Preview of the Fourth European Guidelines on Cardiovascular Disease Prevention in Clinical Practice

Linda Brookes, MSc

Medscape Cardiology.  2007;(0) ?2007 Medscape
Posted 08/07/2007

Joint European Guidelines on Cardiovascular Disease Prevention: Objectives and Goals

Presenter: Ian Graham, MD (Adelaide and Meath Hospital, Trinity College, Dublin, Ireland)

At a session entitled "What Is Happening With the Guidelines?" held at the European Atherosclerosis Society (EAS) 76th Congress, Prof. Graham, MD, gave a preview of the joint European guidelines on cardiovascular disease (CVD) prevention in clinical practice, which will be issued later this year.[1] The fourth European Guidelines on Cardiovascular Disease Prevention in Clinical Practice have been prepared by a task force under the auspices of the European Society of Cardiology (ESC) and will be released later this year during the ESC's annual congress in Vienna, Austria (September 1-5, 2007).

The new guidelines, which have been prepared in cooperation with a number of other European medical and clinical organizations, will update the third version issued in 2003.[2] Prof. Graham, who is chairman of the Joint Task Force that has been preparing the fourth version, stressed that the Task Force did not attempt to write completely new guidelines, but that they represent the common ground between the major organizations involved in their production:

  • ESC, represented by its European Association of Prevention and Rehabilitation and Working Group on Cardiovascular Nursing;

  • European Society of Atherosclerosis;

  • European Society of Hypertension (ESH);

  • European Heart Network;

  • Family Practice (World Organization of National Colleges, Academies and Academic Associations of General Practitioners/Family Physicians - WONCA);

  • International Society of Behavioral Medicine;

  • European Association for the Study of Diabetes (EASD)/International Diabetes Federation Europe; and

  • European Stroke Initiative.

Compared with the 2003 guidelines, preparation of the latest version involved more input from general practitioner and nursing bodies, Prof. Graham explained, noting that the previous guidelines were criticized by general practitioners for not being practical enough. "We have been told repeatedly that people want simpler guidelines," he said. The guidelines will incorporate the updated recommendations from recently issued guidelines by the ESC on diabetes (with the EASD)[3,4] and hypertension (with ESH),[5,6] as well as other European guidelines related to CVD so that there will be no diversity from any other European society guidelines.

The guidelines' authors have tried to stress exercise, weight, and lifestyle, despite the difficulty in doing this in an atmosphere that promotes drug treatment at all times, Prof. Graham noted. This emphasis led to reservations about limitations of current systems of grading evidence, he added. Drug trials are more amenable to these systems than trials of lifestyle changes, such as smoking cessation, he explained, and thus the present system gives excessive weight to drug treatments.

The new guidelines have redefined priorities and objectives, such as the approach in the young. In addition, total events were considered as well as mortality in risk estimation. New sections on sex, heart rate, body mass index (BMI)/waist circumference, other manifestations of CVD, and renal impairment have been added.

The overall objectives of the guidelines, as described by Prof. Graham, are to get the people of Europe to achieve the characteristics of those who tend to stay healthy:

  • No smoking;

  • Healthy food choices (5 portions of fruit and vegetables per day);

  • Physical activity: Walk 3 km daily, or 30 minutes of any moderate activity;

  • BMI < 25 kg/m2 and avoidance of central obesity;

  • Blood pressure < 140 mm Hg systolic blood pressure (SBP);

  • Total cholesterol < 5 mmol/L (~190 mg/dL);

  • Low-density lipoprotein (LDL) cholesterol < 3 mmol/L (~115 mg/dL); and

  • Blood glucose < 6 mmol/L (~110 mg/dL).

Those at low risk for CVD should be helped to maintain this state lifelong, and those at increased total CVD risk should be helped to reduce their risk. The guidelines give highest priority to the highest risk subjects, appropriately, because these people gain most from risk modification, including:

  • Patients with established atherosclerotic CVD

  • Asymptomatic individuals who are at increased risk for CVD because of:

    • Multiple risk factors resulting in markedly raised total CVD risk (≥ 5% 10-year risk for cardiovascular death)

    • Type 2 or type 1 diabetes with microalbuminuria

    • Markedly increased single risk factors, especially if associated with end-organ damage

  • Close relatives of subjects with premature atherosclerotic CVD or of those at particularly high risk.

The goals of CVD prevention in these high-risk individuals are:

  • Blood pressure < 130/80 mm Hg if feasible;

  • Total cholesterol < 4.5 mmol/L (~175 mg/dL) with an option of < 4 mmol/L (~155 mg/dL) if feasible;

  • LDL cholesterol < 2.5 mmol/L (~100 mg/dL) with an option of < 2 mmol/L (~80 mg/dL) if feasible; and

  • Fasting blood glucose < 6 mmol/L (~110 mg/dL) and glycated hemoglobin (HbA1c) < 6.5% if feasible. ("Feasible" is defined as medically feasible or economically feasible, depending on the economy of the region where the patient lives, Prof. Graham noted.)

In any population, however, most deaths come from lower risk people, simply because they are most numerous, Prof. Graham pointed out. Therefore, countries need to have both a clinical high-risk approach and a complementary overall population strategy, he said.

Assessment of Cardiovascular Risk

The new European guidelines will continue to stress assessment of total risk because multiple risk factors usually contribute to the atherosclerosis that causes CVD, Prof. Graham explained. Because these risk factors interact, sometimes multiplicatively, the aim should be to reduce total risk. If a target cannot be reached for one risk factor, total risk can still be reduced by trying harder with others. He pointed out that only 1 trial of multiple risk factors has ever been carried out, the Multiple Risk Factor Intervention Trial (MRFIT),[7] which sought to evaluate the effect of multiple risk factor interventions on coronary heart disease mortality in high-risk men -- and a new study, a kind of "updated MRFIT in terms of setting overall risk targets," is needed, he urged.

As set out in previous versions of the guidelines, total cardiovascular risk in the latest version is assessed with the SCORE (Systemic COronary Risk Evaluation) system, which was developed by the ESC to define the lifestyle, risk factors, and therapeutic targets for CVD prevention. SCORE is representative of typical European populations and has been optimized for coronary prevention in European clinical practice. The previous system involved sex, age, smoking, SBP, and either total cholesterol or the total cholesterol/high-density lipoprotein (HDL) ratio as risk factors. The latest guidelines will contain more information on total events, diabetes, HDL cholesterol, and BMI.

The latest SCORE system has answered the demand for total events charts and deals with the varying definitions of nonfatal events and diagnostic criteria. It has tried to address other problems, such as obesity, exercise, family history, metabolic syndrome, and other new markers that were missing from the previous charts, which have to be dealt with in qualifying statements in print. All of these things are much easier to deal with in the electronic version of SCORE, according to Prof. Graham.

The new system has also had to correct for overprediction of events in countries where mortality has declined and vice versa. They have also had to correct a misunderstanding associated with the previous system's recommendation to treat younger patients by extrapolation to age 60 years. The concept is that patients aged 30-40 years should not be treated as though they were aged 60 years, but should be advised to begin taking lifestyle measures and considering that they may need drug treatment at an earlier age. To incorporate this more clearly, the Task Force has overcome this misunderstanding by production of a relative risk chart for younger people.

Patients who qualify for a low calculated SCORE risk are recommended to receive lifestyle advice. Guidance about drug treatments begins as CVD risk approaches 10% and in the presence of end-organ damage. In the elderly drug treatment is generally not recommended below 10% risk unless a specific indication exists. Patients with known stable CVD, diabetes, or very high single risk factors should be treated similarly to those with high SCORE risks.

Management of Total Cardiovascular Risk

The key message of the new guidelines is management of the individual components of total cardiovascular risk -- such as smoking, diet, exercise, blood pressure, and lipids -- as they affect total risk. Thus, if perfect control of a risk factor is difficult (for example, blood pressure control in the elderly), total risk can still be reduced by reducing other risk factors, such as smoking or blood cholesterol. Also addressed in these new guidelines are:

  • Tips to help behavior change;

  • Why people find it hard to change their lifestyle;

  • Management of smoking;

  • Healthy food choices;

  • Physical activity;

  • Body weight, BMI, or waist circumference;

  • Blood pressure and lipids; and

  • Diabetes and the metabolic syndrome.

Patients with known CVD, those with type 2 diabetes or type 1 diabetes with microalbuminuria, or those with very high levels of individual risk factors are already at increased risk and need management of all risk factors. For all other people, the SCORE risk charts should be used to estimate total risk. This is critically important because many people have mildly raised levels of several risk factors that, in combination, can result in unexpectedly high levels of total risk.

Prof. Graham stressed that women are not really at lower risk, but that the risk is delayed by 10 years. Ultimately a higher percentage of women die of CVD, especially stroke. Women appear to be disadvantaged at all stages of the medical system: at their history and examination; in clinical trial investigations; in interpretation of both; in risk factor advice; and in all aspects of control and treatments, including interventions, and even access to medical positions that might allow input into policy. Women are underrepresented in trials, and as a result, many of the extrapolations to their proper treatment protocols may be unjustified. Major political and societal initiatives are needed to address these shortcomings; however, the Task Force concluded that, unlike US guidelines, separate guidelines for women were not justified.


Prof. Graham does not favor a unifactorial approach as such, ie, searching for and treating individual risk factors, such as hypertension, alone. All risk factors must be looked for and managed in all patients. However, guidelines as to the management of individual risk factors are included in this update. The recommendations for the treatment of blood pressure were taken from the recently published ESC/ESH guidelines ( Table 1 ).[5,6] Patients with established diabetes or renal disease are at "markedly increased" risk, and a blood pressure of < 130/80 mm Hg is desirable, if feasible. Those with target organ damage are at "increased risk" and should be managed for this. For all other people, treatment should be based on SCORE risk. The recommended blood pressure thresholds and targets in the guidelines are the result of negotiated consensus, but not necessarily universal agreement, Prof. Graham noted.


Prof. Graham revealed that opinions varied about the usefulness of a flowchart to guide treatment of lipids, but one was eventually included. Patients with multifactorial CVD, type 2 or type 1 diabetes with microalbuminuria, or with severe hyperlipidemia are already at high risk and should be given dietary and exercise advice together with attention to all other risk factors. The aim in these patients is to reduce total cholesterol to < 4.5 mmol/L (~175 mg/dL) and to < 4 mmol/L (~155 mg/dL) if feasible, and LDL cholesterol to < 2.5 mmol/L (~100 mg/dL) and to < 2 mmol/L (~80 mg/dL) if feasible. This will require statin treatment in many patients, but statins may be recommended for all CVD and most diabetic patients regardless of baseline levels, Prof. Graham noted.

For all other people, treatment of lipids should depend on total risk as estimated by SCORE charts. Those with SCORE risks ≥ 5% should receive lifestyle advice for 3 months, then fasting lipids and SCORE risk level should be reassessed. If SCORE risk remains ≥ 5%, a statin should be prescribed. If total cholesterol is < 5 mmol/L and LDL cholesterol < 3 mmol/L and the SCORE risk is now < 5%, patients should be treated the same as those with a SCORE risk of < 5% at first examination, ie, lifestyle advice to reduce total cholesterol < 5 mmol/L and LDL cholesterol < 3 mmol/L, with regular follow-up. Treatment goals for HDL cholesterol and triglycerides are not defined in the new guidelines, but HDL cholesterol > 1.0 mmol/L (40 mg/dL) for men and > 1.2 mmol/L (45 mg/dL) for women and fasting triglycerides of > 1.7 mmol/L (150 mg/dL) are noted as markers of increased cardiovascular risk.

Metabolic Syndrome

The ESC Task Force has not adopted any of the definitions of the metabolic syndrome issued by the National Cholesterol Education Program (NCEP), the World Health Organization (WHO), or the International Diabetes Federation (IDF), because they apply arbitrary cutpoints to a continuum of risk, Prof. Graham reported. Instead the European guidelines use a simplified definition stating that the metabolic syndrome refers to the combination of several factors that tend to cluster together to increase the risk for diabetes and CVD, including:

  • Obesity;
  • Hypertension;
  • Low HDL cholesterol;
  • Raised triglycerides; and
  • Raised blood sugar.

This implies that, if one component is identified, a systematic search for the others is indicated, together with an active approach to managing all of these risk factors. The guidelines stress that physical activity and weight control can radically reduce the risk of developing diabetes in those with the metabolic syndrome.

Renal Impairment

A new section of the guidelines dedicated to renal impairment was added because, although it is of more minor interest, the Task Force recognized that CVD risk rises progressively from microalbuminuria with preserved glomerular filtration rate to end-stage renal disease, when it is 20 to 30 times that of the general population. This applies to apparently healthy people, hypertensive individuals, and to CVD and heart failure patients, Prof. Graham noted. Renal impairment is associated with high blood pressure, hyperlipidemia, metabolic syndrome, uric acid, homocysteine, and anemia, and particularly vigorous risk factor control is needed in these patients.


Cardioprotective Drugs

The Task Force has tried to simplify the recommendations on when to prescribe cardioprotective drugs in addition to those used to treat blood pressure, lipids, and diabetes. Aspirin is recommended for almost everyone with established CVD and in persons with SCORE risk > 10% once blood pressure has been controlled. Beta-blockers are recommended after myocardial infarction and, in carefully titrated doses, in those with heart failure. Angiotensin-converting enzyme (ACE) inhibitors are advised in patients with left ventricular dysfunction and in diabetic patients with hypertension or nephropathy. However, ACE inhibitors are not advocated in all high-risk patients, Prof. Graham added, as opinions are divided on this. Anticoagulants are recommended in everyone at increased risk for thromboembolic events, particularly atrial fibrillation.

Prof. Graham summarized the new guidelines recommended for drug treatment for CVD prevention as:

  • In all: Consider blood pressure-lowering drugs when blood pressure is ≥ 140/90 mm Hg;

  • In all: Consider statins when total cholesterol is ≥ 5 mmol/L or LDL cholesterol is ≥ 3 mmol/L;

  • In patients with CVD: aspirin, statins for most;

  • In patients with diabetes: Consider glucose-lowering drugs; and

  • In the elderly: Drug treatment in those with < 10% calculated SCORE risk is not usually recommended, unless there is a specific indication.

Screening of Close Relatives

A strong recommendation is made in the new guidelines for screening all close relatives of patients with premature CVD and persons who belong to families with inherited dyslipidemias, such as familial hypercholesterolemia. These people are at increased risk of developing CVD and should be examined for all cardiovascular risk factors, said Prof. Graham, adding that physicians do not do this as often as they should.

Presentation in September 2007

The new guidelines are scheduled to be presented in Vienna on September 3, 2007. The full document will be published simultaneously in the European Journal of Cardiovascular Prevention & Rehabilitation as well as online, with executive summaries in the European Heart Journal and Atherosclerosis. The Task Force is also considering ways to present the guidelines in a special format for general practitioners, who, they acknowledge, have to read numerous guidelines for many different diseases. Pocket versions of the guidelines' executive summary will be produced for practitioners who do not have the time -- or the inclination -- to read the full version, Prof. Graham confirmed.


Presented by: Željko Reiner, MD, PhD (University Hospital Center, Zagreb, Croatia)

Prof. Reiner, who represents the EAS on the Joint European Societies Cardiovascular Prevention Committee, stressed that the need for simple guidelines is borne out by evidence that doctors do not read much and that continuing medical education does not appear to improve clinical performance over time.[8] This has been shown in the European Action on Secondary Prevention through Intervention to Reduce Events (EUROASPIRE) surveys. The first 2, EUROASPIRE I and II, revealed that the management of patients' risk factors has not been effective in achieving the goals for CVD prevention set out in the joint European societies' 1998 guidelines.[9-11] The first EUROASPIRE survey of preventive cardiology practice in 1995-1996 in 9 countries and the second in 1999-2000 in 15 countries showed a high prevalence of unhealthy lifestyles, modifiable risk factors, and inadequate use of drug therapies to achieve blood pressure, lipid, and glucose goals in patients with established coronary heart disease ( Table 2 ).

Comparison of EUROASPIRE I and II showed adverse lifestyle trends, with more smoking among younger (especially female) patients and increasing obesity across all centers. A majority of patients in EUROASPIRE II were still not achieving the blood pressure and lipid targets, and those with diabetes were not achieving blood glucose targets. The second survey also found that only 1 in 10 first-degree relatives (siblings and offspring) of patients with premature coronary disease were assessed for their cardiovascular risk. The surveys also revealed wide variations in preventive cardiology practice between European centers, reflecting differences in healthcare delivery and economics. Drug use increased during the time between the surveys, although not markedly except for lipid-lowering drugs, particularly statins ( Table 3 ).

EUROASPIRE III, which was launched in September 2006, has just been completed, and the principal results and a comparison between EUROASPIRE I, II, and III will also be presented during the ESC Congress in Vienna, Prof. Graham reported.

EUROASPIRE III was carried out in 22 countries. It will identify risk factors in coronary patients, their blood relatives and high-risk individuals, describe their management through lifestyle and use of drug therapies, and provide an objective assessment of clinical implementation of current scientific knowledge. It is based on hospitalized coronary heart disease patients, their blood relatives (if there is premature coronary heart disease), and for the first time apparently healthy individuals in primary care at high risk of developing CVD. The primary care part of the survey is currently still under way and accumulating additional data.

Table 1. Management of Total CVD Risk: Blood Pressure

SCORE CVD Risk Blood Pressure
< 130/85 mm Hg
130-139/ 85-89 mm Hg
Grade 1
140-159/ 90-99 mm Hg
Grade 2
160-179/ 100-109 mm Hg
Grade 3
≥ 180/ 110 mm Hg
< 1%
Lifestyleadvice Lifestyleadvice Lifestyleadvice Drug treatmentif persists Drug treatment
Lifestyle advice Lifestyle advice Consider drug treatment Drug treatment if persists Drug treatment
Lifestyle advice Consider drug treatment Drug treatment Drug treatment Drug treatment
≥ 10%
Lifestyle advice Consider drug treatment Drug treatment Drug treatment Drug treatment

CVD = cardiovascular disease; SCORE = Systemic COronary Risk Evaluation


Table 2. EUROASPIRE I and II: Percentage of Patients With Risk Factors 6 Months After a Proven Episode of Coronary Heart Disease*

BMI ≥ 25 78% 81%
BMI ≥ 30 25% 33%
Blood pressure ≥ 140/90 mm Hg 55% 50%
Cholesterol ≥ 5 mmol/L 67% 59%
Smoking 19% 21%

*Acute coronary syndromes, percutaneous coronary intervention, or coronary artery bypass graft
BMI = body mass index


Table 3. EUROASPIRE I and II: Drug Usage

Aspirin 81% 84%
Beta-blockers 54% 66%
ACE inhibitors 30% 43%
Calcium channel blockers 36% 26%
Lipid-lowering drugs 32% 63%
Statins 19% 58%

ACE = angiotensin-converting enzyme



  1. Graham I. Discussion: what is happening with the guidelines? Program and s of the European Atherosclerosis Society (EAS) 76th Congress; June 10-13, 2007; Helsinki, Finland.
  2. De Backer G, Ambrosioni E, Borch-Johnsen K, et al; Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 8 societies and by invited experts). 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. Eur Heart J. 2003;24:1601-1610.
  3. Ryden L, Standl E, Bartnik M, et al. Guidelines on diabetes, pre-diabetes, and cardiovascular diseases. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J. Published online before print May 17, 2007. Available at: Accessed July 20, 2007.
  4. Ryden L, Standl E, Bartnik M, et al; Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC); European Association for the Study of Diabetes (EASD). Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J. 2007;28:88-136.
  5. Mancia G, De Backer G, Dominiczak A, et al; Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007;25:1105-1187.
  6. Authors/Task Force Members: Mancia G, De Backer G, Dominiczak A, et al. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2007;28:1462-1536. Available at: Accessed July 20, 2007.
  7. Multiple Risk Factor Intervention Trial Research Group. Multiple risk factor intervention trial. Risk factor changes and mortality results. JAMA. 1982;248:1465-1477.
  8. Reiner Z. Discussion: what is happening with the guidelines? Program and s of the European Atherosclerosis Society (EAS) 76th Congress; June 10-13, 2007; Helsinki, Finland.
  9. EUROASPIRE. A European Society of Cardiology survey of secondary prevention of coronary heart disease: principal results. EUROASPIRE Study Group. European Action on Secondary Prevention through Intervention to Reduce Events. Eur Heart J. 1997;18:1569-1582.
  10. EUROASPIRE II Study Group. Lifestyle and risk factor management and use of drug therapies in coronary patients from 15 countries: principal results from EUROASPIRE II Euro Heart Survey Programme. Eur Heart J. 2001;22:554-572.
  11. EUROASPIRE Study Group. Clinical reality of coronary prevention guidelines: a comparison of EUROASPIRE I and II in nine countries. Lancet. 2001;357:995-1001.

Linda Brookes, MSc, freelance medical writer based in London and New York

Disclosure: Linda Brookes, MSc, has disclosed no relevant financial relationships.