An-Najah National University Faculty of Graduate Studies Estimation Ten-Year Risk of Coronary Heart Disease in Patients with Schizophrenia By Saqer M. Al-qoroum Supervisor Prof. Waleed Sweileh Co- supervisor Dr. Samah Al- Jabi This Thesis is Submitted in Partial Fulfillment of the Requirements for the Degree of Masters of Community Mental Health Nursing, Faculty of Graduate Studies, An-Najah National University, Nablus-Palestine. 2013 III االهداء ني اىدي ىذا العمل المتواضع إلى فا إلى من دفعني إلى العمم وبو ازداد الشمعة التي احترقت حتى توصمني إلى ما أنا فيو أبي الغالي... إلى رمز الرجولة والتضحية افتخارا أمي الغالية... إلى من يسعد قمبي يمقياىا إلى روضة الحب والتي تنبت أزكى األزىار لغالية ... شكرازوجتي ا إلى األنامل المالئكية التي تحرك األمل والحياة ...أطفالي ونبض قمبي حمزة وحسام إلى كل من مد لي يد العون ألخطو في طريق العمم اىدي ىذا البحث... IV الشكز والحقذيز أتقدم بالشكر أوال إلى أ.د. وليد صويمح المشرف الرئيسي عمى ىذا البحث لجيوده رشاده وكل ما قدمو لي من مساندة إلتمام ىذا البحثالمتوا ... صل ودعمو وا فيل يمكن شكر الشمس ألنيا تضيء عمى األرض... إلى الدكتورة سماح الجابي المشرف الثاني عمى ىذا البحث لجيودىا ومساعدتيا في إتمام ىذا البحث.. ريض في جامعة النجاح(إلى كل األساتذة األفاضل في الصرح العممي الكبير)كمية التم إلى وزارة الصحة الفمسطينية ممثمة بكافة مراكزىا الصحة النفسية األولية لممساعدة في الوصول إلى المعمومات الالزمة ليذا البحث... V إقرار نا الموقع أدناه مقدم الرسالة التي تحمل العنوان :أ Estimation Ten-Year Risk of Coronary Heart Disease in Patients with Schizophrenia ء من تمت اإلشارة قر بان اشتممت عميو ىذه الرسالة ىي من نتاج جيدي الخاص باستثناأ وان ىذه الرسالة ككل أو إي جزء منيا لم يقدم من قبل لنيل درجة أو لقب عممي أو .إليو حيثما ورد .بحثي لدى إي مؤسسة تعميمية أو بحثية أخرى Declaration The work provided in this thesis, unless otherwise referenced, is the researcher’s own work, and has not been submitted elsewhere for any other degree or qualification. Student's Name: :اسم الطالب Signature :التوقيع Date: :التاريخ VI List of Contents Pages Subject No. III االىداء IV الشكر والتقدير V إقرار VI List of Contents VIII List of Tables IX List of Figures X List of Abbreviations XI Abstract 1 Chapter One: Introduction 2 Definition of Schizophrenia 1.1 4 Epidemiology of Schizophrenia 1.2 5 Coronary Heart Disease in Schizophrenia 1.3 5 Framingham Heart Formula 1.4 6 Study aims and Objectives 1.5 6 General Aim 1.5.1 6 Specific Objectives 1.5.2 6 Study Problem 1.6 7 Research Hypotheses 1.7 7 Significance of the Study 1.8 8 Expected Outcome of the Study 1.9 9 Chapter Two: Literature Review 9 International studies for prevalence CHD risk factors among schizophrenic patients 2.1 14 Modifiable Risk Factors for CHD in Schizophrenia Patients 2.2 14 Sedentary Lifestyle 2.2.1 15 Weight gain and Obesity 2.2.2 16 The Role of Antipsychotics 2.2.3 17 Smoking 2.2.4 18 Hypertension 2.2.5 18 Dyslipidemia 2.2.6 19 Diabetes Mellitus (DM) 2.2.7 19 Studies among Healthy General Population Regarding Ten-Year CHD Risk 2.3 20 Local Studies in north West-Bank 2.4 VII 21 Chapter Three: Methodology 21 Study Design and Site of the Study 3.1 21 Inclusion Criteria 3.2 21 Exclusion Criteria 3.3 22 Sampling Size and Sampling Methods 3.4 23 Data Collection 3.5 24 Measurement of HDL-C and TCH 3.6.1 24 Blood Pressure 3.6.2 24 Coronary Heart Disease Risk Estimation 3.7 25 Data Analysis 3.8 26 Ethical Consideration 3.9 27 Chapter Four: Results 35 Chapter Five: Discussion 35 Introduction 5.1 35 Comparison with Literature 5.2 38 Factors Associated with Risk ≥10% 5.3 40 Limitation 5.4 40 Conclusions 5.5 40 Recommendation 5.6 42 References 54 Appendices الملخص ب VIII List of Tables No. Table Content Page 4.1 Demographic and clinical characteristics of the participants 27 4.2 Frequency of Framingham risk categories stratified by gender 29 4.3 Univariate analysis of factors associated with low (<10%) and intermediate/ high (≥10%) CHD risk categories 33 4.4 Multivariate analysis of factor associated with CHD risk ≥ 10% 34 5.1 Comparative of the prevalence ten-year risk of CHD in different countries in patients with schizophrenia 37 5.2 Comparative of the distribution ten-year risk of CHD in different countries in patients with schizophrenia 38 IX List of Figures No. Figure Figure Page 3.1 Sample collection process for schizophrenia patients 23 3.2 Framingham risk score to estimation ten-year risk of CHD in schizophrenia patients 25 4.1 Frequency of schizophrenic patients in each CHD risk category 29 4.2 Frequency of schizophrenic male and female patients in each CHD risk category 30 4.3 Frequency of schizophrenic patients in each CHD risk category stratified by age group 31 4.4 Frequency of schizophrenic patients in each CHD risk category stratified by duration of psychiatric illness 32 X List of abbreviations Abbreviation Meaning APA American Psychological Association BMI Body Mass Index CHD Coronary Heart Disease CVD Coronary Vascular Disease CATIE Clinical Antipsychotic Trial of Intervention Effectiveness DSM-IV-TR Diagnostic and Statistical Manual of Mental Disorders DM Diabetes Mellitus FHS Framingham Heart Study HDL-C High density lipoprotein-cholesterol LDL Low Density Lipoprotein MS Metabolic Syndrome MOH Ministry Of Health OR Odd Ratio PTSD Post Traumatic Stress Disorder SPSS Statistical Package For Social Sciences TCH Total Cholesterol US United State WHO World Health Organization IRB Institutional Review Board ICD-10 International Classification of Diseases XI Estimation Ten-Year Risk of Coronary Heart Disease in Patients with Schizophrenia By Saqer M. Al-qoroum (11054546) Supervisor Professor: Waleed Sweileh Co- supervisor Dr. Samah Al- Jabi Abstract Background: Studies indicated that patients with schizophrenia have shorter life span than that of general population. Objective: To estimate ten-year risk of coronary heart disease (CHD) in patients with schizophrenia. Methods: A cross-sectional study was carried out in four governmental primary psychiatric health care centers in northern West-Bank (Nablus, Jenin, Qalqilia, and Tulkarem). 112 patients diagnosed with schizophrenia were recruited for the study. A convenience, non-probability sampling method was used. Ten-year risk of CHD was calculated using Framingham risk scoring formula which includes the following variables: age, gender, smoking status, high-density lipoprotein- cholesterol, systolic blood pressure and history of anti-hypertensive drugs hypertension. Risk of CHD was categorized based on total scores into the followings: Ideal (<5%), low (5-9%), intermediate (10-20%) and high (>20%). Descriptive and analytical statistics was conducted using Statistical Package for Social Sciences (SPSS) version 20. XII Results: The mean age of the participants was 43 ± 10.85 years. The majority were males (76; 67%). There was no significant difference between males and females in age (P=0.72), duration of psychiatric illness (P=0.085), systolic blood pressure (P=0.75), diastolic blood pressure (P=0.7) and total cholesterol level (P=0.17). The mean ± standard deviation (SD) ten-year CHD risk score was 5.6 ± 5.8 (median (inter quartile range (Q1 – Q3)): 3 (1 – 9)). The mean ± SD ten-year CHD risk score for females was 1.5 ± 1.58 (median (Q1 – Q3): 0.75 (0.5 – 2)) while that for males was 7.5 ± 6 (median (Q1-Q3): 6 (2–13)). Based on Framingham risk scores, there were 87 (77.7%) patients in low risk, 22 (19.6%) patients in intermediate risk and 3 (2.7%) patients in high risk. Univariate analysis showed that there were significant differences between low <10% risk score and intermediate/high risk ≥ 10% risk score categories with respect to age distribution (P<0.05), gender (P<0.05), smoking (P<0.05), total cholesterol (P<0.05), diastolic blood pressure (P<0.05) and duration of psychiatric illness (P=0.03). However, there was no significant difference between the low <10% and intermediate/high ≥10% categories in terms of systolic blood pressure, waist circumference and HDL-C levels. Multivariate analysis on male patients showed that age [O.R=1.524, 95% CI (1.213-1.914)] and diastolic BP [O.R=1.207, 95% CI (1.045-1.393)] were significant factors associated with intermediate/high ≥ 10% CHD risk. Conclusions: One fifth of schizophrenia patients had a CHD risk ≥ 10%. Efforts to decrease CHD risks among patients with schizophrenia should be directed mainly toward diastolic BP as modifiable risk factor. Key words: Schizophrenia, Framingham Risk Score, CHD, Palestine. 1 Chapter one Introduction The occupied Palestinian territories, in which this study was conducted includes two geographically separate areas: West-Bank and Gaza Strip. In the West Bank, mental health care services are provided by the government and by few nongovernmental organizations. Several governmental psychiatric primary health care centers are located throughout West-Bank. north West-Bank consists of four major cities including Nablus, Jenin, Tulkaram, and Qalqilia [1]. According to the Palestinian Ministry of Health (MOH) annual report, the number of newly reported cases in primary mental health care centers was 774 in 2011; approximately 60% of them were treated for psychiatric illnesses [2]. These numbers indicated that there is a real need for good quality mental healthcare services to maintain the physical health of those patients who have serious cognitive impairment. In the Arab world, mental health services are far away from optimum. There is an urgent need for increased mental health education of the public, psychiatric services and the development of mental health services and policy in all Arab countries [3, 4]. There is also lack of reliable epidemiological studies in the schizophrenia and related disorders in the Arab world which does not enable rational planning for future psychiatric services and research[5]. 2 1.1 Definition of Schizophrenia Psychosis, a disorder characterized by distortion in individual perception of reality and the presence of hallucinations, delusions or disorganized thoughts, is a common disorder with 3 to 5 percent of the general population experiencing related symptoms during their life time [6, 7]. Psychotic disorders are categorized as schizophrenia, bipolar mania, major depression with psychotic features, schizoaffective disorder, Alzheimer’s disease, delirium, brief psychotic disorder, substance induced psychotic disorder, delusional disorder and psychosis secondary to a medical condition [8]. Schizophrenia is diagnosed based on criteria in either the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, version DSM-IV-TR, or the World Health Organization's International Statistical Classification of Diseases and Related Health Problems, the ICD-10 [9, 10]. Both define symptoms and characteristic impairments of schizophrenia in a similar way [11]. There are three types of symptoms which can help in the definition and diagnosis of schizophrenia: positive symptoms, negative symptoms and cognitive impairment [11, 12]. Positive symptoms involve a loss of contact with reality. They include bizarre behaviors, false beliefs (delusions), or perceptual experiences not shared by others (hallucinations). The presence and severity of these symptoms tends to be episodic over time. Negative symptoms are lack of or greatly decreased state of expressing emotions. Examples of negative symptoms could include: lack of facial expression, 3 pleasure in activities, diminished ability to clearly communicate with others and withdrawal from sharing activities with others. Cognitive impairment is considered the third component of diagnosis of schizophrenia. It involves loss of patients’ attention and concentration. Impairment in role functioning and/or substantial change in personal behavior is clinical features of schizophrenia. Often these symptoms emerge years before the psychotic symptoms [11, 12]. These symptoms can be profound and result in the need for assistance in meeting basic needs, such as: housing, food and medical care. Moreover these symptoms can negatively alter a person’s relationship with family and friends. Long-term prognosis for many patients with schizophrenia is not adequate. It is marked by intermittent acute psychotic episodes and impaired psychosocial functioning between acute episodes, with most of the deterioration in psychosocial functioning occurring within 5 years after the first psychotic episode [13]. Schizophrenia leads to poor physical outcomes. The standardized mortality ratio for all-cause mortality is 2.6 for patients with schizophrenia compared to the general population, with excess deaths mainly from suicide during the early phase of the disorder, and later from cardiovascular complications [14]. Persons with mental disorders are less likely to pay attention to symptoms of physical illness. Consequently, they delay seeking treatment for co-morbid conditions such as diabetes and hypertension. Patients with schizophrenia, relative to peers without mental illness, experience a 3-fold increase in cardiovascular mortality between the ages of 18 and 49 and almost a 2-fold increase in 4 mortality between the ages of 50 and 75 years [15]. They have a greater incidence of myocardial infarction than demographically similar persons without schizophrenia [16, 17]. People with mental disorders face stigma and discrimination in most societies [18]. The stigmatization of people who have a mental illness not only adds to difficulties in their daily life: it also prevents them from getting access to treatment and care [19]. Mental health nurse can play an important role in the treatment of the mental disorder because they are in a position to recognize the early signs of illness, make referrals to appropriate mental health professionals and help patients and their families cope with the mental disorder [20]. 1.2 Epidemiology of Schizophrenia Schizophrenia is a psychiatric disorder with a median lifetime prevalence of 4.0 per 1,000 and a morbid risk of 7.2 per 1,000 and the prevalence for males and females is similar [14]. The age at onset is typically in adolescence or early adulthood [21]. With onset after the fifth decade of life and in childhood both being rare [22, 23]. The course of schizophrenia is often more severe with earlier onset [21, 24]. The prevalence of schizophrenia varies across the world, within countries and at the local and neighborhood level [25-28]. The total lifetime prevalence rate of schizophrenia in United Arab Emirates (UAE) was found to be 0.7% and showed no gender differences (0.7% for women, 0.7% for men) [29]. The psychiatric morbidity rate for female in Dubai was found to be 22.7% and the prevalence of psychotic disorders for 5 female was found to be 1.9% [30]. The annual incidence rate of all mental disorders in AL-Ain -UAE was found to be almost 11% [31]. While the average annual incidence rate in Bahrain was 1.29 per 10,000 for all ages [32]. In Morocco the prevalence of schizophrenia was found to be 5.6% [33]. 1.3 Coronary Heart Disease (CHD) in Schizophrenia Coronary heart disease (CHD) refers to the failure of coronary circulation to supply adequate circulation to cardiac muscle and surrounding tissue, a phenomenon that can result in a myocardial infarction [34]. Coronary heart disease is a critical public health issue, nationally and internationally. It was responsible for less than 10% of all global deaths at the beginning of the 20 th century, but in 2005 that number was 30% [35]. In developed countries like the United Kingdom, it was found that 39% of deaths to be related to CHD [36]. In Comparison, Arab countries like Jordan has mortality rate as high as 38.2% associated with CHD [37]. In Palestine, Cardiovascular diseases were the main leading cause of death in 2011 [2]. Many studied have suggested that schizophrenia and other psychotic disorders are associated with increasing mortality rates with CHD being the major cause [38-40]. 1.4 Framingham risk formula The equation of the Framingham ten-year risk of CHD derived from the Framingham Heart Study (FHS) has been validated and widely used in different populations to predict the ten-years risk of CHD including angina, myocardial infarction, and cardiac death [41]. The FHS formula has been applied to several racially and ethnically diverse cohorts and has been 6 found to predict cardiac events reasonably well in Caucasians and African- Americans, but may overestimate risk in Hispanic men and Native American women [42]. The ten-year risk of CHD was calculated using the Framingham scoring which was based on age, gender, total cholesterol, HDL-cholesterol, systolic blood pressure and smoking, this tool is designed for adult aged 20 and older who don’t have heart disease or diabetes. 1.5 Study aims and objectives 1.5.1 General Aim The general aim of the study is to estimate ten-year risk of CHD in patients with schizophrenia. 1.5.2 Specific Objectives 1. To identify impact of gender on ten-year risk of CHD. 1. To identify the association of age, smoking, systolic blood pressure, HDL-C and total cholesterol with high ten-year risk of CHD (≥ 10% Framingham risk score). 1.6 Study problem In Palestine, few studies were conducted about cardiovascular risk factors in schizophrenic patients. Two studies by Sweileh et al (2012) on 250 schizophrenic patients found that metabolic syndrome and pre-diabetes were prevalent among schizophrenic patients. Furthermore, a master thesis by Ebwini et al (2012, An-Najah national university) had found that dyslipidemia is also common among schizophrenic patients. The above findings indicated that risk factors for CVD are common among 7 schizophrenic patients which might explain the high mortality among this category of patients [38-40]. One of the most commonly used indicators of future CHD risk in any person is the Framingham calculator. Therefore, we tried to apply the Framingham calculator to estimate the ten-year CHD risk among this category of patients who are physically neglected and already have a disease and drug – induced physical problems. Ultimately, we would like to compare the results obtained with those published elsewhere to find whether schizophrenic patients in our study had higher risk of CHD than those reported elsewhere. In Palestine, the psychiatric services offered are less than optimum [3, 4]. Therefore, we expect that this category to have higher ten-year CHD risk. 1.7 Research Hypotheses 1- There is no association between ten-year risk of CHD ≥ (10% Framingham risk score) and gender of schizophrenia patients. 2. There is no association between ten-year risk of CHD ≥ (10% Framingham risk score) and duration of illness in patients with schizophrenia. 1.8 Significance of the Study Framingham calculator is an easy and quick method to estimate ten-year CHD risk. Implementing the Framingham calculator in psychiatric primary healthcare canters will help to screen those with high risk and implement interventional methods for modifiable risk factors. This approach will be less costly as opposed to treating this CHD condition and its complications once they are present. In addition to the fact that no published studies have 8 been carried out using Framingham calculator in Palestine in psychiatry to estimate ten-year risk of CHD is an added value to mental health services in Palestine. Patients with schizophrenia, relative to peers without mental illness, experience a 3-fold increase in cardiovascular mortality between the ages of 18 and 49 and almost a 2-fold increase in mortality between the ages of 50 and 75 years [15]. Furthermore, antipsychotic medication used was associated with significant weight gain, dyslipidemia and insulin resistance [43]. Long-term use of antipsychotic medications may play an important role in the increased risk for cardiovascular disease [44, 45]. 1.9 Expected Outcome of the study This study gives information that might be helpful to mental health worker to establish appropriate preventive strategies for CHD risk and effective education about healthy living to reduce the risk of CHD in patients with schizophrenia. In the coming chapter, a literature review of international and local relevant studies about CHD risk among schizophrenic patients will be presented. 9 Chapter Two Literature Review 2.1 International Studies for Prevalence CHD Risk Factors among schizophrenic patients. Goff et al. (2005) conducted a study in the United States (US) to compare the ten-year cardiac risk estimates in schizophrenia patients from the CATIE study and matched controls. Results showed that the ten-year risk of CHD was significantly elevated in male (9.4% vs. 7.0%) and female (6.3% vs. 4.2%) schizophrenia patients compared to controls (P=0.001). Schizophrenia patients had significantly higher rates of smoking (68% vs. 35%), diabetes (13% vs. 3%), hypertension (27% vs. 17%) and lower HDL cholesterol levels (43.7 vs. 49.3 mg/dl) compared to controls (P<0.001). Only total cholesterol levels did not differ between groups. Also, the results found that the ten-year risk of CHD in younger adult schizophrenia patients was increased relative to general population [44]. Jin et al. (2011) compared the ten-year risk of developing CHD among middle-aged and older patients with psychotic symptoms in the general population. Results showed that the mean age of the study sample was 63 (range 40–94) years, 68% were men. The Framingham ten-year risk of CHD was increased by 79% in schizophrenia, 72% in Post Traumatic Stress Disorder (PTSD), 61% in mood disorder with psychosis and 11% in dementia. There were also significant differences in diastolic blood pressure (P<0.01) and HDL-C (P<0.05) among the four diagnostic groups, 11 with schizophrenia and PTSD patients tending to have higher diastolic blood pressure and dementia patients having the highest HDL-C [46]. In Spain, a study was carried out by Bobes et al. (2007) in order to assess the prevalence of CHD and MS in outpatients schizophrenia treated with antipsychotics showed that the overall risk of CHD in 10 years as assessed by FHS was 6.8% and was likewise significantly greater in males than in females: 8.3 versus 4.5 (P<0.001) and 22.1% of patients showed a high/very high risk Framingham (≥10%) function. The abdominal obesity and low HDL-C were more prevalent in women (P<0.001) in both cases. Hypertension and hypertriglyceridemia were more prevalent in men (P<0.01) in both cases. Ten-year risk of CHD was significantly higher in males than in females (P<0.001) [47]. Daumit et al. (2008) performed a randomized study to examine the effects of different antipsychotic treatments on estimates of ten-year risk of CHD calculated by the FHS formula. The results showed that the mean age was 40.7 ± 11.1 years, and the sample was 75% male. Twelve percent of the sample had DM, 58% smoked cigarettes, and 34% had hypertension. CHD risk divided into three categories: risk <5% (39%), risk 5-9% (28%) and risk ≥ 10% (33%). Females' mean ten-year CHD risk was significantly lower than males, at 5.7% compared to 9.5% respectively. Females' lower prevalence of cigarette smoking (50% vs.61%) and higher HDL (47.1 mg/dl vs. 42.0 mg/dl) contributed to lower CHD risk [48]. A study conducted in (2003) to compare cardiovascular risk factors in drug-naive first-episode schizophrenia patients with matched controls. The 11 results showed that the difference between two groups in HDL-C was not significant. But total cholesterol was lower in schizophrenia patients than match control [49]. Phutane et al. (2011) conducted a study in US aimed to estimate ten-year risk of developing coronary heart disease in a sample of first episode psychosis patients referred to an early intervention clinic and compared with matched controls. Risk was classified in three categories: very high ≥ 20%, moderate 10-19%, and low <10%. The results found that the sample was young (mean 22.5 ± 4.4 years); there was no significant difference in total cholesterol or HDL-C between two groups. The rates of current smoking were high among patients (46% of patients compared to 36% of controls), the frequency of elevations in blood pressure in the patients was (29%) compared to (2%) in the control group. The median duration of illness was 29 weeks, with a range from <1 week to 163 weeks. The median (range) ten-year risk of CHD for patients and controls was 1 (0-5) % and 0 (0-9) % respectively. There was no significant difference between the two groups (P=0.119). Both groups were in the low risk category <10%. Males and females did not differ in any of the measured CHD risk factors in the sample [50]. A study conducted in Canada (2010) aimed to evaluate the prevalence of cardiovascular risk factors and cardiovascular disease in people diagnosed with schizophrenia disorder with match control non-schizophrenic patients. This study showed that the people with schizophrenia had a higher 12 prevalence of diabetes and cardiovascular disease than those without schizophrenia particularly at a younger age [51]. Said et al. (2012) conducted a study in Malaysia. This study aimed to determine the prevalence of metabolic syndrome and risk of CHD in patients with schizophrenia receiving antipsychotics. Results showed that the ten-year risk of CHD was significantly higher in patients with metabolic syndrome. The proportion of patients with high/very high risk for CHD (Framingham ≥ 10%) was greater in patients with metabolic syndrome than in those with non-metabolic syndrome (31.5% vs. 11.0%)(P<0.001) and the mean Framingham risk score for the metabolic syndrome group was 7.6% while that for the non-metabolic syndrome group was 5.0% [52]. In a Spanish cross-sectional study of 733 patients with schizophrenia, the most prevalent cardio metabolic risk factor was found to be smoking (71% of patients), followed by hypercholesterolemia (66% of patients)[53]. A study was carried out by Protopopova et al. (2012) in Croatia to predict the risk of premature cardiovascular mortality and assess the prevalence of cardio metabolic risk factors in schizophrenia patients using risk SCORE chart. The results showed that dyslipidaemia was the most frequent cardio- metabolic risk factors and was present in 70% of the patients, and female patients had a higher prevalence of diabetes (12% vs. 3.9%), hypertension (16% vs. 8.8%), increased weight (67% vs. 40%), smoking (18% vs. 12%), average age (47±14 years vs. 40.6±7.6 years) and long duration of psychiatric illness (14.5 years vs. 7.6 years) than males. On the other hand, 13 the male patients had significantly higher weights, waist circumferences and diastolic blood pressures compared to female patients and the male patients had significantly lower HDL levels. According to the risk SCORE chart, there were 13 patients (10%) with a high (≥ 5%) ten-year risk of fatal cardiovascular events [54]. In addition, a large study involving 46,136 people with severe mental illness and 300,426 healthy controls was conducted in UK to estimate the excess mortality and the contribution of antipsychotic medication in severe mental illness and compared with healthy control Study. This study has demonstrated that the risk ratios for CHD mortality in people with severe mental illness compared with controls were 3.22 (95% CI, 1.99–5.21) for people 18-49 years old, 1.86 (95% CI, 1.63–2.12) for those 50-75 years old and 1.05 (95% CI, 0.92–1.19) for those older than 75 years. For stroke deaths, the risk ratios were 2.53 (95% CI, 0.99– 6.47) for those younger than 50 years, 1.89 (95% CI, 1.50–2.38) for those 50-75 years old and 1.34 (95% CI, 1.17–1.54) for those older than 75 years. Compared with healthy controls, people with severe mental illness who were not prescribed any antipsychotics were at increased risk of CHD and stroke than controls [15]. A descriptive study conducted by McCreadie (2003), that aimed to describe the lifestyle of people with schizophrenia and to report risk of CHD showed that the mean age (years) 45±13, 71(70%) were smokers; 25(86%) females and 50(70%)males were obese, 46 (53%) had a raised cholesterol: HDL ratio In addition, mean ± SD 10-year risk of CHD in males was 10.5% ± 8 and in females 7% ± 6 [55]. 14 Moreover, a study conducted in US to determine the prevalence and characteristics of CHD risk factors in patients with chronic schizophrenia disorder. The results showed that the male patients had an increased risk (8.9%) compared with control subjects (6.3%) (P<0.001) and the risk for women was similar for patients (2.6%) and control subjects (2.0%). Total Cholesterol did not differ between patients and control subjects (P=0.294) [56]. 2.2 Modifiable Risk Factors for CHD in Schizophrenia Mortality in schizophrenia is largely due to cardiovascular disease [57]. Many of the established modifiable risk factors could contribute to an increasing incidence of CHD in schizophrenia patients. Modifiable risk factors include lifestyle, weight gain and obesity, cigarette smoking, lipid abnormalities, diabetes mellitus (DM), antipsychotic medication and hypertension [58]. The World Health Organization (2009) has identified the modifiable risk factors for early mortality as hypertension, smoking, raised glucose, physical inactivity, obesity and dyslipidaemia, as being the top six modifiable global mortality risk factors; patients with schizophrenia have high levels of all these risk factors [58, 59]. Hypertension, hyperglycaemia and dyslipidaemia are being less ‘visible’ in schizophrenic patients than the others [60]. 2.2.1 Sedentary Lifestyle Our choices of lifestyle are influenced by a variety of factors such as genes, environment and socio-demographic status [61]. In case of schizophrenia, 15 the illness itself also plays a part [62]. People with schizophrenia on average have a lifestyle which increases their risk for the development of CHD: sedentary lifestyle, lack of regular physical activity, poor diet, substance use and high rates of smoking. Part of these lifestyle factors is influenced by aspects of the illness such as negative symptoms and vulnerability to stress [63-65]. Lifestyle interventions with diet, increased physical activity and smoking cessation, are the first-line treatments to decrease the risk for CHD in people with schizophrenia [34]. A study carried out to compare the lifestyle of people with schizophrenia with that of low social class cohorts found that people with schizophrenia made significantly poorer dietary choices, took less exercise and smoked more heavily than the comparator groups in the general population [55]. A study found that people with schizophrenia tended to do limited exercises than general population and the specific mechanism by which physical activity reduces mortality from cardiovascular disease is unknown but exercise has been shown to improve lipid profiles, glucose tolerance, obesity and hypertension [55]. 2.2.2 Weight gain and obesity Individuals with schizophrenia are more likely than members of the general population to be overweight or obese. Obesity can have serious effects on health and life expectancy through a number of disease processes, including hypertension, coronary artery disease and type II DM [58]. McCredie (2003) also found that women with schizophrenia were significantly more likely to be overweight or obese than women in the 16 general population. Given that poor diet, smoking and excess weight are potentially modifiable factors associated with increased physical morbidity and mortality [55]. The patient’s waist circumference also is a useful risk indicator, a waist circumference of 35 inches or more for women and 40 inches or more for men is associated with increased health risks, including increased risks of high blood pressure, dyslipidemia, and metabolic syndrome [66]. For women, having a waist circumference of 35 inches or more was associated with these risk factors regardless of their body mass index (BMI) category (normal, overweight, or obese). For men, having a high-risk weight measurement incurred somewhat less health risk if their BMI was in the normal range [66]. 2.2.3 The role of antipsychotics Antipsychotic-related weight gain was first reported in association with chlorpromazine in the late 1950s, but it has remained overshadowed by other side effects such as extra pyramidal symptoms and tardivedyskinesia, among the conventional antipsychotics, weight-gain liability appears to be greatest with low-potency drugs, antipsychotic medications contribute substantially to increasing CHD risk factors through effects on weight gain, glucose deregulation and lipid abnormalities [67-70]. Meta-analyses, clinical trials and clinical experience suggest that the atypical antipsychotics can cause marked weight gain during treatment. Not all antipsychotics have the same propensity for causing weight gain but those associated with the greatest gain, clozapine and olanzapine can add 17 up to 4.5 kg after 10 weeks of treatment at standard dose. Also, patients appear to differ in their weight-gain response to specific drugs. Little is known about individual predictors, but most weight gain appears to occur during the first 2 years of treatment, and it accompanies an increase in appetite, especially for sweet and fatty foods, with no clear impact on basal metabolic rate [71]. The largest study comparing cardiovascular risk factors in chronic schizophrenia patients, drawn from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial, with age, gender and race matched controls from the U.S. National Health and Nutrition Examination Survey (NHANES) showed that patients had significantly higher ten-year coronary heart disease risk. This was due to higher rates of smoking, diabetes, and hypertension. Also, the mean (SD) duration of antipsychotic use in the CATIE study was 14.4 (10.7) years [72] and long- term use of antipsychotic medications may play an important role in the increased risk for cardiovascular diseases [44, 45]. Antipsychotic medication use is associated with significant weight gain, dyslipidemia, and insulin resistance [43]. 2.2.4 Smoking Smoking is one of the most obvious modifiable risk factors for heart disease. The prevalence of smoking in schizophrenia greatly exceeds that in the general population (75 – 92% vs. 30 – 40%), respectively [73]. Bobes et al. (2010) analyzed the smoking-associated risks for coronary heart disease in 1704 patients with schizophrenia over 10 years and 18 predicted that smoking cessation would result in an almost 90% reduction in the risk of a coronary heart disease over the next ten-years [73]. 2.2.5 Hypertension Hypertension is an important risk factor for heart disease, Hypertension is often silent, so it is important that all patients are screened [59]. The prevalence of hypertension in schizophrenia is likely to be large [74]. However, meta-analysis found weak evidence to support excess hypertension in patients with mental illness [75]. A study conducted by Daumit, et al. (2007) in patients with schizophrenia has reported high levels of untreated hypertension (50%) [76]. Lewington et al. (2000) reported a twofold increase in stroke death and a twofold increase in ischemic heart disease and vascular death for every 20mmHg increase in systolic blood pressure >115mmHg [77]. 2.2.6 Dyslipidemia Dyslipidemia was defined by the presence of one or more than one abnormal serum lipid concentration [78]. Dyslipidaemia is one of the most significant risks for cardiovascular disease [79]. Elevated cholesterol is associated with coronary heart disease, including ischemic heart disease and myocardial infarction [80]. A 10% increase in cholesterol level is associated with a 20%–30% increase in the risk of coronary heart disease; and lowering the cholesterol level by 10% decreases the risk by 20%– 30% [81]. Newcomer (2007) found that schizophrenic clients are at higher risk of dyslipidemia and at higher risk of dying from cardiovascular diseases 19 [82]..Dyslipidemia has been observed in patients with early-onset schizophrenia [83]. 2.2.7 Diabetes Mellitus (DM) Patients with schizophrenia may be at a higher risk for developing diabetes than the population at large [84]. The high prevalence of diabetes among people with schizophrenia could be related to the high prevalence of obesity, as 90% of individuals with type II diabetes are obese [85]. 2.3 Studies among healthy General Population regarding ten-year CHD risk. A study conducted among adults populations in the US showed that 81.7% had a ten-year risk for CHD <10% and 18.3% had a risk ≥10% and 34% of male patients had a risk ≥10% ten-year risk of CHD, while 5.2% of female patients had a risk ≥10% ten-year risk of CHD (P<0.001). The proportion of the participants with ten-year risk for CHD ≥10% has increased with advancing age and was higher among males than females [86]. A cross-section study that was conducted among Omani Arabs population and aimed to determine the optimal cut points for BMI and waist circumference associated with risk of cardiovascular disease using Framingham risk score showed that men had a higher prevalence of ten- year CHD risk ≥ 10% compared to women (25% vs. 10%) (P=0.001). Furthermore, the total cholesterol was not significantly different between both genders (P=0.787) [87]. 21 2.4 Local Studies in northern West-Bank A study conducted on 250 patients with schizophrenia recruited from 4 psychiatric primary healthcare centers in Northern Palestine found that metabolic syndrome (MS) illness was associated with smoking, abdominal obesity, high systolic and diastolic blood pressure, high triglycerides, low HDL-C and high fasting plasma glucose. Multiple logistic regression analysis showed that only systolic blood pressure, high triglycerides, high fasting plasma glucose and low HDL-C were significant predictors of MS in schizophrenic patients [88]. A study was conducted on 250 patients in order to investigate the prevalence of pre-DM and DM in patients with schizophrenia who used antipsychotic drugs and compare it with those published in the general population. The results showed that the prevalence of pre-DM was significantly higher than that reported in the Palestinian general population and prevalence of DM was not significantly different from that in the general population in Palestine [89]. An unpublished thesis showed that 43.4% of patients with schizophrenia had high total cholesterol level, 41.4% had low HDL-C, 48.2% had high triglyceride levels, and 66.5% had at least one abnormal lipid level[90]. Next chapter, the methodology implemented in this thesis to achieve the objectives will be explained. 21 Chapter Three Methodology 3.1 Study Design and Site of the Study This was a cross-sectional study conducted between July 4 th and September 10 th , 2012 at governmental primary healthcare psychiatric centers in northern West-Bank Governorates (Nablus, Jenin , Tulkaram , Qalqilai). 3.2 Inclusion Criteria Patients attending the governmental primary healthcare psychiatric centers in north West-Bank during the study period and who met the following inclusion criteria were invited to participate: 1- Their ages were ≥ 20 years old. 2- They were diagnosed with schizophrenia as documented by their medical file. 3- They have been diagnosed with schizophrenia for at least 3 years. (Choose three years for inclusion criteria it was randomly to ensure for patients take long duration of antipsychotic medication. Antipsychotic medication used was associated with significant weight gain, dyslipidemia and diabetes mellitus. So, long-duration of antipsychotic medication may increase risk for CHD). 3.3 Exclusion Criteria Schizophrenia patients suffering from CHD or DM were excluded from the study (D.M is a major risk for CHD). Diabetes mellitus and CHD were identified based on patient’s medical file and/ or the current medications. 22 3.4 Sampling Size and Sampling methods The estimated sample size was calculated by using an automated software program was it for random sample [91]. A sample size of approximately 120 patients attending the governmental primary psychiatric healthcare centers in northern West- Bank was needed. Data was collected over a period of 2 months. During the study period, a total of 153 patients were asked to participate (79.1 %.); 32 refused to give a response. A total of 121 patients were available and agreed to do the interview. Eight patients were excluded because of having DM or CHD. A net total of 113 who gave consent for blood withdrawal were included in the study. An error was made in 1 blood sample and therefore analysis was made on 112 patients. The sample recruitment chart is shown in Figure 1. A convenience, non probability sampling method was used. In order to collect the sample, the investigator spent two weeks in each center to recruit patients for the study. The visits were made daily and data from patients who met the inclusion criteria were collected. 23 Figure (3.1) :Sample collection process for schizophrenic patients 3.5 Data Collection Data was collected by researcher itself, through direct and indirect methods. The indirect Methods were included a structured interview questionnaires, the data collection form has been developed for this study. The form included the following variables: age, gender, smoking status, 153 subjects were asked to participate during the study period of July-September 2012 32 refused to participate 121 subjects agreed to participate 8 subjects did not meet the inclusion criteria (diabetics) and were excluded 113 subjects met the inclusion criteria, interviewed and blood samples were withdrawn from those subjects Results of one sample could not be performed because sample of blood was inadequate and therefore, analysis was made on 112 subjects 24 duration of psychiatric illness and other co-morbid chronic diseases. Direct methods were included: blood pressure measurement, body weight, height, waist circumference, HDL and TCH. Age (years) was analyzed as continuous variable: the mean (±SD) age was 43±10.85 years and as categorical variable: coded into 4 categories: ≤ 30, 31–40, 41–50 and >50 for graphic purposes. Duration of the psychiatric illness (was defined as the duration from onset of first psychotic symptom to the date of recruitment). Participants were asked whether they were currently using antihypertensive drug or have other chronic disease. 3.6.1 Measurement of HDL-C and TCH Blood sample were collected from all subjects after 12 hrs overnight fasting blood was collected from an antecubital vein puncture while the subjects was in a sitting position. All these tests were measured using HUMAN kit, Germany central laboratory at An-Najah National University. 3.6.2 Blood Pressure Blood pressure was measured to the nearest 5 mmHg in the right arm when the subjects were in the sitting position after 10 minutes of rest, using a standard mercury sphygmomanometer. The mean of two readings was taken as the individual’s blood pressure. 3.7 Coronary Heart Disease Risk Estimation To determine the ten-year risk of CHD, the published equation derived from the Framingham Heart Study has been used[92]. 25 Risk scores were divided into 4 categories: ideal (<5%), low (5-9%), intermediate (10-20%) and high (>20%) (Figure 2) Figure (3.2) : Framingham risk score for estimating ten-year risk of CHD in schizophrenia patients 3.8 Data Analysis Descriptive statistics for all study variables were computed. These descriptive statistics included frequencies and percentages for all categorical variables. In addition to means, median and standard deviations variables were calculated. The median inter quartile range (Q1-Q3) was used whenever the data were not normally distributed. In addition, the Chi- square or Fisher’s exact tests were used, whenever appropriate, to test for significance between categorical variables. The Student’s t-test was used to compare means of continuous variables. If the assumptions of equality of 26 variance and normality were not met, the Mann-Whitney U test was used as appropriate. Significant difference between males and females regarding the frequency of CHD risk categories was tested using non-parametric Binomial test. All statistical analyses were conducted using Statistical Package for Social Sciences (SPSS; version 20.0; IBM) for Windows. Univariate analysis was used to find significant association between risk factors and high ten-year CHD risk. Variables that showed significance in univariate analysis were used in multivariate analysis to find significant predictors of high ten-year CHD risk. The conventional 5 percent significance level was used throughout the study. Variables: Continuous variables: The following variables were coded in SPSS as continuous variables: TCH, HDL-C, age, systolic BP and diastolic BP Categorical variables: the following variables were coded in SPSS as categorical variables: age, smoking and gender. 3.9 Ethical Consideration Approval to perform the study was obtained from the Palestinian MOH, the college of Graduate Studies at An-Najah National University and Institutional Review Board (IRB). Also, consent form from the patients or their families was obtained prior to interview and taking the blood (Appendix). Next chapter presents the findings of the study regarding ten-year risk of CHD. 27 Chapter Four Result During the study period, 112 patients were included in the study; 76 (67%) were male and 36 (33%) were female. The mean (± SD) age of the participants was 43 ± 10.85 years. The majority were males (76; 67%). The participants had median (Q1 – Q3) duration of psychiatric illness, systolic blood pressure and diastolic blood pressure of 12 (7.25 – 20) years, 120 (115 – 130) mmHg and 80 (70 – 90) mmHg respectively. Lipid profile of the participants showed that the participants had a mean (± SD) HDL-C value of 44.3 ± 8.7 mg/ dL and TCH of 189.4 ± 39.6 mg/ dL. The majority (65; 58%) of the participants were smokers. Females had significantly lower prevalence of smoking (P<0.05) and significantly higher HDL levels (P<0.05) compared to males. However, there was no significant difference between males and females in age, duration of illness, systolic blood pressure, diastolic blood pressure, and TCH levels. Demographic and clinical data of the participants is shown in Table 1. Table 4.1: Demographic and clinical characteristics of the participants Variable Statistic (mean ± SD) or median (Q1 – Q3) (Total; N=112 ) Male 76 (67%) Female 36 (32%) P Age (years) 43 ± 10.85 42.83 ± 10.33 43.64 ± 12 0.72 a Smoker - No - Yes 47 (42%) 65 (58%) 16 (21.1%) 60 (78.9%) 31 (86.1%) 5 (13.9%) <0.01 b Systolic blood pressure (mm/Hg) 120 (115 – 130) 120 (115 – 130) 120 (115 – 135) 0.75 c Diastolic blood pressure (mmHg) 80 (70 – 90) 85 (70 – 90) 80 (70 – 90) 0.7 c High density 44.3 ±8.7 42.25 ± 7 48.66 ± 10.35 <0.01 28 lipoprotein (mg/dl) a Total cholesterol (mg/dl) 189.4 ± 39.6 185.75 ± 39.05 197 ± 40.32 0.17 a Duration of illness (years) 12 (7.25 – 20) 13 (9.25 – 20) 10 (4 – 17.75) 0.085 c Abbreviations: Q1-Q3: inter quartile range, SD: standard deviation. a Significance of differences estimated with Student’s t-test b Significance of differences estimated with Chi-square test c Significance of differences estimated with Mann-Whitney U test The CHD risk scores were unequally distributed with positive skewness. Based on the Framingham risk score, the mean (± SD) CHD risk score was 5.6 ± 5.8 (median: 3; Q1 – Q3: 1 – 9). The mean (± SD) ten-year CHD risk for females was 1.5 ± 1.58 and the median (Q1 – Q3) was 0.75 (0.5 – 2) while that for males was 7.5 ± 6 with a median (Q1-Q3) of 6 (2-13). Framingham ten-year CHD risk calculator categorizes patients into 4 categories based on their total risk score. In our study, there were 63 (56.3%) participants who had a total risk score of < 5% (Ideal); 24 (21.4 %) patients with a total risk score of 5 – 9% (Low risk); 22 (19.6 %) patients with a total risk score of 10 - 20% (Intermediate risk) and there were 3 (2. 7 %) patients with a total risk score > 20% (High risk). Based on this, there were 87 (77.7%) participants with low ten-year risk for CHD and there were 25 (22.3%) participants with intermediate/ high ten-year risk of CHD (Table 2). The distribution of Framingham ten-year risk score categories stratified by gender, age categories, smoking, and illness duration is shown in Figures 3–6. 29 Analysis of gender distribution among the four CHD risk categories showed that there was no significant difference in gender distribution in low risk category. However, there was a significant association between males and intermediate and high CHD risk categories (Table 2). Table4.2: Frequency of Framingham risk categories stratified by gender *Statistical difference was tested using non-parametric Binomial test. Figure (4.1): Frequency of schizophrenic patients in each CHD risk category Category Definition Frequency (%) Male Female P* Ideal (< 5%) 63 (56.3%) 30 (39.5%) 33 (91.7%) 0.154 Low risk 5 – 9% 24 (21.4%) 21 (27.6%) 3 (8.3%) 0.043 Intermediate risk 10 – 20% 22 (19.6%) 22 (28.95%) 0 (0%) < 0.01 High risk >20% 3 (2.7%) 3 (3.95%) 0 (0%) < 0.01 Total 112 (100%) 76 (100%) 36 (100%) 31 Figure (4.2) : Frequency of schizophrenic male and female patients in each CHD risk category 31 Age Categories: 1 ≤ 30; 2: 31 – 40; 3: 41 – 50; 4: >50 years Figure (4.3): Frequency of schizophrenic patients in each CHD risk category stratified by age group 32 Figure (4.4): Frequency of schizophrenic patients in each CHD risk category stratified by duration of psychiatric illness Univariate analysis of potential variables that were associated with intermediate/high CHD risk showed that there were significant differences between the low (<10%) and intermediate/high (≥10%) categories with respect to age distribution (P<0.05), gender (P<0.5), smoking (P<0.05), total cholesterol (P<0.05), diastolic BP (P<0.05) and duration of psychiatric illness (P =0.03). However, there was no significant difference between the 2 categories in terms of systolic blood pressure, waist circumference and HDL-C levels (Table 3). All patients in the CHD risk category ≥ 10% were 33 males and smokers. None of the patients in the CHD risk category were females. Furthermore, there were no smokers in the low <10% CHD risk category. By including the studied risk factors in the logistic regression analysis (Age, diastolic BP, TCH and duration of illness) The results presented in table 4 showed that age was the strongest predictor of CHD risk ≥10% with about [OR= 1.524, 95%CI (1.213-1.914)] followed by diastolic BP about [OR=1.207, 95%CI (1.045-1.393)] and the weak factor for CHD risk ≥10% was TCH which represented about [OR=1.083, 95%CI (1.033- 1.136)]. Table 4.3: Univariate analysis of factors associated with low (<10%) and intermediate/ high (≥10%) CHD risk categories Variable Low Risk Category Framingham score < 10% n = 87 Intermediate / High Risk Category Framingham score ≥ 10% n = 25 P mean ±SD or median (Q1 – Q3) mean ±SD or median (Q1 – Q3) Age (Years)* 40.94 ±11 50.56 ±6.32 < 0.01 a Gender* Male (%) 51 (58.6%) 25 (100%) < 0.01 b Smoking -Yes 0 (0%) 25 (100%) <0.01 b Systolic blood pressure (mm/Hg) 120 (115 - 130) 125 (117 - 130) 0.219 c Diastolic blood pressure (mmHg) 80 (70 - 90) 90 (80 - 95) <0.01 c High density lipoprotein (mg/dl) 44.6 (38.6 - 50.4) 41.7 (37.4 - 47.8) 0.98 c Total cholesterol (mg/dl) 180.5 (153.5 - 211) 215 (183.5 - 243.5) <0.01 c 34 a Significance of differences estimated with Student’s t-test b Significance of differences estimated with Chi-square test c Significance of differences estimated with Mann-Whitney U test Table 4.4: multivariate analysis of factors associated with CHD risk ≥ 10% In the coming chapter, discussion of our results and internationally published studies regarding to CHD risk among schizophrenic patients will be presented. Waist Circumference (cm) 95 (85 - 102.3) 97 (88.5 - 104) 0.484 c Duration of illness (years) 11 (6 - 20) 20 (10.5 - 24.5) 0.03 c B S.E. Wald P O.R 95% C.I.for O.R Lower Upper Age .421 .116 13.121 .000 1.524 1.213 1.914 Diastolic BP .188 .073 6.557 .010 1.207 1.045 1.393 Total Cholesterol .080 .024 10.829 .001 1.083 1.033 1.136 Duration of illness -.059 .061 .935 .334 .942 .836 1.063 35 Chapter five Discussion 5.1 Introduction This study aimed to estimate the ten-year risk of CHD in patients with schizophrenia attending governmental primary psychiatric healthcare centers in northern West-Bank, Palestine. Our results indicated that male gender was significantly associated with ≥10% ten-year CHD risk. Actually, all patients who had ten-year CHD risk ≥10% were males and none were females. Similarly, all patients in the high CHD risk category were smokers and none were in low risk category. Therefore CHD risk ≥ 10% was confined to male smokers. Among male gender, age and diastolic BP were significant predictors of CHD risk ≥ 10%. The findings that there was a significant association between CHD in schizophrenia and modifiable risk factors like diastolic BP may facilitate the development of appropriate preventive strategies. Interventions focused on preventing modifiable risk factor as opposed to treating this CHD condition and its complications once they are present, will not only reduce costs but will provide sufferers with the most effective tools for maintaining and improving their health and well-beings. 5.2 Comparison with literature Current literature does not provide a clear understanding of which risk factors has the best prediction of the development of CHD in patients with schizophrenia. A study in Spain of 1452 patients with schizophrenia concluded that 20.7% had a ten-year CHD risk of ≥10%; male had 36 significantly higher ten-year CHD risk than females (8.3% vs. 4.5%) [47]. In a study of 1125 patients with schizophrenia from US, with a mean age of 40.7 years, 33% had a ten-year CHD risk ≥10% ; 37% among men and 19% among women had a ten-year CHD risk ≥10% (P<0.05) [48]. Another study in US showed that the mean ten-year risk of CHD for male patients with schizophrenia was significantly higher than females (9.4% vs. 6.3%, respectively) [44]. A possible reason for higher CHD risk among males compared to females is the high prevalence of smoking among males. High prevalence of smoking among male patients with schizophrenia has been reported [47, 48]. Table 5 shows a comparison of results obtained in different studies carried out among patients with schizophrenia. The table shows that the result obtained in our study regarding frequency of patients in high CHD risk category is lower than that reported by other studies. One potential explanation for this difference in results obtained is the inclusion criteria. In previous studies reported, diabetic patients were included in the analysis which made the CHD risk higher than that reported in our study. Furthermore, our study included patients whose age was above 20 years older while the reported studies included patients whose age is usually above 30 years old which made the expected CHD risk higher than that reported in our study. 37 Table 5.1: Comparative table of the prevalence of ten-year risk of CHD in Different countries: patients with schizophrenia Country (Author & year) Patients Mean CHD Risk score (Male) Mean CHD risk score (female) Age (years) Tools U.S (Goff, Sullivan et al. 2005). Schizophrenia, out Patients included D.M 9.4% 6.3% 40.4 FHS age 18-65yrs Spain (Bobes, Arango et al. 2007). Schizophrenia, out Patients included D.M 8.3% 4.5% 40.7 FHS. Age 18- 74yrs. U.S (Daumit, Goff et al. 2008). Schizophrenia, out Patients included D.M 9.5% 5.7% 40.7 FHS age 18-65 yrs Scotland (McCreadie 2003). Schizophrenia, Out Patients, non fasting- blood sample 10.5% 7% 45 Compute r program derived from Framingh am assessme nt Canada (Cohn, Prud'homme et al. 2004). Schizophrenia, Out and in Patients included D.M 8.9% 2.6% M=42. 4 F=44.5 FHS age ≥20 yrs. Our study Schizophrenia, out Patients, excluded CHD and D.M 7.5% 1.5% 43 FHS, age ≥20 yrs. In addition, table 6 summarizes a comparison between our study ad previous studies regarding the gender differences and the ten year risk of CHD. 38 Table 5.2: Comparative table of the distribution ten-year risk of CHD in Different countries: patients with schizophrenia In comparison between our study and general population from U.S [86] and Omani Arabs [87], male participants in all studies had higher prevalence of ten year-risk of CHD than female participants. Furthermore, the proportion of participant's ≥10% ten-year risk of CHD increases with advance age in all studies. However we need to care for schizophrenia patients than general population regarding to CHD risk because these group of patients neglected and less likely to pay attention to symptoms of physical illness. 5.3 Factors associated with CHD risk ≥10% Regarding age, our results are in agreement with other published studies. Bobes et al showed that 1.8% of patients with ≥ 10% ten-year CHD risk were ≤34 years and 56.6% of patients with ≥10% risk of developing CHD were > 65 years [47]. Jin et al (2011) suggested that the ten-year risk of CHD could increase by at least 50% in middle aged and older patients with schizophrenia [46]. Study (Author & Years) Risk <10% All Sample Risk ≥10% All Sample Mean CHD Risk ≥10% All Sample Male Risk ≥10% Female Risk ≥10% (Daumit, Goff et al. 2008) 67% 33% NA 37% 19% (Bobes, Arango et al. 2007) 79.3% 20.7% 20.7% 26.5% 11.7% Our study 77.7% 22.3% 33% 32.9% 0% 39 Our results regarding to diastolic blood pressure was a significant predictor of ≥10% ten-year risk of CHD. Another study conducted by Jin et al (2011) showed that schizophrenia patients tending to have higher diastolic blood pressure [46]. Similar findings were obtained by a study conducted in Croatia (2012) which showed that male schizophrenia patients had significantly higher diastolic blood pressure compared to female patients [54]. Our study indicated that patients with ≥10% ten-year CHD risk had longer duration of psychiatric illness (P=0.03). It is possible that the long standing life style risk factors in patients with schizophrenia are increasing their risk of CHD. However, multivariate analysis suggested that the duration of psychiatric illness is not a significant predictor with ≥10% ten-year risk of CHD. Our results regarding to total cholesterol was not significant predictor with ≥10% ten-year risk of CHD. In contrast other published studies showed that total cholesterol was a significant risk factor for CHD, findings was obtained by McCreadie (2003), which showed that 46 (53%) of schizophrenia patients had raised cholesterol: HDL ratio [55]. In a Spanish cross-sectional study, the most prevalent cardio-metabolic risk factor was found to be hypercholesterolemia (66% of patients) [53]. Finally, regarding smoking, the findings of our study are similar to those obtained by Goff et al (2005) and Phutane et al (2011) in which schizophrenic patients had significantly high rates of smoking (68%,46%) [44, 50]. Our results showed that male schizophrenic patients had higher prevalence of smoking than females (78.9%, 13.9%). Similarly finding 41 were obtained by Daumit et al (2008) which showed that female schizophrenia patients had lower prevalence of smoking than males (50%,61%) [48]. 5.4 Limitations of the Study 1-This was a cross-sectional study, convenience sample collected from different primary health care psychiatric centers and it may not be representative of total population of patients with schizophrenia. 2-Due to the high cost analysis of blood sample for each participant, we were unable to include large sample size and compare patients within match control of general population. Final limitation is the absence of data on antipsychotic medications taken by the participants as these data may have been helpful in further interpreting the baseline health data and risk factors for CHD in the participants. 5.5 Conclusions 1- This study confirmed the presence of traditional risk factor for CHD among schizophrenic patients, supporting the need for enhanced monitoring for CHD in this category of neglected patients. 2- Male gender and smoking are associated with high ten-year CHD risk. 3- Among males gender, advancing age and high DBP are significant predictors of CHD risk ≥ 10%. 5.6 Recommendation 1- 1-Efforts to decrease CHD risks among patients with schizophrenia should be implemented, particularly among those with high Framingham risk score. 41 2- 2-Our study emphasize the need of multi-intervention for risk factors of CHD in schizophrenia patients, as risk factor of high diastolic BP can be lessened by strategies and intensified intervention. 3- 3-Mental health nurse should be aware of the blood pressure of each patient with schizophrenia they treat. 4- 4-Psychiatrists should follow guidelines for screening and treating patients who are at a high risk for cardiovascular disease. 5- The importance of routine blood pressure and diet style monitoring for patients with schizophrenia should be noticed, especially among elderly patients. 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Anjah National University., 2012.  Raosoft, http://www.raosoft.com/samplesize.html.  Framingham Heart Study, http://hp2010.nhlbihin.net/atpiii/calculator.asp http://www.raosoft.com/samplesize.html http://hp2010.nhlbihin.net/atpiii/calculator.asp) 54 Appendix 55 An-Najah National University Faculty of Graduate Studies Master of Community Mental Health Nursing Estimation Ten-Year Risk of Coronary Heart Disease in Patients with Schizophrenia Data Collection Form A. Patient demographic factors: A.1 Serial number: ___________ A.2 Registration number: ____________ A.3 Age: ________ years A.4 Date of birth: _________________ A.5 Gender: □ Male □ Female A.6 Weight: _______ K g A.7 Height: _________ cm A.8 waist circumference: _____________cm B. Schizophrenia disease related factors C. . Duration of illness: ____________________ years D. History and disease co-morbidities C1: History of smoking □ Yes □ No C2: Co-morbidities: C2.1□ Nil C2.2□ Hypertension 56 C2.3□Ischemic heart disease C2.4□ Diabetes mellitus C2.5□ Atrial fibrillation C2.6□ Heart failure C2.7□ Hypercholesterolemia C2.8□Renal dysfunction C2.9□ Asthma / COPD C2.10□ Hypercholesterolemia C2.11□ Renal dysfunction C2.12□others: …………… 57 D. Laboratory and clinical investigation: E. Current Medications Drug name Drug dose Frequency Route 1 2 3 4 5 F. Framingham risk score calculator Test First reading Second reading D.1 Blood Pressure Systolic Diastolic D.2 Lipid profile Total cholesterol HDL 58 Appendix 59 النجاح الوطنيةجامعة كلية الذراسات العليا نموذج موافقة عمى المشاركة في بحث الطالب في كمية الدراسات العميا / ماجستير صحة نفسية مجتمعية، جامعة مفيد القرم صقرالباحث: النجاح الوطنية المشرف: البروفيسور وليد صوليح أستاذ في قسم الصيدلة/ كمية الطب وعموم الصحة/ جامعة في قسم الصيدلة/ كمية الطب وعموم الصحة/ مساعد نجاح الوطنية و الدكتورة سماح الجابي استاذ ال جامعة النجاح الوطنية. الجية المشرفة: جامعة النجاح الوطنية / كمية الدراسات العميا / قسم التمريض / الصحة النفسية المجتمعية. عنوان البحث: القمبية التاجية لدى مرضى االنفصام الذهاني االصابة باالمراضتقدير احتمالية القادمة العشر سنواتخالل Estimation Ten-Year Risk of Coronary Heart Disease in Patients with Schizophrenia 61 يحتوي هذا الممف عمى : معمومات وتفاصيل البحث. 1 شيادة الموافقة عمى المشاركة في البحث. 2 ك نسخة كاممة عن ورقة الموافقة عمى المشاركة في البحث()سيقدم لكل مشار معمومات وتفاصيل البحث أخي/ أختي المشارك/ة: نا الباحث صقر القرم طالب ماجستير صحة نفسية مجتمعية في جامعة النجاح الوطنية أ ة االصابة باالمراض القمبيتقدير احتمالية لى المشاركة في بحثي المتعمق بإدعوك أن أيسرني لك كامل الحرية واالرادة في العشر سنوات القادمة. االنفصام الذىاني خالل مرضى التاجية لدى المشاركة في ىذا البحث ولك الحق في اخذ الوقت الكافي لمتفكير في المشاركة من عدميا وسؤال الباحث عما تراه مناسبا والتحدث الي شخص او جية عن ىذا البحث. ن اي جزء يتعمق في البحث االن او فيما بعد واذا كانت ىناك كما يمكنك االستفسار ع كممات او اجزاء غير مفيومة بامكانك سؤال الباحث وستجد/ين الوقت واالجابة الكافيتين. يضمن البحث سرية المعمومات المتعمقة بالمشارك/ة. التاجية لدى االصابة باالمراض القمبية احتماليةييدف ىذا البحث لتقدير :الهدف من البحث . و كذلك ييدف الى التعرف عمى العوامل مرضى االنفصام الذىاني خالل العشر سنوات القادمة . االمراض القمبية التاجية لدى مرضى االنفصام الذىاني الديموغرافية و السريرية المرتبطة بحدوث ي فمسطين.ان مشاركتك ودعمك ليذا البحث سيساىمان في تطوير وتعزيز الواقع الصحي فكما تقدير احتمالية االصابة بعد الموافقة عمى المشاركة في البحث : طبيعة المشاركة في البحث ، سنطمب من باالمراض القمبية التاجية لدى مرضى االنفصام الذىاني خالل العشر سنوات القادمة ك قياس المشارك اخذ عينة دم منو لقياس مستوى الكولسترول الكمي و الكولسترول الجيد و كذل الضغط لديو، تمييا مقابمة شفوية الخذ معمومات تتعمق بالعوامل االجتماعية والديموغرافية التي تمزم االصابة باالمراض القمبية التاجية لدى مرضى االنفصام الذىاني خالل العشر لتقدير احتمالية .سنوات القادمة 61 :اختيار المشاركين –والمراجعين في العيادة النفسية ام الذىاني االنفصسيتم اختيار المشاركين من مرضى .، طولكرم، جنين، قمقيميةنابمسة في كل من المحافظات التالية: مديرية الصح المشاركة طوعية واختيارية وبامكان المشارك االنسحاب من البحث في اي وقت ودون الحاجة البداء االسباب وبدون اي تبعات. :البحثالمدة المتوقعة النهاء اجراءات عشرة دقائق لكل مشارك. :شهادة الموافقة عمى المشاركة في البحث قمت بقراءة المعمومات الواردة في ورقة معمومات البحث واتيحت لي اقرار من المشارك في البحث: الفرصة ان اسال اي سؤال وقد تمت االجابة عمى كافة اسئمتي بشكل كاف، وبناءا عمى ذلك اوقع كة في ىذا البحث.طوعيا عمى المشار اسم المشارك........................................ توقيع المشارك..................................... ...............\..............\التاريخ............... 62 اقرار من الباحث: وواضحة، وبذلت قمت بقراءة المعمومات الواردة في ورقة معمومات البحث بطريقة صحيحة جيدي ان يعي المشارك ان البحث سيتضمن: الخذ عينة دم في محاظات الشمال مديرية الصحة –مقابمة المشارك في البحث العيادة النفسية . 1 .لديو الدم منو و كذلك قياس ضغط التحدث الى المريض شفويا الخذ المعمومات المتعمقة بالعوامل االجتماعية والديموغرافية.. 2 اؤكد عمى ان المشارك اخذ الفرصة الكافية لالجابة عمى اسفساراتو بشكل واضح وصحيح وبذلت ما بوسعي لتحقيق ذلك. اؤكد ان المشارك لم يجبر عمى التوقيع عمى الورقة وان مشاركتو كانت بمحض ارادتو وكامل اختياره. : الباحث صقرمفيد القرم .............توقيع الباحث....................... ................\...............\التاريخ........... جامعة النجاح الوطنية كمية الدراسات العميا مزظي لذىجقذيز ادحمالية اإلصابة باألمزاض القلبية الحاجية االنفصام الذهاني خالل العشز سنوات القادمة إعذاد صقز مفيذ القزم إشزاف ليذ صويلخأ.د. و د. سماح الجابي نفسية الصذة القذمث هذه األطزودة اسحكماال لمحطلبات درجة الماجسحيز لحخصص جمزيط فلسطين –مجحمعية بكلية الذراسات العليا في جامعة النجاح الوطنية في نابلسال 2013 ب ي خالل العشر تقدير احتمالية اإلصابة باألمراض القمبية التاجية لدى مرضى االنفصام الذهان سنوات القادمة إعداد صقر مفيد القرم إشراف أ.د. وليد صويمح د.سماح الجابي الممخص الخمفية: أشارت الدراسات إلى أن المرضى الذين يعانون من مرضى االنفصام الذىاني، لدييم أقصر فترة .حياة من عامة السكان : الهدف ة التاجية عند مرضى االنفصام الذىاني خالل العشر لتقييم احتمالية االصابة باالمراض القمبي سنوات القادمة. المنهجية: المستعرضة في أربعة مراكز لمرعاية الصحية األولية الحكومية المقطعية نفذت ىذه الدراسة لألمراض النفسية في شمال الضفة الغربية )نابمس، جنين، طولكرم، قمقيمية(. تم استخدام عدم مريضًا شخصوا بمرض انفصام الذىان. وتم 112خد العينات، وقد تم اختيار االحتمالية في أ حساب خطر اإلصابة باألمراض القمبية التاجية خالل العشر سنوات القادمة باستخدام صيغة م.التسجيل فرامنغيا ( (Framingham heart study الذي يتضمن المتغيرات التالية: العمر،الجنس وتاريخ أدوية ارتفاع HDL)،الكولسترول الكمي عالي الكثافة)(TCH)كمي،التدخين،الكولسترول ال %(، 9-5٪(، منخفضة)5ضغط الدم.صنفت درجة المخاطر إلى أربع مجموعات: المثالي)> %(. تم التحميل الوصفي واإلحصائي باستخدام الرزم 20%(، عالية) <20-10متوسطة) . SPSS-20)اإلحصائية لمعموم االجتماعية ) ت ج: النتائ ٪(. ولم يكن 67;76) ذكوراً الغالبية وكانت. عاما 10.85 ± 43 المشاركين عمركان متوسط (، طول فترة المرض النفسي P=0.72ىناك فرق كبير بين الذكور واإلناث في العمر ) (P=0.085( ضغط الدم االنقباضي ،)P=0.75(ضغط الدم االنبساطي ،)(P=0.7 الكولسترول ، .P=0.17)الكمي ) االنحراف المعياري لمخاطر اإلصابة باألمراض القمبية التاجية خالل العشر سنوات ± كان متوسط االنحراف المعياري ± (، متوسط Q1 - Q3: 9 - 1؛ 3( )الوسيط: 5.8 ± 5.6 (القادمة Q1 - Q3: 2)الوسيط:(( 1.5± 81.5) اإلناثلمخاطر اإلصابة باألمراض القمبية التاجية عند (.استنادًا إلى صيغة Q1-Q3: 13-2؛ 6( )الوسيط: 6±7.5بينما عند الذكور) 0.50 - مريضًا 87التسجيل فرامنغيام في تصنيف مخاطر اإلصابة باألمراض القمبية التاجية. وكان ىناك مرضى في فئة كبيرة. أظير تحميل أحادي 3مريضًا في فئة متوسطة، و 22في فئة منخفضة، ٪( ومتوسطة / عالية 10ذات داللة إحصائية بين فئة منخفضة )>المتغير أن ىناك فروقًا (، التدخين P<0.05(، نوع الجنس)P<0.05) العمري التوزيع فئات يتعمق فيما( ٪10≤المخاطر ) (P<0.05( الكولسترول الكمي ،)P<0.05( ضغط الدم االنبساطي ،)P<0.05 وطول فترة ) ٪( 10اك فرق كبير بين فئة منخفضة )>(. ومع ذلك، لم يكن ىنP=0.03المرض النفسي ) الكمي والكولسترول الخصر محيط االنقباضي، الدم ضغط حيث من( ٪10 ≤والمتوسطة / عالية ) ,OR= 1.524] [رالعم أن الذكور مرضى عمى المتغيرات متعدد تحميل أظير. الكثافة عالي 95%CI (1.213-1.914) و ضغط الدم االنقباضي[OR=1.207, 95%CI (1.045- كانت العوامل اليامة فقط في التنبؤ بمخاطر االصابة باالمراض القمبية التاجية خالل [(1.393 .العشر سنوات القادمة لدى مرضى االنفصام الذىاني االستنتاجات: باألمراض لإلصابة%( 10≤ عالية ) \كان )ُخْمس( مرضى انفصام الذىان لدييم فئة متوسطة لدى التاجية القمبية باألمراض اإلصابة مخاطر لخفض الجيود توجيو غيوينب التاجية، القمبية .نحو ضغط الدم االنقباضي كعامل خطر قابل لمتعديل أساسا الذىان بانفصام المصابين المرضى