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vi Contents

11 Influences of the Human Gut Microbiome 271

Professor Julie Lovegrove and Dr Gemma Walton

12 Physical Fitness and Physical Activity: Effects on Risk of Cardiovascular Disease 293
Professor Marie Murphy, Professor Steven N. Blair, and Bridget Benelam

13 Diet and Cardiovascular Disease: Where Are We Now? 311

Professor Judith L. Buttriss and Sarah Coe

14 Conclusions of the Task Force 367

15 Recommendations of the Task Force 375

16 Cardiovascular Disease: Answers to Common Questions 393

References415
Index511
 Foreword

Cardiovascular disease, including coronary heart disease, strokes, and diseases of other arteries, is a
major cause of early death and disability. For many years, the major markers of disease risk have been
well recognised; these include high blood cholesterol levels, high blood pressure, obesity, and smoking.
But these markers do not account for all cardiovascular risk. Furthermore, treatments that are highly
effective in altering these markers, for instance, the ‘statin’ drugs used to lower cholesterol, do not
remove risk entirely; typically they reduce it by 30% or less. These observations have prompted a search
for other indicators of risk of cardiovascular disease. A number of such risk markers have emerged.
These include subtle alterations of types of fat in the bloodstream, factors associated with inflamma-
tion and with clotting, lowered resistance to oxidative stress and impaired functioning of blood vessels.
In addition, it has been recognised that experiences throughout the life course, even before birth, may
influence later disease risk. We still know little about how many of these so‐called ‘emerging’ or ‘novel’
risk markers may be altered to reduce risk of cardiovascular disease, especially how they may be influ-
enced by diet, although the rapid changes in risk of cardiovascular disease that occurred throughout
the twentieth century suggest that features of our lifestyle such as diet may play a fundamental role.
In 2005, the first report of this Task Force was published in an attempt to collate all the evidence
relating to these emerging risk factors and the role of nutrition. This report has been popular and
has been much cited. Since that time, however, the field has moved on. Some of the risk factors that
we then considered ‘emerging’ are now well established. Other areas of interest have been added,
in particular, the role of the organisms inhabiting the human gut, the ‘gut microbiota’. The British
Nutrition Foundation felt that it would be appropriate to re‐convene the Task Force to look at the field
again, updating and adding to our previous report.
Some of the authors of the first edition were not available to work on this second edition. We have
therefore brought in new authors, but have been assured consistency by the presence of several of the
original authors, as well as senior staff at the British Nutrition Foundation.
Each chapter in this report was written initially by between one to three the members of the Task Force,
but then all members commented and may have contributed to each chapter. Some of the topics are sim-
ilar to those considered in the previous edition, but others have been added. The topic of ‘early origins
of adult disease’ has evolved into a consideration of life course events. The theme of homocysteine has
widened and now we include a chapter on ‘vitamins’. A previous focus on ‘insulin resistance’ has been
replaced by a consideration of the effects of obesity and the concept of the metabolic syndrome. We have
entirely new chapters on the role of physical activity and inactivity, and on the gut microbiota. As in the
previous edition, we have retained a chapter on ‘factors related to adipose tissue’, which we believe will
be an important area in the future. The Report includes, as is standard for British Nutrition Foundation
reports, a Question and Answer section and a Public Health chapter, in which we hope everyone will
be able to find ‘take‐home messages’ emerging from our work, together with chapters summarising the
conclusions and recommendations of the Task Force. In addition, a glossary and key references for each
chapter can be found at http://www.wiley.com/go/bnf/cardiovascular_diseases.

vii
viii Foreword

I would like to thank all the members of the Task Force who worked hard and willingly on this
project, and also others who corresponded with us. I extend special thanks to the British Nutrition
Foundation staff who participated, both as authors and by providing administrative support. Sarah
Coe has worked particularly hard on this project. Finally, on behalf of all members of the Task Force,
I wish to pay tribute to George Miller, a contributor to the first edition, who has sadly died in the inter-
vening period.
Professor Keith N. Frayn

viii
 List of Common Abbreviations

ATP Adenosine triphosphate NEFA Non‐esterified fatty acid

BMI Body mass index NICE National Institute for Health and Care
CHD Coronary heart disease Excellence
CI Confidence interval NO Nitric oxide
COMA Committee on Medical Aspects of NOS Nitric oxide synthase
Food and Nutrition Policy OR Odds ratio
CRP C‐reactive protein PAI Plasminogen activator inhibitor
CVD Cardiovascular disease PHE Public Health England
DASH Dietary Approaches to Stop PPAR Peroxisome proliferator‐activated
Hypertension receptor
DHA Docosahexaenoic acid PUFA Polyunsaturated fatty acid
DNA Deoxyribonucleic acid PVD Peripheral vascular disease
EFSA European Food Safety Authority PYY Peptide YY
ELISA Enzyme‐linked immunosorbent assay RCT Randomised controlled trial
EPA Eicosapentaenoic acid RNA Ribonucleic acid
FMD Flow‐mediated dilatation RNI Reference nutrient intake
GI Glycaemic index RR Relative risk
GL Glycaemic load SACN Scientific Advisory Committee on
GWAS Genome‐wide association study Nutrition
HDL High‐density lipoprotein SCFA Short‐chain fatty acid
HR Hazard ratio SD Standard deviation
IL Interleukin SFA Saturated fatty acid
IU International units SNP Single nucleotide polymorphism
LDL Low‐density lipoprotein TNF Tumour necrosis factor
LRNI Lower reference nutrient intake tPA Tissue plasminogen activator
MI Myocardial infarction TRL Triglyceride‐rich lipoprotein
miRNA Micro ribonucleic acid VLDL Very low‐density lipoprotein
mRNA Messenger ribonucleic acid vWF von Willebrand factor
MUFA Monounsaturated fatty acid WHO World Health Organization

ix
 About the Companion Website

This book is accompanied by a companion website:

http://www.wiley.com/go/bnf/cardiovascular_diseases

The website includes:

⦁⦁ Key references list
⦁⦁ A web‐only glossary

xi
Terms of Reference

The Task Force was invited by the Council of the

British Nutrition Foundation (BNF) to:

(1) Review the present state of knowledge of the

link between diet, physical activity, and cardio-
vascular disease risk; and
(2) To update the previous Task Force report
‘Cardiovascular Disease: Diet, Nutrition
and Emerging Risk Factors’, drawing con-
clusions, making recommendations, and
identifying areas for future research.

BNF, a registered charity, delivers impartial,

authoritative, and evidence‐based information on
food and nutrition. Its core purpose is to make
nutrition science accessible to all, working with an
extensive network of contacts across academia,
education and the food chain, and through BNF
work programmes focusing on education in schools
and nutrition science communication. For more
information, see www.nutrition.org.uk and www.
foodafactoflife.org.uk.

xiii
 Task Force Membership
British Nutrition Foundation
Chair
Professor Keith N. Frayn, Emeritus Professor of Human Metabolism, University of Oxford, Oxford
Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford OX3 7LJ.
Members
Bridget Benelam
Nutrition Communications
Manager
British Nutrition Foundation
New Derwent House
69‐73 Theobalds Road
London
WC1X 8TA
Professor Steven N. Blair
Faculty Affiliate, Prevention
Research Center
University of South Carolina
Public Health Research
Building, 225
921 Assembly Street
Columbia, SC 29208
Professor Richard Bruckdorfer
Emeritus Professor of
Biochemistry
University College London
Bailey Cottage
Whipsnade
Bedfordshire
LU6 2LG
Professor Judith L. Buttriss
Director General
British Nutrition Foundation
New Derwent House
69‐73 Theobalds Road
London
WC1X 8TA
Professor Robert Clarke
Professor of Epidemiology
and Public Health Medicine
Nuffield Department of University of Oxford
Population Health Churchill Hospital
Clinical Trial Service Unit, Oxford OX3 7LE
University of Oxford
Richard Doll Building Professor Julie Lovegrove
Roosevelt Drive Director of the Hugh Sinclair
Oxford Unit of Human Nutrition
OX3 7LF Food and Nutritional Sciences
University of Reading
Professor Caroline Fall PO Box 226
Professor of International Whiteknights
Paediatric Epidemiology Reading
and Consultant in Child Berkshire
Health MRC Lifecourse RG6 6AP
Epidemiology Unit
University of Southampton
Dr Vidya Mohamed‐Ali
Southampton General
Director
Hospital
Life Sciences Research
Southampton
Division
SO16 6YD
Anti‐Doping Lab Qatar
Professor Gordon Ferns Sports City Road
Professor of Medical Doha
Education, Deputy Dean Qatar
Division of Medical Education,
Mayfield House Professor Marie Murphy
University of Brighton Professor of Exercise and
BN1 9PH Health
Sport and Exercise Sciences
Professor Leanne Hodson Research Institute
Professor Leanne Hodson Room 15E08B
Associate Professor of School of Sport
Diabetes and Metabolism University of Ulster
BHF Senior Research Fellow Jordanstown campus
in Basic Science Shore Road
Oxford Centre for Diabetes, Newtownabbey
Endocrinology and Co. Antrim
Metabolism BT37 0QB
xv
xvi Task Force Membership

Professor Sumantra Ray Sara Stanner 6202 AZ Maastricht

MRC‐EWL Senior Science Director The Netherlands
Medical Advisor & British Nutrition Foundation
Senior Clinician New Derwent House Professor Parveen Yaqoob
Scientist 69‐73 Theobalds Road School Director of Research
Founding Chair, NNEdPro London Food and Nutritional
Global Centre for Nutrition WC1X 8TA Sciences
and Health University of Reading
MRC Elsie Widdowson Professor Coen Stehouwer Whiteknights
Laboratory Professor and Chair PO Box 217
120 Fulbourn Road Department of Internal Medicine Reading
Cambridge Maastricht University Medical Berkshire
CB1 9NL Centre RG6 6AH

Contributors
Dr Mashael AlJaber P.O. Box 2040 Professor Marlien Peters
Senior Scientist 3000 CA Rotterdam Professor, Nutrition,
Life Sciences Research The Netherlands Haemostasis and
Division Cardiovascular
Anti‐Doping Lab Qatar Professor Glenn Gibson diseases
Sports City Road Professor of Food Centre of Excellence for
Doha Microbiology, Head Nutrition (CEN)
Qatar of Food Microbial North‐West University
Sciences Potchefstroom
Dr Lucy Chambers University of Reading 2531
Senior Scientist Whiteknights South Africa
British Nutrition Reading
Foundation Berkshire Dr Gemma Walton
New Derwent House RG6 6AH Lecturer in Metagenomics
69‐73 Theobalds Road Food and Nutritional
London Dr Kalyanaraman Kumaran Sciences
WC1X 8TA Clinical Scientist/Senior University of Reading
Lecturer Whiteknights
Sarah Coe MRC Lifecourse PO Box 217
Nutrition Scientist Epidemiology Unit Reading
British Nutrition University of Southampton Berkshire
Foundation Southampton General RG6 6AH
New Derwent House Hospital
69‐73 Theobalds Road Southampton Professor Christine Williams
London SO16 6YD OBE
WC1X 8TA Director, Food Agriculture
Dr Stacey Lockyer and Health
Dr Moniek P.M. de Maat Nutrition Scientist University of
Associate Professor, British Nutrition Reading
Head Haemostasis Foundation Whiteknights
Laboratory New Derwent House PO Box 217
Erasmus University 69‐73 Theobalds Road Reading
Medical Center London Berkshire
Rotterdam WC1X 8TA RG6 6AH
 Task Force Membership xvii

Secretariat
Sarah Coe London British Nutrition Foundation
Nutrition Scientist WC1X 8TA New Derwent House
British Nutrition 69‐73 Theobalds Road
Foundation Bethany Hooper London
New Derwent House Nutrition Scientist WC1X 8TA
69‐73 Theobalds Road (until April 2015)

Scientific Editor
Sara Stanner New Derwent House WC1X 8TA
Science Director 69‐73 Theobalds Road
British Nutrition Foundation London

Technical Editor
Sarah Coe New Derwent House WC1X 8TA
Nutrition Scientist 69‐73 Theobalds Road
British Nutrition Foundation London

We are grateful to members of the previous Task Force on Cardiovascular Disease: Diet, Nutrition
and Emerging Risk Factors, whose chapters have been updated in this revised edition: Professor
Fredrik Karpe, Dr Simon W. Coppack, and Professor George J. Miller.
 1
The Aetiology and Epidemiology
of Cardiovascular Disease

1.1 Introduction 1 1.6.1 Definition of Risk Factors 17

1.2 Aims 2 1.6.2 Approaches Used to Investigate
1.3 Definitions 2 the Relationship Between Risk
1.3.1 Coronary Heart Disease 3 Factors and Disease 18
1.3.2 Cerebrovascular Disease 3 1.6.3 Interpretation of the Association 18
1.3.3 Peripheral Vascular Disease 4 1.6.4 Conventional Risk Factors for
1.4 Pathogenesis 4 Coronary Heart Disease 19
1.4.1 Atherosclerosis 4 1.6.5 Conventional Risk Factors for
1.4.2 Blood Clotting 6 Cerebrovascular Disease 21
1.4.3 Raised Blood Pressure/ 1.6.6 Smoking and Peripheral
Hypertension 6 Vascular Disease 22
1.4.4 Relationship of Risk Factors 1.6.7 Trends in the Classic
to the Pathological Processes 7 Cardiovascular Risk Factors 23
1.4.5 Genetic Risk Factors for 1.6.7.1 Trends in the US 23
Cardiovascular Disease 7 1.6.7.2 Trends Across Europe 23
1.5 Epidemiology of Cardiovascular 1.6.7.3 Trends in the UK 24
Disease 10 1.6.8 The Emergence of New Risk
1.5.1 The Burden of Cardiovascular Factors 25
Disease 10 1.7 Role of Diet 25
1.5.2 Temporal Trends 10 1.7.1 Dietary Recommendations to
1.5.3 Variation in Cardiovascular Reduce Cardiovascular Disease 25
Disease in the UK 15 1.8 Structure of the Report 27
1.6 Risk Factors for Cardiovascular 1.9 Key Points 28
Disease 17

the British Nutrition Foundation to reconvene

1.1 Introduction
The British Nutrition Foundation Task Force
on Cardiovascular Disease: Diet, Nutrition and
Emerging Risk Factors first reported in 2005
(Stanner 2005). That report has proved to be
very popular and has attracted much interest
but the field has moved on. This encouraged
the Task Force to produce an updated report
on the field.
In the intervening years, many things have
changed. Interest in antioxidant vitamin sup-
plementation has decreased with the publi-
cation of several trials reporting negative, or
adverse, outcomes. At the same time, the scientific

Cardiovascular Disease: Diet, Nutrition and Emerging Risk Factors, Second Edition. Edited by Sara Stanner and Sarah Coe.
© 2019 John Wiley & Sons Ltd. Published 2019 by John Wiley & Sons Ltd.
Companion website: http://www.wiley.com/go/bnf/cardiovascular_diseases

1
2 Cardiovascular Disease
understanding of antioxidant mechanisms has pro-
gressed, so these failed trials can be seen in per-
spective. The importance of physical activity in
protection against cardiovascular disease (CVD)
has been emphasised, along with an understanding
that its opposites, physical inactivity and sedentary
behaviour, have detrimental effects. There has been
an explosion of interest in, and understanding
of, the importance of colonic microorganisms –
sometimes called the microbiome – to human
­ disease and peripheral vascular disease.
health and disease, and this report includes a new
chapter on that topic (Chapter 11).
The epidemiology of CVD has changed subtly.
The global burden of CVD has continued to
increase, particularly reflecting the increased age
and obesity of populations in many countries. A
divergence has opened up in CVD mortality rates,
which are lower in Japan and the Mediterranean
countries such as France, Spain, Portugal, and
Italy, and highest in Eastern European coun-
tries, such as Russia and Ukraine. Mortality from
CVD, including coronary heart disease (CHD)
and stroke, has continued to decrease worldwide,
probably because of improvements in primary
and secondary prevention and improved medical
care. However, concern has been expressed that
improved survival after myocardial infarction (MI)
or stroke may outweigh falling incidence of new
events, leading to an increase in disease prevalence
and, therefore, a greater population burden of
serious morbidity and increased treatment need.
The intervening years have also seen some
controversies over diet and CVD. The wide-
spread acceptance in 2005 of an adverse role
for dietary saturated fat has been challenged,
and this controversy continues – in this report
we will review what evidence is available (see
Section 13.4.3). In the previous edition of this
report we discussed the value of low‐fat diets
in CVD prevention. In the time since, there has
also been great interest in low‐carbohydrate
diets, which have been popularly promoted in
the media as a means of weight loss, including
by a number of celebrities. The UK’s Scientific
Advisory Committee on Nutrition (SACN)
reported on Carbohydrates and Health in 2015
(Scientific Advisory Committee on Nutrition
2015). The report found that ‘the hypothesis
that diets higher in total carbohydrate cause
weight gain is not supported by the evidence
from randomised controlled trials’, but did
emphasise a potentially adverse role for ‘sugars
and sugars‐sweetened foods and beverages’,
especially in relation to risk of type 2 diabetes
(see Section 13.4.4).
1.2 Aims
The aims of this chapter are:
⦁⦁ To introduce and explain the topic of CVD
and its components, CHD, cerebrovascular
⦁⦁ To introduce approaches used to investigate the
relationship between risk factors and disease.
⦁⦁ To distinguish classic, or established, risk
factors from emerging risk factors.
⦁⦁ To explain genetic factors and how they modify
CVD risk and its relationship to diet/nutrition.
⦁⦁ To review the worldwide epidemiology of
CVD and its components.
⦁⦁ To introduce the Task Force’s report on Diet,
Nutrition and Emerging Risk Factors for CVD.
1.3 Definitions
This report is concerned with factors that relate
to the risk of developing CVD and how these
may be influenced by diet. CVD includes arterial
disease affecting the blood supply to the heart
or to the brain, or to the peripheral regions of
the body. The term CVD refers to a number of
individual diseases affecting the cardiovascular
system. In some cases, in this report, we will
use the term ‘cardiovascular diseases’ when we
wish to make this clear. Cardiovascular diseases
account for over half of all deaths in middle age
and one‐third of all deaths in old age in most
developed countries. Globally CVDs account for
30% of all deaths.
There are many links between CVD and met-
abolic derangements, especially type 2 diabetes
and obesity‐related traits. For that reason, the
term ‘cardiometabolic risk’ is often used to cover
the combined risk of both CVD and metabolic
disease, and will be used in this way throughout
this report.
Research over the last decade has led to a
greater understanding of the independent contri-
bution of several factors identified in the initial
report to cardiovascular risk. Although we have
continued to use the term ‘emerging risk factors’
throughout this report to distinguish them from
the classical risk factors, many are now established
in terms of their ability to predict CVD risk.
 The Aetiology and Epidemiology of Cardiovascular Disease
1.3.1 Coronary Heart Disease
CHD is a condition in which the walls of the
arteries supplying blood to the heart muscle
(coronary arteries) become thickened. This
thickening, caused by the development of lesions
in the arterial wall, is called atherosclerosis; the
lesions are called plaques. Atherosclerosis can
restrict the supply of blood to the heart muscle
(the myocardium) and may manifest to the
patient as chest pain on exertion (angina) or
breathlessness on exertion. If the cap covering
the plaque ruptures, exposing the contents to
the circulation, the blood may clot and obstruct
the flow completely, resulting in a MI or heart
attack. CHD is also known as ischaemic heart
disease.
The term acute coronary syndromes is used
to denote a hospitalisation for unstable angina
(angina without an obvious trigger), or throm-
bolysis (treatment to dissolve clots) for suspected
MI or an emergency revascularisation procedure
for relief of ischaemic chest pain at rest.
There are several causes of sudden death, but
most are related to CHD or cerebrovascular dis-
ease (see Section 1.3.2). Sudden cardiac death
may be due to MI or to cardiac arrhythmia.
Cardiac arrhythmias are situations where the
heart rate becomes irregular, and/or too rapid or
too slow. Arrhythmias may be provoked by inter-
current stress or illness but are more common,
and more frequently fatal, in hearts previously
damaged by ischaemic heart disease or any other
cause of cardiac dysfunction, such as raised
blood pressure (hypertension – usually consid-
ered to be 140/90 mm Hg or higher) or excess
alcohol consumption. The main risk factors for
arrhythmias and sudden cardiac death are thus
very similar to those for CHD.
CHD is not the only form of heart disease.
There are congenital abnormalities of the heart,
some with a genetic cause, and acquired abnor-
malities. Among the latter is a grouping of
changes which include impaired ability of the
heart to pump, impaired ability to relax in dias-
tole, and remodelling of the ventricles, especially
thickening of the walls of the left ventricle, often
with dilatation of the left ventricle observed as
left ventricular hypertrophy. Ultimately these
changes may lead to heart failure.
Underlying these changes may be cardio-
myopathy – diseases of the heart muscle.
3
Cardiomyopathy is a natural consequence of a
MI, which results in death of some of the heart
muscle and its replacement with fibrotic scar
tissue. But cardiomyopathy can be unrelated to
coronary and ischaemic disease. Continued dete-
rioration of myocardial function may lead to
heart failure. This is characterised by failure of
the heart to pump sufficiently to perfuse organs
such as the kidney. The kidney will respond
to this by signalling, via the renin‐angiotensin
system, to increase blood pressure, placing further
strain on the heart. Heart failure is manifest by
fluid accumulation (hence swelling of legs, in
particular), shortness of breath, and tiredness.
There is a special form of cardiomyopathy that
occurs in diabetes – diabetic cardiomyopathy,
which is characterised by diastolic dysfunction
(poor relaxation of the heart muscle in diastole).
As diabetes is particularly associated with small
vessel damage, which can lead to ischaemia, this
condition can be difficult to manage.
These deleterious changes in heart function
unrelated directly to CHD are not strictly within
the remit of this report. The primary aetiology is
not related to impaired blood flow to the myocar-
dium (true CHD), unless these are responses to
MI. However, the most common factors under-
lying heart failure are CHD, hypertension, and
diabetes. Thus, there may be much overlap with
CHD in risk factors and natural history, depend-
ing on the origin of heart failure.
1.3.2 Cerebrovascular Disease
Cerebrovascular disease involves interruption
of the blood supply to part of the brain and
may result in a stroke or a transient ischaemic
attack. There are two main types of stroke: isch-
aemic stroke and haemorrhagic stroke. Globally,
in 2010, these accounted for 68% and 32% of
incident strokes, respectively (Krishnamurthi
et al. 2013). However, the contribution of isch-
aemic stroke is greater in Western countries,
with estimates exceeding 80% in many studies
(Heuschmann et al. 2009).
Ischaemic stroke involves a blockage in the
blood supply to the brain. The loss of blood
supply to part of the brain may lead to irrevers-
ible damage to brain tissue. The blockage most
commonly arises from the process of thrombo-
embolism, in which a blood clot formed some-
where else (e.g. in the heart or in the carotid
4 Cardiovascular Disease
artery) becomes dislodged and then occludes
an artery within the brain (cerebral arteries).
Narrowing of the intracerebral arteries with
atherosclerotic plaque may increase the risk,
and may also lead to local formation of a blood
clot. The aetiology is similar to that of CHD. In
haemorrhagic stroke, there is rupture of a blood
vessel supplying the brain, with release of blood
into the brain (haemorrhagic stroke). High blood
pressure (hypertension) is a major risk factor for
haemorrhagic stroke, but otherwise the aetiology
is different and will not be considered in detail in
this report.
1.3.3 Peripheral Vascular Disease
Peripheral vascular disease (PVD) involves ath-
erosclerotic plaques narrowing the arteries sup-
plying regions other than the myocardium and
brain. A common form involves narrowing of
the arteries supplying blood to the legs. The
Box 1.1 Terminology Used in the Report
Saturates, Polyunsaturates, Monounsaturates
Most dietary fat is in the form of triglycerides.
Fats are grouped according to the predomi-
nant type of fatty acid that they contain. As
saturated fats are referred to as saturates on
food labels, this term will be used throughout
this report. Similarly, polyunsaturates and
monounsaturates will be used to denote poly-
unsaturated and monounsaturated fats, respec-
tively. The abbreviations SFA, MUFA, and
PUFA are also in common usage and have
been used in some tables to denote saturated,
monounsaturated, and polyunsaturated fatty
acids, respectively.
Although fatty acids are generally grouped
according to the degree of unsaturation (num-
ber of double bonds), it should be noted that
their chemical and biochemical properties are
also dependent upon chain length, and posi-
tion and geometric configuration of double
bonds (see Section 4.3.1). The position of the
double bonds is normally referred to the ter-
minal (or omega) carbon atom in the chain.
This gives rise to families of unsaturated fatty
acids known commonly as omega‐6 and
omega‐3; in this report we will refer to these as
result may be pain on exercise (claudication). In
more severe cases, impaired blood supply leads
to death of leg tissues, which require amputation
(Baumgartner et al. 2005; Sontheimer 2006).
1.4 Pathogenesis
CVDs, whether affecting the coronary, cerebral,
or peripheral arteries, share a common patho-
physiology involving atherosclerosis and throm-
bosis (or clotting). The causes of CVD and why
it affects some individuals and not others, or why
it more severely affects one region rather than
another, are discussed later in this chapter and
elsewhere in this report.
1.4.1 Atherosclerosis
The term atherosclerosis comes from the Greek
athere, meaning porridge or gruel and referring
to the soft consistency of the core of the plaque
n‐6 and n‐3 polyunsaturates, respectively.
Most double bonds in dietary fatty acids are
in the cis geometrical configuration and,
unless otherwise stated, this should be
assumed to be the case. However, some fatty
acids have double bonds in the trans configu-
ration: these are usually the result either of
hydrogenation in ruminant animals (so are
found in dairy products, for instance) or of
catalytic hydrogenation (hardening) of unsat-
urated vegetable oils. Fats containing such
trans unsaturated fatty acids are generally
referred to as trans fats.
The effects of these different types of fats
will be discussed in subsequent chapters (see
overview in Chapters 4 and 13). For common
food sources of the different types of fatty
acids, see Table 4.1.
Triglycerides
The traditionally used term triglycerides will
be used throughout this report, but a more
biochemically accurate term is triacylglycerols
(often abbreviated to TAG).
For more information on dietary fats and
fatty acid structures, see Gurr et al. (2016).
 The Aetiology and Epidemiology of Cardiovascular Disease 5

(mainly lipid), and sclerosis, meaning hardening.
The lipid of the atherosclerotic plaque is mainly
cholesterol from low‐density lipoprotein (LDL)
particles that have left the circulation. Current
understanding is that the LDL particles must be
chemically modified in some way before they are
taken up by the so‐called scavenger receptors of
macrophages (white blood cells that have become
resident in the arterial wall). This chemical mod-
ification may involve lipid peroxidation (see
Section 9.8), which leads in turn to peroxidation
of the large protein known as apolipoprotein‐
B100 that is associated with each LDL particle.
While uptake of cholesterol by cells is normally
tightly controlled so that cellular cholesterol
levels do not become excessive, lipid uptake by
the scavenger receptor pathway is not subject
to such regulation. Therefore, the macrophages
may engulf large amounts of lipid, giving them a
foamy appearance under the microscope. These
so‐called foam cells are characteristic of the ath-
erosclerotic plaque.
Accumulation of foam cells in the arterial
wall leads to the first visible stage in atheroscle-
rosis, formation of a yellowish, minimally raised
spot (the spots later merging into streaks) in the
arterial wall. These are known as fatty streaks.
The process at this stage must be largely reversible
since more than 40% of infants coming to post‐
mortem examination during the first year of life
have fatty streaks in their aortas (Woolf 1990).
These macrophages send chemical signals that
trigger further events associated with athero-
sclerosis. Blood monocytes and T‐lymphocytes
(other types of white blood cells) adhere to the
cellular lining of an artery, the endothelium.
The monocytes migrate into the subendothelial
space where they differentiate into further mac-
rophages and engulf further lipid. Development
of the atherosclerotic plaque involves prolif-
eration of smooth muscle cells of the arterial
wall and the elaboration of a connective tissue
matrix, forming a fibromuscular cap to the lesion
(Fig. 1.1). These processes may be seen as repar-
ative, and this has led to the description of these
events as the ‘response to injury’ hypothesis of
atherosclerosis.
Within the lesion there may be breakdown of
dead macrophages and release of their contents,
with the formation of a semi‐liquid pool of extra-
cellular lipid. At the same time, calcification of
the arterial wall leads to hardening (lack of elas-
ticity). The lid of the lesion may remain firm,
in which case the lesion may protrude into the

Vessel lumen

LDL particle Proliferation and migration

in plasma of smooth muscle cells Atherosclerotic plaque

Endothelial cells Monocyte Fibrous cap

Collagen
Macrophage
LDL ox
idation
Intima

Foam cell
generation
oxLDL uptake by
macrophages
Foam cell Internal
elastic
Media

lamina
Smooth
muscle
cells

Fig. 1.1 Outline of the development of the atherosclerotic plaque. Low‐density lipoprotein (LDL) particles
from the circulation enter the arterial intima. After oxidation (oxLDL), they may be engulfed by macrophages.
The resultant lipid‐laden macrophages are known as foam cells. Through a process of ‘response to injury’
with proliferation and migration of smooth muscle cells and collagen, the arterial wall becomes thickened and
hardened. The processes involved are described in more detail in the accompanying text and developed in
later chapters (see Figs 5.1 and 9.7).
Another random document with
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Katalog der Ausstellung österreichischer Kunstgewerbe. 1910/1911. 1910.
(Österr. Museum.)
Katalog der Ausstellung österreichischer Kunstgewerbe. 1911/1912. 1911.
(Österr. Museum.)
Katalog der Frühjahrsausstellung österreichischer Kunstgewerbe,
verbunden mit einer Ausstellung der k. k. Kunstgewerbeschule Wien,
Mai bis Juli 1912. 1912. (Österr. Museum.)
Katalog der Ausstellung österreichischer Tapeten-, Linkrusta- und
Linoleumindustrie, verbunden mit einer Ausstellung von
Tapetenentwürfen und von historischen Tapeten, 20. Mai bis Juli
1913. 1913. (Österr. Museum.)
Katalog der Ausstellung österreichischer Kunstgewerbe 1913-1914. 1913.
(Österr. Museum.)

Hans Sibmachers Stick- und Spitzen-Musterbuch. Nach der Ausgabe vom

Jahre 1597 herausgegeben vom k. k. Österr. Museum. 1866. (C.
Gerolds Sohn.)
Preis 8 K.

Originalstickmuster der Renaissance, in getreuen Kopien vervielfältigt und

mit Unterstützung des k. k. Handelsministeriums herausgegeben
1873. Mit Einleitung von R. v. Eitelberger. (Schulbücherverlag.)
Dasselbe. 2. Auflage (R. v. Waldheim.)
Preis 6 K.

Stickmuster, mit Unterstützung des k. k. Unterrichtsministeriums und mit

Benützung der besten Vorbilder entworfen von E. Drahan. (Wien,
Hartinger & Sohn.)
Preis 5 K. 76 h.

Wilh. Hoffmanns Spitzenmusterbuch, nach der Originalausgabe vom

Jahre 1607 photolithographiert. 1876. (Österr. Museum.)
Preis 3 K. 60 h.

Spitzen-Album, gelegentlich der ersten Ausstellung von Spitzen- und

Nadelarbeiten mit Unterstützung des k. k. Handelsministeriums
herausgegeben 1876. 30 Lichtdrucke. (Österr. Museum.)
(Vergriffen.)
Italienische Renaissance-Spitzen- und Stickmusterblätter. 26 Spitzen- und
7 Stickmusterblätter in Lichtdruck nach den Stickmusterbüchern von
Bartolommeo Danieli, des Math. Pagano etc. (Österr. Museum.)
Einzelne Blätter 60 und 50 h.

— — 10 Blätter aus dem Spitzenmusterbuche der Isabetta Catanea

Parasole. Lichtdrucke. (Österr. Museum.)
Venezianische Musterblätter aus dem XVI. Jahrhundert für
Passementerie-Arbeiten und verwandte Techniken.
Photolithographien. Mit Einleitung von R. v. Eitelberger. 1879. (Österr.
Museum.)
Preis 4 K.

Dreger, M., Entwicklungsgeschichte der Spitze. Mit besonderer Rücksicht

auf die Spitzensammlung des k. k. Österr. Museums herausgegeben
mit Unterstützung des k. k. Ministeriums für Kultus und Unterricht. Mit
84 Tafeln. 1901. (A. Schroll.)
Preis 24 K.

Die burgundischen Gewänder der k. k. Schatzkammer. Meßornat für den

Orden vom goldenen Vlies. 12 Blätter Photographien mit Text von J.
Falke. (Österr. Museum.)
(Vergriffen.)

Die byzantinischen Buchdeckel der St. Marcus-Bibliothek in Venedig. 10

Blätter Photographien mit erläuterndem Text von J. Falke. 1867.
(Österr. Museum.)
(Vergriffen.)

Umrisse antiker Tongefäße zum Studium und zur Nachbildung für die
Kunstindustrie sowie für Schulen. Zweite vermehrte Auflage. 19
Blätter Autographien. (Österr. Museum.)
Preis 6 K.

Ornamente antiker Tongefäße zum Studium und zur Nachbildung für die
Kunstindustrie sowie für Schulen. 15 Blätter in mehrfarbigem
Tondruck. (Österr. Museum.)
Preis 10 K.
Salvetat, Über keramische Dekoration und Emaillage. Zwei
Abhandlungen, aus dem Französischen übersetzt. (Österr. Museum.)
Preis 2 K 40 h.

Trachtenbilder von Albrecht Dürer aus der Albertina. 6 Bl. in

Chromoxylographie ausgeführt von F. W. Bader in Wien. (Österr.
Museum.)
Preis 12 K.

Ottavio Stradas Entwürfe für Prachtgefäße in Silber und Gold, gezeichnet

für Kaiser Rudolf II. Faksimiliert. (Becksche Univ.-Buchhandlung [A.
Hölder]).
Preis 15 K.

Gefäße der deutschen Renaissance (Punzenarbeiten). Im Auftrage des

k. k. Handelsministeriums herausgegeben, 16 Tafeln in Folio mit Text
von Franz Schestag. 1876. (Schulbücherverlag.)
Preis 10 K.

Das Wiener Heiligthumbuch. Nach der Ausgabe vom Jahre 1502 samt
den Nachträgen von 1514 mit Unterstützung des k. k.
Handelsministeriums herausgegeben. Mit Einleitung von Franz Ritter.
1882. (Gerold & Comp.)
Preis 8 K.

Möbelformen der französischen Renaissance. Nach den im Österr.

Museum und in andern Sammlungen befindlichen Originalen unter
Leitung von Prof. E. Herdtle aufgenommen und autogr. von Schülern
der Kunstgewerbeschule. 2 Hefte à 6 Tafeln. 1881. (Österr. Museum.)
Preis à 4 K.

Prachtmöbel und Geräte vom Ende des XVIII. und Beginn des XIX.
Jahrhunderts, größtenteils aus dem Besitze Sr. kaiserl. Hoheit
Erzherzogs Albrecht. In Lichtdruck von V. Angerer in Wien,
herausgegeben vom k. k. Österr. Museum. 15 Tafeln. 1884. (Österr.
Museum.)
Preis 24 K.

Falke, J. v., Rahmen. Eine Auswahl aus der Sammlung des k. k. Österr.
Museums auf 50 Lichtdrucktafeln. 1892. (A. Schroll.)
Preis 35 Mk.
— — Holzschnitzereien. Eine Auswahl aus der Sammlung des k. k.
Österr. Museums auf 55 Lichtdrucktafeln. 1893. (A. Schroll.)
Preis 35 Mk.

— — Mittelalterliches Holzmobiliar. 46 Lichtdrucktafeln. 1894. (A. Schroll.)

Preis 40 Mk.

Photographien alter Möbel von der Ausstellung im Österr. Museum 1874.

(Hofphotograph V. Angerer.) Preis der ganzen Kollektion: aufgezogen
84 K, unaufgezogen 56 K, einzelne Blätter:
aufgezogen 1 K 20 h, unaufgezogen 80 h.

Kunstgewerbliche Flugblätter. 55 Bl. in Kart. (R. v. Waldheim.) Preis 6 K.

Einzelne Blätter à 10 h zu beziehen durch das Österr. Museum.
Reproduktionen von Original-Zeichnungen und kunstgewerblichen
Gegenständen. 1883. Bisher 2 Hefte à 12 Bl. (V. Angerer.)
Studien und Entwürfe von Ferdinand Laufberger. Aus seinem Nachlasse
herausgegeben. 1884. 1 Heft mit 12 Bl. (V. Angerer.)
Arbeiten der österreichischen Kunstindustrie aus den Jahren 1868-1893.
Zum 25jährigen Jubiläum der Kunstgewerbeschule des k. k. Österr.
Museums für Kunst und Industrie. Herausgegeben von der Direktion.
Wien, (Gesellschaft f. vervielfält. Kunst.)
Der Wiener Kongreß. Kulturgeschichte, Die bildenden Künste und das
Kunstgewerbe, Theater, Musik in der Zeit von 1800 bis 1825. Mit
Beiträgen von Bruno Bucher, Josef Folnesics, Eugen Guglia, Ludwig
Hevesi, Eduard Leisching, Karl v. Lützow, Hans Macht, Karl Masner,
Alois Riegl, Franz Ritter, Wilhelm Freiherrn v. Weckbecker, Hugo
Wittman unter der Redaktion von Eduard Leisching. 1898. (Artaria &
Co.)
Altorientalische Teppiche. Im Anschluß an das in den Jahren 1892 bis
1896 vom k. k. Handelsmuseum in Wien veröffentlichte Werk
„Orientalische Teppiche“. 4 Lieferungen mit zusammen 25 Tafeln in
farbigem Kombinationsdruck. Mit einem Vorwort von A. v. Scala,
Einleitung von Wilhelm Bode, Text von Friedrich Sarre. 1906-1908.
(Leipzig, Karl V. Hiersemann.)
Preis à Lief. 85 Mk.

Folnesics, Josef und E. W. Braun, Geschichte der k. k. Wiener Porzellan-

Manufaktur. 42 Tafeln und 147 Illustrationen im Text. 1907. (K. k. Hof-
 u. Staatsdruckerei.)
Preis 120 K.

Leisching, Eduard, Zur Geschichte der Wiener Gold- und

Silberschmiedekunst. (Separatabdruck aus „Kunst und
Kunsthandwerk“, VII. Jahrgang.) 1904. (Artaria & Co.)
— — Die Ausstellung von alten Gold- und Silberschmiedearbeiten im k. k.
Österr. Museum. (Separatabdruck aus „Kunst und Kunsthandwerk“,
X. Jahrgang.) 1907. (Artaria & Co.)
Dreger, Moritz, Der Gösser Ornat im k. k. Österr. Museum.
(Separatabdruck aus „Kunst und Kunsthandwerk“, XI. Jahrgang.)
1908. (Artaria & Co.)
Walcher von Molthein, Alfred, Die deutsche Keramik in der Sammlung
Figdor. (Separatabdruck aus „Kunst und Kunsthandwerk“, Jahrg. XII.)
1909. (Artaria & Co.)
Guglia, Eugen, Die Besuchs- und Gelegenheitskarten der Sammlung
Figdor. (Separatabdruck aus „Kunst und Kunsthandwerk“, XIV.
Jahrgang.) 1911. (Artaria & Co.)
Rosenberg, Marc, Studien über Goldschmiedekunst in der Sammlung
Figdor. (Separatabdruck aus „Kunst und Kunsthandwerk,“ XIV.
Jahrgang.) 1911. (Artaria & Co.)
Leisching, Eduard, „Theresianischer und Josefinischer Stil“.
(Separatabdruck aus „Kunst und Kunsthandwerk“, XV. Jahrgang.)
1912.
 *** END OF THE PROJECT GUTENBERG EBOOK FÜHRER
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