Kotulán: CVD 1 Kotulán: CVD 1 Kotulán: CVD 1 Epidemiology and Control of Cardiovascular Disease •Jaroslav Kotulán 2 Kotulán: CVD 2 Kotulán: CVD 2 History • In the 19th century, infectious diseases dominated the public health scene In the 20th century, CVD have come to overshadow all others as a cause of death in industrialized populations Causes - decline in major infectious diseases - increase in the incidence rates of CVD (absolute as well as relative) → changes in lifestyle, origin in social and economic development 3 Kotulán: CVD 3 Kotulán: CVD 3 Cardiovascular diseases (CVD) five main conditions: •hypertension •atherosclerosis •cardiovascular heart disease (CHD) myocardial infarction (heart attack) angina pectoris •stroke •heart failure Other important vascular conditions (less frequent): atherosclerotic peripheral arterial disease, aortic aneurysm, cardiomyopathies, rheumatic heart disease, congenital heart disease, deep vein thrombosis, pulmonary embolism etc. 4 Kotulán: CVD 4 Kotulán: CVD 4 Two main categories of CVD 2. Strokes - also kill, but mainly cause chronic disability their incidence largely reflects hypertension •1. Coronary disease - the main cause of the death. Related to affluence (not inevitably) CHD and stroke have been the first and second leading causes worldwide since 1990 and are two major contributors to disability worldwide They have been under extensive epidemiologic investigations over the past half-century. As a result, understanding of the causes of and means to prevent CHD and stroke have become well established 5 Kotulán: CVD 5 Kotulán: CVD 5 Epidemiologic Methods in Cardiovascular Diseases Population surveys (cross-sectional surveys) The INTERSALT Study demonstrated association between the slope of increasing blood pressure with age and urinary electrolyte excretion in adults among 52 study centers in 32 countries (1986) The case-control study WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception (1996). Increased risk of venous thromboebolism, CHD and stroke - rises with other risk factors, smoking etc. - rises with age - differences among different preparations. Examples of studies:: 6 Kotulán: CVD 6 Cohort studies The Framingam Heart Study is a long-term, ongoing cardiovascular study on residents of the US town of Framingham (Ma). The intensive biennial examination schedule (physical characteristics, life conditions) over its decades-long history have made this a uniquely rich source of data on individual risks of CVD events. The study began in 1948 with 5,209 adult subjects from Framingham, and is now on its third generation of participants Prior to it almost nothing was known about the epidemiology of hypertensive or arteriosclerotic cardiovascular disease. Goal: to identify the common factors that contribute to CVD by following its development over long of time in a large group of participants. A landmark report of the Framinham Study, based on the first 6 years of follow-up, identified serum cholesterol concentration, blood pressure, and electrocardiographic evidence of left ventricular hypertrophy as predictors of CHD development 7 It was in this report that the Framingham Study investigators introduced the term “risk factor” to describe such predictive characteristics. Many other studies were performed in U.S and Europe with designs and methods similar to those of the Framingam Study. Much of the now-common knowledge concerning heart disease, such as the effects of diet, exercise, and common medications such as aspirin, is based on this longitudinal study. Kotulán: CVD Kotulán: CVD 8 Epidemiological Features of CVD •CVD is pervasive throughout the world recognized as a public health problem of global importance, not only of rich, but also of low- and middle-income countries •Atherosclerosis: Early life-onset and lifelong progression → prevention required as early as childhood and adolescence •A strong age gradient in degree of atherosclerosis: from a range of 0-25 percent of initial surface involvement with fibrous plaques at age 20, the percentage approximately doubled by age 30 and continued to increase, although less steeply, to later ages at death 9 Kotulán: CVD 9 Kotulán: CVD 9 Mortality, morbidity •Of an estimated 58 million deaths globally from all causes in 2005, cardiovascular disease (CVD) accounted for 30%. •A substantial proportion of these deaths (46%) were of people under 70 years of age, in the more productive period of life. A significant proportion of this morbidity and mortality could be prevented. WHO: Global Strategy for the Prevention and Control of Noncommunicable Diseases (2000). Convention on Tobacco Control, Global Strategy for Diet, Physical Activity and Health These activities target common risk factors that are shared by CVD, cancer, diabetes and chronic respiratory disease Basic documents 10 Kotulán: CVD 10 Kotulán: CVD 10 CVD Mortality Rate - MALES Nr State Year Mort, *) 1 France 2004 190,6 2 Spain 2004 210,8 3 Switzerland 2004 216,0 4 Iceland 2005 220,4 5 Netherlands 2004 252,7 6 Norway 2004 254,7 7 Portugal 2004 271,1 8 Luxembourg 2005 271,6 9 Ireland 2005 277,3 10 Sweden 2004 277,6 11 Italy 2001 280,0 12 United Kingdom 2004 280,1 13 Austria 2005 287,3 14 Germany 2004 315,2 15 Malta 2005 317,5 16 Finland 2005 321,1 17 Greece 2005 321,3 18 Denmark 2001 321,4 19 Slovenia 2005 360,4 20 Poland 2005 492,8 21 Czechia 2005 508,1 22 Croatia 2005 525,8 23 Slovakia 2005 634,9 24 Hungary 2005 643,9 25 Estonia 2005 692,0 26 Lithuania 2005 750,5 27 Romania 2004 762,0 28 Latvia 2005 804,2 29 Bulgaria 2004 840,5 30 Belarus 2005 995,7 31 Ukraine 2005 1094,1 32 Russia 2005 1145,1 *) Standardized mortality rates per 100 000 European standard population 11 Kotulán: CVD 11 Kotulán: CVD 11 CVD Mortality Rate - FEMALES Nr State Year Mort, *) 1 France 2004 111,5 2 Spain 2004 140,9 3 Switzerland 2004 141,1 4 Iceland 2005 141,6 5 Netherlands 2004 155,8 6 Norway 2004 159,2 7 Ireland 2005 168,3 8 Sweden 2004 171,7 9 United Kingdom 2004 177,4 10 Finland 2005 178,0 11 Italy 2001 184,0 12 Luxembourg 2005 191,4 13 Portugal 2004 194,1 14 Denmark 2001 195,0 15 Austria 2005 203,0 16 Germany 2004 218,6 17 Malta 2005 232,9 18 Slovenia 2005 235,1 19 Greece 2005 265,7 20 Poland 2005 304,1 21 Czechia 2005 351,1 22 Croatia 2005 371,7 23 Estonia 2005 377,4 24 Hungary 2005 401,4 25 Slovakia 2005 417,5 26 Lithuania 2005 436,1 27 Latvia 2004 443,7 28 Belarus 2005 508,5 29 Romania 2004 558,1 30 Bulgaria 2004 560,0 31 Russia 2005 640,5 32 Ukraine 2005 656,3 *) Standardized mortality rates per 100 000 European standard population 12 Kotulán: CVD 12 Kotulán: CVD 12 13 Kotulán: CVD 13 Kotulán: CVD 13 14 Kotulán: CVD 14 Kotulán: CVD 14 15 Kotulán: CVD 15 Kotulán: CVD 15 16 Kotulán: CVD 16 Kotulán: CVD 16 CVD age-adjusted mortality (men aged 40-69 years) CVDgeog 17 Kotulán: CVD 17 Kotulán: CVD 17 CORONARY HEART DISEASE (ischaemic heart disease) In western countries responsible for about 30 per cent of deaths in men 25 per cent death in women = 3/4 of all CV deaths All-ages case fatality is much higher in women than in men Most men in western populations develop ischaemic myocardial scarring perhaps only 10 % will escape significant atherosclerosis 18 Kotulán: CVD 18 Kotulán: CVD 18 Distribution in the world •Association with the affluence is no longer apparent Japan is heavily industrialized but rates are low and are actually falling North Karelia in Finland had until recently the highest rates in the world ► strenuous rural life is an insufficient protection International differences can be explained partly by differences in the major risk factors but there are many exceptions 19 Kotulán: CVD 19 Kotulán: CVD 19 Distribution of cholesterol levels in Japan and Finland CholJapSF 20 Kotulán: CVD 20 Kotulán: CVD 20 Time trends • Coronary heart disease (CHD) is not new, is known as early as in the antiquity • new is its occurrence as a mass disease The epidemic began at different times in different countries rates started to rise in the early 1920s in the US a few years later in the UK but in the Netherlands and Norway there was no major rise until 1950 still later in Eastern Europe In the US the plateau has been reached in the 1960s around 1968, there began a steady decline in coronary mortality amounting by 1985 to 40 per cent fall Substantial declines in coronary mortality are also occurring elsewhere: Canada, Austria, New Zealand, Belgium, The Netherlands, Scandinavia etc. since 1990 also in the CR 21 Kotulán: CVD 21 Kotulán: CVD 21 Aetiology •The main determinants of population incidence are now known but much remains unknown concerning individual susceptibility = rates can be predicted much better then cases 22 Two broad approaches – the individual (or high-risk) approach and the population-wide approach. These two approaches are complementary The North Carelia Project - a great example of intervention studies, with broad implications for prevention policy. Finish men experienced exceptionally high CHD mortality that had increased sharply in the 1950s Kotulán: CVD Concepts of prevention Concern about this led to implementation in 1972 of a multifaceted community-based prevention project in which North Carelia (population 210,000) and Kuopio (population 250,000), both in Eastern Finland, would be intervention and control communities, respectively. 23 Among the many components of the project were programs targeting high blood cholesterol concentration, high blood pressure, and smoking. Extensive community involvement and engagement with health services were major aspects of these programs. Twenty-year changes in risk factors for men included reductions in cholesterol concentrations by 13% and in diastolic blood pressure by 9%, while smoking decreased from 53 to 37%. Kotulán: CVD Observed decrease in mortality: by 68% for women and 55% for men. The project began to influence policy nationwide after its first five years. The mortality change in Finland as a whole has continued to the present North Karelia Project is a powerful demonstration of the potential for an integrated, coordinated, and sustained public health effort to affect the major cardiovascular conditions of our time, CHD and stroke. 24 Kotulán: CVD 24 Deteminants, risk factors: • Unmodifiable: Age, sex, race or ethnicity, and heredity • Modifiable: dietary inbalance - unfavorable macronutrient composition: types and amounts of animal fats (especially saturated), relative to fruits, vegetables, and legumes - excessive sodium intake - excessive energy intake relative to energy expenditure. Physical inactivity: = reduced physical work (locomotion, occupation, leisure time) - failure of matching energy expenditure with energy intake - numerous biological mechanisms related to cardiac metabolism and physiology Dietary imbalance contributes directly to the development of adverse blood lipid profiles (high concentration of LDL-cholesterol Smoking of tobacco: established major risk factor for CVD and for other chronic diseases 25 Kotulán: CVD 25 Kotulán: CVD 25 Prevention: New guidelines (WHO) (two publications) •Prevention of Cardiovascular Disease •Guidelines for assessment and management of cardiovascular risk •World Health Organization, Geneva 2007, 92 pp. Prevention of Cardiovascular Disease Pocket Guidelines for Assessment and Management of Cardiovascular Risk, Europe. (WHO/ISH Cardiovascular Risk Prediction Charts for the European Region) IHS = International Society of Hypertension World Health Organization, Geneva 2007, 20 pp. Edited for 14 regions of the world) http://www.who.int/bookorders/ 26 Kotulán: CVD 26 Kotulán: CVD 26 CVD prevention: Basis of recommendations (the best available evidence) •1. Modification of behaviour • 1.1 Tobacco • 1.2 Diet • 1.3 Physical activity • 1.4 Body weight • 1.5 Alcohol • • 2. Multiple risk factor interventions 3. Blood pressure lowering 4. Lipid lowering 5. Control of glycaemia 6. Aspirin therapy 27 Kotulán: CVD 27 Kotulán: CVD 27 Tobacco •There is a large body of evidence regarding the beneficial effect of smoking cessation on coronary heart disease mortality The age of quitting has a major impact on survival prospects; those who quit between 35 and 44 years of age had the same survival rates as those who had never smoked Recent evidence from the Interheart study has highlighted the adverse effects of use of any tobacco product and, importantly, the harm caused by even very low consumption (1–5 cigarettes a day). Passive cigarette smoking produces a small increase in cardio vascular risk. Bans on advertising of tobacco products in public places and on sales of tobacco to young people are essential components of any primary prevention programme Also ban on smoking in restaurants etc. 28 Kotulán: CVD 28 Kotulán: CVD 28 Diet •Saturated fats as a whole have been shown to raise LDL-cholesterol levels • Saturated fatty acids: (palmitic C16:0, stearic C18:0, myristic C14:0) n-3 (omega 3) polyunsaturated acids linolenic C18:3, eicosapentaenoic C20:5 (EPA), docosahexaenoic C22:6 (DHA) The main dietary sources: fish and fish oils Significant benefit on cardiovascular morbidity and mortality in patients with coronary heart disease Monounsaturated acids (oleic a. C18:1) (abundant in olive oil) and polyunsaturated acids n-6 (omega 6) – (double bond at the sixth carbon atom of the end CH3) linoleic C18:2, arachidonic C20:4, (abundant in soybean and sunflower oil) They lower total cholesterol, LDL cholesterol and triglyceride concentrations We need both n-6 an n-3: production of two types of prostaglandins and leukotrienes (= tisue hormones) 29 Kotulán: CVD 29 Kotulán: CVD 29 Diet (continued) •Dietary cholesterol seems to have a relatively small effect on serum lipids, compared with dietary saturated and trans-fatty acids Reducing or modifying dietary fat reduces the incidence of combined cardiovascular events by 16% and cardiovascular mortality by 9% Current guidelines recommend a diet that provides less than 30% of calories from dietary fat, less than 10% of calories from saturated fats, up to 10% from polyunsaturated fats, and about 15% from monounsaturated fats Trans-fatty acids (margarine) increase LDL-cholesterol and, at high intakes, lower HDL cholesterol and increase the risk of coronary heart disease 30 Kotulán: CVD 30 Kotulán: CVD 30 Diet (continued) Dietary sodium High salt intake is associated with an increased risk of high blood pressure Within the daily intake range of 3 to 12 g, the lower the salt intake achieved, the lower the blood pressure Recommendations on salt intake: < 5 g (90 mmol) per day Fruits and vegetables may promote cardiovascular health through a variety of micronutrients, antioxidants, phytochemicals, flavonoids, fibre and potassium On the basis of the available evidence, a daily intake of at least 400 g of fruit and vegetables is recommended 31 Kotulán: CVD 31 Kotulán: CVD 31 Physical activity •The evidence points to the benefit of continued regular moderate physical activity Physical activity improves endothelial function, which enhances vasodilatation and vasomotor function in the blood vessels. In addition, physical activity contributes to weight loss, glycaemic control, improved blood pressure, lipid profile and insulin sensitivity Body weight Relationship between overweight or obesity and cardiovascular morbidity, CVD mortality and total mortality Obesity is strongly related to major cardiovascular risk factors, such as raised blood pressure, glucose intolerance, type 2 diabetes, and dyslipidaemia. Significant weight loss: reduces total cholesterol and LDL-cholesterol, increases HDL-cholesterol, improves control of blood pressure and diabetes The ideal weight : BMI > 25 kg/m2 32 Kotulán: CVD 32 Kotulán: CVD 32 Alcohol •Many studies have shown a U- or J-shaped association between mortality and alcohol consumption A recent meta-analysis of 54 published studies: there is no level of alcohol consumption that is beneficial with respect to coronary heart disease From both the public health and clinical viewpoints, there is no merit in promoting alcohol consumption as a preventive strategy. Blood pressure lowering Diuretics, beta-blockers, and calcium-channel blockers, angiotensin-converting enzyme (ACE) inhibitors For the endpoint of total cardio vascular mortality, the meta-analyses showed no strong evidence of differences between drug classes The Hypertension Optimal Treatment (HOT) trial found maximal cardiovascular benefit when blood pressure was reduced to 139/83 mmHg Almost all clinical trials have confirmed the benefits of antihypertensive treatment at blood pressure levels of 160 mmHg (systolic) and 100 mmHg (diastolic) and above 33 Kotulán: CVD 33 Kotulán: CVD 33 Lipid lowering •The effectiveness of statins in patients with established atherosclerotic disease (principally coronary artery disease) is well established Risks • From 1987 to 2000 in the USA 30 cases of liver failure attributable to statins – about one per million person-years of use • Few haemorrhagic strokes were observed in the randomized trials (only people with a very low cholesterol concentration) There are currently no data to suggest the superiority of one statin over others in reducing cardiovascular events Control of glycaemia The risk of cardiovascular events is 2–3 times higher in people with type 1 or type 2 diabetes Treatment should aim to achieve: - a fasting blood glucose level of 4–7 mmol/l (72–126 mg/dl); - an HbA1c level of 6.5% or less =glycosylated haemoglobin 34 Kotulán: CVD 34 Kotulán: CVD 34 Aspirin therapy •In randomised controlled trials and meta-analyses aspirin was associated with a 32% reduction in myocardial infarction Risks: Aspirin roughly doubles the risk of gastrointestinal haemorrhage. The excess risks attributable to aspirin are 1–2 per 1000 per year at age 60 and 7 per1000 per year at age 80 The balance of benefit and risk, therefore, needs to be clearly defined before aspirin can recommended for all elderly people 35 Kotulán: CVD 35 Kotulán: CVD 35 Two strategies of control •Their contributions are complementary, each is necessary 1 1. “High risk strategy” - screening for early disease · A simple screening examination: a self-administered chest pain questionnaire and electrocardiogram can give warning of about a half of all the coronary deaths in the next 5 years but – psychological trauma of „labelling“ Some of the main predictors of CHD can be readily identified by screening: - family history - smoking history - blood pressure - serum (total) cholesterol (If these are known, measures of overweight do not improve the prediction.) The value of high risk strategy for CHD prevention is limited it concentrates preventive efforts on the small fraction of persons with highest risk more important fraction is the large group of people where the individual risk is lower most cases of CHD occur in this large low-risk group Resources and organization for effective advice and follow-up is necessary if not, the risk screening is worse than useless 36 Kotulán: CVD 36 Kotulán: CVD 36 2. Mass primary prevention •Primary prevention depends on mass changes – on normalizing averages goal: not to have centred around some „ideal“ value but to lower the whole distribution individual variation is inevitable Targets for population norms are thus defined in terms of desirable average values of risk factors not in desirable individual values 37 Kotulán: CVD 37 Kotulán: CVD 37 Health education – changing the behaviour It needs a major effort of opinion formers, health professionals, community leaders, and local and national government 38 Kotulán: CVD 38 Kotulán: CVD 38 Recommendations of the Second Joint Task Force of European Societies on Coronary Prevention (2001) •Stop smoking •Make healthy food choices •Be physically active •Achieve ideal weight •Achieve blood pressure <140/90 • total cholesterol < 5.0 mmol/l (190 mg/dl) • LDL cholesterol < 3.0 mmol/l (115 mg/dl) • when not achieved by lifestyle changes, lowering drug therapies should be used •Aspirin (75 mg) at high CHD risk 39 Kotulán: CVD 39 Kotulán: CVD 39 The World Health Organization/International Society of Hypertension (WHO/ISH) risk prediction charts •Two categories of people: •1.People with risk factors who had not yet developed clinically manifest cardiovascular disease (primary prevention) •2. People with established CHD, CeVD or peripheral vascular disease (secondary prevention) The charts enable the estimation of total cardiovascular risk of people in the first category The evidence-based recommendations People in the second category have high cardiovascular risk and need intensive lifestyle interventions and appropriate drug therapy. Risk stratification is not required in them. Total CVD risk - the probability of an individual’s experiencing a CVD event (e.g. myocardial infarction or stroke) over a given period of time, for example 10 years (= „10-year risk“) 40 Kotulán: CVD 40 Kotulán: CVD 40 WHO Risk Prediction Chart 41 Kotulán: CVD 41 Kotulán: CVD 41 Risk <10% Individuals in this category are at low risk. Conservative management focusing on lifestyle interventions is suggestedb Risk 10% to <20% Individuals in this category are at moderate risk of fatal or non-fatal vascular events. Monitor risk profile every 6–12 months. Risk 20% to <30% Individuals in this category are at high risk of fatal or non-fatal vascular events. Monitor risk profile every 3–6 months Risk ≥30% Individuals in this category are at very high risk of fatal or non-fatal vascular events. Monitor risk profile every 3–6 months a Excluding people with established CHD, CeVD and peripheral vascular disease b Policy measures that create conducive environments for quitting tobacco, engaging in physical activity and consuming healthy diets are necessary to promote behavioural change. They will benefit the whole population. Recommendations for prevention of cardiovascular disease in people with cardiovascular risk factors (according to individual total risk) a 42 Kotulán: CVD 42 Kotulán: CVD 42 SMOKING CESSATION All nonsmokers should be encouraged not to start smoking. All smokers should be strongly encouraged to quit smoking by a health professional and supported in their efforts to do so. (1++, A) It is suggested that those who use other forms of tobacco be advised to stop. (2+, C) Risk 20% to <30% Nicotine replacement therapy and/or nortriptyline or amfebutamone (bupropion) should be offered to motivated smokers who fail to quit with counselling. (1++, B) Risk ≥30% Nicotine replacement therapy and/or nortriptyline or amfebutamone (bupropion) should be offered to motivated smokers who fail to quit with counselling. (1++, B) Note: 1++ and the like. … levels of evidence; A, B, etc. … grades of recommendations 43 Kotulán: CVD 43 Kotulán: CVD 43 DIETARY CHANGES All individuals should be strongly encouraged to reduce total fat and saturated fat intake. (1+, A) Total fat intake should be reduced to about 30% of calories, saturated fat to less than 10% of calories, transfatty acids intake should be reduced as much as possible or eliminated and most dietary fat should be polyunsaturated (up to 10% of calories) or monounsaturated (10–15% of calories). (1+, A) All individuals should be strongly encouraged to reduce daily salt intake by at least one third and, if possible, to <5 g or <90 mmol per day. (1+, A) All individuals should be encouraged to eat at least 400 g a day of a range of fruits and vegetables as well as whole grains and pulses. (2+, A) PHYSICAL ACTIVITY All individuals should be strongly encouraged to take at least 30 minutes of moderate physical activity (e.g. brisk walking) a day, through leisure time, daily tasks and work-related physical activity. (1+, A) 44 Kotulán: CVD 44 Kotulán: CVD 44 WEIGHT CONTROL All individuals who are overweight or obese should be encouraged to lose weight through a combination of a reduced-energy diet (dietary advice) and increased physical activity. (1+, A) ALCOHOL INTAKE Individuals who take more than 3 units of alcoholc per day should be advised to reduce alcohol consumption. (2++, B) c One unit (drink) = half pint of beer/lager (5 % alcohol), 100 ml of wine (10 % alcohol), 25 ml spirits (40% alcohol) 45 Kotulán: CVD 45 Kotulán: CVD 45 Risk 10% to <20% Individuals with persistent blood pressure ≥140/90 mmHge should continue lifestyle strategies to lower blood pressure and have their blood pressure and total cardiovascular risk reassessed annually depending on clinical circumstances and resource availability. Risk 20% to <30% Individuals with persistent blood pressure ≥140/90 mmHge who are unable to lower blood pressure through lifestyle strategies with professional assistance within 4–6 months should be considered for one of the following drugs to reduce blood pressure and risk of cardiovascular disease: thiazide-like diuretic, ACE inhibitor, calcium channel blocker, beta-blockerd. A low-dose thiazide-like diuretic, ACE inhibitor or calcium channel blocker is recommended as firstline therapy. (1++, A) Risk ≥30% Individuals with persistent blood pressure ≥130/80 mmHg should be given one of the following drugs to reduce blood pressure and risk of cardiovascular disease: thiazide-like diuretic, ACE inhibitor, calcium channel blocker, betablockerd. A low-dose thiazide-like diuretic, ACE inhibitor or calcium channel blocker is recommended as firstline therapy. (1++, A) d Evidence from two recent meta-analyses indicates that for treatment of hypertension, beta-blockers are inferior to calcium-channel blockers and ACE inhibitors in reducing the frequency of hard endpoints. e Reducing blood pressure by 10–15/5–8 mmHg with drug treatment reduces combined CVD mortality and morbidity by about one-third, whatever the pretreatment absolute risk. BLOOD PRESSURE 46 Kotulán: CVD 46 Kotulán: CVD 46 LIPID-LOWERING DRUGS (STATINS) All individuals with total cholesterol at or above 8 mmol/l (320 mg/dl) should be advised to follow a lipid-lowering diet and given a statin to lower the risk of cardiovascular disease. (2++, B) All other individuals need to be managed according to the cardiovascular risk as follows (10 year risk of cardiovascular event <10%, 10 to <20%, 20 to 30%, ≥30%) Risk <10% Should be advised to follow a lipid-lowering dietg 10 to <20% Should be advised to follow a lipid-lowering dietg Risk 20 to <30% Adults >40 years with persistently high serum cholesterol (>5.0 mmol/l) and/or LDL cholesterol >3.0 mmol/l, despite a lipid-lowering diet, should be given a statin. (1+, A) Risk ≥30% Individuals in this risk category should be advised to follow a lipid-lowering diet and given a statin. (1++, A) Serum cholesterol should be reduced to less than 5.0 mmol/l (LDL cholesterol to below 3.0 mmol/l) or by 25% (30% for LDL cholesterol), whichever is greaterf. HYPOGLYCAEMIC DRUGS Individuals with persistent fasting blood glucose >6 mmol/l despote diet control should be given metformin. (1+, A) f Reducing cholesterol level by 20% (approximately 1 mmol/l) with statin treatment would be expected to yield a coronary heart disease mortality benefit of 30%, whatever the pretreatment absolute risk. However, applying this to the general population may not be cost effective. It will lead to a large proportion of the adult population receiving statins. Even in some high-resource settings, current practice is to recommend drugs for this group only if serum cholesterol is above 8mmol/l (320 mg/dl). g There are no clinical trials that have evaluated the absolute and relative benefits of cholesterol lowering to different cholesterol targets in relation to clinical events. 47 Kotulán: CVD 47 Kotulán: CVD 47 NA00763_ Thank you for your attention