Diabetes mellitus is a chronic condition that occurs as a result of has diabetes, World Health Organization (WHO) and the International Diabetes …
Diabetes and Cardiovascular Disease: Time to Act
The mission of the IDF is to work with our member associations to enhance the lives of people with diabetes
International Diabetes Federation, 2001 No part of this publication may be reproduced or transmitted in any form or by any means without the prior written permission of the IDF Executive Office This and other IDF publications are available from: International Diabetes Federation Executive Office 1 rue Defacqz B-1000 Brussels Belgium Tel: 32 2 5385511 Fax: 32 2 5385114 e-mail: idf@idforg http://wwwidforg
ISBN: 2-930229-15-2
Acknowledgements
The International Diabetes Federation IDF would like to thank Merck, Sharp Dohme MSD, USA, for its generous support in making the publication of Diabetes and Cardiovascular Disease: Time to Act possible
IDF also gratefully acknowledges the contribution of the members of the Diabetes and Cardiovascular Disease Editorial Committee: Clive Cockram Chair George Alberti Bjørnar Allgot Abdullah Al Nakhi Pablo Aschner Terrence Dwyer Steve Haffner Jean-Claude Mbanya Cara McLaughlin Viswanathan Mohan Corby Shugars Kelly Stoddard
Special thanks also to Kristen Hynes from the Menzies Research
Centre, Australia, for her help with the mortality figures in Chapter 2
Editor and project manager: Cara McLaughlin Project coordinator: Stefania Sella Project support for mortality data: Lala Rabemananjara
Design and layout: perplex | Aalst, Belgium Printing: Imprimerie L Vanmelle SA, Gent/Mariakerke, Belgium
I N T E R N AT I O N A L D I A B E T E S F E D E R AT I O N
Diabetes and Cardiovascular Disease: Time to Act
Contents
Contents
Preface: A Time Bomb Introduction Executive Summary Chapter 1: Diabetes Classification Risk Factors The Extent of the Problem Future Outlook Chapter 2: Cardiovascular Disease The Cardiovascular Disease Triad The Extent of the Problem Chapter 3: Diabetes and Cardiovascular Disease: Double Jeopardy The Extent of the Problem A Costly Situation How does Diabetes Lead to Cardiovascular Disease? The Cardiovascular Disease Triad in Diabetes The Vicious Cycle Chapter 4: Risk Factors What is a Risk Factor? Cardiovascular Risk Factors Diabetes and Other High Blood Glucose Conditions: A Major Risk Factor Conclusion Chapter 5: Reducing the Risks Management of Risk Factors in the General Population Management of Risk Factors in People with Cardiovascular
Disease Management of Risk Factors in People with Diabetes National Approaches to Prevention: Lifestyle Chapter 6: Treatment of Cardiovascular Disease in Diabetes Treatment of Coronary Heart Disease Treatment of Cerebrovascular Disease Treatment of Peripheral Vascular Disease Conclusion Conclusion: The Way Forward Fact File
7 9 11 13 13 14 14 16 19 19 22 37 37 37 37 40 43 45 45 45 46 51 53 53 55 55 57 59 59 60 60 60 61 63
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65 66 68 77 81 87
Annex 1: Diagnostic Criteria for Diabetes and its Risk States Annex 2: Diabetes Prevalence Annex 3: Coronary Heart Disease and Cerebrovascular Disease Mortality Rates Annex 4: Studies of Diabetes and Heart Disease Glossary Bibliography
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P R E FA C E
A Time Bomb
A Time Bomb D
iabetes is closely associated with cardiovascular disease and therefore an increased risk of heart attack, stroke and amputation of the lower limbs Indeed, heart attack and stroke are the major causes of premature death in people with
diabetes With the rising tide of diabetes around the globe, the double jeopardy of diabetes and cardiovascular disease is set to result in an explosion of these and other cardiovascular complications - unless preventive action is taken now Such action includes striving to prevent diabetes itself and, when diabetes is present, to prevent or delay cardiovascular risk factors in people with the condition Both these objectives can be achieved by common strategies, such as promoting healthy lifestyles, educating healthcare professionals and raising public awareness What is more, these steps can also help prevent the onset of cardiovascular disease in the general population All should pay heed policy makers, the healthcare team and, above all, the public We truly hope that you take the messages spelt out in this publication to heart IDF considers cardiovascular disease to be one of the most serious problems facing people with diabetes, and intends to lead the fight against it from the front This is just the beginning
Professor Sir George Alberti IDF President
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Diabetes and Cardiovascular Disease: Time to
Act
Introduction
Introduction
Aims of the Book
Diabetes and Cardiovascular Disease: Time to Act is the most up-to-date report on global cardiovascular disease and diabetes The objectives of this publication are to raise awareness of the close link between these two diseases and to recommend courses of action to prevent or delay the cardiovascular complications of diabetes
How Should this Book Be Used?
Chapter 1 sets the scene by giving some background information on diabetes More detailed information about diabetes can be found in other IDF publications such as Diabetes Atlas 2000 and Diabetes Slide Show Chapter 2 defines cardiovascular disease and discusses its various clinical manifestations It also provides the most recent global mortality data for coronary heart disease and cerebrovascular disease Chapter 3 looks at cardiovascular disease in the setting of diabetes For those reading this as a stand-alone chapter, there are cross-references to Chapter 2 for background explanations of the clinical manifestations of cardiovascular disease Chapter 4 examines the risk factors for cardiovascular disease It focuses on diabetes as one of the major cardiovascular risk factors Chapter
5 describes how cardiovascular risk factors can be managed, both in the general population and in people with diabetes Again, to put the information in context for those reading this as a stand-alone chapter, there are cross-references to Chapter 4 Chapter 6 reviews the treatment possibilities for established cardiovascular disease in people with diabetes Readers who are unfamiliar with the medical terminology can make use of the glossary Terms included in the glossary are printed in bold when first used in the text The studies of diabetes and heart disease which are referred to in the text are explained in more depth in Annex 4 The first reference to each of these studies is printed in italics The research on which Diabetes and Cardiovascular Disease: Time to Act is based is documented in the bibliography
Who Is It for?
This publication seeks to inform healthcare decision makers of the huge public health burden posed by cardiovascular disease in people with diabetes, and to point to the possibilities of and urgent need for prevention IDFs member associations are encouraged to make use of this book to lobby their governments for investment in preventive strategies Diabetes and
Cardiovascular Disease: Time to Act can also be used as a tool for sensitizing healthcare professionals to the need for an aggressive management of all cardiovascular risk factors in people with diabetes This publication is also a source of background information for member associations public awareness campaigns the theme of World Diabetes Day 2001 being Reducing the Burden: Diabetes and Cardiovascular Disease Finally, anyone with an interest in learning more about diabetes and/or cardiovascular disease can consult this publication
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Diabetes and Cardiovascular Disease: Time to Act
Executive Summary
Executive Summary
Diabetes
Diabetes mellitus is a chronic disease which has been described as a state of raised blood glucose associated with premature mortality It arises when the pancreas fails to produce enough insulin type 1 diabetes, or when the body cannot effectively make use of the insulin produced type 2 diabetes Diabetes is fast becoming a world pandemic Although there is no evidence that type 1 diabetes is preventable, it is clear that modifiable factors exist for type 2 diabetes If action is not taken to
stem the tide of type 2 diabetes, the prospects for world health are bleak
develop independently, as each may accelerate or worsen the others Thus, as diabetes progresses, the heart and blood vessels are exposed to multiple attacks The cardiovascular complications of diabetes are therefore a major cause of illness, death and healthcare costs Cardiovascular death rates are either high or appear to be climbing in countries where diabetes is prevalent When we consider that the number of people with diabetes around the world is predicted to double over the coming decades, the outlook for cardiovascular disease becomes even more alarming The recent decline in cardiovascular disease in the USA, Australasia and western Europe may be compromised significantly by this upsurge in diabetes In other parts of the world where cardiovascular disease has been proliferating in recent years, the additional impact of diabetes threatens to have devastating consequences In short, the predicted escalation in diabetes prevalence is likely to contribute to a cardiovascular disease epidemic, particularly in the developing world - unless preventive measures are taken as a matter of urgency
Cardiovascular
Disease
Cardiovascular diseases are diseases affecting the heart and circulatory system, which, for example, can result in heart attack, stroke and amputation of the lower limbs Cardiovascular disease is a major worldwide public health problem It is the number one cause of death in industrialized countries It is also set to overtake infectious diseases as the most common cause of death in many parts of the less developed world, with levels becoming comparable to those in Western societies a situation which seemed inconceivable a few decades ago
Risk Factors
Because of the soaring prevalence of diabetes worldwide, it now rivals smoking, high blood pressure and lipid disorders as a major risk factor for cardiovascular disease Diabetes also belongs to a special risk category as it so markedly increases the risk of cardiovascular disease People with diabetes have a higher prevalence of many of the other common cardiovascular risk factors than the general population What
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Diabetes and Cardiovascular Disease: Double Jeopardy
Diabetes can lead to cardiovascular damage in a number of ways The processes do not
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Diabetes
and Cardiovascular Disease: Time to Act
Lifestyle modification including healthy eating habits, regular physical exercise, smoking cessation and sustained weight loss in the overweight can be of major benefit in preventing non-communicable diseases such as diabetes and cardiovascular disease On the national level, cardiovascular disease prevention in people with diabetes should in the first place be part of a comprehensive approach to prevention in the whole community It is inevitably easier for people with diabetes to change lifestyle behaviour if this is occurring in the population at large
is more, most of these cardiovascular risk factors have a more harmful effect in the presence of diabetes Many people with diabetes have numerous risk factors This fact becomes even more serious considering that the presence of several risk factors has a multiplicative and not just an additive effect Due to the higher prevalence and impact of cardiovascular risk factors, as well as the role of hyperglycaemia, people with diabetes without overt cardiovascular complications merit an intervention against risk factors which is as aggressive as that which would normally be provided for individuals
with established cardiovascular disease
Treatment
Many of the treatment methods for cardiovascular disease are similar irrespective of whether diabetes is present or not However specific issues related to diabetes include the difficulty of diagnosing silent cardiovascular disease, the need for the aggressive management of all risk factors, and the use of insulin therapy to achieve blood glucose control when a heart attack occurs Since there are many risk factors involved, the treatment and follow-up of cardiovascular disease in people with diabetes can be a complicated, time-consuming and expensive process Hence the value of preventive measures cannot be overemphasized
Reducing the Risks
Many cardiovascular deaths are potentially preventable in both people with and without diabetes if we can systematically address known risk factors While some risk factors are fixed such as age, gender and genetic background, many others are modifiable, such as high blood pressure, lipid abnormalities, obesity and smoking As many people with diabetes who experience a first coronary event die prior to getting to hospital, they cannot benefit from secondary prevention strategies Therefore the
management of risk factors in people with diabetes should precede the onset of cardiovascular disease The cardiovascular risk factors specific to diabetes have been identified by many recent studies and it has been proven possible to reduce their impact dramatically These positive results call for aggressive action to be taken to treat the risk factors that are common in people with diabetes However such approaches are frequently not implemented in clinical practice There is therefore a clear need for greater awareness of treatment possibilities among healthcare professionals
The Way Forward
The good news is that it is possible to slow or stop the consequences of cardiovascular disease in diabetes Action must be taken on four levels prevention, treatment, education and research There can be no doubt that now is the time to act
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Diabetes and Cardiovascular Disease: Time to Act
C HA PT E R 1
Diabetes
Diabetes
Pancreas
Diabetes mellitus is a chronic disease which has been described as a state of raised blood glucose hyperglycaemia associated with premature mortality It arises when the beta cells in the
pancreas fail to produce enough of the hormone insulin, or when the body cannot effectively use the insulin produced
Kidneys
Failure of insulin secretion, action or both leads to raised blood glucose and other metabolic changes which, if uncontrolled, can cause serious complications The most important of these are retinopathy affecting the eyes, nephropathy affecting the kidneys, neuropathy affecting the nerves and cardiovascular disease affecting the circulatory system
Classification
One problem over the years has been the classification of diabetes into different categories Most recently, a World Health Organization WHO Consultation and the American Diabetes Association ADA Expert Committee have divided diabetes into four main types Table 1
Stomach
What was previously known as insulindependent diabetes mellitus IDDM has become type 1 diabetes under this new
Figure 1: The pancreas 1 Type 1 diabetes 2 Type 2 diabetes Insulin required for survival due to a lack of insulin produced by the body as a result of beta cell destruction Characterised by disorders of both insulin action or secretion, either of which may predominate, but both of which are usually present Usually
controlled by diet, exercise and oral hypoglycaemic agents Insulin may be required for metabolic control
3 Other specific types of diabetes Other types of diabetes where the cause is known eg genetic defects in beta cell function or insulin action, diseases of the pancreas, certain other hormonal disorders, or drug induced disorders 4 Gestational diabetes Table 1: The four main types of diabetes Diabetes appearing for the first time in pregnancy
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Risk Factors
No clear-cut modifiable risk factors have been identified for type 1 diabetes The risk factors for type 2 diabetes are shown in Table 3 Certain ethnic groups seem particularly susceptible to the development of diabetes Examples include Amerindians, Pacific island communities, South Asians, Australian aborigines, African-Americans and Hispanics There is also a strong association with age and family history For instance, it has been estimated that if you have a sibling or parent with type 2 diabetes, you have a 40 lifetime risk of developing it yourself These risk factors cannot be altered However, most of
the recent upsurge in diabetes is lifestyle related The dramatic rise in prevalence is closely associated with a lack of physical activity, obesity particularly central obesity and a change to Western-style diets These changes, together with urbanization and mechanization, appear to be inevitable accompaniments of modernization Age Ethnicity Family history Obesity particularly central Physical inactivity Urbanization and mechanization Westernized diet
classification, and non-insulin-dependent diabetes mellitus NIDDM is now type 2 diabetes At present the diagnosis of type 2 diabetes is one of exclusion, that is, it is not one of the other types There are undoubtedly many different causes with a lot of as yet unknown genes involved As we find out more about these, movement of people from the type 2 category into the other specific types category will occur Lesser degrees of abnormal glucose levels are also recognized These include impaired glucose tolerance IGT, blood levels that are higher than normal but below the level of someone with diabetes, and impaired fasting glycaemia IFG, raised fasting levels of glucose IGT is now considered a risk category rather than a type of
diabetes per se, and IFG is a new risk category Both IGT and IFG represent a risk of 25 to 50 of developing diabetes in the next 10 years, but are particularly amenable to lifestyle interventions The other major offshoot of the new classification is the metabolic syndrome This reflects the clustering of type 2 diabetes or IGT with several other major cardiovascular disease risk factors, such as central obesity, abnormal levels of lipids dyslipidaemia, high blood pressure hypertension, insulin resistance and a slightly increased output of protein in the urine microalbuminuria Central obesity Dyslipidaemia Hypertension Impaired glucose regulation or diabetes Insulin resistance Microalbuminuria
Table 3: Risk factors for type 2 diabetes
METABOLIC SYNDROME
The Extent of the Problem
Diabetes is becoming a world pandemic Both type 1 and type 2 diabetes are spreading rapidly across the globe Figure 2 Type 1 diabetes accounts for less than 10 of the total and is a particular problem in young northern Europeans It should be stressed however that it can occur at any age, and that there are as many people in the world with type 1 diabetes over the age of 20 years as there are under
the age of 20
Table 2: Components of the metabolic syndrome Diagnostic criteria for diabetes and its risk states are provided in Annex 1
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RISK FACTORS
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Figure 2: Prevalence estimates of diabetes mellitus, IDF Regions, 2000 Source: International Diabetes Federation 2000
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20 499
No data 2
110 1399
50 799 80 1099
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Diabetes and Cardiovascular Disease: Time to Act
Estimated diabetes prevalence 0 1 2 Papua New Guinea Dominica, Commonwealth of Mauritius 3 4 5 6 7 Bahrain Mexico Trinidad and Tobago Barbados Aruba Bermuda British Virgin Islands Cayman Islands Grenada Hong Kong SAR, PRC St Kitts and Nevis 8 9 10 Pakistan Czech Republic Tonga 3 6 9 12 15 18
Table 4: Top ten countries for diabetes prevalence Source: International Diabetes Federation 2000
Type 2 diabetes, which accounts for about 90 of all cases, is recording the most growth, particularly in rapidly developing countries It is estimated that there are at least 150 million people in the It is estimated that world with
diabetes there are some now This figure is 150 million people expected to double in the world with over the next 25 diabetes now This years The predicted figure is expected to increase is most double over the next striking in India and 25 years China, but no part of the world is spared In addition to these alarming absolute rises in numbers, there is also a worsening trend for the disease to affect younger age groups In
developed countries the sharpest increases affect the over 65s, unlike the situation in developing countries where most new cases are occurring in those between 44 and 65 years of age In all parts of the world type 2 diabetes is also now emerging in children and adolescents, thereby raising the threat of onset of all complications at an earlier age
Fact
Future Outlook
Although there is no evidence that type 1 diabetes is preventable, it is clear that modifiable factors exist for type 2 diabetes If action is not taken to stem the tide of type 2 diabetes, the outlook for world health is bleak Already diabetes consumes up to 10 of
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national health
resources in many countries Can the pandemic be prevented? The answer is yes but only with a high degree of dedication and commitment Experimental studies in China, Tanzania, Finland and Sweden have proven that lifestyle modification can slow the development of diabetes in high-risk groups But a concerted world effort spearheaded by WHO, IDF and its national associations is needed to bring the message home Put as simply as possible, the message to be transmitted is: Eat Less, Walk More
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C HA PT E R 2
Cardiovascular Disease
Cardiovascular Disease
Cardiovascular diseases are diseases affecting the heart and circulatory system In developing countries the most common cause of cardiovascular disease used to be infection of the heart valves However, in recent years there has been a shift away from infectious causes in many developing nations Today the most widespread form of cardiovascular disease around the world is that which starts with damage to the blood vessels The two main processes by which the blood vessels become damaged are atherosclerosis and
hypertension: 1 Atherosclerosis leads to the formation of plaques of atheroma which narrow the diameter of the large and medium-sized arteries This narrowing of the arteries impairs blood flow Plaques are also prone to rupture or to ulcerate and then act as a site for blood clot formation The resulting blood clots, which can block the affected vessel completely, are usually responsible for the more severe clinical manifestations of cardiovascular disease such as heart attack and stroke 2 Hypertension damages the smaller vessels in the circulatory system Over time they become scarred, hardened, narrowed and less elastic Hypertension can also both predispose to and accelerate the development of atherosclerosis
Heart and coronary circulation coronary heart disease
those affecting the heart and coronary circulation coronary heart disease; those affecting the brain and cerebral circulation cerebrovascular disease; and those affecting the lower limbs peripheral vascular disease
Brain and cerebral circulation cerebrovascular disease
Lower limbs peripheral vascular disease
The Cardiovascular Disease Triad
The major clinical manifestations of cardiovascular disease can be divided
into three groups: Figure 3: The cardiovascular disease triad
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Coronary heart disease Angina Heart attack Sudden death Heart failure Cerebrovascular disease Stroke Transient ischaemic attack Dementia Peripheral vascular disease Gangrene Intermittent claudication
Table 5: The major clinical manifestations of cardiovascular disease
CLINICAL MANIFESTATIONS
Coronary Heart Disease
The heart receives a blood supply of its own from the blood vessels known as the coronary arteries The principal manifestations of coronary heart disease include the chronic form resulting from the narrowing of the coronary arteries - angina or the acute forms resulting from the blocking of the coronary arteries - heart attack or sudden death Heart failure is a likely accompaniment of coronary heart disease in either the short or long term
commonly associated with angina If the responsible plaque of atheroma is causing a severe narrowing of the vessel, then angina symptoms may rapidly worsen and occur at rest, and may warn of an impending heart attack Heart attack:
Atherosclerosis can lead to a heart attack if the coronary arteries become blocked The onset of a heart attack is usually heralded by severe central chest pain, which may also radiate to the left arm, shoulder or jaw Severe shortness of breath, sweating and feeling faint are common additional symptoms Sudden death: Sudden death can occur as a consequence of an abrupt loss of the hearts ability to pump blood It may result from a massive heart attack or a severe abnormality of the rhythm of the heartbeat
Aorta
Left coronary artery Right coronary artery
Heart failure: This occurs when damage to the heart muscle is severe enough to prevent it functioning adequately as a pump It manifests itself either acutely with severe shortness of breath or, more chronically, with shortness of breath, reduced exercise tolerance and swelling of the ankles
Cerebrovascular Disease
Figure 4: The heart Angina: This term is used to describe pain in the chest due to a reduced blood supply to the heart ischaemia It results from atherosclerosis in the coronary circulation Typically angina causes central chest pain, which often radiates to the left arm, shoulder or jaw The pain is related to exertion and
is relieved by rest Shortness of breath and sweating are The brain receives its blood supply from four main arteries: the two carotid arteries and the two vertebral arteries The clinical consequences of vascular disease in the cerebral circulation will depend upon which vessels or combinations of vessels are involved
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of the brain is temporarily interrupted without producing permanent damage By definition, recovery occurs within 24 hours These attacks, particularly if frequent, can be a warning sign of an impending stroke They usually result from small blood clots or clumps from plaques of atheroma which get carried into the blood circulation producing transient blockages Occasionally these clots may get carried from the heart or arteries leading to the brain eg carotid arteries, rather than from within the cerebral circulation itself Dementia: This may result from repeated episodes of small strokes which produce progressive damage to the brain over a period of time The main clinical feature of dementia is a gradual loss of memory and intellectual capacity Loss of
motor function in the limbs and incontinence can also occur
Vertebral artery
Carotid artery
Figure 5: The brain
The following situations can occur: Stroke: Stroke occurs when the blood supply to a part of the brain is blocked resulting in the death of an area within the brain If a large vessel is blocked the outcome may be rapidly fatal or may lead to very severe disability If smaller blood vessels are blocked the outcome is less critical and recovery may be good The most common types of disability are the loss of use of one side of the body and speech problems There are three principal types of stroke: Thrombotic: Stroke due to the blockage of an artery leading to or in the brain by a blood clot Haemorrhagic: Stroke due to bleeding from a ruptured blood vessel, usually a consequence of hypertension Embolic: Stroke due to the formation of a blood clot in a vessel away from the brain The clot is carried in the bloodstream until it lodges in an artery leading to or in the brain The thrombotic and haemorrhagic forms are the most common, although they occur with varying frequency in different parts of the globe Transient ischaemic attack: Transient ischaemic attacks arise when
the blood supply to a part
Peripheral Vascular Disease
The lower limbs each receive their blood supply via an artery known as the femoral artery Peripheral vascular disease is said to be present when the blood vessels in this part of the body are affected by atherosclerosis In the absence of diabetes the single most important risk factor is heavy cigarette smoking
Femoral artery
Figure 6: Lower limbs
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Coronary Heart Disease
Data on the incidence of coronary heart disease are now available for many developed countries through the WHO-sponsored MONICA Project, but unfortunately such data are not available for developing nations Consequently, to obtain an idea of the global distribution of the disease it is necessary to examine the available mortality data The data in Tables 6 and 7 and Figures 7 to 14 reflect the most recent mortality rates for coronary heart disease However substantial changes have taken place over time In some developed nations where rates were extremely high by world standards - including the US, many western European countries and Australasia
- mortality has plunged by as much as 50 in the last 30 years In other developed countries where rates were low, such as Japan, the mortality has remained low In others, particularly in eastern Europe, rates have been climbing In many developing nations, particularly in the Pacific and the Middle East, rates have risen to those previously found only in the West On the whole, these trends reflect changes in the prevalence of the risk factors see Chapter 4 For example, there has been a decline in cholesterol levels in the US and other previously high-risk countries such as Finland Population-based levels of treatment for hypertension and a decrease in smoking prevalence have also occurred in many of the countries which have witnessed a reduction in coronary heart disease mortality Availability of treatment for established disease has also improved
The following situations can occur: Gangrene: The term gangrene is used to describe the death of tissue due to a loss of blood supply Severe gangrene can occur as a result of the blockage of a large blood vessel Intermittent claudication: This term describes pain, usually in the calves when walking, and is due to an impaired blood supply
to the calf muscles As with angina, the pain is usually relieved by resting, but if the situation worsens pain at rest can also occur
The Extent of the Problem
Cardiovascular disease is a major worldwide public health problem It is the number one cause of death in industrialized countries It is also set to Cardiovascular overtake infectious disease is the diseases as the most number one cause common cause of of death in death in many parts of industrialized the less developed countries It is also world, with levels set to overtake becoming comparable infectious diseases to those in Western as the most societies a situation common cause of which seemed death in many parts inconceivable a few of the developing decades ago world The manifestations vary between different ethnic groups For example, while Caucasian people are particularly prone to disease of the coronary circulation, Chinese, Japanese and African people are more prone to disease of the cerebral circulation Studies among migrant populations, such as Japanese people living in the USA, suggest that these differences may be due more to variations in external risk factors such as diet than to differences in the genes of the
people themselves
Fact
Cerebrovascular Disease
The data in Tables 8 and 9 and Figures 7 to 14 provide information on cerebrovascular disease mortality from all types of stroke It is necessary to use mortality data for international comparisons because, as with coronary heart disease, incidence data are available for too few countries
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However historical data are lacking to confirm these trends As well as a difference in total trends, there are also differences in the relative frequencies of the type of stroke see page 21 in different parts of the world In Japan and China for
Cerebrovascular disease mortality has also declined markedly in many developed countries during the last half of the twentieth century In developing countries and in the former Soviet Union, rates appear to have shot up They are certainly much higher in many developing countries now than in developed countries
Mortality per 100,000 population per year 0 1 2 3 4 5 6 7 8 9 10 Latvia Russia Turkmenistan Azerbaijan Republic Kazakhstan Republic Estonia Belarus Moldova, Republic of Lithuania
Ukraine 100 200 300 400 500 600 700 800
Table 6: Top ten countries for coronary heart disease in males
Mortality per 100,000 population per year 0 1 2 3 4 5 6 7 8 9 10 Moldova, Republic of Turkmenistan Uzbekistan Azerbaijan Republic Kazakhstan Republic Russia Belarus Latvia Trinidad and Tobago Ukraine 100 200 300 400 500 600 700 800
Table 7: Top ten countries for coronary heart disease in females
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Peripheral Vascular Disease
Data on peripheral vascular disease prevalence outside the context of diabetes are scarce It is therefore currently not possible to provide international comparisons of the kind prepared for coronary heart disease and cerebrovascular disease
example the haemorrhagic form accounts for a higher proportion of cases than is seen in the West The relative frequency of the thrombotic form of stroke appears to mirror the prevalence of coronary heart disease However, reliable data on the worldwide occurrence of each type of stroke are not available
Mortality per 100,000 population per year 0 1 2 3 4 5 6 7 8 9 10 Ukraine Kyrgyz Republic Russia
Guyana Latvia Bulgaria Moldova, Republic of Romania Kazakhstan Republic Yugoslavia 100 200 300 400 500 600 700 800
Table 8: Top ten countries for cerebrovascular disease in males
Mortality per 100,000 population per year 0 1 2 3 4 5 6 7 8 9 10 Ukraine American Samoa Kyrgyz Republic Moldova, Republic of Russia Yugoslavia Kazakhstan Republic Romania St Lucia Guyana 100 200 300 400 500 600 700 800
Table 9: Top ten countries for cerebrovascular disease in females
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All data have been age-standardized across the age range of 35-74 years using the world standard population Age-standardization was calculated from data available on the Global Cardiovascular Infobase website in January 2001, with the following exceptions: Age-standardized rates for ages 35-74 for American Samoa coronary heart disease, Fiji coronary heart disease and cerebrovascular disease and Northern Mariana Islands coronary heart disease and cerebrovascular disease are estimations calculated using rates for ages 35-64 published in Profile of Cardiovascular Diseases, Diabetes Mellitus and Associated
Risk Factors in the Western Pacific Region Menzies Research Centre and World Health Organization Regional Office for the Western Pacific, 1999 Age-standardized rates for ages 35-74 for Brazil coronary heart disease and cerebrovascular disease were estimated using the age-standardized rates for ages 35-64 calculated using data from the Global Cardiovascular Infobase website Note: Coronary heart disease for the Cook Islands consists of heart attack only acute myocardial infarction; International Classification of Diseases code ICD9: 270 Basic Tabulation List The data have been organized according to the seven IDF Regions: Africa, Eastern Mediterranean and Middle East, Europe, North America, South and Central America, South East Asia and Western Pacific Data are not available for all IDF member countries Countries marked with an asterisk are not IDF members Estimations of diabetes prevalence 20-79 age group are also provided in Annex 2 and below the charts in Figures 7 to 14 where available These data come from: International Diabetes Federation 2000 No data available
Sources and Methodology
Tables 6 to 9, Figures 7 to 14 and Annex 3 provide information on coronary heart disease
and cerebrovascular disease mortality in selected countries The data are the latest obtainable for each country They were compiled for Diabetes and Cardiovascular Disease: Time to Act by the WHO Collaborating Centre at the Menzies Research Centre, University of Tasmania, Australia The source of data for all countries except American Samoa, Canada, Cook Islands, Fiji, Northern Mariana Islands, Palau, Taiwan, and Tanzania was the Global Cardiovascular Infobase website http://cvdinfobaseicgcca/ of the WHO Collaborating Centre in Ottawa, Canada This website uses data from the World Health Statistics Annual, World Health Organization, Geneva 1985, 1987, 1988, 1989, 1990, 1991, 1992, 1993, 1994, 1995 and 1996 editions Data for American Samoa were provided by the Medical Records Office, LBJ Medical Center the Causes of Death report which extracts data from death certificates from the Department of Healths Office of Vital Records Data for Canada came from the Health Statistics Division, Statistics Canada 1999 Data for the Cook Islands were provided by the Medical Records Unit of the Ministry of Health Data for Fiji were provided by the Ministry of Health and Social Welfares mortality
database which draws on two sources: medical certificates Cause of Death and Consolidated Monthly Return Data for the Northern Mariana Islands were provided by the Office of Health and Planning Statistics of the Department of Public Health data from death certificates Data for Palau were provided by the Department of Healths Vital Statistics Database which contains data from the death registry Data for Taiwan were from the Department of Healths Office of Statistics Data for Tanzania were extracted from: Walker RW, et al 2000
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171 142
Tanzania
80 21 30 09 73
São Tomé and Príncipe
160 121 90 25 56 12
Botswana
Seychelles
56 16 88 41 85 83 6
39
Zimbabwe
10
South Africa
40
Africa Coronary heart disease mortality Cerebrovascular disease mortality Estimated diabetes prevalence 00 prevalence male per 100,000 population/year male per 100,000 population/year female per 100,000 population/year female per 100,000 population/year
Figure 7: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetes
prevalence
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353
111 35 62 24
22
49
35
Kuwait
70
Egypt
93
205
121
38 17
Bahrain
148
Eastern Mediterranean and Middle East Cerebrovascular disease mortality Coronary heart disease mortality Estimated diabetes prevalence 00 prevalence male per 100,000 population/year male per 100,000 population/year female per 100,000 population/year female per 100,000 population/year
Figure 8: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetes prevalence
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Diabetes and Cardiovascular Disease: Time to Act
436
370
215 221 138
431
213 72 43 127 52 35 61 39 74 65 40 159 118
Belgium
65 49 41
Germany
42 158 154 95
Austria
38
Hungary
66
Ireland, Republic of
32
Czech Republic
117
89 22 41 22
France
40
141
60 39 38
Italy
71
235 178 122 87 114 110 71 78 49 58 166
Croatia
53
33
Albania
Greece
59
Europe 1
50
Coronary heart disease mortality Cerebrovascular disease mortality Estimated diabetes prevalence 00 prevalence male per 100,000
population/year male per 100,000 population/year female per 100,000 population/year female per 100,000 population/year
Figure 9: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetes prevalence
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616 745 602 625
316
86
76 47
Finland
55 232 205
426
256
276 195
147 291
230
228 162
228 176 202 218 155
Estonia
45
Kazakhstan Republic Belarus
14 638
Latvia
Georgia, Republic of
73
291
168 125
Azerbaijan Republic
427 448 359
244 317 283 177 166 119 135 124 79 57 39 205 204
Kyrgyz Republic
37
Israel Bulgaria
41 72
Armenia
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245 153
45
53
48 74 55 36
Luxembourg
38
178
Norway
38 58 48 35
293
Netherlands
36
106 59 46
United Kingdom
35
173 115 57 66
Slovenia
80 91 56 31 32
Spain
61
147 117 84 42 232
Portugal
54 113 64 47
Malta
99
Europe 2 Coronary heart disease mortality Cerebrovascular disease mortality Estimated diabetes prevalence 00 prevalence male per 100,000
population/year male per 100,000 population/year female per 100,000 population/year female per 100,000 population/year
Figure 10: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetes prevalence
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566 504 592 458
219
259 312 65 48 30 107 77 368 220 65 200 149 282 225 688
Sweden
64
Poland
57
102
Ukraine
35 344
Lithuania
32
Moldova, Republic of
236 214
267 454 161 145 122
Russia
291
197 153
Tajikistan
Uzbekistan
658
352 351 351 9 272 209 209 196 158 128 86 155 280 3 41 34 223 170
Turkey
194 45
Turkmenistan Yugoslavia
Macedonia
55
Romania
03
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183
62 224 34 24
Canada
90 42 32 53 50 99
175
64
United States of America
80
Antigua and Barbuda
208 143 83 77 92 48
Martinique Bahamas
85 184 185 130 127 61 67 56 48
St Lucia Mexico
142 133 108 112 62 98 121 56
119
Barbados
132
Belize
34 177 160 374 312
89 54 101 108 129 227 184 123 46 180 182
Jamaica
80
25
Dominica,
Commonwealth of
150
Trinidad and Tobago
141
Guyana
31
North America Coronary heart disease mortality Cerebrovascular disease mortality Estimated diabetes prevalence 00 prevalence male per 100,000 population/year male per 100,000 population/year female per 100,000 population/year female per 100,000 population/year
Figure 11: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetes prevalence
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222 170
134 85 77
69 43 22
57 62 40 61 49
Cuba
86
33
45
Puerto Rico
41 89 173 100 223
Dominican Republic
53
Nicaragua
43 25 24 30
82
76 110 94 75
Guatemala
29
Colombia
40
Venezuela
41
65 40
58
46 219
El Salvador
48 145 84 53 40 103 88 80
Suriname Costa Rica
34 96 56 73 47 117 73 121 74 42
Panama
29 35 55 18 41
Brazil
32 123 61 119 96
Ecuador
30 28 14 23 20 181 107 65 74
Paraguay
45
Peru
37
121 96 49 59
140
122 68 39
Uruguay
45
Chile
14
Argentina
33
South and Central America Coronary heart disease mortality Cerebrovascular disease mortality Estimated diabetes prevalence 00 prevalence male per 100,000
population/year male per 100,000 population/year female per 100,000 population/year female per 100,000 population/year
Figure 12: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetes prevalence
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Diabetes and Cardiovascular Disease: Time to Act
92 25 44 24
Sri Lanka
371 29
248 181 139
Mauritius
150
South East Asia Cerebrovascular disease mortality Coronary heart disease mortality Estimated diabetes prevalence 00 prevalence male per 100,000 population/year male per 100,000 population/year female per 100,000 population/year female per 100,000 population/year
Figure 13: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetes prevalence
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128 181 153 225 98 150 38 14 76 51 114 121 78 191 51 25 45 16 73 41
Taiwan
91
Japan
74
Mongolia
Korea, Republic of
61
China, Peoples Republic of
27 174
77 56 80 34 65 0 47
Northern Mariana Islands
Hong Kong SAR, PRC
121
317 256 171
242 152 70 114 102 56 44
41
87
Guam
125
American Samoa
Singapore, Republic of
113 58
111 63
Philippines
31
214
479
37
48 37 164
309
228
Palau
73 34 29 100 66 177 117
149
129
0 60 48
Australia
60
Cook Islands
Fiji
New Zealand
80
Western Pacific
91
Coronary heart disease mortality Cerebrovascular disease mortality Estimated diabetes prevalence 00 prevalence male per 100,000 population/year male per 100,000 population/year female per 100,000 population/year female per 100,000 population/year
Figure 14: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetes prevalence
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C HA PT E R 3
Diabetes and Cardiovascular Disease: Double Jeopardy
A Costly Situation
Diabetes is already consuming up to 10 percent of total national healthcare budgets in many countries About half of this expense can be attributed to the costs of managing diabetes complications As reflected in the patterns of hospital admissions for the treatment of complications, cardiovascular complications account for the bulk of this Figure 15 It is therefore clear that
the current situation has enormous implications in both human and economic terms The public health impact of cardiovascular disease in diabetes is exacerbated by the following factors: Type 2 diabetes is occurring at an earlier age, thereby precipitating the threat of the premature onset of cardiovascular complications The discovery of insulin has extended the life expectancy of people with type 1 diabetes significantly Each year of prolonged life brings about a greater risk of cardiovascular complications
Double Jeopardy
The Extent of the Problem
In the previous two chapters we saw the extent of both diabetes and cardiovascular disease amongst the general population This chapter brings the two diseases together and addresses specifically the topic of People with cardiovascular disease diabetes are two to in the setting of four times more diabetes likely to develop cardiovascular People with diabetes disease than people are two to four times without diabetes more likely to develop cardiovascular disease than people without diabetes, making it the most common complication of diabetes The data presented in Chapter 2 show that cardiovascular death rates are either high or appear to
be climbing in countries where diabetes is prevalent When we consider that the number of people with diabetes around the world is predicted to double over the coming decades, the outlook for cardiovascular disease becomes even more alarming The recent decline in cardiovascular disease in the USA, Australasia and western Europe may be compromised significantly by this upsurge in diabetes In other parts of the world, where cardiovascular disease has been proliferating in recent years, the additional impact of diabetes threatens to have devastating consequences In short, the predicted escalation in diabetes prevalence is likely to contribute to a cardiovascular disease epidemic, particularly in the developing world - unless preventive measures are taken as a matter of urgency
Fact
How does Diabetes Lead to Cardiovascular Disease?
All types of diabetes can lead to diseases within the heart and circulatory system in a number of ways In many people with diabetes these different factors co-exist, resulting in progressive damage to the heart and blood vessels As we saw in the previous chapter page 19, the two main processes which lead to cardiovascular disease are atherosclerosis and
hypertension
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United Kingdom Neuropathy Eye disorders Kidney disease Total cardiovascular disease Acute complications Other
Argentina All microvascular Cardiovascular disease Infections Other acute Other
Figure 15: Proportion of hospital bed days used for the treatment of diabetic complications Source: International Diabetes Federation 1999
1 Atherosclerosis Not only are people with diabetes at increased risk of developing atherosclerosis, but the process also tends to be accelerated, more severe and more widespread This can cause serious clinical consequences in younger individuals Since atherosclerosis damages the medium and large blood vessels, the term macroangiopathy is often used to indicate its presence in people with diabetes Atherosclerosis in diabetes results from a complex interplay between a number of risk factors These are described in more detail in Chapter 4 2 Hypertension Hypertension is at least twice as common in people with diabetes as in the general population, and is also more frequent in people with impaired glucose tolerance As well as
atherosclerosis and hypertension, there are other damaging effects which are specific to diabetes: microangiopathy, autonomic neuropathy and other abnormalities of the blood vessels These processes worsen vascular function and therefore make the consequences of
atherosclerosis/macroangiopathy and hypertension more difficult to withstand In addition, they lead to other diabetic complications such as nephropathy and impotence 3 Microangiopathy Microangiopathy refers to damage to the small blood vessels and capillaries, and is largely restricted to people with diabetes It is a direct result of chronic hyperglycaemia Other factors such as hypertension and dyslipidaemia also contribute The causal link between hyperglycaemia and microangiopathy has been emphasized by a number of recent clinical trials, all of which show that the microangiopathic complications of diabetes are the most readily preventable with good glycaemic control The largest of these studies are the Diabetes Control and Complications Trial DCCT in type 1 diabetes and the United Kingdom Prospective Diabetes Study UKPDS in type 2 diabetes Microangiopathy adversely affects capillary function leading to a shortage of
supply of oxygen and nutrients to the tissues, and a leakage of proteins into the tissue spaces Capillaries
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Autonomic neuropathy Microangiopathy Retinopathy Heart rate disturbances Postural fall in blood pressure Gastrointestinal dysfunction
throughout the body are affected, but damage to the microcirculation of the eyes, kidneys and nerves is responsible for the major clinical manifestations retinopathy, nephropathy, neuropathy and the diabetic foot 4 Autonomic Neuropathy Diabetes can affect different components of the nervous system One component, known as the autonomic nervous system, provides a nerve supply to the internal organs of the body, including the heart and blood vessels Damage to this system is known as autonomic neuropathy Damage to the autonomic nervous system can be a direct result of chronic hyperglycaemia or, in turn, can follow microangiopathy involving the small vessels which supply blood to the nerves themselves, thereby causing a vicious cycle of nerve and blood vessel damage Damage to the nerve supply of the heart affects the regulation
of the pulse rate In the blood vessels, manifestations such as a fall in blood pressure on standing or exercising can produce disabling symptoms and can affect measures aimed at treating hypertension Loss of the nerve supply to small blood vessels can also impair the regulation of blood flow This is an important contributory factor to the development of diabetic foot ulcers Autonomic neuropathy is an important cause of impotence in men with diabetes It can also affect the function of the bladder, stomach and intestine
Nephropathy
Dysfunction of bladder Impotence Neuropathy
Diabetic foot
Figure 16: Clinical outcomes of microangiopathy and autonomic neuropathy
Microangiopathy Damage to small blood vessels and capillary circulation Retinopathy Nephropathy Neuropathy Diabetic foot
WHAT IS IT?
Autonomic neuropathy Damage to the nerve supply of the internal organs of the body Problems with the pulse rate Postural fall in blood pressure Foot ulcers Impotence Gastro-intestinal dysfunction
Other blood vessel damage Damage to the inner or outer lining of blood vessels Impaired regulation of blood flow Weakened vessel walls Aggravated microangiopathy and atherosclerosis/
macroangiopathy
Table 10: Abnormalities of the cardiovascular system specific to diabetes
CLINICAL OUTCOME
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To complicate matters further, common chronic diabetes complications such as neuropathy and nephropathy can themselves have adverse effects on the heart and circulation As a result, as diabetes progresses the heart and blood vessels are exposed to multiple attacks, all of which can interact with each other to produce severe consequences
5 Other Abnormalities of Blood Vessels Diabetes can also damage blood vessel walls in other ways, which can interact with both atherosclerosis/macroangiopathy and microangiopathy to aggravate the situation The inner lining of blood vessels known as the endothelium can be damaged, for example affecting the ability of the blood vessels to relax or dilate This may impair the regulation of the blood flow Endothelial dysfunction is an important component of both macroangiopathy and microangiopathy, but can also appear early in the course of diabetes before the onset of detectable vascular disease The outer layers of the vessel
wall, composed of muscle or elastic tissue, can also be damaged This can impair the regulation of the blood flow and may weaken the vessel wall
The Cardiovascular Disease Triad in Diabetes
In practice the most important clinical manifestations of diabetic vascular disease can be divided into the same three groups described in Chapter 2: those affecting the coronary circulation, those affecting the cerebral circulation and those affecting the lower limbs The clinical manifestations described in Chapter 2 still apply but are particularly severe and may be modified by the presence of additional factors or complications related to diabetes
Outer lining
Coronary Heart Disease
Inner lining endothelium
Middle muscle layer
Figure 17: Blood vessel
Angina see page 20: When autonomic neuropathy is present, the typical pain of angina People with type 2 which is usually diabetes have the associated with same risk of heart ischaemia may not be attack as people experienced, leading to without diabetes silent ischaemia This who have already may manifest itself just had a heart attack with shortness of breath
Fact
Coronary heart disease Angina including silent ischaemia Heart attack
including silent heart attack Sudden death Heart failure Fainting attacks
CLINICAL MANIFESTATIONS
Cerebrovascular disease Stroke Transient ischaemic attack Dementia
Peripheral vascular disease Gangrene Intermittent claudication Foot ulcers
Table 11: The clinical manifestations of cardiovascular disease in diabetes
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50 40 Incidence 30 20 10 0 People without diabetes People with diabetes Mortality
50 40 30 20 10 0 People without diabetes People with diabetes
No prior heart attack
Prior heart attack
Men
Women
Figure 18: Heart attacks in people with and without diabetes over a period of seven years Adapted from: Haffner SM, et al 1998
Figure 19: Deaths in people with and without diabetes in the year following a first heart attack Adapted from: Miettinen H, et al 1998
or other more vague symptoms such as nausea or sweating Heart attack see page 20: People with type 2 diabetes with no prior history of heart attacks have as great a risk of having a heart attack in the future as people without diabetes who have already experienced a heart attack
Figure 18 Also, since people with diabetes often have People with diabetes widespread vascular can have a heart disease, the attack without even consequences of a realizing it heart attack are often more severe than in people without diabetes, resulting in greater difficulty with emergency treatments When autonomic neuropathy is present, heart attacks can be silent, with an absence of chest pain and presentation with less specific symptoms This means that the diagnosis can
easily be overlooked and, in effect, people with diabetes can have a heart attack without Men with diabetes even realizing it are subject to sudden death 50 For these and other more often and reasons, people with women with type 2 diabetes have a diabetes 300 higher risk of death more often than following a heart attack their counterparts Figure 19 without diabetes of the same age Sudden death see page 20: In diabetes, sudden death can also result from abnormalities in the hearts rhythm provoked by autonomic neuropathy Men with diabetes are subject to sudden death 50 more People with diabetes often and women with have a two to threediabetes 300 more fold greater risk of often than their heart failure
counterparts without compared to people diabetes of the same without diabetes age
Fact
Fact
Fact
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amputation compared to the general population The factors which predispose to this greater risk are described below
Heart failure see page 20: Heart failure is a common complication of diabetes and again carries a high short-term mortality rate In diabetes, heart failure may also occur as a consequence of microangiopathy People with diabetes have a two to three-fold greater risk of heart failure compared to people without diabetes Fainting attacks: Autonomic neuropathy can lead to fainting attacks by causing either disturbances of the heart rhythm or a fall in blood pressure on standing or exertion
Fact
Cerebrovascular Disease
Strokes occur twice as often in people with diabetes and hypertension as in those with hypertension alone Stroke see page 21: Strokes occur twice as often in people with diabetes and hypertension as in those with hypertension alone The clinical features are generally similar to those seen in people without diabetes However the additional
involvement of microangiopathy in diabetes can lead to a worse outcome
Transient ischaemic attacks occur between two and six times more frequently in people with diabetes
Transient ischaemic attack see page 21: Transient ischaemic attacks mini-strokes occur between two and six times more frequently in people with diabetes
Gangrene see page 22: Although lower-limb gangrene also occurs in people without diabetes, the vascular disease which is particular to diabetes makes it much more common Diabetic gangrene can also result from disease of the smaller blood vessels producing localized damage, for example in the toes People with diabetes over the age of 70 have a 70-fold increased risk of lower-limb gangrene compared to people without diabetes People with of the same age diabetes over the age of 70 have a Intermittent claudication 70-fold increased see page 22: risk of lower-limb Intermittent claudication gangrene compared calf pain occurs three to people without times more often in men diabetes of the with diabetes and almost same age nine times more often in women with diabetes than in their counterparts without diabetes The presence of extensive, severe vascular disease in
diabetes may influence the type of treatment chosen and may hamper its success in particular surgical treatment Foot ulcers: Foot ulcers can occur as a result of either localized gangrene usually affecting the toes or diabetic neuropathy usually arising at pressure points or weight-bearing areas of the feet The underlying predisposing factors are many and complicated but the vascular complications of diabetes, particularly microangiopathy and autonomic neuropathy, are very important
People with diabetes are 15-40 times more likely to require a lower-limb amputation compared to the general population
Dementia see page 21: The additive effects of multiple small strokes, together with microangiopathy affecting the small blood vessels to the brain, lead to an increased likelihood of dementia in people with diabetes
Peripheral Vascular Disease
People with diabetes account for the majority of cases of lower-limb amputation resulting from vascular disease In fact they are 15-40 times more likely to require such an
Fact Fact
Fact
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80 70 60
Mortality
50 40 30 20
10 0 Cardiovascular disease Strictly diabetes-related Other
Figure 20: Causes of death in people with diabetes in the US Adapted from: Geiss LS, et al 1995
The Vicious Cycle
As we have seen, diabetes can lead to cardiovascular damage in a number of ways These processes do not develop independently, as each may accelerate or worsen the others This means that when people with diabetes develop for example a heart attack or stroke, the prognosis is worse than for people without diabetes because of the vicious cycle caused by the combined vascular abnormalities associated with diabetes Indeed, cardiovascular disease is the leading cause of death in people with diabetes in developed countries Figure 20
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C HA PT E R 4
Risk Factors
Risk Factors
What is a Risk Factor?
A risk factor is a condition that places an individual at risk of developing a health-related problem The term has become widely used to address the causes of chronic, multifactorial diseases such as diabetes and cardiovascular disease A risk factor can be genetic or acquired It may be identified as a
single measurement eg a physical feature such as weight, a disease eg hypertension or a lifestyle characteristic eg smoking In order to be considered a risk factor for a disease, the condition must be associated with that disease in a manner which is beyond chance alone A causal link is therefore implied However, a risk factor will not necessarily always lead to the development of the disease A risk factor must be distinguished from a risk marker and a disease marker A risk marker is a condition which is associated with a higher risk of developing a disease, but the association has not yet proven to be causal A disease marker is a condition which indicates that a disease is already present The ultimate purpose of identifying a risk factor is to modify it in order to prevent the disease If the modification of the risk factor results in a significant reduction of the disease outcome, that risk factor is a main target for intervention If the risk factor cannot be modified but its association with the disease is strong eg gender or age, it may be used to select high-risk subjects who could benefit from special preventive interventions
Cardiovascular Risk Factors
Advancing age
Diabetes and other high blood glucose conditions Dyslipidaemia Genetic background High alcohol consumption Hypertension Insulin resistance Left ventricular hypertrophy Male gender Menopause Obesity Sedentary lifestyle Smoking
Table 12: Risk factors for cardiovascular disease in the general population
The risk factors for cardiovascular disease in the general population are listed in alphabetical order below: Advancing age: The risk of cardiovascular disease grows with age It is significantly higher in men over 45 years of age and in women over 55 years of age Diabetes and other high blood glucose conditions: As described in Chapter 3, diabetes is closely associated with a greater risk of the premature onset of cardiovascular disease Dyslipidaemia: Elevated blood levels of total cholesterol and of low-density lipoprotein LDL cholesterol, as well as low levels of high-density lipoprotein HDL cholesterol are risk factors for cardiovascular disease There is a continuous relationship between the levels and the risk In some cases raised
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Diabetes and Cardiovascular Disease: Time to Act
effect
of excess weight is more pronounced when the fat is concentrated mainly in the abdomen central obesity, as often happens in men This can be identified by a high waist/hip ratio Sedentary lifestyle: Diminished physical activity has been shown in the population at large to be associated with an intensified risk of cardiovascular disease Smoking: Cigarette smoking in particular is a risk factor for cardiovascular disease The risk starts with any daily amount and can be rapidly abolished by stopping the habit It is important to emphasize that the presence of multiple cardiovascular risk factors has a multiplicative and not an additive effect upon the incidence of coronary heart disease in the general population Figure 21
triglyceride levels in the blood are also an independent risk factor Genetic background: Although the responsible genes have not been identified, a high risk of cardiovascular disease may be hereditary and can be identified in people with parents or siblings who have a history of cardiovascular disease at a premature age ie before 55 years of age in men and 65 years of age in women High alcohol consumption: Excess alcohol intake can worsen other risk factors such as
hypertension Hypertension: Arterial pressure above the normal range 135mm Hg systolic and 85mm Hg diastolic constitutes a risk factor for cardiovascular disease As with lipids, there is a continuous relationship between the levels and risk Risk may commence at lower levels of blood pressure in some susceptible individuals Insulin resistance: Recently it has been shown that people with resistance to the action of insulin at the cellular level have a greater risk of cardiovascular disease Left ventricular hypertrophy: The increased thickness of the hearts left ventricular muscle is also a risk factor for cardiovascular disease Initially it is a silent condition which has to be investigated by cardiac tests It is mainly present in people with hypertension Male gender: Men have a higher risk of cardiovascular disease than women of the same age Menopause: Pre-menopausal women are protected from developing cardiovascular disease because the oestrogen made in their ovaries protects their hearts The risk of cardiovascular disease increases in women after the menopause because the protective effect of oestrogen is lost Obesity: Excess body fat has a marked adverse influence on risk factors
such as hypertension, dyslipidaemia, diabetes and other forms of impaired glucose regulation It can be identified by a high body mass index BMI The adverse
Diabetes and Other High Blood Glucose Conditions: A Major Risk Factor
Because of the soaring prevalence of diabetes worldwide, it now rivals smoking, hypertension and cholesterol disorders as a major risk factor for cardiovascular disease Diabetes also belongs to a special risk category as it so markedly increases the risk of cardiovascular disease Figure 22
Other Cardiovascular Risk Factors in People with Diabetes
A Higher Prevalence
All cardiovascular risk factors apply to people with diabetes Indeed they are even stronger determinants in this group Figures 23 to 26 and Table 13 This may be partly explained by the fact that people with diabetes have a higher prevalence of many cardiovascular risk factors, notably lipid disorders, hypertension, obesity and insulin resistance These risk factors are interrelated and are more prominent in type 2 diabetes than type 1
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Estimated rate of coronary heart disease
60 50 40 30 20 10 0 120 220 50 160 220 50 160 259 50 160 259 35 Risk factors 160 259 35 160 259 35 160 259 35 Systolic blood pressure mm Hg Cholesterol mg/dL HDL cholesterol mg/dL Diabetes Cigarette smoking Left ventricular hypertrophy
Men
Women
Figure 21: Estimated coronary heart disease rate according to various combinations of risk factors over 10 years Adapted from: Kannel WB 1996
10 8 Relative risk 1 0 Total cardiovascular disease Coronary heart disease Heart failure Intermittent claudication Stroke Men 6 4 2
Women
Figure 22: Relative risk of cardiovascular events in people with diabetes Adapted from: Wilson PWF, et al 1992 The relative risk is the relation between the cardiovascular risk of people with diabetes and the cardiovascular risk of the general population which equals one Therefore a relative risk ratio of two for people with diabetes here indicates a doubling of cardiovascular risk compared to the general population; a relative risk ratio of four indicates a quadrupling of risk, etc
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100
Prevalence
80 60 40 20 0
London Moscow Berlin New Dehli Hong Kong Tokyo Havana Arizona Men Women
Figure 23: Prevalence of high cholesterol levels 465 mmol/l in people with diabetes
50
Prevalence
40 30 20 10 0 London Moscow Berlin New Dehli Hong Kong Tokyo Havana Arizona Men Women
Figure 24: Prevalence of hypertension blood pressure 160/95 mm Hg in people with diabetes These prevalence rates would be even higher if the current cut-off values were applied
35 30 25 20 15 10 5 0 London Moscow Berlin New Dehli Hong Kong Tokyo Havana Arizona
Body mass index
Men Women
Figure 25: Mean body mass index kg/m2 in people with diabetes see glossary for BMI values
80 70 60 50 40 30 20 10 0 London Moscow Berlin New Dehli Hong Kong Tokyo Havana Arizona
Prevalence
Men Women
Figure 26: Prevalence of cigarette smoking in people with diabetes Figures 23 to 26: Cardiovascular risk factors in people with diabetes in different populations Adapted from: Keen H, et al 1985
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Prevalence Prevalence is at least double in people with type 2 diabetes Prevalence is similar in people with diabetes
Prevalence is higher in people with diabetes Most commonly seen in people with long-standing high blood pressure, but is also seen in the absence of elevated blood pressure in people with diabetes Prevalence is stronger in people with diabetes Weight distribution is also usually different, with more central obesity which is linked with a tendency to develop coronary heart disease People with diabetes smoke less presumably due to medical advice
Risk factor Hypertension High blood cholesterol High triglycerides with low HDL Left ventricular hypertrophy
Obesity
Smoking
Table 13: Prevalence of cardiovascular risk factors in people with diabetes compared to people without diabetes
A Stronger Impact
It has also been demonstrated that most cardiovascular risk factors have a more harmful impact in the presence of diabetes For example, having diabetes lowers by ten years the risk attributed to age in both men and post-menopausal women As regards the risk attributed to gender, women with diabetes lose the pre-menopausal protective effect of oestrogen and therefore have the same agerelated risk as men This implies that there should be a higher relative priority given to the public
health and clinical management of cardiovascular risk in women with diabetes than in the general population, where females are relatively protected from at least the coronary heart component of cardiovascular disease Also, although prevalence rates are similar, the cardiovascular risk attributed to high blood cholesterol is doubled in the presence of diabetes
The Role of Hyperglycaemia
people with diabetes, along with the treatment of diabetes itself But even when other risk factors are taken into account, people with diabetes are still more likely to die as a result of cardiovascular About 50 of the disease This implies that excess risk of some other factor is cardiovascular responsible This factor disease in type 2 could be related to diabetes can be diabetes itself Since the explained by the main characteristic of higher incidence diabetes is high blood and/or higher glucose, it is tempting to impact of assume that conventional risk hyperglycaemia is the factors main cardiovascular risk factor in this group The United Kingdom Prospective Diabetes Study UKPDS has shown that there is a significant linear correlation between haemoglobin A1c which reflects mean blood glucose levels
over the past three months and macrovascular events in type 2 diabetes It appears however that any increase in glucose levels above normal is associated with a higher risk of coronary heart disease Figure 27 This
49
Fact
About 50 of the excess risk of cardiovascular disease in type 2 diabetes can be explained by the higher incidence and/or the stronger impact of conventional risk factors The implication of this is that the lowering of these other risk factors should also be a priority in
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Coronary heart disease mortality incidence rate per 1000 persons per year
5 4 3 2 1 0 Normal glucose levels Impaired glucose tolerance Newly-diagnosed diabetes IGT Known diabetes
Figure 27: Mean coronary heart disease mortality rates by degree of glucose tolerance Adapted from: Eschwège E, et al 1985
includes impaired fasting glycaemia IFG and impaired glucose tolerance IGT It is important to note that the risk associated with IGT is approximately double that seen in people with normal glucose levels, and already approaches the level of risk of people with newly-diagnosed
diabetes As the relationship between glucose levels and risk is continuous, the risk becomes even higher with established diabetes, particularly if it is poorly controlled or of long duration Although proof of a direct causal relationship is still missing and the exact mechanisms are not fully understood, there is no doubt that raised glucose levels constitute a risk factor for cardiovascular disease in both people with and without diabetes
Multiple Risk Factors
three times greater than in the general population Figure 28
Type 1 Diabetes
People with type 1 diabetes also have an increased risk of coronary heart disease, although few studies have been carried out to People with type 1 attest this It seems diabetes over the prudent on the basis of age of 30 years clinical judgment to have a coronary consider that people heart disease risk with type 1 diabetes similar to people over the age of 30 years with type 2 are similar to people diabetes with type 2 diabetes as regards coronary h 
eart disease risk People with type 1 diabetes who suffer from diabetic nephropathy, regardless of age, should be treated as being at particularly high risk
Fact
Many people with diabetes have several
risk factors As we saw in Figure 21, the presence of several risk factors has a multiplicative and For each risk factor not just an additive present, the risk of effect The situation is cardiovascular death even more serious in is about three times people with diabetes greater in people as, for each risk factor with diabetes as present, cardiovascular compared to people mortality is about without the condition
Fact
New Cardiovascular Risk Factors and Diabetes
Microalmubinuria, which is a well-known disease marker for early diabetic nephropathy, has also been shown to be a risk factor for cardiovascular disease in people with diabetes The explanation seems to be related to the
50
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150
Cardiovascular disease mortality per 10,000 persons per year
120 90 60 30 0 1 2 3 Number of risk factors smoking, high cholesterol levels, hypertension 0
People without diabetes
People with diabetes
Figure 28: Impact of multiple risk factors in the presence of diabetes Adapted from: Stamler J, et al 1993
fact that microalbuminuria indicates the presence of vascular damage A number
of other new cardiovascular risk factors have also been identified, although most of them are still considered as risk markers The more noteworthy of these are homocysteine, lipoprotein a and Creactive protein At the present time there is insufficient evidence available to justify including them as part of a routine risk assessment
Conclusion
Due to the higher prevalence and impact of cardiovascular risk factors, as well as the role of hyperglycaemia, people with diabetes without overt cardiovascular complications merit an intervention against risk factors which is as aggressive as that which would normally be provided for individuals with established cardiovascular disease
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C HA PT E R 5
Reducing the Risks
Reducing the Risks
Management of Risk Factors in the General Population
Many cardiovascular deaths are potentially preventable if we can modify known risk factors While some risk factors are fixed such as age, gender and genetic background, many others are modifiable Table 14 Given that risk factors often occur together, all should be treated to gain the
most benefit in terms of reducing cardiovascular disease Diabetes and other high blood glucose conditions Dyslipidaemia High alcohol consumption Hypertension Insulin resistance Obesity Sedentary lifestyle Smoking
Dyslipidaemia see page 45: There is strong evidence that reducing elevated levels of LDL cholesterol diminishes the risk of coronary heart disease High levels of HDL cholesterol are also known to decrease the risk of coronary heart disease Therefore raising HDL cholesterol in people with low HDL cholesterol levels may provide benefit It is also likely that lowering high triglycerides has a similar effect Reducing lipid levels may also be beneficial in the prevention of stroke and peripheral vascular disease
The first line of treatment is lifestyle modification by improving diet, taking more physical exercise and losing excess body weight If these measures fail then drug treatment can also be prescribed A group of drugs called statins are particularly useful for lowering LDL cholesterol Another group known as fibrates can be used to target triglycerides Combinations of these can be used if required Hypertension see page 46: The lowering of elevated blood pressure
substantially cuts the risk of stroke and coronary heart disease If lifestyle measures including salt restriction are insufficient then antihypertensive drugs eg angiotensin converting enzyme ACE inhibitors, beta blockers, calcium channel blockers, diuretics should also be administered It is worth noting that many people will require more than one drug Insulin resistance see page 46: Insulin resistance is usually either caused or aggravated by obesity, particularly abdominal obesity Hence diet to promote the loss of excess weight, together with exercise to improve muscle metabolism and aid weight loss can improve insulin sensitivity When diabetes is present, tight glucose control can also enhance
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Table 14: Modifiable cardiovascular risk factors in the general population Modifiable cardiovascular risk factors in the general population are listed in alphabetical order below: Diabetes and other high blood glucose conditions: Although, as stated in Chapter 4, high glucose levels constitute a cardiovascular risk factor in people with and without diabetes, there is at present no evidence that the treatment of minor increases in blood glucose which fall short of overt diabetes
decreases the subsequent development of cardiovascular disease At the very least however, the finding of any rise in glucose levels should promote a careful search for and treatment of other cardiovascular risk factors
MODIFIABLE RISK FACTORS
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Obesity see page 46: Sustained weight loss in the overweight is of benefit for all cardiovascular diseases It is also instrumental in decreasing other risk factors such as raised blood pressure and high lipids
insulin sensitivity Drugs which specifically target insulin resistance are now becoming available, but it is not yet known whether decreasing insulin resistance will in itself slow or prevent the development of cardiovascular disease
Risk factor Diabetes and other high blood glucose conditions
Treatment Lifestyle modifications Drugs: oral hypoglycaemic agents, insulin
Results of treatment Although it prevents coronary heart disease, at present the effect of blood glucose lowering alone may not be as strong as the modification of other major risk factors Decreases the risk of coronary heart disease May also be
beneficial in the prevention of peripheral vascular disease and stroke Lowers the risk of stroke and coronary heart disease
Dyslipidaemia
Lifestyle modifications: eg diet, physical exercise and lowering excess body weight Drugs: statins, fibrates or a combination of the two Lifestyle modifications: drink in moderation
High alcohol consumption Hypertension
Lifestyle modifications: Reduces the risk of stroke and eg salt restriction coronary heart disease Drugs: beta blockers, calcium channel blockers, ACE inhibitors, diuretics, etc Lifestyle modifications: diet, exercise Tight glucose control in diabetes Lifestyle modifications: achieving normal body weight, increasing physical activity Lifestyle modifications: increasing in particular aerobic physical activity It is not yet known whether decreasing insulin resistance will in itself slow or prevent the development of cardiovascular disease Prevents all cardiovascular diseases Decreases other risk factors such as blood pressure, high glucose and high lipids Reduces body fat, raises HDL cholesterol levels, lowers LDL cholesterol and triglyceride levels, increases insulin sensitivity, and lowers blood glucose and blood
pressure Prevents coronary heart disease, stroke and peripheral vascular disease
Insulin resistance
Obesity
Sedentary lifestyle
Smoking
Lifestyle modifications: stopping smoking
Table 15: Management of cardiovascular risk factors in the general population
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be pursued as aggressively as it would be in individuals with established vascular disease As is the case for the general population, the first line of action in managing risk factors in people with diabetes should be lifestyle modifications If this is not sufficient then drugs can also be prescribed The lifestyle and drug measures summarized in Table 15 also apply to people with diabetes In addition, screening for microalbuminuria see page 50 is important, and specific interventions can help delay its progression Although people with diabetes and their physicians may be reluctant to add another drug to an already overwhelming regimen of medication, a number of recent studies have shown the extent to which some risk factors can be modified by medication in people with the condition The results of these
studies are summarized below and in Table 16
Sedentary lifestyle see page 46: There is compelling evidence that aerobic physical activity reduces the risk of coronary heart disease People who exercise regularly have less body fat, higher HDL cholesterol levels, lower LDL cholesterol and triglyceride levels, greater insulin sensitivity, lower blood glucose and blood pressure, and usually have an improved sense of well-being Smoking see page 46: Stopping smoking is of major benefit in the prevention of coronary heart disease, stroke and peripheral vascular disease, even in those who have smoked for a very long time Some risk factors cannot be easily measured and others may remain to be identified For this reason, certain interventions may be found to be very effective even though they do not target a specific measured risk factor A good example of this is aspirin, which has proved of major benefit in preventing coronary heart disease
Dyslipidaemia
A subgroup analysis of the Scandinavian Simvastatin Survival Study 4S showed the benefits of decreasing LDL cholesterol levels with a statin in people with diabetes and coronary heart disease This produced an even greater reduction in the
rate of coronary events than in people without diabetes 55 versus 32 In the diabetes group there was a saving of one life for every four patients treated, as opposed to one in 13 in the group of people without the condition In the Cholesterol and Recurrent Events Trial CARE the people studied also had coronary heart disease, but had lower cholesterol levels Statin therapy in this study cut the risk of coronary events by a similar degree in people with and without diabetes The aim of the Veterans Affairs HDL Intervention Trial VA-HIT was to use fibrate therapy to raise HDL cholesterol and lower triglycerides in men with documented coronary heart disease and low HDL cholesterol In the diabetic group there was a 22 relative risk reduction of a first non-fatal heart attack or
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Management of Risk Factors in People with Cardiovascular Disease
Even greater attention should be paid to risk factors in people who have already developed cardiovascular disease For instance smoking must be avoided, and all people with coronary heart disease should be taking aspirin unless a specific contraindication to its use is present Meticulous attention to blood pressure and lipid control is also
vital
Management of Risk Factors in People with Diabetes
As many people with diabetes who experience a first coronary event die prior to getting to hospital, they cannot benefit from secondary prevention strategies In view of this, as well as the increased overall risk associated with diabetes, the management of risk factors in people with diabetes should precede the onset of heart or other vascular disease and should
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Hyperglycaemia
Data from the UKPDS suggest that there is benefit in tightly controlling blood glucose in people with diabetes This was particularly evident in a group of overweight subjects who were treated with an oral hypoglycaemic agent metformin, in whom a 37 reduction in heart While attacks was recorded, cardiovascular and also when blood deaths have glucose lowering and declined in those blood pressure control without diabetes in were combined The developed countries, latter finding emphasizes in men with the importance of diabetes the treatment strategies decrease has been aimed at multiple risk modest, while in factors women with diabetes the
rates It is worth noting that, have actually over time, a combination increased of different oral agents and insulin is required for blood glucose control in type 2 diabetes In type 1 diabetes there was also a hint in the DCCT that tight control of blood glucose improves cardiovascular outcomes
coronary heart disease death, and a significant decline in cerebrovascular events It is thus clear that lipid lowering with either statins or fibrates is beneficial in people with type 2 diabetes, particularly if they already have coronary heart disease Although there is evidence to suggest the same benefit for people with diabetes but without coronary heart disease, this remains to be confirmed
Fact
Hypertension
In the part of the UKPDS that dealt with hypertension, people with type 2 diabetes were randomized to intensive or conventional treatment using either a beta blocker or an ACE inhibitor The average blood pressure was improved by 10 mm Hg systolic and 5 mm Hg diastolic This resulted in a reduction of the risks for heart failure 56, stroke 44 and deaths related to diabetes 32 Current practice is to aim for normal blood pressure values, particularly in those with other risk factors
and those who have already experienced a cardiovascular event
Strategy Lipid control
Complication Coronary heart disease mortality Major coronary heart disease event Any atherosclerotic event Cerebrovascular disease event Cardiovascular disease Heart failure Stroke Diabetes-related deaths
Reduction of complication 36 1 55 1 37 1 62 1 51 2 56 3 44 3 32 3 37 3
Blood pressure control Blood glucose control
1 2
Heart attack
The 4S Study Hypertension Optimal Treatment HOT Randomised Trial 3 UKPDS Table 16: Highest percentage reduction of the risk of diabetic complications in people with type 2 diabetes shown in recent studies Adapted from: International Diabetes Federation 1999
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exist However it should be noted that the relationship between risk factors and disease is generally continuous and additional benefits may be obtained by lowering risk factors even further Risk factors Dyslipidaemia Targets Decrease LDL cholesterol levels 115mg/dl or 3 mmol/l Raise HDL cholesterol levels 46 mg/dl or 12 mmol/l Lower triglycerides 150 mg/dl or 17 mmol/l Lower
blood pressure 135/85 mm Hg
Putting the Theory into Practice
These positive results call for aggressive action to be taken to treat the cardiovascular risk factors that are common in people with diabetes Despite these findings, a recent US study revealed that while cardiovascular disease mortality and particularly coronary heart disease related deaths have declined in those without diabetes, in men with diabetes the decrease has been a modest 13, while in women with diabetes the rates have actually increased by 23 Figure 29 This suggests that approaches proven to reduce cardiovascular disease in people with diabetes are frequently not implemented in clinical practice There is therefore a clear need for improved awareness of treatment possibilities among healthcare professionals Guidelines with specific targets for cardiovascular risk factors in people with type 1 and type 2 diabetes have been published by the European and Western Pacific Regions of IDF Many other national and regional guidelines also
Hypertension
Hyperglycaemia Reduce hyperglycaemia HbA1c 7 Table 17: Targets for common cardiovascular risk factors in people with diabetes These levels are based on IDF Europes
guidelines Other guidelines, for example those from the USA or Latin America, may give slightly different target values
Other Risk Factors
In people with diabetes other factors are also associated with cardiovascular disease, such as increased stickiness of the blood and hardening of arteries It is not known at this stage whether treatment of such factors is beneficial
30
Coronary heart disease mortality
20 10 0 -10 -20 -30 -40 People without diabetes People with diabetes
National Approaches to Prevention: Lifestyle
Preventing Diabetes and Cardiovascular Disease
The global changes in lifestyle such as a higher intake of fat, salt and calories, as well as decreased physical activity have led to an upsurge in cardiovascular disease and type 2 diabetes In many countries specific manifestations of lifestyle changes include an increase in the amount of junk food consumed and the replacement of physical activity by
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Men
Women
Figure 29: Changes in coronary heart disease mortality rates in the USA Adapted from: Gu K, et al 1999
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curb smoking include raising
government taxes, restricting smoking in the workplace and public places, and banning advertising and sponsorship by tobacco companies The implementation of national programmes which focus upon primary prevention is essential Economies of scale can potentially be achieved by linking or integrating programmes Examples include programmes relating to environmental pollution, public transport services, urban planning and architecture The WHO concept of the Healthy City applies with great force to primary prevention programmes Factors which hamper success include the hostile modern environment particularly in urbanized settings, the impact of consumerism, the interest of multinational companies and socio-economic pressures A healthy, balanced diet less fat, salt, refined sugar, alcohol and calories; more fibre, fruit and vegetables Regular physical activity eg aerobic exercises A healthy social life and relaxation techniques to combat stress Smoking cessation Sustained weight loss in the overweight Table 18: Lifestyle behaviour to be promoted
television, video games and internet browsing Increasing urbanization and mechanization are also responsible for the general decline in
physical activity levels It is obvious that lifestyle modification can be of major benefit in preventing noncommunicable diseases such as cardiovascular disease and diabetes Although they may be challenging for the individual to implement, lifestyle changes are cheap, effective and free of side effects On the national level, a broad population-based approach to prevention is probably more costeffective than merely targeting high-risk individuals, although both methods can be effectively combined Ideally a population-based approach should begin in childhood when health-risk behaviour begins Parents, teachers and peer groups should be involved in imparting health education to children, as a sharp rise in the prevalence of childhood obesity and young-onset type 2 diabetes has been recently reported from several countries Healthy eating habits should be encouraged, emphasizing a reduction in total calories, fat and sugar, and an increase in the intake of fibre, fruit and vegetables The healthy option should be made more accessible and affordable for all In the UK for example free fruit is now being given to school children and wide publicity is being given to the message that everybody
should eat five portions of fruit and vegetables a day Regular physical exercise, eg aerobic exercises like walking, jogging, swimming or cycling, can help to prevent diabetes and reduce cardiovascular disease risk factors Relaxation techniques can also play a role in the prevention of cardiovascular disease Exercise can be promoted by initiatives such as providing public sports facilities in the community Cigarette smoking rates have already started falling in the Western world but unfortunately they are on the increase in developing countries Some of the successful measures to
Preventing Cardiovascular Disease in People with Diabetes
Cardiovascular disease prevention in people with diabetes should in the first place be part of a comprehensive approach to prevention in the whole community It is inevitably easier for people with diabetes to change lifestyle behaviour if this is occurring in the population at large There should be national guidelines on lifestyle modification leading to an overall healthier population, with particular emphasis on people with diabetes These kinds of activities tend to be more successful when based on local initiatives ie the bottom-up approach Such
initiatives are being promoted by IDF and WHO
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C HA PT E R 6
Treatment of Cardiovascular Disease in Diabetes
and by prescribing drugs eg aspirin, betablockers, nitrates and long-acting calcium channel blockers When unstable angina develops, the risk of heart attack is very high and rapid preventive treatment in an intensive or coronary care unit may be required People with diabetes who have experienced an acute heart attack benefit to the same degree, and in some cases even more, from therapeutic interventions that are used in people without diabetes Table 19 Treatment Aspirin Effectiveness in people with diabetes Equally effective Equally effective Particularly advantageous if started within 24 hours Equally effective
Treatment
This chapter deals in general terms with the main issues relating to the treatment of cardiovascular disease in diabetes Specific details with regard to the exact implementation and choice of treatment regimes is beyond the scope of this publication Many of the treatment modalities for cardiovascular disease are similar irrespective
of whether diabetes is present or not However specific issues related to diabetes include the difficulty of diagnosing silent cardiovascular disease, the need for the aggressive management of all risk factors, and the use of insulin therapy to achieve blood glucose control when a heart attack occurs
Treatment of Coronary Heart Disease
Assessment
An electrocardiogram ECG may be helpful for screening people at risk, particularly Caucasians and south Asians over the age of 40 The first step is to screen patients with angina or any other coronary heart disease symptoms However, in view of the often silent, asymptomatic nature of coronary heart disease in people with type 2 diabetes, the diagnosis often needs to be made by exercise cardiac stress testing If the symptoms and/or the test findings are highly suggestive of coronary heart disease, the person will require further investigation In these patients all cardiovascular risk factors must be reexamined and treated aggressively
Beta-blockers ACE inhibitors Statins
Clot dissolving Useful within the first agents thrombo12 hours, although slightly lytic therapy less effective in diabetes Table 19: Treatments for patients who have
experienced an acute heart attack and their effectiveness in people with diabetes compared to the general population
Treatment
People with stable angina are usually treated by tight control of cardiovascular risk factors
Intensive insulin therapy for tight blood glucose control when the patient is in hospital has also proven to decrease death rates, and may be beneficial for at least three months following hospitalization The DIGAMI Study from Sweden stresses the importance of controlling blood glucose levels during the acute phase and demonstrates that intensive insulin treatment also improves survival over the longer term,
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been suggested to be even stronger than in people without diabetes Resources need to be made available for the rehabilitation of stroke patients, which may be particularly complicated in people with diabetes due to the presence of other complications
with a 24 reduction in death rates after three and a half years This means a saving of one life for every nine patients on intensive insulin treatment
Fact
Intensive insulin treatment in
those who have experienced an acute heart attack improves survival over the short and long term with a 24 reduction in deaths after three and a half years
If people with diabetes require revascularization a procedure to either open up blocked blood vessels angioplasty or to bypass them using implanted vessels from other parts of the body bypass surgery - bypass has proven to be a judicious choice, particularly when several coronary vessels are involved, which is frequently the case in diabetes The use of tiny metal devices called stents to keep arteries open has also improved the prognosis of some patients with diabetes and coronary heart disease Heart failure is a complication of coronary heart disease which occurs more frequently in people with diabetes It is usually treated with drugs such as water tablets diuretics, ACE inhibitors, beta-blockers and digitalis
Treatment of Peripheral Vascular Disease
Almost all people with diabetes who have established vascular disease including diabetic foot problems, microvascular disease, macrovascular disease, neuropathy and a history of amputations present a higher risk of amputation in another limb as well as a greater risk of heart
attack and cardiovascular death In people with both diabetes and peripheral vascular disease, revascularization performed by an expert team can be a good alternative to amputation The use of pharmacological interventions depends on the nature of the underlying disease However the benefit of drugs is unproven The best treatment of the diabetic foot is prevention This can only be achieved by educating people with diabetes about foot care Although not all foot complications can be prevented, dramatic reductions in their frequency can be achieved through the implementation of diabetic foot programmes by a multidisciplinary team involving primary healthcare professionals, community carers and the diabetes team There should also be better access to amputation, rehabilitation, prostheses and chiropody facilities for all patients
Treatment of Cerebrovascular Disease
As well as being a risk factor for stroke, diabetes and other high blood glucose conditions have adverse effects on both the short and long-term prognosis for stroke victims Hyperglycaemia in the acute phase of stroke has been associated with high death rates, regardless of the presence or absence of diabetes Tight glucose
control improves the time of recovery The standard therapies of intervention in stroke in people without diabetes are also helpful in people with diabetes Indeed, the effect of aspirin on cardiovascular events including stroke in people with diabetes has
Conclusion
Since there are many risk factors involved, the treatment and follow-up of cardiovascular disease in people with diabetes can be a complicated, time-consuming and expensive process Therefore the value of the preventive measures outlined in Chapter 5 cannot be overemphasized
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CONCLUSION
The Way Forward
Conclusion
Fact
The contents of this publication can leave the reader in no doubt as to the magnitude of the problems posed by diabetes and its cardiovascular complications, which are a major cause of illness, death and healthcare costs It It is possible to take is also manifest that action to slow or these problems are stop the global in perspective consequences of and are rapidly cardiovascular worsening disease in diabetes Now is the time to The good news is that act it is possible to take action
to slow or stop the consequences of cardiovascular disease in diabetes But there can be no doubt that now is the time to act Action must be taken on four levels: 1 Prevention 2 Treatment 3 Education/Awareness 4 Research
simultaneously help to reduce other cardiovascular risk factors such as hypertension, obesity and dyslipidaemia The lifestyle changes required can be summarized very simply by the IDF slogan Eat Less, Walk More Early screening for diabetes and its complications This will enable intervention in the early stages of cardiovascular complications However it must be recognized that this may lead to a shortterm rise in the use of resources as a result of an increased identification of new cases This should be viewed as an advantage rather than a disadvantage, since early detection has obvious long-term benefits Investment in national programmes aimed at primary and secondary prevention of diabetes and its cardiovascular complications These programmes can be integrated or linked with other health or environmental programmes
Treatment Prevention
Investment in primary and secondary prevention strategies is potentially the most effective measure in the long term, in both
human and economic terms It is necessary to adopt an uncompromising multifactorial approach to prevent or slow the progression of cardiovascular disease in people with diabetes Fundamental aspects of prevention include: Promoting a healthy lifestyle Primary prevention of diabetes by lifestyle modification has the advantage that it will Adequate healthcare resources need to be made available not only for prevention, but also for the treatment of established diabetes and its cardiovascular complications This means the provision of essential medical treatment, so that the best possible prognosis can be ensured At the very least we should aim for a similar decline in cardiovascular disease mortality for people with diabetes around the world as that which has been witnessed in people without diabetes in many developed countries in recent years
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associations must work together with other nongovernmental organizations and WHO to put a halt to the double scourge of diabetes and cardiovascular disease, and to make governments aware that action must be taken
urgently
Education/Awareness
Education and awareness at all levels and strata of society is the key to success Governments: Decision makers need to be made aware of the close link between diabetes and cardiovascular disease and that, if measures are not taken to prevent diabetes in the first place, a global explosion of cardiovascular disease is waiting to happen Given that there is a lot of overlap in the prevention techniques for the two diseases, investment in prevention can yield a high return Healthcare professionals: As reported in this book, the cardiovascular risk factors in diabetes have been identified by many recent studies A number of these risk factors are modifiable and it has been proven possible to reduce their impact dramatically Healthcare professionals must be made aware of the importance of systematically and aggressively implementing these findings in clinical practice Public: People with diabetes in particular need to be aware of the common cardiovascular risk factors and the lifestyle and other measures that can be taken to decrease or delay their chance of developing cardiovascular disease
Research
Expanded basic and clinical research is needed in order
to gain a better understanding of the factors that contribute to the excess risk of premature cardiovascular disease in people with diabetes In the future new therapies should aim to decrease the cardiovascular risk of people with diabetes to the same level as that of people without diabetes
Conclusion
It is hoped that Diabetes and Cardiovascular Disease: Time to Act will prompt action on all these planes Success can only be achieved through teamwork and collaboration IDF and its member
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Fact File
Ten facts and figures about diabetes and cardiovascular disease: 1 It is estimated that there are at least 150 million people in the world with diabetes now This figure is expected to double over the next 25 years Cardiovascular disease is the number one cause of death in industrialized countries It is also set to overtake infectious diseases as the most common cause of death in many parts of the less developed world People with diabetes are two to four times more likely to develop cardiovascular disease than people without diabetes, making it the most common
complication of diabetes People with type 2 diabetes have the same risk of heart attack as people without diabetes who have already had a heart attack People with diabetes can have a heart attack without even realizing it Strokes occur twice as often in people with diabetes and high blood pressure as in those with high blood pressure alone Transient ischaemic attacks mini-strokes occur between two and six times more frequently in people with diabetes People with diabetes are 15 to 40 times more likely to require a lower-limb amputation compared to the general population For each risk factor present, the risk of cardiovascular death is about three times greater in people with diabetes as compared to people without the condition
2
3
4
5 6
7
8
9
10 While cardiovascular disease mortality and in particular coronary heart disease related deaths have declined in those without diabetes in developed countries, in men with diabetes the decrease has been a modest 13, while in women with diabetes the rates have actually increased by 23
The good news is that it is possible to take action to slow or stop the consequences of cardiovascular disease in diabetes Now is the time to
act
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ANNEX 1
Diagnostic Criteria for Diabetes and its Risk States
Venous plasma glucose concentration, mmol l-1 mg dl1 70 126 111 200
Diagnostic Criteria
In the majority of affected individuals the diagnosis of diabetes is straightforward However it may cause problems for those with minor degrees of hyperglycaemia If someone has typical symptoms of diabetes and a clearly raised plasma glucose level, the diagnosis is clear A person with ketones in the urine and high glucose does not present a problem either However in the person without symptoms, two abnormal results on separate occasions are needed Diagnostic values are shown in Table 20 The cut-off points are based on the risk of subsequently developing the specific complications of diabetes: retinopathy, nephropathy and neuropathy To distinguish between different types of diabetes, further tests may be needed, but this is usually not required in the clinical setting Diabetes mellitus Fasting or 2h post glucose load Impaired glucose tolerance IGT Fasting if measured and 2h post glucose load
70 126 78
140 61 110 and 70 126 78 140
Impaired fasting glycaemia IFG Fasting and if measured 2-h post glucose load
Table 20: Diagnostic values for diabetes and its risk states Please note that these values refer to venous plasma glucose Values for whole venous blood and capillary blood are slightly different For more information on this and the diagnosis and classification of diabetes in general, see Alberti KGMM 1999
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ANNEX 2
Diabetes Prevalence
Diabetes Prevalence
Estimated diabetes prevalence
Prevalence 20-79 age group 0 Papua New Guinea Dominica, Commonwealth of 65 age group Mauritius Bahrain Mexico 35-64 age group Trinidad and Tobago 35-69 age group Barbados Aruba Bermuda British Virgin Islands Cayman Islands Grenada Hong Kong SAR, PRC St Kitts and Nevis Pakistan Czech Republic all age groups Tonga Singapore, Republic of Macao SAR, PRC Netherlands Antilles Malta 35-69 age group Saudi Arabia Egypt 20 age group Fiji Taiwan Puerto Rico Cuba all age groups Slovakia Bahamas Jamaica New Zealand all age groups Slovenia USA 20 age group Qatar Japan all age
groups Georgia, Republic of Israel Syria Italy Kuwait Hungary Lebanon all age groups Sweden Malaysia 35 age group Jordan Denmark 60-74 age group Korea, Republic of Spain 10-74 age group Australia Greece India Poland 45-64 age group Finland Macedonia Portugal Croatia Dominican Republic all age groups Albania 2 4 6 8 10 12 14 16
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Estimated diabetes prevalence continued
Prevalence 20-79 age group 0 Canada 18-74 age group Cyprus El Salvador Haiti Indonesia 15-74 age group Estonia Paraguay Turkey Uruguay Germany Suriname Belgium Bulgaria all age groups Honduras Iraq Venezuela Bolivia Colombia France South Africa Austria Iran Luxembourg Norway Kyrgyz Republic Peru Switzerland Thailand Netherlands Ukraine all age groups United Kingdom Belize Costa Rica Sudan 25 age group Argentina Brazil Ireland, Republic of Lithuania all age groups Tunisia Guyana Philippines Ecuador Guatemala Panama Sri Lanka China, Peoples Republic of Libya Morocco Bangladesh 15 age group Iceland Chile over 20 age group Kazakhstan Republic all age groups Kenya Mozambique Congo, Dem Republic of
Uganda Zambia Ethiopia Madagascar Zimbabwe Cameroon Gabon Tanzania Senegal Congo, Republic of Côte dIvoire Togo Ghana Mali Nigeria Gambia Romania all age groups 2 4 6 8 10 12 14 16
crude value Source: International Diabetes Federation 2000
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ANNEX 3
Coronary Heart Disease and Cerebrovascular Disease Mortality Rates
Mortality per 100,000 population per year 300 400 500 600 700 800
Mortality Rates
Coronary heart disease in males 0
Latvia Russia Turkmenistan Azerbaijan Republic Kazakhstan Republic Estonia Belarus Moldova, Republic of Lithuania Ukraine Fiji Uzbekistan Armenia Hungary Czech Republic Kyrgyz Republic Georgia, Republic of Trinidad and Tobago Mauritius Ireland, Republic of Kuwait Romania Yugoslavia American Samoa Bulgaria Finland New Zealand United Kingdom Tajikistan Poland Norway Singapore, Republic of Croatia Malta United States of America Venezuela Cuba Austria Suriname Sweden Germany Palau Macedonia Bahamas Bahrain Canada Uruguay Mongolia Guyana Netherlands Israel Colombia Slovenia Guam Puerto Rico Greece Australia
100
200
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Coronary heart disease in males continued
Mortality per 100,000 population per year 0
Luxembourg Cook Islands Costa Rica Italy Argentina Belgium Belize St Lucia Mexico Philippines Paraguay Chile Seychelles Portugal Brazil Albania Barbados Dominica, Commonwealth of Antigua and Barbuda Panama Sri Lanka Spain Jamaica France South Africa Hong Kong SAR, PRC Northern Mariana Islands China, Peoples Republic of El Salvador Egypt Nicaragua Dominican Republic Taiwan Japan Guatemala Korea, Republic of Ecuador Peru São Tomé and Príncipe Zimbabwe Turkey
100
200
300
400
500
600
700
800
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Coronary heart disease in females
Mortality per 100,000 population per year 0
Moldova, Republic of Turkmenistan Uzbekistan Azerbaijan Republic Kazakhstan Republic Russia Belarus Latvia Trinidad and Tobago Ukraine Armenia Estonia Kyrgyz Republic Georgia, Republic of Lithuania Mauritius Fiji Tajikistan Hungary Czech Republic Romania Cuba Cook Islands Yugoslavia Ireland, Republic of Bahrain
Bulgaria New Zealand Singapore, Republic of Malta Kuwait Venezuela Belize United Kingdom Suriname Colombia Mongolia United States of America Croatia Macedonia Finland Costa Rica Bahamas Israel Poland Norway Austria Australia Brazil Germany Guam Puerto Rico Mexico Uruguay Sweden Barbados Canada Paraguay St Lucia Netherlands Philippines Slovenia Panama Seychelles Jamaica Antigua and Barbuda China, Peoples Republic of Chile Greece Guyana Luxembourg Belgium
100
200
300
400
500
600
700
800
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Coronary heart disease in females continued
Mortality per 100,000 population per year 0
Portugal South Africa American Samoa El Salvador Nicaragua Italy Argentina Palau Hong Kong SAR, PRC Albania Dominican Republic Spain São Tomé and Príncipe Guatemala Taiwan Dominica, Commonwealth of Sri Lanka Egypt France Ecuador Japan Korea, Republic of Peru Zimbabwe Turkey Northern Mariana Islands
100
200
300
400
500
600
700
800
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Cerebrovascular disease in
males
Mortality per 100,000 population per year 0
Ukraine Kyrgyz Republic Russia Guyana Latvia Bulgaria Moldova, Republic of Romania Kazakhstan Republic Yugoslavia Mauritius Estonia Cook Islands Belarus China, Peoples Republic of Turkmenistan Georgia, Republic of Hungary Uzbekistan Macedonia Korea, Republic of Trinidad and Tobago St Lucia Croatia Jamaica Antigua and Barbuda Northern Mariana Islands Tanzania Azerbaijan Republic Seychelles Czech Republic Mongolia American Samoa Lithuania Portugal Tajikistan Bahamas Armenia Taiwan Argentina Barbados Brazil Paraguay Belize Slovenia Philippines Albania Dominica, Commonwealth of Poland Uruguay Singapore, Republic of Fiji Chile Venezuela Martinique Suriname South Africa Cuba Colombia São Tomé and Príncipe Greece Finland Panama Japan Hong Kong SAR, PRC Austria Ireland, Republic of Malta Germany Nicaragua New Zealand Italy United Kingdom El Salvador Israel
100
200
300
400
500
600
700
800
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Cerebrovascular disease in males continued
Mortality per 100,000 population per year 0
Zimbabwe Mexico Spain Guam Ecuador
Norway Costa Rica Luxembourg Belgium Egypt Palau Sweden Netherlands Dominican Republic Sri Lanka Puerto Rico United States of America France Turkey Bahrain Kuwait Australia Canada Botswana Guatemala Peru
100
200
300
400
500
600
700
800
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Cerebrovascular disease in females
Mortality per 100,000 population per year 0
Ukraine American Samoa Kyrgyz Republic Moldova, Republic of Russia Yugoslavia Kazakhstan Republic Romania St Lucia Guyana Latvia Turkmenistan Bulgaria Belarus Jamaica Macedonia Georgia, Republic of Uzbekistan China, Peoples Republic of Estonia Tanzania Mauritius Dominica, Commonwealth of Azerbaijan Republic Armenia Trinidad and Tobago Tajikistan Croatia Korea, Republic of Hungary Mongolia Lithuania Belize Paraguay Czech Republic Seychelles Singapore, Republic of Portugal South Africa Suriname Taiwan Cuba Bahamas Colombia Venezuela Brazil Uruguay São Tomé and Príncipe Albania Argentina Slovenia Fiji Poland Antigua and Barbuda Philippines Chile Greece Northern Mariana Islands Barbados Nicaragua Ireland, Republic of Mexico Luxembourg Martinique
New Zealand Malta Panama Finland Hong Kong SAR, PRC El Salvador United Kingdom Guam Japan Ecuador Dominican Republic
100
200
300
400
500
600
700
800
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Cerebrovascular disease in females continued Mortality per 100,000 population per year 0
Costa Rica Austria Germany Zimbabwe Israel Italy Palau Norway Egypt Belgium Netherlands Turkey Spain United States of America Guatemala Sweden Australia Sri Lanka Canada Puerto Rico France Kuwait Peru Bahrain Botswana Cook Islands
100
200
300
400
500
600
700
800
For information on sources and methodology, see page 25
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ANNEX 4
Studies of Diabetes and Heart Disease
Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction Study DIGAMI
The objective of the DIGAMI study was to determine the long-term effect of intensive insulin treatment initiated at the time of an acute heart attack on 620 people with diabetes Patients were randomly assigned to either intensive insulin treatment
or standard treatment During an average follow-up of over three years a significant mortality risk reduction 24 was recorded in the intensively treated group
Studies
Cholesterol and Recurrent Events Trial CARE
The objective of the CARE study was to assess the effect of a statin on the risk of fatal or nonfatal heart attacks in people with coronary heart disease and high cholesterol levels 14 of the participants had diabetes The study demonstrated a 25 reduction of major coronary events in people with diabetes on statin therapy Total cholesterol levels were cut by 19, LDL cholesterol by 27, and triglycerides by 13 HDL cholesterol was increased by 4
Diabetes Control and Complications Trial DCCT
The DCCT was a clinical study conducted from 1983 to 1993 by the US National Institute of Diabetes and Digestive and Kidney Diseases NIDDK The DCCT involved 1440 volunteers who had type 1 diabetes for at least one year but no longer than 15 years They also were required to have no, or only early signs of, diabetic eye disease The study compared the effects of two treatment regimens - standard therapy and intensive control - on the complications of diabetes Volunteers were randomly assigned
to each treatment group The study showed that keeping blood glucose levels as close to normal as possible slowed the onset and progression of diabetic eye, kidney and nerve diseases
Hypertension Optimal Treatment Randomized Trial HOT
The HOT study is the largest trial ever conducted of the results of treating hypertension Almost 18,800 patients from 26 countries were followed up for an average of just under four years 8 of the patients had diabetes HOTs objective was to find out how far blood pressure should be lowered using antihypertensive drugs in order to achieve the maximum decreases in strokes and heart attacks in people with hypertension Compared to the people with diabetes in the group with diastolic blood pressure kept at 90 or below, those in the group 80 or below had a 51 reduction in major cardiovascular events and a 30 reduction in strokes
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Scandinavian Simvastatin Survival Study 4S
The objective of the diabetes sub-study of the 4S was to assess the effect of a statin on mortality and the risk of a major coronary event in people with coronary heart
disease and high cholesterol levels 5 of the total participants had diabetes The study found that major coronary events were halved in people with diabetes on statin therapy Total cholesterol was reduced by 27, LDL cholesterol by 36, triglycerides by 11, and HDL cholesterol was increased by 7
MONICA Project
The WHO MONICA Project is the largest community-based study on heart disease ever undertaken The results show that heart disease rates are related to changes in major coronary risk factors and to the introduction of new medical treatments The MONICA Project studied more than 30 populations mainly from Europe from the mid-1980s to the mid-1990s More than seven million men and women aged between 35 and 64 years of age were monitored to examine if and how certain coronary risk factors and new treatments for heart disease contribute to the rise or fall of heart disease rates in these communities Risk factors such as cigarette smoking, blood pressure, blood cholesterol and body weight were studied Treatments taken into consideration included aspirin, beta blockers, ACE inhibitors, clot dissolving agents and coronary artery surgery Heart disease rates fell in most of the populations
studied, as did cigarette smoking in men, blood pressure and blood cholesterol Smoking in women showed a mixed picture and weight rose in both men and women in most populations Taking all populations as a whole, the decline in smoking seems to have contributed most to the reduction in the risk of heart disease in men In women, the decrease in blood pressure emerged as the strongest determinant Overall, it was found that the relation between the fall in heart disease rates and the change in risk factors was more apparent in men than in women
United Kingdom Prospective Diabetes Study UKPDS
The UKPDS recruited over 5000 patients with newly-diagnosed type 2 diabetes between 1977 and 1991 and followed them for 10 years The study confirmed that when people with type 2 diabetes aggressively lowered blood glucose maintaining HbA1c levels around 7, their risk of blindness and kidney failure fell by 25 In a group of overweight people treated with an oral hypoglycaemic agent metformin the impact on microvascular complications was not as strong, but there was a significant reduction in the risk of a fatal or non-fatal heart attack 37 and all-cause mortality 36 When high blood pressure was
aggressively tackled, major reductions in the risk of stroke 44 and heart failure 56 were achieved in addition to the eye and kidney benefits
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Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial VA-HIT
The objective of the VA-HIT study was to assess the effect of fibrate therapy on mortality and the risk of a major coronary event in people with coronary heart disease and nearnormal LDL cholesterol but low HDL cholesterol 25 of the participants had diabetes The study found that by increasing HDL cholesterol by just under 8 and decreasing triglycerides by 25, the risk of a major cardiovascular event was cut by 22 in people with diabetes This was the first trial to demonstrate a diminished risk of cardiac events from an intervention that raised HDL levels but did not reduce LDL levels
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Glossary
Glossary
ALBUMINURIA ANGINA ANGIOPLASTY
A condition where too much protein albumin is secreted in the urine, usually an indication
of kidney disease When only tiny amounts of albumin are excreted this is called microalbuminuria
organs These nerves are not under a persons conscious control and function automatically
BETA BLOCKER
Discomfort in the chest caused by an inadequate supply of blood to the heart muscles Can be stable or unstable
Drugs that block the action of the hormone adrenaline that makes the heart beat faster and more vigorously, thereby relieving stress to the heart muscle Beta blockers are often used to slow the heart rate, lower blood pressure, prevent angina attacks, prevent irregular heartbeats and reduce the risk of heart attacks in people who have already had one
BETA CELL
Surgery whereby a balloon is inflated inside a blocked artery to open it up
ANGIOTENSIN CONVERTING ENZYME ACE INHIBITOR
Beta cells are found in the Islets of Langerhans in the pancreas They produce and release insulin
BLOOD PRESSURE
A type of drug used for blood pressure control and heart failure Studies indicate that it may also help prevent or slow the progression of kidney disease in people with diabetes
ARTERY
A vessel carrying blood from the heart to various parts of the body
ATHEROMA
Fatty material that can
build up within the walls of the arteries
ATHEROSCLEROSIS
A measure of the force of the blood being pushed by the heart through the arteries This pressure is created when the heart beats, forcing blood around the body and also by the elastic resistance of the arteries themselves Blood pressure is written as two numbers The higher number systolic shows the pressure created by the heart contracting or pumping out the blood The lower number diastolic indicates the pressure when the heart is relaxing between beats The pressure is measured on a blood pressure gauge in millimetres of mercury mm Hg
BLOOD VESSEL
Hardening and thickening of the walls of the arteries as a result of deposits of atheroma on their inner lining This build-up of atheroma may slow down or stop blood flow
AUTONOMIC NEUROPATHY
An artery, vein or capillary
BODY MASS INDEX BMI
Disease of the nerves affecting mostly internal organs such as the bladder, the cardiovascular system, the digestive tract and the genital
A key index for assessing body weight in relation to height The BMI is a persons weight in kilograms kg divided by their height in meters m squared In the West a person is considered overweight when
his/her BMI is
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Cholesterol is carried in the blood stream by particles called lipoproteins When total cholesterol is measured in the blood, it includes cholesterol carried by low-density lipoproteins LDL and high-density lipoproteins HDL
CIRCULATORY SYSTEM
above 25, obese when it is above 30 and severely obese when it is above 35 In Asia the recently-recommended corresponding BMIs are 23, 25 and 30 respectively
BYPASS SURGERY
An operation whereby a blood vessel is taken from another part of the body and is used to redirect the flow of blood around a blocked or narrowed part of a heart vessel
CALCIUM CHANNEL BLOCKER
The system composed of the heart and blood vessel tree
CORONARY ARTERY
A drug used to treat angina and to lower blood pressure
CAPILLARY
The coronary arteries are blood vessels that deliver oxygenated blood to the muscle of the heart
CORONARY ARTERY DISEASE
Capillaries are the smallest of the blood vessels They join the arteries to the veins
CARDIOVASCULAR DISEASE
Coronary artery disease begins when atheroma is deposited within a coronary
artery
CORONARY HEART DISEASE
Cardiovascular diseases are defined as diseases and injuries of the circulatory system: the heart, the blood vessels of the heart, and the system of blood vessels throughout the body and to and in the brain Stroke is the result of a blood flow problem within, or leading to, the brain and is considered a form of cardiovascular disease
CAROTID ARTERY
Any disease of the heart caused by coronary artery disease, although it usually refers to heart attack and angina
C-REACTIVE PROTEIN
C-reactive protein is a protein whose plasma concentrations increase or decrease by 25 or more during inflammatory disorders
DEMENTIA
The two carotid arteries are located on each side of the front of the neck These arteries provide the principal blood supply from the heart to the head and neck
CENTRAL OBESITY
Significant loss of intellectual abilities such as memory and judgement, severe enough to interfere with social or occupational functioning
DIABETES MELLITUS
An abnormal accumulation of fat around the abdomen which can be assessed by measuring the ratio of the waist to the hip circumference This form of obesity is strongly associated with cardiovascular and diabetes
risk Also known as visceral or abdominal obesity
CEREBROVASCULAR DISEASE
Damage to the blood vessels in the brain, which may result in a stroke
CHOLESTEROL
Diabetes mellitus is a chronic condition that arises when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin produced This causes hyperglycaemia which seriously damages many of the bodys systems, especially the blood vessels and nerves There are two main types of diabetes: type 1 diabetes and type 2 diabetes
DIGITALIS
A waxy, fat-like substance used by the body to build cell walls It is either produced in the liver or absorbed from the animal fats we eat
A plant-based drug used to treat heart failure and certain abnormalities of the heart rhythm
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during some cases of pregnancy but usually disappears when pregnancy is over However women who have had gestational diabetes are at a much greater risk of developing type 2 diabetes at a later stage in their lives
HAEMOGLOBIN A1C HBA1C
DIURETIC
Diuretics increase the output of water and salt in the urine They are used
to treat heart failure and to lower blood pressure
DYSLIPIDAEMIA
Abnormal levels of lipids fats in the blood
ELECTROCARDIOGRAM ECG
A test using electrodes placed on the chest, arms and legs to record the rhythm and electrical activity of the heart
ENDOTHELIUM
The layer of flat cells that lines the cavities of the heart and of the blood and lymph vessels
EXERCISE CARDIAC STRESS TESTING
Haemoglobin Hb is the protein in the red blood cells which carries oxygen to the cells HbA1c corresponds to a small part of Hb normally less than 6 which joins with the glucose present in the blood Because the glucose stays attached to it throughout the life of the red cell about three months, a test to measure HbA1c reflects what the persons average blood glucose level was for that period of time
HEART ATTACK
The most widely used screening test for heart disease The patient exercises on a treadmill, whose speed and elevation increases progressively During this test the heart rate, heart rhythm, electrocardiogram and blood pressure are monitored
FEMORAL ARTERY
Also called myocardial infarction; results from permanent damage to an area of the heart muscle This happens when the blood supply to the
area of the heart is interrupted because of narrowed or blocked blood vessels In the majority of cases this is due to coronary artery disease
HEART FAILURE
The femoral arteries provide the blood supply to the lower limbs
FIBRATE
Fibrates are cholesterol-lowering drugs that are primarily effective in lowering triglycerides and, to a lesser extent, in increasing high-density lipoprotein cholesterol levels
FOOT ULCER
Heart failure occurs when the heart muscles become overworked from the strain of pushing blood through narrow, hard blood vessels
HIGH-DENSITY LIPOPROTEIN HDL
A break in the skin or a deep sore that can occur in people with diabetes because of nerve and/or vessel damage to the foot
GANGRENE
Cholesterol is carried in the blood stream by lipoproteins The high-density lipoprotein HDL recovers cholesterol from cells, vessel walls and other lipoproteins and thus tends to prevent or reverse the build-up of plaque in the arteries That is why HDL cholesterol is considered good or protective
HOMOCYSTEINE
The death of body tissue due to the loss of blood supply to that tissue, sometimes permitting bacteria to invade it and accelerate its decay
GESTATIONAL
DIABETES
Researchers believe that homocysteine may contribute to the build-up of fatty substances in the arteries, increase the stickiness of blood platelets clotting, and make blood vessels less flexible and less able to widen to permit increased blood flow
HYPERGLYCAEMIA
A carbohydrate intolerance of varying degrees of severity with onset or first recognition during pregnancy Gestational diabetes develops
A raised level of glucose in the blood
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different amounts of lipids and proteins See high-density lipoprotein and low-density lipoprotein
LIPOPROTEIN A
HYPERTENSION
Persistently elevated blood pressure
IMPAIRED FASTING GLYCAEMIA IFG
Raised fasting levels of glucose
IMPAIRED GLUCOSE TOLERANCE IGT
Blood glucose levels that are higher than normal but below the level of a person with diabetes
IMPOTENCE
High levels of Lipoprotein a or Lpa, are thought to increase the risk of coronary heart disease by preventing the breakdown of clots that may form on atherosclerotic plaques
LOW-DENSITY LIPOPROTEIN LDL
The loss of a mans ability to have an erect penis, often
referred to as erectile dysfunction
INSULIN
A hormone whose main action is to enable the body cells to absorb glucose from the blood and use it for energy It also regulates lipid and protein metabolism Insulin is produced by the beta cells in the pancreas
INSULIN RESISTANCE
Cholesterol is carried in the blood stream by lipoproteins The low-density lipoprotein LDL carries most of the cholesterol from the liver to the cells If there is an excess of cholesterol or it cannot be properly delivered to the cells, LDL cholesterol tends to accumulate in the vessel walls, where it can lead to damage and contribute to the development of atherosclerosis Therefore LDL cholesterol is considered bad cholesterol
MACROANGIOPATHY
A state in which a given level of insulin produces a less than expected biological effect
INTERMITTENT CLAUDICATION
Disease of the large blood vessels Usually refers to the complications of diabetes resulting from atherosclerosis
METABOLIC SYNDROME
A cramp-like pain due to ischaemia mostly in the calf and leg muscles, brought on by walking and relieved by rest
ISCHAEMIA
Ischaemia is a usually temporary shortage of oxygen in a part of the body
KETONE
A condition
whereby a series of clinical problems such as central obesity, abnormal glucose tolerance, lipid abnormalities, hypertension, insulin resistance and microalbuminuria tend to be present in the same subject This syndrome is considered a very important risk factor for cardiovascular disease
METFORMIN
Ketones are chemicals that the body produces when there is not enough insulin in the blood and it must break down fat for its energy When ketones build up in the blood, the body disposes of them via the urine
LEFT VENTRICULAR HYPERTROPHY
An oral hypoglycaemic agent that decreases glucose production from the liver and glucose absorption from the gut It also slightly decreases insulin resistance
MICROALBUMINURIA
When the heart muscle of the left ventricle becomes abnormally thickened
LIPOPROTEIN
See albuminuria
MICROANGIOPATHY
A lipoprotein is a particle composed of protein and lipids that transports the lipids in the bloodstream and lymph system Lipoproteins are of varying size and density and contain
Disease of the very small blood vessels Usually refers to the chronic complications of diabetes resulting from damage to the
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SILENT ISCHAEMIA
capillaries such as retinopathy or nephropathy
NEPHROPATHY
Silent ischaemia occurs when someone experiences an episode of ischaemia without knowing it as no pain is involved
STABLE ANGINA
Diabetic nephropathy kidney damage results in large amounts of urine protein and hypertension, and is slowly progressive leading to kidney failure It usually does not occur until many years of diabetes and can be delayed by tight control of blood glucose
NEUROPATHY
Stable angina occurs when individuals experience angina on a regular basis and can be given medication to treat it
STATIN
A class of drug that lowers cholesterol
STROKE
Diabetic neuropathy refers to damage to the nerve fibres caused by diabetes Long nerves are most affected and so the process is usually first noticed in the feet with a numbness and loss of sensation
NITRATES
A sudden loss of function in part of the brain as a result of the interruption of its blood supply by a blocked or burst artery
SUDDEN DEATH
Drugs that dilate blood vessels They are effective in treating angina
ORAL HYPOGLYCAEMIC AGENTS
This term refers to the death of a person
resulting from an abrupt loss of heart function
TRANSIENT ISCHAEMIC ATTACK
Drugs that lower the level of glucose in the blood They work for some people with type 2 diabetes if their pancreas still produces some insulin They can help the body in several ways such as causing the cells in the pancreas to release more insulin
PANCREAS
Mini-strokes that produce stroke-like symptoms and signs which clear completely within 24 hours Transient ischaemic attacks are strong predictors of stroke
TRIGLYCERIDE
The pancreas is an organ situated behind the lower part of the stomach which produces insulin
PERIPHERAL VASCULAR DISEASE
The major form of fat made in the liver A triglyceride consists of three molecules of fatty acid combined with a molecule of the alcohol glycerol Most of the fat we eat is composed of triglycerides The rest is cholesterol
TYPE 1 DIABETES
Peripheral vascular disease refers to diseases of blood vessels outside the heart and brain It often involves a narrowing of the vessels that carry blood to leg muscles
RETINOPATHY
Retinopathy is a disease of the retina of the eye which may cause visual impairment and blindness
REVASCULARIZATION
Type 1 diabetes occurs most
frequently in children and adolescents, but is now also increasingly found in adults About 10 of people with diabetes have type 1 The symptoms vary in intensity and include excessive thirst, excessive passing of urine, weight loss and lack of energy Insulin is a lifesustaining medication for people with type 1 diabetes, who require daily insulin injections for survival
TYPE 2 DIABETES
The procedure by which a blocked vessel can be either dilated angioplasty or bypassed bypass surgery
About 90 of people with diabetes have type 2, which occurs mainly in adults Some people with type 2 diabetes have no early symptoms
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and are only diagnosed several years after the onset of the condition, when various diabetic complications are already present Type 2 diabetes is usually controlled by diet, exercise and oral hypoglycaemic agents Insulin injections may also be required
UNSTABLE ANGINA
If an attack of angina differs from a persons regular pattern stable angina, appearing suddenly, with greater intensity or when at rest, it is considered unstable It may warn of an
impending heart attack
VEIN
A vessel carrying blood back from various parts of the body to the heart
VERTEBRAL ARTERY
The two vertebral arteries follow the vertebral column at the back of the neck They carry blood from the heart to the brain
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Bibliography
Bibliography
Abbott RD, Donahue RP, Kannel WB, Wilson PWF The impact of diabetes on survival following myocardial infarction in men vs women: the Framingham Study JAMA 1989;261:1884 Alberti KGMM The diagnosis and classification of diabetes mellitus Diabetes Voice, Bulletin of the International Diabetes Federation 1999;44:35-41 American Diabetes Association; National Heart, Lung and Blood Institute; Juvenile Diabetes Foundation International; National Institute of Diabetes and Digestive and Kidney Disease; American Heart Association Diabetes mellitus: a major risk factor for cardiovascular disease Circulation 1999;100:1132-1133 BARI investigators Influence of diabetes on five-year mortality and morbidity in a randomized trial comparing CABG and PTCA in patients with multivessel disease Circulation
1997;96:17611769 Barnett AH, Dodson PM, et al Hypertension and Diabetes London: Science Press, 2000 Biermann EL Atherogenesis in diabetes Review Arterioscler Thromb 1992;12:647-656 DAgostino RB, Russell MW, Huse DM, et al Primary and subsequent coronary risk appraisal: new results from the Framingham Study Am Heart J 2000;139:272-281 Detre KM, Lombardero MS, Brooks MM, et al The effect of previous coronary-artery bypass surgery on the prognosis of patients with diabetes who have acute myocardial infarction NEJM 2000;342:989-997 Eckel RH, et al Natural history of macrovascular disease and classic risk factors for atherosclerosis Diabetes Care 1999;22suppl 3:C21-C24 Eshwège E, et al Coronary heart disease mortality in relation with diabetes, blood glucose and plasma insulin levels: the Paris Prospective Study, ten years later Hormone and Metabolic Research 1985;153:41-46 European Diabetes Policy Group Guidelines for a desktop guide to type 2 diabetes mellitus, 19981999, International Diabetes Federation European Region Diabet Med 1999;16:1-21 Fitzgerald AP, Jarrett RJ Are conventional risk factors for mortality relevant in type 2 diabetes? Diabet Med 1991;8:475-480 Friedland DJ Guide
for assessing the validity of a study In: Friedland DJ, Go AS, Davoren JB, et al eds Evidence-Based Medicine Stamford: Appleton Lange, 1998:153-182
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Geiss LS, et al Mortality in non-insulin-dependent diabetes In Harris MI: Diabetes in America 2nd ed Bethesda: National Institutes of Health, 1995:233-257 Goldberg RA Cardiovascular disease in diabetic patients Med Clin North Am 2000;84:81-93 Grundy SM, Benjamin IJ, Burke GL, et al Diabetes and cardiovascular disease A statement for healthcare professionals from the American Heart Association Circulation 1999;100:11341146 Gu K, Cowie CC, Harris MI Diabetes and decline in heart disease mortality in US adults JAMA 1999;281:1291-1297 Haffner SM, DAgostino RB, Mykkanen L, et al Insulin sensitivity in subjects with type 2 diabetes Relationship to cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study Diabetes Care 1999;22:562-568 Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without
previous myocardial infarction NEJM 1998;339:229-234 Hamalainen H, Aunola S, Rastas M, Marniemi J, Tuomilehto J Improved glucose tolerance and fibrinolysis by an intensive lifestyle intervention in subjects with impaired glucose tolerance Diabetes Research and Clinical Practice 2000;50suppl:474 Hanefeld M, Fischer S, Julius U, et al Risk factors for myocardial infarction and death in newly detected NIDDM: the Diabetes Intervention Study, 11-year follow-up Diabetologia 1996;39:1577-1583 Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, Menard J, Rahn KH, Wedel H, Westerling S Effects of intensive blood pressure lowering and low dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment HOT Randomized Trial Lancet 1998;351:1755-1762 Harpaz D, Gottlieb S, Graff E, Boyko V, Kishon Y, Behar S for the Israeli Bezafibrate Infarction Prevention Study Group Effects of aspirin treatment on survival in non-insulin dependent diabetic patients with coronary artery disease Am J Med 1998;105:494-499 Heart Outcomes Prevention Evaluation Study Investigators Effects of ramipril on cardiovascular and microvascular outcomes in people with
diabetes mellitus: results of the HOPE study and the MICRO-HOPE sub-study Lancet 2000;355:253-259 Herliz J, Karlson BW, Edwardsson N, Emanuelson H, Hjalmarson A Prognosis in diabetics with chest pain or other symptoms suggestive of acute myocardial infarction Cardiology 1992;80:237-45 Hoogeven EK, Kostense PJ, Jakobs C, et al Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes Five-year follow-up of the Hoorn Study Circulation 2000;101:1506-1511 International Diabetes Federation Diabetes Atlas 2000 Brussels: IDF, 2000
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International Diabetes Federation Diabetes Health Economics: Facts, Figures and Forecasts Brussels: IDF, 1999 International Diabetes Federation IDF Bulletin 1997;42suppl Jarrett RJ, Viberti GC, Argyropoulos A, et al Microalbuminuria predicts mortality in non-insulindependent diabetes Diabet Med 1984;1:17-19 Kannel WB Blood pressure as a cardiovascular risk factor JAMA 1996;275:1571-1576 Kannel WB, McGee DL Diabetes and cardiovascular disease The Framingham Study JAMA 1979;241:2035-2038 Kannel WB, Wilson PWF, Zhang TJ The
epidemiology of impaired glucose tolerance and hypertension Am Heart J 1991;121:1268-1273 Keen H, et al WHO study on vascular complications in diabetic patients Diabetologia 1985;28:615640 Kendall MJ, Lynch KP, Hjalmarson A and Kjekshus Jß-Blockers and sudden cardiac death Ann Intern Med 1995;123:358-367 Malmberg K, Rydén L, Efendic S, Herlitz J, Nicol P, Waldenstrom A, et al Randomized trial of insulinglucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction DIGAMI study: effects on mortality at one year Am Coll Cardiol 1995;26:57-65 Malmberg K, Yusuf S, Gerstein HC, Borwn J, Zhao F, Hunt D, Piegas L, Calvin J, Keltai M, Budaj A for the OASIS Registry Investigators Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction Results of the OASIS Organization to Assess Strategies for Ischemic Syndromes Registry Circulation 2000;102:1014-1019 Marso SP, Ellis SG, Gurm HS, et al Proteinuria is a key determinant of death in patients with diabetes after isolated coronary artery bypass grafting Am Heart J 2000;139:939-944 Marso SP, Lincoff AM, Ellis SG, et al Optimizing the
percutaneous interventional outcomes for patients with diabetes mellitus Results of the EPISTENT diabetic substudy Circulation 1999;100:2477-2484 Miettinen H, Lehto S, Salomaa VV, et al Impact of diabetes on mortality after the first myocardial infarction Diabetes Care 1998;21:69-75 Morishita E, Asakura H, Jokaji H, et al Hypercoagulability and high lipoprotein a levels in patients with type II diabetes mellitus Atherosclerosis 1996;120:7-14 Niskanen LK, Penttilla I, Parviainen M, et al Evolution, risk factors and prognostic implications of albuminuria in NIDDM Diabetes Care 1996;19:486-493 Pearson TA Chairman Workshop V What is a risk factor and what is not Theoretical and practical implications Am J Med 1991;90suppl 2A:50S-52S
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Diabetes and Cardiovascular Disease: Time to Act
Pyörälä K, Laakso M, Uusitupa M Diabetes and atherosclerosis: an epidemiologic review Review Diabetes Metab Rev 1987;3:463-524 Savage PJ Cardiovascular complications of diabetes mellitus: what we know and what we need to know about their prevention Ann Intern Med 1996;124:123-126 Simons LA, Simons J Diabetes and coronary heart disease
NEJM 1998;339:1714-1715 Stamler J, Vaccaro O, Neaton JD, Wentworth D Diabetes, other risk factors and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial Diabetes Care 1993;16:434-444 Stratton IM, Adler AI, Neil HA, et al Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes UKPDS 35: prospective observational study BMJ 2000;321:405-412 UK Prospective Diabetes Study UKPDS Group Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes UKPDS 34 Lancet 1998;352:854-865 UK Prospective Diabetes Study UKPDS Group Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes BMJ 1998;317:703-713 Walker RW, et al Stroke mortality in urban and rural Tanzania Lancet 2000;355:1684-1687 Wilson PWF, Kannel WB Epidemiology of hyperglycemia and atherosclerosis In: Ruderman N, et al eds Hyperglycemia, Diabetes, and Vascular Disease New York: Oxford University Press, 1992:21-29 Wingard DL, Barrett-Connor E Heart disease and diabetes In: Harris MI Diabetes in America 2nd ed Bethesda: National Institutes of Health,
1995;429-448 World Health Organization World Health Statistics Annual 1996 Geneva: WHO, 1988 Yudkin JS, Chaturvedi N Developing risk stratification charts for diabetic and non-diabetic subjects Diabet Med 1999;16:219-227 Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G Effects of an angiotensin-convertingenzyme inhibitor, ramipril, on cardiovascular events in high risk patients The Heart Outcomes Prevention Evaluation Study Investigators NEJM 2000;342:145-153 Zuanetti G, Latini R, Maggioni AP, et al Effect of the ACE inhibitor lisinopril on mortality in diabetic patients with acute myocardial infarction Data from the GISSI-3 study Circulation 1997;96:4239-4245
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