RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA,BANGALORE
M.D.(BIOCHEMISTRY)
RAJARAJESWARI MEDICAL COLLEGE AND HOSPITAL
BANGALORE-560074.
Study of serum uric acid and vitamin d levels in essential hypertension AT RAJARAJESWARI MEDICAL COLLEGE AND HOSPITAL
By:
DR. MANJULA H S
PG IN BIOCHEMISTRY,
DEPARTMENT OF BIOCHEMISTRY,
RAJARAJESWARI MEDICAL COLLEGE,
BANGALORE-5
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA
BANGALORE.
ANNEXURE - II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / Name of the candidate AND ADDRESS (in block letters) / DR. H.S.MANJULANO 746/5, 9TH CROSS, M.C.LAYOUT
VIJAYANAGAR
BANGALORE – 560040
2. / name of the institution / RAJARAJESWARI MEDICAL COLLEGE AND HOSPITAL,
KAMBIPURA, MYSORE ROAD,
Bangalore – 560074
3. / Course of study and subject / M D (Bio-Chemistry)
4. / Date of admission to course / 30-05-2013
5. / title of the topic / Study of serum uric acid and vitamin d levels in essential hypertension
6. / Brief resume of the intended work:
6.1 : Need for the study:
Hypertension is sustained elevation of systemic arterial pressure. Elevated blood pressure is defined as systolic blood pressure >140mm hg and /diastolic blood pressure >90mmhg. About 95% cases fall in the category of essential hypertension. Pathogenesis of essential hypertension is multifactorial. Genetic factors play an important role. Others factors involved in pathogenesis of essential hypertension are sympathetic nervous system hyperactivity, defect in natriuresis, elevated levels of intracellular Na+, Ca+2 and high plasma renin activity which can account for approximately 10%of essential hypertension. Hypertension long recognized as a risk factor for both stroke and myocardial infarction, is an important target for preventive intervention. 1
Essential hypertension remains a major modifiable risk factor for cardiovascular disease despite important advances in our understanding of its pathophysiology and the availability of effective treatment strategies. High blood pressure increases risk of cardiovascular disease for millions of people worldwide and there is evidence that the problem is only getting worse. In the past decade age adjusted rates of stroke incidence has risen, and the slope of the age adjusted rate of decline in coronary artery disease has leveled off. The incidence of end stage renal disease and prevalence of heart failure have also increased. A major contributor to these trends is inadequate control of BP in the hypertensive population. There is strong positive and continuous correlation between blood pressure and risk of cardiovascular disease (stroke myocardial infarction and heart failure) renal disease and mortality.2
Essential hypertension tends to be familial and is likely to be the consequence of an interaction between environmental and genetic factors. The prevalence of essential hypertension increases with age and individuals with relatively high blood pressure at younger ages are at increased risk for the subsequent development of hypertension. It is likely that essential hypertension represents a spectrum of disorders with different underlying pathophysiologies. In the majority of patients with established hypertension, peripheral resistance is increased and cardiac output is normal or decreased; however, in younger patients with mild or labile hypertension, cardiac output may be normal.3
When plasma renin activity [PRA] is plotted against 24hr sodium excretion 10-15% of patients have high PRA and 25% have a vasoconstrictor form of hypertension whereas low-renin patients may have volume dependent hypertension. Inconsistent association between plasma aldosterone and blood pressure have been described in patients with essential hypertension. The association between aldosterone and blood pressure is more striking in African Americans, and PRA tends to be low in hypertensive African Americans. This raises the possibility that subtle increases in aldosterone may contribute to hypertension in at least some groups of patients who do not have overt primary aldosteronism.3
URIC ACID
Uric acid is the end product of purine metabolism in humans. Humans convert the major purine nucleosides, adenosine and guanosine to Uric acid through intermediates1. Over production of Uric acid causes gout, renal insufficiency. Hyperuricemia is also associated with hypertension, nephrolithiasis, pyelonephritis etc.1 The association of hyperuricemia with hypertension has long been recognized. Decreased renal blood flow and decreased tubular secretion of uric acid have been associated with hyperuricemia with hypertension.4 Experimental evidence supports a causative role for uric acid in the pathogenesis of hypertension.4
Recent experimental and clinical evidence supports the possibility that an elevated uric acid level may lead to hypertension. Numerous studies have reported that hyperuricemia carries an increased relative risk for hypertension developing within five years, independent of other risk factors. Studies of uric acid levels and the development of hypertension have generally been consistent, continuous, and of similar magnitude. Hyperuricemia is also common among adults prehypertension, especially when microalbuminuria is present. The observation that hyperuricemia precedes the development of hypertension indicates that it is not simply a result of hypertension per se.6
Melvil R Hayden and Suresh C Tyagi explained the potential mechanisms involved with the association of hyperuricemia and hypertension include the following.
1. Decreased renal blood flow (decreased glomerular filtration rate) stimulating urate reobsorption.
2. Microvascular (capillary) disease resulting in local tissue ischemia.
3. Ischemia with associated increased lactate production that blocks urate secretion in the proximal tubule and increased uric acid synthesis due to increased RNA-DNA break down and increased purine (adenine and guanine) metabolism, which increases uric acid and ROS through the effect of xanthine oxidase (XO).
4. Ischemia induces increased xanthine oxidase production and increased serum uric acid and reactive oxygen species (ROS)7
Vitamin D
There are two main sources of Vitamin D available to humans, from direct exposure to sunlight (Solar UV-B) and from the diet or dietary supplements. Solar UV-B radiation penetrates the skin and converts 7-dehydrocholestrol to previtamin D3, inturn, converts rapidly to Vitamin D3.9
Vitamin D deficiency is widely prevalent across all ages, races, geographical regions and socioeconomic strata. It plays an important role in skeletal development and calcium homeostasis. Several recent studies suggest its association with diabetes, hypertension, cardiovascular diseases, certain types of malignancy and immunologic dysfunction.9
Hydroxylation of 25(OH) D to 1.25 dihydroxy Vitamin D and signaling through the Vitamin D receptor occur in various tissues not traditionally involved in calcium homeostasis. Laboratory studies indicate that 1,25 dihydroxy Vitamin D suppresses renin expression and vascular smooth muscle cell proliferation; Clinical studies demonstrate an inverse association between ultraviolet radiation, a surrogate marker for Vitamin D synthesis, and blood pressure.10
The aim of the study is to estimate serum uric acid and vitamin D levels in patients with essential hypertension. To evaluate their role in etiopathogenesis of essential hypertension and to prevent further complications like cardiovascular ,renal disorders and stroke.
6.2 Review of literature:
Bashiara A Charles et al proved in their study that hyperuricemia has been implicated in multiple physiologic outcomes including hypertension renal dysfunction. Hyperuricemia is suspected to influence the development of hypertension via its role in vascular endothelial cell dysfunction and activation of rennin angiotensin system.
Elevated serum Urid acid level has been associated with increased risk for developing hypertension (NAS) Todd et al.
Melvin R Hayden et al proved hypertension is strongly associated with hyperuricemia. Serum Uric acid levels are elevated in hypertension and present in 25% of untreated hypertensive subjects, 50% of subjects taking diuretics. Mechanism -> 1. Decrease renal blood flow (decreased glomerular filtration rate) stimulates urate reabsorbtion. 2. Microvascular (Capillary) disease resulting in local tissue ischemia. 3. Ischemia associated with increased lactate production that blocks urate secretion in proximal convoluted tubule and increased Uric acid synthesis due to RNA-DNA breakdown and increased purine metabolism. 4. Ischemia induces increased xanthine oxidase production and serum uric acid levels.
In 1951 Gertler et al sparked the interest of the medical community when they reported an increased association Serum Uric acid with Cardiovascular disease. This was followed rapidly by other reports linking hyperuricemia to hypertension as well as stroke, myocardial infarction and heart failure.
The study published by Cannon et al in the New England journal of medicine in 1966 reestablished the strong relationship between Uric acid and hypertension.
Vitamin D:
Martin et al formed that a low Vitamin D level was associated with higher risk of having hypertension.
Formen et al prospectively investigated the independent association between plasma 25(OH) D levels and risk of incident hypertension.
Vitamin D effects on the renin angiotension aldosterone system have been extensively investigated by experimental studies by Katharina Kienrich et al.
Genetic research done by Dr. Vimal Karani [Institude of child health, University college London UK]. Showed through observation studies that low 25(OH) D concentrations were likely to be associated with increases in blood pressure and hypertension.
6.3 Objectives of the study:
1) To study serum uric acid and Vitamin D level in essential Hypertension.
2) To study the above parameters in control groups and compare both the groups.
7. / Materials and Methods:
7.1 Source of data:
Inclusion criteria
1. Fifty essential Hypertension patients attending general medicine OPD, Rajarajeswari Medical College and Hospital, Bangalore.
2. Fifty normal subjects without essential hypertension between the age group of 25-75 years.
Exclusion criteria:
3. Patients with secondary hypertension and complications of Cardiovascular, renal disorders and stroke.
4. History of multiple transfusions, renal disease.
5. Pregnancy, anaemia and history of any other medical or surgical illness.
CONTROL GROUP:
1) Normal volunteers in the age group of 25-75years will be screened for same parameters which are done for cases.
7.2 Method of collection of data
1. Blood sample from the study and control group will be drawn under full aseptic precautions, after obtaining informed consent.
2. Fasting blood sample will be collected in Clot Activator and fluoride EDTA vacuum evacuated tubes from both study and control group under full aseptic precautions after obtaining informed consent.
The biochemical parameters are estimated using the following methods:
1. 25 (OH) D by chemiliuminiscence
2. Serum Uric acid by enzymatic photometric method by fully automated analyser.
Statistical Analysis:
The data collected will be tabulated and analyzed using descriptive statistics namely frequency, percentage and analytical studies to find out the difference using the ‘t’ test.
7.3 Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so please describe briefly.
Yes, the study requires investigations to be conducted on patients as mentioned above after obtaining the informed consent from patients. There will be no financial liabilities on patients.
7.4 Has ethical clearance been obtained from your institution in case of -.-?
Yes, the ethical clearance has been obtained from the ethical clearance committee of Rajarajeswari Medical College and Hospital, Bangalore.
8. / List of references:
1. Javeed.S, Khawaja.T. M et al, 2005. “The Effect of Essential Hypertension on Serum uric acid level”. Bio-15Vol 21July.
2. Carretero.O.A, Oparil.S, 2000. “Clinical Cardiology; New frontiers”. AHA journals:329-335.
3. Longo, Fauci, et al. “Essential hypertension”. Harrison principle of internal medicine 18th edition vol 2:2047 – 48.
4. Perlstein T.S,Gumieniak O, et al,2006. “Uric Acid and Development of Hypertension: Normative Aging Study”. AHA journal, 1031 – 1036.
5. Charles.B.A, Sheiner D, et al, 2001. “A Genome-wide association study of Serum Uric acid in African Americans”. BMC Medical Genome.
6. Feig.D.I, Hee Kang.D, et al, 2008. “ Uric acid and Cardivasculor Risk”. N Engl J Med. 359 (17):1811 – 1821.
7. Hayden.M.R, Tyagi.S.C. 2004. “Uric Acid: A new look at an old risk marker for Cardivascular disease, metabolic syndrome, type 2 diabetes mellitus: The urate redox shuttle”. Nutrition & Metabolism Bio med central.
8. Mazalli. M, Kanbay. M, et al. 2010 “Uric Acid and Hypertension: cause or effct?”. Curr Rheumatol rep 12:108-117.
9. Ullah.M. I, UWaifo.G.I, et al. 2010. “ Does vitamin D deficiency cause hypertension? Current evidence from clinical studies and potential mechanisms”. International Journal of Endocrinology. doi: 10.1155/2010/579640
10. Forman.J.P, Giovannucci. E, et al. 2007. “Plamsa 25-Hydroxyuitamina D levels and risk of Incident Hypertension”. Hypertension AHA 107.087288. 49:1063-1069.
11. Kienreich. K, Grubler. M, et al. 2013. “Vitamin D, arterial hypertension and cerebrovascular disease”. IJMR, 137(4): 669-679
12. Vimal. K, 2013. “Genetic research clarifies link between hypertension and vitamin D deficiency. (Institute of child health, University College London UK)
9. / Signature of the candidate
10. / Remark of the guide
11. / NAME AND
DESIGNATION
(in block letters)
11.1 GUIDE
11.2 SIGNATURE
11.3 CO-GUIDE
11.4 SIGNATURE
11.5 HEAD OF THE DEPARTMENT
11.6 SIGNATURE
12 / 12.1 REMARKS OF THE PRINCIPAL
12.2 SIGNATURE