Rajiv Gandhi University Of Health Sciences, Karnataka,

Bangalore .

“A COMPARATIVE STUDY OF HEART RATE

VARIABILITY BETWEEN HYPERTENSIVE AND
NORMOTENSIVE SUBJECTS”

By
Dr. MANGALA GOWRI S.R., M.B.B.S.

Dissertation submitted to the

Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore

In partial fulfillment
of the requirements for the degree of

DOCTOR OF MEDICINE
in
PHYSIOLOGY

Under the guidance of

Dr. KANYAKUMARI M.D.

Professor

Department of Physiology
J.J.M. Medical College
Davangere.

2012

I
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 ACKNOWLEDGEMENT

I am ever grateful to GOD for his blessings on me.

It gives me immense pleasure to take this opportunity to thank everyone who

has helped me during the course of my study and in preparing this dissertation.

It is with this sense of heartful gratitude and appreciation that I would like to

express my sincere thanks to my guide and teacher Dr. KANYAKUMARI.M.D.,

Professor, Department of Physiology, J.J.M. Medical College, Davangere, who,with

her knowledge and expertise has provided able guidance and constant encouragement

not only during the preparation of this dissertation but also throughout my

postgraduate course.

It gives me immense pleasure to express my sincere thanks and gratitude to

my respected teacher, Dr. N. PRABHU RAJ M.D. Professor and Head, Department of

Physiology for his suggestions, supervision, encouragement and constant support

throughout my postgraduate course.

I wish to express my sincere thanks and gratitude to my beloved Professors

Dr. B. JINADATHA M.D. and Dr. N.J. SHANMUKHAPPA M.D. for their constant

encouragement, valuable suggestions and for being a constant source of inspiration.

I have no words to express my sincere thanks to my Professors,

Dr. S. CHANDRASEKHARAPPA M.Sc.,Ph.D., Dr. NAGARAJA S. B.Sc,MBBS,MD,

Dr. R.S. KOUJALAGI M.D., Dr. SURESH Y. BONDADE M.D. and Dr. S.V. BRID

M.D. Department of Physiology, for their guidance, interest and ever extending help

whose ocean of knowledge has been an inspiration during my post graduate study.

VI
 I am grateful to Sri. L.B. PATIL M.Sc., Dr. S. SMILEE JOHNCY M.D.,

Dr. V. BHAGYA M.D., Dr. AJAY K.T. M.D., Dr. CHAITRA B M.D., Dr. SUNITHA

M.D. and Dr. JAYALAKSHMI M.K. M.D. Assistant Professors and

Mr. DHANYAKUMAR M.Sc., Lecturer, Department of Physiology, for their advice

and suggestions.

I am extremely thankful to Dr. H.R. CHANDRASEKHAR M.D. Principal,

J.J.M. Medical College, Dr. H. GURUPADAPPA M.D. Director for Post Graduate

Studies and Research, J.J.M. Medical College, Davangere, for their valuable help and

co-operation during this study.

I thank my seniors Dr. SMRITI SHETTY C M.D., Dr. PRABHULING

MANAKAR M.D. , Dr. K. NAWAZUDDIN M.D. and my postgraduate colleagues

Dr. BEENA V.K, Dr. ANSHUL SHARMA, Dr. SHWETHA P.C, Dr. SOWMYA

B.A, Dr. SHILPA D, Dr. LAKSMI T, Dr. AFTAB BEGUM, Dr. SANTOSH

LAKSMI, Dr. AFREEN ITAGI BEGUM and Dr. SUHAS S.H. for their co-

operation and timely help during my study.

I express my thanks to my friends Dr. MEGHANA NARJAL, Dr. DIVYA,

Dr. KAVANA M.D., Dr. SURAJ and all my friends and students for their support and

encouragement.

I am grateful to Mr. D.K. SANGAM, Bio-Statistician, for his guidance in

statistical analysis of this study.

I thank Dr. P.S. MAHESH, Chief Librarian and other staff members of

Library and Information Center, for their assistance.

VII
 I am thankful to all the technical and non technical staff of the Department of

Physiology for their co-operation during my study. I thank all the subjects who have

voluntarily participated in this study.

My thanks to ZEN COMPUTERS TECHNOLOGY, Davangere, for the

meticulous computerized laser output of this dissertation.

I affectionately thank my parents Sri G.N. RAJASEKHARAPPA and

Smt. MANJULA and my sister Dr. RESHMA S.R for their abundant love,

endurance support, innumerable sacrifices and unceasing encouragement that has

moulded me into a person I am today.

I thank my husband Dr. VINAY G M.D.. and my Mother- in- law

Smt. SHAKUNTHALAMMA and all my family members, for their love, co-

operation and encouragement.

Last but not the least, I humbly acknowledge all the subjects who were a part

of the study without whose cooperation, the present study would not have been

feasible.

VIII
 LIST OF ABBREVIATIONS USED

ANS – Autonomic Nervous System

BMI – Body Mass Index

BP – Blood Pressure

DBP – Diastolic Blood Pressure

ECG – Electrocardiogram

ESRD – End Stage Renal Disease

GABA – Gamma Amino Butyric Acid

HF – High Frequency

HF (n.u) – High Frequency in normalized units

HRV – Heart Rate Variability

IML – Intermediolateral Horn

ISO – Isoprenaline

IVLM – Intermediate Venterolateral Medulla

LF – Low Frequency

LF (n.u) – Low Frequency in normalized units

LF/HF – Low Frequency power to High Frequency power ratio

LVH – Left Ventricular Hypertrophy

mmHg – Millimeter of Mercury

ms2 – Milliseconds square

NE – Nor Epinephrine

NTS – Nucleus of Tractus Solitarius

PNN 50% – Percentage of differences between adjacent normal RR interval

> 50 msec.

RMSSD – Root Mean Square Successive Differences.

RSV – Respiratory Sinus Arrhythmia

IX
RVLM – Rostral Ventro Lateral Medullary nucleus

SBP – Systolic Blood Pressure

SDNN – Standard Deviation of Normal to Normal intervals.

TINN – The Triangular Interpolation of NN interval histogram.

X
 ABSTRACT

Background :

Hypertension is the most common disease and it markedly increases both

mortality and morbidity. Hypertension is associated with autonomic dysregulation.

Heart rate variability is a useful non invasive, powerful tool for quantitative

assessment of cardiac autonomic function.

Objective :

To assess the cardiac autonomic nerve function status in patients with essential

hypertension by analyzing frequency and time domain measures of heart rate

variability.

Methods :

50 hypertensive and 50 normotensive male subjects between the age group of

40-60 years were selected. Computerised ECG system with Niviqure Software was

used for the study. Frequency domain measures such as very low frequency, high

frequency and LF/HF ratio and time domain measures such as mean RR intervals,

mean HR, SDNN, RMSSD, PNN 50%, HRV ∆ Index and TINN were assessed to

observe both sympathetic and parasympathetic nerve function status. Heart rate

variation during deep breathing (HRV db) was done to assess sympathovagal balance.

Statistical analysis was done by using unpaired t-test was used.

Results :

Frequency domain parameters like low frequency and LF/HF ratio were

significantly (< 0.001) reduced in hypertensive subjects compared to normotensives.

Time domain parameters like SDNN, RMSSD, PNN 50%, HRV ∆ index and TINN.

XI
 Mean heart rate was higher in subjects with high blood pressure (0.001). HRV

during deep breathing (HRV db) was significantly (0.001) lower in hypertensive

subjects compared to normotensive subjects.

Conclusion :

Impaired cardiac autonomic nerve function characterized by sympathetic

overactivity and reduced vagal activity was found in hypertensive patients.

Key words : Hypertension; mean heart rate; Frequency domain measures; Time

domain measures; HRV (db).

XII
 TABLE OF CONTENTS

Page No.

1. Introduction 1-2

2. Objectives 3

3. Review of literature 4-35

4. Methodology 36-41

5. Results 42-58

6. Discussion 59-63

7. Conclusion 64-65

8. Summary 66

9. Bibliography 67-74

10. Annexures

1. Proforma 75-76

2. Written consent 77

3. Master chart 78-81

XIII
 LIST OF TABLES

Sl. No. Tables Page No.

1. Anthropometric parameters between normotensive and 49

hypertensive subjects

2. Blood pressure parameters between normotensive and 49

hypertensive subjects

3. Spectral analysis of heart rate variability between normotensive 50

and hypertensive subjects

4. Time domain analysis of heart rate variability between 50

normotensive and hypertensive subjects

5. Comparison of heart rate response to deep breathing between 51

normotensive and hypertensive subjects

6. Comparison of spectral analysis of heart rate variability 51

depending on duration of hypertension

7. Comparison of time domain analysis of heart rate variability 52

depend ing on duration of hypertension

XIV
 LIST OF FIGURES

Sl. No. Figures Page No.

1. Basic pathway involved in the medullary control of 13

circulation by the vagus nerves

2. Basic pathways involved in the medullary control of 14

circulation by the sympathetic system

3 Relationship between time and frequency domain measures 27

4 Procedure of recording of HRV 41

5 Instruments used in HRV 41

XV
 LIST OF GRAPHS

Sl. No. Graphs Page No

1. Distribution of Normotensive and Hypertensive subjects. 53

2. Comparison of blood pressure parameters between 53

Normotensive and Hypertensive subjects.

3. Comparison of peak frequency between Normotensive and 54

Hypertensive subjects.

4. Comparison of power in msec2 /Hz between Normotensive and 54

Hypertensive subjects.

5. Comparison of frequency domain in normalized unit between 55

Normotensive and Hypertensive subjects.

6. Comparison of LF / HF ratio between Normotensive and 55

Hypertensive subjects.

7. Comparison of time domain analysis between Normotensive 56

and Hypertensive subjects.

8. Comparison of RR(ms) interval between Normotensive and 56

Hypertensive subjects.

9. Comparison of PNN50% between Normotensive and 57

Hypertensive subjects.

10. Comparison of RR ∆ index between Normotensive and 57

Hypertensive subjects.

11. Comparison of TINN (ms) between Normotensive and 58

Hypertensive subjects.

12. Comparison of heart rate response to deep breathing between 58

Normotensive and Hypertensive subjects.

XVI
Introduction
 INTRODUCTION

Hypertension is the most common disease and it markedly increases both

mortality and morbidity. The adverse effects of hypertension principally involve the

blood vessels, the retina, the heart and the kidneys including central nervous system.1

Hypertension is a chronic condition which doubles the risk of cardiovascular

disease, including coronary heart disease, congestive heart failure, ischaemic and

haemorrhagic stroke, renal failure and peripheral arterial disease. In addition, rare

endocrine disorders may present with hypertension. Hypertension is therefore of

interest to any physician involved in clinical medicine.

It is one of the major risk factors for cardiovascular mortality, which accounts

for 20-50% of all deaths. 2

The mechanism that result in hypertension remain largely unknown in most

individuals and the disorder is multifactorial.

Approximately 40-60% is explained by genetic factors. Important

environmental factors include a high salt intake, heavy consumption of alcohol,

obesity, lack of exercise.3

The autonomic nervous system plays a crucial role in blood pressure and heart

rate control and may thus be an important pathophysiological factor in development

of hypertension.4

It has been well established that hypertension is associated with autonomic

dysregulation.5

1
 An increased sympathetic drive combined with decreased parasympathetic

inhibition is found in patients with hypertension.6

Heart rate variability is an index of cardiac autonomic regulation.7 The heart is

not a metronome and its beats do not have the regularity of a clock, so changes in

heart rate, defined as heart rate variability.

Heart rate variability is an useful non invasive, powerful tool for quantitative

assessment of cardiac autonomic function. It is an accurate reliable, reproducible, yet

simple to measure and to process.8

The role of the autonomic nervous system in essential hypertension is a

important area of investigation and hence the present study is taken up to compare

measures of Heart rate variability between hypertensive and normotensive subjects.

2
Objectives
 OBJECTIVES

1. To compare HRV in supine position between hypertensive and normotensive

subjects.

2. To compare HRV during deep breathing between hypertensive and normotensive

subjects.

3. To compare HRV depending on duration of hypertension.

3
Review of Literature
HISTORICAL REVIEW :

NEURAL CONTROL OF CIRCULATION : 9

• Weber and Weber [1845] : Showed vagal stimulation slows and sympathetic

stimulation accelerates the heart.

• Bernard [1851-1858]: Observed that sympathetic nerve section causes

vasodilation; stimulation induces vasoconstrictio n. Section of the cervical cord

causes hypotension.

• Ludwig and Cyon [1867] : Showed that reflex inhibition of heart rate and

hypotension result from stimulation of the central end of the depressor [aortic

branch] of the vagus.

• Goltz [1864] : Paralysis of solar sympathetic plexus results in venodilation and

failure of venous return to heart.

• Ludwig's laboratory [1870-73]: Transection of medulla below the acoustic striae

causes hypotension. Stimulation of structures of the lower part of the fourth

ventricle induces hypertension. The concept of the vasomotor centre is introduced.

• Karplus and Kreidl [1909] : Showed that electrical stimulation of hypothalamus

promotes hypertension.

• Hering [1920] : Showed that the carotid sinus contain stretch receptors whose

afferent pass via the glossopharyngeal nerve to the medulla inducing reflex vagal

stimulation and sympathetic vasomotor inhibition.

• Alexander [1946] : Showed that medullary cardiovascular centres - pressor and

depressor area.

4
• Ewing et al [1970]: Devised simple bedside tests of short term heart beat

differences to detect autonomic neuropathy in diabetic patients.

• Mc Allen and Spyer [1977] : Showed nucleus ambiguous as cardiac vagal cenre.

HISTORY OF HEART RATE VARIABILITY :10

• Hon and Lee [1965]: Observed that fetal distress was preceded by alterations in

interbeat intervals before any appreciable change occurred in heart rate itself.

• Wolf et al [1977]: Showed association of postinfarction mortality with reduced

HRV.

• Akselrod et al [1981]: Introduced power spectral analysis of heart rate fluctuations

to quantitatively evaluate beat-to-beat cardiovascular control.

• Kleiger et al [1987] : Confirmed that HRV was a strong and independent predictor

of mortality after an acute myocardial infarction

• Hyano et al [1991] : Showed that RR interval fluctuation in relation to respiration

can be used as an non invasive index of vagal nerve excitation in humans

• Task Force of the European Society of Cardiology the North American Society of

Pacing Electrophysiology [1996]: Established Standards for measurement of

HRV.

5
THE CARDIOVASCULAR AUTONOMIC NERVOUS SYSTEM 11,12

The autonomic nervous system regulating cardiovascular function maintains

circulatory homeostasis of the organism, ensuring adequate tissue perfusion under

varying environmental and internal demands. This rapid adaptation of the circulation

is mainly accomplished through reflex mechanism. Mecha nical and chemosensory

input from different systemic and central receptors are conveyed by afferent nerve

fibres to medullary centres for integration, and efferent fibres in turn transmit

impulses from the central nervous system to the heart and blood vessels, modulating

their activity. The medullary centres also receive input from higher brain centres and

the hypothalamus, important for influencing cardiovascular responses to emotion,

stress and exercise. Anatomically and functionally the autonomic nervous system is

divided into the sympathetic and the parasympathetic divisions. The efferent limbs of

both divisions consist of myelinated preganglionic nerve fibres connected with

unmyelinated postganglionic fibres synaptic clusters called ganglia. Post ganglionic

fibres inturn innervate the effector organs.

Sympathetic nervous system / thoracolumbar outflow :

Preganglionic sympathetic fibres arise in the lateral horns of the spinal

segments T1 – L3 . Most preganglionic fibres travel only a short distance in the spinal

nerve, before branching off into the sympathetic ganglia which are arranged as two

paravertebral chains (truncus sympatheticus) extending from the cervical to the sacral

region. Some fibres only traverse these sympathetic ganglionic chains, synapsing in

separate cervical (the cervical or the stellate) or abdominal (the iliac or mesenteric)

ganglia. The chemical neurotrans mitter in sympathetic preganglionic nerve endings is

acetylcholine. In most post ganglionic nerve endings, the transmitter is noradrenalin.

6
 A few preganglionic fibres traversing through the greater mesenteric nerve

synapse with chromaffin cells in the adrenal medulla. Stimulation of these cholinergic

preganglionic fibres results in the release of adrenaline and to a lesser extent

noradrenaline into the bloodstream. The actions of adrenaline and noradrenaline are

mediated by specific G-protein coupled adrenergic receptors on the surface of the cell.

Pharmacologically, these adrenoceptors are divided into α and β receptors. Two main

subtypes of α receptors and three main subtypes of β receptors have been identified.

Parasympathetic nervous system / craniosacral outflow:

Parasympathetic outflow arises in the motor nuclei of cranial nerves III, VII,

IX and X in the brainstem and from the spinal segments S2 – S4 . Preganglionic fibres

synapse with the postganglionic fibres within or close to the effector orga n. The

chemical neurotransmitter in both pre and post ganglionic parasympathetic nerve

endings is acetylcholine (cholinergic nerve fibres). The actions of acetylcholine are

mediated through nicotinic and muscarnic acetylcholine is mediated through nicotinic

and muscarnic acetylcholine receptors. The nicotinic receptors are ligand- gated ion

channels, mediating the effects of acetylcholine in the autonomic ganglia. The

muscarnic receptors are G-protein coupled receptors, mediating the parasympathetic

impulses to the effectors organs.

1. Cardiac innervation :

a) Sympathetic innervation :

The preganglionic (small, myelinated) sympathetic fibres arise from lateral

horn cells of T1 to T5 spinal segments. They emerge via the ventral root and enters

paravertebral sympathetic chain via white rami communicantes. These fibres relay in

the superior, middle and inferior cervical ganglion and post ganglionic sympathetic

7
fibres run in the superior, middle and inferior cardiac nerve and form cardiac plexus

and supply

i) Nodal tissues – SA node, AV node

ii) Muscles of atria and ventricles sympathetic fibres to the heart are epicardial.

Parasympathetic supply:

Parasympathetic supply to the heart is via two vagus nerves with their cell

bodies located in the medulla oblongata. These are nucleus tractus solitarius, the

dorsal motor nucleus of va gus and the nucleus ambiguous. Preganglionic fibres (long,

myelinated) travel in the vagi to synapse with ganglionic cells which are located near

the SA node, AV node and in the atria. From here post ganglionic fibres (small,

unmyelinated) arise and are distributed to the SA node, AV node and muscles of atria.

The right vagus mainly innervates right atrium and SA node. Therefore, stimulation of

right vagus strongly inhibits heart rate. The left vagus predominately innervates the

left atrium, AV node and the bundle of His. Therefore, stimulation of left vagus slows

or blocks AV nodal conduction.13

8
Cholinergic and adrenergic receptors of the autonomic nervous system14

Receptor type Agonists and order of Main locations

potency

Cholinergic

Nicotinic Acetylcholine, Postsynaptic neurons of autonomic

Nicotine >> Muscarine ganglia, neuromuscular junctions,

Central nervous system (CNS).

Muscarinic Acetylcholine, Heart, vascular and nonvascular

(M1 – M5 ) Muscarine >> Nicotine smooth muscle, glands, CNS.

Adrenergic

α1 Phenylephrine, Vascular and nonvascular smooth

Epinephrine(E)= muscle, heart, CNS.

Norepinephrine(NE)

>> Isoprenaline(ISO)

α2 Clonidine, Presynaptic, vascular smooth muscle,

E = NE >> ISO platelets, CNS.

β1 Dobutamine, Heart

ISO > E = NE

β2 Salbutamol, Vascular and nonvascular smooth

ISO > E >> NE muscle, skeletal muscle, heart.

β3 BRL 37344, Adipose tissue, heart.

ISO = E > NE

9
Their stimulation produces the following effects:

Sympathetic Parasympathetic

Sinoatrial node ↑ Heart Rate (HR) HR ↓ (m2 > m3 )

(β1 > β 2 )

Atrial muscle ↑ Contractility (β 1 > β2 ) Contractility ↓ (m2 > m3 )

Conduction velocity

Atrioventricular node Automaticity and Contractility ↓ (m2 > m3 )

↑ Contractility (β 1 > β2 )

Velocity

Ventricle muscle ↑ Contractility (β 1 > β2 )

Vascular smooth muscle Vasoconstriction (α 1)

Vasodilation (β 2 , m3 )

The cardiac pacemaker (SA node) activity is tonically influenced by both

parasympathetic and sympathetic systems. However, in basal conditions,

parasympathetic or vagal tone is more than the sympathetic tone. Therefore, normally

the heart rate is the function of the vagal tone.

Medullary control of the cardiovascular system:

One of the major sources of excitatory input to sympathetic nerves controlling

the vasculature is neurons located near the pial surface of the medulla in the rostral

ventrolateral medulla (RVLM) popularly known as vasomotor centre (VMC). They

secrete excitatory transmitter glutamate.

The activity of RVLM neurons is determined by fibres from baroreceptors,

fibres from other parts of the nervous and from the carotid and aortic chemoreceptors.

10
 The baroreceptors are stretch receptors in the walls of the heart and blood

vessels. The carotid sinus and aortic arch receptors (high pressure region of

circulation) monitor the arterial circulation. Receptors are also located in the walls of

the atria at the entrance of the superior and inferior venae cavae, pulmonary veins, as

well as in the pulmonary circulation (low pressure region of the circulation),

collectively referred as the cardiopulmonary receptors.

The baroreceptors are stimulated by distention of the structures in which they

are located, and so they discharge at an increased rate when the pressure in these

structures rises. Their afferent fibres pass via the glassopharyngeal and vagus nerves

to the medulla. Most of them end in the nucleus of the tractus solitarius, and the

excitatory transmitter they secrete is glutamate excitatory projections extend from the

NTS to the caudal ventrolateral medulla, where they stimulate GABA secreting

inhibitory neurons that project to the RVLM. Excitatory projections also extend from

the NTS to the vagal motor neurons in the nucleus ambiguous and dorsal motor

nucleus. Thus, increased baroreceptor discharge inhibits the tonic discharge of

sympathetic nerves and excites the vagal innervation of the heart. These neural

changes produce arteriodilation, venodilation, bradycardia and a decrease in cardiac

output.

Impulses from the carotid and aortic chemoreceptors although primarily act

on the respiratory centres, also excite the neurons of vasomotor area in certain

conditions. They contribute very little to the regulation of arterial pressure in normal

conditions. Stimuli like hypoxia and hypercapnea act directly on the vasomotor area

to increase its activity.

11
 There are descending tracts to the vasomotor area from the cerebral cortex,

particularly the limbic cortex that relay in the hypothalamus. These fibres are

responsible for the blood pressure rise and tachycardia produced by emotions such as

sexual excitement and anger. The connections between the hypothalamus and the

vasomotor area are reciprocal, with afferents from the brain stem closing the loop.

Inflation of the lungs causes vasodilation and a decrease in blood pressure. This

response is mediated via vagal afferents from the lungs that inhibit vasomotor

discharge. Pain usually causes rise in blood pressure via afferent impulses in the

reticular formation converging in the RVLM.

12
Fig. 1 : Basic pathway involved in the medullary control of circulation by the
vagus nerves[NTS- Nucleus of Tractus Solitarius; Pyr- Pyramid; XII-
Hypoglossal nucleus]

13
Fig. 2 : Basic pathways involved in the medullary control of circulation by the
sympathetic system[ solid lines indicate stimulation; dashed lines indicate
inhibition; NTS - Nucleus of Tractus Solitarius;RVLM - Rostra l Venterolateral
Medulla; IVLM - Intermediate Venterolateral Medulla; CVLM - Caudal
Venterolateral Medulla; GABA – Gamma Amino Butyric Acid ; IML-
Intermediolateral horn;Glu- Glutamate; IX- Glossopharyngeal nerve;
X- Vagus nerve]

14
HISTORY OF HYPERTENSION :

Though the disease was believed to exist since antiquity it was possible to

recognize it only after the discovery of a device to measure it. Blood circulation was

discovered as early as the year 1616 by William Harvey. First report of direct blood

pressure dates from 1726 by Stephen Hales who cannulated horse crural artery and

assessed the height of blood column before and after hemorrhage.

The monoaural stethescope was discovered by Lennac in 1819. Biural

stethoscope came to America in 1852. Vierordt , a German scientist was the first

person to device an instrument to measure blood pressure in the year 1853.Though

this instrument was cumbersome he is the pioneer in establishing the principles of

estimating blood pressure by obliterating the pulse which is followed even today.

In the year 1896, Riva Rocci introduced the sphygmomanometer cuff. In the

year 1905, Nikolai Korotkoff devised auscultatory method of measuring arterial

pressure and measured diastolic and systolic pressure levels for first time. Evaluation

of antihypertensive therapy began in 1920. Progress began with arrival of thiazide

diuretics in late 1960s.

Epidemiology:

It has been estimated that hypertension accounts for 6% of deaths world wide.

Recent evidence suggests that the prevalence of hypertension may be

increasing, possibly as a consequence of increasing obesity. Obesity and weight gain

are strong, independent risk factors for hypertension.

15
 Both environmental and genetic factors may contribute to regional and racial

variations of blood pressure and hypertension prevalence. It is estimated that 60% of

hypertensives are > 20% overweight.

Family studies controlling for a common environment indicate that blood

pressure heritability are in the range of 15-35%. In twin studies, heritability estimates

of blood pressure are ~ 60% for males and 30-40% for females.1

AETIOLOGY AND CLASSIFICATION OF HYPERTENSION

Classification of BP: (for adults aged 18 yrs or older)

JNC-VII classification: (American Medical Association) 15

BP classification Systolic BP (mm Hg) Diastolic BP (mm Hg)

Normal < 120 < 80

Pre hypertension 120-139 80-89

Stage I HT 140-159 90-99

Stage II HT ≥ 160 ≥ 100

ESSENTIAL HYPERTENSION:

Essential hypertension is characterized by a sustained increase in systolic

pressure of greater than 140 mm Hg and a diastolic BP greater than 90 mm Hg. It is

the arterial hypertension of unknown aetiology. About 95% of total hypertensives

belong, to this group. It is also known as primary or idiopathic hypertensio n.16

The pressure required to move the blood through the circulatory bed is

provided by the pumping action of the heart (cardiac output; CO) and the tone of the

arteries (peripheral resistance; PR).

16
 Cardiac output and peripheral resistance are the two determinants of arterial

pressure. Cardiac output is determined by stroke volume and heart rate; stroke volume

is related to myocardial contractility and to the size of vascular compartment.

Peripheral resistance is determined by functional changes in small arteries and

arterioles. The hemodynamic hallmark of primary hypertension, a persistently

elevated vascular resistance may be reached through a number of different paths

before the final destination; these may converge into either structural thickening of the

vessel walls or functional vasoconstriction. There is complex interaction between

multiple factors.17

Factors influencing development of Essential Hypertension are ;

a) Genetic and familial

b) Socio-economic status

c) Dietary factors like high salt intake, high alcohol intake and caffeine.

d) Obesity and smoking

e) Hormonal factors - like high renin.

f) Neurotransmitters - acetyl-choline, nor-adrenaline, serotonin, dopamine and others.

Some mechanisms stipulated as causing essential hypertension are:

1. Genetic predisposition: Hypertension is one of the most common complex genetic

disorders with genetic heritability averaging about 30 to 60%. Essential

hypertension is almost certainly polygenic disorder involving multiple genes, each

having small effect on blood pressure.18 ,19

2. The fetal environment: Low birth weight as a consequence of fetal under nutrition

has been repeatedly found to be followed by an increased incidence of blood

17
 pressure in later life with an overall estimate that a 1 kg lower birth weight is

associated with 2-4 mm Hg higher systolic blood pressure in adulthood.20

3. Renin angiotensin system: Approximately 20% of patients who have hypertension

have suppressed plasma renin activity. They have sodium retention and renin

suppression due to excessive production of an unidentified mineralocorticoid.

They have salt sensitivity to blood pressure and are responsive to diuretics.

Another set of hypertensive patients also salt sensitive have a reduced adrenal

response to salt restriction. The y are termed as non modulators because of the

absence of sodium mediated modulation of target tissue responses to angiotensin.

They make up about 25-30% of hypertensive population.21

4. Vascular hypertrophy: Excess sodium intake and renal sodium retention increases

the fluid volume and cardiac output thereby causing functional contraction and

structural remodeling leading to vascular hypertrophy.22

5. Cell membrane defect: Abnormality in the transport of sodium across cell

membrane leads to abnormal accumulation of calcium in vascular smooth

muscle.22

6. Endothelial cell dysfunction: Hypertensive patients have been shown to have a

reduced vasodilatory response to various stimuli of nitric oxide. Endothelin 1

causes prolonged and pronounced vasoconstriction in hypertensives.22,23

7. Sympathetic nervous activity: Young hypertensives tend to have increased

circulating levels of catecholamines, augmented sympathetic nerve traffic in

muscle, faster heart rate and heightened vascular reactivity to alpha adrenergic

agonists.24

18
8. Hyperinsulinemia: Hyperinsulinemia in hypertension arises as a consequence of

resistance to effects of insulin on peripheral glucose utilization. In obese as well as

20% of non obese hypertensives there is insulin resistance and also decreased

hepatic uptake of insulin which contributes to hyperinsulinemia.22

9. Sensitivity to sodium: A high sodium diet produces HTN in about one half of the

population, which suggests a variable degree of sensitivity of BP to sodium.25

Multiple mechanisms of sodium sensitivity have been proposed. The possible

mechanisms are a defect in renal sodium excretion26 , increased activity of sodium

hydrogen exchanger, enhanced sympathetic activity, augmented calcium entry

into vascular smooth muscle and impaired nitric oxide synthesis. Sensitivity to

sodium increases with age and perhaps more in women than in men. In a recent

study, it has been reported that intake of sodium modifies the release of Nitric

oxide. Excess sodium intake induces HTN by increasing fluid volume and preload

there by increasing cardiac output.27 Sodium excess may increase blood pressure
28
in multiple other ways as well affects vascular reactivity and renal perfusion. 26

10. Impact of stress on Hypertension:

People exposed to repeated psychogenic stressors may develop HTN. Its

effects are likely to depend on an interaction of at least three factors : the nature of the

stressor, its perception by the individual and his physiological susceptibility.

Offspring of hypertensive parents manifest with exaggerated cardiovascular responses

to stress.29 Healthy offspring of hypertensives have been found to exhibit greater

cardiovascular reactions to stressors involving isometric exercises, mental arithmetic

test, the cold pressor test in comparison to offspring of normotensives.30 Stressors

such as mental arithmetic test, tend to elicit greater β adrenergic activation (leading to

19
greater increases in heart rate, forearm blood flow) while stressors such as the cold

pressor test tend to elicit greater α adrenergic activation (leading to greater

vasoconstriction). Offspring of hypertensives display reduced baroreflex sensitivity,

which might make them particularly susceptible to the predominant effects of active

stressors on the heart. Genetic risk for hypertens ion may be accompanied by an

increase in emotionality which explains the greater cardiovascular reactivity to stress

in offspring of hypertensives. Studies suggest diminished neuropsychological

functioning in offspring of hypertensives which reinforces the idea of behavioral

differences between offspring of hypertensives and normotensives.31

PATHOPHYSIOLOGICAL CHANGES IN PRIMARY HYPERTENSION:1

The cause of primary hypertension is multifactorial. Several abnormalities

contribute to primary hypertension. The se defects may be in nervous system, heart,

kidneys, vasculature and hormonal system. Abnormalities in one system can affect

others.

Neural factors : Increased activity of sympathetic nervous system, increased levels of

norepinephrine and enhanced activity and sympathetic nervous system may promote

sodium retention, which may raise blood pressure.

Renal sodium mechanism: Due to renal sodium retention, cardiac output is increased

followed by an increase in peripheral resistance.

Renin-Angiotensin Aldosterone system:

Some patients with primary hypertension have high levels of renin activity.

The role of renin-angiotensin-aldosterone system is the cause of primary

hypertension.

20
Cardio-vascular factors : In young adults with primary hypertension cardiac output is

increased and total peripheral resistance is normal. This is due to increased

sympathetic nervous activity and increased intravascular volume. In older patients the

cardiac output is relatively normal and peripheral resistance is increased. The cause

for increased peripheral resistance is due to enhanced vascular tone which may be

secondary to stimuli arising outside the immediate cardio-vascular system, such as

increased sympathetic activity, increased plasma catecholamine levels or increased

angiotensin-II. There are several abnormalities the vascular tree itself which could

increase the peripheral resistance, including decrease in the number of arterioles with

increasing age, hypertrophy of smooth muscle cells of arterioles, altered sensitivity of

the arteriolar wall to circulating vasoconstrictors and increased permeability of

smooth muscle cell membranes to sodium.

Pathophysiological changes in arteries:

In larger arteries, the internal elastic lamina is thickened, smooth muscles

hypertrophied and fibrous tissue deposited. The vessels dilate and become tortous,

and their walls become less compliant. Atheroma is perpetuated. In smaller arteries

hyaline atherosclerosis occurs in the wall, the lumen narrows and aneurysm may

develop. These structural changes associated with long standing hypertension affect

peripheral resistance vessels in the kidneys. They lead to an increase in peripheral

vascular resistance, a further rise in blood pressure and acceleration of atheroma

within vessel walls.

21
SECONDARY HYPERTESION:1

It is the arterial hypertension of known etiology. About 5% of total

hypertensives belong to this group.

The causes of secondary hypertension are;

a) Coarctation of aorta.

b) Renal disease

c) Endocrine disorders

d) Pregnancy

e) Drugs and etc.

PATHOLOGIC CONSEQUENCES OF HYPERTENSION:1

Hypertension is a risk factor fo r all clinical manifestations of atherosclerosis.

It is an independent predisposing factor of heart failure, coronary heart disease,

stroke, renal disease and peripheral arterial disease.

Effects on heart:

Heart disease is most common cause of death in hypertensive patients.

Increased systemic pressure imposes excessive workload on heart. At first heart

compensates by increase in wall thickness of left ventricle leading to concentric left

ventricle hypertrophy. Ultimately the function of this chamber deteriorates, the cavity

dilates and symptoms and signs of heart failure appear. Angina pectoris may appear

because of combination of

1. Accelerated coronary artery disease and

2. Increased myocardial oxygen demand as a consequence of increased myocardial

mass.

22
 Hypertension is a major risk factor for myocardial infarction and ischemia.

Prevalence of silent myocardial infarction is significantly increased in hypertensive

subjects and they have a greater risk for mortality after an initial MI.

Effects on nervous system:

Neurologic effects of long standing hypertension may be divided into retinal

and central nervous system changes. Retina is the only tissue in which the arteries and

arterioles can be examined directly. Repeated ophthalmoscopic examination provides

the opportunity to observe the vascular effects of hypertension. A useful guide is the

Keith Wagener Barker classification of fundoscopic changes.

Hypertension is an important risk factor for brain infarction and hemorrhage.

The incidence of stroke rises progressively with increasing blood pressure levels,

particularly systolic blood pressure in individuals >65 years. Hypertension may

accelerate brain function decline with age. Cerebral blood flow remains unchanged

over a wide range of arterial pressures through a process termed autoregulation of

blood flow. In patients with malignant hypertension there is failure of autoregulation

of cerebral blood flow resulting in vasodilation and hyperperfusion. Signs and

symptoms of hypertensive encephalopathy may include severe headache, nausea and

vomiting, focal neurologic signs, and alterations in mental status. Untreated,

hypertensive encephalopathy may progress to stupor, coma, seizures and death.

Effect on kidney:

Hypertension is a risk factor for renal injury and ESRD. Renal risk appears to

be more closely related to systolic than to diastolic blood pressure. Whether it is

"essential" or of known etiology, hypertension results in development of intrinsic

lesions of the renal arterioles (hyaline arteriolosclerosis) that eventually lead to loss of

23
function (nephrosclerosis). Arteriosclerotic lesions of the afferent and efferent

arterioles and glomerular capillary tufts are the most common renal vascular lesions in

hypertension and result in a decreased glomerular filteration and tubular dysfunction.

Renal disease may manifest as a mild to moderate elevation of serum

creatinine concentration, microalbuminuria or proteinuria. Microalbuminuria in

hypertensive patients has been correlated with LVH and carotid artery thickness. Any

agent or group of agents that adequately lowers BP to levels less than 130/85 mm Hg

will delay the progression of nephropathy.

Measures of cardiovascular autonomic nervous system:

There are different methods to assess the effects of autonomic nervous system

on the cardiovascular system in humans. Besides the assessment of end organ

responses such as blood pressure and heart rate, the most widely used measurements

are plasma norepinephrine (NE) assays, norepinephrine spillover technique,

microneurographic recordings of postganglionic muscle and skin sympathetic nerves

and power spectrum analysis of blood pressure and heart rate variability.32

Autonomic functions can be evaluated by a number of invasive and non invasive tests.

The non invasive tests are routinely performed to indicate cardiac ANS activity.

The commonly used cardiovascular function tests are: 33

i) Heart rate and blood pressure response to standing.

ii) Heart rate response to tilting

iii) Heart rate variation with respiration

iv) Valsalva ratio

v) Isometric exercise

vi) Cold pressor test.

24
HEART RATE VARIABILITY (HRV)

The last two decades have witnessed the recognition of a significant

relationship between the ANS and cardiovascular mortality, including sudden cardiac

death, experimental evidence for an association between propensity for lethal

arrhythmias and signs of either increased sympathetic or reduced vagal activity has

spurred efforts for the development of quantitative markers of autonomic activity.

HRV represents one of the most promising such markers. The apparently easy

derivation of this measure has popularized its use. As many commercial devices now

provide an automated measurement of HRV, the cardiologist has been provided with

a seemingly simple tool for both research and clinical studies.

HRV refers to the beat to beat alterations in HR under resting conditions, the

ECG of healthy individuals exhibit periodic variation in R-R intervals. This rhythmic

phenomenon, known as respiratory sinus arrhythmia (RSA), fluctuates with the phase

of respiration, cardio-acceleration during inspiration and cardio-deceleration during

expiration. RSA is predominantly mediated by respiratory gating of parasympathetic

efferent activity of the heart. Vagal efferent traffic to the sinus node occurs primarily

in phase with expiration and is absent or attenuated during inspiration. Atropine

abolishes RSA.

Reduced HRV has thus been as a marker of reduced vagal activity.34

Heart rate variability is a marker of cardiac parasympathetic and sympathetic

activity. 35,36,37

25
Heart rate variability10

Heart is not a metronome and its beats do not have the regularity of the clock.

HRV refers to the oscillations of the intervals between consecutive heart beats which

are related to the influence of the ANS on the sinus node. The influence of the ANS

on the heart is dependent on information from baroreccptors, chemoreceptors,

respiratory system, renin - angiotensin - aldosterone system, thermo regulatory system

and so on. Change in patterns of HRV provides a sensitive and early indicator of

health impairments. High HRV is a sign of good adaptation showing efficient

autonomic mechanisms. Conversely, low HRV is often an indicator of abnormal and

inadequate adaptation of the ANS which may indicate the presence of physiological

malfunction in the individual. Several methods of measuring the variation in heart rate

have been developed, each of which falls under the broader description of being either

time domain or frequency domain analyses.

Time domain analysis

Time domain methods determine RR intervals in continuous

electrocardiographic recordings. Each QRS complex is detected and the normal to

normal (NN) intervals (interval between R waves in successive normal QRS

complexes) are calculated. Various parameters are calculated from NN intervals as

shown in table.

Various time domain measures in HRV

Variable Units Description

SDNN ms Standard deviation of all NN intervals
RMSSD ms square root of the mean of the sum of the squares of
differences between adjacent NN interval
PNN50 % percent of difference between adjacent NN intervals greater
than 50 ms
TINN Hz Triangular interpolation of NN interval histogram

26
 Most of the conventional time domain parameters (i.e SDNN, RMSSD and

PNN50%) are markers of parasympathetic activity.

Frequency domain analysis

This analysis describes the periodic oscillations of the heart rate signal

decomposed at different frequencies and amplitudes. It provides information on the

amount of their relative intensity in heart's sinus rhythm. Power spectral analysis can

be performed in two ways. First, non parametric method where fast fourier transform

is used to evaluate spectral components of the signal. This is characterized by discrete

peaks for the several frequency components. Second, parametric method, the

autoregressive model estimation, results in a continuous smooth spectrum of activity.

It was shown over one hundred years ago by Baron Jean Baptiste Fourier that any

waveform that exists in the real world can be generated by adding up sine waves. This

has been illustrated in that a simple waveform is composed of two sine waves. By

picking the amplitudes, frequencies and phases of these sine waves correctly, we can

generate a waveform identical to our desired signal. Conversely, we can break down

our real world signal into these same sine waves.

Figure 3 : Relationship between time and frequency domain measures

27
 Figure 3 is a three dimensional graph of this addit ion of sine waves. Two of

the axes are time and amplitude, familiar from the time domain. The third axis is

frequency which allows us to visually separate the sine waves which add to give us

our complex waveform. If we view this three-dimensional graph along the frequency

axis we get the view in Figure 3. This is the time domain view of the sine waves.

Adding them together at each instant of time gives the original waveform. However,

if we view our graph along the time axis as in Figure, we get a totally different

picture. Here we have axes of amplitude versus frequency, what is commonly called

the frequency domain. Every sine wave we separated from the input appears as a

vertical line. Its height represents its amplitude and its position represents its

frequency. Since we know that each line represents a sine wave, we have uniquely

characterized our input signal in the frequency domain. This frequency domain

representation of our signal is called the spectrum of the signal. Each sine wave line

of the spectrum is called a component of the total signal.

Various frequency domain measures in HRV

Variable Units Description Frequency range

Total power ms2 Variance of all NN intervals < 0.4 Hz

ULF ms2 ultra low frequency < 0.003 Hz

VLF ms2 very low frequency < 0.003-0.04 Hz

LF ms2 low frequency power 0.04-0.15 Hz

HF ms2 high frequency power 0.15-0.4 Hz

LF/HF ratio ratio of low-high frequency power -

Very low frequency (VLF) – Possibly renin angiotensin system

Low frequency (LF) - Parasympathetic and sympathetic influences
High frequency (HF) - Parasympathetic influences
LF: HF ratio- Sympatho - vagal balance

28
 The spectral components are evaluated in terms of frequency (Hz) and

amplitude (ms squared). The amplitude is assessed by the area of each component.

The components of frequency analysis are explained

The LF and HF powers may be expressed in normalized values (nu). This

tends to minimize the effect of changes in VLF on LF and HF components.

HF or LF norm (nu) = LF or HF * 100 / TP - VLF

Physiological correlation of frequency components of HRV 10

The HF component is attributed mainly to the efferent vagal activity on sinus

node, as seen in clinical and experimental observations of autonomic manoeuvres

such as electrical vagal stimulation, muscarinic receptor blockade, and vagotomy.

Controversy exists in the interpretation of LF component. There are different theories

in the literature proposing different origins for LF component. Among all, baroreflex

feedback loop remains dominant. It seems that a change in blood pressure is sensed

by arterial baroreceptors, which adjust heart rate through the central nervous system

via both fast vagal action and the slower sympathetic action. The delay in the

sympathetic branch of the baroreflex in turn determines a new oscillation which is

sensed by the baroreflex and induces a new oscillation in heart rate.

LF/HF ratio Considered as an expression of autonomic balance representing

the optimum co-operation between sympathetic and parasympathetic nervous

systems. Regarding VLF and ULF, physiological explanation is not well established

and they seem to be related to oscillations due to renin - angiotensin - aldosterone

system, thermoregulation and the peripheral vasomotor tone.

29
PHYSIOLOGICAL FACTORS INFLUENCING HRV:

Age: HRV decreases with age 38

Circadian rhythm: HRV is maximum during sleep.39

Body position

Food ingestion

Associated with body mass index

Gender

Respiration

Physical fitness

Medication

30
REVIEW OF LITERATURE:

Studies have showed that LF was greater and HF smaller in hypertension as

compared to normotension, thus suggesting an enhanced sympathetic activity and a

reduced vagal activity in hypertension.40

Hayano et al studies have showed that the time and frequency domain analysis

in use provides an accurate and common measure of cardiac vagal tone at rest.35

Chakko et al studies on hypertensive subjects was associated with reduced

standard deviation of RR intervals.Hourly measurement of PNN 50% was

significantly lower in hypertensive patients. He also showed that PNN 50% is a

sensitive measure of parasympathetic activity. PNN50% was lower among the

hypertensive subjects compared with controls, indicating decreased vagal tone.41

In hypertensives, during controlled breathing induced a significant decrease in

low frequency normalized units and in the LF/HF ratio on the RR spectrum both in

control subjects and in hypertensive subjects.42

Studies have shown, with increasing age, the parasympathetic spectral power

components decrease and black subjects have a lower LF, higher HF and higher HF /

LF ratio than whites. Women have a lower LF and a higher HF/LF ratio than men.43

In the study of Huikuri et al, treated hypertension was associated with

decreased SDNN and VLF and LF components of heart rate variability and decreased

LF/HF ratio. The body mass index was larger and systolic and diastolic blood

pressure were higher among the hypertensive subjects than in normotensives. In long

standing hypertension there was reduction in very low and low frequency power

31
spectrum components, suggesting that low HR variability may contribute to increased

cardiac mortality.44

Singh et al reported data from the Framingham Heart Study showed that,

among normotensive men, presence of reduced LF was associated with a greater risk

for developing hypertension. Mean heart rate were higher in hypertensive men and

women compared with the normotensives. All HRV measures, with the exception of

the LF / HF ratio, were significantly reduced in subjects with hypertension compared

with those with normal blood pressure.45

Studies have showed increased sympathetic tone has been found in

hypertensive individuals. The LF/HF ratio was significantly higher and the PNN 50

was significantly lower in white with high blood pressure compared to blacks.46

Guzzetti S and his co workers showed low frequency normalized units and

LF/HF ratio was significantly lower in the group of black hypertensive patients

compared to white.47

The studies done in year 2000, have confirmed that age, sex and obesity

contribute to variation in some measures of HRV. In healthy subjects, aging decreases

spectral power of all HRV components. Female sex was associated with a higher HF

normalized unit, a lower LF normalized unit and a lower LF / HF in normal

subjects.48

Kaftan et al studies showed time domain measures like standard deviation of

RR interval calcula ted at 5 minute intervals, HRV ∆ index, Square root of the mean

squared differences of successive RR intervals and the high frequency part of the

frequency domain measure of HRV were all decreased, where as the low frequency

32
part of the frequency domain measures and LF / HF ratio were increased in

hypertensives cases.49

The decrease of HF power and the increase of the LF/HF ratio on standing

were significantly blunted at higher blood pressure, both when measured

conventionally and by ambulatory monitoring.50

In a study, compared with normotensive controls, hypertensive patients had

lower total power, lower low frequency power, lower high frequency power, lower

root mean square successive difference and PNN50. Hypertensive women had higher

HF nu and lower LF nu and LF/HF ratio than hypertensive men.51

A high heart rate was considered a risk factor for development of high DBP in

young adults. The authors suggest that some individuals who develop hypertension

have increased sympathetic tone (manifested by higher heart rates prior to blood

pressure elevation), which can lead to smooth muscle cell proliferation, with

subsequent reduced compliance of the peripheral vasculatur e and, consequently,

raised DBP.5

The study clearly showed that mean values of HRV is reduced in treated

hypertensive subjects compared with age matched normotensives.7

Individuals with hypertension have increased sympathetic tone manifested by

higher heart rate.52

Lucini D et al studies have shown subjects with blood pressure more than

133mm Hg and 163 mm Hg have significantly higher LF ( nu) and LF / HF ratio ,

where as HF(nu) was significantly lower compared to subjects with blood pressure

lower than 103 mm Hg.53

33
 Hypertens ive subjects were slightly older, had higher heart rates, higher body

mass indexes than their normotensive controls. All absolute measures of heart rate

variability were reduced in hypertensive subjects as compared with their

normotensive controls. LF power as well as HF power was lower in hypertensive men

when compared with their normotensive counterparts.54

The SDNN (standard deviation of all R-R intervals) PNN50 (percentage of

successive differences between the R-R intervals > 50 ms) and LF (low frequenc y

spectrum between 0.04 and 0.15 Hz) were significantly smaller in the hypertensive

group when compared with those in the normotensive. After administration of the

angiotensin ll-converting enzyme inhibitors, correction was observed in all parameters

of heart rate variability in the hypertensive group.55

Study done in Korea showed that SDNN and RMSSD were significantly lower

in hypertension and diabetes group.56

Sloan RP et al studies showed that the indices of HR variability were greater

in younger compared to older, compared to men, women had lower levels of LF

power and study also showed blacks had lower levels of LF power, and lower LF/HF

ratio compared to black.57

Studies have showed that mean heart rate, systolic blood pressure and diastolic

blood pressure was significantly higher in hypertensive subjects.58

HRVdb was significantly lower in hypertensives compared to normotensives.

Logarithm of high- frequency (HF) spectral power of RR intervals was significantly

lower in hypertensives compared to normo tensives in the supine position.5

34
 Studies have showed there was significant improvement in HRV after

supervised integrated exercise and yoga for 9 months.59

Studies showed that mean SDNN and RMSSD were significantly lower in

both treated and untreated hypertensives.8

The mean total power, LF power and HF power were significantly lower in

both treated and untreated hypertensives.60

35
Methodology
 METHODOLOGY

The present study was conducted in the Department of Physiology, J.J.M

Medical College, Davangere.

50 hypertensive male subjects attending out patient and inpatient blocks of

Bapuji hospital and Chigateri Government Hospital, Dava ngere and 50 age matched

normotensive male subjects from general population and healthy attendants of

patients of Bapuji hospitals and Chigateri Government Hospital, Davangere were

selected.

Inclusion Criteria :

• 40-60 years hypertensive male sub jects

• 40-60 years normotensive male subjects.

Exclusion Criteria :

• Age less than 40 years and more than 60 years

• Subjects with diabetes mellitus, congestive cardiac failure, symptomatic

coronary artery disease, atrial fibrillation.

• Smokers and alcoholics

• Secondary hypertension – like pheochromocytoma, renal artery disease etc.

• History of drug treatment other than antihypertensives.

All subjects were explained about the procedures to be undertaken and written

informed consent was obtained from them. All subjects were clinically examined and

detailed history was taken with reference to duration of hypertension, family history,

personal history like smoking, alcoholism etc and previous drug history. Physical

36
examination was done. Height and weight was noted and BMI(Body mass index)

calculated as per Quetlets index.

Weight (kilogram)
Body mass index =
Height 2 (meter)

Test was performed 2-3 hours after light breakfast in sequence. Blood pressure

was recorded in supine position using mercury sphygmomanometer. A standard adult

size cuff measuring 23 cm by 12 cm was used for all subjects. Three readings were

taken and average of second and third was used for the study. Subjects were rested in

supine position for atleast 10 minutes, after which resting ECG was recorded with the

subjects remaining supine for 5 minutes.

Deep breathing test : The deep breathing test was conducted with the subjects in

supine position. Before beginning the test, subjects were taught to breathe at a rate of

6 respiration cycles per minute. 5 seconds for each inspiration and 5 seconds for each

expiration. Heart rate variation during deep breathing was given by the formula,

Heart rate variability =[60,000/short RR interval (msec)] – [60,000/long RR

interval (msec)] measured in beats per minute.61

Equipment :

ECG was acquired using digital ECG system, an instantaneous heart rate at

RR intervals were continuously plotted using Niviqure software on a Microsoft

window based computer. The digital ECG system to save multiple records and

provided with additional filter settings, calculation tools, automated analysis and auto

report generation facilities.

HRV refers to the regulation of sinoatrial node, the natural pacemaker of the

heart by sympathetic and parasympathetic branches of the autonomic nervous system.

37
It is the beat-to-beat fluctuations in the rhythm of the heart rate, as defined by the

degree of balance in sympathetic and vagus nerve activity.

A normal one cycle ECG signal is made up of several waves.

The peak with the highest amplitude is called the R wave. An R-R interval is

the time that elapses between two successive R waves.

Acquiring R-R intervals :

To analyze HRV, we must obtain the R-R intervals.

Acquiring raw Preprocessing Extracting R peaks

ECG signals ECG signals RR intervals

Process of acquiring R-R intervals HRV analysis methods

R-R intervals

Preprocessing

Time domain Frequency Time frequency Nonlinear

domain and domain

Linear measures of HRV :

Linear measures of HRV include various time and frequency domain indices.

Time domain indices provide information on total variability over a period of time.

The time domain indices could be derived from direct measurements of the

R-R intervals or from the differences between R-R intervals. Time domain indices

like heart rate, SDNN, RMSSD, PNN50%, HRV∆ index and TINN were obtained.

38
 Frequency domain indices provide information on both total variability as well

as its distribution as a function of frequency. Various spectral methods are available.

Spectral analyses of R-R intervals derived from short term recordings of 2 to 5min

yields 3 separate bands.

a) A very low frequency (VLF) band located in the less than 0.04Hz.

b) A LF band located in the 0.04-0.15Hz range.

c) A HF band with a very large range from 0.15-0.50 Hz.

The HF component is decreased by sitting or parasympathetic blocking drugs

and is increased by sympathetic blocking drugs. Therefore, the HF comp onent is

thought to provide a quantitative and specific index of vagal cardiac function, on the

other hand, the LF component is increased while standing, LF component in humans

has been interpreted as an indicator mainly of sympathetic influence. Consequently,

the LF/HF ratio is considered to be a convenient index of sympatho- vagal interaction.

Interpretation of LF component is controversial. It is considered by some as a marker

of sympathetic modulation and by others as a parameter that includes both

sympathetic and parasympathetic influences.

39
STATISTICAL ANALYSIS :

The results were given as Mean ± Standard Deviation and range values.

Comparisons were performed using students t-test for 2 group comparisons.

The p value of 0.05 or less was considered as statistical significance.

Formulae used for analysis of data :

∑ xi Where xi = 1, 2, ……..n
Mean, x =
n
n = Total number of cases evaluated

∑ (xi – x)2
Standard Deviation (SD) =
n- 1

Variance = SD2

SD
Standard Error, SE =
n

Difference between groups

Students t-test, t =
Standard error of difference

40
Fig. 4 : Procedure of recording of HRV

Fig. 5 : Ins truments used in HRV

41
Results
 RESULTS

The present study entitled “A comparative study of heart rate variability

between hypertensive and normotensive subjects” was conducted in the Department

of Physiology, J.J.M Medical College, Davangere.

50 normotensive males and 50 hypertensive males were analyzed for the

results (Graph 1). The age of subjects ranged from 40-60 years.

The results obtained were expressed as Mean ± Standard deviation. On

analysis of anthropometric parameters of the 50 normotensive subjects, the mean age

(years) was 48.4 ± 6.3; the mean height (m) is 1.61 ± 0.04; the mean weight (kg) was

61.04 ± 4.11; the mean BMI (kg/m2 ) was 23.33 ± 2.2 (Table1).

On analysis of anthropometric parameters of the 50 hypertensive subjects, the

mean age (years) was 51.6 ± 5.4; the mean height (m) was 1.63 ± 0.04; the mean

weight (kg) was 63 ± 5.53; the mean BMI (kg/m2 ) was 24.00 ± 1.98 (Table 1).

Statistical analysis was done by Tukey’s test.

Blood pressure :

The mean systolic blood pressure (mm Hg) in normotensive subjects was

118.8 ± 9.1. The mean systolic blood pressure (mm Hg) in hypertensive subjects was

147.8 ± 6.7 (Table 2, Graph 2).

The mean diastolic blood pressure in normotensive subjects was 77.6 ± 5.2.

The mean diastolic blood pressure in hypertensive subjects was 90.3 ± 3.5 (Table 2,

Graph 2).

42
 The mean pulse pressure in normotensive subjects was 41.2 ± 7.46. The mean

pulse pressure in hypertensive subjects was 57.56 ± 7.24 (Table 2, Graph 2).

The mean of mean arterial pressure in normotensive subjects was 91.33 ±

5.73. The mean of mean arterial pressure in hypertensive subjects was 109.59 ± 3.5

(Table 2, Graph 2).

The increase in the systolic blood pressure , diastolic blood pressure, pulse

pressure and mean arterial pressure in hypertensive subjects compared to

normotensive subjects was highly significant (p < 0.001) (Table 2, Graph 2).

Very low frequency (VLF) :

Mean VLF (Hz) in normotensives was 0.017 ± 0.01 and in hypertensives was

0.017 ± 0.01.The changes between both group s was not significant(Table 3, Graph 3).

Mean VLF (ms2 ) in normotensive was 229.95 ± 345.4 and in hypertensives

was 2187.2 ± 534.9. The changes between both groups was not significant (Table 3,

Graph 4).

LOW FREQUENCY MEASURES:

LF Peak frequency (Hz) :

Mean low frequency (Hz) in normotensives was 0.08 ± 0.03 and in

hypertensives was 0.07 ± 0.02. It was significantly (p < 0.001) reduced in

hypertensive subjects compared to normotensives (Table 3, Graph 3).

43
LF Power (ms 2 ) :

Mean LF (ms 2 ) in normotensives was 1076.2 ± 496.6 and in hypertensives was

787.9 ± 484.2. It was significantly lower in hypertensive subjects compared to

normotensives (p<0.01) (Table 3 ,Graph 4).

LF in normalized units:

Mean LF (nu) was 49.70 ± 16.41 in normotensive subjects and 43.00 ± 12.00

in hypertensives. There was significant reduction in LF (nu) in hypertensives

compared to normotensives (p <0.01) (Table 3, Graph 5).

HIGH FREQUENCY MEASURES:

HF Peak frequency (Hz) :

Mean HF (Hz) was 0.26 ± 0.11 in normotensive subjects and 0.25 ± 0.15 in

hypertensives. There was no significant changes in both groups (Table 3, Graph 3).

HF Power (ms 2 ):

Mean HF (ms 2 ) was 356.3 ± 223.2 in normotensive subjects and 339.3 ± 174.9

in hypertensives. There was reduction in values in hypertensives. But it was not

statistically significant compared to normotensives (Table 3, Graph 4).

HF in normalized units:

Mean HF (nu) was 48.41 ± 17.17 in normotensives and 49.87 ± 15.30 in

hypertensives. The changes were not statistically significant between two groups

(Table 3, Graph 5).

44
LF/HF ratio :

Mean LF / HF ratio in normotensives was 1.64 ± 0.74 and in hypertensives

was 0.93 ± 0.37. There was statistically significant reduction in LF / HF ratio in

hypertensive subjects compared to normotensives (p < 0.001) (Table 3, Graph 6).

The test was carried out using Tukey’s test, Unpaired t test.

TIME DOMAIN PARAMETERS

SDNN (ms):

Mean SDNN in normotensives was 66.96 ± 10.01 and in hypertensives it was

59.16 ± 9.54. There was highly significant reduction of SDNN (ms) in hypertensives

than in normotensives. (p < 0.001) (Table 4, Graph 7).

RMSSD :

Mean RMSSD was 30.92 ± 12.40 in normotensive subjects and 18.99 ± 11.49

in hypertensives. RMSSD was highly significantly reduced in hypertensives

compared to normotensives. (p < 0.001) (Table 4, Graph 7).

RR (ms) :

Mean RR (ms) in normotensive subjects was 949.15 ± 140.38 and in

hypertensive subjects was 848.39 ± 166.82. The RR (ms) was significantly reduced in

hypertensives compared to normotensive subjects. (p < 0.001) (Table 4, Graph 8).

PNN 50% :

Mean PNN 50% in normotensive subjects was 6.19 ± 2.74 and hypertensive

subjects was 1.60 ± 2.04. There was highly significant reduction in hypertensive

subjects compared to normotensives. ( p < 0.001) (Table 4, Graph 9).

45
Heart rate (bpm) :

Mean heart rate in normotensive subjects was 65.81 ± 8.68 and in

hypertensives was 71.34 ± 7.91. There was significantly increased heart rate in

hypertensives compared to normotensives. (p < 0.001) (Table 4, Graph 7).

RR ∆ Index :

Mean RR ∆ index was 0.07 ± 0.02 in normotensive subjects and 0.05 ± 0.01 in

hypertensive subjects. The reduction in RR ∆ index value in hypertensives was highly

significant compared to normotensives. (p < 0.001) ((Table 4, Graph 10).

TINN (ms) :

Mean TINN (ms) in normotensives was 301.84 ± 198.90 and in hypertensives

was 128.84 ± 79.38. The reduction in TINN (ms) value in hypertensives compared

with normotensive subjects was highly significant (p < 0.001) (Table 4, Graph 11).

The statistical analysis was done using Unpaired t test.

Heart rate response to deep breathing (HRV db) :

Mean HRVdb in normotensive subjects was 26.36 ± 7.28 and hypertensive

subjects was 20.17 ± 3.57. HRV during deep breathing was significantly reduced in

hypertensive subjects. (p < 0.001) (Table 5, Graph 12).

Duration of hypertension :

Mean VLF (Hz), LF (Hz), HF (Hz) were 0.02 ± 0.01, 0.06 ± 0.04, 0.26 ± 0.13

respectively in hypertensive subjects less than 5 years duration of disease.

Mean VLF (Hz), LF (Hz), HF (Hz) were 0.02 ± 0.01, 0.08 ± 0.03, 0.26 ± 0.15

respectively in hypertensive subjects more than 5 years of duration of disease.

46
 LF (Hz) was significantly reduced in hypertensives with more than 5 years

duration. (p < 0.01) (Table 6).

Mean VLF (ms2 ), LF (ms2 ), HF (ms2 ) were 2138.63 ± 590.67, 858.00 ±

130.40, 323.19 ± 128.8 respectively in hypertensive subjects less than 5 years

duration of disease.

Mean VLF (ms2 ), LF (ms2 ), HF (ms2 ) were 2210.00 ± 514.32, 696.20 ±

312.40, 346.88 ± 194.20 respectively in hypertensive subjects more than 5 years

duration of disease.

LF (ms2 ) was significantly reduced in hypertensives with more than 5 years

duration. (p < 0.01)

Mean LF (nu), HF (nu) were 46.78 ± 13.34, 58.79 ± 16.68 respectively in

hypertensives less than 5 years of duration.

Mean LF (nu), HF (nu) were 41.27 ± 11.01, 45.67 ± 12.82 respectively in

hypertensives more than 5 years of duration.

HF (nu) was significantly reduced in patients with longer duration of

hypertension. (p < 0.01) (Table 6).

Mean LF/HF ratio was 0.84 ± 0.31 with hypertension less than 5 years and

0.98 ± 0.38 in more than 5 years hypertensive subjects. There was no significant

change in the LF/HF depending on duration of hypertension. (Table 6).

47
 Heart rate, SDNN, RMSSD were 71.40 ± 7.53, 58.94 ± 9.11, 28.40 ± 15.49

respectively with duration less than 5 years and 71.32 ± 8.20, 59.26 ± 9.87, 14.57 ±

4.89 respectively with duration more than 5 years.

TINN, RR, PNN 50%, RR∆ index were 179.63 ± 113.29, 880.90 ± 117.42,

3.99 ± 1.95, 0.05 ± 0.01 respectively is hypertensives with less than 5 years duration

of disease.

TINN, RR, PNN50%, RR∆ Index was 104.9 ± 41.04, 833.09 ± 185.20, 0.47 ±

0.63, 0.05 ± 0.01 respectively in patients with more than 5 years of hypertension.

RMSSD, TINN, PNN 50% were reduced in hypertensive subjects with

duration more than 5 years and it was highly significant. (p < 0.001) (Table 7).

48
 TABLE 1
ANTHROPOMETRIC PARAMETERS BETWEEN NORMOTENSIVE AND
HYPERTENSIVE SUBJECTS
Normotensive
Normotensive Hypertensive subjects V/S
subjects subjects Hypertensive
subjects
Mean SD Mean SD t-value* p -value
Age (yrs) 48.4 6.3 51.6 5.4 2.89 0.005, S
Height (mt) 1.61 0.04 1.63 0.04 0.08 0.96, NS
Weight (kg) 61.04 4.11 63 5.53 0.01 0.97, NS
BMI(kg/m2 ) 23.33 2.2 24.00 1.98 1.62 0.11, NS
* Unpaired t-test
NS – Not significant
HS- Highly significant
S- Significant
TABLE 2
BLOOD PRESSURE PARAMETERS BETWEEN NORMOTENSIVE AND
HYPERTENSIVE SUBJECTS
Normotensive Hypertensive Normotensive V/S
subjects subjects Hypertensive subjects
Mean SD Mean SD t-value * p-value
Systolic BP
118.8 9.1 147.8 6.7 18.10 < 0.001, HS
(mm Hg)

Diastolic BP
77.6 5.2 90.3 3.5 14.49 < 0.001, HS
(mm Hg)

Pulse pressure
41.2 7.46 57.56 7.24 4.46 0.001, HS
(mm Hg)

Mean arterial
pressure 91.33 5.73 109.59 3.5 5.71 < 0.001, HS
(mm Hg)

* Unpaired t-test
NS – Not significant
HS- Highly significant
S- Significant

49
 TABLE 3
SPECTRAL ANALYSIS OF HEART RATE VARIABILITY BETWEEN
NORMOTENSIVE AND HYPERTENSIVE SUBJECTS
Normotensive
Normotensive Hypertensive subjects
Measurement subjects subjects V/S Hypertensive
subjects
Mean SD Mean SD t value * p- Level
Peak VLF 0.017 0.01 0.017 0.01 0.31 0.76, NS
frequency LF 0.08 0.03 0.06 0.02 3.40 0.001, S
(Hz) HF 0.26 0.11 0.25 0.15 0.13 0.90, NS
VLF 2299.5 345.4 2187.2 534.9 1.25 0.22, NS
Peak Power
LF 1076.2 496.6 787.9 484.2 2.95 0.01, S
(msec2 /Hz)
HF 356.3 223.2 339.3 174.9 0.42 0.67, NS
Frequency LF 49.70 16.41 43.00 12.00 2.32 0.02 , S
in HF 48.41 17.17 49.87 15.30 -0.45 0.66, NS
normalized
units (nu) LF/HF 1.64 0.74 0.93 0.37 6.07 0.00, S
* Unpaired t-test
NS – Not significant
HS- Highly significant
S- Significant

TABLE 4
TIME DOMAIN ANALYSIS OF HEART RATE VARIABILITY BETWEEN
NORMOTENSIVE AND HYPERTENSIVE SUBJECTS
Normotensive
Normotensive Hypertensive
subjects V/S Hypertensive
Measurement subjects subjects
subjects
Mean SD Mean SD t value * P Level
SDNN (ms) 66.96 10.01 59.16 9.54 3.99 0.000, HS
RR (ms) 949.15 140.38 848.39 166.82 3.27 0.001, S
PNN50% 6.19 2.74 1.60 2.04 9.51 0.000, HS
RMSSD 30.92 12.40 18.99 11.49 4.99 0.000, HS
HR/bpm 65.81 8.68 71.34 7.91 -3.33 0.001, S

RR ? Index 0.07 0.02 0.05 0.01 5.63 0.000, HS

TINN (ms) 301.84 198.90 128.84 79.38 5.71 0.000, HS

* Unpaired t-test
NS – Not significant
HS- Highly significant
S- Significant

50
 TABLE 5

COMPARISON OF HEART RATE RESPONSE TO DEEP BREATHING

BETWEEN NORMOTENSIVE AND HYPERTENSIVE SUBJECTS .

Normotensive
Normotensive Hypertensive
subjects V/S
subjects subjects
Measurement Hypertensive subjects
Mean SD Mean SD t value * p Level

HRV (db) 26.36 7.28 20.17 3.57 5.4 0.001, HS

* Unpaired t-test
HS- Highly significant

TABLE 6

COMPARISON OF SPECTRAL ANALYSIS OF HEART RATE

VARIABILITY DEPENDING ON DURATION OF HYPERTENSION.

Duration of Hypertension
Measurement < 5 yrs > 5 yrs < 5 yrs v/s > 5 yrs
Mean SD Mean SD t value * p Level
Peak VLF 0.02 0.01 0.02 0.01 0.57 0.57, NS
Frequency LF 0.06 0.04 0.08 0.03 -2.34 0.02, S
(Hz) HF 0.26 0.13 0.26 0.15 -0.06 0.96, NS
VLF 2138.63 590.67 2210.00 514.32 -0.44 0.66, NS
Peak Power LF 858.00 130.40 696.20 312.40 1.99 0.05, S
(msec2 /Hz) HF 323.19 128.80 346.88 194.20 -0.44 0.66, NS
Frequency in LF 46.78 13.34 41.27 11.01 1.54 0.13, NS
normalized HF 58.79 16.68 45.67 12.82 3.06 0.00, S
unit (nu)
LF/HF
0.84 0.31 0.98 0.38 1.28 0.21, NS
* Unpaired t-test
NS – Not significant
HS- Highly significant
S- Significant

51
 TABLE 7

COMPARISON OF TIME DOMAIN ANALYSIS OF HEART RATE

VARIABILITY DEPENDING ON DURATION OF HYPERTENSION.

Duration of Hypertension
Measurement < 5 yrs > 5 yrs < 5 yrs v/s > 5 yrs
Mean SD Mean SD t value * P Level
HR/bpm 71.40 7.53 71.32 8.20 0.04 0.97, NS
SDNN (ms) 58.94 9.11 59.26 9.87 -0.11 0.91, NS
RMSSD 28.40 15.49 14.57 4.89 4.77 0.00, HS
TINN (ms) 179.63 113.29 104.94 41.04 3.43 0.00, HS
RR (ms) 880.90 117.42 833.09 185.20 0.94 0.35, NS
PNN50% 3.99 1.95 0.47 0.63 9.60 0.00, HS
RR ?Index 0.05 0.01 0.05 0.01 1.78 0.08, NS
* Unpaired t-test
NS – Not significant
HS- Highly significant
S- Significant

52
 Graph 1 : Distribution of Normotensive and Hypertensive subjects

Normotensive subjects
50 50 Hypertensive subjects

Graph 2 : Comparison of blood pressure parameters between Normotensive and

Hypertensive subjects

160 147.8

140
118.8
120 109.59
Mean values (mm Hg)

100 90.3 91.33

77.6
80 Normotensive subjects
57.56 Hypertensive subjects
60
41.2
40

20

0
SBP DBP PP MAP

53
 Graph 3 : Comparison of peak frequency between Normotensive and

Hypertensive subjects.

0.30
0.26
0.25
0.25
Mean values (Hz)

0.20
Normotensive
0.15 Subjects
Hypertensive
Subjects
0.10 0.08
0.06
0.05
0.02 0.01
0.00
VLF( Hz) LF( Hz) HF( Hz)

PEAK FREQUENCY

Graph 4 : Comparison of peak power in msec2 /Hz between Normotensive and

Hypertensive subjects.

2500
2299.5
2187.2

2000
2
/Hz)
Mean values (m sec

1500 Normotensive
Subjects
1076.2 Hypertensive
1000 Subjects
787.9

500 356.3 339.3

0
VLF(ms2) LF(ms2) HF(ms2)
PEAK POWER (msec2/Hz)

54
 Graph 5 : Comparison of frequency domain in normalized unit between

Normotensive and Hypertensive subjects.

52
49.70 49.87
50
48.41
48
Mean values (nu)

46 Normotensive
Subjects
44 Hypertensive
43.00 Subjects
42

40

38
LF(nu) HF(nu)
NORMALISED UNIT (nu)

Graph 6 : Comparison of LF / HF ratio between Normotensive and

Hypertensive subjects.

1.64
1.80
1.60
LF/HF
1.40
1.20
Mean values

0.93
1.00
0.80
0.60
0.40
0.20
0.00
Normotensive Subjects Hypertensive Subjects

55
 Graph 7: Comparison of time domain analysis between Normotensive and

Hypertensive subjects.

80
71.3
70 65.8 67.0

59.2
60
Normotensive
Mean values

50 Subjects
Hypertensive
40 Subjects
30.9
30

19.0
20

10

0
HR/bpm SDNN(ms) RMSSD

TIME DOMAIN ANALYSIS

Graph 8 : Comparison of RR(ms) interval between Normotensive and

Hypertensive subjects

1000

949.15
950
Mean values (ms)

900

848.39
850

800

750

700
Normotensive Subjects Hypertensive Subjects

56
 Graph 9 : Comparison of PNN50% between Normotensive and Hypertensive

subjects

7.0
6.19
6.0

5.0
Mean PNN 50%

4.0

3.0

2.0 1.60

1.0

0.0
Normotensive Subjects Hypertensive Subjects

Graph 10 : Comparison of RR ∆ index between Normotensive and Hypertensive

subjects

0.08
0.07
0.07

0.06
Mean Values

0.05 0.05

0.04

0.03

0.02

0.01

0.00
Normotensive Subjects Hypertensive Subjects

57
Graph 11 : Comparison of TINN (ms) between Normotensive and Hypertensive

subjects

350.0 301.8

300.0

250.0
Mean values (ms)

200.0
128.8
150.0

100.0

50.0

0.0
Normotensive Subjects Hypertensive Subjects

Graph 12 : Comparison of heart rate response to deep breathing between

Normotensive and Hypertensive subjects

30
26.36
25

20.17
20
Mean HRV (db)

15

10

0
Normotensive Subjects Hypertensive Subjects

58
Discussion
 DISCUSSION

Hypertension is the most prevalent non communicable disorder in the world. It

is a big concern because of the devasting effects of its chronic complications.

Hypertension is a multisystem disorder that affect many organs of the body including

cardiovascular system.1

Cardiac function is regulated by various intrinsic and extrinsic mechanisms.

Heart rate is regulated mainly by the autonomic nervous system. Sympathetic nervous

activity increases the heart rate, where as parasympathetic (vagal) activity decreases

heart rate. When both systems are active, the vagal effects usually dominate. The

following reflexes regulate heart rate: baroreceptor, chemoreceptor, pulmonary

inflation, atrial receptor (Bainbridge) and ventricular receptor reflexes.7

This study “A comparative study of heart rate variability between hypertensive

and normotensive subjects” analyzes the effect of hypertension on cardiac autonomic

functions of hypertension patients.

Heart rate variability test was performed on 100 male subjects who were

divided into 2 groups, 50 hypertensive patients and 50 normotensive subjects. All the

subjects were in between the age group of 40-60 years. Hypertensive subjects were

again grouped into two groups based on the duration of hypertension i.e duration of

hypertension more tha n 5 years and less than 5 years.

The differences in the mean value of each parameter between hypertensive

subjects and normotensive subjects and the difference between in each parameters in

hypertensive patients based on duration of hypertension were analyzed and discussed.

59
FREQUENCY DOMAIN ANALYSIS:

Very low frequency (VLF) :

In our study there was not a statistically significant change in very low

frequency values between hypertensive and normotensive subjects.

Low frequency (LF):

In our study, there was a statistically significant reduction in the value of LF

peak frequency (Hz), LF power (ms2 ) and LF (nu) in hypertensive subjects compared

to normotensive subjects. Similar findings were found in studies of Tabassum R et

al8 , Huikuri et al44 , Singh et al45 , Guzzetti et al47 Sevre K et al51 , Virtaen R et al54 and

DaSilva Menezes A et al.55

Some studies reported controversial results in Frequency domain analysis of

heart rate variability in hypertensive individuals. Usually, the LF spectrum is said to

be modulated by sympathetic and parasympathetic activities. Our findings regarding

LF may be consequent to the reduction observed in the parasympathetic activity in

hypertensive individuals. Some studies reported that when the heart rate varied under

strictly controlled circumstances. The LF spectrum was mainly influenced by

sympathetic activity. However other data suggest that the heart rate variability is

calculated under unrestricted conditions, The LF spectrum reflects mainly the

parasympathetic activity, in accordance with our finings.45

High frequency (HF):

In our study, there was reduction in high frequency values in hypertensive

subjects but it was not statistically significant compared to normotensive subjects.

High frequency measures parasympathetic activity and our study showed there

was reduction in parasympathetic activity in hypertensive subjects.

60
LF/HF ratio:

In our study there was a statistically significant reduction in LF/HF ratio in

hypertensive subjects compared to normotensives. LF/HF ratio measures the

sympathovagal balance. Our study showed there was sympathovagal imbalance in

hypertensive subjects compared to normotensives.

Similar findings were found in studies of Radalli A et al42 , Huikuri et al44 ,

Guzzetti S et al47 and Makimattila S et al.48

TIME DOMAIN ANALYSIS:

Heart rate (bpm):

In our study, there was significantly increased heart rate in hypertensives

compared to normotensives.

Similar findings were found in studies of Singh et al45 , Purcell H et al52 ,

Virtanen R et al54 and Ahmad R et al58 . Fast resting heart rate is significantly

correlated with higher blood pressure, and increased heart rate is prospectively related

to the development of hypertension. Individuals with hypertension have increased

sympathe tic tone manifested by higher heart rate. 52

SDNN (ms):

In our study there was a statistically significant reduction in SDNN (ms) in

hypertensive subjects compared to normotensives.

Similar findings were found in studies of Chaco et al41 , Huikuri et al44 , Da

silva Menezes A et al55 , Park SB et al56 and Tabassum et al.60

61
RR (ms) :

In our study RR (ms) interval in normotensive subjects was significantly

reduced in hypertensive compared to normotensive subjects.

Similar findings were found in Pavithran P et al5 studies.

RMSSD :

In our study RMSSD was significantly reduced in hypertensives compared to

normotensives.

Similar findings were found in studies of Park SB et al56 and Tabassum R et al.60

Decreased values of SDNN, RMSSD indicating decreased HRV and lower RR

interval and higher heart rate are suggestive of decrease vagal modulation and higher

sympathetic activity in essential hypertension.

PNN 50% :

In our study PNN 50% was significantly reduced in hypertensive subjects

compared to normotensives.

Similar findings were found in Chaco et al41 , Huikuri HV et al44 Sevre K et

al51 and DaSilva Menezes A et al.55

PNN 50% is a sensitive measure of parasympathetic activity, it was lower

among hypertensive subjects, indicating decreased vagal tone.

RR ∆ index :

In our study, RR ∆ index was significantly reduced in hypertensive subjects.

62
TINN (ms) :

In our study, TINN (ms) value in hypertensives was significantly reduced.

RR ∆ index and TINN (ms) represents the parasympathetic activity and they are

significantly reduced in hypertensives.

Heart rate response to deep breathing (HRVdb) :

In our study, HRV during deep breathing was significantly reduced in

hypertensive subjects. Pavithran P et al5 and Radalli A et al42 studies also showed

reduced HRV during deep breathing.

The heart rate response to timed deep breathing (HRV db) is a classic test of

parasympathetic modulation of RR intervals. The fact that HRV db is reduced in

hypertensives is thus clear evidence of diminished vagal modulation of RR intervals

in this group.

Duration of hypertension:

In our study LF frequency (Hz) and LF power (ms2 ) was significantly reduced

in hypertensives with more than 5 years duration.

Similar findings were found in Huikuri et al44 studies. In long standing

hypertension there was reduction in very low and low frequency power spectrum

components, suggesting that low HR variability may contribute to increased cardiac

mortality.

RMSSD, TINN, PNN 50% was reduced in hypertensive subjects with duration

more than 5 years, showing significant lower parasympathetic activity in longer

duration.

63
Conclusion
 CONCLUSION

The conclusions of this study are :

• Significant increase in systolic blood pressure, diastolic blood pressure, pulse

pressure and mean arterial pressure in hypertensive subjects.

• Significant increase in heart rate in hypertensive subjects because of increase

sympathetic activity.

• Significant reduction in LF peak frequency (Hz), LF power (ms2 ) and LF

normalized units in hypertensive subjects.

• Significant reduction in LF / HF ratio in hypertensive subjects.

• Significant reduction in Time domain parameters like SDNN, RMSSD, RR

interval, HRV ∆ Index, TINN, PNN 50% in hypertensive subjects showing

decrease parasympathetic activity.

• Significant reduction in heart rate variation during deep breathing (HRVdb)

seen in hypertensive subjects showing sympatho-vagal imbalance.

• Very low frequency, HF peak frequency (Hz), HF power (ms2 ), HF in

normalized units are not significantly altered.

• There was significant reduction in low frequency, RMSSD, TINN, PNN 50%

in hypertensive subjects with duration more than 5 years, showing significant

lower parasympathetic activity in longer duration.

This study concluded that testing cardiovascular autonomic tests is important

in hypertensive patients to look for its dysregulation.

In conclusion, cardiovascular reflex effects can be assessed using heart rate

variability test effectively for physiological and clinical investigations in the field, by

64
the patients bed side, or in the laboratory using more elaborate equipment,

physiologists, clinicians and medical students can make use of these tests to assess or

understand cardiovascular autonomic tests in man in health or disease.

Our study shows that HRV is significantly reduced in hypertensive patients

compared to controls. Since reduced HRV is associated with cardiac arrhythmias,

suggesting that these hypertensive patients may have risk for occurrence of cardiac

arrhythmias.

These simple noninvasive measures can be used to detect differences in

cardiac autonomic balance that may be markers for autonomic impairment.

Our study concluded that, impaired cardiac autonomic function characterized

by sympathetic over activity may occur in hypertensive patients and also showed

sympathovagal balance is hypertensive patients is towards higher sympathetic and

lower vagal modulation.

65
Summary
 SUMMARY

The present study was conducted between January 2010 to August 2011 in the

department of Physiology, J.J.M. Medical College, Davangere. The work, was

undertaken to study the effect of hypertension on heart rate variability by correlating

in between hypertensive subjects and normotensive individuals.

Hundred healthy adult male subjects (50 hypertensive subjects were selected

from Bapuji hospital, Davangere and 50 healthy adults male subjects were randomly

selected from general population of Davangere) in the age group between 40-60 years

were selected for the study. The heart rate variability tests were assessed in terms of

frequency and time domain analysis. The results were compared and analysed

between hypertensive subjects and normotensive subjects.

The heart rate variability tests were performed by using computerized ECG

system with Niviqure software. The blood pressure was measured. The data was

documented and statistically analyzed. By giving suitable class intervals, intra

hypertensive groups were made to assess the effect of duration of hypertension on

heart rate variability tests.

Reduction in LF values, LF/ HF ratio ,Time domain parameters like SDNN,

RMSSD, RR interval, HRV ∆ Index, TINN, PNN 50% in hypertensive subjects

showing decrease parasympathetic activity. Significant reduction in heart rate

variation during deep breathing (HRVdb) seen in hypertensive subjects showing

sympatho- vagal imbalance.

66
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74
Annexures
 ANNEXURE – I

PROFORMA

Name : Date :

Age : Sex :

Address : Occupation :

Personal history :

• Smoker/Non smoker

• Alcoholic / Non alcoholic

• Any exercise

• History of any drug intake

Suffering from any medical illness :

Diabetes mellitus, Asthma, Muscular disorders,etc.

Duration of hypertension:

Past history :

Family history :

General physical examination :

Built :

Nourishment :

Pallor :

Temperature :

Weight (kg) :

Height (m) :

Wt
BMI = 2
(kg/m2 ) :
Ht

75
Systemic examination :

Cardiovascular system:

Respiratory system:

Per Abdomen:

Central nervous system:

Study parameters :

Systolic BP (mm Hg) :

Diastolic BP (mm Hg) :

Pulse pressure (mm Hg) :

Mean arterial pressure (mm Hg) :

Frequency domain measures :

VLF
Peak frequency (Hz) LF
HF
VLF
Power (ms 2 ) LF
HF
LF
Frequency in normalized
HF
units
LF/HF
Time domain measures :
Hear rate (bpm)
SDNN (ms)
RMSSD(ms)
RR (ms)
TINN (ms)
HRV ∆ Index
PNN 50%

Heart rate variation during deep breathing :

76
 ANNEXURE – II

WRITTEN INFORMED CONSENT

I voluntarily agree to participate in the study entitled “A COMPARATIVE

STUDY OF HEART RATE VARIABILITY BETWEEN HYPERTENSIVE

AND NORMOTENSIVE SUBJECTS”. The procedure and its consequences have

been explained to me in my own language.

Signature of the Signature of the

Investigator Participant

77
 NORMOTENSIVE SUBJECTS

FREQUENCY IN
SBP DBP PP MAP PEAK FREQUENCY PEAK POWER (msec2/Hz) NORMALISED UNIT TIME DOMAIN ANALYSIS
SL. Ht wt LF/ HRV
Name Age BMI (mm (mm (mm (mm (nu)
No (m) (Kg) HF (db)
Hg) Hg) Hg) Hg) VLF LF HF VLF LF HF SDNN PNN RR ? TINN
LF (nu) HF (nu) RR (ms) RMSSD HR/bpm
(Hz) (Hz) (Hz) (ms2) (ms2) (ms2) (ms) 50% Index (ms)
1 RAJU 41 1.6 56 21.81 138 80 58 196.00 0.027 0.088 0.213 2400 1521 400 64.92 35.077 1.854 61.46 839.77 7.02 19.66 71.42 0.075 175 32

2 GONAYA 46 1.62 54 20.61 110 76 34 144.00 0.013 0.08 0.427 2500 784 347 23.94 76.06 0.315 71.2 1011.19 6.75 24.8 61.67 0.073 165 40

3 NAGARAJ 43 1.54 60 25.31 140 84 56 196.00 0 0.088 0.33 1681 2250 401 71 11.7 3.1 56.2 1112 5 74 73.7 0.076 600 15

4 NAZER 49 1.72 62 21.01 124 80 44 168.00 0.04 0.06 0.187 1681 1500 246 51.2 48.7 1.05 72.1 914.09 6.01 38.51 65.28 0.071 770 34

5 GADIGEPPA 46 1.69 58 20.35 126 80 46 172.00 0.013 0.113 0.167 2500 641 100 72.34 27.34 2.616 75.18 1087 10 12.14 54.43 0.047 150 24

6 GANESH 49 1.59 63 25.01 118 74 44 162.00 0.013 0.14 0.447 1700 1300 676 61.87 38.12 1.613 76.25 912.57 3.5 32.82 65.42 0.094 685 23

7 GADIGEPPA 49 1.67 59 21.22 132 82 50 182.00 0.013 0.14 0.193 2401 676 256 55.46 44.54 1.214 68.96 839.34 6.9 18.05 71.09 0.0747 175 21

8 NAGARAJ 48 1.53 58 24.78 120 86 34 154.00 0.013 0.13 0.193 2401 700 246 55.78 43.8 1.245 67.8 854.9 14 19 76.9 0.08 180 26

9 RAMAPPA 43 1.54 52 21.94 108 68 40 148.00 0.013 0.047 0.18 2500 756 81 66.82 32.18 2.108 70.15 951.49 3.9 17.59 62.58 0.04 125 30

10 MYLAPPA 42 1.6 61 23.82 110 70 40 150.00 0.013 0.06 0.433 2401 1089 676 46.64 53.33 0.875 80.9 1120.63 2.47 25.32 53.19 0.069 165 18

11 MUTTANNA 44 1.58 59 23.69 128 78 50 178.00 0.033 0.06 0.187 2500 1681 346 51.27 48.72 1.052 91.6 1266 7.32 35.19 55.87 0.096 590 31

12 KONAPPA 42 1.61 60 23.16 120 80 40 160.00 0.013 0.053 0.22 2500 1024 784 40.59 59.41 0.683 75.89 826.95 5.1 37.51 72.3 0.08 395 22

13 YOGENDRA 43 1.63 64 24.15 114 80 34 148.00 0.013 0.053 0.27 2500 1024 784 40.59 59.41 0.683 75.89 826.95 5.1 37.51 72.31 0.08 395 20

14 RAJAMANI 41 1.65 59 21.69 100 70 30 130.00 0.027 0.12 0.153 2500 784 729 46.596 53.406 0.872 55.78 775.74 5.1 15.93 76.82 0.03 65 8

15 PRASAD 43 1.66 61 22.18 112 70 42 154.00 0.013 0.06 0.18 2001 1116 342 42.723 57.277 0.746 61.75 732.92 4.44 29.67 81.42 0.031 270 30

16 GURU 45 1.58 68 27.31 118 70 48 166.00 0.022 0.047 0.349 2500 589 324 24.491 75.509 2.1 62.37 776.12 6.53 37 76.9 0.043 116 24

17 PARAMESH 42 1.59 66 26.19 126 76 50 176.00 0.04 0.053 0.16 2500 1401 376 65.219 34.781 1.875 61.7 920.5 3.87 36.38 65 0.083 160 20

18 GIRISH 43 1.57 60 24.39 128 78 50 178.00 0.02 0.047 0.447 2500 1089 567 20.48 79.512 2.7 56 1157.35 11.8 32 51.56 0.13 325 43

19 SANDEEP 41 1.55 59 24.48 130 82 48 178.00 0.02 0.073 0.353 2500 623 144 53.492 46.506 1.15 58 1020.25 9.8 47.27 58.7 0.082 245 20

20 ANANDANNA 58 1.61 60 23.16 110 82 28 138.00 0.013 0.053 0.193 2500 561 64 78.16 21.88 2.98 54.1 900 5.9 34 63.3 0.068 115 32

21 KRISHNA 59 1.64 58 21.64 138 86 52 190.00 0.013 0.073 0.487 2500 689 49 75.8 24.2 2.12 60 933 4.8 32 60.33 0.067 480 25
ACHARI
22 MALLESHAPPA 59 1.66 67 24.36 128 84 44 172.00 0.013 0.053 0.427 2500 625 400 24.371 75.629 2.1 52.07 793.72 6.2 38.3 75.5 0.038 360 19

23 MALLAPPA 51 1.68 70 24.82 118 80 38 156.00 0.03 0.133 0.153 2500 676 169 65.75 34.75 1.92 66.73 943 3.2 18.89 63.2 0.068 105 34

24 HONNAPPA 56 1.65 69 25.36 120 80 40 160.00 0.013 0.1 0.187 2401 1681 276 49.749 50.251 0.99 73.85 856.53 4.19 31.39 69.98 0.089 215 25

25 VIJAYA 59 1.66 65 23.63 110 70 40 150.00 0.013 0.062 0.187 2500 576 441 42.4 57.595 0.736 72.01 943.98 4.3 30.1 70 0.065 200 19

78
26 NARENDRA 50 1.64 59 22.01 112 70 42 154.00 0.013 0.047 0.16 1500 1441 309 25.32 74.67 2.99 77.78 940.44 4.8 31 63.46 0.057 610 23

27 MUDEGOWDAPPA 58 1.6 60 23.43 116 72 44 160.00 0.01 0.131 0.294 1100 769 145 14.6 26.1 2.5 70.1 923 4.3 16 67.9 0.042 535 22

28 MURUGESH 55 1.59 56 22.22 112 70 42 154.00 0.01 0.08 0.153 2401 545 198 40.039 59.98 2.09 70.44 816 5.57 30.19 73.16 0.076 200 19

29 PAKIRAPPA 58 1.62 60 22.91 110 68 42 152.00 0.01 0.047 0.2 2401 1321 102 31.43 68.56 2.08 61 1083.57 4.7 34 55.32 0.06 390 30

30 NAGAppa 52 1.65 69 25.36 118 82 36 154.00 0.013 0.06 0.2 2401 1089 237 34.26 65.732 2.1 51.8 1021.42 6.7 28 58.62 0.04 190 32

31 VISHWARDYA 51 1.62 60 22.81 110 70 40 150.00 0.01 0.067 0.47 1936 803 168 52. 64 47.35 2.01 67.67 913.03 9.66 29 65.3 0.08 160 34

32 RUDRASWAMY 55 1.64 66 24.87 108 78 30 138.00 0.0133 0.053 0.16 2500 1065 158 63.31 36.69 1.726 43.1 1185 5.25 27.91 53.26 0.071 180 36

33 MANTESH 53 1.59 65 25.79 118 80 38 156.00 0.013 0.087 0.211 2401 576 196 65.245 37.74 2.2 61.7 1164.1 4.6 29.04 51.225 0.065 190 38

34 NAGARAJ 43 1.54 60 25.35 112 70 42 154.00 0 0.088 0.33 1681 1250 401 71 11.7 3.1 56.2 1112 5 74 73.7 0.076 600 30

35 NAZER 49 1.72 62 21.01 116 74 42 158.00 0.04 0.06 0.187 1681 1500 246 51.2 48.7 1.05 72.1 914.09 6.01 38.51 65.28 0.071 770 25

36 GONAYA 55 1.69 58 20.35 110 76 34 144.00 0.013 0.113 0.167 2500 641 100 72.34 27.34 2.616 75.18 1087 10 12.14 54.43 0.047 150 23

37 Md. YUNOUS 49 1.59 63 25.01 120 80 40 160.00 0.013 0.14 0.447 1700 2500 676 61.87 38.12 1.613 76.25 912.57 3.5 32.82 65.42 0.094 685 29

38 RAMESH 49 1.67 59 21.22 122 84 38 160.00 0.013 0.14 0.193 2401 676 256 55.46 44.54 1.214 68.96 839.34 6.9 18.05 71.09 0.0747 175 28

39 C.N . KUMAR 48 1.53 58 24.96 120 82 38 158.00 0.013 0.13 0.193 2401 700 246 55.78 43.8 1.245 67.8 854.9 14 19 76.9 0.08 180 34

40 JAGADEESH 43 1.54 52 21.94 118 76 42 160.00 0.013 0.047 0.18 2500 656 81 66.82 32.18 2.108 70.15 951.49 3.9 17.59 62.58 0.04 125 30

41 KUMAR SWAMY 42 1.6 61 23.82 124 80 44 168.00 0.013 0.06 0.433 2401 1089 676 46.64 53.33 0.875 80.9 1120.63 2.47 25.32 53.19 0.069 165 40

42 SADASHIVAPPA 58 1.58 59 13.69 122 80 42 164.00 0.033 0.06 0.187 2500 1681 346 51.27 48.72 1.052 91.6 1266 7.32 35.19 55.87 0.096 590 22

43 PRAKASH 42 1.61 60 23.16 108 76 32 140.00 0.013 0.053 0.22 2500 1024 784 40.59 59.41 0.683 75.89 826.95 5.1 37.51 72.3 0.08 395 25

44 NAVEEN 57 1.63 64 24.15 130 80 50 180.00 0.013 0.053 0.27 2500 1024 784 40.59 59.41 0.683 75.89 826.95 5.1 37.51 72.31 0.08 395 27

45 SHAMBANNA 41 1.65 59 21.69 134 80 54 188.00 0.027 0.12 0.153 2500 784 729 46.596 53.406 0.872 55.78 775.74 5.1 15.93 76.82 0.03 65 29

46 SHIVPRASAD 43 1.66 61 22.18 124 82 42 166.00 0.013 0.06 0.18 2001 2116 342 42.723 57.277 0.746 61.75 732.92 4.44 29.67 81.42 0.031 270 30

47 HANUMANTHAPPA 45 1.58 68 27.31 106 86 20 126.00 0.022 0.047 0.349 2500 789 324 24.491 75.509 2.1 62.37 776.12 6.53 37 76.9 0.043 116 33

48 BASAVRAJ 42 1.59 66 26.29 110 80 30 140.00 0.04 0.053 0.16 2500 2401 376 65.219 34.781 1.875 61.7 920.5 3.87 36.38 65 0.083 160 31

49 CHANDRANNA 60 1.57 60 24.38 118 78 40 158.00 0.02 0.047 0.447 2500 1089 567 20.48 79.512 2.7 56 1157.35 11.8 32 51.56 0.13 325 28

50 HALAPPA 41 1.55 59 24.48 116 80 36 152.00 0.02 0.073 0.353 2500 923 144 53.492 46.506 1.15 58 1020.25 9.8 47.27 58.7 0.082 245 29

79
 HYPERTENSIVE SUBJECTS

FREQUENCY IN
SBP DBP PP MAP PEAK FREQUENCY PEAK POWER NORMALISED TIME DOMAIN ANALYSIS
SL. Ht wt (mm (mm (mm (mm (msec2/Hz) HRV
No Name Age (m) (Kg) BMI UNIT (nu) LF/HF (db) Duration Duration
Hg) Hg) Hg) Hg) VLF LF HF VLF LF HF LF HF SDNN RR PNN RR ? TINN
RMSSD HR/bpm
(Hz) (Hz) (Hz) (ms2) (ms2) (ms2) (nu) (nu) (ms) (ms) 50% Index (ms)
1 ACHARYA 60 1.65 68 25 156 94 62 218.00 0.031 0.053 0.207 2401 625 360 48.275 51.722 0.93 58.35 870.27 3.69 81 70.23 0.064 230 8 5 LT 5 yrs

2 KRISHNA 56 1.58 55 22.08 166 98 68 234.00 0.013 0.047 0.227 2500 900 144 46.84 23.155 2.02 51.95 899.08 0 10.39 66.3 0.038 80 7 8 MT 5 yrs
MURTHY
3 SANGAPPA 58 1.59 65 25.75 142 92 50 192.00 0.02 0.023 0.48 2500 425 347 54.76 45.216 1.21 59.51 925.52 0 9.02 64.46 0.025 60 9 9 MT 5 yrs

4 MAHENDRAPPA 46 1.56 56 23.04 146 90 56 202.00 0.013 0.053 0.387 2500 741 400 57.45 72.552 0.79 68.2 840.53 4.54 24.92 76.55 0.075 175 14 4 LT 5 yrs

5 GANGANNA 53 1.6 67 26.17 150 98 52 202.00 0.02 0.04 0.413 2401 625 361 41.06 58.935 0.70 65.1 832 1.23 19.96 71.9 0.06 120 13 7 MT 5 yrs

6 RAJU 40 1.66 70 25.45 148 90 58 206.00 0.017 0.023 0.473 1206 750 345 39.97 40.02 1.00 76.37 890.16 2.53 26.58 72.12 0.063 175 21 6 MT 5 yrs

7 MALLESHAPPA 59 1.62 59 22.51 144 94 50 194.00 0.013 0.054 0.167 2401 526 225 24.32 35.67 0.68 49.78 772.25 0 6.58 77.16 0.029 60 15 8 MT 5 yrs

8 KOTRAPPA 55 1.61 54 20.84 142 96 46 188.00 0.02 0.061 0.453 2500 644 841 31.44 68.532 0.46 53.8 831.07 0 11.37 71.54 0.029 50 13 8 MT 5 yrs

9 SAIFULLA 55 1.64 59 22.01 138 90 48 186.00 0.02 0.047 0.113 2500 196 144 34.541 65.49 0.53 56.09 830.09 0.51 14.16 71.7 0.027 45 5 7 MT 5 yrs

10 M BASAPPA 50 1.59 62 24.51 144 90 54 198.00 0.013 0.052 0.173 2500 1024 361 46.12 43.85 1.05 51.83 729.55 0.66 13.35 81.54 0.032 100 22 8 MT 5 yrs

11 RAMESH 42 1.56 60 24.69 146 94 52 198.00 0.013 0.072 0.153 2500 169 529 29.62 70.375 0.42 56.07 818.01 0.47 14.89 77.82 0.04 58 22 8 MT 5 yrs

12 GURUBASAVARAJ 52 1.62 59 22.51 152 92 60 212.00 0.025 0.047 0.347 2500 889 321 44.49 75.509 0.59 59.28 769.96 5.76 33.21 77.49 0.04 116 35 5 LT 5 yrs

13 NAGRAJ 50 1.64 70 26.11 150 90 60 210.00 0.013 0.055 0.473 2500 961 196 31.81 28.18 1.13 79.77 1118.5 0.83 19.52 56.32 0.059 140 16 6 MT 5 yrs

14 SHANMUGAPPA 56 1.66 68 24.72 148 94 54 202.00 0.027 0.063 0.373 2500 529 324 53.4 46.5 1.15 55.11 726.15 0 12.31 77.51 0.049 110 15 9 MT 5 yrs

15 SHANKAR 48 1.62 54 20.61 140 96 44 184.00 0.013 0.067 0.016 2401 786 453 31.56 38.24 0.83 55.13 776.39 0 12.49 76.78 0.045 115 18 7 MT 5 yrs

16 SANNAPPA 59 1.59 59 23.41 142 90 52 194.00 0.018 0.075 0.153 2500 1156 729 45.82 44.17 1.04 55.35 777.3 0 12.56 76.68 0.055 125 18 10 MT 5 yrs

17 MAHESHANNA 49 1.68 71 25.17 140 88 52 192.00 0.013 0.071 0.447 2500 361 121 35.96 44.03 0.82 74.74 105.58 0.52 19.67 60.7 0.049 140 20 9 MT 5 yrs

18 GANGANNA 53 1.66 69 25.05 152 90 62 214.00 0.018 0.042 0.421 2401 643 357 41.06 58.935 0.70 65.1 832 1.23 19.96 71.9 0.06 120 19 10 MT 5 yrs

19 HALLAPPA 58 1.59 67 26.58 166 92 74 240.00 0.02 0.073 0.48 2401 1225 345 54.76 45.216 1.21 59.51 925.52 0 9.02 64.46 0.025 60 23 10 MT 5 yrs

20 SURENDRANNA 46 1.56 62 25.51 154 90 64 218.00 0.013 0.053 0.387 2500 741 400 57.45 72.552 0.79 68. 2 840.53 4.54 24.92 76.55 0.075 175 19 3 LT 5 yrs

21 SHIVANNA 53 1.6 65 25.39 156 94 62 218.00 0.02 0.07 0.413 2500 825 361 51.06 58.935 0.87 65.1 832 1.23 19.96 71.9 0.06 120 18 4 LT 5 yrs

22 CHANDRSHEKAR 40 1.54 64 27.01 142 88 54 196.00 0.04 0.063 0.4 73 1206 1050 478 59.973 40.02 1.50 76.37 890.16 2.53 26.58 72.12 0.063 175 18 2 LT 5 yrs

23 UMMANNA 59 1.62 59 22.51 148 92 56 204.00 0.013 0.07 0.167 2401 1024 225 24.32 35.67 0.68 49.78 772.25 0 6.58 77.16 0.029 60 18 10 MT 5 yrs

24 ANNAYYA 55 1.61 59 22.72 144 90 54 198.00 0.02 0.031 0.453 2500 444 841 31.44 68.532 0.46 53.8 831.07 0 11.37 71.54 0.029 50 19 9 MT 5 yrs

25 MUDASSIR 55 1.64 54 20.14 148 90 58 206.00 0.02 0.047 0.113 2500 196 144 34.541 65.49 0.53 56.09 830.09 0.51 14.16 71.7 0.027 45 19 10 MT 5 yrs

80
26 PRABULING 50 1.7 78 26.98 144 88 56 200.00 0.013 0.04 0.173 2500 1024 361 36.13 43.85 0.82 51.83 729.55 0.66 13.35 81.54 0.032 100 19 8 MT 5 yrs

27 SADANAND 42 1.7 71 24.56 144 88 56 200.00 0.013 0.147 0.153 1204 869 529 69.62 70.375 0.9 9 56.07 818.01 0.47 14.89 77.82 0.04 58 18 2 LT 5 yrs

28 CHIKKANNA 52 1.62 60 22.91 146 92 54 200.00 0.025 0.057 0.234 2500 689 321 54.49 75.509 0.72 59.28 769.96 5.76 33.21 77.49 0.04 116 19 4 LT 5 yrs

29 PEERYA NAIK 50 1.64 70 26.02 140 90 50 190.00 0.013 0.05 0.2802 2500 961 196 51.81 28.18 1.84 79.77 1118.5 0.83 19.52 56.32 0.059 140 18 9 MT 5 yrs

30 HALESHAPPA 56 1.66 69 25.09 166 84 82 248.00 0.027 0.107 0.173 1204 529 324 53.4 46.5 1.15 55.11 726.15 0 12.31 77.51 0.049 110 18 10 MT 5 yrs

31 KENCHANANNA 48 1.62 68 25.92 148 86 62 210.00 0.013 0.067 0.016 2401 925 345 41 38.24 1.07 55.13 776.39 0 12.49 76.78 0.045 115 24 6 MT 5 yrs

32 SHEKARAPPA 59 1.59 66 26.19 140 88 52 192.00 0.014 0.054 0.153 2500 1156 456 76 44.17 1.72 55.35 777.3 0 12.56 76.68 0.055 125 22 9 MT 5 yrs

33 AKBAR ALI 55 1.64 69 25.65 154 88 66 220.00 0.02 0.047 0.113 2500 196 144 34.541 65.49 0.53 56.09 830.09 0.51 14.16 71.7 0.027 45 21 10 MT 5 yrs

34 KOTRAPPA 50 1.72 72 24.41 152 92 60 212.00 0.013 0.03 0.173 2500 1024 361 36. 14 43.85 0.82 51.83 729.55 0.66 13.35 81.54 0.032 100 19 12 MT 5 yrs

35 H P PATIL 42 1.56 62 25.51 150 90 60 210.00 0.013 0.147 0.153 2500 869 529 39.62 70.375 0.56 56.07 818.01 0.47 14.89 77.82 0.04 58 21 4 LT 5 yrs

36 SIDDALINGAPPA 52 1.62 68 25.95 152 90 62 214.00 0.025 0.047 0.123 2500 889 321 34.49 75.509 0.46 59.28 769.96 5.76 33.21 77.49 0.04 116 20 3 LT 5 yrs

37 VASU DEVA 50 1.64 59 21.93 142 80 62 204.00 0.013 0.05 0.234 2500 961 196 31.71 28.18 1.13 79.77 1118.5 0.83 19.52 56.32 0.059 140 19 10 MT 5 yrs

38 BABU SAAB 56 1.66 68 24.72 146 90 56 202.00 0.027 0.06 0.373 1204 529 324 53.4 46.5 1.15 55.11 726.15 0 12.31 77.51 0.049 110 18 12 MT 5 yrs

39 SHAKIR ULLA 48 1.62 63 24.04 156 92 64 220.00 0.013 0.067 0.016 2401 525 450 41.76 38.24 1.09 55. 13 776.39 0 12.49 76.78 0.045 115 19 8 MT 5 yrs

40 CHENNESHAPPA 59 1.59 63 25.01 158 92 66 224.00 0.012 0.051 0.153 1305 956 729 35.82 44.17 0.81 55.35 777.3 0 12.56 76.68 0.055 125 29 13 MT 5 yrs

41 DIVAKAR 45 1.76 62 20.06 140 90 50 190.00 0 0.054 0.113 1000 769 145 14.6 26.1 0.56 62.1 923 4.3 16 70 0.042 489 19 2 LT 5 yrs

42 HANUMANTAPPA 56 1.72 60 20.33 144 92 52 196.00 0.012 0.051 0.153 2401 345 198 40.039 47.9 0.84 61.5 987 2.1 17 69 0.076 200 18 9 MT 5 yrs

43 IYAZ AHAMED 44 1.7 59 20.41 144 88 56 200.00 0.0023 0.076 0.2 2401 1025 143 41.53 43.9 0.95 42 1083.57 4.7 21.8 55.32 0.06 390 23 3 LT 5 yrs

44 NARESHANNA 49 1.68 66 23.41 148 80 68 216.00 0.011 0.06 0.1987 2401 989 178 34.26 47 0.73 51.8 1021.42 6.7 28 60 0.04 190 12 2 LT 5 yrs

45 RENUKERADYA 53 1.58 60 24.08 140 90 50 190.00 0.013 0.053 0.47 1204 803 168 52.64 47.35 1.11 40 913.03 3.01 29 62.89 0.06 160 19 4 LT 5 yrs

46 KARUNAKAR 47 1.66 59 21.45 148 88 60 208.00 0.0032 0.053 0.16 1204 465 158 53 36.69 1.44 43.1 1185 1.2 27.91 53.26 0.071 180 17 6 MT 5 yrs

47 SURENDRAPPA 56 1.7 69 23.87 140 90 50 190.00 0.013 0.082 0.1123 2401 1076 196 54 37.74 1.43 61.7 1164.1 4.6 19.6 61.3 0.065 190 19 3 LT 5 yrs

48 DHARMANNA 58 1.59 58 23.01 146 92 54 200.00 0.025 0.047 0.114 2500 889 321 34.49 75.509 0.46 59.28 769.96 5.76 33.21 77.49 0.04 116 23 3 LT 5 yrs

49 PALAKSHAPPA 55 1.62 70 26.71 152 88 64 216.00 0.013 0.046 0.473 1204 961 196 31.81 28.18 1.13 79.77 1118.5 0.83 19.52 56.32 0.059 140 18 12 MT 5 yrs

50 CHENNAVEERAPPA 53 1.69 66 23.15 154 90 64 218.00 0.027 0.053 0.373 1204 529 324 53.4 46.5 1.15 55.11 726.15 0 12.31 77.51 0.049 110 16 11 MT 5 yrs

81