Authors

• Nenad Lakušić — Specijalna bolnica za medicinsku rehabilitaciju Krapinske Toplice, Krapinske Toplice, Hrvatska — ORCID: 0000-0002-2329-2582
• Gordana Kamenečki — Specijalna bolnica za medicinsku rehabilitaciju Krapinske Toplice, Krapinske Toplice, Hrvatska — ORCID: 0000-0001-7921-5239
• Ivana Sopek Merkaš — Specijalna bolnica za medicinsku rehabilitaciju Krapinske Toplice, Krapinske Toplice, Hrvatska — ORCID: 0000-0002-0888-5005
• Duško Cerovec — Specijalna bolnica za medicinsku rehabilitaciju Krapinske Toplice, Krapinske Toplice, Hrvatska — ORCID: 0000-0002-5675-4202
• Krunoslav Fučkar — Specijalna bolnica za medicinsku rehabilitaciju Krapinske Toplice, Krapinske Toplice, Hrvatska — ORCID: 0000-0002-2723-8356
• Ivo Darko Gabrić — Klinički bolnički centar Sestre milosrdnice, Zagreb, Hrvatska — ORCID: 0000-0003-4719-4634
• Matias Trbušić — Klinički bolnički centar Sestre milosrdnice, Zagreb, Hrvatska — ORCID: 0000-0001-9428-454X
• Jasna Čerkez Habek — Klinička bolnica „Sveti Duh“, Zagreb, Hrvatska — ORCID: 0000-0003-3177-3797

Abstract

In addition to the somatic consequences of acute coronary syndrome (ACS) that include different levels of intolerance to exertion, incapacity for work, symptoms of chronic heart failure, angina pectoris, the manifestation of various arrhythmias, etc., the development of a whole range of psychosomatic and mental disorders is also possible already in the early subacute and chronic phases of the disease, and if these mental disorders are not actively treated in a timely fashion they can contributed to unwanted outcomes and increased mortality in this group of patients. ACS is associated with chronic stress, anxiety, and depression and can be a trigger for later development of posttraumatic stress disorder (PTSD) with an average prevalence rate of 15% in patients with ACS. Several studies have shown that patients with symptoms of PTSD associated with ACS, especially if untreated, have increased mortality and higher rates of myocardial reinfarction. Since PTSD associated with ACS or cardiac surgery can be neglected or underestimated, the aim of this review was to raise awareness about this issue that is present in everyday clinical practice.

Keywords

posttraumatic stress disorder, acute coronary syndrome, cardiac surgery

DOI

Full Text

Coronary heart disease (CHD) is the main cause of mortality in developed countries. Although the global mortality rate from CHD has been in a downward trend over the last four decades, CHD is still responsible for approximately one third of all deaths in persons above the age of 35 (1). It is estimated that the global number of deaths from cardiovascular diseases will increase from the current 17.5 million to about 23 million by 2030 (2, 3). Although a continuous positive trend of reduced mortality from cardiovascular diseases (CVD) has been observed in Croatia over the last 15 years, with an even greater improvement for cerebrovascular diseases, they are still the top cause of mortality. There were 23,190 deaths from CVD in Croatia in 2016, which is 45% of total deaths. With a standardized mortality rate of 314/100,000, Croatia is among the European countries that have a moderately high mortality rate (4). ## The association between coronary heart disease and chronic stress and anxiety In addition to the somatic consequences of acute coronary syndrome (ACS) that include different levels of intolerance to exertion, incapacity for work, symptoms of chronic heart failure, angina pectoris, the manifestation of various arrhythmias, etc., the development of a whole range of psychosomatic and mental disorders is also already possible in the early subacute and chronic phases of the disease, and if these mental disorders are not actively treated in a timely fashion they can contribute to unwanted outcomes and increased mortality in this group of patients (5). Acute and chronic stress and anxiety have long been recognized and are now clearly established as risk factors for the development of acute myocardial infarction (AMI) (6). For instance, the INTERHEART study divided sources of chronic stress into stress at work, stress at home, and stress related to financial and existential issues. Patients with first AMI reported significantly more stress in all of these categories in comparison with the control group (7). Furthermore, two-year follow-up of almost 34 thousand male healthcare workers in the USA aged between 42 and 77 that initially had no disease diagnosis found that relative risk for fatal CVD was three times higher for those with the highest levels of anxiety in comparison with participants with the lowest levels of anxiety (8). ## The association between heart disease and depression A wide spectrum of evidence indicates depression as a strong risk factor for CVD, both in persons without manifested CHD or with previously established CHD. A review of 53 studies and 4 meta-analyses by the American Heart Association (AHA) found that depression after acute coronary syndrome constitutes a risk factor for adverse outcomes, including increased all-cause mortality and cardiovascular mortality (9). Several potential pathophysiological mechanisms of association between depression and AMI have been suggested, including dysfunction of the hypothalamic-pituitary-adrenal axis, inflammatory and prothrombotic changes, low levels of omega-3 fatty acids, low sinus frequency variability, etc., as well as lack of treatment compliance (10). The largest analysis of the association between depression and AMI is related to a study conducted on more than 93,000 postmenopausal women aged 50 to 79 that participated in the Women’s Health Initiative study. At baseline, 16% of participants reported depression and 12% had previous depression in their medical history. In four years of follow-up, patients with current or previous depression had significantly higher rates of cardiovascular mortality and total mortality from all causes compared with participants without depression (11). Despite the lack of convincing and indubitable evidence that treating depression improves survival after ACS, AHA has nevertheless concluded and recommended consideration of a holistic assessment of coronary patients and treatment of clinically significant or long-lasting depression (9). ## Posttraumatic stress disorder and its association with acute coronary syndrome and cardiac surgery procedures Posttraumatic stress disorder (PTSD) is a relatively common entity in psychiatric practice that is defined as a complex somatic, cognitive, and affective disorder caused by different forms of psychological trauma. PTSD is characterized by intrusive thoughts, nightmares, and memories of past traumatic events, avoidance of reminders of trauma, and sleep disorders, all of which leads to significant social, professional, and interpersonal dysfunction (12). Diagnosing PTSD can be challenging due to the heterogenicity of presentation and resistance from the patient in discussing past traumas. Different forms of trauma can cause PTSD, including all kinds of sexual abuse, divorce, death of a loved one, active participation in military operations, etc., and it is also common amongst civilians in warzones, refugees, during natural disasters, etc (12). The total prevalence of all-cause PTSD is between 6-9% in national samples of the general population of the United States and Canada (13). According to research from the World Health Organization, a somewhat lower prevalence was found outside America and is approximately 2% in economically moderately developed nations (14). Although the greater part of the pathophysiology of PTSD is still unclear, a review of the literature yields intriguing reports. Magnetic resonance imaging of brain structures in patients with PTSD found reduced volumes of the hippocampus, left amygdala, and the frontal cingulate cortex in comparison with the control group without PTSD (15, 16). Other reports found elevated norepinephrine levels in the central nervous system with downregulation of adrenergic receptors, chronic reduction of glucocorticoid levels, etc (17, 18). Furthermore, it is thought that certain genetic predispositions can contribute to individual sensitivity to PTSD through interaction with external factors (19). Other than the previously described association between ACS and chronic stress, anxiety, and depression, ACS can also be a trigger for subsequent development of PTSD just like other traumas, with a prevalence of PTSD between 4% to as much as 25% among persons suffering from ACS (average prevalence of 10-15%) (20-22). Although data on PTSD after stroke are less extensive than the literature on PTSD and ACS, there are some reports that one out of every four cases of stroke or transitory ischemic attacks can be associated with subsequent development of PTSD (23, 24). Additionally, cardiac surgery procedures (25) and especially long hospital stays in the intensive care unit and complicated postoperative progression (26) have a high chance of leading to subsequent development of PTPS. Symptoms that indicate PTSD in patients who underwent prolonged treatment in an intensive care unit include affective and behavioral reactions to stimuli that cause “flashbacks”, severe anxiety and hyperexcitation, and intrusive memories and avoidance of experiences that cause the symptoms (27). A meta-analysis of 24 observational studies that included 2383 coronary patients found that the prevalence of PTSD associated with ACS was 12% (21). Furthermore, data from three studies on 609 patients who fulfilled the quality criteria for meta-analysis show that risk of repeated myocardial infarctions or sudden death was twice as high in patients with PTSD after ACS in comparison with those without PTSD symptoms (21). Additionally, multiple studies have demonstrated that patients with PTSD symptoms associated with previous ACS, especially if untreated, have increased mortality and higher rates of myocardial reinfarction (28, 29). ## Experience with patients included in the cardiovascular rehabilitation program Experience in the treatment and rehabilitation of patients who had AMI or underwent a cardiac surgery procedure shows that despite the abovementioned facts and data from the literature, at least a portion of patients with symptoms of PTSD associated with ACS or cardiac surgery is not recognized (30) and remain untreated in the subacute and chronic phase of the disease, which leads to a cascade of the previously described adverse events and outcomes. It is a common occurrence in clinical practice for a previously “healthy” person who has not had any experience of hospital treatment to develop ACS. Rapid onset of the symptoms, emergency hospitalization, urgent interventional and sometimes surgical treatment, staying in an intensive care unit, early complications that can include malignant arrhythmias and resuscitation procedures (“proximity to death”), copious amounts of newly-introduced medications, sudden (temporary) incapacity for work, worrying about future existential needs, etc., can of course lead to a varied spectrum of psychogenic manifestations such as acute anxiety and depression. Depending on various factors and predispositions, personality traits, previous illnesses, compensation mechanisms, family support, etc., some of these patients will gradually adjust to their new state, but some of them will develop symptoms of PTSD associated with ACS. This group of patients is less cooperative in further treatment and less motivated for regular, long-term medication treatment and cardiological controls (31), has a lower quality of life (32), and the whole family of the patient often suffers from some of the consequences of the patient’s condition. In the Krapinske Toplice rehabilitation center (and in two other Croatian rehabilitation centers (33, 34)) the psychologist is and important and integral part of the team, so we fairly often successfully discover elements of PTSP after ACS or heart surgery (30). Unfortunately, the hospital in Krapinske Toplice does not have regular psychiatric consultations available. After completion of their rehabilitation program we therefore refer these patients to a clinical psychiatric evaluation and further treatment as well as psychosocial support. ## Conclusion The aim of this review was to raise the awareness of cardiologists regarding this issue in everyday clinical practice. In addition to a cardiologist, anesthesiologist, and cardiac surgeon, a psychologist and psychiatrist should be an integral part of every serious wider “Heart Team”. Such a holistic approach would achieve the desired effect not just on the somatic, but also on the total psychological stability of these seriously ill patients (35), which would ultimately improve quality of life and reduce the incidence of new unwanted cardiovascular events and mortality. Given that current studies and available data indicate the prevalence of PTSD associated with ACS has a fairly wide range of 4% to as much as 25% (22), a study would ideally be conducted with a representative sample to determine its prevalence in Croatia and long-term outcomes for these patients.

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