حنين عبدالكريم محمدباقر الشماع

Abstract Background Hypertension is a complicated condition in which many mechanisms collaborate, causing cardiovascular and cerebrovascular implications that are now among the most common causes of death globally. Currently, 1.13 billion individuals are suffering from hypertension, as reported by the World Health Association. The level of incidence of hypertension rises substantially with age, and due to the continuing aging of the population around the world, both the overall incidence of hypertension and the adverse outcomes continue to keep growing. Serum magnesium plays a role in controlling blood pressure by its vasodilatory effect through competition for binds site of calcium. Some clinical trials and reports suggest that hypertensive individuals possess deficient serum magnesium levels that connect to adverse consequences on blood pressure levels. However, magnesium deficiency is linked to a higher risk of heart failure, strokes, and cardiovascular disease, as well as a worsening of their other medical conditions. Aim of the study 1- To study the relation between serum magnesium level and severity of hypertension. 2- To study the impact of serum magnesium level on the prevalence of coronary artery disease and stroke in hypertensive patients. 3- To assess the effect of serum magnesium level on the lipid level. Patients and Methods This study is a cross-sectional study that included 150 hypertensive patients, 102 females and 48 males, aged 25-75 years with mean ± SD (59.53 ± 10.4). All the patients were screened for evidence of coronary artery diseases and stroke. Measurements of serum magnesium levels were done for each participant by the xylidyl blue technique (magnesium liquicolor-human reagent), lipid profile, blood urea, and creatinine level measurements by the chemical biochemistry analyzer Mindray. Results There was a significant inverse relationship between the number of antihypertensive drugs and mean serum magnesium level. The study demonstrates that serum magnesium level is significantly reduced in patients who were administered beta blockers. There was no significant effect of age, sex, and smoking on mean serum magnesium level. However, mean serum magnesium level was significantly less in obese patients (p < 0.05). Although the result shows a significant difference in serum magnesium level between controlled and uncontrolled hypertensive patients, there was no significant relation between mean serum magnesium level and associated comorbid conditions, including DM, IHD, and CVA (p > 0.05). Moreover, the statin therapy (lipid-lowering agents) shows no significant effect on mean serum magnesium level. In addition, there was no significant association between serum lipid profile (cholesterol, triglyceride, HDL, and LDL) and mean serum magnesium level (p > 0.05). Conclusion This study demonstrates that in hypertensive patients, serum magnesium levels were significantly low in patients with multiple antihypertensive drugs and those on beta-blockers; serum magnesium levels were significantly low in uncontrolled hypertensive patients compared to controlled hypertensive patients; and serum magnesium levels were significantly reduced in obese hypertensive patients. List of Contents Content Page Abstract (in English) I-III List of contents IV-VII List of tables VII List of figures VIII List of abbreviations IX-XII CHAPTER ONE: INTRODUCTION 1-5 1.1. Hypertension 1 1.2. Aims of the study. 5 CHAPTER TWO: REVIEW OF LITERATURE 6-22 2.1 Blood pressure physiology 6 2.2 Hypertension 6 2.2.1 Hypertension epidemiology 7 2.2.2 Hypertension pathophysiology 8 2.2.3 Hypertension diagnosis 9 2.2.4 Hypertension comorbidities and complication 10 2.2.5 Hypertension management 13 2.3 Magnesium 14 2.3.1 Magnesium homeostasis 15 2.3.2 Magnesium cardiovascular mechanisms 15 2.3.3 Cardiovascular complication associated with magnesium deficiency 19 CHAPTER THREE: PATIENTS AND MATERIALS 23-30 3.1. patients 23 3.1.1 Research papulation 23 3.1.2 Apparatuses and equipment 24 3.2 Methods 25 3.2.1 Full medical history 25 3.2.2 Clinical examination 26 3.2.2.1 Blood pressure assessment 26 3.2.2.2 The determination of the body mass index 27 3.2.3 Collection of blood sample 27 3.2.4 Biochemical analysis 27 3.2.4.1 Magnesium measurement 27 3.2.4.2 Analyses of lipid profile, serum creatinine, and blood urea 28 3.2.5 Study design 29 3.2.6 Evaluation of statistics 30 CHAPTER FOUR: RESULTS 31-38 4.1 Demographic data 31 4.2 The effect of age, sex, BMI, and smoking on mean serum magnesium level. 32 4.3 The relation between mean serum magnesium level and number of antihypertensive drugs. 33 4.4 The relation between mean serum magnesium level and the type of antihypertensive drugs 34 4.5 The relation between mean serum magnesium level and statin therapy 35 4.6 The association between lipid profile and mean serum magnesium level 35 4.7 The relation between mean serum magnesium level and associated comorbid condition 36 4.8 The effect of mean serum magnesium level on the control of hypertension. 38 CHAPTER FIVE: DISCUSSION 39-51 5.1. The effect of age, sex, BMI, and smoking on mean serum magnesium level. 39 5.2. The relation between mean serum magnesium level and number of antihypertensive drugs. 41 5.3. The relation between mean serum magnesium level and the type of antihypertensive drugs 43 5.4. The relation between mean serum magnesium level and statin therapy 44 5.5. The association between lipid profile and mean serum magnesium level 45 5.6. The relation between mean serum magnesium level and associated comorbid condition 46 5.7. The effect of mean serum magnesium level on the control of hypertension. 50 CONCLUSIONS AND RECOMMENDATIONS 52-53 LIMITATIONS 54 CHAPTER SIX : REFERANCES 55-67 APPENDICES 68-74 Abstract (in Arabic) 75 Thesis title (in Arabic) 77 List of Tables Table no. Table Title Page Table 2-1 Categorization of hypertension based on office blood pressure measurement 10 Table 3.1 Equipment, chemical, and instruments. 25 Table 3.2 Blood pressure categorizations 26 Table 4.1 Demographic and clinical characteristics of the patients 31 Table 4.2 The effect of age, sex, BMI, and smoking on mean serum magnesium level. 32 Table 4.3 The relation between mean serum magnesium level and the type of antihypertensive drugs 34 Table 4.4 The association between lipid profile and mean serum magnesium level 36 Table 4.5 Comparison between mean serum magnesium level and associated comorbid condition 37 List of Figures Figure no. Figure Title Page Figure 2.1 Complication of atherosclerosis in coronary artery diseases 12 Figure 2.2 Magnesium antihypertensive function 18 Figure 2.3 Insulin resistance lowers the DCT's capacity to reabsorb Mg2+ through the prourine in type 2 diabetes 20 Figure 3.1 Spectrophotometer V-1000 (AOELAB-China) analyzer for magnesium assessment. 28 Figure 3.2 Chemical biochemistry analyzer Mindray (BS-230-Korea) for lipid profile assessment. 29 Figure 4.1 The relation between mean serum magnesium level and number of antihypertensive drugs. 33 Figure 4.2 The relation between mean serum magnesium level and statin therapy 35 Figure 4.3 The relation between mean serum magnesium level and number of co-morbidities (DM , CVA , IHD) 37 Figure 4.4 The effect of mean serum magnesium level on the control of hypertension. 38 List of abbreviations Abbreviations Meaning ABPM Ambulatory blood pressure monitoring ACC/AHA American College of Cardiology/ American Heart Association ACEi Angiotensin-converting enzyme inhibitors AF Atrial fibrillation AMI Acute myocardial infarction ARBs Angiotensin receptor blockers ATP Adenosine triphosphate AT-2 Angiotensin 2 receptor B.U Blood urea BBB Blood-brain barrier BMI Body mass index BP Blood pressure Ca2+ Calcium CAD Coronary artery disease CCDs Calcium channel blockers CHD Coronary heart diseases CKD Chronic kidney disease CVA Cerebrovascular accident CVD Cardio vascular disease DBP Diastolic blood pressure DCT Distal convoluted tubules DM Diabetes mellitus DNA Deoxyribonucleic acid ECG Electrocardiogram eGFR Estimated glomerular filtration rate eNOS Endothelial NO synthase ESRD End-stage renal disease HDL High density lipoprotein HF Heart failure HDL-C High density lipoprotein cholesterol HMG-CoA 3-Hydroxy-3-Methylglutaryl-Coenzyme A IHD Ischemic heart diseases IL-6 Interleukin-6 IL-8 Interleukin-8 IP3 inositol-1,4,5-trisphosphate K+ Potassium LCAT lecithin–cholesterol acyl transferase LDL Low density lipoprotein L-Glu L-glutamate LMICs Low- and middle-income countries LVH Left ventricular hypertrophy Mg+ Magnesium MI Myocardial infarction Na+ Sodium NaCl Sodium chloride NCDs Non-communicable diseases NMDA N-methyl-D-aspartate NO Nitric oxide PAD Peripheral artery diseases PCT Proximal convoluted tubules PVN hypothalamic paraventricular nucleus RAAS Renin-angiotensin-aldosterone system RAS Renin-angiotensin system RDA Recommended dietary allowance RNA Ribonucleic acid ROS Reactive oxygen species RVLM rostral ventrolateral medulla SBP Systolic blood pressure SD Standard deviation SGLT2is Sodium-glucose cotransporter 2 inhibitors SNS Sympathetic neural system TG Triglyceride TGF-β Transforming growth factor β TNF-α Tumor necrosis factor- α VSMCs vascular smooth muscle cells WHO World health organization