychological factors and heart failure by Ogilvie et al.[24] covered 6782 individuals with an average of 9.2 years of follow-up. Although in this study the existence of psychological factors was proved to have no relationship with heart failure, during the detailed analysis, researchers still noticed that patients in poor health condition with higher degree of psychological stress in comparison with those of lower degree suffer a 2-fold higher risk.

The influence of physical illness on mental state

The impact of the physical illness on patients' mental state is not only due to the somatic pain, but also the concerns and worries aroused by costs, prognosis, and the rehabilitation process.

Lotufo et al.[25] conducted a detailed classification of 15,105 participants in their research. The data from this research indicated that the risk ratio for GAD in male patients with angina is 2.4 ([95% CI, 1.9–3.0]), for mixed anxiety and depression disorder is 1.7 ([95% CI, 1.3–2.2]), for MDD is 5.3 ([95% CI, 3.0–9.6]), while in female participants, the risk ratio for the disorders listed above is 2.4 ([95% CI, 2.1–2.8]), 1.7 ([95% CI, 1.4–2.0]), and 3.5 ([95% CI, 2.5–4.9]), respectively. Anyhow, patients with angina present a higher incidence for mental disorders than average.

Similarly, in a prospective cohort study of 505 patients with nonobstructive coronary artery stenosis, scientists also realized the ascent in the morbidity of mental abnormality.[26] Besides, women found in that situation exhibit more anxiety, depressive symptoms, and activity limitation. After studying the mental status of 113 patients after heart transplantation, Doering et al.[27] also noticed that the female patients are more likely to have severe anxiety and depressive symptoms in the first 6 months after surgery. Although the discrepancy between men and women is no longer significant in the 9th month, the total incidence rate of mental abnormality is still far beyond the normal level.


  The Effect Of Behavioral Change Top


As mentioned above, a precise diagnosis of mental disorder contains three essential parts: psychological, somatic, and behavioral symptoms. Unfortunately, as the form cannot be easily defined and standardized, the behavioral symptoms are frequently neglected by the researchers. In fact, the changes in behavioral patterns have taken place long before the irreversible mental disorder settles. It is easy to ignore that, on one hand, physical illness and negative emotion can result in the behavioral change, but on the other hand, the comparatively fixed behavioral pattern in patients with mental disorder can also exert impact on somatic symptoms and mental state.

In the study on the impact of depression on CHD patients, Ye et al.[28] discovered that the risk ratio for a depressed patient with coronary artery disease to experience AMI is 1.41 ([95% CI, 1.51–1.72]), yet after the correction of behavioral symptoms (drinking, smoking, exercises, and medicine compliance), the correlation seems no longer significant (RR: 1.14 [95% CI, 0.93–1.40]). This inspiring result not only reminds all the researchers to reexamine the conclusion that depressive mood can give rise to the incidence of cardiovascular diseases, but also hint a much more complicated mechanism that underlies the interaction of mind and body.

Although there are only scarce researches exploring the effect of behavioral factors at present, some associations between behavioral changes and heart diseases have all the same been demonstrated. For example, Laugsand et al.[29] found in their study that there is a dose-dependent relationship between insomnia and the incidence of heart failure. That is, compared to patients without sleep disorder, patients with more severe sleep difficulties suffer a greater risk of heart failure. Rozanski et al.[30] proved an increased risk of cardiovascular events in the patients with long-term social isolation and lack of emotional support. Kim et al.[31],[32] discovered that possessing a clear purpose in life helps lower the possibility of stroke and myocardial infarction.

In fact, on the expedition in revealing the mystery of physical and mental illnesses, a comprehensive understanding of behavioral changes is absolutely indispensable. We are glad to see that the behavioral symptoms have been paid much more attention in the recent years, but to fully comprehend the effect or even to utilize the mechanism in treatment, there is still a long way to go.


  The Treatment for Physical and Mental Illness Top


Traditional pharmacologic therapy

Although the new generation of psychotropic drugs (e.g. SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin and noradrenaline reuptake inhibitor)) has manifested prominently less side effects on the cardiovascular and endocrine systems, drug safety still remains the most noteworthy concern in the treatment of the physical and mental illnesses.

Jiang et al.[33] performed a double-blind randomized clinical trial in which escitalopram (n = 64) and placebo (n = 63) were given for the treatment of 127 patients. Results suggested that patients with escitalopram are more likely to be exempted from MSIMI compared with those taking placebo (34.2% vs. 17.5%, respectively). However, there is no significant discrepancy for ESIMI. Similarly, in the study of 235 patients from Stewart et al.,[34] it has been revealed that, in contrast to conventional treatment, combination therapy of antidepressants and psychological counseling could markedly reduce the incidence of cardiovascular events.

The sad thing is contradictory arguments have also been widely proposed. Brauer et al.[35] conducted a case–control study of 1546 participants to figure out the influence of taking antipsychotic drugs on the morbidity of myocardial infarction and they realized that in patients treated with first-generation antipsychotic drugs in the first 30 days, the HR of myocardial infarction is 2.82 ([95% CI, 2.0–3.0]), while with the second-generation antipsychotic drugs, HR is 2.5 ([95% CI, 1.18–5.32]). In another word, the initial administration of antipsychotic drugs could increase the risk of myocardial infarction. Weeke et al.[36] got an analogical conclusion suggesting that taking antipsychotic drugs may lead to a 50%–60% increase of out-of-hospital cardiac arrest.

In another study exploring the effects of antipsychotics on depressed patients with congenital heart disease,[37] only male patients exhibited a worse outcome after taking medicine (HR: 1.44 [95% CI, 1.17–1.84]). However, no direct evidence has been found to point out that the ascent in mortality was caused by the side effect of the antipsychotic drugs.

Due to the possible elevated risk of suicide, increased incidence, and mortality of cardiovascular diseases induced by the mental disorder, it is apparently not wise to discard the antipsychotic drugs for the uncertain adverse effects on cardiovascular system. Yet more research and risk assessment should be made so as to precisely guide the doctors when dealing with the physical and mental illnesses.

Novel rapid-onset antidepressants

In contrast with the traditional antidepressants which take weeks to act, the novel type of rapid-onset antidepressants, the NMDA-receptor antagonists, presents a more robust and rapid therapeutic effect. The current researches about this drug mainly focused on three aspects: strengthening the antidepressant effect, reducing side effects, and selecting applicable biomarkers.[38]

Lifestyle intervention, stress-management training, and self-management intervention

Ramirez et al.[39] after enrolling 5997 participants into the 8-week lifestyle intervention program (e.g. exercise, proper rest, and planned nutrient intake) discovered that lifestyle intervention indeed effectively improves the cardiovascular and psychological health of elderly patients. Stress management training (SMT) as another effective treatment is also highly recommended. In the study of 151 discharged CHD patients with a 12-week comprehensive cardiac rehabilitation training (CR) or heart rehabilitation training combined with SMT (CR + SMT), Blumenthal et al. noticed that CR + SMT significantly reduces patient's stress level as well as the reoccurrence of cardiovascular events.[40]

Similar positive outcomes have also been acquired by Jonkman et al.[41] in the correlation research of self management interventions and prognosis of heart failure patients. However, in the subgroup analysis of participants with severe depressive symptoms, an increase of mortality instead of beneficial effect is observed, which reminds of great caution when applying self-management strategies in those patients.

Exercise therapy

After a 30-month follow-up of 2322 patients with chronic heart failure, Blumenthal et al.[42] observed that, compared with the general nursing, the HR of death or rehospitalization for patients receiving aerobic exercise is 0.89 (95% CI, 0.81–0.99). Besides, the depressive symptoms are at the same greatly improved. In another article, Blumenthal et al.[43] made a further comparison between antipsychotic therapy and exercise therapy and revealed that both aerobic exercise and antipsychotic drugs could significantly improve the depressive symptoms compared with the placebo group. Yet no significant difference exists between these two kinds of therapy when judged by the efficacy. However, aerobic exercise therapy may be slightly superior in improving the heart rate variability.


  Conclusion Top


Due to the diversity and complexity in elucidating the fundamental mechanism, we choose this superficial but vivid way to present the external interaction between mental abnormalities and heart diseases. According to the latest researches, psychological stress, especially self-perceived stress, is closely related to the prognosis of heart illnesses; psychological stress could mediate the occurrence of myocardial ischemia. Research outcomes become more systematic and reliable and behavioral cardiology begins to be valued; doctors are still struggling with the balance between efficacy and side effect of antipsychotics, while nondrug therapies such as exercise therapy and SMT have achieved remarkable performances. In essence, an ideal therapeutic schedule must be the one that could simultaneously cure the discomfort both in mind and body, and that is the reason we try our best to solve the puzzle of this complex interrelationship. We have reasons to believe that the vigorous development of psycho-cardiology will not only bring the gospel to patients, but also promote the development and transition of a new medical model, and ultimately enhance the health status of the whole human race.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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