Diabetes and
Cardiovascular Disease:
Time to Act
The mission of the IDF is to work with our member associations to enhance...
© International Diabetes Federation, 2001
No part of this publication may be reproduced or transmitted in any form or by a...
Acknowledgements
The International Diabetes Federation (IDF) would like to thank
Merck, Sharp & Dohme (MSD), USA, for its ...
Diabetes and Cardiovascular Disease:Time to Act
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  1. 1. 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.
  2. 2. © 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@idf.org http://www.idf.org ISBN: 2-930229-15-2
  3. 3. 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
  4. 4. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 5 ] ContentsPreface:A Time Bomb 7 Introduction 9 Executive Summary 11 Chapter 1: Diabetes 13 Classification 13 Risk Factors 14 The Extent of the Problem 14 Future Outlook 16 Chapter 2: Cardiovascular Disease 19 The Cardiovascular Disease Triad 19 The Extent of the Problem 22 Chapter 3: Diabetes and Cardiovascular Disease: Double Jeopardy 37 The Extent of the Problem 37 A Costly Situation 37 How does Diabetes Lead to Cardiovascular Disease? 37 The Cardiovascular Disease Triad in Diabetes 40 The Vicious Cycle 43 Chapter 4: Risk Factors 45 What is a Risk Factor? 45 Cardiovascular Risk Factors 45 Diabetes and Other High Blood Glucose Conditions:A Major Risk Factor 46 Conclusion 51 Chapter 5: Reducing the Risks 53 Management of Risk Factors in the General Population 53 Management of Risk Factors in People with Cardiovascular Disease 55 Management of Risk Factors in People with Diabetes 55 National Approaches to Prevention: Lifestyle 57 Chapter 6:Treatment of Cardiovascular Disease in Diabetes 59 Treatment of Coronary Heart Disease 59 Treatment of Cerebrovascular Disease 60 Treatment of Peripheral Vascular Disease 60 Conclusion 60 Conclusion:The Way Forward 61 Fact File 63 Contents
  5. 5. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 6 ] Annex 1: Diagnostic Criteria for Diabetes and its Risk States 65 Annex 2: Diabetes Prevalence 66 Annex 3: Coronary Heart Disease and Cerebrovascular Disease Mortality Rates 68 Annex 4: Studies of Diabetes and Heart Disease 77 Glossary 81 Bibliography 87
  6. 6. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 7 ] ATime Bomb ATime BombP R E F A C E 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
  7. 7. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 9 ] 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. 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. IDF’s 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. 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.
  8. 8. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 11 ] 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. 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. Diabetes and Cardiovascular Disease: Double Jeopardy Diabetes can lead to cardiovascular damage in a number of ways.The processes do not 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. 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
  9. 9. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 12 ] 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. 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. 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. 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. 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.
  10. 10. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 13 ] DiabetesDiabetes 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. Pancreas Kidneys Stomach Figure 1:The pancreas 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). What was previously known as insulin- dependent diabetes mellitus (IDDM) has become type 1 diabetes under this new DiabetesC H A P T E R 1 1 Type 1 diabetes • Insulin required for survival due to a lack of insulin produced by the body as a result of beta cell destruction. 2 Type 2 diabetes • 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 • Diabetes appearing for the first time in pregnancy. Table 1:The four main types of diabetes
  11. 11. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 14 ] 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 2: Components of the metabolic syndrome Diagnostic criteria for diabetes and its risk states are provided in Annex 1. 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 Table 3: Risk factors for type 2 diabetes 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. METABOLIC SYNDROME RISKFACTORS
  12. 12. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 15 ] Figure 2: Prevalence estimates of diabetes mellitus, IDF Regions, 2000 Source: International Diabetes Federation (2000) Nodata 2.0%–4.99% <2% 5.0%–7.99% 8.0%–10.99% 11.0%–13.99% ≥14.0%
  13. 13. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 16 ] 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 world with diabetes now.This figure is expected to double over the next 25 years.The predicted increase is most striking in India and 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. 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 Estimated diabetes prevalence (%) 0 3 6 9 12 15 18 Tonga Czech Republic Pakistan Aruba Barbados Trinidad and Tobago Mexico Bahrain Dominica, Commonwealth of Papua New Guinea1 2 3 4 5 6 7 8 9 10 Mauritius Bermuda BritishVirgin Islands Grenada St Kitts and Nevis Hong Kong SAR, PRC Cayman Islands Table 4:‘Top ten’ countries for diabetes prevalence Source: International Diabetes Federation (2000) It is estimated that there are some 150 million people in the world with diabetes now.This figure is expected to double over the next 25 years. Fact
  14. 14. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 17 ] 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’.
  15. 15. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 19 ] Cardiovascular DiseaseCardiovascular 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. The Cardiovascular DiseaseTriad The major clinical manifestations of cardiovascular disease can be divided into three groups: • 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). Lower limbs (peripheral vascular disease) Brain and cerebral circulation (cerebrovascular disease) Heart and coronary circulation (coronary heart disease) Figure 3:The cardiovascular disease triad Cardiovascular DiseaseC H A P T E R 2
  16. 16. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 20 ] 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. Left coronary artery Aorta Right coronary artery 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 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 heart’s ability to pump blood. It may result from a massive heart attack or a severe abnormality of the rhythm of the heartbeat. 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 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. Coronary heart disease Cerebrovascular disease Peripheral vascular disease • Angina • Stroke • Gangrene • Heart attack • Transient ischaemic • Intermittent • Sudden death • attack claudication • Heart failure • Dementia Table 5:The major clinical manifestations of cardiovascular disease CLINICAL MANIFES- TATIONS
  17. 17. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 21 ] 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 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. 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
  18. 18. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 22 ] 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 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. 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. 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. 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. 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 developing world. Fact
  19. 19. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 23 ] Mortality (per 100,000 population per year) 0 100 200 300 400 500 600 700 800 Ukraine Lithuania Moldova, Republic of* Belarus* Estonia Kazakhstan Republic Azerbaijan Republic Turkmenistan* Russia Latvia*1 2 3 4 5 6 7 8 9 10 Mortality (per 100,000 population per year) 0 100 200 300 400 500 600 700 800 Ukraine Trinidad and Tobago Latvia* Belarus* Russia Kazakhstan Republic Azerbaijan Republic Uzbekistan* Turkmenistan* Moldova, Republic of*1 2 3 4 5 6 7 8 9 10 Table 6:‘Top ten’ countries for coronary heart disease in males Table 7:‘Top ten’ countries for coronary heart disease in females 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. 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
  20. 20. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 24 ] Mortality (per 100,000 population per year) 0 100 200 300 400 500 600 700 800 Yugoslavia* Kazakhstan Republic Romania Moldova, Republic of* Bulgaria Latvia* Guyana Russia Kyrgyz Republic Ukraine1 2 3 4 5 6 7 8 9 10 Mortality (per 100,000 population per year) 0 100 200 300 400 500 600 700 800 Guyana St Lucia* Romania Kazakhstan Republic Yugoslavia* Russia Moldova, Republic of* Kyrgyz Republic Ukraine1 2 3 4 5 6 7 8 9 10 American Samoa* Table 8:‘Top ten’ countries for cerebrovascular disease in males Table 9:‘Top ten’ countries for cerebrovascular disease in females 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. 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.
  21. 21. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 25 ] 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://cvdinfobase.ic.gc.ca/) 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 Health’s 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 Welfare’s 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 Health’s Vital Statistics Database which contains data from the death registry. • Data for Taiwan were from the Department of Health’s Office of Statistics. • Data for Tanzania were extracted from: Walker RW, et al (2000). 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.
  22. 22. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 26 ] Figure 7: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetes prevalence 25 12 – – Botswana* 121 160 90 56 Seychelles* 88 85 83 41 South Africa 56 39 616 Zimbabwe 80 73 21 30 São Tomé and Príncipe* 171 142 – Tanzania – – – 4.0% 1.0% – 0.9% male (per 100,000 population/year) female (per 100,000 population/year) Cerebrovascular disease mortality male (per 100,000 population/year) female (per 100,000 population/year) Coronary heart disease mortality prevalence (%) Estimated diabetes prevalence 0.0 Africa
  23. 23. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 27 ] Figure 8: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetes prevalence 35 22 111 353 Kuwait49 3524 62 Egypt 38 17 121 205 Bahrain 9.3% 7.0% 14.8% male (per 100,000 population/year) female (per 100,000 population/year) Cerebrovascular disease mortality male (per 100,000 population/year) female (per 100,000 population/year) Coronary heart disease mortality prevalence (%) Estimated diabetes prevalence 0.0 Eastern Mediterranean and Middle East
  24. 24. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 28 ] Figure 9: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetes prevalence male (per 100,000 population/year) female (per 100,000 population/year) Cerebrovascular disease mortality male (per 100,000 population/year) female (per 100,000 population/year) Coronary heart disease mortality prevalence (%) Estimated diabetes prevalence 0.0 Belgium 52 35 138 43 France 41 22 89 22 Hungary 213 118 436 159 Greece 78 58 166 49 Germany 61 39 215 72 Italy 60 38 141 39 65 49 370 127 Ireland, Republic of 65 40 221 74 Austria 110 71 114 33 Albania Croatia 178 122 235 87 154 95 431 158 Czech Republic 3.2% 4.0% 7.1% 5.3% 5.0% 5.9% 6.6% 3.8% 4.2%4.1% 11.7% Europe (1)
  25. 25. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 29 ] Finland 76 47 316 86 Israel 57 39 177 79 Estonia 232 147 616 205 228 162 602 230 Belarus* Bulgaria 283 166 317 119 Kazakhstan Republic 276 195 625 256 218 155 426 202 Georgia, Republic of 168 125 638 291 Azerbaijan Republic Latvia* 291 176 745 228 359 244 427 204 Kyrgyz Republic 4.1% 7.2% 3.7% – 7.3% 1.4% – – 4.5% 5.5% 135 124 448 205 Armenia* –
  26. 26. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 30 ] Figure 10: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetes prevalence 64 47 232 113 Malta 53 48 153 45 Luxembourg 55 36 245 74 Norway 48 35 178 58 Netherlands 147 84 117 42 Portugal 56 32 91 31 Spain 59 46 293 106 United Kingdom 115 66 173 57 Slovenia 6.1% 5.4% 8.0% 9.9% 3.8% 3.6% 3.8% 3.5% male (per 100,000 population/year) female (per 100,000 population/year) Cerebrovascular disease mortality male (per 100,000 population/year) female (per 100,000 population/year) Coronary heart disease mortality prevalence (%) Estimated diabetes prevalence 0.0 Europe (2)
  27. 27. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 31 ] 149 102 566 200 Lithuania 344 214 688 236 Russia 107 65 259 77 Poland 48 30 219 65 Sweden 458 312 504 220 Ukraine 223 170 658 352 Turkmenistan* 41 34 9 3 Turkey 272 209 351 128 Yugoslavia* 196 158 209 86 Macedonia 282 225 592 368 Moldova, Republic of* 280 194 351 155 Romania 145 122 267 161 Tajikistan*197 153 454 291 Uzbekistan* – 5.5% 0.3% 4.5% – 6.4% 5.7% 3.2% – 3.5% – – –
  28. 28. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 32 ] male (per 100,000 population/year) female (per 100,000 population/year) Cerebrovascular disease mortality male (per 100,000 population/year) female (per 100,000 population/year) Coronary heart disease mortality prevalence (%) Estimated diabetes prevalence 0.0 42 32 224 90 United States of America 56 48 127 67 Mexico 119 98 133 108 Belize 177 160 89 54 Jamaica 312 182180 46 Guyana 143 77 208 83 Bahamas 184 123 374 227 Trinidad and Tobago 108 129 101 25 Dominica, Commonwealth of 175 64 99 53 Antigua and Barbuda* 121 56 112 62 Barbados 3.4% 8.0% 3.1% 92 48 – – Martinique* – 184 185 130 61 St Lucia* – – 5.0% 8.0% 8.5% 14.2% 15.0% 14.1% 13.2% 34 24 183 62 Canada North America Figure 11: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetes prevalence
  29. 29. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 33 ] Paraguay Argentina Chile Cuba Guatemala Nicaragua Panama Peru Suriname Uruguay Venezuela Colombia Dominican Republic Puerto Rico 24 30 43 25 73 47 96 56 61 49 62 40 85 77 222 134 45 41 57 33 43 22 170 69 82 76 173 100 94 75 223 110 88 80 219 103 119 96 123 61 107 74 181 65 122 68 140 39 96 59 121 49 23 2028 14 8.6% – 2.9% El Salvador 58 46 65 40 4.8% Costa Rica 53 40 145 84 3.4% 2.9% Ecuador 55 4135 18 3.0% 3.7% 1.4% 3.3% 4.5% 4.5% 4.2% 4.1% 4.0% 8.9% 5.3% Brazil 121 74 117 73 3.2% male (per 100,000 population/year) female (per 100,000 population/year) Cerebrovascular disease mortality male (per 100,000 population/year) female (per 100,000 population/year) Coronary heart disease mortality prevalence (%) Estimated diabetes prevalence 0.0 South and Central America Figure 12: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetes prevalence
  30. 30. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 34 ] 248 139 371 181 Mauritius 44 24 92 25 Sri Lanka 2.9% male (per 100,000 population/year) female (per 100,000 population/year) Cerebrovascular disease mortality male (per 100,000 population/year) female (per 100,000 population/year) Coronary heart disease mortality prevalence (%) Estimated diabetes prevalence 0.0 15.0% South East Asia Figure 13: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetes prevalence
  31. 31. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 35 ] Figure 14: Mortality rates for coronary heart disease and cerebrovascular disease and estimated diabetes prevalence 225 150 76 51 China, Peoples' Republic of 102 87 242 114 Singapore, Republic of 111 63 125 58 Philippines 34 29 164 73 Australia 153 114 181 98 Mongolia* 2.7% – 191 121 38 14 Korea, Republic of 6.1% 73 4145 16 Japan 7.4% 65 47 80 34 Hong Kong SAR, PRC 3.1% 6.0% 60 48 309 117 New Zealand 8.0% 56 44 171 70 Guam* – 128 78 25 51 Taiwan 9.1% 11.3% male (per 100,000 population/year) female (per 100,000 population/year) Cerebrovascular disease mortality male (per 100,000 population/year) female (per 100,000 population/year) Coronary heart disease mortality prevalence (%) Estimated diabetes prevalence 0.0 – American Samoa* 317 256 152 41 – 37 214 3748 Palau* 9.1% Fiji* 177 479 66 100 – Northern Mariana Islands* 77 56 174 0 – Cook Islands* 129 149 0 228 12.1% Western Pacific
  32. 32. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 37 ] Double Jeopardy Diabetes and Cardiovascular Disease: Double Jeopardy C H A P T E R 3 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 cardiovascular disease in the setting of diabetes. 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.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. 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. 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. People with diabetes are two to four times more likely to develop cardiovascular disease than people without diabetes. Fact
  33. 33. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 38 ] 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 Neuropathy Kidney disease Total cardiovascular disease Acute complications Other United Kingdom Eye disorders Figure 15: Proportion of hospital bed days used for the treatment of diabetic complications Source: International Diabetes Federation (1999) Argentina All microvascular Other acute Cardiovascular disease Infections Other
  34. 34. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 39 ] 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. Autonomic neuropathy Microangiopathy Nephropathy Heart rate disturbances Postural fall in blood pressure Diabetic foot Retinopathy Neuropathy Gastro- intestinal dysfunction Impotence Dysfunction of bladder Figure 16: Clinical outcomes of microangiopathy and autonomic neuropathy Microangiopathy Autonomic neuropathy Other blood vessel damage • Damage to small • Damage to the nerve • Damage to the inner blood vessels and supply of the internal or outer lining of blood capillary circulation. organs of the body. vessels. • Retinopathy • Problems with the • Impaired regulation • Nephropathy pulse rate of blood flow • Neuropathy • Postural fall • Weakened vessel walls • Diabetic foot in blood pressure • Aggravated • Foot ulcers microangiopathy • Impotence and atherosclerosis/ • Gastro-intestinal macroangiopathy dysfunction Table 10:Abnormalities of the cardiovascular system specific to diabetes WHAT ISIT? CLINICAL OUTCOME
  35. 35. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 40 ] 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. Outer lining Middle muscle layer Inner lining (endothelium) Figure 17: Blood vessel 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. 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. Coronary Heart Disease Angina (see page 20):When autonomic neuropathy is present, the typical pain of angina which is usually associated with ischaemia may not be experienced, leading to silent ischaemia.This may manifest itself just with shortness of breath Coronary heart disease Cerebrovascular disease Peripheral vascular disease • Angina (including • Stroke • Gangrene • silent ischaemia) • Transient ischaemic • Intermittent • Heart attack (including • attack • claudication • silent heart attack) • Dementia • Foot ulcers • Sudden death • Heart failure • Fainting attacks Table 11:The clinical manifestations of cardiovascular disease in diabetes CLINICAL MANIFESTATIONS People with type 2 diabetes have the same risk of heart attack as people without diabetes who have already had a heart attack. Fact
  36. 36. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 41 ] 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 widespread vascular disease, the consequences of a 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 even realizing it. For these and other reasons, people with type 2 diabetes have a higher risk of death following a heart attack (Figure 19). Sudden death (see page 20): In diabetes, sudden death can also result from abnormalities in the heart’s rhythm provoked by autonomic neuropathy. Men with diabetes are subject to sudden death 50% more often and women with diabetes 300% more often than their counterparts without diabetes of the same age. 0 10 20 30 40 50 Incidence(%) People without diabetes People with diabetes No prior heart attack Prior heart attack Figure 18: Heart attacks in people with and without diabetes over a period of seven years Adapted from: Haffner SM, et al (1998) 0 10 20 30 40 50 Mortality(%) People with diabetesPeople without diabetes Men Women Figure 19: Deaths in people with and without diabetes in the year following a first heart attack Adapted from: Miettinen H, et al (1998) People with diabetes can have a heart attack without even realizing it. Fact People with diabetes have a two to three- fold greater risk of heart failure compared to people without diabetes. Fact Men with diabetes are subject to sudden death 50% more often and women with diabetes 300% more often than their counterparts without diabetes of the same age. Fact
  37. 37. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 42 ] 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. Cerebrovascular Disease 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 attack (see page 21): Transient ischaemic attacks (mini-strokes) occur between two and six times more frequently in people with diabetes. 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 amputation compared to the general population. The factors which predispose to this greater risk are described below. 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 of the same age. Intermittent claudication (see page 22): Intermittent claudication (calf pain) occurs three times more often in men with diabetes and almost 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. Strokes occur twice as often in people with diabetes and hypertension as in those with hypertension alone. Fact Transient ischaemic attacks occur between two and six times more frequently in people with diabetes. Fact People with diabetes are 15-40 times more likely to require a lower-limb amputation compared to the general population. Fact People with diabetes over the age of 70 have a 70-fold increased risk of lower-limb gangrene compared to people without diabetes of the same age. Fact
  38. 38. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 43 ] Figure 20: Causes of death in people with diabetes in the US Adapted from: Geiss LS, et al (1995) 0 10 20 30 40 50 60 70 80 OtherStrictly diabetes-relatedCardiovascular disease Mortality(%) 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).
  39. 39. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 45 ] Risk Factors Risk FactorsC H A P T E R 4 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 RISKFACTORS
  40. 40. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 46 ] 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 heart’s 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 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). 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.
  41. 41. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 47 ] 0 10 20 30 40 50 60 Estimatedrateofcoronaryheartdisease(%) Risk factors Men Women Systolic blood pressure (mm Hg) Cholesterol (mg/dL) HDL cholesterol (mg/dL) Diabetes Cigarette smoking Left ventricular hypertrophy 120 220 50 – – – 160 220 50 – – – 160 259 50 – – – 160 259 35 – – – 160 259 35 + – – 160 259 35 + + – 160 259 35 + + + Figure 21: Estimated coronary heart disease rate according to various combinations of risk factors over 10 years Adapted from: Kannel WB (1996) 0 2 4 6 8 10 StrokeIntermittent claudication Heart failureCoronary heart disease Total cardiovascular disease Relativerisk Men Women 1 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.
  42. 42. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 48 ] Figure 26: Prevalence of cigarette smoking in people with diabetes ArizonaHavanaTokyoHong KongNew DehliBerlinMoscowLondon 0 10 20 30 40 50 60 70 80 Prevalence(%) Men Women Figures 23 to 26: Cardiovascular risk factors in people with diabetes in different populations Adapted from: Keen H, et al (1985) Figure 23: Prevalence of high cholesterol levels (≥ 4.65 mmol/l) in people with diabetes ArizonaHavanaTokyoHong KongNew DehliBerlinMoscowLondon 0 20 40 60 80 100 Prevalence(%) 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) ArizonaHavanaTokyoHong KongNew DehliBerlinMoscowLondon 0 10 20 30 40 50 Prevalence(%) Men Women Figure 25: Mean body mass index (kg/m2 ) in people with diabetes (see glossary for BMI values) ArizonaHavanaTokyoHong KongNew DehliBerlinMoscowLondon 0 5 10 15 20 25 30 35 Bodymassindex Men Women
  43. 43. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 49 ] 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 disease.This implies that some other factor is responsible.This factor could be related to diabetes itself. Since the main characteristic of diabetes is high blood glucose, it is tempting to assume that hyperglycaemia is the 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 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 age- related 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 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 Risk factor Prevalence Hypertension • Prevalence is at least double in people with type 2 diabetes. High blood cholesterol • Prevalence is similar in people with diabetes. High triglycerides with low HDL • Prevalence is higher in people with diabetes. Left ventricular hypertrophy • 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. Obesity • 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. Smoking • People with diabetes smoke less (presumably due to medical advice). Table 13:Prevalence of cardiovascular risk factors in people with diabetes compared to people without diabetes About 50% of the excess risk of cardiovascular disease in type 2 diabetes can be explained by the higher incidence and/or higher impact of conventional risk factors. Fact
  44. 44. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 50 ] 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 Many people with diabetes have several risk factors. As we saw in Figure 21, the presence of several risk factors has a multiplicative and not just an additive effect.The situation is even more serious in people with diabetes as, for each risk factor present, cardiovascular mortality is about 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 attest this. It seems prudent on the basis of clinical judgment to consider that people with type 1 diabetes over the age of 30 years are similar to people with type 2 diabetes as regards coronary heart disease risk. People with type 1 diabetes who suffer from diabetic nephropathy, regardless of age, should be treated as being at particularly high risk. 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 0 1 2 3 4 5 Known diabetesNewly-diagnosed diabetesImpaired glucose tolerance (IGT) Normal glucose levels Coronaryheartdiseasemortality (incidencerateper1000personsperyear) Figure 27: Mean coronary heart disease mortality rates by degree of glucose tolerance Adapted from: Eschwège E, et al (1985) 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. Fact People with type 1 diabetes over the age of 30 years have a coronary heart disease risk similar to people with type 2 diabetes. Fact
  45. 45. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 51 ] 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 C- reactive 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. Figure 28: Impact of multiple risk factors in the presence of diabetes Adapted from: Stamler J, et al (1993) 0 30 60 90 120 150 People without diabetes People with diabetes Cardiovasculardiseasemortality (per10,000personsperyear) Number of risk factors (smoking, high cholesterol levels, hypertension) 0 1 2 3
  46. 46. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 53 ] Reducing the Risks Reducing the RisksC H A P T E R 5 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 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. 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 MODIFIABLE RISKFACTORS
  47. 47. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 54 ] 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. 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. Risk factor Treatment Results of treatment Diabetes and other • Lifestyle modifications Although it prevents coronary high blood glucose • Drugs: oral hypoglycaemic heart disease, at present the effect conditions agents, insulin. of blood glucose lowering alone may not be as strong as the modification of other major risk factors. Dyslipidaemia • Lifestyle modifications: eg diet, Decreases the risk of coronary physical exercise and lowering heart disease. May also be beneficial excess body weight. in the prevention of peripheral • Drugs: statins, fibrates or a vascular disease and stroke. combination of the two. High alcohol • Lifestyle modifications: Lowers the risk of stroke and consumption drink in moderation. coronary heart disease. 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. Insulin resistance • Lifestyle modifications: It is not yet known whether diet, exercise. decreasing insulin resistance will • Tight glucose control in in itself slow or prevent the diabetes. development of cardiovascular disease. Obesity • Lifestyle modifications: Prevents all cardiovascular achieving normal body weight, diseases. Decreases other risk increasing physical activity. factors such as blood pressure, high glucose and high lipids. Sedentary lifestyle • Lifestyle modifications: Reduces body fat, raises HDL increasing in particular cholesterol levels, lowers LDL aerobic physical activity. cholesterol and triglyceride levels, increases insulin sensitivity, and lowers blood glucose and blood pressure. Smoking • Lifestyle modifications: Prevents coronary heart disease, stopping smoking. stroke and peripheral vascular disease. Table 15: Management of cardiovascular risk factors in the general population
  48. 48. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 55 ] 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. 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 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. 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
  49. 49. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 56 ] 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. 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 Complication Reduction of complication Lipid control • Coronary heart disease mortality 36%1 • Major coronary heart disease event 55%1 • Any atherosclerotic event 37%1 • Cerebrovascular disease event 62%1 Blood pressure control • Cardiovascular disease 51%2 • Heart failure 56%3 • Stroke 44%3 • Diabetes-related deaths 32%3 Blood glucose control • Heart attack 37%3 1 The 4S Study 2 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) 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 attacks was recorded, and also when blood glucose lowering and blood pressure control were combined.The latter finding emphasizes the importance of treatment strategies aimed at multiple risk factors. It is worth noting that, over time, a combination 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. While cardiovascular deaths have declined in those without diabetes in developed countries, in men with diabetes the decrease has been modest, while in women with diabetes the rates have actually increased. Fact
  50. 50. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 57 ] 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 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 Targets Dyslipidaemia • Decrease LDL cholesterol levels (<115mg/dl or 3 mmol/l* ) • Raise HDL cholesterol levels (>46 mg/dl or 1.2 mmol/l* ) • Lower triglycerides (<150 mg/dl or 1.7 mmol/l* ) Hypertension • Lower blood pressure (<135/85 mm Hg) Hyperglycaemia • Reduce hyperglycaemia (HbA1c <7%) Table 17:Targets for common cardiovascular risk factors in people with diabetes * These levels are based on IDF Europe’s 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. 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 -40 -30 -20 -10 0 10 20 30 People with diabetesPeople without diabetes Coronaryheartdiseasemortality(%) Men Women Figure 29: Changes in coronary heart disease mortality rates in the USA Adapted from: Gu K, et al (1999)
  51. 51. Diabetes and Cardiovascular Disease:Time to Act I N T E R N A T I O N A L D I A B E T E S F E D E R A T I O N [ 58 ] 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 non- communicable 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 cost- effective 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 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 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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