European guidelines on cardiovascular disease prevention in clinical practice;Third Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of eight societies and by invited experts)

Introduction

The rationale for an active approach to the prevention of cardiovascular diseases (CVD) is firmly based on five observations:

Cardiovascular disease is generally due to a combination of several risk factors, and, in recognition of the multi-factorial nature of this group of diseases, the European Atherosclerosis Society, the European Society of Cardiology, and the European Society of Hypertension agreed in the early 1990s to collaborate to suggest guidelines for prevention of coronary heart disease in clinical practice. The result was a set of recommendations published in 1994. A revision of these early guidelines was published in 1998 by the Second Joint Task Force, which set lifestyle, risk factor and therapeutic goals for coronary prevention.

In this second report the original three societies were joined by the European Society of General Practice/Family Medicine, the European Heart Network, and by the International Society of Behavioural Medicine.

Since completion of this report, important new data have been published. Therefore the Third Joint Task Force provides a second revision of the joint European guidelines. The Task Force has been joined by the European Association for the Study of Diabetes and by the International Diabetes Federation Europe. These new guidelines differ from the previous ones in several important aspects:

These guidelines are specifically intended to encourage the development of national guidance on cardiovascular disease prevention. Implementation of these guidelines is possible only through collaboration between very different professional groups at the national level. The guidelines should be considered as the framework in which all necessary adaptations can be made in order to reflect different political, economic, social and medical circumstances.

The Third Joint Task Force recognises that these guidelines which are targeted at those at highest CVD risk should be complemented by strategies aimed at whole populations at the national and European level as a contribution to a public health policy to reduce the enormous burden of cardiovascular disease in European populations.

Medical priorities

Preventive efforts are most efficient when they are directed at those at highest risk. The present recommendations therefore define the following priorities for CVD prevention in clinical practice:

Objectives of cardiovascular prevention

The objectives of these guidelines are to reduce the incidence of first or recurrent clinical events due to coronary heart disease, ischaemic stroke and peripheral artery disease. The focus is prevention of disability and early deaths. To this end, the current guidelines address the role of lifestyle changes, the management of major cardiovascular risk factors and the use of different prophylactic drug therapies in the prevention of clinical CVD.

Intermediate end-points such as left ventricular hypertrophy, carotid artery plaques and to a lesser extent endothelial dysfunction as well as alteration in the electrical stability of the myocardium have been shown to increase the risk of cardiovascular morbidity, indicating that sub-clinical organ damage has clinical relevance. Accordingly such measurements may be incorporated in more sophisticated models to assess the risk for future CVD events.

Total cardiovascular risk as a guide to preventive strategies: the SCORE system

Patients with established cardiovascular disease have declared themselves to be at high total risk of a further vascular event. Therefore, they require the most intensive lifestyle intervention, and where appropriate drug therapies.

In asymptomatic, apparently healthy subjects, preventive actions should be guided in accordance with the total CVD risk level. Those at highest total risk should be identified and targeted for intensive lifestyle interventions and where appropriate, drug therapies. Several models have been developed to assess the risk for CVD in asymptomatic subjects. Using different combinations of risk factors these models are all based on a multifactorial risk analysis in populations that have been followed for several years.

These guidelines recommend a new model for total risk estimation based on the SCORE (Systematic Coronary Risk Evaluation) system. The new risk chart based on the SCORE study represents several advantages compared to the previous chart. The SCORE risk assessment system is derived from a large dataset of prospective European studies and predicts any kind of fatal atherosclerotic end-point such as fatal CVD events over a 10-year period. In SCORE the following risk factors are integrated: gender, age, smoking, systolic blood pressure and either total cholesterol or the cholesterol/high-density lipoprotein (HDL) ratio. Since this chart predicts fatal events the threshold for being at high risk is defined as ≥ 5%, instead of the previous ≥ 20% in charts using a composite coronary end-point. Using SCORE it is now possible to produce risk charts tailored for individual countries provided reliable national mortality information is available.

Practitioners should use total CVD risk estimates when decisions are taken to intensify preventive actions, i.e. when dietary advice should be more specified, when the physical activity prescription should be more individualized, when drugs should be prescribed, dosages adapted or combinations started to control risk factors; these decisions should usually not be based on the level of any one risk factor alone; neither should they be linked to only one arbitrary cut point from the continuous total CVD risk distribution.

Total CVD risk can easily be derived from printed charts (see illustrations in Figures 1 & 2) or from the web where in addition the SCORECARD system will provide physicians and patients with information on how total risk can be reduced by interventions (both lifestyles and drugs) that have been proven to be efficacious and safe in descriptive cohort studies and/or in randomised controlled trials.

Both the SCORE and the SCORECARD system also allows the estimation of total CVD risk to be projected to age 60 which may be of particular importance for guiding young adults at low absolute risk at the age of 20 or 30 but already with an unhealthy risk profile which will put them at much higher risk when they grow older. Furthermore, both systems allow the use of relative risk estimates that, in addition to total absolute risk, may be of interest in particular cases.

New imaging methods to detect asymptomatic individuals at high risk for cardiovascular events

Magnetic resonance imaging (MRI) allows in vivo imaging of the arterial wall and differentiation of plaque components. Coronary calcifications can be detected and quantified by computed tomography (EB-CTor MS-CT). The resulting calcium score is an important parameter to detect asymptomatic individuals at high risk for future CVD events, independent of the traditional risk factors. Furthermore, carotid intima-media thickness, measured by ultrasound, is a risk factor for cardiac events and stroke. Left ventricular hypertrophy, either detected by ECG or by echocardiography has also been shown to be an independent risk factor for CVD mortality and morbidity in hypertensive subjects. Each of these measurements has its limitations, yet they may be included in sophisticated models for risk assessment, which may be more precise than current models based on classical risk factors.

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Fig. 1

Ten-year risk of fatal CVD in high-risk regions of Europe by gender, age, systolic blood pressure, total cholesterol and smoking status.

Management of CVD risk in clinical practice

Behavioural risk factors

Changes in many patterns of individual behaviour are necessary in a large majority of patients with established CVD or at high risk of CVD, but recent surveys suggest a serious gap between recommendations for behavioural change and the advice actually provided by physicians in routine clinical practice. The management of behavioural risk factors is similar for patients with CVD and high-risk people, but changing risk behaviours (unhealthy diet, smoking, sedentary lifestyle), which have lasted for many years, needs a professional approach.

For many people it can be difficult to change lifestyle according to a physician's advice. This difficulty pertains especially to people and patients who are socially and economically disadvantaged, who exercise little control over monotonous and unrewarding jobs, who are in a stressful family situation, or who live alone and lack social support.

Moreover, negative emotions, including depression, anger and hostility, may constitute barriers to preventive efforts, both in patients and in high-risk people. The physician can recognize these barriers by using a simple set of questions. Although physician's awareness is helpful and in some cases sufficient, persistent and severe negative emotions can require expert consultation and behavioural or pharmacological treatment. As psychosocial risk factors are independent of standard risk factors, efforts to relieve stress and counteract social isolation should be emphasised whenever possible.

Strategic steps (adapted from the Report of the US Preventive Services Task Force) that may be used to enhance the effectiveness of behavioural counselling include:

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Develop a therapeutic alliance with the patient.

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Ensure that patients understand the relationship between behaviour, health and disease.

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Help patients to understand the barriers to behavioural change.

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Gain commitments from patients to behavioural change.

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Involve patients in identifying and selecting the risk factors to change.

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Use a combination of strategies including reinforcement of patients’ own capacity for change.

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Design a lifestyle modification plan.

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Monitor progress through follow-up contact.

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Involve other health care staff wherever possible.

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Fig. 2

Ten-year risk of fatal CVD in low-risk regions of Europe by gender, age, systolic blood pressure, total cholesterol and smoking status.

Stop smoking tobacco

All smokers should be professionally encouraged to permanently stop smoking all forms of tobacco. Strategies that may help can be summarised into the following five A's:

A - Ask: systematically identify all smokers at every opportunity.

A - Assess: determine the patient's degree of addiction and his/her readiness to cease smoking.

A - Advise: urge strongly all smokers to quit.

A - Assist: agree on a smoking cessation strategy including behavioural counselling, nicotine replacement therapy and/or pharmacological intervention.

A - Arrange: a schedule of follow-up visits.

Make healthy food choices

Making healthy food choices is an integral part of total risk management. All individuals should receive professional advice on food and food choices to compose a diet associated with the lowest risk of cardiovascular disease.

A sound diet reduces risk by several mechanisms including weight reduction, lowering of blood pressure, effects on lipids, control of glucose and reduction of the propensity to thrombosis.

Patients with arterial hypertension, diabetes, and hypercholesterolaemia or other dyslipidemias should receive specialist dietary advice.

Increase physical activity

Physical activity should be promoted in all age groups—from children to the elderly—and all patients and high risk people should be professionally encouraged and supported to increase their physical activity safely to the level associated with the lowest risk of CVD. Although the goal is at least half an hour of physical activity on most days of the week, more moderate activity is also associated with health benefits.

Healthy people should be advised to choose enjoyable activities which fit into their daily routine, preferably 30 to 45 minutes, four to five times weekly at 60–75% of the average maximum heart rate. For patients with established CVD, advice must be based on a comprehensive clinical judgement including the results of an exercise test. Other expert committees have given detailed recommendations for CVD patients.

Management of other risk factors

Blood pressure

The risk of cardiovascular diseases increases continuously as blood pressure rises from levels that are considered to be within the normal range. The decision to start treatment, however, depends not only on the level of blood pressure, but also on an assessment of total cardiovascular risk and the presence or absence of target organ damage. In patients with established CVD the choice of anti-hypertensive drugs depends on the underlying cardiovascular disease.

A guide to blood pressure management in asymptomatic people is given in Figure 3. The decision to lower blood pressure with drugs depends not only on the total cardiovascular risk but also on presence of target organ damage. Drug therapy should be initiated promptly in individuals with a sustained systolic blood pressure (SBP) ≥ 180 mmHg and/or a diastolic blood pressure (DBP) ≥ 110 mmHg regardless of their total cardiovascular risk assessment.

Individuals at high risk of developing CVD with sustained SBP of ≥ 140 mmHg and/or DBP ≥ 90 mmHg also require drug therapy. For such individuals, drugs should be used to lower blood pressure to < 140/90 mmHg. Similar elevation of blood pressure in low risk people without target organ damage should be followed closely, and lifestyle advice should be given. Drug treatment might be considered after asking the patients’ preference.

With few exceptions, individuals with SBP < 140 mmHg and/or DBP < 90 mmHg do not need drug therapy. Patients with a high or very high cardiovascular risk profile and patients with diabetes can benefit from reducing blood pressure below the goal of SBP < 140 mmHg and/or DBP < 90 mmHg.

Anti-hypertensive drugs should not only lower blood pressure effectively. They should have a favourable safety profile and be able to reduce cardiovascular morbidity and mortality. Five classes of drugs currently meet these requirements: diuretics, beta-blockers, ACE inhibitors, calcium-channel blockers and angiotensin II antagonists.

In many clinical trials, blood pressure control has been achieved by the combination of two or even three drugs, and drug combination therapy is often also necessary in routine clinical practice. In patients with several diseases requiring drug therapy, polypharmacy can become a major problem and good clinical management is required to resolve it. In all patients, blood pressure reduction should be obtained gradually. For most patients, the goal of therapy is blood pressure less than 140/90 mmHg, but for patients with diabetes and individuals at high total CVD risk, the blood pressure goal should be lower.

Plasma lipids

In general, total plasma cholesterol should be below 5 mmol/l (190 mg/dl), and LDL cholesterol should be below 3 mmol/l (115 mg/dl). For patients with clinically established CVD and patients with diabetes the treatment goals should be lower: total cholesterol < 4.5 mmol/l (175 mg/dl) and LDL cholesterol < 2.5 mmol/l (100 mg/dl).

No specific treatment goals are defined for HDL cholesterol and triglycerides, but concentrations of HDL cholesterol and triglycerides are used as markers of increased risk. High-density lipoprotein cholesterol < 1.0 mmol/l (40 mg/dl) in men and < 1.2 mmol/l (46 mg/dl) in women, and similarly, fasting triglycerides > 1.7 mmol/l (150 mg/dl), serve as markers of increased cardiovascular risk. Values of HDL cholesterol and triglycerides should also be used to guide the choice of drug therapy.

Asymptomatic people at high multifactorial risk of developing cardiovascular disease, whose untreated values of total and LDL cholesterol are already close to 5 and 3 mmol/l, respectively, seem to benefit from further reduction of total cholesterol to < 4.5 mmol/l (175 mg/dl), and from further reduction of LDL cholesterol to < 2.5 mmol/l (100 mg/dl), with moderate doses of lipid lowering drugs. However, these lower values are not goals of therapy for patients with higher untreated values because high-dose therapy, the merits of which have not yet been documented, would be needed to reach such lower goals.

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Fig. 3

Guide to blood pressure management.

In asymptomatic individuals (see Figure 4), the first step is to assess total cardiovascular risk and to identify these components of risk that are to be modified. If the 10-year risk of cardiovascular death is < 5% and will not exceed 5% if the individuals’ risk factor combination is projected to age 60, professional advice concerning a balanced diet, physical activity and stopping smoking should be given to keep the cardiovascular risk low. Risk assessment should be repeated at five-year intervals. Note that assessment of total risk does not pertain to patients with familial hypercholesterolaemia, since total cholesterol < 8 mmol/l (320 mg/dl) and LDL cholesterol < 6 mmol/l (240 mg/dl) by definition places a patient at high total risk of CVD.

If the 10-year risk of cardiovascular death is ≥ 5%, or will become ≥ 5% if the individuals’ risk factor combination is projected to age 60, a full analysis of plasma lipoproteins should be performed, and intensive lifestyle advice, particularly dietary advice, should be given. If values of total and LDL cholesterol fall below 5 mmol/l (190 mg/dl) and 3 mmol/l (115 mg/dl), respectively, and the total CVD risk estimate has become < 5%, then these persons should be followed at yearly intervals to ensure that cardiovascular risk remains low without drugs. In contrast, if total CVD risk remains ≥ 5%, lipid lowering drug therapy should be considered to lower total and LDL cholesterol even further. The goals in such persistently high-risk individuals are to lower total cholesterol to < 4.5 mmol/l (175 mg/dl) and to lower LDL cholesterol to < 2.5 mmol/l (100 mg/dl). As stated earlier, these lower values are not goals of therapy for patients with higher untreated values.

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Fig. 4

Guide to lipid management in asymptomatic subjects. Estimate total fatal CVD risk using the SCORE chart. Use initial total cholesterol (or ratio of total to HDL-cholesterol) to estimate risk. (TC: total cholesterol, LDL-C: LDL cholesterol, HDL-C: HDL cholesterol).

The first clinical trials which documented the clinical benefits (improved survival) of lipid lowering therapy with statins were restricted to individuals < 70 years and total cholesterol > 5 mmol/l. Recently published trials indicate that such treatment can also be effective in the elderly and in subjects with lower cholesterol levels.

Some individuals require combination therapy. In patients with several diseases requiring drug therapy, polypharmacy can become a major problem and good clinical management is required to resolve it. In some patients, goals cannot be reached even on maximal therapy, but they will still benefit from treatment to the extent to which cholesterol has been lowered.

Diabetes

It has been demonstrated that progression to diabetes can be prevented or delayed by lifestyle intervention in individuals with impaired glucose tolerance.

In patients with type 1 and type 2 diabetes, there is convincing evidence from randomised controlled trials that good metabolic control prevents microvascular complications. Regarding the prevention of cardiovascular events, there are also good reasons to aim for good glucose control in both types of diabetes. In type 1 diabetes, glucose control requires appropriate insulin therapy and concomitant professional dietary therapy. In type 2 diabetes, professional dietary advice, reduction of overweight and increased physical activity should be the first treatment aiming at good glucose control.

Drug therapy must be added if these measures do not lead to a sufficient reduction of hyperglycaemia.

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Table 1

Treatment goals in patients with type 2 diabetes

		Goal
HbA1c (DCCT-standardized)	HbA1c (%)	≤ 6.1
Venous plasma glucose	Fasting/pre-prandial
	mmol/l	≤ 6.0
	mg/dl	< 110
Self-monitored blood glucose	Fasting/pre-prandial
	mmol/l	4.0–5.0
	mg/dl	70–90
	Post-prandial
	mmol/l	4.0–7.5
	mg/dl	70–135
Blood pressure	mmHg	< 130/80
Total cholesterol	mmol/l (mg/dl)	< 4.5(175)
LDL cholesterol	mmol/l (mg/dl)	< 2.5(100)

Recommended treatment targets for type 2 diabetes are given in Table 1.

Treatment goals for blood pressure and lipids are generally more ambitious in patients with diabetes.

The metabolic syndrome

In clinical practice, the definition given by the US National Cholesterol Education Program can be provisionally used for the identification of individuals with the metabolic syndrome. The diagnosis of the metabolic syndrome is made, when three or more of the following features are present:

People with the metabolic syndrome are usually at high risk of cardiovascular disease. Lifestyle has a strong influence on all the components of the metabolic syndrome and therefore the main emphasis in the management of the metabolic syndrome should be in professionally supervised lifestyle changes, particularly efforts to reduce body weight and increase physical activity. Elevated blood pressure, dyslipidemia and hyperglycaemia (in the diabetic range) may, however, need additional drug treatment as recommended in the present guidelines.

Other prophylactic drug therapies

In addition to drugs needed to treat blood pressure, lipids and diabetes, the following drug classes should also be considered in the prevention of CVD in clinical practice:

In asymptomatic high-risk people there is evidence that low dose aspirin can reduce the risk of cardiovascular events in people with diabetes, in people with well-controlled hypertension and in men at high multifactorial CVD risk.

Screening close relatives

Close relatives of patients with premature coronary heart disease (men > 55 years and women > 65 years) and persons who belong to families with familial hypercholesterolaemia or other inherited dyslipidemias should be examined for cardiovascular risk factors, because all of these persons are at increased risk of developing cardiovascular disease.