Cardiovascular Disease E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Serie: British Nutrition Foundation
• Sprache: Englisch

Seitenzahl: 1566

Veröffentlichungsjahr: 2018

Beschreibung

A comprehensive, accessible summary of the latest research in heart disease risk factors

Cardiovascular Disease (CVD) is a major cause of early death and disability across the world. The major markers of risk—including high blood cholesterol, smoking, and obesity—are well known, but studies show that such markers do not account for all cardiovascular risk. Written by a team of renowned experts in the field, this comprehensive and accessible book examines the evidence for emerging and novel risk factors, and their relationship with diet and nutrition.

Fully updated throughout, Cardiovascular Disease: Diet, Nutrition and Emerging Risk Factors, 2^nd Edition covers everything from the epidemiology of cardiovascular disease, to genetic factors, to inflammation and much more – offering invaluable advice on reducing risk factors and preventing CVD. This new edition:

• Authoritatively reports on the link between emerging aspects of diet, lifestyle and cardiovascular disease risk
• Focuses on novel risk factors of CVD, including the human gut microbiome and fetal and childhood origins, and how it can be prevented
• Features recommendations for interventions and future research
• Includes references, commonly asked questions that summarise the take-home messages, and an online glossary

Cardiovascular Disease: Diet, Nutrition and Emerging Risk Factors, 2^nd Edition is an important book for researchers and postgraduate students in nutrition, dietetics, food science, and medicine, as well as for cardiologists and cardiovascular specialists.

Leseprobe

Table of Contents

Cover

Foreword

List of Common Abbreviations

About the Companion Website

Terms of Reference

Task Force Membership

1 The Aetiology and Epidemiology of Cardiovascular Disease

1.1 Introduction

1.2 Aims

1.3 Definitions

1.4 Pathogenesis

1.5 Epidemiology of Cardiovascular Disease

1.6 Risk Factors for Cardiovascular Disease

1.7 Role of Diet

1.8 Structure of the Report

1.9 Key Points

2 The Fetal and Childhood Origins of Cardiometabolic Disease

2.1 Introduction

2.2 Aims

2.3 Cohort Studies

2.4 Cohort Studies in Low‐ and Middle‐Income Countries

2.5 Other Early Life Factors

2.6 Famine Studies

2.7 Gestational Diabetes, Maternal Overweight, and Excess Pregnancy Weight Gain

2.8 Research in Animal Models, Underpinning and Driving DOHaD Concepts

2.9 Randomised Controlled Trials of Interventions in Pregnancy, Infancy, and Childhood

2.10 Genetic Markers Linking Birthweight and Adult Disease

2.11 Mechanisms of Programming and Epigenetics

2.12 Conclusion

2.13 Key Points

2.14 Recommendations for Future Research

3 Obesity, Metabolic Syndrome and Type 2 Diabetes

3.1 Introduction to Obesity, Metabolic Syndrome, and Type 2 Diabetes

3.2 Aims

3.3 Obesity

3.4 Fat Distribution

3.5 Metabolic Syndrome and Cardiometabolic Risk

3.6 Insulin Resistance

3.7 Type 2 Diabetes

3.8 Obesity, Metabolic Syndrome, and Their Links with Other Risk Factors

3.9 Key Points

3.10 Recommendations for Future Research

4 Lipid‐Related Factors

4.1 Introduction

4.2 Aims

4.3 Background

4.4 LDL‐Cholesterol

4.5 Interventions to Reduce LDL‐Cholesterol

4.6 Atherogenic Lipoproteins

4.7 Plasma Triglycerides

4.8 Postprandial Lipaemia: Atherogenic Lipoprotein Phenotype

4.9 Small, Dense LDL

4.10 HDL‐Cholesterol and HDL Subfractions

4.11 Remnant‐Like Particles

4.12 Lipoprotein(a)

4.13 Non‐Esterified Fatty Acids

4.14 Genetic Variability and Cardiovascular Risk

4.15 Conclusion

4.16 Key Points

4.17 Recommendations for Future Research

5 Inflammation‐Related Factors

5.1 Introduction

5.2 Aims

5.3 Biology and Hypotheses

5.4 The Immune System

5.5 Inflammation and Atherosclerosis

5.6 Risk Factors: What Is Currently Known?

5.7 Other Emerging Risk Markers for Cardiovascular Disease

5.8 Multiple Inflammatory Markers in Risk Prediction

5.9 Influence of Chronic Inflammatory Disease on Cardiovascular Disease Risk

5.10 Infectious Burden, Inflammation, and Atherosclerosis

5.11 Pharmacological Agents with Anti‐Inflammatory Effects in Cardiovascular Disease

5.12 Dietary Factors and Inflammation

5.13 Conclusion

5.14 Key Points

5.15 Recommendations for Future Research

6 Adipose Tissue‐Derived Factors

6.1 Obesity, Adipose Tissue, and Cardiovascular Disease

6.2 Aims

6.3 Adipose Tissue Distribution

6.4 Types of Adipose Tissue

6.5 Adipose Tissue‐Derived Signals and Cardiovascular Disease

6.6 Leptin

6.7 Acylation‐Stimulating Protein

6.8 Adiponectin

6.9 Adipose Tissue‐Derived Cytokines

6.10 Cytokine Receptors

6.11 Role of TNF‐alpha in Adipose Tissue

6.12 Acute and Chronic Release of IL‐6

6.13 Angiotensinogen

6.14 Resistin

6.15 Peroxisome Proliferator‐Activated Receptors

6.16 MicroRNA

6.17 Other Adipose Factors Associated with Cardiovascular Disease

6.18 Nutritional Regulation of Adipocyte Factors

6.19 Physical Activity and Adipokines

6.20 Genetic Determinants of Adipokines

6.21 Conclusion

6.22 Key Points

6.23 Recommendations for Future Research

7 Endothelial and Vascular Function

7.1 Introduction

7.2 Aims

7.3 Vascular Function and the Endothelium

7.4 Estimates of Endothelial and Vascular Dysfunction

7.5 Aetiology of Endothelial Damage: Association with Classical and Novel Risk Factors

7.6 Endothelial Dysfunction as an Integrated Pathway for Cardiovascular Disease Risk

7.7 Endothelial Function Measures as Independent Predictors of Coronary Heart Disease

7.8 Relevant Genetic Studies

7.9 Prevention and Reversibility of Endothelial Dysfunction

7.10 Effects of Coronary Heart Disease Preventative Modalities on Other Risk Factor Pathways

7.11 Dietary Modulations ofEndothelial Function

7.12 Do Nutrient‐Induced Endothelial Effects Correlate with Results from Endpoint Studies?

7.13 Key Points

7.14 Recommendations for Future Research

8 The Haemostatic System: Coagulation, Platelets, and Fibrinolysis

8.1 Introduction

8.2 Aims

8.3 The Haemostatic System

8.4 The Fibrinolytic System

8.5 The Concept of Hypercoagulability

8.6 Haemostatic Risk Factors for Vascular Disease

8.7 Genetics and Cardiovascular Disease Risk

8.8 Dietary Characteristics and Haemostasis

8.9 Key Points

8.10 Recommendations for Future Research

9 Oxidative Stress and Cardiovascular Disease

9.1 Introduction

9.2 Aims

9.3 Biology and Hypotheses

9.4 The Role of Lipoproteins in Normal Biology

9.5 The Nature and Origin of Free Radicals and Reactive Oxygen and Nitrogen Species

9.6 Molecular Targets for Oxidative Stress

9.7 Oxidative Stress in the Early Stages of Cardiovascular Disease

9.8 Oxidation of LDL and Uptake by Macrophages

9.9 Oxidation of LDL in the Artery Wall

9.10 The Nature of the Oxidising Species for LDL

9.11 Oxidative Stress at Later Stages in Cardiovascular Disease

9.12 Evidence for the Presence of Oxidation Products in the Artery Wall and the Circulation

9.13 Oxidative Stress and Thrombosis

9.14 Alternative Mechanisms for Oxidative Stress

9.15 Oxidative Stress in Other Conditions Related to Cardiovascular Disease

9.16 The Importance of Diet and Dietary Antioxidants

9.17 Measurable Factors for Oxidative Stress in Cardiovascular Disease

9.18 Relationships of the Markers of Oxidant Stress to Intake of Dietary Antioxidants

9.19 Conclusion

9.20 Key Points

9.21 Recommendations for Future Research

10 Vitamins and Risk of Cardiovascular Disease

10.1 Introduction

10.2 Aims

10.3 Homocysteine, B Vitamins, and Cardiovascular Diseases

10.4 Vitamin D

10.5 Vitamin E

10.6 Vitamin C

10.7 Beta‐Carotene

10.8 Key Points

10.9 Recommendations for Future Research

11 Influences of the Human Gut Microbiome

11.1 Introduction

11.2 Aims

11.3 Microbiota of the Gastrointestinal Tract

11.4 Substrates and Products of Microbial Fermentation

11.5 The Gut Microbiome, Physical Activity, and the Importance in Athletes

11.6 Impact of Prebiotics, Probiotics, and Synbiotics on the Colonic Microbiome

11.7 Cholesterol Assimilation, Binding, and Bile Acid Deconjugation

11.8 Gut Microbiome and Metabolic Conditions

11.9 Faecal Microbiome Transplant

11.10 Organic Acids

11.11 Gut Wall Integrity

11.12 Key Points

11.13 Recommendations for Future Research

12 Physical Fitness and Physical Activity: Effects on Risk ofCardiovascular Disease

12.1 Introduction

12.2 Aims

12.3 Definitions and Recommendations

12.4 Role of Physical Activity and Physical Fitness in Promoting Cardiovascular Health

12.5 Sedentary Behaviour and Cardiovascular Health

12.6 Interactions Between Physical Activity, Sedentary Behaviour, and Eating Behaviour, and Potential Effects on Cardiovascular Risk Factors

12.7 Interventions to Increase Physical Activity, Improve Physical Fitness, and Reduce Sedentary Behaviour

12.8 Conclusion

12.9 Key Points

12.10 Recommendations for Future Research

13 Diet and Cardiovascular Disease: Where Are We Now?

13.1 Introduction

13.2 Aims

13.3 Diet, Nutrition and Emerging Risk Factors for Cardiovascular Disease: Findings of the Task Force

13.4 Changes in Emphasis Regarding Macronutrients

13.5 Change in Emphasis: Dietary Patterns

13.6 Dietary Patterns with a Focus on Change in Macronutrients

13.7 Current Dietary Recommendations for Primary Prevention in the UK

13.8 How Do the UK Recommendations Compare with Recommendations in Other Countries?

13.9 Current Dietary Trends in the UK and Comparison of These with the Current Guidelines: What Are the Biggest Successes and Challenges?

13.10 Other Lifestyle Factors Relating to Cardiovascular Disease Risk

13.11 Need for Behaviour Change

13.12 Key Points

13.A Emerging Risk Factors: Synthesis of the Available Information on Diet and Cardiovascular Disease

14 Conclusions of the Task Force

14.1 Chapter 1

14.2 Chapter 2

14.3 Chapter 3

14.4 Chapter 4

14.5 Chapter 5

14.6 Chapter 6

14.7 Chapter 7

14.8 Chapter 8

14.9 Chapter 9

14.10 Chapter 10

14.11 Chapter 11

14.12 Chapter 12

14.13 Chapter 13

15 Recommendations of the Task Force

15.1 Priorities for Future Research

15.2 Priorities for Future Research: Identifying Effective Interventions to Encourage Physical Activity

15.3 Priorities for Future Research: Identifying Effective Dietary Interventions

15.4 General Recommendations

16 Cardiovascular Disease

16.1 Epidemiology of Cardiovascular Disease

16.2 Main Factors Influencing Cardiovascular Disease Risk

16.3 Nutrition During Pregnancy and Fetal Growth

16.4 Diabetes, Obesity, and the Metabolic Syndrome

16.5 Lipid‐Related Factors

16.6 Inflammation

16.7 Factors Relating to Adipose (Fat) Tissue

16.8 The Role of the Endothelium

16.9 Diet and Blood Clotting

16.10 Diet and Oxidative Stress

16.11 Vitamins

16.12 The Gut Microbiome

16.13 Physical Activity

16.14 Diet and Cardiovascular Disease

References

Index

End User License Agreement

List of Tables

Chapter 1

Table 1.1 Causes and risk factors commonly associated with hypertension....

Table 1.2 Conventional risk factors for cardiovascular disease (CVD)....

Table 1.3 Emerging risk factors for cardiovascular disease covered in...

Table 1.4 Committee on Medical Aspects of Food Policy (COMA) recommen...

Chapter 2

Table 2.1 Maternal, infant, and adult characteristics according to ti...

Chapter 3

Table 3.1 World Health Organization adult body mass index (BMI) class...

Table 3.2 Major co‐morbidities of obesity.

Table 3.3 Diagnostic criteria for metabolic syndrome.

Table 3.4 Factors contributing to hypertension in obesity.

Chapter 4

Table 4.1 Food sources of commonly consumed fatty acids.

Table 4.2 Methods used to determine lipid‐related cardiovascular risk...

Table 4.3 Functions of the major apolipoproteins in plasma.

Table 4.4 Typical plasma concentrations and approximate residence tim...

Table 4.5 Summary of the relationship between CVD, diet, and novel li...

Chapter 5

Table 5.1 Relative evaluation of inflammatory risk factors.

Table 5.2 Associations between hs‐CRP and cardiovascular outcomes fro...

Chapter 6

Table 6.1 Signals derived from adipose tissue (Karastergiou and Mohamed‐A...

Table 6.2 Adipokines: cellular source and main functions.

Chapter 7

Table 7.1 Assessment of endothelial dysfunction in humans.

Table 7.2 Measures of endothelial function showing promise as potenti...

Table 7.3 Results of prospective studies employing direct endothelial...

Table 7.4 Influence of dietary factors on estimates of endothelial fu...

Chapter 8

Table 8.1 Circulating and cell‐bound proteins.

Table 8.2 Haemostatic risk factors for cardiovascular disease: streng...

Table 8.3 Associations between dietary factors and haemostatic risk f...

Table 8.4 Examples of micronutrients with platelet function modulator...

Chapter 9

Table 9.1 Common diseases in which oxidative damage has been demonstr...

Table 9.2 Typical fatty acid and antioxidant content of low‐density l...

Table 9.3 Oxygen‐centred free radicals and reactive oxygen species.

Table 9.4 Effects of free radical damage on cellular components.

Table 9.5 Nitrogen‐centred free radicals and reactive nitrogen specie...

Table 9.6 Oxidative modifications of proteins.

Table 9.7 Products formed during the oxidation of low‐density lipopro...

Table 9.8 Sources of dietary antioxidants.

Table 9.9 Basic structures of phenolic and polyphenolic compounds....

Table 9.10 Properties of an ideal assay method to measure lipid perox...

Chapter 10

Table 10.1 Dietary reference values and safe upper levels of vitamin ...

Table 10.2 Completed randomised trials of vitamin D for prevention of...

Table 10.3 Selected characteristics of ongoing trials of high dose vi...

Table 10.4 Selected characteristics of antioxidant vitamin trials for...

Chapter 11

Table 11.1 Typical estimated daily amounts of dietary nutrients persi...

Chapter 12

Table 12.1 The six most commonly reported physical activities reporte...

Chapter 13

Table 13.1 Recommendations for cardiovascular disease risk reduction ...

Table 13.2 Summary of practical dietary advice to reduce risk of coro...

Table 13.3 Summary of global recommendations for dietary fat and carb...

Table 13.4 Levels of energy under‐reporting from the National Diet and Nu...

Table 13.5 Sources of saturates in the UK diet (adults aged 19–64 yea...

Table 13.6 Comparison of average daily intakes of macronutrients by a...

Table 13.7 Changes in contributions (percentage of total intake per p...

Table 13.8 Recommendations for intake of oil‐rich fish.

Table 13.9 Household purchase trends (g/person/week) in Britain for c...

Table 13.10 Average daily consumption of fruits and vegetables (g/day...

Table 13.11 European Commission‐authorised health claims relating to ...

Table 13.12 Intakes of salt and sodium among young people in the UK c...

List of Illustrations

Chapter 1

Fig. 1.1 Outline of the development of the atherosclerotic plaque. Low‐density ...

Fig. 1.2 Mechanism of blood clotting. Key: a, activated; ADP, adenosine diphosp...

Fig. 1.3 Proportion of global deaths under the age of 70 years, by cause of dea...

Fig. 1.4 CVD death rates per 100 000 by sex in selected countries, 2008.

Fig. 1.5 Deaths by cause in men and women aged under 75 years in the UK, 2010.

Fig. 1.6 Percentage change in coronary heart disease death rates, by sex, in se...

Fig. 1.7 Death rates from stroke, men, and women of all ages, latest available ...

Fig. 1.8 Age‐specific death rates from stroke, 1968–2006, in England and Wales,...

Fig. 1.9 Prevalence of cardiovascular disease reported by the General Household...

Fig. 1.10 Trends in coronary heart disease death rates per 100 000 population i...

Fig. 1.11 Proportions of deaths by cause in UK and South Asian men, 2008 in Eng...

Fig. 1.12 Mortality from coronary heart disease versus serum total cholesterol ...

Fig. 1.13 Obesity prevalence of adults (16 years and over) in England from 1993...

Fig. 1.14 A schematic diagram depicting a proposed model for research into nutr...

Chapter 2

Fig. 2.1 General schema for the developmental origins hypothesis.

Fig. 2.2 Hazard ratios for death from coronary heart disease for men born in He...

Fig. 2.3 Associations of birthweight, and conditional height and relative weigh...

Fig. 2.4 Subscapular skinfold among girls born to mothers who developed gestati...

Fig. 2.5 In animal experiments, a wide range of fetal exposures, including unde...

Fig. 2.6 Hypothalamic pathways regulating appetite and feeding behaviour. NPY, ...

Chapter 3

Fig. 3.1 Components of daily energy expenditure.

Fig. 3.2 Relationship between body mass index (BMI) and all‐cause mortality. Da...

Fig. 3.3 Effect of body mass index (BMI) on coronary heart disease (CHD) risk d...

Fig. 3.4 Subcutaneous and intra‐abdominal fat imaged by magnetic resonance imag...

Fig. 3.5 Characterisation of the two extremes of body fat distribution as ‘appl...

Fig. 3.6 Opposite relationships of waist and hip circumference with risk (odds ...

Fig. 3.7 Different degrees of fat accumulation in the liver, imaged by magnetic...

Fig. 3.8 Prevalence of metabolic syndrome by quintiles of cardiorespiratory fit...

Fig. 3.9 Insulin resistance in abdominally obese men. Data are shown for abdomi...

Fig. 3.10 Postulated schema by which high fat diets produce metabolic and cardi...

Chapter 4

Fig. 4.1 Relationship between plasma triglycerides and the related atherogenic/...

Fig. 4.2 Relation between proportional reduction in incidence of major vascular...

Fig. 4.3 Effects of statins on different sub‐types of major vascular event. In ...

Fig. 4.4 Major lipoproteins in plasma responsible for cholesterol transport.

Ve

...

Fig. 4.5 Pathway for production of small, dense low‐density lipoprotein (LDL). ...

Fig. 4.6 Modulation of high‐density lipoprotein (HDL) subclasses, movement of c...

Fig. 4.7 The isolation of

remnant‐like particles

(

RLP

) is based on an imm...

Fig. 4.8 Total plasma cholesterol response to a low‐fat diet (US National Chole...

Chapter 5

Fig. 5.1 Diagrammatic representation of the development of an atherosclerotic l...

Fig. 5.2 Interrelationships between inflammatory risk factors. CRP, C‐reactive ...

Fig. 5.3 Roles of key adhesion molecules in the attachment and transendothelial...

Chapter 6

Fig. 6.1 Adipose tissue types. Brown adipose tissue is abundant at birth and st...

Fig. 6.2 Adipose tissue hypertrophy and its local effects in obesity. COX, cycl...

Fig. 6.3 Endocrine paracrine effects of adipose microRNA (miRNA) on cardiovascu...

Chapter 7

Fig. 7.1 Role of the endothelium. The endothelium synthesises several molecules...

Fig. 7.2 Schematic drawing of ultrasound imaging of the brachial artery with up...

Fig. 7.3 An example of the recording obtained by the

pulse wave velocity

(

PWV

) ...

Fig. 7.4 Non‐contact assessment of skin perfusion using

laser speckle contrast

...

Fig. 7.5 Normal endothelial vasodilator function. Representative recording of a...

Fig. 7.6 Measures of endothelial dysfunction may provide an amalgamation of ris...

Chapter 8

Fig. 8.1 The coagulation pathway. The suffix ‘a’ indicates the activated factor...

Fig. 8.2 Regulation of platelet activation through phosphorylation of

vasodilat

...

Fig. 8.3 Natural anticoagulant mechanisms.

Thrombomodulin

(

TM

) supports the act...

Chapter 9

Fig. 9.1 The origin of reactive oxygen species in human tissues. H

2

O, water; H

2

Fig. 9.2 Reaction of nitric oxide (NO) with superoxide anion to form peroxynitr...

Fig. 9.3 Reactivity of peroxynitrite (ONOOH) with macromolecules.

Fig. 9.4 The nitration of tyrosine residues by peroxynitrite.

Fig. 9.5 Free radical attack on polyunsaturated lipids.

Fig. 9.6 Free radical reactions modify the lipids and proteins of low‐density l...

Fig. 9.7 Mechanisms of oxidation of low‐density lipoprotein (LDL) in atheroscle...

Fig. 9.8 Modification of high‐density lipoprotein (HDL) function by myeloperoxi...

Fig. 9.9 Contribution of plasma constituents to the antioxidant capacity using ...

Chapter 10

Fig. 10.1 Formulae of methionine, homocysteine, and related metabolites.

Fig. 10.2 Metabolism of homocysteine. BHM, betaine homocysteine methyltransfera...

Fig. 10.3 Odds ratios and 95%

confidence intervals

(

CI

) of coronary heart disea...

Fig. 10.4 Effects of folic acid on coronary heart disease (a) and stroke (b) in...

Fig. 10.5 Effects of methylenetetrahydrofolate reductase (MTHFR) on coronary he...

Fig. 10.6 Regulation of vitamin D status. UVB, ultraviolet B.

Fig. 10.7 Association of plasma 25(OH)D with vascular and non‐vascular mortalit...

Fig. 10.8 Association of plasma 25(OH)D with all‐cause mortality: meta‐analysis...

Fig. 10.9 The effect of supplementation with vitamin D on plasma levels of 25‐h...

Fig. 10.10 Effects of antioxidant vitamins on major vascular events. Source: My...

Chapter 11

Fig. 11.1 A schematic representation of diet:microbe interactions and how they ...

Fig. 11.2 Changes to the microbiota during ageing.

Fig. 11.3 Generalised view of levels of positive and negative bacteria in the h...

Chapter 12

Fig. 12.1 Schematic showing relationship between physical activity, physical fi...

Fig. 12.2 Risk of cardiovascular disease (CVD) and coronary heart disease (CHD)...

Fig. 12.3 Comparison of weight loss from randomised controlled trials with diet...

Chapter 13

Fig. 13.1 Fat, carbohydrates and heart disease: Estimated percentage changes in...

Fig. 13.2 Age‐adjusted mortality rates of coronary heart disease in North Karel...

Fig. 13.3 Comparison of two strategies for eating 1565 kcal during a day with d...

Fig. 13.4 UK Government's Eatwell Guide.

Fig. 13.5 Fatty acid composition of edible oils and fats.

Fig. 13.6 Recent trends in the percentage of food energy derived from saturates...

Fig. 13.7 Changes in intake of fat and saturates over time from dairy products ...

Fig. 13.8 Changes in intake of fat and saturates over time from fats and oils, ...

Fig. 13.9 Average daily consumption of fruits and vegetables (g/day), including...

Fig. 13.10 Average daily consumption of fruits and vegetables (g/day), includin...

Fig. 13.11 An example of the colour‐coded multiple traffic light scheme used in...

Guide

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Cardiovascular Disease

Diet, Nutrition and Emerging Risk Factors

Second Edition

The Report of a British Nutrition Foundation Task Force

Edited by

Sara Stanner and Sarah Coe

Chaired by Keith N. Frayn

This edition first published 2019© 2019 by John Wiley & Sons Ltd.Edition History [John Wiley and Sons 1e, 2005]

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Library of Congress Cataloging‐in‐Publication Data

Names: Frayn, K. N. (Keith N.) | Stanner, Sara, and Coe, Sarah, editors.Title: Cardiovascular disease : diet, nutrition and emerging risk factors / chaired by Professor Keith N. Frayn ; edited by Sara Stanner MSc RNutr FAfN, Science Director, British Nutrition Foundation, New Derwent House and Sarah Coe BSc ANutr, Nutrition Scientist, British Nutrition Foundation, New Derwent House.Description: Second edition. | London : Published by Blackwell Publishing for the British Nutrition Foundation, 2019. | Series: British nutrition foundation | Includes bibliographical references and index. |Identifiers: LCCN 2018029734 (print) | LCCN 2018031717 (ebook) | ISBN 9781118829905 (Adobe PDF) | ISBN 9781118829899 (ePub) | ISBN 9781118829912 (paperback) Subjects: LCSH: Cardiovascular system–Diseases–Nutritional aspects. | Cardiovascular system–Diseases–Risk factors. |BISAC: HEALTH & FITNESS / Nutrition.Classification: LCC RC669 (ebook) | LCC RC669 .C2765 2019 (print) | DDC 616.1/0654–dc23 LC record available at https://lccn.loc.gov/2018029734

Cover Design: WileyCover Image: © Attitude/Shutterstock

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 inflammation 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 influenced 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 similar 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.

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 intervening period.

Professor Keith N. Frayn

List of Common Abbreviations

ATP

Adenosine triphosphate

BMI

Body mass index

CHD

Coronary heart disease

CI

Confidence interval

COMA

Committee on Medical Aspects of Food and Nutrition Policy

CRP

C‐reactive protein

CVD

Cardiovascular disease

DASH

Dietary Approaches to Stop Hypertension

DHA

Docosahexaenoic acid

DNA

Deoxyribonucleic acid

EFSA

European Food Safety Authority

ELISA

Enzyme‐linked immunosorbent assay

EPA

Eicosapentaenoic acid

FMD

Flow‐mediated dilatation

GI

Glycaemic index

GL

Glycaemic load

GWAS

Genome‐wide association study

HDL

High‐density lipoprotein

HR

Hazard ratio

IL

Interleukin

IU

International units

LDL

Low‐density lipoprotein

LRNI

Lower reference nutrient intake

MI

Myocardial infarction

miRNA

Micro ribonucleic acid

mRNA

Messenger ribonucleic acid

MUFA

Monounsaturated fatty acid

NEFA

Non‐esterified fatty acid

NICE

National Institute for Health and Care Excellence

NO

Nitric oxide

NOS

Nitric oxide synthase

OR

Odds ratio

PAI

Plasminogen activator inhibitor

PHE

Public Health England

PPAR

Peroxisome proliferator‐activated receptor

PUFA

Polyunsaturated fatty acid

PVD

Peripheral vascular disease

PYY

Peptide YY

RCT

Randomised controlled trial

RNA

Ribonucleic acid

RNI

Reference nutrient intake

RR

Relative risk

SACN

Scientific Advisory Committee on Nutrition

SCFA

Short‐chain fatty acid

SD

Standard deviation

SFA

Saturated fatty acid

SNP

Single nucleotide polymorphism

TNF

Tumour necrosis factor

tPA

Tissue plasminogen activator

TRL

Triglyceride‐rich lipoprotein

VLDL

Very low‐density lipoprotein

vWF

von Willebrand factor

WHO

World Health Organization

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

Terms of Reference

The Task Force was invited by the Council of the British Nutrition Foundation (BNF) to:

Review the present state of knowledge of the link between diet, physical activity, and cardiovascular disease risk; and

To update the previous Task Force report ‘Cardiovascular Disease: Diet, Nutrition and Emerging Risk Factors’, drawing conclusions, 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.

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 Population Health

Clinical Trial Service Unit, University of Oxford

Richard Doll Building

Roosevelt Drive

Oxford

OX3 7LF

Professor Caroline Fall

Professor of International Paediatric Epidemiology and Consultant in Child Health MRC Lifecourse Epidemiology Unit

University of Southampton

Southampton General Hospital

Southampton

SO16 6YD

Professor Gordon Ferns

Professor of Medical Education, Deputy Dean

Division of Medical Education,

Mayfield House

University of Brighton

BN1 9PH

Professor Leanne Hodson

Professor Leanne Hodson

Associate Professor of Diabetes and Metabolism

BHF Senior Research Fellow in Basic Science

Oxford Centre for Diabetes, Endocrinology and Metabolism

University of Oxford

Churchill Hospital

Oxford OX3 7LE

Professor Julie Lovegrove

Director of the Hugh Sinclair Unit of Human Nutrition

Food and Nutritional Sciences

University of Reading

PO Box 226

Whiteknights

Reading

Berkshire

RG6 6AP

Dr Vidya Mohamed‐Ali

Director

Life Sciences Research Division

Anti‐Doping Lab Qatar

Sports City Road

Doha

Qatar

Professor Marie Murphy

Professor of Exercise and Health

Sport and Exercise Sciences Research Institute

Room 15E08B

School of Sport

University of Ulster

Jordanstown campus

Shore Road

Newtownabbey

Co. Antrim

BT37 0QB

Professor Sumantra Ray

MRC‐EWL Senior Medical Advisor & Senior Clinician Scientist

Founding Chair, NNEdPro Global Centre for Nutrition and Health

MRC Elsie Widdowson Laboratory

120 Fulbourn Road

Cambridge

CB1 9NL

Sara Stanner

Science Director

British Nutrition Foundation

New Derwent House

69‐73 Theobalds Road

London

WC1X 8TA

Professor Coen Stehouwer

Professor and Chair

Department of Internal Medicine

Maastricht University Medical Centre

6202 AZ Maastricht

The Netherlands

Professor Parveen Yaqoob

School Director of Research

Food and Nutritional Sciences

University of Reading

Whiteknights

PO Box 217

Reading

Berkshire

RG6 6AH

Contributors

Dr Mashael AlJaber

Senior Scientist

Life Sciences Research Division

Anti‐Doping Lab Qatar

Sports City Road

Doha

Qatar

Dr Lucy Chambers

Senior Scientist

British Nutrition Foundation

New Derwent House

69‐73 Theobalds Road

London

WC1X 8TA

Sarah Coe

Nutrition Scientist

British Nutrition Foundation

New Derwent House

69‐73 Theobalds Road

London

WC1X 8TA

Dr Moniek P.M. de Maat

Associate Professor, Head Haemostasis Laboratory

Erasmus University Medical Center Rotterdam

P.O. Box 2040

3000 CA Rotterdam

The Netherlands

Professor Glenn Gibson

Professor of Food Microbiology, Head of Food Microbial Sciences

University of Reading

Whiteknights

Reading

Berkshire

RG6 6AH

Dr Kalyanaraman Kumaran

Clinical Scientist/Senior Lecturer

MRC Lifecourse Epidemiology Unit

University of Southampton

Southampton General Hospital

Southampton

SO16 6YD

Dr Stacey Lockyer

Nutrition Scientist

British Nutrition Foundation

New Derwent House

69‐73 Theobalds Road

London

WC1X 8TA

Professor Marlien Peters

Professor, Nutrition, Haemostasis and Cardiovascular diseases

Centre of Excellence for Nutrition (CEN)

North‐West University

Potchefstroom

2531

South Africa

Dr Gemma Walton

Lecturer in Metagenomics

Food and Nutritional Sciences

University of Reading

Whiteknights

PO Box 217

Reading

Berkshire

RG6 6AH

Professor Christine Williams OBE

Director, Food Agriculture and Health

University of Reading

Whiteknights

PO Box 217

Reading

Berkshire

RG6 6AH

Secretariat

Sarah Coe

Nutrition Scientist

British Nutrition Foundation

New Derwent House

69‐73 Theobalds Road

London

WC1X 8TA

Bethany Hooper

Nutrition Scientist

British Nutrition Foundation

New Derwent House

69‐73 Theobalds Road

London

WC1X 8TA(until April 2015)

Scientific Editor

Sara Stanner

Science Director

British Nutrition Foundation

New Derwent House

69‐73 Theobalds Road

London

WC1X 8TA

Technical Editor

Sarah Coe

Nutrition Scientist

British Nutrition Foundation

New Derwent House

69‐73 Theobalds Road

London

WC1X 8TA

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.

1The Aetiology and Epidemiology of Cardiovascular Disease

1.1 Introduction

1.2 Aims

1.3 Definitions

1.3.1 Coronary Heart Disease

1.3.2 Cerebrovascular Disease

1.3.3 Peripheral Vascular Disease

1.4 Pathogenesis

1.4.1 Atherosclerosis

1.4.2 Blood Clotting

1.4.3 Raised Blood Pressure/Hypertension

1.4.4 Relationship of Risk Factors to the Pathological Processes

1.4.5 Genetic Risk Factors for Cardiovascular Disease

1.5 Epidemiology of Cardiovascular Disease

1.5.1 The Burden of Cardiovascular Disease

1.5.2 Temporal Trends

1.5.3 Variation in Cardiovascular Disease in the UK

1.6 Risk Factors for Cardiovascular Disease

1.6.1 Definition of Risk Factors

1.6.2 Approaches Used to Investigate the Relationship Between Risk Factors and Disease

1.6.3 Interpretation of the Association

1.6.4 Conventional Risk Factors for Coronary Heart Disease

1.6.5 Conventional Risk Factors for Cerebrovascular Disease

1.6.6 Smoking and Peripheral Vascular Disease

1.6.7 Trends in the Classic Cardiovascular Risk Factors

1.6.7.1 Trends in the US

1.6.7.2 Trends Across Europe

1.6.7.3 Trends in the UK

1.6.8 The Emergence of New Risk Factors

1.7 Role of Diet

1.7.1 Dietary Recommendations to Reduce Cardiovascular Disease

1.8 Structure of the Report

1.9 Key Points

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 British Nutrition Foundation to reconvene the Task Force to produce an updated report on the field.

In the intervening years, many things have changed. Interest in antioxidant vitamin supplementation has decreased with the publication of several trials reporting negative, or adverse, outcomes. At the same time, the scientific understanding of antioxidant mechanisms has progressed, so these failed trials can be seen in perspective. 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 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 countries, 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 widespread 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 disease and peripheral vascular disease.

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 metabolic 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 contribution 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.

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 thrombolysis (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 disease (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 intercurrent 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 considered 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 abnormalities. Among the latter is a grouping of changes which include impaired ability of the heart to pump, impaired ability to relax in diastole, 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 cardiomyopathy – diseases of the heart muscle. 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 deterioration 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 myocardium (true CHD), unless these are responses to MI. However, the most common factors underlying heart failure are CHD, hypertension, and diabetes. Thus, there may be much overlap with CHD in risk factors and natural history, depending 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: ischaemic 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 ischaemic 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 irreversible damage to brain tissue. The blockage most commonly arises from the process of thromboembolism, in which a blood clot formed somewhere else (e.g. in the heart or in the carotid 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 atherosclerotic plaques narrowing the arteries supplying regions other than the myocardium and brain. A common form involves narrowing of the arteries supplying blood to the legs. The 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).

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 predominant 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 polyunsaturated and monounsaturated fats, respectively. 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 (number of double bonds), it should be noted that their chemical and biochemical properties are also dependent upon chain length, and position and geometric configuration of double bonds (see Section 4.3.1). The position of the double bonds is normally referred to the terminal (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 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 configuration: 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 unsaturated 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).

1.4 Pathogenesis

CVDs, whether affecting the coronary, cerebral, or peripheral arteries, share a common pathophysiology involving atherosclerosis and thrombosis (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 (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 modification 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 atherosclerotic plaque.

Accumulation of foam cells in the arterial wall leads to the first visible stage in atherosclerosis, 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 atherosclerosis. 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 macrophages and engulf further lipid. Development of the atherosclerotic plaque involves proliferation 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 reparative, and this has led to the description of these events as the ‘response to injury’ hypothesis of atherosclerosis.

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).

Within the lesion there may be breakdown of dead macrophages and release of their contents, with the formation of a semi‐liquid pool of extracellular lipid. At the same time, calcification of the arterial wall leads to hardening (lack of elasticity). The lid of the lesion may remain firm, in which case the lesion may protrude into the arterial lumen, obstructing flow but not causing acute damage. Some plaque caps, however, become unstable and are damaged, exposing the contents of the plaque. This results in the normal response to vessel wall damage – thrombus formation (blood clotting).

1.4.2 Blood Clotting

The process of blood clotting will be described fully in Chapter 8, but, briefly, it begins when the endothelial lining of a blood vessel is damaged, exposing cells, and surfaces that are normally covered by the endothelium (Fig. 1.2). This may happen at the site of an atherosclerotic plaque, especially following rupture of the plaque cap. Proteins thus exposed activate the clotting pathway. Formation of a clot depends upon a cascade of proteolytic reactions, with enzymes initially in an inactive, precursor (or ‘zymogen’) form becoming activated sequentially. Because of the cascade nature of this process, there is amplification, each enzyme catalysing the production of many of its product enzymes. In the course of this activation process, blood platelets are drawn to the site of injury where they aggregate and form a primary plug. Upon this is built a mesh of fibrils of the protein fibrin, formed by cleavage of the circulating precursor protein fibrinogen. If the coagulation process is brought about by bleeding outside the blood vessel, then the product is known as a clot. If it is brought about by damage to the endothelium, as, for instance, at the site of an atherosclerotic plaque, then the product is known as a thrombus. Part of the thrombus may become loose and then be carried to other sites where it can lodge and obstruct flow, the process of thromboembolism (e.g. in ischaemic stroke).

Fig. 1.2 Mechanism of blood clotting. Key: a, activated; ADP, adenosine diphosphate; F, factor; PAI‐1, plasminogen activator inhibitor‐1; tPA, tissue plasminogen activator; TxA2, thromboxane A2; vWF, von Willebrand factor (see Chapter 8 for definitions).

Source: British Nutrition Foundation (2003).

Not surprisingly, there is also a pathway for the dissolution of clots or thrombi, the fibrinolytic pathway (also known as fibrinolysis); the process of coagulation is a balance between the activities of the coagulation and fibrinolytic pathways. As will be described later, components of both these pathways may be risk markers for CVD.

1.4.3 Raised Blood Pressure/Hypertension

Blood is pumped around the body by the left ventricle of the heart. The pressure resulting from this process is opposed by the resistance of the vessels through which the blood flows, and the balance of these two opposing forces is known as blood pressure. Blood pressure is conventionally recorded as systolic (highest) over diastolic (lowest) pressure and needs to be sufficiently high to ensure adequate blood flow to the brain and other tissues, but not so high that it creates extra work for the heart and risks tissue damage.

Elevated blood pressure is strongly related to death from CHD or stroke, and indeed to death from all forms of disease involving blood vessels (Prospective Studies Collaboration 2002