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PREVALENCE PATTERN AND OUTCOME OF HYPERTENSIVE EMERGENCIES AMONG ADULT MEDICAL PATIENTS ADMITTED TO BUGANDO MEDICAL CENTRE BY GRAHAME MTUI (MD) A DISSERTATION TO BE SUBMITTED IN PARTIAL FULFILMENT FOR REQUIREMENT OF THE AWARD OF MASTERS OF MEDICINE (INTERNAL MEDICINE) OF CATHOLIC UNIVERSITY OF HEALTH AND ALLIED SCIENCES–BUGANDO, MWANZA TANZANIA 2014 CERTIFICATION The undersigned certify that they have ready and hereby recommend acceptance for examination by Catholic University of Health and Allied Sciences (CUHAS) a dissertation entitled: Prevalence pattern and outcome of hypertensive emergencies among adult medical patients admitted to Bugando Medical Centre. __________________________________ __________________ Prof. Johannes B Kataraihya MD, MMED (Internal Medicine) Date Associate Professor Catholic University of Health and Allied sciences __________________________________ ___________________ Dr. Robert N Peck MD, MMED (Internal Medicine) Senior Lecturer Catholic University of Health and Allied Sciences i Date DECLARATION & COPYRIGHT I, Grahame Geofrey Mtui, hereby declare that this dissertation is my own original work and that it has not been presented and will not be presented to any other university for a similar or any other degree award. Signature______________________ Date__________________________ “This dissertation is a copyright material protected under the Berne Convention, the copyright Act of 1999 and other international and national enactments, on that behalf, on intellectual property. It may not be reproduced by any means, in full or in part, except for short extracts in fair dealing, for research or private study, critical scholarly review or discourse with acknowledgement, without the written permission of the Director of Graduate studies, on behalf of both the author and the “Catholic University of Health and Allied Studies (CUHAS)” ii TABLE OF CONTENTS CERTIFICATION ..................................................................................................................i DECLARATION & COPYRIGHT ....................................................................................... ii TABLE OF CONTENTS..................................................................................................... iii LIST OF FIGURES .............................................................................................................. vi LIST OF TABLES ..............................................................................................................vii ACKNOWLEDGEMENTS ............................................................................................... viii OPERATIONAL DEFINITIONS ......................................................................................... ix ABBREVIATIONS .............................................................................................................. xi ABSTRACT ...................................................................................................................... xiii CHAPTER 1: INTRODUCTION .......................................................................................... 1 1.1 BACKGROUND ......................................................................................................... 1 1.2 STATEMENT OF THE PROBLEM AND RATIONALE ............................................ 4 1.3 RESEARCH QUESTION ............................................................................................ 4 1.4 HYPOTHESIS ............................................................................................................. 4 1.5 STUDY OBJECTIVES ................................................................................................ 5 1.5.1 Broad Objective: .................................................................................................... 5 1.5.2 Specific objectives: ................................................................................................ 5 CHAPTER 2: LITERATURE REVIEW ................................................................................ 6 2.1 Prevalence of hypertension and hypertensive emergencies ........................................... 6 iii 2.2 Factors associated with hypertensive emergencies ........................................................ 9 2.3 Outcome of hypertensive emergencies........................................................................ 10 CHAPTER 3: METHODOLOGY........................................................................................ 13 3.1 STUDY AREA .......................................................................................................... 13 3.2 STUDY DESIGN ....................................................................................................... 13 3.3 STUDY POPULATION ............................................................................................. 13 3.3.1 Inclusion Criteria ................................................................................................. 13 3.3.2 Exclusion criteria: ................................................................................................ 13 3.4 SAMPLE SIZE .......................................................................................................... 14 3.5 DATA COLLECTION ............................................................................................... 14 3.6 DATA PROCESSING AND ANALYSIS: ................................................................. 16 3.7 ETHICAL CONSIDERATION .................................................................................. 17 CHAPTER 4: RESULTS ..................................................................................................... 18 4.1 Enrolment .................................................................................................................. 18 4.2 Baseline socio-demographic and clinical characteristics ............................................. 19 4.3 Prevalence of hypertensive emergencies ..................................................................... 19 4.4 Outcomes ................................................................................................................... 21 4.5 Factors associated with hypertensive emergencies ...................................................... 22 4.6 Predictors of in-hospital fatality rates ......................................................................... 26 4.7 Predictors of 3 months fatality rates ............................................................................ 29 CHAPTER 5: DISCUSSION ............................................................................................... 32 iv 5.1 Prevalence of hypertension and hypertensive emergencies ......................................... 32 5.2 Patterns of hypertensive emergencies ......................................................................... 34 5.3 Factors associated with hypertensive emergencies ...................................................... 35 5.4 Fatality ....................................................................................................................... 37 5.5 Predictors of in-hospital and 3-months fatality............................................................ 38 CHAPTER SIX ................................................................................................................... 40 6.1 CONCLUSION .......................................................................................................... 40 6.2 LIMITATIONS .......................................................................................................... 41 6.3 RECOMENDATIONS ............................................................................................... 42 REFERENCES .................................................................................................................... 43 APPENDICES ..................................................................................................................... 46 APPENDIX 1: QUESTIONNAIRE ................................................................................. 46 APPENDIX 2: INFORMED CONSENT – ENGLISH VERSION .................................... 56 APPENDIX 3: INFORMED CONSENT – KISWAHILI VERSION ................................ 58 APPENDIX 4: ETHICAL CLEARANCE CERTIFICATE .............................................. 61 v LIST OF FIGURES Figure 1: Overview of study enrolment .................................................................... 18 vi LIST OF TABLES Table 1: Baseline characteristics of 647 patients admitted to BMC from October 2013 until December 2013. .............................................................................................. 20 Table 2: Types of hypertensive emergencies among 82 consecutive adults admitted to BMC with hypertensive emergency. ........................................................................ 21 Table 3: Overlap between hypertensive emergencies among 82 consecutive adults admitted to BMC with hypertensive emergency ....................................................... 21 Table 4: In hospital, 1 month and 3 months post-discharge outcomes among 82 adults admitted with hypertensive emergency .................................................................... 22 Table 5: Factors associated with hypertensive emergencies among 82 adults admitted with hypertensive emergencies to BMC by Univariate Analysis .............................. 24 Table 6: Factors associated with hypertensive emergencies among 82 adults admitted to BMC by Multivariable logistic regression. ........................................................... 26 Table 7: Baseline Predictors of in hospital mortality among 82 adults admitted to BMC with hypertensive emergencies and followed up until discharge by univariate logistic regression .................................................................................................... 27 Table 8: Baseline Predictors of in hospital mortality among 82 adults admitted to BMC with hypertensive emergencies and followed up until discharge by Multivariable logistic regression .............................................................................. 29 Table 9: Baseline Predictors of 3 month mortality among 82 adults admitted to BMC with hypertensive emergencies and followed up until 3 months after discharge by univariate logistic regression ................................................................................... 29 Table 10: Baseline Predictors of 3 month mortality among 82 adults admitted to BMC with hypertensive emergencies and followed up until 3 months after discharge by multivariable logistic regression.......................................................................... 31 vii ACKNOWLEDGEMENTS I wish to express my sincere gratitude to all who have made the completion of this dissertation possible. I would like to thank very much my supervisors Prof J. Kataraihya and Dr R. Peck for their tireless efforts in the supervision of my work from the beginning to the end. Their guidance, comments, critiques, support and patience have enabled the completion of this difficult job. I would like to express my sincere gratitude to all members of the department of Internal Medicine BMC/CUHAS, for their constructive comments, cooperation, support and assistance in all stages of this study. Also to my colleagues especially Dr Taibali Abderasul and Dr Missana Yango for being hand in hand from beginning of the study to the end especially during data collection, without forgetting Ms Rim Elchaki (Medical student from Weill Cornell) for her assistance during data entry. I greatly appreciate the help from Ms Eugenia for processing my samples as well as Dr Hassani (Opthalmologist) for his assistance during fundus examination. Special thanks to my family (my lovely wife Lilian Shao, my daughter Charisma) and my parents for being supportive throughout my research. viii OPERATIONAL DEFINITIONS Hypertension: Defined by the average of two systolic blood pressures (SBP) >140 and/or diastolic blood pressures (DBP) > 90 mmHg and/or current use of antihypertensive medications at the time of admission. Severe Hypertension: Defined as average systolic blood pressure (SBP) >180 and or diastolic blood pressure (DBP) ≥110 mmHg. Hypertensive Emergency: Is severe hypertension associated with end organ damage. Acute Kidney Injury defined as an absolute increase in serum creatinine concentration of ≥26.4umol/L from baseline or percentage increase in serum creatinine concentration of ≥ 50% or decreased urine output less than 0.5mls/kg/hr for more than six hours (1). In the absence of baseline creatinine RIFLES criteria will be used which suggest back-calculating an estimated baseline creatinine concentration using the four variable MDRD equation, assuming a baseline GFR of 75ml/min/1.73m2 (2). Renal dysfunction: Defined as eGFR<60ml/min/1.73m2 (calculated using Chronic Kidney Disease – Epidemiology equation). Acute myocardial infarction: Was defined according to the previous World Health Organization’s criteria for acute, evolving or recent myocardial infarction which requires combination of two of three characteristics: typical symptoms (i.e. chest discomfort), typical rise and gradual fall of troponin or more rapid rise and fall of CK-MB, and ECG changes indicative of ischemia (ST segment elevation or depression) involving the development of pathological Q-waves. ix Hypertensive Encephalopathy: Patients who had severe hypertension and alteration of mental status with no focal neurological deficits which resolve after lowering the blood pressure were considered as hypertensive encephalopathy. Acute Pulmonary Oedema: Defined as presence of dyspnoea and bilateral basal crackles confirmed by chest x-ray by radiologist. Hypertensive Retinopathy: Acute onset of blurred vision with retinal changes by fundoscopy classified into mild, moderate, and severe. Mild - Retinal arteriolar narrowing, wall thickening or opacification, and arteriovenous nicking (nipping). Moderate - Hemorrhages, either flame or dot-shaped, cotton-wool spots, hard exudates, and microaneurysms. Severe - Some or all of the above, as well as papilledema. Hypertensive Stroke: severe hypertension with sudden onset of neurological deficits and confirmed by CT scan of the brain whether ischemic, hemorrhagic or both. x ABBREVIATIONS BMC.................................................Bugando Medical Centre BMI..................................................Body Mass Index BP.....................................................Blood Pressure CKD.................................................Chronic kidney disease CT scan.............................................Computed Tomography Scan CUHAS............................................Catholic University of Health and Allied Sciences CVS..................................................Cardiovascular System CXR..................................................Chest X-ray DBP..................................................Diastolic Blood Pressure ECG..................................................Electrocardiography eGFR .................................................Estimated glomerular filtration rate GCS...................................................Glasgow Coma Scale GFR...................................................Glomerular filtration rate HF......................................................Heart Failure HIV...................................................Human Immunodeficiency Virus HTN...................................................Hypertension ICU...................................................Intensive Care Unit JNC...................................................Joint National Committee xi KDOQI............................................ Kidney Disease Outcome Quality Initiative LOC...................................................Loss of Consciousness LVH..................................................Left Ventricular Hypertrophy MAP..................................................Mean Arterial Blood Pressure MDRD..............................................Modification of Diet in Renal Disease SBP...................................................Systolic Blood Pressure SSA...................................................Sub Saharan Africa STEMI...............................................ST Elevation Myocardial infarction USA...................................................United States of America WHO..................................................World Health Organisation xii ABSTRACT Background: Hypertension is increasingly common in sub-Saharan Africa (SSA) and hypertensive emergencies are among the medical emergencies that cause morbidity and mortality among hypertensive patients. In Tanzania, the prevalence of hypertension is high with low levels of detection, treatment and control. Data regarding the types of hypertensive emergencies, associated factors and outcomes are lacking. Objectives: To determine prevalence, patterns, predictors and outcome of hypertensive emergencies among adult patients admitted to Bugando Medical Centre (BMC). Methodology: This was an analytical cross-sectional study with a prospective followup to determine the outcomes conducted on all adult patients admitted in medical wards as well as in adult intensive care unit (AICU) between October and December 2013. These patients were interviewed using a modified WHO STEPS questionnaire and screened for signs and symptoms of hypertensive emergencies. Patients with severe hypertension underwent fundoscopy, chest x-ray, 12 lead electrocardiogram, and serum creatinine. Brain CT scan was requested in those with stroke/altered mental status and an echocardiogram for those with heart failure or acute myocardial infarction. These patients were then followed up until discharge and three months thereafter. Results: A total of 647 patients were enrolled into the study with a median age of 45 years [32-61.5] and females were 48.2%. Eighty-two patients (12.7%) met the criteria for hypertensive emergency, the majority (85.4%) had more than one emergency and the commonest type was hypertensive retinopathy (62.2%). Hypertensive emergency xiii was significantly associated with female gender and age above 45 years. During hospitalisation 30% of patients with hypertensive emergencies died, and by three months more than 50% were dead. Hypertensive emergency with impaired renal function was found a statistically significant predictor of fatality both in hospital and at three months. Conclusion: Hypertensive emergency is one among the common causes of admission in medical wards of BMC associated with high fatality. Associated factors include female gender and age above 45 years. Hypertensive emergency with impaired renal function was significantly associated with both in hospital and three months case fatality rates. xiv CHAPTER 1: INTRODUCTION 1.1 BACKGROUND Hypertension is an established risk factor for cardiovascular, cerebrovascular, and renal disease (3). Acute elevations in blood pressure (BP) can result in acute endorgan damage with significant morbidity and mortality. Prompt recognition, evaluation, and appropriate treatment of these conditions are crucial to prevent permanent end organ damage. Worldwide, hypertension is still an important public challenge and its prevention, detection, treatment and control should receive high priority (4). However in subSaharan Africa (SSA) most countries are still battling with infectious diseases such as Human Immunodeficiency Virus (HIV), malaria, and tuberculosis, and most governments in the region have limited resources and health budgets. An increasing burden of hypertension in this region is therefore likely to be of grave consequence. Treatment and control rates are likely to be even lower than the dismal rates in Europe and North America. In Tanzania, the prevalence of hypertension is also high with low levels of detection, treatment and control (5,6). Recent analysis of data from Bugando Medical Centre (BMC) indicate that hypertension related diseases were the number one cause of death, admission and hospital days in patients over the age of 50 years, accounting for 28.9% of deaths, 28.5% of admissions and 27.8% of hospital stay in this age group and that hypertensive emergencies were the most common reason for admissions among persons with hypertension (7). 1 Hypertensive emergency is a situation in which uncontrolled hypertension is associated with acute end-organ damage such as hypertensive encephalopathy, retinopathy, dissecting aortic aneurysm, ischemic heart disease, acute pulmonary oedema, and acute kidney injury. Most commonly hypertensive emergencies occur in the setting of severe elevations in BP, such as diastolic BP (DBP) ≥ 130 mmHg. Most patients presenting with hypertensive emergency have chronic hypertension, although the disorder can present in previously normotensive individuals. Hypertensive emergencies most commonly occur due to poor treatment, noncompliance with or withdrawal from prescribed antihypertensive agents as well as acute accelerated hypertension in a patient with existing primary as well as secondary hypertension. However in Africa, adverse socio-economic status, obesity, cigarette smoking and poor compliance to antihypertensive agents have been associated with poor BP control hence complications (8). The presentation of hypertensive emergencies depends on the organs involved. For hypertensive encephalopathy, patients may present with headache, nausea and vomiting, visual disturbances, confusion, rarely focal or generalised weakness etc. If not adequately treated cerebral haemorrhage or stroke, coma and death occur, but with proper treatment it can be completely reversible. Hypertension has profound effects on various parts of the eyes. Classically, elevated blood pressure results in a series of retinal microvascular changes called hypertensive retinopathy, comprised of generalized and focal retinal arteriolar narrowing, arteriovenous nicking, (more closely related to aging than to BP), retinal haemorrhages, microaneurysms and, in severe cases, optic disc and macular oedema. Fundoscopy is a useful tool in recognising these changes. The cardiovascular system is affected as increased cardiac 2 workload leading to cardiac failure; this is accompanied by left ventricular hypertrophy, congestive heart failure (with impaired or preserved left ventricular ejection fraction), myocardial ischemia, and/or myocardial infarction. The renal system is impaired when high BP leads to arteriosclerosis, fibrinoid necrosis, and an overall impairment of renal protective auto regulatory mechanisms. This may manifest as worsening renal functions or decreased urine output. Morbidity and mortality depend on the extent of end organ damage on presentation and degree to which blood pressure is controlled subsequently. Therefore treatment of these emergencies requires immediate, accurate diagnosis and therapy to interrupt ongoing or prevent impending target-organ damage. Delay in initiating effective therapy or too rapid reduction of BP can produce severe complications involving these target organs. It is recommended to use short acting intravenous antihypertensive agents, with a goal to reduce mean arterial pressure (MAP) by 20-25% over four to six hours (9). 3 1.2 STATEMENT OF THE PROBLEM AND RATIONALE Hypertension is increasingly common in SSA. In a recent study at Bugando, hypertension-related conditions were 2nd only to HIV as a cause of admission, death and hospital days among adult medical inpatients. Hypertensive emergency was the most common hypertension-related condition but the types of hypertensive emergencies and the out-of-hospital outcomes could not be determined from this study (7). Data regarding the types of hypertensive emergencies seen in sub-Saharan Africa, the presenting features and the outcomes are lacking. The prevalence and clinical picture and outcome of hypertensive emergencies in East Africa have not been clearly described. Data on these patterns are important for improving clinicians’ awareness. Addressing the risk factors to the community will also improve awareness, overall morbidity and mortality among these patients will be improved. Therefore there is an essential need to conduct an epidemiological profile on the prevalence, predictors, and outcome of hypertensive emergencies in Tanzania. 1.3 RESEARCH QUESTION What are the prevalence, patterns, associated factors and outcome of hypertensive emergencies among adult patients admitted in BMC? 1.4 HYPOTHESIS We hypothesized that 10% adult admissions to BMC meet criteria for hypertensive emergency and most common hypertensive emergencies are pulmonary oedema and encephalopathy but hypertensive renal dysfunction is commonly undiagnosed. We also hypothesized that adherence to anti-hypertensives at 3 months after discharge is less or equal to 25%. 4 1.5 STUDY OBJECTIVES 1.5.1 Broad Objective: To determine prevalence, pattern, associated factors and outcome of hypertensive emergencies among adult patients admitted to BMC. 1.5.2 Specific objectives: 1. To determine the prevalence of hypertensive emergencies among adults admitted to the medical wards of BMC. 2. To determine the pattern of hypertensive emergencies (i.e. types of emergencies) among adults admitted to BMC. 3. To determine factors associated with hypertensive emergencies among adults admitted to BMC. 4. To determine the case fatality rates both in-hospital and after 3 months among hypertensive patients admitted to BMC 5. To determine the predictors for fatality among patients with hypertensive emergencies admitted to BMC. 5 CHAPTER 2: LITERATURE REVIEW 2.1 Prevalence of hypertension and hypertensive emergencies More than quarter of the world’s adult population had hypertension in 2000 and this proportion will increase to 29% (1.56 billion) by 2025 (4). According to the seventh joint national committee for hypertension, JNC VII (3), hypertension is the most common primary diagnosis in USA affecting almost 25% of the people. About 30% are unaware they have hypertension, and control rate is still below 50%. Hypertension is also considered a major public health problem in SSA with low levels of detection, treatment and control (5,10). A study done among civil servants in Accra Ghana involving seven ministries showed the prevalence of hypertension to be 30.2 % and BP control to below 140/90 mmHg was only 11.4%. This study also showed 47.5% of hypertensive patients had target organ damage associated with high SBP and DBP. Hypertensive retinopathy accounted for 70% of the target organ damage with 1% having grade 3 retinopathy, and none had grade 4 retinopathy. In addition, 13.4% of the participants had albuminuria (30-300 mg/d) (11). Hypertensive emergency is one of the most common complications of hypertension worldwide. A retrospective study done in Brazil to assess the prevalence of hypertensive crisis among adult patients attending emergency unit of the universityaffiliated hospital showed the proportion of hypertensive emergencies among hypertensive crisis as high as 39.6%. Most cases of hypertensive emergencies corresponded to cerebrovascular lesions (58%), with ischemic stroke being the 6 commonest, followed by hemorrhagic stroke, and subarachnoid haemorrhage. Thirtyeight percent corresponded to cardiovascular complications, including acute pulmonary edema, followed by acute myocardial infarction. Diabetes, present in more than 26% of patients with hypertensive emergency was found to be a statistically significant risk factor for the development of hypertensive emergencies (12). A study done in Iran showed that among hypertensive patients, 39.9% had hypertensive retinopathy (women 45.6%, men 33%). Among these patients 42.4%, 20%, 2.4% had retinopathy grade 1, 2, and 3 respectively. Prevalence rate of retinopathy in patients suffering from severe hypertension was 84.6%. Most common ophthalmic findings were arteriovenous narrowing 35.5%, arteriovenous nicking 17.12%, and cotton wool spots 9% (13). However in a large multicentre study done in Italy on hospital admissions for hypertensive crisis in the emergency departments showed a prevalence of hypertensive crisis of 1,546/333,407 (0.46%) and 391/1,546 (25.3% ) of them had hypertensive emergencies. Among patients with hypertensive emergencies, 121 (30.9%) had acute pulmonary edema, 86 (22.0%) had stroke, including 60 ischemic strokes and 26 hemorrhagic strokes, 70 (17.9%) had myocardial infarction, 31 (7.9%) had acute aortic dissection, 23 (5.9%) had acute renal failure and 19 (4.9%) had hypertensive encephalopathy. Two patients had both acute pulmonary edema and stroke (14). Another multicentric study on cardiovascular emergencies in SSA by Bertrand E et al involving more than 600 patients demonstrated that severe hypertension (32.2%) was 7 the commonest presentation followed by heart failure (27.5%) and stroke (20.3%). The most common emergency resulting in death included was stroke 31.9% (15). In another study done in Nigeria among hypertensive patients, only 14.2% had self reported hypertension and of these only 18.6% had been on medication in the past three months. Of these only 27.3% had controlled BP (16). In the same study 43% had evidence of target organ damage whereby hypertensive retinopathy accounted for 2.2% and the commonest retinopathy was grade 1 (40.2%), followed by grade 2 (37.6%) (16). Microalbuminuria was found in 12.3%, and gross proteinuria in 15.2%. In spite of the low levels of angina and myocardial infarction, ischemic changes and evidence of old infarcts were found in the ECGs of 12.3% of the population studied (16). In Sudan, a prevalence of hypertension of 7.5% has been reported. A study by Hussain et al in Sudan showed that among patients with hypertension, only 46.0% had both SBP and DBP controlled to below 140/90 mmHg. Analysis of end organ damage showed that 63.6% could be considered as being at Stage 1 of the WHO classification, i.e., they did not exhibit any type of target organ involvement. On the other hand, 11.1% had Stage 2 involvement in the form of albuminuria, elevated plasma creatinine (1.2 to 2 mg/dl), LVH and retinal vessel narrowing. Moreover, WHO Stage 3 target organ damage was detected in 25.3% with angina pectoris occurring at a frequency of 9.6% while myocardial infarction and renal failure were each seen in 1.5% of patients. Severe retinopathy (haemorrhages or exudates with or without papilloedema) occurred in only 3.5% of all patients and 14% of those with Stage 3 target organ damage (8). 8 An observational study done in Angola on characteristics of 123 patients aged 45 or under hospitalized for hypertensive emergencies showed a prevalence of hypertensive emergency of 4.3% and the most frequent forms of presentations were hypertensive encephalopathy and hemorrhagic stroke consisting of 9.8% and 82.1% respectively (17). Furthermore a study done on hypertensive emergencies at the University Hospital Centre in Brazzaville, Congo showed a prevalence of 4% among hypertensive patients. The disease underlying hypertensive emergency was stroke (50%), heart failure (26.3%), hypertensive encephalopathy (14.4%), malignant hypertension (11.8%) and renal failure in 13.1% (18). 2.2 Factors associated with hypertensive emergencies A study done in USA showed that less effective control of systolic blood pressure on an out-patient basis is an independent risk factor for hypertensive crisis leading to emergency department presentation. It was not known whether the poor control was due to non-adherence, inadequate response to specific antihypertensive medication or both (19). In another study done in USA in outpatients clinics, old age, multi drug regimens, lack of knowledge by the patients of their target SBP and report of hypertension medication side effects were the independent predictors of poor control of hypertension (20). Furthermore non-adherence with antihypertensive medications, which adversely affects the adequate control of hypertension, lack of a primary care physician, and the lack of insurance, have all been shown to be risk factors for hypertensive crisis (21). 9 Another study done in Switzerland on risk factors for promoting hypertensive crisis identified several potential risk factors including female gender, higher grades of obesity, the presence of hypertension or coronary heart disease, the presence of somatoform disorders, a high number of antihypertensive drugs and non adherence to medication (22). Very few studies have been done to determine associated factors or predictors of hypertensive emergency among adults in SSA. A study done in South Africa on determinants of target organ damage in black hypertensive patients attending primary health care services found renal impairment in 26%, LVH in 35% and ischemic ECG patterns in 49% of participants. Uncontrolled hypertension and older age were most often associated with target organ damage (23). Another study at the University Hospital Centre in Congo showed the predictors of hypertensive emergencies being obesity, history of hypertension and low socioeconomic status (18). 2.3 Outcome of hypertensive emergencies In general, the outcomes of hypertensive emergency are poor although most of this data comes from high or middle-income countries. In United Kingdom it was shown that renal function continues to deteriorate in some patients with malignant hypertension despite a good degree of control of their blood pressures having been achieved at follow up (24). In Thailand, a study on hypertensive emergencies among patients admitted to the medical wards of Siriraj Hospital in 2003 showed hypertensive emergencies are usually found in patients with a history of hypertension and diabetes mellitus or kidney failure and the average hospital stay was 9.8 days and in hospital mortality was 15% (25). A study done in Mexico City, on about 9000 patients with hypertensive crisis who are admitted to a coronary care unit showed 10 overall mortality rate for patients with hypertensive crisis in the unit to be 3.7%. Among patients with hypertensive emergencies, 4.6% died and mortality among hypertensive urgency cases was 0.8% (26). Furthermore a study on practice pattern, outcomes and end-organ dysfunction for patients with acute severe hypertension in USA revealed hospital mortality of 6.9% with aggregate 90-day mortality rate of 11%, and 59% had acute/worsening end-organ dysfunction during hospitalisation. The 90-day readmission rate was 37% of which one quarter was due to recurrent acute severe hypertension (27). Nevertheless, another observational cross sectional study done in the United States to describe the frequency of rehospitalisation for patients with acute severe hypertension found 90-day readmission rate was 35% (354/1,009) of patients discharged home alive, and 41% (144/354) were readmitted more than once. Also 18 (1.9%) patients were dead at 90 days (28). Very few studies have been done regarding the outcomes of hypertensive emergency in Africa. A five-year review of hypertensive related admissions into the medical wards of the University of Nigeria Teaching Hospital showed a case fatality of 42.6%. Forty five percent of deaths occurred during acute hypertensive crises such as cerebral vascular accidents, hypertensive encephalopathy, and acute renal failure (29). In our own data from BMC on hypertensive related admissions, hypertensive emergency contributed to17.5% of all hypertensive related deaths (7). Patients with hypertensive emergencies require immediate reduction of BP (within 46 hours) to prevent and/or arrest progressing end organ damage and to prevent death. This may be best achieved in intensive care unit (ICU) with the use of short acting, titrable intravenous ant-hypertensive agents such as esmolol (9). Limitations in ICU 11 beds and intravenous anti-hypertensive drug supplies may lead to delayed reduction in BP. In a study done in Congo the length of treatment of a hypertensive emergency averaged 14.7 hrs (range from 5 to 48hrs) (18). From Angolan study by Garcia GM et al on hypertensive emergency among patients of 45 years or under admitted to one of the hospitals, the in hospital mortality was 31/123 (25.2%), hemorrhagic stroke being the most common cause of death and old age was a significant predictor of mortality with p=0.03(17). Another study by Mayer et al on clinical practice, complications, and mortality in neurological patients with acute severe hypertension attending emergency department found that neurologic emergencies account for approximately 30% of hospitalized patients with severe acute hypertension, and the majority of those who die. It also showed mortality at 90 days was substantially higher in neurologic than in nonneurologic patients (24% vs. 6%, p<.0001). In a multivariable analysis, neurologic patients who died experienced lower minimal blood pressure values (median 103/45 vs. 118/55 mm Hg, p<.0001) and were less likely to experience recurrent hypertension requiring intravenous treatment (29% vs. 51%, p=.0001) than those who survived. Mortality was also associated with an increased frequency of neurologic deterioration (32% vs. 10%, p<.0001) (30). Furthermore European registry for Studying the Treatment of Acute hyperTension (Euro-STAT) in patients with acute hypertension among adult patients treated with intravenous antihypertensive therapy while in the emergency department found that treatment was associated with hypotension in almost 10% of patients. Overall 30-day mortality was 4%, and new or worsening end-organ damage occurred in 19% of patients (31). 12 CHAPTER 3: METHODOLOGY 3.1 STUDY AREA The study was conducted on the male and female medical wards and adult ICU (AICU) of the Bugando Medical Centre (BMC), with a total bed capacity of 170. BMC is a tertiary consultant and teaching hospital located in Mwanza. The city is located on the southern shores of Lake Victoria in the northwest part of The United Republic of Tanzania. The hospital is a referral centre for seven neighbouring regions Mara, Kagera, Shinyanga, Kigoma, Tabora Simiyu and Geita. 3.2 STUDY DESIGN This was analytical cross-sectional study with a prospective component to determine the outcomes. 3.3 STUDY POPULATION All adults admitted in Bugando medical wards or Adult ICU during the study period were eligible for enrolment. 3.3.1 Inclusion Criteria i. Age above 18 yrs ii. Informed consent by patient or the next of kin (in case patient has altered mental status) 3.3.2 Exclusion criteria: i. Patients who died before screening were not included in the study. 13 3.4 SAMPLE SIZE The sample size was calculated using Leslie Kish formula (1965): N= Z2 P ( 1 – P) d2 Where N = sample size Z = score for 95% Confidence Interval which is 1.96 P = prevalence of hypertensive emergency in previous study (5.8%) (7). d = tolerable error set at 5%. N = 84 which was the minimum number of patients to be enrolled. However in order to increase the power of the study for detecting predictors we enrolled all consecutive admissions for three months and reached a sample size of 647 patients. 3.5 DATA COLLECTION In this study, all adult medical inpatients were interviewed within 12 hours of admission in order to determine eligibility. We measured BP on all enrolled adults admitted to medical wards of BMC at the time of admission. BP was measured in the sitting position (for very sick patients who could not sit we raised the head of the bed to 45 degrees) by use of a mercury sphygmomanometer with appropriate cuff size after resting for five minutes. BP was measured three times beginning in the right arm and then the left arm and then in the arm that had a higher blood pressure as according to standard guidelines with time interval of 5 minutes between each measurement. 14 The average of the first two readings was taken as patient’s BP. Patients who met the inclusion criteria underwent an interview after obtaining the informed consent through a structured questionnaire (modified WHO STEPS questionnaire for non communicable disease) including history taking, physical examination, and laboratory investigations. All patients with hypertension were screened for symptoms and signs of hypertensive emergencies (i.e. hypertensive encephalopathy, stroke, acute pulmonary oedema, acute myocardial infarction, acute renal dysfunction or acute retinopathy). They also underwent fundoscopy (confirmed by opthalmologist), CXR (read by radiologist), 12 lead ECG, and serum creatinine. Brain CT scan was requested in patients with symptoms or signs of encephalopathy or stroke to confirm and rule out other intracranial complications and an echocardiogram was requested in all patients with symptoms or signs of heart failure or myocardial infarction. Body weight to the nearest 0.5kg was measured without shoes and in light clothes using DETECTOR scale (WEB CITY, U.S.A) as well as height to the nearest 0.5 centimetres was measured and then BMI was then calculated in kg/m2. Venopunctures were performed for all patients to check for serum creatinine level using the COBAS automated Integra 400 Plus analyzer, after cleansing the skin with 70% alcohol to remove contaminating microorganisms. Renal dysfunction was then defined as eGFR<60ml/min/1.73m2 (calculated using CKD – EPI equation) and is classified according to the standard KDOQI CKD classification, which is as follows: Stage 0 risk of renal damage but eGFR>90ml/ml/1.73m2 ; Stage 1 - renal damage but eGFR>90ml/min/1.73m2 ; Stage 2 - renal damage + eGFR = 60-89ml/min/1.73m2 ; Stage 3 - renal damage + eGFR = 30-59ml/min/1.73m2 ; Stage 4 - renal damage + eGFR = 15-29ml/min/1.73m2 ; and Stage 5 - renal damage + eGFR<15ml/min/1.73m2. 15 A 12 lead electrocardiography was also done using a Torino Italy made Bobcare, EPG 6 View ECG model page writer by trained nurse officer and interpretation was done by the investigator with assistance of experienced physician. Any doubt was cleared by an experienced cardiologist. In addition all investigation results and clinical evaluation were documented in the patient’s files. All patients who had hypertensive emergency were then followed until discharge and then to 3 months thereafter at the medical outpatient clinic. For those who did not return to the BMC clinic after 3 months, a phone call was made to the patient or the next of kin in order to determine survival/mortality, compliance to medications/follow-up and whether readmission had occurred. All results were provided to the respective clinicians who decided about management of patients according to BMC protocol as soon as they were available. 3.6 DATA PROCESSING AND ANALYSIS: Data were double entered into Microsoft Excel and cleaned. Analysis was perfomed using STATA Version 13 (San Antonio, Texas). Results were described using proportions (%) for categorical data and means or median for continuous variables according to distribution. Categorical variables were compared using Chi - Square or Fisher’s Exact Test while continuous variables were compared using t-Test or Rank Sum Test. P values < 0.05 were considered significant. Predictors with significant pvalue by univariate analysis were included in the multivariate analysis which was perfomed using logistic regression. For predictors, odds ratio is reported with 95% confidence intervals. 16 The primary outcome in this study (dependent variable) was the prevalence of hypertensive emergencies while secondary outcomes were the pattern of hypertensive emergencies seen, the predictors of hypertensive emergency and case fatality rates both in-hospital and after three months among patients with hypertensive emergencies. Independent variables that were investigated include age, gender, work status, education level, history of hypertension, kidney disease and level of BP, also obesity, compliance to ant-hypertensive agents, smoking, alcohol, HIV status and socio-economic status. 3.7 ETHICAL CONSIDERATION Permission to conduct this study was granted by the Joint Research and Publication Committee of CUHAS / BMC certificate No. CREC/057/2013. Patients were only involved after both verbal and written consent. This project was supported by grants from Tanzanian Ministry of Health and Social welfare. 17 CHAPTER 4: RESULTS 4.1 Enrolment A total of 682 patients were admitted during the study period. Seventeen (2.5%) died before screening. Twelve (1.8%) patients were not eligible as they were less than 18 years of age. Therefore 665 patients were eligible. However, 6 (0.9%) were not willing to participate in the study. Of the remaining 647 enrolled in the study: 91 (14.1%) patients had severe hypertension and 82 (12.7%) had hypertensive emergencies. These patients were followed up until discharge and three months after discharge as presented in Figure 1 below: Figure 1: Overview of study enrolment 682 PATIENTS ADMITTED DURING STUDY PERIOD 17 DIED BEFORE SCREENING 665 SCREENED 682 12 PATIENTS < 18YRS (1.8%) 6 CONSENT REFUSALS 647 INCLUDED IN THE STUDY 82 (12.7%) 565 (87.3%) HYPERTENSIVE EMERGENCY OTHER CONDITIONS 18 4.2 Baseline socio-demographic and clinical characteristics Of 647 patients enrolled in our study, the median age was 45 years [32-61.5] and 312 (48.2%) were females. The majority of patients 643 (99.7%) were of African origin and 305 (47.7%) had a primary level of education. The majority of patients were farmers (peasants) 301 (46.8%). Out of enrolled patients 163 (25.4%) reported history of hypertension and only 76/163 (46.6%) were on treatment for hypertension two weeks prior to admission. Of the patients enrolled, 110 patients (17%) had loss of consciousness, 68 (10.5%) had impaired vision, 163 (25.2%) had headache, 90 (13.9%) had chest pain and 214 (33.1%) had shortness of breath within 24 hrs prior to admission. Furthermore 215 (33.2%) of our cohort had hypertension at the time of admission. The median current body mass index was 22.6 [20.3 to 25.3] kg/m2, whereby the majority had a normal BMI and 10.7% (69 patients) were obese. One hundred seventeen patients (18.5%) were known HIV positive while 5.1% were diagnosed HIV positive during admission. More details are provided in Table 1 below. 4.3 Prevalence of hypertensive emergencies Out of 647 patients, 91 (14.1%) had severe hypertension and 82 (12.7%) met criteria for hypertensive emergency. A majority of these patients 70/82 (85.4%) had more than one emergency. The most common forms of emergencies seen in this study were hypertensive retinopathy 51 (62.2%) followed by hypertensive encephalopathy 41(50%) and the least common was hypertensive stroke 18 (22%) as illustrated in Tables 2 and 3 below. All patients who presented with severe hypertension with acute blurred vision (within 24 hours of admission) underwent fundoscopy where- by 11/51 (21.6%) had mild 19 retinopathy, 22/51 (43.1%) moderate retinopathy and 18/51 (35.3%) had severe retinopathy. Table 1: Baseline characteristics of 647 patients admitted to BMC from October 2013 until December 2013. Characteristic Female Age in years Ethnicity * African Other Education * Incomplete primary Complete primary Complete secondary University Work status * Government or business Self employed Farmer Water source * Tap water Lake or pond water Electricity * Toilet * Modern flush toilet Pit latrine Smoker * Never Previous Smoker Current Smoker Alcohol* Never Prior to last month In last month or current History of HTN * History of kidney disease * History of HF * History of diabetes* Urine output * Increased Normal Decreased BMI * Underweight BMI <18.5 Normal BMI>=18.5 & BMI <25 Overweight BMI>=25 & BMI<30 Obese BMI>30 Hypertension HIV rapid test Not done/refused Known New positive New negative NOTE: *some data missing Number (%) or Median [IQR] 312 (48.2%) 45 [32-61.5] 643 (99.7%) 2 (0.3%) 238 (37.0%) 305 (47.4%) 100 (15.6%) 153 (23.8%) 189 (29.4%) 301 (46.8%) 290 (45.2%) 352 (54.8%) 258 (40%) 247 (38.3%) 398 (61.7%) 520 (80.6%) 90 (14.0%) 35 (5.4%) 404 (62.4%) 190 (29.4%) 53 (8.2%) 163 (25.4%) 28 (4.3%) 81 (12.6%) 48 (7.5%) 13 (2.0%) 552 (85.7%) 79 (12.3%) 22.6 [20.3-25.3] 83 (12.9%) 390 (60.6%) 102 (15.8%) 69 (10.7%) 215 (33.2%) 25 (3.9%) 117(18.1%) 32 (5.0%) 473 (73.1%) 20 Table 2: Types of hypertensive emergencies among 82 consecutive adults admitted to BMC with hypertensive emergency. Pattern Hypertensive retinopathy Hypertensive encephalopathy Pulmonary edema Impaired renal function Ischemic heart disease Hypertensive stroke Frequency (%) 51(62.2) 41(50.0) 39(47.6) 37(45.1) 20 (24.4) 18 (22.0) Table 3: Overlap between hypertensive emergencies among 82 consecutive adults admitted to BMC with hypertensive emergency Type or Pattern Multiple Hypertensive emergencies Hypertensive retinopathy alone Hypertensive Encephalopathy alone Hypertensive stroke alone Impaired renal function alone Hypertensive pulmonary edema alone Hypertensive Ischemic heart disease alone TOTAL Frequency (%) 70 (85.4) 5 (6.1) 3 (3.7) 1 (1.2) 1 (1.2) 1 (1.2) 1 (1.2) 82 (100) 4.4 Outcomes Of 82 patients with hypertensive emergency, the average length of hospital stay was 6 [3-9] days and 25/82 (30.5%) died during admission. At one month post discharge, 6 (7.3%) patients were lost to follow up. A total of 37/76 (48.7%) of the patients still in follow-up had died. Among the living patients still in follow up, 5/39 (12.8%) had been readmitted to the hospital, 28/39 (71.8%) were attending clinic and medication use was 39/39 (100%). At three months, 40/76 (52.6%) had died. Among the living patients, 4/36 (11.1%) were readmitted, clinic follow up was 29/36 (80.6%) and medication use was (33/36) 91.7% as shown in Table 4 below. 21 Table 4: In hospital, 1 month and 3 months post-discharge outcomes among 82 adults admitted with hypertensive emergency Outcome Number (%) or Median [IQR] In-hospital case fatality rate Duration of Hospital Stay One month outcome: 1 month case fatality rate 1 month medication use 1 month clinic follow up 1 month readmission rate Three month outcomes 3 month case fatality rate 3 month medication use 3 month clinic follow up 3 month readmission rate Loss to follow up NB:* = some data missing 25/82 (30.5%) 6 [3-9] 37/76 (48.7%) * 39/39 (100%) 28/39 (71.8%) 5/39 (12.8%) 40/76 (52.6%) 33/36 (91.7%) 29/36 (80.6%) 4/36 (11.1%) 6/57 (10.5%) 4.5 Factors associated with hypertensive emergencies Factors significantly associated positively with hypertensive emergencies by univariate analysis include female gender (OR 2.03, 95% CI 1.26-3.28, p= 0.004), age (OR 1.04, 95% CI 1.03-1.05, p= <0.001), use of alcohol prior to last month before admission (OR 1.98, 95% CI 1.21-3.25, p= 0.007), prior history of hypertension (OR 15.29, 95% CI 8.76-26.67, p= <0.001), electricity at home (OR 1.69, 95% CI 1.062.69, p= 0.028), history of diabetes mellitus (OR 2.88, 95% CI 1.45-5.72, p= 0.002), history of loss of consciousness (OR 6.05, 95% CI 3.66-9.99, p= <0.001), impaired vision (OR 15.73, 95% CI 8.89-27.83, p= <0.001), headache (OR 7.33, 95% CI 4.4512.08, p= <0.001), and chest pain 24 hours prior to admission (OR 2.32, 95% CI 1.324.07, p= 0.003). The following were negatively associated with hypertensive emergency: self-employment (OR 0.51, 95% CI 0.27-0.96, p= 0.037), primary level of education (OR 0.54, 95% CI 0.32-0.9, p= 0.017) and use of pit latrine at home (OR 0.49, 95% CI 0.31-0.78, p= 0.003). Clinical characteristics positively associated with 22 hypertensive emergency were displaced apex beat (OR 5.96, 95% CI 3.61-9.84, p= <0.001), presence of crepitations on the lung bases (OR 1.66, 95% CI 1.01-2.73, p= 0.045), heart failure by Framingham criteria (OR 1.86, 95%CI 1.12-3.08, p= 0.02), renal dysfunction (OR 2.18, 95% CI 1.36-3.50, p= 0.001), and obesity (OR 3.47, 95% CI 1.83-6.56, p= <0.001) but positive HIV status (OR 0.23, 95% CI 0.97-0.53, p=0.001) had negative association as illustrated in table 5 below. 23 Table 5: Factors associated with hypertensive emergencies among 82 adults admitted with hypertensive emergencies to BMC by Univariate Analysis Predictors Hypertensive Number (%) or Median Emergencies (IQR) (N=82) Hypertensive without emergency (N=215) 109 (50.7) 59 [48-68] 23 (10.7) 24 (11.2) 39 (18.1) 49 (22.8) 80 (37.2) Odds ratio [95% CI] p-value 2.03[1.26-3.28] 1.04[1.03-1.05] 1 1.88[0.67-5.34] 5.23[2.05-13.33] 6.63[2.68-16.40] 8.13[3.48-19.01] 0.004 <0.001 1.36[0.8-2.31] 0.51[0.27-0.96] 1 0.26 0.037 39(47.6) 29(35.4) 14(17.1) * 41 (50.6) 40 (49.4) 42 (51.2) 62(28.8) 56(26.1) 97(45.12) * 90(42.3) 89(41.8) 34(16.0) * 119 (55.9) 94 (44.1) 110 (51.2)* 44 (53.7) 38 (46.3) Female Age(years) <35 years 35-44.9 45-54.9 55-64.9 >65 years Work status Professional Self-employed Farmer Education Incomplete primary Complete primary Complete secondary Water source Tap water Lake or pond water Electricity Toilet Modern flush toilet Pit latrine Smoking Never Previous Current Alcohol Never Prior last month Current /in last month BP measured by health professional History of HTN 52 (63.4) 61 [51-69] 7 (8.5) 8 (9.8) 15 (18.3) 19 (23.2) 33 (40.2) History of kidney disease History of HF Treatment of HTN Treatment of HF Treatment HTN last 2 weeks History of diabetes Urine output Increased Normal 27(32.9) 14(17.1) 41(50) 0.23 0.001 <0.001 <0.001 1 0.54[0.32-0.9] 0.83[0.43-1.61] 0.017 0.58 1 0.78[0.49-1.24] 1.69[1.06-2.69] 0.29 0.028 111 (51.6) 104 (48.4) 1 0.49[0.31-0.78] 0.003 69 (84.2) 6 (7.3) 7 (8.5) 165 (76.7) 35 (16.3) 15 (7.0) 1 0.47[0.20-1.11] 1.63[0.69-3.89] 0.09 0.27 40(48.8) 34(41.5) 8(9.8) 64 (78.1) 105(48.8) 89(41.4) 21(9.8) 164 (76.3) 1 1.98[1.21-3.25] 1.62[0.71-3.67] 4.30[2.48-7.44] 0.007 0.25 <0.001 63 (76.8) 147 (68.4) 15.29[8.76-26.67] <0.001 5 (6.1) 17 (7.9) 1.52[0.56-4.13] 0.41 12 (14.8)* 60 (73.2) 8 (9.8) 27 (32.9) 50 (23.4)* 135 (62.8) 44 (20.6)* 78 (36.3) 1.25[0.64-2.42] 15.34[8.94-26.32] 0.89[0.41-1.93] 4.93[2.86-8.48] 0.52 <0.001 0.76 <0.001 13(16.1)* 38(17.8)* * 5(2.4) 172(80.8) 2.88[1.45-5.72] 0.002 1.32[0.29-6.07] 1 0.73 2(2.4) 67(81.7) 24 Decreased LOC in past 24hrs Impaired vision 24hrs Headache past24hr Chest pain past 24h Shortness of breath past 24h Orthopnea past 24 hours PND past 24 hours Displaced apex Crepitations Bilateral edema Elevated JVP Murmur Framingham criteria met Renal dysfunction BMI Underweight Normal Overweight Obese Waist circumference Hip circumference WHR SBP1 DBP1 Anti-hypertensive started in ED Pulse rate GCS Oxygen saturation RBG HIV rapid test Not done Positive Negative 13(15.9) 38(46.9)* 38(46.9)* 52(64.2)* 20(24.7)* 34(42)* 36(16.9) 67(31.3)* 54(25.2)* 97(45.3)* 37(17.3)* 90(42.1) 1.43[0.75-2.7) 6.05[3.66-9.99] 15.73[8.89-27.83] 7.33[4.45-12.08] 2.32[1.32-4.07] 1.55[0.96-2.49] 0.28 <0.001 <0.001 <0.001 0.003 0.07 25(30.5) 70(32.6) 1.58[0.95-2.63] 0.08 19(23.2) 56(68.3) 28(34.2) 18(22.2)* 10(12.2) 12(14.8)* 27(32.9) 59(27.4) 129(60.0) 74(34.6)* 62(29.1)* 30(14.0)* 32(15.1)* 69(32.1) 1.30[0.75-2.27] 5.96[3.61-9.84] 1.66[1.01-2.73] 0.94[0.54-1.65] 1.43[0.69-2.93] 1.29[0.66-2.50] 1.86[1.12-3.08] 0.35 <0.001 0.045 0.84 0.34 0.46 0.02 37(45.1) 2.18[1.36-3.50] 0.001 4(4.9) 36(43.9) 24(29.3) 18(22) 90[81.5-100] 99.5[90-108] 0.92[0.89-0.95] 190[175-211] 115[110-127] 64(78) 85(39.5) * 8(3.8) 105(49.3) 50(23.5) 50(23.5) 89[80-100] 97[86-106] 0.91[0.89-0.94] 160[140-190] 100[90-115] 95(44.2) 0.5[0.17-1.44] 1 3.03[1.71-5.36] 3.47[1.83-6.56] 1.06[1.04-1.07] 1.06[1.04-1.08] 5.37[0.34-84.03] 1.08[1.06-1.09] 1.13[1.11-1.16] 42.10[22.95-77.23] 0.20 92.5[80-105] 15[11-15] 93.5[88-96] 7.3[6.2-9.4] 90[80-100] 15[15-15] 95[92-96] 6.9[5.7-9.4] 1[0.99-1.01] 0.77[0.7-0.85] 0.96[0.94-0.98 1.03[0.99-1.07] 0.84 <0.001 0.001 0.17 2(2.4) 6(7.3) 74(90.2) 4(1.9) 15(7.0) 196(91.2) 0.47[0.11-2.03] 0.23[0.97-0.53] 1 0.31 0.001 <0.001 <0.001 <0.001 <0.001 0.23 <0.001 <0.001 <0.001 All variables significantly associated with hypertensive emergencies in the univariable analysis were included in multivariate analysis except the clinical characteristics that are results of hypertension like displaced apex beat, impaired vision, chest pain, loss of consciousness and headache. By multivariable analysis, the only factors significant associated with hypertensive emergency are presented in table 6 below. 25 Table 6: Factors associated with hypertensive emergencies among 82 adults admitted to BMC by Multivariable logistic regression. Predictors Female gender Age Oxygen saturation Odds ratio[95% CI] 2.17[1.18-4.00] 1.02[1.01-1.04] 0.97[0.94-0.997] p-value 0.012 0.008 0.031 4.6 Predictors of in-hospital fatality rates By univariate analysis, among adults with hypertensive emergency, in hospital case fatality rate was significantly positively associated with current use of alcohol (OR 5, 95% CI 1.01-24.77, p=0.049), loss of consciousness within 24 hrs prior to admission (OR 6.2, 95% CI 2.11-18.1, p=0.001), renal dysfunction (OR 3.05, 95% CI 1.15-8.10, p=0.026), hypertensive encephalopathy (OR 6.86, 95% CI 2.24-20.97, p=0.001), hypertensive stroke (OR 7.85, 95% CI 2.48-24.87, p=<0.001), and hypertensive emergency with impaired renal function (OR 3.05, 95% CI 1.15-8.10, p=0.03). Predictors that were negatively associated with fatality by univariable analysis were history of hypertension (OR 0.28, 95% CI 0.10-0.82, p=0.02), chest pain within 24 hours prior to admission (OR 0.18, 95% CI 0.39-0.86, p=0.032), Glasgow Coma Score (OR 0.65, 95% CI 0.52-0.81, p=<0.001), and hypertensive emergency with ischemic heart disease (OR 0.19, 95% CI 0.04-0.89, p=0.04) as illustrated in Table 7 below. 26 Table 7: Baseline Predictors of in hospital fatality rates among 82 adults admitted to BMC with hypertensive emergencies and followed up until discharge by univariate logistic regression Predictors Number (%) or Median (IQR) Female Age (years) Work status Professional Self-employed Farmer Education Incomplete primary Complete primary Complete secondary Water source Tap water Lake or pond Electricity Toilet Modern flush Pit latrine Smoking Never Previous Current Alcohol Never Prior last month Current /in last month BP measured by health professional History of HTN History of kidney disease History of HF Treatment of HTN RX HTN last 2weeks History of diabetes Urine output Increased Normal Decreased LOC in past 24h Impaired vision past 24 hours Headache past 24hrs Chest pain past 24hr Shortness of breath past 24h Died during hospitalization (N=25) 13(52) 59.6[25-83] Alive during hospitalization (N=57) 39(68.42) 58.1[26-89] Odds ratio [95%CI] p-value 0.5[0.19-1.31] 1.01[0.98-1.04] 0.16 0.67 9(36) 6(24) 10(40) 18(31.6) 8(14) 31(54.4) 1.55[0.53-4.53] 2.33[0.65-8.33] 1 0.42 0.20 13(52) 7(28) 5(20) 26(45.6) 22(38.6) 9(15.8) 1 0.64[0.22-1.87] 1.11[0.31-3.99] 0.412 0.872 12(48) 13(52) 14(56) 29(51.8) 27(48.2) 28(49.1) 1 1.16[0.45-2.99] 1.32[0.51-3.39] 0.75 0.567 14(56) 11(44) 30(52.6) 27(47.4) 1 0.87[0.34-2.25] 0.778 20(80) 2(8) 3(12) 49(86) 4(7) 4(7) 1 1.23[0.21-7.23] 1.84[0.38-8.96] 0.82 0.45 10(40) 10(40) 5(20) 16(64) 30(52.6) 24(42.1) 3(5.3) 48(84.2) 1 1.25[0.45-3.49] 5[1.01-24.77] 0.33[0.11-0.98] 0.67 0.049 0.047 15(60) 1(4) 48(84.2) 4(7) 0.28[0.10-0.82] 0.55[0.59-5.21] 0.02 0.60 4(16) 15(60) 5(20) 2(8.3) 8(14.3)* 45(79) 22(38.6) 11(19.3) 1.14[0.31-4.22] 0.4[0.14-1.11] 0.40[0.13-1.21] 0.38[0.78-1.86] 0.84 0.08 0.11 0.23 0(0) 23(92) 2(8) 19(76) 14(56) 2(3.5) 44(77.2) 11(19.3) 19(33.9)* 24(42.9) 1 0.35[0.71-1.70] 6.2[2.11-18.01] 1.7[0.66-4.39] 0.19 0.001 0.28 19(76) 2(8) 8(32) 33(58.9) 18(32.1) 26(46.4) 2.21[0.76-6.38] 0.18[0.39-0.86] 0.54[0.20-1.46] 0.14 0.032 0.23 27 Orthopnea past 24hrs Crepitations Bilateral edema Elevated JVP Framingham criteria met Renal dysfunction BMI Underweight Normal Overweight Obese Waist circumference Hip circumferen WHR SBP1 DBP1 Anti-hypertensive started in ED Pulse rate GCS Oxygen saturation RBG HIV rapid test Not done Positive Negative HT Encephalopathy HT stroke HT retinopathy HT impaired renal function HT Pulmonary Edema HT Ischemic Heart Disease NB: *= data missing 5(20) 8(32) 3(12) 2(8) 5(20) 20(35.1) 20(35.1) 15(26.8)* 8(14) 22(38.6) 0.46[0.15-1.42] 0.87[0.32-2.37] 0.37[0.97-1.43] 0.53[0.10-2.71] 0.40[0.13-1.21] 0.18 0.79 0.15 0.45 0.11 16(64) 21(36.8) 3.05[1.15-8.10] 0.026 1(4) 13(52) 7(28) 4(16) 87.5[65-107] 94.6[70-114] 0.93[0.86-1.23] 198[100-259] 119[70-169] 18(72) 3(5.3) 23(40.4) 17(29.8) 14(24.6) 90.4[35-121] 99.7[63-152] 0.90[0.44-1.09] 191[140-278] 117[70-177] 46(80.7) 0.59[0.56-6.27] 1 0.73[0.24-2.22] 0.51[0.14-1.86] 0.99]0.95-1.02] 0.97[0.94-1.01] 56[0.06-53447] 1.01[0.99-1.02] 1.01[0.98-1.03] 0.61[0.21-1.83] 0.66 95[56-130] 11[3-15] 56[55-98] 8[4.8-18.2] 91[56-140] 14[8-15] 91.6[30-99] 8.6[4.4-23.1] 1.01[0.99-1.04] 0.65[0.52-0.81] 0.96[0.92-1.01] 0.98[0.86-1.12] 0.41 <0.001 0.08 0.77 0(0) 2(8) 23(92) 20(80) 12(48) 18(72) 16(64) 2(3.5) 4(7) 51(89.5) 21(36.8) 6(10.5) 33(57.9) 21(36.8) 1.11[0.19-6.49] 1 6.86[2.24-20.97] 7.85[2.48-24.87] 1.87[0.67-5.18] 3.05[1.15-8.10] 0.91 11(44) 2(8) 28(49.1) 18(31.6) 0.814[0.32-2.09] 0.19[0.04-0.89] 0.67 0.04 0.58 0.31 0.41 0.129 0.25 0.32 0.69 0.38 0.001 <0.001 0.23 0.03 By multivariate analysis all variables significantly associated with in hospital fatality in the univariable analysis were included and only significant associations are presented in table 8 below. Renal dysfunction was not included due to collinearity with “HTN Emergency with impaired renal function”, chest pain was not included due to collinearity with “HTN Emergency with Ischemic Heart Disease” and both GCS and loss of consciousness were not included due to collinearity with “HTN Emergency with Encephalopathy.” 28 Table 8: Baseline Predictors of in hospital fatality rates among 82 adults admitted to BMC with hypertensive emergencies and followed up until discharge by Multivariable logistic regression Predictors Hypertensive Emergency with impaired renal function Hypertensive stroke Odds ratio [95% CI] 27.53[3.74-202.91] p-value 0.001 31.17[3.73-260.77] 0.002 4.7 Predictors of 3 months fatality rates The following predictors were significantly positively associated with 3-months fatality rates by univariate logistic regression: loss of consciousness past 24 hours prior to admission (OR 2.83, 1.11-7.23), hypertensive encephalopathy (OR 2.62, CI 1.04–6.62) and hypertensive emergency with impaired renal function (OR 4.33, CI 1.64-11.44). Negative predictors were: Glasgow Coma Score (OR 0.76, 0.61-0.94) and oxygen saturation (OR 0.92, 0.85-0.99), as shown in the table 9 below: Table 9: Baseline Predictors of 3 months fatality rates among 82 adults admitted to BMC with hypertensive emergencies and followed up until 3 months after discharge by univariate logistic regression Predictors Number (%) or Median (IQR) Female Age(years) Work status Professional Self-employed Farmer Education Incomplete primary Complete primary Complete secondary Water source Tap water Lake or pond Electricity Toilet Modern flush Pit latrine Smoking Never Previous Death by 3months (N=40) 24(60) 58.2[25-83] Alive by 3months (N=36) 22(61.1) 58.6[35-89] Odds ratio [95% CI] p-value 0.95[0.38-2.40] 0.998[0.97-1.03] 0.92 0.91 15(37.5) 6(15) 19(47.5) 11(30.6) 8(22.2) 17(47.2) 1.22[0.44-3.37] 0.67[0.19-2.33 1 0.70 0.53 22(55) 11(27.5) 7(17.5) 13(36.1) 17(47.2) 6(16.7) 1 0.38[0.14-1.06] 0.69[0.19-2.50] 0.07 0.57 19(48.7)* 20(51.3)* 24(60) 20(55.6) 16(44.4) 18(50) 1 1.32[0.53-3.27] 1.5[0.60-3.72] 0.55 0.38 23(57.5) 17(42.5) 20(55.6) 16(44.4) 1 0.92[0.37-2.29] 0.86 34(85) 3(7.5) 29(80.6) 3(8.3) 1 0.85[0.16-4.55] 0.85 29 Current Alcohol Never Prior last month Current /last month History of HTN History of kidney disease History of HF Treatment of HTN Treatment of HTN last 2week History of diabetes Urine output Increased Normal Decreased LOC past 24hrs Impaired vision past 24 hours Headache past 24h Chest pain past 24hrs Shortness of breath past 24 hrs Crepitations Framingham criteria met Renal dysfunction BMI Underweight Normal Overweight Obese Waist circumferen Hip circumferen WHR SBP1 DBP1 Pulse rate GCS Oxygen saturation RBG HIV rapid test Not Positive Negative HT Encephalopathy HT stroke HT retinopathy HT impaired renal function Pulmonary Edema Hypertensive IHD 3(7.5) 4(11.1) 0.64[0.13-3.10] 0.58 19(47.5) 15(37.5) 6(15) 27(67.5) 2(5) 17(47.2) 18(50) 1(2.8) 31(86.1) 3(8.3) 1 0.75[0.29-1.92] 5.37[0.59-49.2] 0.33[0.11-1.06] 0.58[0.09-3.68] 0.54 0.14 0.06 0.56 7(17.5) 26(65) 11(27.5) 5(14.3)* 29(80.6) 14(38.9) 1.27[0.364.44] 0.45[0.16-1.28] 0.60[0.23-1.56] 0.71 0.13 0.29 5(12.8)* 7(19.4) 0.61[0.17-2.13] 0.44 1(2.5) 34(85) 5(12.5) 24(61.5)* 18(46.2)* 1(2.78) 29(80.6) 6(16.7) 13(36.1) 18(50) 0.85[0.05-14.25] 1 0.71[0.20-2.57] 2.83[1.11-7.23] 0.86[0.45-2.12] 0.91 27(69.2)* 6(15.4)* 22(61.1) 12(33.3) 1.43[0.55-3.72] 0.36[0.12-1.11] 0.46 0.08 19(47.5) 11(31.4)* 1.97[0.77-5.08] 0.16 16(40) 15(37.5) 8(22.2) 9(25) 2.33[0.85-6.40] 1.8[0.67-4.84] 0.10 0.24 25(62.5) 10(27.8) 4.33[1.64-11.44] 0.003 3(7.5) 19(47.5) 9(22.5) 9(22.5) 87.5[35-121] 96.7[63-152] 0.91[0.44-1.23] 196.4[100-259] 118.7[70-170] 93.2[56-140] 12.3[3-15]* 87[30-98] 8.1[4.8-18.2] 0(0) 15(41.7) 13(36.1) 8(22.2) 92.2[68-114]* 100.4[[70-120] 0.92[0.72-1.09]* 192[140-278] 117.9[70-177] 91.8[63-140] 14.2[10-15] 93[56-99] 9.2[4.4-23.1]* 1 0.55[0.18-1.62] 0.89[0.28-2.86] 0.98[0.94-1.01] 0.98[0.95-1.01] 0.21[0.001-51.96] 1.005[0.99-1.02] 1.002[0.99-1.02] 1.004[0.98-1.03] 0.76[0.61-0.94] 0.92[0.85-0.99] 0.93[0.82-1.05] 0.28 0.84 0.17 0.25 0.58 0.53 0.88 0.74 0.01 0.03 0.23 0(0) 3(7.5) 37(92.5) 25(62.5) 12(30) 23(57.5) 25(62.5) 1(2.8) 3(8.3) 32(88.9) 14(38.9) 6(16.7) 24(66.7) 10(27.8) 0.86[1.16-4.59] 1 2.62[1.04-6.62] 2.14[0.71-6.48] 0.68[0.27-1.72] 4.33[1.64-11.44] 0.87 22(55) 6(15) 13(36.1) 12(33.3) 2.16[0.86-5.44] 0.35[0.12-1.07] 0.101 0.07 30 0.60 0.03 0.74 0.04 0.18 0.41 0.003 NB: *=one data missing By multivariate analysis all variables significantly associated with 3 months fatality rates in the univariable analysis were included + age & sex and only significant associations are presented. However renal dysfunction and GCS/LOC were omitted due to collinearity with the variables for “HTN Emergency with impaired renal function” and “HTN Emergency with Encephalopathy” respectively. Hypertensive emergency with impaired renal function was a positive predictor (OR 6.40, 2.0619.84) as well as hypertensive encephalopathy (OR 4.42, 1.41-13.84) as in table 10 below. Table 10: Baseline Predictors of 3 months fatality rates among 82 adults admitted to BMC with hypertensive emergencies and followed up until 3 months after discharge by multivariable logistic regression Predictors Odds ratio[95% CI] p-value Hypertensive Emergency with 6.40 [2.06-19.84] impaired renal function 0.001 4.42 [1.41-13.84] 0.011 Hypertensive encephalopathy 31 CHAPTER 5: DISCUSSION This study was conducted to determine the prevalence, patterns, and factors associated with hypertensive emergencies as well as predictors of fatality among hypertensive patients admitted to BMC. To the best of our knowledge this is the first study to be done in Tanzania whereby these patients were followed up until three months post discharge to determine survival/fatality rates, readmission rates, whether patients were still using medications and whether they were being followed up at the clinics. We found that hypertensive emergency was one among the causes of admission in medical wards. A majority of patients had hypertensive retinopathy. Hypertensive emergency was significantly associated with age gender and oxygen saturation. Thirty percent of patients with hypertensive emergencies died during hospitalization and at three months post discharge more than 50% had died with hypertensive encephalopathy and hypertensive kidney disease being significant predictors. 5.1 Prevalence of hypertension and hypertensive emergencies In this study a total of 647 patients were enrolled whereby 163 (25.4%) reported history of hypertension and 145 (88.9%) were prescribed and used medication at some point in their life but only 76/163 (46.6%) of these were on treatment for hypertension for the past two weeks prior to admission. However 215 (33.2%) were then found to be hypertensive by average BP measurements and/or being on medication. Furthermore 68 /480 (14.2%) had no history of hypertension but were found to be hypertensive by average BPs. This prevalence is higher compared to the prevalence of hypertension in USA based on publication of many hypertension 32 observational studies and clinical trials reported by the JNC7 where the prevalence was 25% (3). This increase supports the fact that hypertension is increasing in SSA. Also this reported prevalence is higher compared to study done in Nigeria among hypertensive patients whereby only 14.2% had self reported hypertension and of these only 18.6% had been on medication in the past three months (16). Also prevalence of hypertension from our study (33.2%) is higher as compared to a previous 3 year prospective study at BMC on all patients admitted to medical wards to determine the contribution of hypertension to death, admissions, and hospital days which reported a prevalence of hypertension of 14.6% (7). The lower prevalence in the BMC study is due to the fact that the diagnosis recorded was the primary diagnosis that indicated the reason for admission and possibly missed other patients who had hypertension as a secondary diagnosis. In our study also 91 (14.1%) had severe hypertension. This prevalence is higher compared to a multicentre study done in Italy on adults admitted to the emergency departments where the prevalence was 0.46% (14). We got the higher percentages due to the fact that majority of hypertensive patients (more than 50%) were not on medication and the increased number of hypertensive cases contributes to the increase in hypertensive crisis. The prevalence of hypertensive emergencies in our study is 12.7%. This prevalence is higher than a study done on hypertensive emergencies at the University Hospital Centre in Brazzaville Congo which showed a prevalence of 4% which is likely lower because of the retrospective nature of their study (18). Also our prevalence is higher than in a study done in Angola where the prevalence of hypertensive emergency was 4.3% but this was done only in patients under 45 years of age (17). Furthermore this prevalence is higher compared to the previous 3- year prospective study in BMC 33 among patients admitted in the medical ward which found the prevalence of hypertensive emergency of 5.8% (7). Also poor compliance as more than 50% of hypertensive patients were not on medication contributed to increased prevalence in our study. 5.2 Patterns of hypertensive emergencies Majority of patients 70 (85.4%) with hypertensive emergencies in our study had multiple hypertensive emergencies. The most common forms were hypertensive retinopathy (62%), hypertensive encephalopathy (50%), acute pulmonary oedema (47.6%) and hypertensive kidney disease (45.1%). The least common form was hypertensive stroke (22%). Twenty seven patients were suspected to have stroke and severe hypertension however only 18/27 (66.7%) were confirmed by CT scan. Of note, all those suspected to have stroke that had confirmatory CT scans did actually have strokes. Hypertensive retinopathy being the commonest pattern could be due to possibility that these patients had retinopathies even before they had severe hypertension. This is similar to a study done in Accra Ghana which showed hypertensive retinopathy to account for 70% of the target organ damage (11). Also in Iran, 39.9% of hypertensive patients had hypertensive retinopathy and among these patients 42.4%, 20%, 2.35% had retinopathy grade 1, 2, and 3 respectively (13). However in our study moderate (grade 2) retinopathy was the commonest presentation. Moreover hypertensive encephalopathy was the second most common emergency type (50%) higher than in 14% in Congo (18) and 4.9% in Italy (14). 34 In our study acute pulmonary oedema accounted for 47.6% of emergencies higher than in other studies as most of the patients had also heart failure contributing to pulmonary oedema. But in the Italian study, 121 (30.9%) had acute pulmonary edema, and two patients only had both acute pulmonary edema and stroke (14) but in our study most patients (85%) had multiple emergencies. In Brazil also acute pulmonary oedema was one of the most common hypertensive emergencies (12). Hypertensive kidney diseases were previously undiagnosed because of limited facilities in our setting. Our study has shown 45% of patients with severe hypertension had renal dysfunction, higher than in Congo where renal failure was found in 13.1% of patients with severe hypertension (18), and also higher than in Italy where 23 (5.9%) had acute renal failure (14). Also hypertensive stroke in our study was lower compared to other studies as some patients failed to undergo CT scan for confirmation. In Congo study the most common diseases underlying hypertensive emergency was stroke, 50% (18) while in Italian study stroke accounted for 22% (14). 5.3 Factors associated with hypertensive emergencies Female gender 52 (63.4%) was found to have two fold increase in odds for developing hypertensive emergencies by univariable logistic regression (OR 2.03, 95% CI 1.26-3.28, p=0.004) and by multivariate analysis (OR 2.17, 95% CI 1.184.00, p=0.012). These findings are similar to a study previously done in Switzerland whereby female gender was one of the risk factors for promoting hypertensive crisis (22). This support the epidemiological high prevalence of hypertension in women than in men therefore higher chances of complications. Also we had more hypertensive females than men suggesting women’s tendency to seek medical care 35 than men in our setting. However our results are different from the Italian study where patients with hypertensive emergencies had higher risk of being men (OR 1.34, 95% CI 1.06–1.70) than in women suggesting men’s lower compliance to screening and treatment of hypertension (14). Also in this analysis an increase in age above 45 years was found to be significant risk of hypertensive emergencies (OR 1.04 95% CI 1.03-1.05, p=<0.004) as shown in univariate analysis as well as in multivariate analysis (OR 1.02, 95% CI 1.01-1.04, p=0.008). These findings are similar to studies done in USA where old age was one of the independent predictors of poorly controlled hypertension (20). There were also similar findings in a South African study, in which old age was most commonly associated with target organ damage among black hypertensive patients attending primary health care services (23). Also low oxygen saturation was significantly associated with hypertensive emergency both in univariable and multivariable models. Low oxygen saturation was due to pulmonary oedema seen in patients who had heart failure. Furthermore our study showed history of diabetes mellitus was a significant predictor of hypertensive emergencies (OR 2.88, 95% CI 1.45-5.72, p=0.002), in univariable analysis, although it was not found to be significant in multivariate model. This is similar to a study done in Brazil in which diabetes mellitus was found in 20% of patients and was found to be statistically significant factor for development of hypertensive emergencies (12). Also a study in Ghana showed that the participants diagnosed with diabetes had increased odds of developing target organ damage compared to those with no diagnosis of diabetes. This was however not statistically significant (11). 36 Moreover obesity is associated with an almost 4 fold increase in risk of hypertensive emergencies (OR 3.47, 95% CI 1.83-6.56), p=<0.001 but was not significant in multivariate analysis. This is the same as in Switzerland (22) as well as in the Congo study (18) where obesity is a significant predictor of hypertensive emergency. Our study also found high socio-economic status is significantly associated with hypertensive emergencies by univariable analysis but not in multivariable model where patients with electricity had more than two times the odds of having hypertensive emergency while use of pit latrine used by majority with low income and poverty was protective for hypertensive emergencies. This can be explained by the current adoption of western cultures including diet changes, smoking, obesity, as well as life changes associated with urbanisation which are all associated with cardiovascular complications. However a study by Ellenga et al in Congo showed low socio-economic status was significantly associated with hypertensive emergencies (18). 5.4 Fatality Fatalities due to hypertensive emergencies in SSA are generally unacceptably high, in our study 25 (30.5%) patients with hypertensive emergencies died during hospitalisation. This fatality rate is almost similar to Angolan study by Garcia GM et al where the in hospital fatality rate was 25.2% though their population was under 45 years of age (17). But the fatality rate is very high compared to a previous study done in USA among patients with acute severe hypertension where the hospital fatality was 6.9% (27). The higher fatality in our study was due to the fact that majority of our patients were admitted when very sick with multiple emergencies at presentation compared to patients in the USA and other high income countries. For the same reason by three-months post discharge in our study 40 (52.6%) patients died. This 37 fatality rate is very high compared to that in USA where three month fatality rate was 11% (27). Another study done in Thailand on hypertensive emergencies showed the in hospital fatality as high as 15% (25), while in Mexico city 4.6% of patients with hypertensive emergencies admitted to coronary care unit died (26). The fatality rates may also be lower due to better care of these patients in developed countries compared to our Tanzanian hospital. Furthermore in our study 3 month readmission rate was 11.1% which is lower compared to a study done in USA where the 90-day readmission rate was 37% (27). The reason for lower readmission rates could be due to lower number of patients on follow up in our study because the majority died. A prior 3-year prospective study in BMC among patients admitted in the medical ward showed that hypertension contributed to 33.9% of non-communicable disease deaths and 15.3% of all deaths. Hypertensive emergencies contributed to 17.5% of all deaths where 55/314 patients died during hospitalisation (7). Diagnostic facilities are lacking in our hospital such as cardiac biomarkers and consistent CT scan availability. We should improve on diagnostic facilities for early diagnosis and early management of these hypertensive emergencies to reduce fatality rates. 5.5 Predictors of in-hospital and 3-months fatality rates Very few studies were done on predictors of in-hospital fatality among patients with hypertensive emergencies. In our study, hypertensive emergency with impaired renal function was found to be a significant predictor of in hospital fatality in both univariable (OR 3.05, 95% CI 1.15-8.10), p=0.03 and multivariable models (OR 27.53, 95% CI 3.74-202.91), p=0.001. This is due to inconsistence presence of diagnostics for kidney diseases as well as lack of advanced management of kidney disease like dialysis or renal replacement therapy in our settings. Therefore early detection and treatment of kidney diseases are warranted. 38 Hypertensive stroke was also found to be a statistically significant predictor of inhospital fatality during hospitalisation by univariable and multivariable models with OR 7.85 and OR 31.17 respectively. Majority of strokes can be prevented by life style modification and tight BP management. Furthermore very few data in Africa exist on predictors of 3-months fatality for hypertensive emergencies. Hypertensive encephalopathy was a significant positive predictor of 3 months fatality (OR 2.62, CI 1.04–6.62), p=0.04 by univariable analysis as well as by multivariable analysis (OR 4.42[1.41-13.84], p=0.01. This is similar to a study done on neurological patients with acute severe hypertension attending emergency department or ICU where fatality at 90 days was statistically significantly higher in neurological than in non neurological patients and was associated with high frequency of neurological deterioration (30). Hypertensive emergency with impaired renal function was also a predictor of fatality rates (OR 6.40, CI 2.06-19.84), p= 0.001 by multivariate logistic regression. This was initially underestimated in our setting; therefore emphasis should be put on kidney diseases in terms of diagnostics and research. 39 CHAPTER SIX 6.1 CONCLUSION Hypertensive emergency is one among common causes of admission among patients admitted to BMC medical wards and is associated with high fatality rates, 30% in hospital and 52% at three months post discharge. The most common forms of hypertensive emergency include retinopathy, encephalopathy, pulmonary oedema and impaired renal function. Factors commonly associated with hypertensive emergency include female gender, as well as age above 45 years. Predictors of in-hospital fatality rate among patients with hypertensive emergencies include hypertensive stroke and hypertensive emergency with impaired renal function which are both associated with a 30 times increased odds of death. Predictors of 3-months fatality rate among patients with hypertensive emergencies include hypertensive emergency with impaired renal function and hypertensive encephalopathy associated with 6 and 4 times increased odds of deaths respectively. 40 6.2 LIMITATIONS This was a single centre study involving a referral hospital population therefore results may not be generalised to other health facilities or to the general population. Some confirmatory investigations such as CT scan were not possible in all cases as well as cardiac biomarkers could not be done due to expenses. It was difficult in some of the cases to know whether end organ damages in this study were from the currently severely elevated blood pressure, old previous lesion or a result of some other chronic diseases. 41 6.3 RECOMENDATIONS All patients should be educated on importance of consistence use of medication on discharge so as to reduce the case fatality rate post discharge, which is unacceptably high (more than 50% at three months). In order to reduce fatality rates among patients with hypertensive emergencies, screening for kidney disease as early as possible seems essential. There is a need of educating the community on importance of lifestyle modification such as dietary modification and exercise so as to reduce the risks of hypertension, also to have habit of checking their blood pressures for early detection and treatment so as to avoid the complications of hypertension which are fatal. 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Determinants of target organ damage in black hypertensive patients attending primary health care services in Cape Town: the Hi-Hi study. American Journal of Hypertension. 2008 Aug;21(8):896–902. 24. Lip GY, Beevers M, Beevers DG. Does renal function improve after diagnosis of malignant phase hypertension? Journal of Hypertension. 1997 Nov;15(11):1309–15. 25. Roubsanthisuk W, Wongsurin U, Buranakitjaroen P. Hypertensive emergencies remain a clinical problem and are associated with high mortality. Journal of the Medical Association of Thailand = Chotmaihet thangphaet. 2010 Jan;93 Suppl 1:S54–61. 26. González Pacheco H, Morales Victorino N, Núñez Urquiza JP, Altamirano Castillo A, Juárez Herrera U, Arias Mendoza A, et al. Patients with hypertensive crises who are admitted to a coronary care unit: clinical characteristics and outcomes. Journal of Clinical Hypertension. 2013 Mar;15(3):210–4. 27. Katz JN, Gore JM, Amin A, Anderson F a, Dasta JF, Ferguson JJ, et al. Practice patterns, outcomes, and end-organ dysfunction for patients with acute severe hypertension: the Studying the Treatment of Acute hyperTension (STAT) registry. American Heart Journal. Mosby, Inc.; 2009 Oct;158(4):599– 606.e1. 28. Gore JM, Peterson E, Amin A, Anderson FA, Dasta JF, Levy PD, et al. Predictors of 90-day readmission among patients with acute severe hypertension. The cross-sectional observational Studying the Treatment of Acute hyperTension (STAT) study. American Heart Journal. 2010 Sep;160(3):521–527.e1. 29. Arodiwe EB, Ike SO, Nwokediuko SC. Case fatality among hypertensionrelated admissions in Enugu, Nigeria. Nigerian Journal of Clinical Practice. 2009 Jun;12(2):153–6. 30. Mayer SA, Kurtz P, Wyman A, Sung GY, Multz AS, Varon J, et al. Clinical practices, complications, and mortality in neurological patients with acute severe hypertension: the Studying the Treatment of Acute hyperTension registry. Critical Care Medicine. 2011 Oct;39(10):2330–6. 31. Vuylsteke A, Vincent J, De La Garanderie DP, Anderson FA, Emery L, Wyman A, et al. Characteristics, practice patterns, and outcomes in patients with acute hypertension: European registry for Studying the Treatment of Acute hyperTension (Euro-STAT). Critical Care. BioMed Central Ltd; 2011 Jan;15(6):R271. 45 APPENDICES APPENDIX 1: QUESTIONNAIRE Thank you for participating in our study. I will read each question loud and wait for your response. For some questions I will also read loud some answers from which you can choose. Please take as long as you need to remember or think about your answer. If a question is unclear, please say, I will repeat and explain it. Please remember all your answers will be kept confidential and this questionnaire does not have your name on it. First, I would like to ask you some questions about yourself and socio-economic status Q Code Questions and Filters Coding Categories 01 INITIAL Write interviewer’s Initials Interviewer initials 02 DATE Write date of interview |__|__| |__|__|__| |__|__|__|__| N Day 03 |__|__|__| Month INTID Enrolment ID number |__|__|__| INTNU BMC number |__|__|__|__|__|__|__|__| 46 Year Q Code Questions and Filters Coding Categories PHONE Contact phone number(s) |__|__|__|__|__|__|__|__|__|patient N 05 |__|__|__|__|__|__|__|__|__|__|N/kin |__|__|__|__|__|__|__|__|__|__|N/kin or close relative/neighbour 06 SEX Sex Male 1 Female 2 07 AGE Age 08 ETHN What is your ethnic background? African 1 09 EDLEV |__|__|__| Years Asian 2 others 3 What is the highest level of Non or incomplete primary school formal education you have 1 Complete primary school 2 Secondary school 3 University/ college 4 completed? 47 Q Code Questions and Filters Coding Categories EMPL Which of the following best Government or Business employee N 10 describes your main work status 1 Self employee (Petty trader) 2 Farmer (Peasant) 3 in the past 12 months? What is the source of water you Tape water are using? 11 12 ELEC Lake/pond water TOILET 2 Do you have Electricity inside YES your home? 13 1 1 NO 2 What type of toilet do you use at Modern flash toilet home? Pit latrine 1 2 Now I am going to ask you some question about various health behaviors. This includes things like smoking, drinking alcohol etc QN Code Question and filters Coding categories 14 TOB1 Have you ever smoked cigarettes, cigar or Yes 1 48 QN Code Question and filters Coding categories pipes? No Years |__|__| 2 ( skip to Qn 17) 15 TOB2 Duration of smoking 16 TOB4 On average, how many cigarettes do you Cigarettes └─┴─┘ smoke each day? 17 ALC1 Have you ever consumed an alcoholic Yes 1 drink such as beer, wine, spirits, No 2 (skip to QN 22) fermented cider or local made? 18 ALC2 Before you became hypertensive, how many occasions did you have at least one └─┴─┘ alcoholic drink? 19 ALC3 In that time above, when you drank alcohol, on average, how many standard drinks └─┴─┘ alcoholic drinks did you have during one drinking occasion? Duration? 20 ALC4 During the past 30 days, on how many occasions did you have at least one 49 duration(yrs) └─┴─┘ QN 21 Code ALC5 Question and filters Coding categories alcoholic drink? └─┴─┘ Duration of alcohol use Years └─┴─┘ HISTORY OF RAISED BLOOD PRESSURE 22 HBP1 Have you ever had your blood pressure Yes measured by a doctor or other health 1 No 2 worker? 23 HBP2 Have you ever been told by a doctor or Yes other health worker that you have raised 1 No 2 blood pressure or hypertension? 24 HTDR1 Have you ever been prescribed any drugs YES for hypertension? 25 HTDR2 NO In the past 2 weeks, have you taken drugs Yes (medication) for hypertension? 26 HTTH No Have you ever seen a traditional healer for Yes 50 1 2 1 2 1 QN Code 27 Question and filters Coding categories raised blood pressure or hypertension? No 2 HBTHE Are you currently taking any herbal or Yes traditional remedy for your raised blood 1 No 2 pressure? 28 HXDM Have you ever been told by a doctor or Yes other health worker that you have raised 1 No 2 blood sugar or diabetes? SECTION4. PHYSICAL MEASUREMENTS QN Code Question Response 29 HEIGH Height Centimetres (cm) 30 Weight WEIGH Kilograms (kg) └─┴─┴ ─┘. └─┘ └─┴─┴ 31 PREG 32 33 WC HC Yes 1 No 2 in Centimetres (cm) └─┴─┴ For women: Are you pregnant? Waist circumference in Centimetres (cm) Hip circumference 51 ─┘.└─┘ └─┴─┴─┘ QN Code Question Response Reading 1 Systolic mmHg└─┴─┴─┘ BP on the Right arm Diastolic mmHg└─┴─┴─┘ Reading 2 Systolic mmHg└─┴─┴─┘ BP on the left arm Diastolic mmHg └─┴─┴─┘ Reading 3 Systolic mmHg└─┴─┴─┘ BP on the arm with higher BP Diastolic mmHg└─┴─┴─┘ HR Heart rate (beats per minute) Reading └─┴─┴─┘ RBG Random blood glucose mmol/L┴─┴─┘.└─┘ SCRT1 Serum creatinine on admission 34 BP1 35 BP2 36 BP3 37 38 39 (ummol/L)└─┴─┴─┘.└─┘ 40 (ummol/L)└─┴─┴─┘.└─┘ 1 SCRT3 Serum creatinine at 3month Not done 41 Urine output in the first 24 in UROUT the hospital |__|__|__|__| mls 52 2 FOR THE PAST 24HRS IS THERE A HISTORY OF? 42 RUOP 1 NO 2 YES 1 NO 2 YES 1 NO 2 YES 1 NO 2 YES 1 NO 2 Chest pain? 47 SOB YES Headache? 46 CHSTP 2 Impaired vision? 45 HDZ NO Loss of consciousness? 44 IMPVIS 1 Decreased urine output? 43 LOC YES Shortness of breathing? 48 GCS Glasgow Coma Score. ┴─┴─┘ S02 SO2 (%)└─┴─┴─┘ 49 50 DSAB YES 1 NO 2 Displaced apex beat 51 CREPS Crepitations in both lung bases YES 1 on examination. 2 NO 53 52 CXR Normal 1 Pulmonary oedema 2 Cardiomegally 3 CXR findings Normal Other............................4 1 53 STEMI Others...................2 4 ECG findings Non-specific STdepression 3 ECG 54 Non-specific TWIs 4 LVH (cornel criteria) 5 Fundoscopy findings (to be FUNDO confirmed by opthalmologist) 55 CTSCN CT scan findings( if done) 56 ECHO ECHO findings 54 Normal 1 Mild retinopathy 2 Moderate retinopathy 3 Normal CT scan Severe retinopathy 14 Hemorrhagic stroke 2 Ischaemic stroke 3 Mixed stroke 4 Diffuse cerebral edema 5 SWMA 1 lesions Space occupying 6 Thrombus 2 LVH 3 HHD 4 57 ┴─┴─┘ days DURTN Duration of hospital stay 58 IHOUT Died 1 Alive 2 Died 1 In hospital Outcome 59 3MOUT 3 months outcome Follow Alive up mortality DIED/ALIVE 2 60 Clinic visit last 3 month? ALIVE If alive Y/N Readmission in last 3month Y / N Still on medication? 55 Y/N APPENDIX 2: INFORMED CONSENT – ENGLISH VERSION You are invited to participate in a study on hypertensive emergencies. We are studying the prevalence, pattern, predictors and outcome of hypertensive emergencies among patients admitted at our hospital, Bugando medical centre. Participation is strictly voluntary and unwillingness to participate in this study will not affect your treatment in one way or another. If you are willing to participate, you need to sign this form indicating your willingness. You may withdraw from the study at any time and such a decision will be respected, and will not affect your treatment. Participants will undergo an interview, a physical examination, a urine test, a blood test, ECG, and CXR. Other investigations will depend on the condition of the patients. The blood test may involve some pain at the time of drawing the blood sample but overall, there is no physical harm expected from participation. To minimize risk of microbial infections, the needle site will be sterilized. When the results of the research are published or discussed in conferences or used in any form, no information will be included that would reveal your identity. Participants will benefit from this study by knowing their status and if they have any hypertensive related complications they will receive treatment according to Tanzanian guidelines. In case of any questions regarding this study, please contact: Dr. GRAHAME MTUI, principal Investigator, Catholic University of health and allied sciences, Dept of Internal Medicine: P.O.Box 1464, Mwanza. Tel: +255-754936350. 56 Or in any case of any information about your rights as a study participant, please contact; Prof. Kongolla, Director, Research and Publications Committee, Catholic University of health and allied sciences. P.O.Box 1464, Mwanza. I have understood the above information. I understand that my participation is voluntary and that I am free to withdraw at any time, without giving any reason, without my medical care or legal rights being affected. ____________________ _______________ Signature of Patient / Next of Kin Date 57 APPENDIX 3: INFORMED CONSENT – KISWAHILI VERSION Ninafanya utafiti miongoni mwa watu wenye ugonjwa wa msukumo mkubwa wa damu. Utafiti huu unafanyika kwa wagonjwa wote wanaolazwa kwenye idara ya tiba katika hospitali ya rufaa ya Bugando Mwanza. Watakaokubali kushiriki itawapasa kusaini fomu kuonyesha kukubali kwao. Aidha, tutawahoji maswali kadhaa, kuwapima na kuchukua mkojo pamoja na damu kwa ajili ya utafiti huu. Faida utakayopata katika utafiti huu ni kujua kiwango chako cha msukumo wa damu na kama kuna madhara yanayotokana na kuwa na msukumo mkubwa wa damu mwilini mwako mfano matatizo kwenye ubongo, macho, mapafu moyo pamoja na kwenye figo. Utapatiwa matibabu ya madhara hayo kilingana na mwongozo wa nchi yetu. Mbali na faida, utasikia maumivu kidogo kwa kuchomwa sindano wakati wa kuchukua damu kwa ajili ya vipimo. Taarifa zote utakazotupatia zitakuwa siri na zitatumika tu kwa ajili ya kuboresha huduma na utabibu kwa wagonjwa. Ushiriki wako ni wa hiari kabisa, aidha unayo haki ya kujitoa katika utafiti huu wakati wowote ule utakapojisikia kufanya hivyo. Uamuzi wako kushiriki ama kutoshiriki hautaathiri hata kidogo haki yako ya kupata huduma na tiba kama mgonjwa mwingine yeyote yule. Iwapo utakuwa na swali lolote kuhusu utafiti huu au kama umedhurika, unaweza kuwasiliana na Dr. GRAHAME MTUI mtafiti mkuu; Chuo Kikuu Cha Sayansi za Afya na Tiba Bugando; Idara ya Tiba; SLP 1464, Mwanza. Simu: +255-754-936350 58 Au endapo utakuwa na swali lolote kuhusu haki zako kama mshiriki katikia utafiti huu wasiliana na: Prof Kongola; Mkurugenzi wa Kamati ya Tafiti na Matoleo Chuoni, Chuo Kikuu Cha Afya na Tiba Bugando, SLP: 1464, Mwanza. Nitafurahi kama utakubali kushiriki katika utafiti huu. MTAFITI Mimi ____________________________ nathibitisha kuelewa maelezo yaliyoandikwa hapo juu na kuridhika na maelezo niliyopewa kwa maswali yangu yote. Nami, kwa hiari yangu mwenyewe, bila kushurutishwa na mtu, ninakubali kushiriki kwenye utafiti huu. Mgonjwa/Msindikizaji:______________ Tarehe:________________ 59 60 APPENDIX 4: ETHICAL CLEARANCE CERTIFICATE 61