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© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Guidelines on cardiovascular risk assessment and management

David A. Wood1,2,*

1Cardiovascular Medicine at the National Heart and Lung Institute, Imperial College, London, UK
2Hammersmith Hospitals NHS Trust, London, UK

* Corresponding author. E-mail address: d.wood{at}imperial.ac.uk


   Abstract
Top
 Abstract
Lifestyle modification
 Treatment targets
 Conclusion
 Key points
 References
 
Cardiovascular disease is the major cause of premature death in most European populations. The underlying pathology is usually atherosclerosis. Cardiovascular disease is closely related to lifestyle and modifiable physiological factors, and risk factor modification has been shown to reduce cardiovascular morbidity and mortality. The current joint European Guidelines differ from previous ones in that the emphasis has moved from coronary heart disease prevention to cardiovascular disease prevention. The Systematic Coronary Risk Evaluation system is recommended to assess an individual's total cardiovascular risk. The guidelines define priorities for intervention and address lifestyle change and management of major cardiovascular risk factors to reduce cardiovascular events. Reduction of overweight and obesity is an important component in reducing cardiovascular risk.

Key Words: Atherosclerosis • Cardiovascular disease • Guidelines • Lifestyle modification • Obesity • SCORE • Treatment targets

Cardiovascular disease is the major cause of death in adults in most European countries. It results in substantial disability and loss of productivity and contributes significantly to the escalating costs of health care, especially in the context of an ageing population. Cardiovascular disease accounts for 49% of all deaths in Europe and for 30% of all premature deaths (those occurring before 65 years). It is the major cause of premature death in most European populations: one in eight men and one in 17 women die from cardiovascular disease before 65 years.

There are marked differences in cardiovascular disease mortality rates between countries. Trends of age and gender-standardized cardiovascular mortality from 1980 show down-sloping curves in Nordic, western, and southern Europe (except Greece) but stable or rising curves in central and eastern European countries. However, as cardiovascular disease is strongly related to age, its prevalence is rising. This, together with an improved cardiovascular disease treatment and survival rate, means that an increasing number of individuals in Europe are living with impaired cardiovascular health and are at risk of recurrent disease (re-infarction, recurrent stroke, heart failure, and sudden death). Therefore, the overall burden of cardiovascular disease is expected to increase in the coming decade.1

The development of cardiovascular disease is strongly related to lifestyle factors such as diet, physical inactivity, and tobacco smoking. These promote adverse changes in biochemical and physiological characteristics, which in turn accelerate the development of atherosclerosis and associated thrombotic complications. It is increasingly clear that these cardiovascular risk factors interact with each other synergistically.

There is now considerable evidence that lifestyle modification and risk factor management can slow the development of cardiovascular disease, both before and after the occurrence of an acute event. This evidence has been synthesized into recommendations on cardiovascular disease prevention in clinical practice, published by the Joint European Societies.2

The Third Joint Task Force, which produced the 2003 joint European Guidelines, is a collaboration of eight groups: the European Society of Cardiology, European Society of Atherosclerosis, European Society of Hypertension, European Society of General Practice/Family Medicine, European Heart Network, International Society of Behavioural Medicine, European Association for the Study of Diabetes, and the International Diabetes Federation Europe.

The 2003 European Guidelines differ from previous ones in that the emphasis has moved from coronary heart disease prevention to cardiovascular disease prevention. The latest World Health Organization statistics show that in women, coronary heart disease accounted for 23% of deaths, stroke for 18%, and other cardiovascular disease for 15%. (In contrast, cancer accounted for 27% of deaths in women.) The situation for men is similar. Therefore, it is important to target all patients with atherosclerotic disease, not just those with coronary artery disease.

The guidelines define priorities and thresholds for treatment and treatment targets. The top priority is patients with established atherosclerotic disease, i.e. established coronary heart disease, peripheral artery disease, and cerebrovascular atherosclerotic disease. The second priority group is asymptomatic, apparently healthy, individuals who are identified as being at high risk of developing atherosclerotic cardiovascular disease in the foreseeable future, on the basis of a clustering of risk factors. This group of high-risk individuals includes patients with diabetes.

Different multi-factorial risk models have been developed to assess the risk for development of cardiovascular disease. The European Guidelines recommend the use of the SCORE (Systematic Coronary Risk Evaluation) system.3 The SCORE risk assessment system is derived from a large data set of prospective European studies. From an individual's age, gender, smoking habit, systolic blood pressure, and total cholesterol/HDL cholesterol ratio, it provides an estimate of their total risk of developing fatal cardiovascular disease over a period of 10 years. The importance of this approach is that the absolute risk of developing cardiovascular disease depends on the presence of multiple risk factors. Addressing a single risk factor, such as blood pressure, lipids, or glucose, in isolation misses the fundamental challenge of addressing all risk factors simultaneously, in order to reduce the risk of cardiovascular disease.

The third priority group is close relatives of patients with early-onset atherosclerosis and asymptomatic individuals at particularly high risk (e.g. families with familial hypercholesterolaemia or other forms of inherited dyslipidaemia).

From epidemiological studies, a great deal is known about the underlying causes of atherosclerosis and its thrombotic complications. However, it is a widely held misconception that the established cardiovascular risk factors (Figure 1) only explain about half of all the cardiovascular disease in the population. The recent INTERHEART case–control study4 clearly demonstrates the overwhelming importance of these risk factors.



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  		Figure 1 Lifestyles and characteristics associated with the risk of cardiovascular events (adapted from De Backer et al.2).

 
INTERHEART assessed potentially modifiable risk associated with myocardial infarction in 52 countries from each of the major regions of the world. It involved 262 centres and over 15 000 patients with an initial myocardial infarction and a similar number of healthy controls. Analysis was based on 12 461 cases and 14 637 controls. The study showed convincingly that the major risk factors for cardiovascular disease are apoB/apoA-1 ratio, smoking, diabetes, hypertension, abdominal obesity, psychosocial factors, consumption of fruit and vegetables, alcohol, and regular exercise (Table 1). All these risk factors were significantly related (P<0.0001)—either directly or inversely—to the risk of a first myocardial infarction, with the exception of alcohol, which had a weaker association (P=0.03). Daily consumption of fruits or vegetables, moderate or strenuous exercise, and consumption of alcohol three or more times a week were protective.


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  		Table 1 Data from the INTERHEART study showing risk of acute myocardial infarction associated with risk factors in the overall population4
 
These risk factors collectively accounted for about 90% of the population attributable risk and hence are the major causes of atherosclerosis and its complications. The same associations were found in men and women at all ages and in all regions of the world. After multi-variate analysis, raised apoB/apoA-1 ratio and current smoking were the two strongest risk factors.

The INTERHEART study has highlighted the importance of multiplicative risk. With all nine risk factors (current or former smoking, history of diabetes or hypertension, abdominal obesity, psychosocial stress, irregular consumption of fruits and vegetables, no alcohol intake, avoidance of regular exercise, and raised plasma lipids), the odds ratio was 129 when compared with not having any of these risk factors. Substituting the odds ratios for current smoking, the extremes of abdominal obesity (top vs. lowest tertile) and apoB/apoA-1 ratio (top vs. lowest quintile) increased the odds ratio for all risk factors combined to 333, i.e. the chance of having an initial myocardial infarction is 333 times that of the healthy population (Figure 2).



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  		Figure 2 Risk of acute myocardial infarction associated with exposure to multiple risk factors.4 The odds ratios are based on current vs. never smoking, top vs. lowest tertile for abdominal obesity, and top vs. lowest quintile for apoB/apoA-1. (Adapted with permission from Yusuf et al.4)

 
It is important to note that several of these cardiovascular risk factors—apoB/apoA-1 ratio, diabetes, hypertension, abdominal obesity, diet, and physical activity—are included in the definitions of the metabolic syndrome and are closely related to obesity and the distribution of fat.


   Lifestyle modification
Top
 Abstract
 Lifestyle modification
Treatment targets
 Conclusion
 Key points
 References
 
Lifestyle modification is the foundation of any preventive cardiology programme, and the European Guidelines address the issue of lifestyle change. The aim is to help patients with coronary heart disease or other atherosclerotic disease and healthy high-risk individuals to stop smoking, to make healthy food choices, to be physically active and, as part of that, to reduce weight and the distribution of weight.

The rising tide of obesity in Europe, and elsewhere in the world, is of medical and public health concern. In several European countries, including Finland, the UK, Germany, Hungary, and Belgium, around one-fifth of the adult population are obese [defined by body mass index (BMI) >30 kg/m2]. In most countries, obesity prevalence is similar in men and women, with the exception of Turkey where prevalence is considerably higher in women than men.

It is not only the current prevalence of obesity that is of concern, but also the time trends in obesity. Between 1981 and 1998, some European countries, including the UK, showed a rapid increase in obesity prevalence, whereas in others, such as Italy and Sweden, obesity prevalence remained at a lower, although not ideal, level. Trends in obesity prevalence in men and women have followed the same direction in the individual countries.

There are powerful social, economic, and cultural determinants of obesity in different European populations. This population burden impacts upon our patients. The European Society of Cardiology EUROASPIRE (EUROpean Action on Secondary Prevention through Intervention to Reduce Events) surveys of risk factor management in patients with established coronary heart disease highlight the need for more effective lifestyle intervention. The surveys show considerable potential to reduce risk in patients with established coronary heart disease, because many are not achieving the lifestyle and risk factor goals.

EUROASPIRE I was carried out in 1995–1996 in nine European countries5 to assess risk factor management in patients with established coronary heart disease (following acute myocardial infarction or ischaemia, coronary artery bypass surgery, or coronary angioplasty). A second similar survey, EUROASPIRE II,6 was carried out in 1999–2000 in 15 European countries to see whether preventive cardiology had improved since the first survey. In EUROASPIRE I, 3569 patients were interviewed and in EUROASPIRE II, 5556 patients were interviewed.

In EUROASPIRE I, 25.3% of patients were obese (BMI ≥30 kg/m2). In EUROASPIRE II, the prevalence of obesity in these high-risk patients had increased to 32.8%.7 The increase in obesity was seen across each of the participating countries.

In addition, in EUROASPIRE II, the majority of patients was found to have gained weight following the development of coronary heart disease.8 Between hospital admission for the index event and interview [carried out at least 6 months (median 1.4 years), after hospital discharge], 24.3% of patients had a weight increase of ≥5 kg (Figure 3). The overall prevalence of overweight (BMI 25–29.9 kg/m2) at the time of interview was 48.2% (51.2% in men and 38.6% in women). Thus, around three-quarters of patients with coronary heart disease were either overweight or obese. Furthermore, 28.1% of patients had abdominal overweight (waist circumference >80 cm in women and >94 cm in men) and 51.7% had abdominal obesity (waist circumference >88 cm in women and >102 cm in men).



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  		Figure 3 Distribution of weight changes between time of hospital admission for acute coronary event or procedure and time of interview (≥6 months after the index event) in EUROASPIRE II. (Adapted with permission from De Bacquer et al.8)

 
These data indicate the considerable challenge that we face in terms of lifestyle intervention in patients with coronary heart disease and other atherosclerotic disease, as well as in high-risk individuals in the population.


   Treatment targets
Top
 Abstract
 Lifestyle modification
 Treatment targets
Conclusion
 Key points
 References
 
The more successful we are at achieving lifestyle changes, the lower the requirement for antihypertensive and lipid lowering and glucose lowering therapies. The European Guidelines set the following targets in high risk patients for blood pressure and lipid levels:

  • blood pressure <140/90 mmHg,
  • total cholesterol <4.5 mmol/L (175 mg/dL),
  • LDL cholesterol <2.5 mmol/L (100 mg/dL).
When these targets are not achieved by lifestyle change, blood pressure lowering and cholesterol lowering drugs should be used. It is important to recognize that lifestyle impacts on the ability to control blood pressure and lipids, despite the use of antihypertensive and lipid lowering therapies. This was demonstrated in the EUROASPIRE II analysis.8 Among patients being treated with lipid lowering agents, 42.7% of normal weight patients were still above the cholesterol target of 5 mmol/L. In contrast, 49.6% of overweight patients and 52.7% of obese patients were still above the target cholesterol level. A similar situation pertained for control of blood pressure in patients taking blood pressure lowering drugs: 42.4% of normal weight patients were still above the blood pressure target of 140/90 mmHg compared with 51.1% of overweight patients and 56.0% of obese patients.

The definition of metabolic syndrome in the European Guidelines is the same as that used in the National Cholesterol Education Program. The diagnosis of metabolic syndrome is made when three or more of the following features are present:

  • waist circumference >102 cm in males and >88 cm in women,
  • serum triglycerides ≥1.7 mmol/L (≥150 mg/dL),
  • HDL cholesterol <1 mmol/L (<40 mg/dL) in males or <1.3 mmol/L (<50 mg/dL) in females,
  • blood pressure ≥130/85 mmHg,
  • plasma glucose ≥6.1 mmol/L (≥110 mg/dL).
This is a pragmatic clinical definition. It does not depend on the measurement of insulin, and once again it emphasizes the multi-factorial nature of the causes of atherosclerosis and its complications and the development of diabetes. More recently, a consensus definition developed by the International Diabetes Federation has emphasized the importance of central obesity.9 Individuals are defined as having a metabolic syndrome if they are centrally obese (defined as waist circumference ≥94 cm for Europid men and ≥80 cm for Europid women, with ethnicity specific values for other groups) and have any two of the following four factors:
  • raised triglyceride level: >150 mg/dL (1.7 mmol/L), or specific treatment for this lipid abnormality;
  • reduced HDL cholesterol: <40 mg/dL (0.9 mmol/L) in males and <50 mg/dL (1.1 mmol/L) in females, or specific treatment for this lipid abnormality;
  • raised blood pressure: systolic BP ≥130 mmHg or diastolic BP ≥85 mmHg, or treatment of previously diagnosed hypertension;
  • raised fasting plasma glucose (FPG): ≥100 mg/dL (5.6 mmol/L), or previously diagnosed Type 2 diabetes. (If >5.6 mmol/L or 100 mg/dL, OGTT is strongly recommended but is not necessary to define the presence of the syndrome.)
For patients with Type 2 diabetes, the treatment goals in the European guidelines include glycaemic targets. In addition, there are clearly defined blood pressure and lipid targets for patients with diabetes, supported by recent evidence from randomized controlled trials (Table 2). It is now clear that in the diabetic population and in patients with impaired glucose regulation, it is as important to address blood pressure and lipids as it is to address the glucose level. The European guidelines have lower blood pressure and lipid targets in patients with Type 2 diabetes than in other patient groups:
  • blood pressure <130/80 mmHg,
  • total cholesterol <4.5 mmol/L (<175 mg/dL),
  • LDL cholesterol <2.5 mmol/L (<100 mg/dL).
In terms of other prophylactic medication, there are five different classes of recommended drugs: antiplatelet therapies, beta-blockers, ACE-inhibitors, lipid lowering therapies (principally statins), and anticoagulants. These drugs have all been shown to reduce the risk of all-cause mortality in selected patient populations with established atherosclerotic disease. Aspirin (at least 75 mg) should be considered for all coronary heart disease patients and for those with cerebral atherosclerosis and peripheral atherosclerotic disease. Beta-blockers are recommended following myocardial infarction, and ACE-inhibitors are recommended in patients with symptoms or signs of heart failure at the time of myocardial infarction, or patients with chronic left ventricular dysfunction (ejection fraction <40%). Anticoagulants are recommended in selected patients with coronary heart disease.


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  		Table 2 Treatment goals in patients with Type 2 diabetes (adapted from De Backer et al.2)
 
In healthy high-risk individuals, the armamentarium is more limited because the trial evidence is more limited. Aspirin (75 mg) is recommended in treated hypertensive patients and in men at particularly high risk of coronary heart disease.

The lifestyle, risk factor, and therapeutic targets are important to achieve in our patients to reduce the incidence of first or recurrent clinical atherosclerotic events and to reduce the disability associated with cardiovascular disease. The data from INTERHEART4 can be used to assess to what extent the risk of developing myocardial infarction could be reduced if effective lifestyle change is achieved (Figure 4). It shows, for example, that if a person stops smoking, they reduce their risk by about 65%. By not smoking, eating fruit and vegetables, taking exercise, and moderate alcohol consumption, the risk of developing myocardial infarction could be reduced by 81%.



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  		Figure 4 Reduced risk of acute myocardial infarction associated with not smoking, daily fruit/vegetables, regular physical activity, and moderate alcohol. (Adapted with permission from Yusuf et al.4)

 

   Conclusion
Top
 Abstract
 Lifestyle modification
 Treatment targets
 Conclusion
Key points
 References
 
Implementing preventive strategies based on current scientific knowledge would avert the majority of premature coronary heart disease worldwide. For patients, this would mean both a better quality of life in terms of less disability and also a longer life. The challenge for physicians is to translate this knowledge into effective preventive care.


   Key points
Top
 Abstract
 Lifestyle modification
 Treatment targets
 Conclusion
 Key points
References
 

  • The priority group for cardiovascular disease prevention is patients with established cardiovascular disease.
  • In asymptomatic, apparently healthy individuals, preventive strategies should depend on the assessment of the individual's total cardiovascular risk.
  • The prevalence of overweight and obesity is increasing in patients with coronary heart disease. This has a major impact on cardiovascular risk and can also limit the response to antihypertensive and lipid lowering therapy.
  • The INTERHEART study has shown that nine modifiable risk factors account for 90% of the population attributable risk of myocardial infarction.

Conflict of interest: The author has lectured at Abbott-sponsored symposia.


   References
Top
 Abstract
 Lifestyle modification
 Treatment targets
 Conclusion
 Key points
 References
 

  1. European Society of Cardiology. Cardiovascular Diseases in Europe: Euro Heart Survey and National Registries of Cardiovascular Diseases and Patient Management. 2004 Sophia Antipolis, France: ESC.
  2. De Backer G, Ambrosioni E, Borch-Johnsen K et al. European Society of Cardiology Committee for Practice Guidelines. 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). Eur J Cardiovasc Prev Rehabil 2003;10(Suppl. 1):S1–S78.[CrossRef][ISI][Medline]
  3. Conroy RM, Pyorala K, Fitzgerald AP et al. SCORE project group. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J 2003;24:987–1003.[Abstract/Free Full Text]
  4. Yusuf S, Hawken S, Ounpuu S et al.; INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case–control study. Lancet 2004;364:937–952.[CrossRef][ISI][Medline]
  5. EUROASPIRE Study Group. EUROASPIRE: a European Society of Cardiology survey of secondary prevention of coronary heart disease: principal results. Eur Heart J 1997;18:1569–1582.[Abstract/Free Full Text]
  6. 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. Eur Heart J 2001;22:554–572.[Abstract/Free Full Text]
  7. EUROASPIRE Study Group. Clinical reality of coronary prevention guidelines: a comparison of EUROASPIRE I and II in nine countries. Lancet 2001;357:995–1001.[CrossRef][ISI][Medline]
  8. De Bacquer D, De Backer G, Cokkinos D et al. for the EUROASPIRE II study group. Overweight and obesity in patients with established coronary heart disease: are we meeting the challenge? Eur Heart J 2004;25:121–128.[Abstract/Free Full Text]
  9. International Diabetes Federation. The IDF consensus worldwide definition of the metabolic syndrome. http://www.idf.org (14 April 2005).

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