"ESTIMATION OF SERUM URIC ACID IN ESSENTIAL HYPERTENSION"

SYNOPSIS OF DISSERTATION SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA

In partial fulfillment of regulations for the award of

M.D. Degree in General Medicine

Submitted by

Dr. KIRANKUMAR METI . M.B.B.S.

POST GRADUATE STUDENT IN

GENERAL MEDICINE (M.D.)

Under the guidance of

Prof Dr. SHASHIKANTHA., M.B.B.S., M.D.,

PROFESSOR,

DEPARTMENT OF GENERAL MEDICINE,

A.I.M.S., B.G.NAGARA-571448.

DEPARTMENT OF GENERAL MEDICINE

ADICHUNCHANAGIRI INSTITUTE OF MEDICAL SCIENCES,

B.G.NAGARA-571448

2011


RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA

ANNEXURE II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1 / NAME OF THE CANDIDATE
AND ADDRESS
(in block letters) / Dr. KIRANKUMAR METI
P.G. IN GENERAL MEDICINE,
ROOM NO. 100,KALPATHRU BHAVAN
A.I.M.S., B.G. NAGARA,
MANDYA DISTRICT -571448
2. / NAME OF THE INSTITUTION /

ADICHUNCHANAGIRI INSTITUTE OF

MEDICAL SCIENCES, B.G.NAGARA.
3. / COURSE OF STUDY AND SUBJECT /

M.D. IN GENERAL MEDICINE

4. / DATE OF ADMISSION TO COURSE / 15 th JUNE 2011
5. / TITLE OF THE TOPIC / “ESTIMATION OF SERUM URIC ACID LEVEL IN ESSENTIAL HYPERTENSION”
6. / BRIEF RESUME OF INTENDED WORK
6.1  NEED FOR THE STUDY
6.2 REVIEW OF LITERATURE
6.3 OBJECTIVES OF THE STUDY / APPENDIX-I
APPENDIX-IA
APPENDIX-IB
APPENDIX-IC
7 / MATERIALS AND METHODS
7.1  SOURCE OF DATA
7.2 METHOD OF COLLECTION OF DATA : (INCLUDING SAMPLING PROCEDURE IF ANY)
7.3 DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER ANIMALS, IF SO PLEASE DESCRIBE BRIEFLY.
7.4 HAS ETHICAL CLEARENCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.3 / APPENDIX-II
APPENDIX-IIA
APPENDIX-IIB
YES
APPENDIX-IIC

YES

APPENDIX-IID
8. / LIST OF REFERENCES /

APPENDIX – III

9. / SIGNATURE OF THE CANDIDATE /
10. /

REMARKS OF THE GUIDE

/ Hypertension is one of the risk factor for significant cardiovascular and cerebrovascular morbidity and mortality. Elevation of serum uric acid level in hypertension is associated with increased cardiovascular morbidity. Serum uric acid level in hypertensives gives additional information regarding the severity and duration of hypertension. Hence this study has been carried out in rural hospital.
11. / 11.1 NAME OF THE GUIDE / Dr. SHASHIKANTHA. M.B.B.S, M.D. PROFESSOR,
DEPARTMENT OF GENERAL MEDICINE,
A.I.M.S, B.G.NAGARA.
11.2 SIGNATURE OF THE GUIDE
11.3 CO-GUIDE (IF ANY) / Dr. M.SHIVANNA. M.B.B.S, M.D.
ASSOCIATE PROFESSOR,
DEPARTMENT OF GENERAL MEDICINE,
A.I.M.S, B.G.NAGARA.
11.4 SIGNATURE
11.5 HEAD OF DEPARTMENT / Dr. MOHAN. M.E. M.B.B.S., M.D.
PROFESSOR & HEAD,
DEPARTMENT OF GENERAL MEDICINE,
A.I.M.S, B.G.NAGARA.
11.6 SIGNATURE
12 / 12.1 REMARKS OF THE CHAIRMAN
AND PRINCIPAL / The facilities required for the investigation will be made available by the college
Dr. M.G. SHIVARAMU.,M.B.B.S.,M.D.
PRINCIPAL,
AIMS, B.G. NAGARA.
12.2 SIGNATURE

APPENDIX-I

6.BRIEF RESUME OF THE INTENDED WORK:

APPENDIX –I A

6.1 NEED FOR THE STUDY:

Patients with blood pressure greater than 140 mm Hg systolic and 90 mm Hg diastolic with no definable cause are said to have primary, essential or idiopathic hypertension , 90% of all hypertensives fall into this group.

Hypertension is one of the leading causes of global burden of disease. Approximately 7.6 million deaths (13-15% of total) and 92 million disability adjusted life years worldwide were attributable to high blood pressure in 2001. Hypertension doubles the risk of cardiovascular diseases, including coronary heart disease, congestive heart failure, ischemic and hemorrhagic stroke, renal failure and peripheral arterial disease1.

Uric acid (UA) is the end product of endogenous and dietary purine nucleotide metabolism in humans. A growing body of data suggests a putative pathogenetic role for hyperuricemia in atherosclerosis and cardiovascular disease (CVD), especially in patients with diabetes mellitus, heart failure, and hypertension.2

Importantly, prospective studies have demonstrated independent and significant associations of increased UA levels and cardiovascular events.3, 4

As regards blood pressure, elevated levels of UA have been identified as an independent predictor of hypertension incidence and progression.5

This study is done to know the association between serum uric acid levels and essential hypertension and association of serum uric acid level and severity and duration of essential hypertension.

APPENDIX –I B

6.2  REVIEW OF LITERATURE

Uric acid end product of purine metabolism was first discovered in 1776.

A Swedish chemist Scheele isolated it from a urinary tract stone. In 1797, a British chemist Wallaston detected uric acid in a tophus. About 50 years later Alfred Baring Garrod , a British physician showed by chemical isolation that uric acid was abnormally high in gouty patients. Serum uric acid was first noted to be associated with increased blood pressure by Frederic Mohammed in 1870s.

According to the seventh report of Joint National Committee on Prevention , Detection, Evaluation and treatment of high blood pressure (JNC 7), blood pressure greater than 140 mm Hg systolic and 90 mmHg diastolic is termed as hyprtension.6

Hyperuricemia is defined as serum uric acid level above 7 mg/dl in men and above 6 mg/dl in women.

In a study by Dzielak Dj and Kivlinghu SD on serum uric acid a risk factor in cardiovascular disease found that hyperuricaemia in untreated hypertensive patients ranges from 25-50%. Furthermore elevated serum uric acid has been reported to increase the probability of developing hypertension by 87% and to increase mortality rate in ischemic heart disease.7

Culleton B-F in his study on uric acid and cardiovascular disease found that serum uric acid may provide additional prognostic information in patients with essential hypertension.8

Serum uric acid level is independent predictor of hypertension incidence and longitudinal BP progression.9,10,11,12

Canmpo-C,Garcia Puig et al13 in their study on relationship between severity of essential hypertension and prevalence of hyperuricemia found that serum uric acid were directly related to the severity of hypertension.

Levels of serum uric acid did show a high positive correlation with the severity of PIH in relation to hypertension and proteinuria15

APPENDIX –IC
6.3 AIMS AND OBJECTIVES OF STUDY

1.  To study the relationship between serum uric acid and essential hypertension.

2.  To study the association of serum uric acid to –

a.  Severity of essential hypertension

b.  Duration of essential hypertension

APPENDIX-II

7.0 MATERIALS AND METHODS

APPENDIX-IIA

7.1 SOURCE OF DATA:

The data will be obtained from 100 patients diagnosed to have Essential Hypertension attending Sri Adichunchanagiri Hospital and Research Centre, B.G.Nagar .

The study population comprised of 50 males and 50 female patients fulfilling inclusion criteria as cases and 50 males and 50 female normotensive subjects as control.

This study conducted for duration of 18 months.

APPENDIX-IIB

7.2 METHOD OF COLLECTION OF DATA

INCLUSION CRITERIA :

All patients between 40-70 years of age with essential hypertension of both the genders will be included in the study as cases. The diagnosis of essential hypertension will be established according to JNC 7 criteria. 6

·  Systolic blood pressure equal to or greater than 140 mm Hg

·  Diastolic blood pressure equal to or greater than 90 mm Hg

Same number age and sex matched normotensives as controls.

EXCLUSION CRITERIA:

Patients with

·  Secondary hypertension .

·  Age <40 ;>70 years.

·  Diabetes, hypothyroidism, hyperparathyroidism.

·  Ischemic heart disease, congestive cardiac failure.

·  Gout.

·  Obesity (body weight exceeding 25% of ideal weight).

·  Alcohol abuse.

·  Renal insufficiency, glomerulonephritis, pyelonephritis, hereditary nephropathy.

·  Patients on Drugs – Levodopa, Ethambutol, Pyrazinamide, Nicotinic acid.

·  Cytotoxic drugs , low dose aspirin,Thiazide diuretics.

Information will obtained from detailed history with special emphasis on duration and treatment of hypertension, vital signs, complete general physical examination including height and weight and systemic examination including ophthalmoscopic examination of fundus will be recorded.

The grading of hypertensive retinopathy is done according to Keith-Wagener-Barker classification.1

Grade 1: Narrowing of A-V ratio (normal A:V=3:4).The arteriolar light reflex is seen as broadened yellow line with red blood column.

Grade 2: There is A-V crossing defect ( A-V nipping ). The arterioles are seen like broad yellow line (copper wire) without blood column.

Grade 3: Exudates and hemorrhages are seen with broad white line ( silver wire )appearance of arteriole.

Grade 4: Presence of papilloedema in a case of hypertensive encephalopathy

The blood pressure measurement is taken with the individual seated quietly in a chair with feet on the floor for 5 min in a private, quiet setting with a comfortable room temperature. No caffeine for preceding hour, no smoking for preceding 30min, no external adrenergic stimulants eg., phenyleprine in nasal decongestants .At least two measurements should be made. The center of the cuff should be at heart level, and the width of the bladder cuff should equal at least 40% of the arm circumference; the length of the cuff bladder should be enough to encircle at least 80% of the arm circumference. It is important to pay attention to cuff placement, stethoscope placement, and the rate of deflation of the cuff (2 mmHg/s). Systolic blood pressure is the first of at least two regular "tapping" Korotkoff sounds, and diastolic blood pressure is the point at which the last regular Korotkoff sound is heard.1

Hypertension is classified according to JNC 7 criteria.

Classification / Systolic, mmHg / Diastolic, mmHg /
Normal / <120 / <80
Prehypertension / 120–139 / 80–89
Stage 1 hypertension / 140–159 / 90–99
Stage 2 hypertension / 160 / 100
Isolated systolic hypertension / 140 / <90

When systolic and diastolic blood pressures fall under different categories, the higher category is selected.

Hyperuricemia is defined as serum uric acid level above 7 mg/dl in men and above 6 mg/dl in women.

Serum uric acid is measured by Henry Craway’s method.14 Before collecting the blood samples, patients were advised to proceed on overnight fast of 12 hrs.

Statistical Methods :

The data obtained will be analyzed by descriptive statistics by means of percentage, proportions, age and depicted via bar charts, pie charts.

Tests applied – Chi square, ANOVA, F test.

Type of study:

Case control study.

APPENDIX-II C

7.3 Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so describe briefly?

YES

INVESTIGATIONS:

o  Blood routine

o  Urine routine

o  Random blood sugar

o  Serum lipid profile

o  Serum electrolytes

o  Blood urea , serum creatinine

o  Serum uric acid

o  ECG

o  Chest X-ray

APPENDIX-IID

PROFORMA APPLICATION FOR ETHICS COMMITTEE APPROVAL

SECTION A
a / Title of the study / “estimation of serum uric acid level in essential hypertension”
b / Principle investigator
(Name and Designation) / DR. KIRANKUMAR METI., M.B.B.S.
P.G. IN GENERAL MEDICINE,
A.I.M.S, B.G.NAGARA.
c / Co-investigator
(Name and Designation) / Prof DR. SHASHIKANTHA.,M.B.B.S,MD.
PROFESSOR,DEPARTMENT OF MEDICINE ,
A.I.M.S., B.G. NAGARA,
MANDYA DISTRICT -571448
d / Name of the Collaborating
Department/Institutions / NA
e / Whether permission has been obtained from the heads of the collaborating departments & Institution / NA
Section – B
Summary of the Project / APPENDIX I
Section – C
Objectives of the study / APPENDIX IC
Section – D
Methodology / APPENDIX IIB
A / Where the proposed study will be undertaken / ADICHUNCHANAGIRI HOSPITAL AND RESEARCH CENTRE, B.G.NAGARA
B / Duration of the Project /
18 MONTHS
C / Nature of the subjects:
Does the study involve adult patients?
Does the study involve Children?
Does the study involve normal volunteers?
Does the study involve Psychiatric patients?
Does the study involve pregnant women? / YES
NO
NO
NO
NO
D / If the study involves health volunteers
I.  Will they be institute students?
II.  Will they be institute employees?
III.  Will they be Paid?
IV.  If they are to be paid, how much per session? / NO
NO
NO
NA
E / Is the study a part of multi central trial? / NO
F / If yes, who is the coordinator?
(Name and Designation)
Has the trial been approved by the ethics Committee of the other centers?
If the study involves the use of drugs please indicate whether.
I. The drug is marketed in India for the indication in which it will be used in the study.
II. The drug is marketed in India but not for the indication in which it will be used in the study
III. The drug is only used for experimental use in humans.
IV. Clearance of the drugs controller of India has been obtained for:
  Use of the drug in healthy volunteers
  Use of the drug in-patients for a new indication.
  Phase one and two clinical trials
  Experimental use in-patients and healthy volunteers. / NA
NA
NA
NA
NA
NA
NA
NA
G / How do you propose to obtain the drug to be used in the study?
-  Gift from a drug company
-  Hospital supplies
-  Patients will be asked to purchase
-  Other sources (Explain) / NA
H / Funding (If any) for the project please state
-  None
-  Amount
-  Source
-  To whom payable / NA
I / Does any agency have a vested interest in the out come of the Project? / NO
J / Will data relating to subjects /controls be stored in a computer? / NO
K / Will the data analysis be done by
-  The researcher?
-  The funding agent / YES
NO
L / Will technical / nursing help be required form the staff of hospital.
If yes, will it interfere with their duties?
Will you recruit other staff for the duration of the study?
If Yes give details of
I.  Designation
II.  Qualification
III.  Number
IV.  Duration of Employment / NO
NO
NO
NA
NA
NA
NA
NA
M / Will informed consent be taken? If yes
Will it be written informed consent:
Will it be oral consent? Will it be taken from the subject themselves?
Will it be from the legal guardian? If no, give reason: / NO
NA
NA
NA
NA
N / Describe design, Methodology and techniques / APPENDIX II

Ethical clearance has been accorded.

Chairman,

P.G Training Cum-Research Institute,

A.I.M.S., B.G.Nagara.

Date :

PS : NA – Not Applicable


APPENDIX - III

LIST OF REFERENCES:

1.  1.Naomi D.L. Fisher, Gordon H, Williams.”Hypertensive vascular disease” Chapter 247 in Harrisons Principles of internal Medicine , 18th edition,edited by Dennis L Kasper, Anthony S Fauci , Dan L Longo, Stephen L, Hauser, J Carry Jameson, New York ; McGraw Hill 2011pp.2047-2048.