Thesis

1. PROTOCOL FOR SUBMISSION OF THESIS FOR THE DEGREE OFDOCTOR OF
MEDICINE ( M.D.MEDICINE)
TITLE OF THESIS
ESTIMATION OF URIC ACID IN HYPERTENSION AND ITS CORRELATIONWITH
GRADING OF HYPERTENSION AND CARDIOVASCULAR RISK
NAME OF THE CANDIDATE: DR. A.L.S.VARAPRASAD
DEPARTMENT OF MEDICINE
POST GRADUATE INSTITUTE OF MEDICAL EDUCATION AND RESEARCHSHARDA
HOSPITAL
GREATER NOIDA
DEPARTMENT OF MEDICINE SHARDA
HOSPITAL,GREATER NOIDA

2. Title of the Thesis : ESTIMATION OF URIC ACID IN HYPERTENSIONAND ITS CORRELATION WITH GRADING OF
HYPERTENSION AND CARDIOVASCULAR RISK
Signature:
Name of Candidate: Dr A.L.S.VARAPRASAD
Signature:
Name of Supervisor: Prof.(Dr.) A.K.GADPAYLE
DEPARTMENT OF MEDICINE
SHARDA HOSPITAL,GREATER NOIDA
Name of Co –Supervisor : Prof(Dr). Bhaskar Charana Kavi
Department of Biochemistry
SHARDA HOSPITAL,GREATER NOIDA
Signature :
Name of Head of Department : Dr. V.P.S.PUNIA
Head
Department of Medicine
SHARDA HOSPITAL,GREATER NOIDA
Signature:

3. UNDERTAKING
1. prevent irreversible adverse effects.
2. Research will be conducted by professionally competent persons.
Research will be conducted in a fair, honest, Impartial and transparent manner. Researcher will be accountable for maintaining
proper records. I/We abide by the ethical guidelines for biomedical research on human subject – (As per
The ICMR guidelines) while conducting the research project being submitted for Ethical Committee consideration.
1.The study does not include any new intervention or any drug trial.
2.Adequate number of patients will be available for the study.
3.Project is considered to be absolutely essential for the advancement of knowledge and for the benefit of all.
4.Only subjects, who volunteer for the project will be included. Their informed consent shall be obtained prior to commencement of the
researchproject and subjects will be kept fully appraised of all consequences.
5.Privacy and confidentiality of the subjects shall be maintained and withoutthe consent of the subject no disclosure will be made.
6.Proper precautions shall be taken so as to minimize risk and

4. 7.Research will be conducted keeping in view the public interest in large.
8.Research reports, materials and data will be preserved.
9.Result of the research will be made known through scientific publication.
10.Professional and moral responsibilities will be of the researchers directlyor indirectly connected with the research.
11.The protocol has been discussed in the department & hospital and hasbeen approved.
SUPERVISOR INVESTIGATOR
Prof.(Dr.) A.K.Gadpayle Dr A.L.S.VARPRASAD
Signature Signature
Co-Supervisor
Prof(Dr.) Bhaskar Charan Kavi
Signature

5. DECLARATION FROM THE CANDIDATE
I, Dr A.L.S.VARAPRASAD, Post Graduate Student, Department of Medicine,SHARDA HOSPITAL , hereby
declare that no similar study has been conducted in the last five years in sharda university,on the following subject “
estimation of uric acid in hypertension and its correlation with grading of hypertension and cardiovascular risk“& all
the work will be done by myself under the guidance of my supervisor & all the data will be genuine.
Signature
Dr A.L.S.VARAPRASAD

6. DECLARATION FROM THE SUPERVISOR
I, Dr. A.K.Gadpayle, Department of Medicine, SHARDA Hospital, hereby declare that facilities for work in
the subject of this thesis do exist in this Department/Hospital and will be provided to the candidate. I shall
guide the candidate and shall see the data being included in the thesis will be genuine and work will be done
by the candidate himself.
Signature
Prof.(Dr.) A.K.Gadpayle
SHARDA HOSPITAL,GREATER NOIDA

7. DECLARATION FROM THE CO-SUPERVISOR
I, Dr. Bhaskar Charana Kavi, Department of Bio Chemistry, SHARDA Hospital, hereby declare that facilities
for work in the subject of this thesis do exist in this Department/Hospital and will be provided to the candidate.
I shall guide the candidate and shall see the data being included in the thesis will be genuine and work will be
done by the candidate himself.
Signature
Prof(Dr). Bhaskar Charana Kavi
SHARDA HOSPITAL,GREATER NOIDA

8. CERTIFICATE
This is to certify that DR.A.L.S.VARAPRASAD is pursuing Doctor of Medicine in department of Medicine& is
permitted to conduct the study ESTIMATION OF URIC ACID IN HYPERTENSION AND ITS CORRELATION
WITH GRADING OF HYPERTENSION AND CARDIOVASCULAR RISK at sharda hospital,greater.noida
Signature
Name of Head of Department Dr.v.p.s.punia
Head
Department of Medicine
Sharda hospital,G.noida

9. INDEX PAGES
Introduction
Research Question
Hypothesis
Review of Literature
Aims and Objectives
Materials and Methods
Annexures
1.Proforma
2.References
3.Consent Form(English)
4.Consent Form(Hindi)
5.Patient Information Sheet (English)
6.Patient Information Sheet(English)

10. INTRODUCTION
Hypertension a major public health problem and risk factor for cardiovascular diseases in developed and
developing countries. Hypertension is the leading modifiable risk factor for cardiovascular mortality
worldwide. Hypertension is a multifactorial disease with interaction of multiple environmental and genetic
determinants. Hypertension causes high morbidity and mortality if untreated in adult population. The
treatment of hypertension not only protects individuals from hypertensive complications but also provides
the potential for a reduction in overall burden of cardiovascular disease mortality in the population (1).
Importance of prevention and treatment of hypertension should therefore be assigned a high priority to
reduce high risk of morbidity and mortality.
Raised serum uric acid has been reported to be associated with an increased risk of coronary heart disease
and is commonly encountered with essential hypertension, even untreated hypertension, and type 2 diabetes,
which are in turn associated with coronary heart disease (2)

11. Study reveals that hyperuricemia decreases renal blood circulation apparently a reflection of
nephrosclerosis. Compare to normotensive there is 5 times higher chance of occurring
hypertensive in 25-50% of individuals having hyperuricemia with untreated primary
hypertension.(3)In India relation of s. uric acid with severity of hypertension was carried
out(3)however correlation of s. uric acid in hypertension with cardiovascular events is not
studied hence this study is undertaken
RESEARCHQUESTION
Is there any association of serum acid levels with severity of Hypertension andincreased risk of
cardiovascular disease?
HYPOTHESIS
There is positive association of serum uric acid levels with severity ofhypertension and
increased risk of cardiovascular disease

12. REVIEW OF THE LITERATURE
HYPERTENSION
Benefits (minus the risks and costs) of action exceed the risks and costs (minus the
benefits) of inaction”(4) The best operational definition for hypertension is “the level at which the
Table-1) Classification of Blood Pressure
Based on the seventh report of the Joint National Committee on prevention, detection, evaluation and
treatment of high blood pressure (JNC 7 report) BP is classified into the following stages –
Classification Of BP For Adults > 18 years OLD (
Classification of BP Systolic BP mm hg Diastolic BP mm hg
Normal < 120 <80
Pre hypertension 120-139 80-89
Stage 1 hypertension 140-159 90-99
Stage 2 hypertension ≥ 160 ≥ 100

13. In contrast with the classification provided in the JNC VI report, a new category designated
prehypertension has been added and stages 2 and 3 have been Combined(5).
Patients with prehypertension are at increased risk for progression to hypertension; those in the 130/80
to 139/89 mm hg BP range are at twice the risk to develop hypertension as those with lower values(6)

14. Increased SUA in Hypertension
The mechanisms underlying the increase in SUA and its potential prognostic implications in patients with
essential hypertension are still not completely known. Uric acid, a final product of purine metabolism, is bound
for 5% to plasma proteins, is freely filtered at the glomerulus as a function of renal blood flow, is 99%
reabsorbed in the proximal tubule, secreted by the distal tubule, and subjected
to considerable postsecretory reabsorption. Fractional secretion of uric acid is about 7% to 10%
A direct association exists between SUA and renal vascular resistance in subjects with essential hypertension(7)
Uric acid is also commonly associated with hypertension. It is present in 25%
of untreated hypertensive subjects, in 50% of subjects taking diuretics, and in >75% of subjects with malignant
hypertension. The increase in serum uric acid in hypertension may be due to the decrease in renal blood flow that
accompanies the hypertensive state, since a low renal blood flow will stimulate urate reabsorption. Hypertension
also results in microvascular disease, and this can lead to local tissue Ischemia(8)

15. Several cohort studies conducted over the past 5 decades showed a link between serum uric acid (SUA)
and subsequent cardiovascular (CV) disease.(9) However, in some of these studies such association did not
remain significant after adjustment for concomitant risk factors for CV disease(10) or it was detected only
in women. Thus, the role of SUA as an independent risk marker remains controversial.(11) An increase in
SUA might be simply a marker of obesity, hyperinsulinemia and glucose
intolerance,(12) hypertension, hyperlipidemia and renal disease.(13)
The assessment of the independent prognostic value of SUA is clinically relevant in the specific setting of
essential hypertension, in which hyperuricemia is frequent(14) and cardiovascular risk stratification is of
utmost importance.

16. AIMS AND OBJECTIVES
To study the correlationship between serum uric acid levels and hypertension.
To study the correlation between grading of hypertension to the serum uric acidlevels.
To study the correlation between cardiovascular disease and serum uric acid levels.Inclusion criteria for
cases
HYPERTENSIVE patients on basis of jnc 7 WITH AGE ABOVE 18 Years
Patients who give consent for study.
EXCLUSION CRITERIA
1.Patients were excluded if they had any of the following -
2.Diabetes Mellitus,
3.Ischaemic Heart Disease,
4.All cases of secondary hypertension,
5.Clinical Findings of gout or extra- articular manifestations of hyperuricemia
6.Obesity ( body weight exceeding 25% of body weight )
7.H/o alcohol abuse
8.H/o drugs known to cause hyperuricemia, e.g. thiazide diuretics

17. 9.H/o pre-eclampsic toxemia
10.H/o malignancy,lymphoma
11.H/o Renal disease
An informed bilingual written consent will be taken from the patient/relativesfor
inclusion. Thorough clinical examination including blood pressure measurement will
be done in all the patients presenting as per Performa.

18. STUDY DESIGN,MATERIALS AND METHODS
Sample Size: There will be 50 cases of HTN based on JNC 7. who arenon critical patients of either sex age>18 years and
50 controls for the study who are normal healthy individuals similar to each other in terms of age, sex, and other
demographic terms without having intake of drug causing hyperuricemia.
Study Design
. Observational study
. Cross sectional in nature
Method of measurement of outcome of interest
Standard statistical methods will be used to measure the outcome.
Data collection method
Patient’s detailed history will be taken along with thorough physicalexamination and relevant investigations will be done.
Investigations will include as per proforma

19. DIAGNOSIS OF HYPERTENSION:
Person will be seated quietly for at least 5 minutes in a chair (rather than on anexam table), with feet on the floor and arm supported at
the heart level. Anappropriate sized Cuff (cuff bladder encircling at least 80 percent of the arm) will be used toensure accuracy. At
Least two measurements will be made at 5 minutes interval and average will betaken. SBP Will be the point at which first of two or more
sounds will be heard (phase 1), and DBP is the Point before the disappearance of sounds (phase 5).Diagnosis of hypertension will be
based on JNC 7
JNC guidelines for the management of arterial hypertension. As listed
Below.
Classification Of BP For Adults > 18 years OLD (
Classification of BP Systolic BP mm hg Diastolic BP mm hg
Normal < 120 <80
Pre hypertension 120-139 80-89
Stage 1 hypertension 140-159 90-99
Stage 2 hypertension ≥ 160 ≥ 100

20. STATISTICALANALYSIS
Analysis of the data will be done by appropriate statistical methods.
PROFORMA
PARTICULARS OF THE PATIENT
NAME: OPD/CR NO:
AGE/SEX:
OCCUPATION:
SOCIAL STATUS: ADDRESS:
EDUCATIONAL STATUS:INCOME:
CHIEF COMPLAINTS:
HISTORY OF PRESENT ILLNESS:HISTORY OF PAST ILLNESS: PERSONAL
HISTORY:
FAMILY HISTORY:
DRUG HISTORY:
EXAMINATION
GENERAL PHYSICAL EXAMINATION:
BUILT AND NUTRITION
Height
Weight
BMI
Waist circumference
Waist Hip Ratio
VITALS
TEMPERATURE

21. PULSE-
Carotid artery, femoral artery, renal artery bruit:RESPIRATION-
BP-Right arm-1) 2) 3) Mean-BP-Left arm -1) 2) 3) Mean-
Pallor , _Icterus , _Pedal edema , _Cyanosis , _Juglarvenous pressure , Clubbing ,
Hydration.
SYSTEMIC EXAMINATIONCVS:
CHEST:
P/A:
CNS:
Fundus examination
Investigations
Complete Hemogram with ESR
Blood sugar: Fasting, Post prandial Fasting serum insulin level by ELISA HbA1C
Kidney Function Test: Blood Urea, Serum Creatinine, Serum Uric Acid ,Serum Sodium, Serum Potassium,
eGFR
Serum Lipid Profile: LDL Cholesterol , HDLCholesterol ,

22. VLDL ,
Triglycerides______.
Electrocardiogram
Echocardiography
Ultrasound Abdomen and KUB
Urine examination-routine and microscopyUrine examination-culture and sensitivity X-Ray
Chest PA View

23. REFERENCES
1. G Antonakoudis, I Poulimenos, K Kifnidis et al . Blood pressure control and cardiovascular risk reduction. Hippokratia. 2007 ;
11: 114–119
2. Frohlich ED “Uric acid: A risk factor for coronary heart disease.” JAMA 1993; 270:378-379.
3.Kaplan NM. Systemic Hypertension: Mechanism and Diagnosis. In: Braunwald’s textbook of Cardiovascular Medicine 9th edition.
Elsevier Saunders. 37:935-72.
4.Norman M Kaplan, Braunwald’s textbook of Cardiovascular Medicine 7th edition, “Systemic Hypertension: Mechanism and Diagnosis”;
Elsevier Saunders 37:962.
5.Aram V. Chobanian, George L. Bakris, et al “ The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation,
and Treatment of High Blood Pressure” JAMA,2003, May 21,vol 289; 2561-2562.
6.Vasan RS, Larson MG, Leip EP et al “ Assessment of frequency of progression to hypertension in non-hypertensive participants in the
Framingham Heart Study” Lancet 2001; 358: 1682-1686..

24. 7. Richard J. Johnson; Duk-Hee Kang; Daniel Feig; Salah Kivlighn; John Kanellis et al: “Is There a Pathogenetic
Role for Uric Acid in Hypertension and Cardiovascular and Renal Disease?” Hypertension. 2003;41:1183.
8. Puig JG, Ruilope LM. “Uric acid as a cardiovascular risk factor in arterial hypertension.” Journal of
Hypertension. 1999; 17:869–872
9. Gertler MM, Garn SM, Levine SA. Serum uric acid in relation to age and physique in health and coronary heart
disease. Ann Intern Med.1951; 34:1421–1431.
10. Reunanen A, Takkunen H, Knekt P, Aromaa A. Hyperuricemia as a risk factor for cardiovascular
mortality. Acta Med Scand Suppl.1982; 668:49–59.MedlineGoogle Scholar
11. Vaccarino V, Krumholz HM. Risk factors for cardiovascular disease: one down, many more to evaluate. Ann
Intern Med.1999; 131:62–63.CrossrefMedlineGoogle Scholar
12. Modan M, Halkin H, Karasik A, Lusky A. Elevated serum uric acid: a facet of
hyperinsulinaemia. Diabetologia.1987; 30:713–718.CrossrefMedlineGoogle Scholar

25. 13. Messerli FH, Frohlich ED, Dreslinski GR, Suarez DH, Aristimuno GG. Serum uric acid in
essential hypertension: an indicator of renal vascular involvement. Ann Intern
Med.1980; 93:817–821.CrossrefMedlineGoogle Scholar
14. Puig JG, Ruilope LM. Uric acid as a cardiovascular risk factor in arterial hypertension. J
Hypertens.1999; 17:869–872

26. CONSENT FORM
I -exercising my free power of choice hereby give my consent for myself/my patient to
be included in the study entitled ESTIMATION OF URIC ACID IN HYPERTENSION AND ITS CORRELATION WITH
GRADING OF HYPERTENSION AND CARDIOVASCULAR RISK
been informed to my satisfaction by Dr. A.L.S.VARAPRASAD about the nature, purpose, likely duration of the study and
what I/my patient will be expected to do along with the name of the investigation that are to be carried out
I m aware of my/my relative right to opt out of the study at any time during the course of the study without having to give the
reason for doing so.
in my own language.I best understand and give my full,free and voluntary consent for the same.
I understand that the medical records that reveal my/my patients identity will be kept confidential.
Signature of the Attending Physician Signature/LeftThumb Impression of
Name: Dr. A.L.S.VARAPRASAD patient/relative
Date: Name:

27. सहमति पत्र
मैं - अपनी पसंद की स्विंत्र शक्ति का प्रयोग करिे हुए, अपने / अपने रोगी को उच्च रिचाप में यूररक
एतसड क
े आकलन और उच्च रिचाप और हृदय संबंधी जोक्तिम की ग्रेतडंग क
े साथ इसक
े सहसंबंध शीर्षक
वाले अध्ययन में शातमल होने क
े तलए अपनी सहमति देिा हं।
डॉ. ए.एल.एस.वरप्रसाद द्वारा अध्ययन की प्रक
ृ ति, उद्देश्य, संभातवि अवतध और जांच क
े नाम क
े साथ
मुझसे/मेरे रोगी से क्या करने की अपेक्षा की जाएगी, क
े बारे में मेरी संिुति क
े तलए सूतचि तकया गया है।
मुझे अध्ययन क
े दौरान तकसी भी समय ऐसा करने का कारण बिाए तबना अध्ययन से बाहर तनकलने क
े
मेरे/मेरे ररश्तेदार क
े अतधकार क
े बारे में पिा है।
मेरी अपनी भार्ा में। मैं सबसे अच्छी िरह समझिा हं और इसक
े तलए अपनी पूणष, स्विंत्र और स्वैक्तच्छक
सहमति देिा हं।
मैं समझिा/समझिी हूँ तक मेरे/मेरे मरीजों की पहचान प्रकट करने वाले मेतडकल ररकॉडष को गोपनीय रिा
जाएगा।
उपक्तथथि तचतकत्सक क
े हस्ताक्षर नाम क
े हस्ताक्षर/बाएं अंगूठे का तनशान: डॉ. ए.एल.एस.वरप्रसाद
रोगी/ररश्तेदार
तदनांक: नाम:

28. PATIENT INFORMATION SHEET
Investigator: Dr. A.L.S.VARAPRASAD
Supervisor:
Prof(Dr.) A. K. GADPAYLE
PROF.GENERAL MEDICINE
SHARDA UNIVERSITY
PROCEDURE:
If you are a newly detected hypertensive , fulfilling the inclusion and exclusion
criteria , your consent to participate in this study will be taken. Your clinical history
will be taken and clinical examination will be performed and recorded inthe
proforma. You will undergo routine investigations apart from tests for liver/kidney
functions, HBA1C, fasting serum URIC ACID. 5-10 ml of blood will be drawn for
investigations. The laboratory examinations will be performed at the hospital. Your
treatment would be done according to standard protocol being followed at the hospital.

29. BENEFITS OF PARTICIPATING IN THE STUDY:
The study will help to detect grading and cardivascular risk in hypertensives based on uric acid levels so that early
management can be done which would delaythe progression and its complications.
ALTERNATIVES TO PARTICIPATION:
You are free not to participate in the study or to withdraw from the study at any time. If you choose not to participate
or withdraw from the study, you will receive the usual care. You have the right to refuse any individual examination
or procedure.
CONFIDENTIALITY:
All the information that you provide during the study will be kept confidential.
CONTACT US:
In the event that at any time during the course of the study you feels that you have not been adequately informed
about the risks, benefits, alternative procedures or rights as study subject or feel under stress to continue against your
wishes you can contact:
Prof(Dr.) A. K. GADPAYLE
Medical Superintendent
Sharda hospital

30. रोगी सूचना पत्र
अन्वेर्क: डॉ. ए.एल.एस.वरप्रसाद
पयषवेक्षक: प्रो (डॉ.) ए.क
े . गडपयले प्रो. जनरल मेतडतसन शारदा तवश्वतवद्यालय
प्रतिया:
यतद आप एक नए पाए गए उच्च रिचाप से ग्रस्त हैं, जो समावेश और बतहष्करण मानदंडों को पूरा करिे हैं, िो इस अध्ययन में भाग लेने क
े
तलए आपकी सहमति ली जाएगी। आपका नैदातनक इतिहास तलया जाएगा और नैदातनक परीक्षण तकया जाएगा और प्रोफामाष में दजष तकया
जाएगा। लीवर/गुदे क
े कायों, एचबीए1सी, फाक्तटंग सीरम यूररक एतसड क
े परीक्षणों क
े अलावा आपको तनयतमि जांच से गुजरना होगा। जांच
क
े तलए 5-10 तमली िून तनकाला जाएगा। प्रयोगशाला परीक्षण अस्पिाल में तकए जाएं गे। आपका इलाज अस्पिाल में मानक प्रोटोकॉल क
े
अनुसार तकया जाएगा।
अध्ययन में भाग लेने क
े लाभ:
अध्ययन से यूररक एतसड क
े स्तर क
े आधार पर उच्च रिचाप से ग्रस्त रोतगयों में ग्रेतडंग और हृदय संबंधी जोक्तिम का पिा लगाने में मदद
तमलेगी िातक प्रारंतभक प्रबंधन तकया जा सक
े तजससे प्रगति और इसकी जतटलिाओं में देरी हो सक
े ।
भागीदारी क
े तवकल्प
आप तकसी भी समय अध्ययन में भाग लेने या अध्ययन से हटने क
े तलए स्विंत्र हैं। यतद आप अध्ययन में भाग नहींलेने या वापस लेने का तवकल्प
चुनिे हैं, िो आपको सामान्य देिभाल प्राप्त होगी। आपको तकसी भी व्यक्तिगि परीक्षा या प्रतिया को अस्वीकार करने का अतधकार है।

31. गोपनीयिा:
अध्ययन क
े दौरान आपक
े द्वारा प्रदान की जाने वाली सभी जानकारी गोपनीय रिी जाएगी।
संपक
ष करें:
इस घटना में तक अध्ययन क
े दौरान तकसी भी समय आपको लगिा है तक आपको अध्ययन तवर्य क
े रूप में जोक्तिमों, लाभों,
वैकक्तल्पक प्रतियाओं या अतधकारों क
े बारे में पयाषप्त रूप से सूतचि नहींतकया गया है या अपनी इच्छा क
े तवरुद्ध जारी रिने क
े तलए
िनाव में हैं, िो आप संपक
ष कर सकिे हैं:
प्रो (डॉ.) ए.क
े . गडपयले
तचतकत्सा अधीक्षक शारदा अस्पिाल