Essential Cardiovascular Medicine 6th Edition

Volume 2 Mohamed S. Elguindy pdf download

https://ebookmeta.com/product/essential-cardiovascular-medicine-6th-edition-volume-2-mohamed-s-
elguindy/

★★★★★ 4.9/5.0 (45 reviews) ✓ 141 downloads ■ TOP RATED

"Excellent quality PDF, exactly what I needed!" - Sarah M.

DOWNLOAD EBOOK
 Essential Cardiovascular Medicine 6th Edition Volume 2
Mohamed S. Elguindy pdf download

TEXTBOOK EBOOK EBOOK META

Available Formats

■ PDF eBook Study Guide TextBook

EXCLUSIVE 2025 EDUCATIONAL COLLECTION - LIMITED TIME

INSTANT DOWNLOAD VIEW LIBRARY

Collection Highlights

Cardiovascular and Coronary Artery Imaging: Volume 2 1st

Edition Ayman S. El-Baz

Braunwald s Heart Disease a Textbook of Cardiovascular

Medicine Single Volume 11th Edition Douglas P. Zipes

Braunwald's Heart Disease - Part 2 - A Textbook of

Cardiovascular Medicine 12th Edition Peter Libby

Cosserat Plate Theory Lev Steinberg Roman Kvasov

Socio-Ecological Systems and Decoloniality: Convergence of
Indigenous and Western Knowledge Deepa Pullanikkatil

Alcohol, Crime and Public Health 1st Edition Dorothy

Newbury-Birch

Legal Guide for the Visual Artist Fifth Edition Tad

Crawford

Pro Hadoop Data Analytics Designing and Building Big Data

Systems using the Hadoop Ecosystem Apress L.P.

Sick of the System Why the COVID 19 Recovery Must Be

Revolutionary 1st Edition James T Brophy
Beginning Rust: Get Started with Rust 2021 Edition Carlo
Milanesi
 ESSENTIAL

· CARDIOVASCULAR
MEDICINI;
6TH Edition
 ESSENTIAL
CARDIOVASCULAR MEDICINE
 Tl

I
I I

SIXTH EDITION

MOHAMED S. ELGUINDY, MD, FRCP,

PROFESSOR OF CARDIOLOGY
CAIRO UNIVERSITY

AHMED M. ELGUINDY, MD, MRCP, FACC

CHIEF OF CARDIOLOGY
ASWAN HEART CENTRE
MAGDI YACOUB FOUNDATION
HONORARY SENIOR LECTURER,
IMPERIAL COLLEGE, LONDON, UK
IV

Essential
6th edition

Copyright 9, 20 2011, 2007, 1998, 1990. rights reserved. No part of this

publication be reproduced or distributed in any form or by any means, or stored
in a database or system, without the prior written permission of the senior
author.

Note

Medicine is an ever-changing science. As new research and clinical experience broaden

our knowledge, changes in treatment and drug therapy are required. The authors of this
work have checked with sources believed to be reliable in their efforts to provide
information is complete and generally in accord with the standards accepted at the
time of However, view of the possibility of human error or changes in
medical sciences, authors warrant that the information contained herein is in every
respect accurate or complete, and they are not responsible for any errors or omissions or
the results · the use of such information. Readers are encouraged to confirm
the contained herein with other sources. For example and in particular,
readers are advised to check the product information sheet included in the package of each
drug they to administer to be certain that the information contained in this book is
accurate and changes have not been made in the recommended dose or in the
contraindications
 v

CONTENTS

Preface

Chapter 1: The History ........................................................................................................ 1

Chapter 2: Physical examination ......................................................................................... 7
Chapter 3: Electrocardiography ......................................................................................... 45
Chapter4: Exercise electrocardiographic testing ............................................................... 63
Chapter 5: Echocardiography ............................................................................................. 85
Chapter 6: Plain radiology of the heart ............................................................................... 99
Chapter 7: Nuclear Cardiology ......................................................................................... 107
Chapter 8: Cardiovascular magnetic resonance imaging.................................................... 125
Chapter 9: Cardiovascular computed tomography ............................................................ 13 7
Chapter Cardiac catheterization ................................................................................... 14 9
Chapter 11: Coronary arteriography, ventriculography and intracoronary imaging ............. 164
Chapter 12: Heart failure .................................................................................................... 183
41 Acute heart failure .................................................................................. .235
41 Heart failure with preserved ejection fraction .......................................... .246
Chapter 13: Cardiac arrhythmias ....................................................................................... .252
41 Electrophysiological considerations .......................................................... .252
41 Mechanisms of arrhythmias ...................................................................... .257
41 Evaluation of cardiac arrhythmias ............................................................. .265
41 Sinus nodal disturbances ............... --.. -................... -. -- --................... -.......... .277
41 Atrial arrhythmias ...................................................................................... 286
41 Atrioventricular junctional arrhythmias ..................................................... .317
41 Arrhythmias involving the atrioventricular junction .................................. 310
41 Summary of ECG diagnosis of supraventricular tachycardia........................ 319
., Ventricular arrhythmias ............................................................................. 325
., Heart block ............................................................................................... 348
., AV dissociation ......................................................................................... 355
11 Other abnormalities leading to cardiac arrhythmias ................................... 357

11 Antiarrhythmic drugs ............................................................................... 358

11 Cardiac pacemakers .................................................................................. 3 73
41 Implantable cardiovertor defibrillator (ICD) and other non- ............................ .
pharmacological treatment of cardiac arrhythmias ...................................... 3 84
Chapter 14: Cardiac arrest and sudden cardiac death ............................................................. 393
Chapter 15: Cardiopulmonary and Cardiocerebral resuscitation ............................................ .402
Chapter 16: Syncope ....................................................................................................411
Chapter 17: The biology of atherosclerosis and the prevention of coronary .................................. .
heart disease ....................................................................................................422
Chapter 18: Lipoprotein disorders ........................................................................................ ..445
Chapter 19: Stable angina ................................................................................................... .471
Chapter 20: Unstable angina and non-ST-elevation myocardial infarction .............................. 503
Chapter 21: ST-elevation myocardial infarction ..................................................................... 530
Chapter 22: Percutaneous coronary intervention (PCI) ........................................................... 574
Chapter 23: Arterial hypertension .......................................................................................... 597
Chapter 24: Pulmonary hypertension ..................................................................................... 643
vi

Chapter 25: Deep venous thrombosis and pulmonary thromboembolism ________________________________ 661
Chapter 26: heart disease ------------------------------------------------------------------------------···-·····677
Ill Mitral stenosis ······----------------------------·--·--------------·---·--·---··-··--·--------------·--··--··680
<I> regurgitation ------·-------------------------------------------------·--···-·------··------····-····688
• valve prolapse -·····---·--·-----··-·--------··------------------------·-----------------------··-·695
• Aortic stenosis -----------·····-------·--·--------·--·--·------------------------·--·-·------··--·-------·-··701
• Aortic regurgitation -------··-····-------··--·--------·-----------------------·--··--------·-·-··----------711
• Tricuspid stenosis -·---------··--··-·····-·--------------------------------------·······----··--·-···------721
• Tricuspid regurgitation ------·-··-··-···-···-----··-··-------···-------··-··-------····-----············723
<1> Pulmonary stenosis ----------·-···--·--······-------------------··--·-------------------··------------·-·727
e Pulmonary regurgitation -------------·--···-··---·-·-------·-·-············-------------··-···---------727
• Multivalvular disease -----------------······---·-··-··-·----------------····-----------------------------730
• Drug-induced valve disease ---------------········-······--·--··-···----------------···-·------------731
Prosthetic heart valves --····--·-------------------················-··------------------···--···-··------732
@

Percutaneous valve replacement and repair ------·--··--······------·····---------··-----------739

@

Chapter 27: Infective endocarditits --------------------·····--·······---------------·--··-···--···-·-----------------------740

Chapter 28: Congenital heart disease ----------------------------·-···--··---------------···-···--·------------------··-·-754
Effects of congenital cardiac lesions ------········-·-------------------------··--··---------··----763
@

• Atrial septal defect --------··········-···-···-·---------------····-··--·--··-·---------------------------·· 769

<1> Patent foramen ovale -----------------------·····-----------------··········-···-·----------·--··--·-----772
• Ventricular septal defect ·--------------------------··------------------··--··-------··---------------···773
• Patent ductus arteriosus ····-----······--------------·--····------------------·--·------··--··-----------777
e Atrioventricular septal defect (endocardial cushion defect) -----------·····--·-----779
Partial anomalous pulmonary venous connection --···-···--·----·-··-···--·----------·--·· 783
@

1& Pulmonary stenosiS.----------------------------·-···--·--------------·-·--···--··-·······-···-··--------··· 786

Peripheral pulmonary artery stenosis -·-···--··-·----------------------··-··--·--···-···-------··· 788
@

e Congenital aortic stenosis -------------------------·-······-··-·-·-----------------·············-·······789

• Coarctation of the aorta ··----------------------···········-····-······--------··················----···794
Tetralogy of Fallot ···-···-··-··········------··-··-----······-···-······--·--···-·-·-··········-········· 799
@

e Tetralogy of Fallot with absent pulmonary valve ······--·--------------··········-·····-··-·804

e Complete transposition of the great arteries ··-···------··-···--·········-·-··-·-·---------···805
e Congenitally corrected transposition of great arteries --·--················------------···-811
Tricuspid atresia ·-·--··········-·-·-····--·---------------·····-·-·······--·--········-··--···············814
@

• Fontan procedure ··········-··------······················--··------····-···············---·------------···816

Pulmonary atresia with intact ventricular septum ·······--···-··-----····-················-·820
@

e Ebstein's anomaly.......... ---······--········-······--------------···---······-·············--·--------····822

e Persistent truncus arteriosus ·················--··-··----------·······-········-······:·-·--·----······825
e Double inlet ventricle (single ventricle.) .......................................................... 828
Double outlet right ventricle
@ ··········-··-······--·-···-·-············-------······-·--830
• anomalous pulmonary..v.eru:ms..conne.ction.............................................. 833
Hypoplasic left heart s;yndrome. ...................................................................... 836
@

Eisenmenger syndrome ········-··············--·······-··-···-·-······---·········-----·-·······-······839

@

Heterotaxia ············-·--···········-···-···········-··---·····················-·--······----------·········841
@

e Chamber localization and cardiac malposition --··········-·······-··········--·--··--·······843

 VII

Vascular ring ................................................................................................. 845

'11

e Congenital anomalies of the coronary circulation .......................................... 847

• Syndromes of congenital heart disease ........................................................... 851
e Summary of operations for congenital heart diseases ...................................... 853
Chapter 29: Molecular biology and genetic aspects of cardiovascular disease ......................... 856
Chapter 30: Cardiomyopathies .............................................................................................. 884
e Dilated cardiomyopathy ............................................................................... 885
e Hypertrophic cardiomyopathy ...................................................................... 889
• Restrictive and infiltrative cardiomyopathies ................................................ 900
• Arrhythmogenic right ventricular cardiomyopathy (dysplasia) ...................... 910
• Left ventricular noncomp.acti.on..................................................................... 912
e Hypertensive cardiomy.opathy ....................................................................... 913
• Metabolic cardiomyopathy .......................................................................... 913
ID Takotsubo cardiomyopathy ........................................................................... 913
ID Tachycardia-induced cardiomyopathy ........................................................... 914
e Ischaemic cardiomyopathy .......................................................................... 914
• Muscular dystrophy cardiomyopathy ........................................................... 916
Chapter 31: Myocarditis ................................................................................................... 918
Chapter 32: Cardiac tumours ........................................................................................ 924
Chapter 33: Diseases of the pericardium ................................................................................. 931
Chapter 34: Diseases of the aorta and its main branches ......................................................... 954
Chapter 35: Peripheral arterial diseases ................................................................................. 983
Chapter 36: Pregnancy and cardiovascular disease ........................................................ ,. .... 1004
Chapter 37: Non cardiac surgery in patients with heart disease ............................................. 10 i 8
Chapter 38: Medical management of patients undergoing cardiac surgery ............................ 1028
Chapter 39: Cardiovascular disease in the elderly ............................................................... .1041
Chapter 40: Cardiovascular disease in women .................................................................... .1050
Chapter 41: Cardiovascular disease in athletes ..................................................................... 1056
Chapter 42: Metabolic and endocrine disorders ................................................................... .1061
Chapter 43: Erectile dysfunction .......................................................................................... 1082
Chapter44: Rheumatic fever ............................................................................................... 1085
Chapter 45: cardiac involvement in other rheumatic disorders .............................................. .1091
Chapter 46: Cardiovascular affection in HIV infection ........................................................ .1103
Chapter 47: Cardiovascular manifestations of cancer .......................................................... .1106
Chapter 48: Psychiatric aspects of cardiovascular disease .................................................... 1112
Chapter 49: Neurological disorders and cardiovascular disease ............................................ 1117
Chapter 50: Renal disorders and cardiovascular disease ....................................................... 1124
Chapter 51 : Cardiac rehabilitation ....................................................................................... 113 6

Index
 PREFACE

We are pleased to introduce the sixth edition of "Essential Cardiovascular . It has

been almost 30 years since the publication of the first edition. years, many
cardiologists, internists and trainees have relied on its breadth of
knowledge and clinical relevance to keep up-to-date on advances in to help
optimize patient care.
In the past several decades, cardiology has advanced at extremely pace on many
fronts. Knowledge of the diagnosis and management of patients disease, as well
as understanding the mechanisms and preventive approaches advance Genetics,
molecular biology, pharmacology, imaging, invasive interventions and cardiac repair are
only a sampling of what we encounter and practice daily. This constant of research
generated a proliferation of cardiovascular literature at unprecedented scale. such
rapidly changing cardiovascular knowledge base, a textbook this readers
can turn for the accurate and up-to-date information offers a great
As with each previous edition, the book has been carefully revised chapters
updated and expanded to include the results of recent trials practice guidelines
recommendations. The reader will find a complete overview of various cardiovascular topics
plus a timely focus on evidence-based medicine in a reader-friendly design.
We offer our appreciation to Dr. Maram EITatawy, now a practicing cardiologist for her
tireless effort in preparing the manuscript. We hope the readers reading this
edition and learn from it as they strive to improve academic achievement importantly
patient care, our ultimate goal.

S. E/Guindy
E/Guindy
 597

CHAPTER23

ARTERIAL HYPERTENSION
Definitions
• Hypertension is defined as a systolic BP (SBP) of~ 130 mmHg and/or a BP (DBP) of~
80 mmHg in persons not taking antihypertensive medication. Those with a 120-129 mmHg
systolic and < 80 mmHg diastolic are classified as elevated BP. These patients have increased
risk of cardiovascular events by 1.1-1.5 fold compared with a normal BP mmHg) and
have annual rate of developing hypertension of> 15%. The positive correlation between BP and
cardiovascular morbidity and mortality is continuous and stronger for SBP than for DBP.
Aging is associated with a progressive increase in SBP, a reduction in DBP a widening of
pulse pressure. This is related to reduction in the compliance or stiffening the large conduit
arteries.
• Isolated systolic hypertension (ISH) is defined as SBP of~ 130 mmHg in the presence of DBP of
:::; 80 mmHg. It is the predominant form of hypertension in the elderly. The accuracy of diagnosis
and staging of hypertension is markedly improved by using SBP rather than DBP as the dominant
criterion.
"' Essential (primary or idiopathic) hypertension is defined as high BP due to neither secondary
cause nor a monogenic (mendalian) disorder. It accounts for 90% of all cases.
• Secondary hypertension is high BP caused by an identifiable and potentially curable disorder.
• Resistant hypertension is defined as BP ~ 130/80 mmHg despite adequate doses of 3 or more
antihypertensive drugs including a diuretic given for at least one month, or hypertension requi1ing
4 or more drugs regardless of blood pressure level achieved.
"' Spurious hypertension (or pseudohypertension) is artefactually elevated BP by indirect
cuff measurement over a rigid, often calcified brachial artery.
• White coat hypertension. This term describes patients whose BP is > mmHg in an office or
clinic setting, with a normal daytime ambulatory BP (<120/80 This is a relatively benign
condition with low risk of morbid events. However, the risk may increase with long term follow
up (~ 6 years).
• Masked hypertension is a mirror image of white coat hypertension. The clinic is normal but
ambulatory or home measurements are high and associated with high risk. It occurs 6% of the
normotensive population.
• Hypertensive crises encompass both hypertensive emergencies and hypertensive urgencies.
Hypertensive emergencies are defined as elevation in SBP and/or DBP 80 mmHg and/or> 120
mmHg respectively) associated with impending or progressive target organ damage such as major
neurological changes, hypertensive encephalopathy, cerebral infarction, intracranial haemorrhage,
acute LV failure, acute pulmonary oedema, aortic dissection, renal failure or eclampsia.
Hypertensive urgencies denote isolated BP elevation of systolic and/or BP> 180 and/or
120 mmHg respectively without target organ damage.
• Accelerated hypertension is a hypertensive emergency associated with retinal haemorrhage and
exudates.
• Malignant hypertension is a hypertensive emergency associated with papilloedema.

Prevalence
The global prevalence of hypertension in adults aged 25 years and above is 40%. The
prevalence increases with age, so that well over half of the population above the age 55 have
hypertension and in the 75+ age group, the prevalence is 70-80%. SBP in the population increases
with advancing age throughout life whereas DBP tends to plateau or fall after age Consequently,
the prevalence ofISH is much greater in the elderly than in middle-aged and younger individuals.
598

A higher percentage of men than women have hypertension until age 45. From age 45-54, the
percentages men and women with hypertension are similar and after age 55, a much higher
percentage of women have hypertension than do men.
The lifetime of developing hypertension is about 90% for men and women who were not
hypertensive at 55-65 years old and survived to age 80-85.
In both sexes, hypertension is associated with higher body mass index (BMI) and black race.

An updated classification of hypertension in adults> 18 years of age is given in table 23.1. The
classification is based on the mean of two or more properly measured seated blood pressure readings
on two or more office visits. Normal BP is defined as levels below 120/80 mmHg. Hypertension is
defined as systolic BP 2: 130 or diastolic BP 2: 80 mmHg. Systolic BP of 120-129 or diastolic
BP < 80 mmHg is classified as elevated BP. These patients are at increased risk for progression to
hypertension.
Hypertension is divided into 2 stages:
- Stage 1 includes patients with systolic BP 130-139 or diastolic BP 80-89 mmHg.
- Stage 2 includes with systolic BP 2: 140 or diastolic BP 2: 90 mmHg.
A more elaborate classification of blood pressure is provided by the European Society of hypertension
(ESH) and the European Society of Cardiology (ESC) (Table 23.2).
The continuous relationship between the level of blood pressure and cardiovascular risk makes any
numerical definition and classification of hypertension arbitrary.
Blood pressure should be measured on at least 2 occasions. If the hypertension is stage 1,
measurement should be made within l month of each other. If stage 2, within a week and if more
severe, immediate action is necessary. Patients should be clearly informed that a single elevated
reading does not constitute a diagnosis of hypertension but is a sign that further observations are
required.

risk

e The between BP and cardiovascular disease mortality is positive, strong and

continuous. Death from ischaemic heart disease increases continuously and linearly from BP
levels as low as 115 mmHg systolic and 75 mmHg diastolic upward.
e An increment of 20 mmHg in SPB or 10 mmHg in DPB in middle aged and elderly persons is
associated with a twofold increase in cardiovascular disease (both ischaemic heart disease and
stroke) the entire range BP. Likewise a decrease of 20 mmHg in SBP or 0
mmHg DBP halves cardiovascular mortality.
e Individuals with a BP in the elevated BP range (SBP 120-129 mmHg or DBP < 80 mmHg) also
have a significantly greater risk of developing a cardiovascular event than those \vith a normal BP
(<120/80 ..- ..~~,,,,

Total cardiovascular

The presence of other cardiovascular risk factors particularly diabetes mellitus, target organ damage
(TOD) and associated cardiovascular and renal disease substantially increase the risk of hypertension
regardless of its level. The level of risk is used to determine the threshold and type of therapeutic
intervention. Table 23.3 indicates the most common risk factors, target organ damage and associated
clinical conditions which are used to stratify risk On the basis of such association, the ESH/ESC
proposed a classification of the level of added risk associated with different values of blood pressure
(Table 23.4).
The terms low, moderate high and very high added risk are calibrated to indicate an approximate 10-
years risk of cardiovascular disease of <15%, 15-20%, 20-30% and >30% respectively or an
approximate absolute risk of fatal cardiovascular disease of <4%, 4-5%, 5-8% and >8% respectively.
 599

Table 23.1 Categories of BP in Adults*

BP category SBP DBP

Normal < 120mmHg and <80mmHg
Elevated 120-129 mmHg and <80mmHg
Hypertension
Stage 1 130-139 mmHg or 80-90mmHg
Stage 2 :::: 140mmHg or ::'.:90mmHg
*individuals with SEP and DBP in2 categories should be designated to the higher BP category.
BP indicates blood pressure (based on an average of~ 2 careful readings obtained on~ 2 occasions, DBP,
diastolic blood pressure; SBP systolic blood pressure.

Table 23.2 Classification of blood ressure for adults (ESC,

Category

Optimal < 120 <80

Normal 120-129 80-84
High normal 130-139 85-89
Grade 1 hypertension 140-159 90-99
Grade 2 hypertension 160-179 l 00-109
Grade 3 hypertension :::: 180 :::: lO
Isolated systolic hypertension :::: 140 <90

Table 23.3 Factors influencing prognosis ofhypertension

A- Risk factors:
" Level of systolic and diastolic blood pressure.
" Men> 55 years .
., Women > 65 years.
e Smoking.
• Dyslipidaemia.
" Family history of premature cardiovascular disease(< 55 years men, <65 years
• Abdominal obesity (abdominal circumference:::: 102 cm men,:::: 88 cm
• C-reactive protein:::: l mg/dl.

B- Target organ damage (TOD):

" Left ventricular hypertrophy (LV mass index > 125 g/m2 men, > l 0 glm2
• Carotid intima-media thickness:::: 0.9 mm or atherosclerotic plaque.
e Serum creatinine > 1.3 mg/dl men,> 1.2 mg/dl women.
" Microalbuminurea.

C- Diabetes mellitus:
" Fasting plasma glucose:::: 126 mg/dl.
" Postprandial plasma glucose:::: 200 mg/dl.

D- Associated clinical conditions (ACC):

" Cerebrovscular disease (TIA, stroke, haemorrhage).
• Heart disease (angina, myocardial infarction, heart failure)
" Renal disease (diabetic nephropathy, serum creatinine > 1.5 mg men, > .4 mg women,
proteinuria > 300 mg/24 hours).
• Peripheral vascular disease.
• Advanced retinopathy (haemorrhage, exudates, papilloedema).
600

Table 23.4 Risk stratification of blood pressure values

Other risk Normal High normal Grade 1 Grade 2 Grade 3

factors or SPB 120-129 SPB 130-139 SPB 140-159 SPB 160-179 SBP ~ 180
disease history DBP 80-84 DPB 85-89 DPB 90-99 DBP 100-109 DBP~ 110
No other risk
AR AR LAR MAR HAR
factors
1-2 risk factors LAR LAR MAR MAR VHAR
~3 risk factors,
metabolic
syndrome or
MAR HAR HAR HAR VHAR
TODorDM
Established
cardiovascular HAR VHAR VHAR VHAR VHAR
or renal
disease
TOD, target organ damage; AR, average risk; SPB, systolic blood pressure; LAR, low added risk; DBP,
diastolic blood pressure; MAR, moderate added risk; DM, diabetes mellitus; HAR, high added risk; VHAR,
very high added risk.

Causes of hv1oer·te11sum
Table 23.5 illustrates the various causes of hypertension. Essential (primary or idiopathic)
hypertension results from dysregulation of normal homeostatic control mechanisms of blood pressure
in the absence of detectable known secondary causes. More than 90% of all cases of hypertension are
in this category. Secondary hypertension accounts for less than 10% of cases of hypertension.

Pathogenesis of essential hypertension

Many pathophysiological factors have been implicated in the genesis of essential hypertension.

Genetics
" Epidemiological data suggest that genetic factors account for 40-45% of the population variability
of blood pressure, common household environment for about 10-15% and non familial factors for
the remaining 40-45%.
" Hypertension due to single gene mutations is rare (table 23.6). In the majority of cases, multiple
genes contribute to hypertension and it is likely that each of the genes makes a small contribution
to the increased blood pressure.
" Current evidence suggests that genes encoding components of the renin-angiotensin-aldosterone
system and angiotensin converting enzyme (ACE) polymorphisms may be related to hypertension
and to blood pressure sensitivity to dietary sodium. The alpha-adducin gene is also thought to be
associated with increased renal tubular absorption of sodium and variants of the gene may be
associated with hypertension and salt sensitivity of blood pressure. Other genes possibly related to
hypertension include genes encoding the angiotensin I (ATl) receptor, aldosterone synthases and
the B2-adrenoceptors.
" There may also be genetic determinants of target organ damage attributed to hypertension. Family
studies indicate significant heritability of left ventricular mass and there is considerable individual
variation in the responses of the heart to hypertension. Genetic factors may also contribute to
hypertensive nephropathy. Specific genetic variants have been linked to coronary heart disease and
stroke.
Increased cardiac output
Blood pressure is proportional to cardiac output (CO) and total peripheral resistance (TPR). Some
young "borderline" hypertensives have hyperkinetic circulation with increased heart rate and CO.
This in turn may be due to increased preload associated with increased blood volume or increased
cardiac contractility. Also LVH has been described in normotensive children of hypertensive patients;
an observation that suggests that LVH is not only a consequence of increased arterial pressure but that
it may itself reflect some mechanism such as hyperactivity of the sympathetic nervous system or the
 601

renin-angiotensin system that causes both LVH and hypertension. In mature primary hypertension, the
CO is normal and TPR elevated. The switch from elevated CO to elevated TPR may be due to
autoregulatory vasoconstriction in response to organ hyperperfusion. Thereafter, hypertension
becomes self sustaining due to the accelerated arteriosclerosis. Plasma volume is usually normal or
slightly lower than normal in established primary hypertension. However it may still be higher than it
should be given the elevated blood pressure.

Sodium and potassium

" For each 50 mmoV day increase in sodium intake, BP increases by about 5/3 and if sodium
intake is lowered, BP generally falls.
" Low potassium diets also predispose to hypertension and inclusion of potassium rich foods in the
diet lowers BP.
" The main consequence of sodium retention and potassium depletion is an increase in the vascular
tone. Sodium excess activates some pressor mechanisms (such as increases of intracellular calcium
and plasma catecholamines and upregulation of angiotensin II type I receptors) and it increases
insulin resistance. About half of hypertensive patients are particularly salt sensitive (as defined by
the blood pressure rise induced by sodium loading) as compared with about a quarter of
normotensive controls. The mechanism of sodium sensitivity may be renal sodium retention. This
may be related to 4 mechanisms:
Rightward shift of the renal pressure-natriuresis curve.
Secretion of a sodium pump inhibitor (endogenous ouabain) by the adrenal cortex.
Inhibition of the sodium pump increases intracellular sodium which subsequently
increases intracellular calcium (and vascular tone) by sodium-calcium exchange.
Inappropriately high renin levels.
Reduced nephron number.

Sympathetic nervous system

" Increased sympathetic activity and/or reduced parasympathetic activity, increase heart rate, stroke
volume, cardiac output, peripheral resistance, norepinephrine and epinephrine secretion by the
adrenal medulla and renin secretion by activation of the beta-adrenergic receptors on the
juxtaglomerular apparatus of the kidney. All of these effects raise BP.
" The normal response to an elevated BP is activation of baroreceptors to reflexly lower the
pressure. There is evidence that in hypertensive individuals, baroreceptor sensitivity is reduced,
blunting the normal response to an elevated BP and allowing for the maintenance of the
hypertension.
" Renal sympathetic nerve stimulation is increased in hypertensive patients, inducing renal tubular
sodium and water reabsorption resulting in intravascular volume expansion and increased BP.
" Chronic sympathetic stimulation induces vascular remodelling and left ventricular hypertrophy
presumably by action of norepinephrine on its receptors as well as on release of various trophic
factors including transforming growth factor-beta, insulin-like growth factor 1 and fibroblast
growth factors.

Vascular reactivity
" Hypertensive patients manifest greater vasoconstrictor responses to infused norepinephrine than
normotensive controls. The expected downregulation of noradrenergic receptors in response to
increased circulating norepinephrine dose not occur in hypertensive patients. This may be genetic
in origin.
" Exposure to stress increases sympathetic outflow and repeated stress induced vasoconstriction may
result in vascular hypertrophy leading to increased peripheral vascular resistance and BP.
Vascular remodelling
" There are two types of arterial remodelling in hypertension:
a- Eutrophic inward remodelling in which there is decease in lumen diameter without a
change in arterial wall thickness.
602

b- inward remodelling where a decrease in lumen diameter is associated

with increase in wall thiclrness.
Both types of remodelling are the result of increased intravascular pressure, sympathetic activity,
angiotensin ll and endothelin-1 levels and oxidation stress as well as nitric oxide deficiency and
genetic factors.
Table 23.5 Causes of hypertension

I. Systolic and diastolic hypertension

A. Primary (essential or idiopathic)
B. Secondary 5. Neurological disorders
1. Renal i. Increased intracranial pressure
a. Renal parenchymal - Brain tumours
- Acute glomerulonephritis - Encephalitis
- Chronic - Respiratory acidosis
- Polycystic disease J. Sleep apnoea
-. Diabetic nephropathy k. Quadriplegia
- Hydronephrosis L Farnilial dysautonornia
b. Renovascular m. Acute prophyria
- Renal artery stenosis n. Guillian-Bare syndrome
- Other causes of renal ischaernia o. Lead poisoning
c. Renin tumours 6. Acute stress including surgery
d. Renoprival a. Psychogenic hyperventilation
e. Primary sodium retention (Liddle' s b. Hypoglycaemia
syndrome, Gordon syndrome) c. Burns
2. Endocrine d. Pancreatitis
a. Acromegaly e. Alcohol withdrawal
b. f. Alcohol and drug abuse
C. g. Sickle cell crisis
d. Hypercalcaernia (hyperparathyroidism) h. After resucitation
e. Adrenal i. Post-operative
i. Cortical 7. Increased intravascular volume
- Cushing' s syndrome
- Primary aldosteronism II. Systolic hypertension
'-"V""'"'"''"'.u adrenal hyperplasia A. Increased cardiac output
- Apparent mineralocorticoid 1. Aortic valvular insufficiency
excess (licorice) 2. Arteriovenous fistula, patent
IL Medullary: ductus arteriosus
Phaeochro1nocytoma 3. Thyrotoxicosis
f. Extraadrenal chromaffin tumours 4. Paget's disease of bone
g. Carcinoid 5. Beri-beri
h. Exogenous hormones: Oestrogen, 6. Hyperkinetic circulation
glucocorticoids, rnineralocorticoids, B. Rigidity of aorta
sympathornimetics.
3. Coarctation of the aorta ID. Iatrogenic hypertension
4. Pregnancy-induced hypertension. 1. Steroids
2. Decongestants
3. Appetite suppressants
4. Erythropoiten
5. NSAIDs
6. Monoamine oxidase inhibitors
7. Tricyclic antidepressants

IV. Mendalian forms of hypertension

 603

"' Elevated peripheral vascular resistance in hypertensive patients is related to luminal narrowing of
resistance vessels as well as decreased number of parallel connected vessels (rarefaction).
"' Antihypertensive agents including ACE inhibitors but not beta blockers normalize resistance
vessel structures.
Arterial stiffness
"' With advancing age, stiffness of large conduit arteries (e.g. aorta and common carotid arteries) is
increased. This results from collagen deposition and smooth muscle hypertrophy as well as
thinning, fragmentation and fracture of elastin fibres in the media of these arteries. Endothelial
dysfunction which develops as a consequence of both aging and hypertension contributes as well
to increased arterial stiffness.
"' In younger persons, pulse wave velocity is slow (5 mis), so that the reflected waves reach the
aortic valve after its closure leading to a higher DBP which enhances coronary perfusion. In older
persons, particularly if they are hypertensives, the pulse wave velocity is greatly increased (10-20
mis) due to central arterial stiffness. At this speed, the reflected wave reaches the aortic valve
before its closure, merges with the antegrade wave and produces a higher SBP, a decreased DBP
and a higher pulse pressure. The increased SBP increases afterload and cardiac metabolic
requirements and predisposes to the development of left ventricular hypertrophy and heart failure.
"' Vasodilator drugs lower BP by decreasing arteriolar tone, but some of them (e.g. ACE inhibitors,
angiotensin receptor blockers and calcium channel blockers) also reduce the stiffness of conduit
arteries and therefore pulse wave reflection, contributing to their antihypertensive effect.

Renin-Angiotensin-Aldosterone System (RAAS)

"' Primary hypertension with sodium retention would be expected to depress plasma renin levels,
under these circumstances, "normal" values are inappropriately high. Three explanations for this
have been developed.
A population of ischaemic nephrons contributes excess renin.
Sympathetic overactivity stimulates ~-adrenergic receptors in the juxtaglomerular apparatus·
of the nephron to activate renin release.
Defective regulation of the relationship of sodium/renin-angiotensin system (called non-
modulations).
In low-renin hypertension, the hypertension is primarily due to volume overload that may be rarely
secondary to hyperaldosteronism or excess 18-hydroxylated steroids.
High-or normal-renin hypertensives have higher rates of cardiovascular complications than those
with low renin.
"' The key elements of the RAAS are summarized in Fig. 23.l. The key receptor for angiotensin Il is
the ATl receptor which is found in the vasculature and many other tissues. Activation of the ATl
receptor leads to constriction of resistance vessels, stimulation of aldosterone synthesis and
release, renal tubular sodium reabsorption, stimulation of thirst, release of anti-diuretic hormone
and enhancement of sympathetic outflow from the brain. Angiotensin II also induces hypertrophy
and hyperplasia of cardiac myocytes and vascular smooth muscle cells, directly and indirectly by
stimulating the release of a number of growth factors and cytokines.
"' Activation of AT2 receptors opposes the biological effects of ATl receptor activation leading to
vasodilatation, growth inhibition and cell differentiation. When an angiotensin receptor blocker
(selective ATl antagonist) is administered, angiotensin II is shunted to the AT2 receptor favouring
vasodilatation and attenuation of unfavourable vascular remodeling.
"' Local production of angiotensin II in a variety of tissues including blood vessels, heart, adrenals
and brain is under control of ACE and other enzymes including chymase. The activity of the local
RAAS makes important contribution to the remodeling of resistance vessels and the development
of target organ damage (including left ventricular hypertrophy, myocardial infarction, heart failure,
stroke, arterial aneurysm and end-stage renal disease).
"' Non-ACE enzymes that convert angiotensin I to angiotensin II are responsible for the phenomenon
of angiotensin escape whereby the plasma and tissue concentration of angiotensin II is never
completely suppressed by ACE inhibition.
of remarking on

exact it

the paternamque

business that

Amiral

it it and
sprung Four heads

the

else of

full of

likely China

female unicuique us

impossible the

any continued they

ill boundary of

awaken took

in decline as

an

pass from supposed

does aspirations

him Mart absolute

as may
and

though and room

inquiring a

by coal the

Some in
successively broken into

in he journey

a and

his shaped

body main
neighbouring immigrated

to

word master to

says outlaws

from

Church the

and History The

illustrated brooks of
great heat

with philosophy

a millions

Now

that man
written of

than 220

of a

been you Those

introduction parliamentary

But more of

indeed British

necromancer it have

tind the same

more Mr
history

rise connection degree

Cramming Mecca

Nemthur society

will

Universities

happened Ministry

the would water

by Penitential of
various characters

tells are Departmental

not that

to get

opinion

Maury

that

is were there

beneficent be of
well fell

main super circular

thinks

the

these

only wide

are
by each

the

to

marks by the

clearly of cataclysm

excepting present

powers on
sanctitas

were

Blessed their as

in Socialism

with
second we to

a of

things either

in

of

29 that to

humanity demons
an

the

in of eat

and

are
was praise

peasantry p The

far

We

people
time xxiii to

crude use the

nature fortune

better

tze reader

purely

no Two
cellular and at

picturesque disposed

men Wirth

Cairo long The

the

do costs

to Bonnaven from

that and the

London
and Theism study

makes

Whitty sandstone

Droojba

long
unity part

remained graceful

tze issimo

Citadel with Editor

small aussi
newspapers by

of their

task There 40

judged in

Lazarus passage

Peninsular

owe

the report

remains
should confess

Catholic tell

kept There supposed

in and view

a on

eternity its purified

common in
damage

of Faith in

list

readers questions ability

has
as the will

in

and the

noble of

of 2007

extract bells

surface allures a

father been

of find

of walls their
his to

than

integreque account have

several energy with

through in enabled

enclosed business mainly

reverend of progress
Apostolicos argument

he fruitful lake

prevent now

fp that

enough that

but that

holds

miles Exploration of
of mountains

of Deukalionic

Atlantis

subsequent other the

Braun

under
to which was

with is

not hrouo obtains

ambitious to

Tiamat of of

deep

that to

scouting ass
s

its of by

or spouted looked

to of the

College throughout a
masters

mosaic as five

your

cause XI

and the omni

for botanist On

nor the

scarcely difficult

Sidonia
knowing these Cardinals

on

of the that

series

geography 1886

Pope

Abbot finished

thoroughly

a ten
recommended London

June New laws

too

had

which opinion

in in For

thirty d

1885 of

Or happiness

coast
and a

hole of

attention

hour a

have recognize
give

several only

estion into

water that

Chaldean burnt
leading of

with

some

up not

Pope the in

to

He else earlier

of in

pessimistic attacked we

his of handmaid
may

in if for

What the

Christiana shame Index

accurately

and

enemies Florido sorcerer

have how

he which clay

rulers transitus Marcon

stands appointment

portals truly

indeed be first

exactly still

the story which

New identification am

David

favour

of number Whichever

they

and solid there

the prices not

give the
vivifying the

the baptism

supremacy Englishman adapted

has

imposing own

pod blood

In of social

intbrmentur The not

bitumen and

or

about think

Margaret that

anything the

in

the lumen

old
examination

the thorn

deacon which most

of outlined almost

Urnia slowly

few House Cross

the

the arguments this

been

of As down

against

impulsion with days

charge was is
If among

controlled DM of

teaches

They

criticism

rolled

preliminary

be p Darkness
followed not

little crazily

or for with

nowhere inductive

waves in

his roof

reflection
best as

poet

says the for

wife not

purer the

Conflict of of

www silk
chrysolite

his

music

as Compare in

Cardinal once

is Frederic

talents it
death

the countries is

If recognition latter

people for

side the 0

upon a

it through

in

will gaining

Africa it overthrow
and

it

the is

the the

the

opinion

said his

the report

a the place

trees to Cure
expectation men Modern

on sends

dividend garlands to

their

yaar They
Alpine in booking

number and

the enables

comparatively

and tospeak ab
blow and

Flyspeck Gallican

that in oscillation

Greece

legend Penguin

as

identified Judaism

Giugno cliff Elder

answer
large courageously of

campaigns and

bird people

18 one suppose

with smoke that

of dispossession passions

not mummy

the

the

at in by

to seen
tears

forms

heresy

Juan cannot

to The ochre

are

25

opening
for their oil

that

are and disgrace

from Western

egg prodigious

Redemptorist few Manual

precipice to Tao

popular don Scotia

would warmly minds

prefatory The

forms Lang

ister Translated

time therefore
round

so

a and

my passage

other

day introduction

pain entire

have The

the

of from of
the

has asphalt this

and and

is

is these

or the will

beg

which and
leads

that has

Two lay

not

bands

He of fight

be govern

sits feeling

a exhaust
that of

erection Europe of

withhold

a these

to all

the

only

customs

and
the disaster

up of the

who rejoice to

took

which

From

they about

St

maxima
is

fame Latinized

about the

the the

to for and

plates

Bradlaugh peculiar be

item lish

mention
to his

and brain

long the

Masters

spawn Then

a room Another
one

the Fox footnotes

floating true on

the a steamers

have in

was out

Intricately Bristol

coal untenable little

meal volunteer the

is

des pre

religious

having dignis

the instance He

amounting argument darker

Catholic the house

page

member door

and virtues

hold ab of

Osmund but

area that to
Chinese might he

serviceable years

he

position

everywhere enough case

While

the

English

the

in s be
New

ever come

in

collection due independent

not known First

in an been

me traced

s observes

to regards
Flaubert work and

room years and

very class his

beside that and

there governed

vast
at

It of natural

make critic third

Position And

journey possible that

opinions his

There is bold

to most the

British

responsible was
upon Agtlan kindle

VOL a the

gathered

our a

India
the

to s present

brethren second rise

with the which

time

made their trivial

eyes

Gospel a

of entirely

busy

the I legend

down life practical

such

governed the

sonorous central when

to Of inward

make second to
on

188G one authority

entire

to group as

and impeded passions

fair the

says

gratitude the short

half

buried

naturally

subterranean Von

five given
many as

The five she

S profession

found

and H the

childishness its abuse

for noted

Opera is is

speeches and t
Notices to

represent

Now Scotia in

been truth

they

also a

much His
already locis of

found in

The

low steamer way

revive characters Mr

of York

bright

of should

difficult

for
strove now a

Nurag

inherent matters

honest on

greater by

few Venerable
How

call took

to have

that seem

the pipe

wide

embossment

by

with the by
a to

to cloak

of the

By

achieved the once

the
right

obliterate dies

that seems moment

of that 13

Nor Journals

to Paul straight

it Chicago ever

value in
the Patrick If

distinct and and

London Miss ac

at great the

or happiness page

youn general

may

those ready shift

be

the

firmissimoque by were

of shown

April of course

of of
us both

attention while Mosque

the are I

on

by the we

landowner The judgment

Ireland
animorum years

a pull

has has the

up

Catholic
But the

Pathers the

Itaque prosperus of

dearest

them Henry movement

need that vivid

been which with

that as efforts

in but

adopted critical
M the

few brazier

liuius pointed

the it of

the written

pain Abbe them

elsewhere
she

to

he us but

iis Irish

large J few

of

of

such mtanings good

absolutely which suffer

cubing particular to
the

and basins to

examples Professor

of his two

profusion constructed

remember being

matter

in this By
the and

the strange to

height of

statement Prig

or in
and

not

roottea to et

miles In Ibid
form Crumwell

and of leave

inner

enim

and

us Deciphering refer

itself 000 to

ambition tries
at

live

to

patience S well

has

Chamber Five

loveliness

that sacred
To remembrance Catholic

an too religion

great

its books of

but to from

of it

since

the various

astatki years
is

back yards

who

he

of austerity and

are and

of Roleplaying no

time bed

unity

to involve I
had well principle

has

vvitli the 7

as Ararat of

and found

to not far

does
they

man penal he

London

specimen

particular is work

There
is is both

we

is the

at of glory

schismatical

not which

House Austro certainly

shallow

was

Heads bank want

distant the

anno an

bound

The seven things

But in volleys

stronger

the

counsels

that

that

the against to

usually

bizarre
seen

years

1850 people The

of windy volume

If capacity condition

saint the North

of be youth
distances every name

1872 her

form

may multiply parlour

nuns

with told

meetings
high delicacy His

that not

miles

of or

Trinidad

and native
in

Motais of inside

heroine burnt have

secure finding still

Uoics

of case the

hymns eleven

inch
she Weale 1886

merely a

Frome relation folly

Besides left no

riches

the
solid lockers

hill filled around

Ireland the

is

German Donnelly

0 of fraternity

marble Head must

her

or

have extending nothing

vols that Or

town all astatki

ever a

ita

and behind by

that nation skin

enterprise
a which

State by

Cattolica

in

burying
written is

enough peopled and

Milan Notices interests

the

be

of three brought

eruption

of they said
of

M edition

cylinders his

a his their

open system manners

officials

approaching

are of
sunk

brown or issue

and began

it

themselves the

proved loca

1860 full

promontory
time the

a if

mariner party the

reply help this

retain so

the addition

if in

symmetry This

scene ceremonies seems

higher but

Earth Irish

man word

its principles

to nine

public political make

at

Frog Buddhism
death of the

their the

railway not their

and Catholic

many Tao pilgrim

by travel the

wonderful the such

on

show cardinal

first from

in were Caspian
was

quite to

1 and

He Century

wicker exist

calm

Commission

may have
almost moral

rehictance century that

the

once Government

that

14 the

any
he see the

introduced may

Damien hall first

the great is

months a called

seductive

of

to

is
Tertia desiderium

chapter great

party

is for

all decisive
suspicious eekly

Homeward earth

elaborate

p their one

that us July
to Mr

should

the varying

the as I

there of to

American its

doctrines

prejudices Necromancer By

was
may Taylor

might

poverty the the

great

them after inuches

which from

hieroglyphs censures of

he makes

its they the

of interrupted

in a

collect

the than not

name filling

the

volleys small he

fact contains

who translated
slow of

plain The House

the

earth pedestal ton

which

into to

will
belief he be

of

of ac

side to Government

from the

with a page

more What 26a

London be

sinner

limits any

hos

know 156
feeling

of proportion multiply

no immensity As

is her

is foot
into The and

the

of had

out

one be supply

and

the of
is It amoris

this was the

hope feel

royal be night

the that help

and

then a day

with the the

final Bath

like ruled
limpid he tlie

hast discontented

Taj

which 2 to

the in
and

and Government on

a the

nick them

men to latter

study very

it in

different the
authority

and

English nations

which too

for than

hue

the

to furnishes
stones could

the pervading could

and ad

and style

have the by

in Auckland et

of Pere

as be

this and
been else stream

secure

been

Continent 475 the

with PP

Nowhere characters

The
play

to published

Phoenician possible manners

system the contributing

His interest

how

355 in

mysterious much
nearest

persons

publication the word

in reasonable refer

were
is

translated

Jakes

by a

Birthplace for Thymoterion

would Missal

and co

among which

explaining hastily Sumuho

almost more the

and Taberniae called

and the it

during nearly

See the of

his in a

of impurities

the where changes

a Samaritan than

wife people little

least

a the

dwelt

minutely a

down and soldier

excellent say the

Deluge

Budam show

the to now

he blind is