IS SCREENING OF DEPRESSIVE SYMPTOMS USEFUL AT THE PATIENTS WITH CARDIOVASCULAR DISEASE?

Elena Clinescu 1, Ioana Daha2, Cornelia Clinescu3 , Gheorghe Andrei Dan 4

1

Resident in Psychiatry at the Clinical Hospital of Psychiatry Prof. Dr. Al. Obregia, Berceni Road No. 10-12, Bucharest, Romania. Tel. +0400-740631669. E-mail: ecalinescu@yahoo.com. 2 MD internal medicine and cardiology, Dept. of Cardiology, Colentina Hospital, Bucharest. 3 Resident in cardiology at Institute for Cardiovascular Diseases "C.C.Iliescu", Bucharest. 4 Cardiologist senior, MD, PhD, University Professor at Univ. of Medicine and Pharmarmacy "Carol Davila" Bucharest; Head Dept. of Cardiology, Colentina Hospital, Bucharest. Received December 08, 2010, Revised February 28, 2011, Accepted April 06, 2011.

Abstract: The influence of affective disease on the cardiovascular system is a known fact, even though, because of opposite scientific results, a correlation between depressive symptoms and the etiology, evolution or prognosis of cardiovascular disease hasn't been proved yet. Our approach is the result of numerous studies showing the negative influence that depressive symptoms have on the evolution and prognosis of cardiovascular diseases. We are trying, through this article to draw attention on the importance of searching depressive symptoms on patients with cardiovascular disease, in order to prevent a possible severe coronary event, to improve the clinical condition of the patient and to provide the best medical care for patients suffering from cardiovascular disease. Key words: correlations, prognostic factors, depression, anxiety, ischemic heart disease. Rezumat: Influena tulburrilor din sfera psihoafectiv asupra sistemului cardiovascular constituie un truism, cu toate c, rezultatele tiinifice contradictorii nu pot susine, pn n prezent, o legatur clar ntre simptomele depresive i etiopatogenia, evoluia i prognosticul bolilor cardiovasculare. Demersul nostru este urmarea numeroaselor studii care arat c, simptomele depresive influeneaz negativ evoluia i prognosticul bolilor cardiovasculare. ncercm, prin acest articol, s atragem atenia asupra importanei screening-ului simptomelor depresive la pacienii cu boli cardiovasculare n scopul prevenirii unui posibil eveniment coronarian sever, mbuntirii strii clinice i acordrii de ngrijiri medicale optime a pacienilor cu boli cardiovasculare. Cuvintele cheie: corelaii, factori de prognostic, depresie, anxietate, boala cardiac ischemic

Demographic ageing and industrialization, which includes urbanization associated with a changing lifestyle - with a powerful influence of stress, diet and sedentary lifestyle - led to a continuous increase in the incidence and prevalence of depressive and cardiovascular disease, especially in developed countries. Depression lifetime prevalence is 7% - 14% for males and 20% - 25% for females (1, 2). Most studies show that depression has the higher lifetime prevalence (approximately 17%) of all mental disorders (3). Follow-up studies after 2006 show that the incidence of depression is approximately 20% (2). About 30% of the population over 60 years with a somatic disease has associated depressive symptoms (1). 1

A study carried out by the World Health Organization, World Bank and Harvard University concluded that, ever since 1990, depression is the fourth disease cause worldwide (1, 4). Depression has been designated by WHO in 2001 as a worldwide chronic disease, with the potential to become the leading cause of morbidity by 2020 (5). Cardiovascular diseases represent 48% of all deaths in Europe, with coronary artery disease as the most common cause (1 in 5 deaths) (6). Since 1950 cardiovascular diseases have become the leading cause of death in developed countries, the same thing happened in developing countries since 2001, so that, these days, cardiovascular diseases are the leading cause of death worldwide. In Romania, the prevalence of cardiovascular diseases also comes first, with more than 37 cases per 100 people examined, age over 15 years. It is estimated that in Romania there are about 7 million people with cardiovascular disease (2.8 million representing those with ischemic heart disease). The incidence of cardiovascular diseases in Romania was 256,4 / 100.000 inhabitants in 2004 (7). The relationship between the "state of mind" and the heart can be found in vocabulary and literary works from ancient times, although, for a long period of time, there were no scientific data to confirm it. In 1628, William Harvey was the first to accurately describe the circulatory system and later expressed his opinion on the relationship between the heart and mind: "for each mental condition associated with pain or pleasure, hope or fear, an agitation occurs, whose influence extends to the heart ". This possible association has received little attention for more than 300 years. Only in the mid 70s reports appear about the impact of negative emotions on prognosis of myocardial infarction and also reports of a possible causal relationship between depression and myocardial infarction. In 1993, Frasure-Smith and colleagues published the outcomes of a prospective study, showing that, among other factors, depression is a significant predictor of mortality from myocardial infarction, and major depression is an independent risk factor for mortality in the first 6 months after a myocardial infarction (8). After 1993, numerous studies revealed consistent correlations between depression, anxiety and ischemic heart disease and also mortality from ischemic heart disease. Other studies considered that there is no significant relationship between depressive disorders and ischemic heart disease or cardiovascular disease evolution and prognosis. A recent meta-analysis which includes 22 studies suggested that the effects of post myocardial infarction depression on the cardiac prognosis have been mistaken with the severity of cardiac infarction. However, post myocardial infarction depression was associated with a risk 2 - 2.5 times higher of all-cause mortality, cardiac mortality and new cardiovascular events. Among the studies that reported a statistically significant effect of depression on the severity of myocardial infarction, four studies have found depression to be an independent risk factor for myocardial infarction and other four studies found a less significant connection between depression and myocardial infarction (9). Note that there are studies that failed to confirm a statistical significant relationship between depression and myocardial infarction prognosis. A baseline survey which included people from 52 countries on five continents, published in 2004 (the INTERHEART study) has identified nine risk factors, easy to prove, responsible of over 90% of cases for risk of a cardiovascular event: smoking, dyslipidemia, hypertension, diabetes, obesity, diet, sedentary lifestyle, use of ethanol, psychosocial factors (work-related stress and other stressful events, the perception of inability to control existential situations, lack of social support) (10). Beside these risk factors the predisposing role of hereditary factors (genetic 2

vulnerability) is well known , in particular, family history for premature ischemic heart disease (IHD), defined as IHD in first degree relatives, males, age <50 years and females, age <65 years ) (11). The role of age is obvious, over 83% of people with coronary heart disease are over 65 years, and the risk for IHD in both sexes increases with age, with specification that the incidence of IHD is lower in women than in men before the age of 50 years; after menopause, cardiovascular risk in women gradually increases, becoming similar to that of men in the eighth decade for life (11). It is estimated that depressive symptoms and in particular major depressive disorder is undiagnosed and untreated. Studies show that among patients with mental disorders, 30% - 60% are not diagnosed (12). So, both patients with cardiovascular disease and patients with other somatic diseases may have undiagnosed depressive symptoms (13). Costs associated with somatic patients hospitalized for various diseases are double for those suffering of depression than for those without depression (14). Costs for the treatment of depressive disorder in 1990's America, were approximately 44 billion$, and the only way to reduce these costs was to restrict patient access to mental health care (15, 16, 17). Of those who seek help and treatment for depressive symptoms, more than half addressed themselves to the family doctor instead of seeking help from the mental health care system. In America, in 1997, only two out of 10 patients with depression were receiving psychiatric treatment from a psychiatrist (18). It is estimated that the prevalence of depression (major depressive disorder) among patients with heart disease is between 15 and 23% (19, 20, 21, 22, 23, 24). Depression is about two times more common in women with cardiovascular disease than in men (25). In patients with known cardiac disease, depressive disorder is responsible for an increase of approximately 3-4 fold increased risk of cardiovascular mortality (20, 26, 27, 28, 29). Diagnosis and treatment of major depression is important because many international studies have shown that depressive symptoms are a predictor for development of cardiovascular disease and unfavorable prognosis. In this respect we will discuss the changes, the factors predictive role without reference to other cardiac markers (troponin, natriuretic peptides, etc.) and neuromediators of depression (serotonergic, noradrenergic, dopaminergic, etc.). Depression is associated with multiple physiological changes that can adversely contribute to the development and prognosis of heart disease. Patients with depressive symptoms present in response to emotional stress, the activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal cortical system. Following the activation of the two systems appear: hipercortizolemia, high levels of catecholamine in the blood, abnormal platelet activation, increased inflammatory markers and endothelial dysfunction. These physiological changes are also present in depressed patients without heart disease. The disappearance of the two systems stressors should return to their basal position (30, 31, 32). Genetic predisposition, such as the serotonin transporter gene polymorphism with environmental factors could explain why some people adapt to stress factors, while others develop depression (33). Excessive activation of hypothalamic-pituitary-adrenal cortical growth is manifested by the corticotrophin releasing factor (CRH), elevated levels of cortisol and catecholamines (adrenaline and noradrenalin) and resistance to dexamethasone suppression test. Catecholamines leads to vasoconstriction, which may be beneficial in the short term heart rate response to stress, but long term can lead to heart failure. Increased levels of catecholamines in the blood are related to cardiac mortality by left ventricular dysfunction and heart failure (34, 35, 36, 37).

Increased activation of blood platelets leads to platelet aggregation and increase clot formation. In response to activation, platelets secrete serotonin, which acts as an agonist at 5HT2 receptors and directly contribute to increased platelet aggregation and arterial vasoconstriction (38, 39, 40). It have shown similarities between the platelets 5HT2A receptors and 5HT2A receptors on the serotonergic neurons. It was also shown that platelets and brain serotonin transporter (SERTS) are encoded by the same genes. Serotonin-mediated platelet activation is assumed to be the "key" that would explain some pathogenetic relationship between depression and cardiovascular disease (41). Increased inflammatory response was detected in patients with depression by increasing levels of acute phase proteins (for ex. protein C reactive nonspecific inflammatory marker) and non inflammatory cytokines (eg. interleukins 1 and 6, tumor necrosis factor). It has been shown in multiple studies that these inflammatory markers meet in acute coronary syndrome, heart failure, and atherosclerosis. (42, 43, 44). Behavioral changes dont influence the evolution and unfavorable prognosis of depression associated with cardiovascular disease through directly mechanisms, but may become a barrier to the provision of optimal care. Thus, patients with depressive disorder may be less adherent to therapy, lifestyle modifications (eg. stop smoking, exercise, weight monitoring) and even heart dispensary (return to control, monitor cardiac function), compared with those without depression. Another clinical possibility is depressive disorder secondary to cardiac disease not associated with multiple other co-morbidities. In this case the negative outcome is due to the worsening of the heart disease and not by the depressive disorder itself (45). Numerous studies support the need to establish early detection and treatment of depression in patients with cardiovascular disease for the following reasons: - poor diagnosed depression in patients with medical conditions and therefore those with cardiovascular disease - as a co-morbidity, depression contributes to the worsening of the symptoms , prognosis and the growth of mortality from cardiovascular disease - if depression influences the physiological mechanisms of cardiovascular disease, early diagnosis and treatment of depression may lead to an evolution and a better prognosis by returning to the basal function of these mechanisms - if depression affects cardiovascular disease through behavioral changes, early diagnosis and treatment of depression can improve adherence to therapy, changing lifestyles and cardiology dispensary. Current knowledge explains not only through specific mechanisms (genetic, physiological, biochemical, etc.): (a) the relationship between depression and cardiovascular disease development and prognosis, (b) if a patient with depression may reduce the risk of cardiovascular death and serious cardiovascular events. Social, demographic and medical variables dont allow early diagnosis of depressive symptoms, including patients with cardiovascular disease. Identification of biochemical markers for depression used in research, remains a goal in current practice. It has been shown that antidepressants are serotonin reuptake mechanism (SSRIs) (SADHART study, CREATE study) are more effective than tricyclic antidepressants (adverse side effects fewer in number) in patients with cardiovascular disease, especially in elderly patients (27, 50). The mechanism by which SSRIs reduce the risk of cardiovascular events such as inhibition of platelet serotonin uptake, mobilization of intracellular calcium secondary to 4

increased bleeding time (known side effect of SSRIs), leading to lower risk of developing coronary thrombus (27, 50). Dual Antidepressants have also proven efficacy and tolerability in patients who had myocardial infarction and depression (study MIND - IT). Psychotherapy based on cognitive - behavioral interventions (ENRICHD study) was also taken into account (51, 52). These studies, however, failed to demonstrate statistically significant benefits of the treatment of depression in cardiovascular disease. The most effective ways of treatment (psychopharmacological or psychotherapeutic) of patients with depression and cardiovascular disease remain to be determined. Future studies will identify the most effective ways of screening and treatment approach (psychopharmacological and psychotherapeutic), and monitoring of patients with depression and cardiovascular disease. Investigative strategies should be based on additional prospective studies of patients with cardiovascular disease and depression. At present, although specific mechanisms are not known exactly which depression influences unfavorable evolution and prognosis of cardiovascular disease, many studies consider that early diagnosis and treatment of depressive symptoms in patients with cardiovascular disease, contribute to the improvement of the clinical condition, the quality of life and increase survival of these patients.

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