If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
2016 European Guidelines on cardiovascular disease prevention in clinical practice
The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR)
Corresponding author: Arno W. Hoes, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85500 (HP Str. 6.131), 3508 GA Utrecht, The Netherlands, Tel: +31 88 756 8193, Fax: +31 88 756 8099.
Action in Diabetes and Vascular disease: PreterAx and Diamicron MR Controlled Evaluation
AF
atrial fibrillation
AMI
acute myocardial infarction
apoA1
apolipoprotein A1
apoB
apolipoprotein B
ARB
angiotensin receptor blocker
BEUC
Bureau Européen des Unions de Consummateurs
BMI
body mass index (weight (kg)/height (m2))
BP
blood pressure
CAC
coronary artery calcium
CAD
coronary artery disease
CAPRIE
Clopidogrel versus Aspirin in Patients at Risk for Ischaemic Events
CARDS
Collaborative Atorvastatin Diabetes Study
CHANCE
Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events
CHARISMA
Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilisation, Management, and Avoidance
CI
confidence interval
CKD
chronic kidney disease
CR
cardiac rehabilitation
CT
computed tomography
CTT
Cholesterol Treatment Trialists’ Collaboration
CURE
Clopidogrel vs. Placebo in Patients with ACS without ST-segment elevation
CV
cardiovascular
CVD
cardiovascular disease
DALYs
disability-adjusted life years
DASH
Dietary Approaches to Stop Hypertension
DBP
diastolic blood pressure
DCCT
Diabetes Control and Complications Trial
DHA
docosahexaenoic acid
DM
diabetes mellitus
DPP-4
dipeptidyl peptidase-4
eGFR
estimated glomerular filtration rate
ECDA
European Chronic Disease Alliance
ECG
electrocardiogram
ED
erectile dysfunction
EHN
European Heart Network
EMA
European Medicines Agency
EPA
eicosapentaenoic acid
EPIC
European Prospective Investigation into Cancer and Nutrition
EPODE
Ensemble Prévenons l’Obésité des Enfants
ESC
European Society of Cardiology
EU
European Union
FDA
Food and Drug Administration (USA)
FDC
fixed dose combination
FH
familial hypercholesterolaemia
GLP-1
glucagon-like peptide 1
GP
general practitioner
GOSPEL
Global Secondary Prevention Strategies to Limit Event Recurrence After Myocardial Infarction
HbA1c
glycated haemoglobin
HBPM
home blood pressure measurements
HDL-C
high-density lipoprotein cholesterol
HF
heart failure
HF-ACTION
Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training
HOPE
Heart Outcomes Prevention Evaluation
HPS
Heart Protection Study
HRQoL
health-related quality of life
HR
heart rate
hsCRP
high-sensitivity C-reactive protein
HYVET
Hypertension in the Very Elderly Trial
ICD
International Classification of Diseases
IMT
intima–media thickness
INVEST
International Verapamil-Trandolapril Study
LDL-C
low-density lipoprotein cholesterol
Lp(a)
lipoprotein(a)
LV
left ventricle/left ventricular
LVH
left ventricular hypertrophy
MET
metabolic equivalent
MHO
metabolically healthy overweight/obesity
MI
myocardial infarction
MUFA
monounsaturated fatty acids
NGO
non-governmental organization
NHS
National Health Service (UK)
NICE
National Institute for Health and Care Excellence
NNT
number needed to treat
NRI
net reclassification index
NRT
nicotine replacement therapy
OASIS
Organization to Assess Strategies in Acute Ischemic Syndromes
ONTARGET
ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial
OSAS
obstructive sleep apnoea syndrome
OR
odds ratio
PA
physical activity
PAD
peripheral artery disease
PLATO
Ticagrelor vs. Clopidogrel in Patients with ACS with and without ST-segment elevation
PCOS
polycystic ovary syndrome
PCSK9
proprotein convertase subtilisin/kexin type 9
PROactive
Prospective Pioglitazone Clinical Trial in Macrovascular Events
PROGRESS
Perindopril Protection Against Recurrent Stroke Study
PROCAM
Prospective Cardiovascular Munster Study
PWV
pulse wave velocity
RA
rheumatoid arthritis
RCT
randomized controlled trial
RESPONSE
Randomised Evaluation of Secondary Prevention by Outpatient Nurse Specialists
RM
repetition maximum
ROS
reactive oxygen species
RPE
rating of perceived exertion
RR
relative risk
SAVOR-TIMI 53
Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus –Trombolysis in Myocardial Infarction
SBP
systolic blood pressure
SGLT2
sodium-glucose co-transporter 2
SNP
single nucleotide polymorphism
SCORE
Systematic Coronary Risk Estimation
SPARCL
Stroke Prevention by Aggressive Reduction in Cholesterol Levels
TIA
transient ischaemic attack
TRITON
Prasugrel vs. Clopidogrel in Patients with ACS
UKPDS
United Kingdom Prospective Diabetes Study
VADT
Veterans Affairs Diabetes Trial
VALUE
Valsartan Antihypertensive Long-Term Use Evaluation
VLDL
very low-density lipoprotein
VO2
oxygen uptake
WHO
World Health Organization
Tabled
1Classes of recommendations
Classes of recommendations
Tabled
1Level of evidence
Level of evidence
1. What is cardiovascular disease prevention?
1.1 Definition and rationale
Cardiovascular disease (CVD) prevention is defined as a coordinated set of actions, at the population level or targeted at an individual, that are aimed at eliminating or minimizing the impact of CVDs and their related disabilities.
CVD remains a leading cause of morbidity and mortality, despite improvements in outcomes. Age-adjusted coronary artery disease (CAD) mortality has declined since the 1980s, particularly in high-income regions.
CAD rates are now less than half what they were in the early 1980s in many countries in Europe, due to preventive measures including the success of smoking legislation. However, inequalities between countries persist and many risk factors, particularly obesity
National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants.
National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants.
have been increasing substantially. If prevention was practised as instructed it would markedly reduce the prevalence would markedly reduce the of CVD. It is thus not only prevailing risk factors that are of concern, but poor implementation of preventive measures as well.
EUROASPIRE IV: a European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries.
and (ii) at the individual level, i.e. in those subjects at moderate to high risk of CVD or patients with established CVD, by tackling unhealthy lifestyles (e.g. poor-quality diet, physical inactivity, smoking) and by optimising risk factors. Prevention is effective: the elimination of health risk behaviours would make it possible to prevent at least 80% of CVDs and even 40% of cancers.
Healthy lifestyle through young adulthood and the presence of low cardiovascular disease risk profile in middle age: the Coronary Artery Risk Development in (Young) Adults (CARDIA) study.
1.2 Development of the 6th Joint Task Force guidelines
The present guidelines represent an evidence-based consensus of the 6th European Joint Task Force involving 10 professional societies.
By appraising the current evidence and identifying remaining knowledge gaps in managing CVD prevention, the Task Force formulated recommendations to guide actions to prevent CVD in clinical practice. The Task Force followed the quality criteria for development of guidelines, which can be found at http://www.escardio.org/Guidelines-&-Education/Clinical-Practice-Guidelines/Guidelines-development/Writing-ESC-Guidelines. For simplification and in keeping with other European Society of Cardiology (ESC) guidelines, the ESC grading system based on classes of recommendation and levels of evidence has been maintained, recognising that this may be less suitable to measure the impact of prevention strategies, particularly those related to behavioural issues and population-based interventions.
This document has been developed to support healthcare professionals communicating with individuals about their cardiovascular (CV) risk and the benefits of a healthy lifestyle and early modification of their CV risk. In addition, the guidelines provide tools for healthcare professionals to promote population-based strategies and integrate these into national or regional prevention frameworks and to translate these in locally delivered healthcare services, in line with the recommendations of the World Health Organization (WHO) global status report on non-communicable diseases 2010.
European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): the Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts).
has been structured around four core questions: (i) What is CVD prevention? (ii) Who will benefit from prevention? (iii) How to intervene? (iv) Where to intervene?
Compared with the previous guidelines, greater emphasis has been placed on a population-based approach, on disease-specific interventions and on female-specific conditions, younger individuals and ethnic minorities. Due to space restrictions for the paper version, the chapter on disease-specific intervention is on the web, together with a few tables and figures for more detail see web addenda.
A lifetime approach to CV risk is important since both CV risk and prevention are dynamic and continuous as patients age and/or accumulate co-morbidities. This implies that, apart from improving lifestyle and reducing risk factor levels in patients with established CVD and those at increased risk of developing CVD, healthy people of all ages should be encouraged to adopt a healthy lifestyle. Healthcare professionals play an important role in achieving this in their clinical practice.
1.3 Cost-effectiveness of prevention
Key messages
•
Prevention of CVD, either by implementation of lifestyle changes or use of medication, is cost effective in many scenarios, including population-based approaches and actions directed at high-risk individuals.
•
Cost-effectiveness depends on several factors, including baseline CV risk, cost of drugs or other interventions, reimbursement procedures and implementation of preventive strategies.
Tabled
1Recommendation for cost-effective prevention of cardiovascular disease
Recommendation for cost-effective prevention of cardiovascular disease
aClass of recommendation.bLevel of evidence.cReference(s) supporting recommendations.
In 2009, costs related to CVD amounted to €106 billion, representing ∼9% of the total healthcare expenditure across the European Union (EU).
Thus, CVD represents a considerable economic burden to society and effective preventive measures are necessary. There is consensus in favour of an approach combining strategies to improve CV health across the population at large from childhood onward, with specific actions to improve CV health in individuals at increased risk of CVD or with established CVD.
Most studies assessing the cost-effectiveness of CVD prevention combine evidence from clinical research with simulation approaches, while cost-effectiveness data from randomized controlled trials (RCTs) are relatively scarce.
Long-term impact on healthcare resource utilization of statin treatment, and its cost effectiveness in the primary prevention of cardiovascular disease: a record linkage study.
Cost-effectiveness strongly depends on parameters such as the target population’s age, the overall population risk of CVD and the cost of interventions. Hence, results obtained in one country may not be valid in another. Furthermore, changes such as the introduction of generic drugs can considerably change cost-effectiveness.
A report from the National Institute for Health and Care Excellence (NICE) estimated that a UK national programme reducing population CV risk by 1% would prevent 25 000 CVD cases and generate savings of €40 million/year. CAD mortality rates could be halved by only modest risk factor reductions and it has been suggested that eight dietary priorities alone could halve CVD death.
In the last three decades, more than half of the reduction in CV mortality has been attributed to changes in risk factor levels in the population, primarily the reduction in cholesterol and blood pressure (BP) levels and smoking. This favourable trend is partly offset by an increase in other risk factors, mainly obesity and type 2 DM.
Several population interventions have efficiently modified the lifestyle of individuals. For example, increased awareness of how healthy lifestyles prevent CVD has helped to reduce smoking and cholesterol levels. Lifestyle interventions act on several CV risk factors and should be applied prior to or in conjunction with drug therapies. Also, legislation aimed at decreasing salt and the trans fatty acid content of foods and smoking habits is cost effective in preventing CVD.
Long-term impact on healthcare resource utilization of statin treatment, and its cost effectiveness in the primary prevention of cardiovascular disease: a record linkage study.
Importantly, a sizable portion of patients on lipid-lowering or BP-lowering drug treatment fails to take their treatment adequately or to reach therapeutic goals,
Most cost-effectiveness studies rely on simulation. More data, mainly from RCTs, are needed.
2. Who will benefit from prevention? When and how to assess risk and prioritize
2.1 Estimation of total cardiovascular risk
All current guidelines on the prevention of CVD in clinical practice recommend the assessment of total CVD risk since atherosclerosis is usually the product of a number of risk factors. Prevention of CVD in an individual should be adapted to his or her total CV risk: the higher the risk, the more intense the action should be.
The importance of total risk estimation in apparently healthy people before management decisions are made is illustrated in supplementary Figure A (see web addenda) and in Table 1 derived from the high-risk Systemic Coronary Risk Estimation (SCORE) chart (http://www.escardio.org/Guidelines-&-Education/Practice-tools/ CVD-prevention-toolbox/SCORE-Risk-Charts). This shows that a person with a cholesterol level of 7 mmol/L can be at 10 times lower risk than someone with a cholesterol level of 5 mmol/L if the former is a female and the latter is a male hypertensive smoker.
Table 1Impact of combinations of risk factors on risk
Table 1Impact of combinations of risk factors on risk
CVD = cardiovascular disease; F = female; M = male; SBP = systolic blood pressure.
A recent meta-analysis on CV risk reduction by treatment with BP-lowering drugs does, however, support the concept that absolute risk reduction is larger in those individuals at higher baseline risk.
This was confirmed in a further meta-analysis that also showed a greater residual risk during treatment in those at higher baseline risk, supporting earlier intervention.
Effects of blood pressure lowering on outcome incidence in hypertension: 3. Effects in patients at different levels of cardiovascular risk—overview and meta-analyses of randomized trials.
Effects of blood pressure lowering on outcome incidence in hypertension: 2. Effects at different baseline and achieved blood pressure levels—overview and meta-analyses of randomized trials.
Although clinicians often ask for decisional thresholds to trigger intervention, this is problematic since risk is a continuum and there is no exact point above which, for example, a drug is automatically indicated nor below which lifestyle advice may not usefully be offered.
The risk categories presented later in this section are to assist the physician in dealing with individual people. They acknowledge that although individuals at the highest levels of riskgain most from risk factor interventions, most deaths in a community come from those at lower levels of risk, simply because they are more numerous compared with high-risk individuals. Thus a strategy for individuals at high risk must be complemented by public health measures to encourage a healthy lifestyle and to reduce population levels of CV risk factors.
It is essential for clinicians to be able to assess CV risk rapidly and with sufficient accuracy. This realization led to the development of the risk chart used in the 1994 and 1998 Guidelines. This chart, developed from a concept pioneered by Anderson,
used age, sex, smoking status, blood cholesterol and systolic BP (SBP) to estimate the 10- year risk of a first fatal or non-fatal CAD event. There were several problems with this chart, which are outlined in the Fourth Joint European Guidelines on prevention.
European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): the Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts).
European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).
The SCORE charts have been developed to estimate risk in both high- and low-risk European populations; its applicability to non-Caucasian populations has not been examined.
2.2 When to assess total cardiovascular risk?
Tabled
1Recommendations for cardiovascular risk assessment
Recommendations for cardiovascular risk assessment
BP = blood pressure; CV = cardiovascular; CVD = cardiovascular disease; DM = diabetes mellitus.aClass of recommendation.bLevel of evidence.
Screening is the identification of unrecognized disease or, in this case, of an unknown increased risk of CVD in individuals without symptoms. CV risk assessment or screening can be done opportunistically or systematically. Opportunistic screening means without a predefined strategy, but is done when the opportunity arises [e.g. when the individual is consulting his or her general practitioner (GP) for some other reason]. Systematic screening can be done in the general population as part of a screening programme or in targeted subpopulations, such as subjects with a family history of premature CVD or familial hyperlipidaemia.
While the ideal scenario would be for all adults to have their risk assessed, this is not practical in many societies. The decision about who to screen must be made by individual countries and will be resource dependent.
In a meta-analysis, GP-based health checks on cholesterol, BP, body mass index (BMI) and smoking were effective in improving surrogate outcomes, especially in high-risk patients.
A large study of CV risk assessment in the general population found that although there were overall improvements in risk factors, there was no impact on CV outcomes at the population level.
A Cochrane review of RCTs using counselling or education to modify CV risk factors in adults from the general population, occupational groups or those with specific risk factors (i.e. DM, hypertension) concluded that risk factor improvements were modest and interventions did not reduce total or CV mortality in general populations, but reduced mortality in high-risk hypertensive and DM populations.
Although the benefits of treating asymptomatic conditions such as hypertension, DM and dyslipidaemia on morbidity and mortality outcomes have been documented, a Cochrane review of the existing trials concluded that general health checks (including screening for these conditions) do not reduce all-cause or CV morbidity or mortality.
However, most studies were performed three to four decades ago, and thus risk factor interventions were not contemporary. Perhaps application of medical treatment in addition to the lifestyle interventions that were the core component of most trials would improve efficacy.
Most guidelines recommend a mixture of opportunistic and systematic screening.
European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): the Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts).
Lipid Modification: Cardiovascular Risk Assessment and the Modification of Blood Lipids for the Primary and Secondary Prevention of Cardiovascular Disease.
National Institute for Health and Care Excellence,
London2014
European Association for Cardiovascular Prevention & Rehabilitation
Reiner Z.
Catapano A.L.
De Backer G.
Graham I.
Taskinen M.R.
Wiklund O.
Agewall S.
Alegria E.
Chapman M.J.
Durrington P.
Erdine S.
Halcox J.
Hobbs R.
Kjekshus J.
Filardi P.P.
Riccardi G.
Storey R.F.
Wood D.
ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) the European Atherosclerosis Society (EAS).
Screening in people at relatively low risk of CVD is not particularly effective in reducing the risk of CV events. The costs of such screening interventions are high and these resources may be better used in people at higher CV risk or with established CVD. In many countries, GPs have a unique role in identifying individuals at risk of but without established CVD and assessing their eligibility for intervention (see section 4a.1.1). A modelling study based on the European Prospective Investigation of Cancer–Norfolk (EPIC-Norfolk) cohort data concluded that, compared with the National Health Service (NHS) national strategy to screen all adults 40–74 years of age for CV risk, inviting the 60% of the population at the highest risk according to an integrated risk score was equally effective in preventing new cases of CVD and had potential cost savings.
A general concern in screening, including CV risk assessment, is its potential to do harm. False positive results can cause unnecessary concern and medical treatment. Conversely, false negative results may lead to inappropriate reassurance and a lack of lifestyle changes. However, current data suggest that participating in CV screening in general does not cause worry in those who are screened.
Psychological consequences of screening for cardiovascular risk factors in an un-selected general population: results from the Inter99 randomised intervention study.
More research is needed on how certain subgroups, such as older people, the socially deprived and ethnic minorities, react to screening.
Despite limited evidence, these guidelines recommend a systematic approach to CV risk assessment targeting populations likely to be at higher CV risk, such as those with a family history of premature CVD. Thus systematic CV risk assessment in men <40 years of age and women <50 years of age with no known CV risk factors is not recommended. Additionally, screening of specific groups with jobs that place other people at risk, e.g. bus drivers and pilots, may be reasonable, as is screening for CV risk factors in women before prescribing combined oral contraception, although there are no data to support the beneficial effects. Beyond this, systematic CV risk assessment in adults <40 years of age with no known CV risk factors is not recommended as a main strategy due to the low cost-effectiveness. Systematic CV assessment may be considered in adult men >40 years of age and in women >50 years of age or post-menopausal with no known CV risk factors. Risk assessment is not a one-time event; it should be repeated, for example, every 5 years.
2.3 How to estimate total cardiovascular risk?
Key messages
•
In apparently healthy persons, CV risk in general is the result of multiple, interacting risk factors. This is the basis for the total CV risk approach to prevention.
•
SCORE, which estimates the 10 year risk of fatal CVD, is recommended for risk assessment and can assist in making logical management decisions and may help to avoid both under- and overtreatment. Validated local risk estimation systems are useful alternatives to SCORE.
•
Individuals automatically at high to very high CV risk (Table 5) do not need the use of a risk score and require immediate attention to risk factors.
•
In younger persons, a low absolute risk may conceal a very high relative risk and use of the relative risk chart or calculation of their “risk age” may help in advising them of the need for intensive preventive efforts.
•
While women are at lower CV risk than men, their risk is deferred by ∼10 years rather than avoided.
•
The total risk approach allows flexibility; if perfection cannot be achieved with one risk factor, trying harder with others can still reduce risk.
Tabled
1Recommendation for how to estimate cardiovascular risk
Recommendation for how to estimate cardiovascular risk
CV = cardiovascular; DM = diabetes mellitus; SCORE = Systematic Coronary Risk Estimation.aClass of recommendation.bLevel of evidence.cReference(s) supporting recommendations.
2.3.1 Ten-year cardiovascular risk
Many CV risk assessment systems are available for use in apparently healthy individuals (Table 2), including Framingham,
Adding social deprivation and family history to cardiovascular risk assessment: the ASSIGN score from the Scottish Heart Health Extended Cohort (SHHEC).
Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the prospective cardiovascular Munster (PROCAM) study.
2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
A novel risk score to predict cardiovascular disease risk in national populations (Globorisk): a pooled analysis of prospective cohorts and health examination surveys.
In practice, most risk estimation systems perform rather similarly when applied to populations recognizably comparable to those from which the risk estimation system was derived. Since 2003, the European Guidelines on CVD prevention in clinical practice recommend use of the SCORE system, because it is based on large, representative European cohort datasets. The SCORE risk function has been externally validated.
ACC = American College of Cardiology; AHA = American Heart Association; ARIC = Atherosclerosis Risk in Communities; ATP = Adult Treatment Panel; BMI = body mass index; BP = blood pressure; CAD = coronary artery disease; CARDIA = Coronary Artery Risk Development in Young Adults; CHS = Cardiovascular Health Study; CVD = cardiovascular disease; DM = diabetes mellitus; HDL-C = high-density lipoprotein cholesterol; J BS = Joint British Societies; LDL-C = low-density lipoprotein cholesterol; NCEP = National Cholesterol Education Program; NICE = National Institute for Health and Care Excellence; no. cigs = number of cigarettes; PROCAM = Prospective Cardiovascular Munster Study; SBP = systolic blood pressure; SIGN = Scottish Intercollegiate Guidelines Network; SHHEC = Scottish Heart Health Extended Cohort.
Table 3 lists the advantages of the SCORE risk charts.
Table 3Advantages and limitations in using the SCORE risk charts
Table 3Advantages and limitations in using the SCORE risk charts
The SCORE system estimates the 10 year risk of a first fatal atherosclerotic event. All International Classification of Diseases (ICD) codes that could reasonably be assumed to be atherosclerotic are included, including CAD, stroke and aneurysm of the abdominal aorta. Traditionally most systems estimated CAD risk only; however, more recently a number of risk estimation systems have changed to estimate the risk of all CVDs.
2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
The choice of CV mortality rather than total (fatal plus non-fatal) events was deliberate, although not universally popular. Non-fatal event rates are critically dependent upon definitions and the methods used in their ascertainment. Critically, the use of mortality allows recalibration to allow for time trends in CV mortality. Any risk estimation system will overpredict in countries in which mortality has fallen and underpredict in those in which it has risen. Recalibration to allow for secular changes can be undertaken if good quality, up-to-date mortality and risk factor prevalence data are available. Data quality does not permit this for non-fatal events. For these reasons, the CV mortality charts were produced and have been recalibrated for a number of European countries.
Naturally, the risk of total fatal and non-fatal events is higher, and clinicians frequently ask for this to be quantified. The SCORE data indicate that the total CV event risk is about three times higher than the risk of fatal CVD for men, so that a SCORE risk of fatal CVD of 5% translates into a fatal plus non-fatal CV risk of ∼15%; the multiplier is about four in women and somewhat lower than three in older persons, in whom a first event is more likely to be fatal.
As noted in the introduction, thresholds to trigger certain interventions are problematic since risk is a continuum and there is no threshold at which, for example, a drug is automatically indicated. Obviously, decisions on whether treatment is initiated should also be based on patient preferences.
A particular problem relates to young people with high levels of risk factors, where a low absolute risk may conceal a very high relative risk requiring intensive lifestyle advice. Several approaches to communicating about risk to younger people are presented below (refer also to section 2.5.1). These include use of the relative risk chart or ’risk age’ or ’lifetime risk’. The aim is to communicate that lifestyle changes can reduce the relative risk substantially as well as reduce the increase in risk that occurs with ageing.
Another problem relates to older people. In some age categories, the vast majority, especially of men, will have estimated CV death risks exceeding the 5–10% level, based on age (and gender) only, even when other CV risk factor levels are low. This could lead to excessive use of drugs in the elderly. This issue is dealt with later (see section 2.3.5). It should be noted that RCT evidence to guide drug treatments in older persons is limited (refer to section 2.5.2).
The role of high-density lipoprotein cholesterol (HDL-C) in risk estimation has been systematically re-examined using the SCORE database.
Prevention of coronary heart disease in clinical practice. Recommendations of the Task Force of the European Society of Cardiology, European Atherosclerosis Society and European Society of Hypertension.
The high-density lipoprotein-adjusted SCORE model worsens SCORE-based risk classification in a contemporary population of 30,824 Europeans: the Copenhagen General Population Study.
Assessing HDL-C is particularly important at levels of risk just below the threshold for intensive risk modification of 5%, where many of these subjects will qualify for intensive advice if their HDL-C is low.
SCORE charts incorporating HDL-C are illustrated in supplementary Figures B-I (see web addenda). In these charts, HDL-C is used categorically. The electronic version of SCORE, HeartScore (http://www.HeartScore.org), has been modified to take HDL-C into account on a continuous basis and is therefore more accurate.
The role of a plasma triglyceride as a predictor of CVD has been debated for many years. Fasting triglycerides relate to risk in univariable analyses, but the effect is attenuated by adjustment for other factors, especially HDL-C.
Dealing with the impact of additional risk factors such as body weight, family history and newer risk markers is difficult within the constraint of a paper chart. It should be stressed, however, that although many other risk factors have been identified, their contribution is generally very modest to both absolute CV risk estimations and in terms of reclassification of an individual to another risk category
Table 4Examples of risk modifiers that are likely to have reclassification potential (see following sections for
Table 4Examples of risk modifiers that are likely to have reclassification potential (see following sections for
ABI = ankle-brachial blood pressure index; BMI = body mass index; CVD = cardiovascular disease; CT = computed tomography.
The SCORE risk charts are shown in Figure 1, Figure 2, Figure 3, Figure 4, including a chart of relative risks (Figure 3). Instructions on their use follow.
Figure 1SCORE chart: 10-year risk of fatal cardiovascular disease in populations of countries at high cardiovascular risk based on the following risk factors: age, sex, smoking, systolic blood pressure, total cholesterol. CVD = cardiovascular disease; SCORE = Systematic Coronary Risk Estimation.
Figure 2SCORE chart: 10-year risk of fatal cardiovascular disease in populations of countries at low cardiovascular risk based on the following risk factors: age, sex, smoking, systolic blood pressure, total cholesterol. CVD = cardiovascular disease; SCORE = Systematic Coronary Risk Estimation.
Figure 4SCORE chart (for use in high-risk European countries) illustrating how the approximate risk age can be read off the chart. SCORE = Systematic Coronary Risk Estimation.
Please note that Figure 3 shows relative not absolute risk. Thus a person in the top right-hand box, with multiple CV risk factors, has a risk that is 12 times greater than a person in the bottom left with normal risk factor levels. This may be helpful when advising a young person with a low absolute but high relative risk of the need for lifestyle change.
2.3.2 Cardiovascular risk age
The risk age of a person with several CV risk factors is the age of a person of the same gender with the same level of risk but with ideal levels of risk factors. Thus a 40-year-old with high levels of some risk factors may have the risk age of a 60-year-old (Figure 4), because the risk equals that of a 60-year-old with ideal risk factor levels (i.e. nonsmoking, total cholesterol of 4 mmol/L and BP of 120 mmHg).
Risk age is an intuitive and easily understood way of illustrating the likely reduction in life expectancy that a young person with a low absolute but high relative risk of CVD will be exposed to if preventive measures are not adopted.
Table A showing different risk factor combinations is included in the web addenda to provide a more accurate estimation of risk ages. Risk age is also automatically calculated as part of the latest revision of HeartScore.
Risk age has been shown to be independent of the CV endpoint used,
which bypasses the dilemma of whether to use a risk estimation system based on CV mortality or on total CV events. Risk age can be used in any population regardless of baseline risk and secular changes in mortality, and therefore avoids the need for recalibration.
At present, risk age is recommended to help communicate about risk, especially to younger people with a low absolute risk but a high relative risk.
2.3.3 Lifetime vs. 10-year cardiovascular risk estimation
Conventional CV risk prediction schemes estimate the 10 year risk of CV events. Lifetime CV risk prediction models identify high-risk individuals both in the short and long term. Such models account for predicted risk in the context of competing risks from other diseases over the remaining expected lifespan of an individual.
Notably, 10 year risk identifies individuals who are most likely to benefit from drug therapy in the near term. Drug treatment starts to work quite rapidly, and drug treatment can be largely informed by short-term risk, such as 10 year risk. One problem with short-term risk is that it is mostly governed by age and consequently few younger individuals, in particular women, reach treatment thresholds. It has therefore been argued that lifetime risk estimation may enhance risk communication, particularly among younger individuals and women.
Evidence for the role of lifetime risk in treatment decisions is lacking. Sufficient data for robust lifetime risk estimations, as well as meaningful risk categorization thresholds, are also lacking. Providing lifetime CV risk estimates for some groups at high risk of mortality due to competing non-CVD causes can be difficult to interpret. Importantly, evidence of the benefits of lifelong preventive therapy (e.g. BP- or lipid-lowering drugs) in younger individuals with low short-term but higher lifetime risks is lacking. For these reasons, we do not recommend that risk stratification for treatment decisions be based on lifetime risk. However, like risk age and relative risk, it may be a useful tool in communicating about risk to individuals with high risk factor levels but who are at a low 10 year absolute risk of CV events, such as some younger people. Whatever approach is used, if absolute risk is low, a high relative risk or risk age signals the need for active lifestyle advice and awareness that drug treatment may need consideration as the person ages. Both risk age and lifetime risk are closer to relative than absolute risk, and none provides an evidence base for drug treatment decisions.
2.3.4 Low-risk, high-risk and very-high-risk countries
The countries considered here are those with national cardiology societies that belong to the ESC, both European and non-European.
2.3.4.1 What are low-risk countries?
The fact that CVD mortality has declined in many European countries means that more now fall into the low-risk category. While any cut-off point is arbitrary and open to debate, in these guidelines the cut-off points for calling a country ’low risk’ are based on age-adjusted 2012 CVD mortality rates in those 45-74 years of age (<225/100 000 in men and < 175/100 000 in women).
Thus the following countries are defined as low risk: Andorra, Austria, Belgium, Cyprus, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Israel, Italy, Luxembourg, Malta, Monaco,The Netherlands, Norway, Portugal, San Marino, Slovenia, Spain, Sweden, Switzerland and the United Kingdom.
2.3.4.2 What are high-risk and very-high-risk countries?
High-risk countries are Bosnia and Herzegovina, Croatia, Czech Republic, Estonia, Hungary, Lithuania, Montenegro, Morocco, Poland, Romania, Serbia, Slovakia, Tunisia and Turkey.
Very-high-risk countries present levels of risk that are more than double that of low-risk countries (i.e. CVD mortality >450/100 000 for men and >350/100 000 for women). Additionally, the male:female ratio is smaller than in low-risk countries, suggesting a major problem for women. The very high-risk countries are Albania, Algeria, Armenia, Azerbaijan, Belarus, Bulgaria, Egypt, Georgia, Kazakhstan, Kyrgyzstan, Latvia, former Yugoslav Republic of Macedonia, Moldova, Russian Federation, Syrian Arab Republic, Tajikistan, Turkmenistan, Ukraine and Uzbekistan.
2.3.5 How to use the risk estimation charts
•
The SCORE charts are used in apparently healthy people, not for those with established CVD or at very high risk or high risk for other reasons [e.g. DM (see section 3a.8) or chronic kidney disease (CKD; see section 2.4.5.1)], who need intensive risk advice anyway.
•
Use of the low-risk chart is recommended for the countries listed above. Use of the high-risk chart is recommended for all other European and Mediterranean countries, taking into account that the high-risk charts may underestimate the risk in very-high-risk countries (see above). Note that several countries have undertaken national recalibrations to allow for time trends in mortality and risk factor distributions. Such charts are likely to better represent risk levels.
•
To estimate a person’s 10 year risk of CV death, find the table for their gender, smoking status and (nearest) age. Within the table, find the cell nearest to the person’s BP and total cholesterol. Risk estimates will need to be adjusted upwards as the person approaches the next age category.
While no threshold is universally applicable, the intensity of advice should increase with increasing risk. The effect of interventions on the absolute probability of developing a CV event increases with an increasing baseline risk; that is, the number of individuals needed to treat (NNT) to prevent one event decreases with increasing risk.
- Low- to moderate-risk persons (calculated SCORE <5%): should be offered lifestyle advice to maintain their low- to moderate-risk status.
– High-risk persons (calculated SCORE ≥5% and <10%): qualify for intensive lifestyle advice and may be candidates for drug treatment.
– Very-high-risk persons (calculated SCORE ≥10%): drug treatment is more frequently required. In persons >60 years of age, these thresholds should be interpreted more leniently, because their age-specific risk is normally around these levels, even when other CV risk factor levels are ’normal’. In particular, uncritical initiation of drug treatments of all elderly with risks greater than the 10% threshold should be discouraged.
Use of the risk charts should be qualified by knowledge of the following aspects:
•
The charts assist in risk estimation but must be interpreted in light of the clinician’s knowledge and experience and in view of the factors that may modify the calculated risk (see below).
•
Relative risks may be high in young persons, even if 10 year absolute risks are low, because events usually occur later in life. The relative risk chart or estimating risk age may be helpful in identifying and counselling such persons.
•
The lower risk in women is explained by the fact that risk is deferred by 10 years—the risk of a 60-year-old woman is similar to that of a 50-year-old man. Ultimately, more women than men die of CVD.
•
The charts may be used to give some indication of the effects of reducing risk factors, given that there will be a time lag before risk reduces and that the results of RCTs in general give better estimates of the benefits of interventions. Those who stop smoking generally halve their risk.
2.3.6 Modifiers of calculated total cardiovascular risk
Apart from the conventional major CV risk factors included in the risk charts, there are other risk factors that could be relevant for assessing total CVD risk. The Task Force recommends additional risk factor assessment if such a risk factor improves risk classification [e.g. by calculation of a net reclassification index (NRI)] and if the assessment is feasible in daily practice. In general, reclassification is of most value when the individual’s risk lies close to a decisional threshold, such as a SCORE risk of 5%. In very-high-risk or very-low-risk situations, the impact of additional risk factors is unlikely to alter management decisions. While the presence of risk modifiers may move an individual’s estimated risk upward, absence of these modifiers should lead to lowering an individual’s estimated risk.
Table 4 lists examples of factors that fulfil the aforementioned criteria. Several other factors that are frequently discussed in the literature, but may not have the ability to reclassify subjects, are discussed in subsequent paragraphs. Also discussed further in this section are the roles of ethnicity and of specific conditions or diseases that may be associated with a higher than calculated risk, such as CKD, autoimmune diseases, etc. The way modifiers are related to CV risk may be very different. Social deprivation and being overweight, for example, are important as ’causes of the causes’ of CVD, in that they may be associated with higher levels of conventional risk factors. Family history may reflect a shared environment, genetic factors or both. Markers such as computed tomography (CT) calcium scoring are indicators of disease rather than risk factors for future disease.
2.3.7 Risk categories: priorities
Individuals at highest risk gain most from preventive efforts, and this guides the priorities, which are detailed in Table 5.
Table 5Risk categories
Table 5Risk categories
ACS = acute coronary syndrome; AMI = acute myocardial infarction; BP = blood pressure; CKD = chronic kidney disease; DM = diabetes mellitus; GFR = glomerular filtration rate; PAD = peripheral artery disease; SCORE = systematic coronary risk estimation; TIA = transient ischaemic attack.
2.3.8 Risk factor targets
Risk factor goals and target levels for important CV risk factors are presented in Table 6.
Table 6Risk factor goals and target levels for important cardiovascular risk factors
Table 6Risk factor goals and target levels for important cardiovascular risk factors
BMI = body mass index; HbAlc = glycated haemoglobin; HDL-C = high-densitylipoprotein cholesterol; LDL-C = low density lipoprotein cholesterol.aBlood pressure <140/90 mmHg is the general target. The target can be higher in frail elderly, or lower in most patients with DM (see chapter 3.a.8) and in some (very) high-risk patients without DM who can tolerate multiple blood pressure lowering drugs (see chapter 3.a.9).bNon-HDL-C is a reasonable and practical alternative target because it does not require fasting. Non HDL-C secondary targets of <2.6, <3.3 and <3.8 mmol/L (<100, <130 and <145 mg/dL) are recommended for very high, high and low to moderate risk subjects, respectively. See section 3a.7.10 for more details.cA view was expressed that primary care physicians might prefer a single general LDL-C goal of 2.6 mmol/L (100 mg/dL). While accepting the simplicity of this approach and that it could be useful in some settings, there is better scientific support for the three targets matched to level of risk.dThis is the general recommendation for those at very high-risk. It should be noted that the evidence for patients with CKD is less strong.
2.3.9 Conclusions
Estimation of total CV risk remains a crucial part of the present guidelines. The priorities (risk categories) defined in this section are for clinical use and reflect the fact that those at highest risk of a CVD event gain most from preventive measures. This approach should complement public actions to reduce community risk factor levels and promote a healthy lifestyle. The principles of risk estimation and the definition of priorities reflect an attempt to make complex issues simple and accessible. Their very simplicity makes them vulnerable to criticism. Above all, they must be interpreted in light of the physician’s detailed knowledge of his/her patient and in light of local guidance and conditions.
Gaps in evidence
•
There are no recent RCTs of a total risk approach to risk assessment or risk management.
•
The young, women, older people and ethnic minorities continue to be underrepresented in clinical trials.
•
A systematic comparison of current international guidelines is needed to define areas of agreement and the reasons for discrepancies.
2.4 Other risk markers
2.4.1 Family history/(epi)genetics
Key messages
•
Family history of premature CVD in first-degree relatives, before 55 years of age in men and 65 years of age in women, increases the risk of CVD.
•
Several genetic markers are associated with an increased risk of CVD, but their use in clinical practice is not recommended.
Tabled
1Recommendations for assessment of family history/(epi)genetics
Recommendations for assessment of family history/(epi)genetics
CVD = cardiovascular disease.aClass of recommendation.bLevel of evidence.cReference(s) supporting recommendations.
2.4.1.1 Family history
Familial history of premature CVD is a crude but simple indicator of the risk of developing CVD, reflecting both the genetic trait and the environment shared among household members.
In the few studies that simultaneously assessed and reported the effects of family history and genetic scores, family history remained significantly associated with the incidence of CVD after adjusting for the genetic scores.
and that conventional CV risk factors can partly explain the impact of family history.
A family history of premature CVD is simple, inexpensive information that should be part of the CV risk assessment in all subjects. Family history can be a risk modifier to optimal management after the calculated risk using SCORE lies near a decisional threshold: a positive family history would favour more intensive interventions, while a negative family history would translate into less intensive treatment.
Genetic screening and counselling is effective in some conditions, such as familial hypercholesterolaemia (FH) (see section 3a.7.9). This paragraph will focus on genetic screening for high CV risk in the general population.
Several recent genome-wide association studies have identified candidate genes associated with CVD. Since the effect of each genetic polymorphism is small, most studies have used genetic scores to summarize the genetic component. There is a lack of consensus regarding which genes and their corresponding single nucleotide polymorphisms (SNPs) should be included in agenetic risk score and which method should be used to calculate the genetic score.
The association of genetic scores with incident CVD has been prospectively studied, adjusting for the main CV risk factors, and most studies have found a significant association, with the relative risks varying between 1.02 and 1.49 per increase in one score unit.
The ability of genetic scores to predict CV events beyond traditional CV risk factors (i.e. defined by the NRI) was found in about half of the studies. The NRI is a statistical measure quantifying the usefulness of adding new variables to a risk prediction equation.
The biggest improvements in the NRI were observed in participants at intermediate risk, while little or no improvement was observed in participants at high risk.
One study estimated that one additional CAD event for every 318 people screened at intermediate risk could be prevented by measuring the CAD-specific genetic score in addition to established risk factors.
A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring,.
Genetic variants identified in a European genome-wide association study that were found to predict incident coronary heart disease in the atherosclerosis risk in communities study.
Recently, a genetic risk score based on 27 genetic variants enabled the identification of subjects at increased risk of CAD, who would benefit the most from statin therapy, even after adjustment for family history.
and replication studies are needed to confirm positive findings.
Currently, many commercial tests are available, allowing an almost complete assessment of an individual’s genome, and strong pressure is being applied to use this information to predict genetic risk and to make genetic testing a routine measure.
Given the lack of agreement regarding which genetic markers should be included, how genetic risk scores should be calculated and uncertainties about improvement in CV risk prediction, the use of genetic markers for the prediction of CVD is not recommended.
2.4.1.3 Epigenetics
Epigenetics studies the chemical changes in DNA that affect gene expression. Methylation of genes related to CV risk factors is associated with variation in CV risk factor levels,
No information exists, however, regarding the effect of epigenetic markers in improving CVD risk prediction beyond conventional risk factors. Thus, epigenetic screening of CVD is not recommended.
Gaps in evidence
•
The impact of adding family history to the current SCORE risk equation should be assessed.
•
Future studies should assess the power of different genetic risk scores to improve CVD risk prediction in several different populations, the number of events prevented and the cost-effectiveness of including genetic data in the risk assessment.
2.4.2 Psychosocial risk factors
Key messages
•
Low socio-economic status, lack of social support, stress at work and in family life, hostility, depression, anxiety and other mental disorders contribute to the risk of developing CVD and a worse prognosis of CVD, with the absence of these items being associated with a lower risk of developing CVD and a better prognosis of CVD.
•
Psychosocial risk factors act as barriers to treatment adherence and efforts to improve lifestyle, as well as to promoting health in patients and populations.
Tabled
1Recommendation for assessment of psychosocial risk factors
Recommendation for assessment of psychosocial risk factors
aClass of recommendation.bLevel of evidence.cReference(s) supporting recommendations.
Low socio-economic status, defined as low educational level, low income, holding a low-status job or living in a poor residential area, confer an increased risk of CAD; the relative risk (RR) of CAD mortality risk is 1.3–2.0.
Adding social deprivation and family history to cardiovascular risk assessment: the ASSIGN score from the Scottish Heart Health Extended Cohort (SHHEC).
People who are isolated or disconnected from others are at increased risk of developing and dying prematurely from CAD. Similarly, a lack of social support increases CAD risk and worsens the prognosis of CAD.
Acute mental stressors may act as triggers of acute coronary syndrome (ACS). These stressors include exposure to natural catastrophes, as well as personal stressors (e.g. defeat or other serious life events) resulting in acute strong negative emotions (e.g. outbursts of anger or grief).
After the death of a significant person, the incidence rate of acute myocardial infarction (AMI) is elevated 21-fold during the first 24 hours, declining steadily during the subsequent days.
Chronic stress at work (e.g. long working hours, extensive overtime work, high psychological demands, unfairness and job strain) predicts premature incident CAD in men [relative risk (RR) ∼1.2–1.5].
Long working hours and risk of coronary heart disease and stroke: a systematic review and meta-analysis of published and unpublished data for 603 838 individuals.
Psychosocial aspects in cardiac rehabilitation: from theory to practice. A position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation of the European Society of Cardiology.
Vital exhaustion, most likely representing somatic symptoms of depression, significantly contributed to incident CAD (population attributable risk 21.1% in women and 27.7% in men). The NRI improved significantly.
Psychosocial aspects in cardiac rehabilitation: from theory to practice. A position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation of the European Society of Cardiology.
Hostility is a personality trait, characterized by extensive experience of mistrust, rage and anger and the tendency to engage in aggressive, maladaptive social relationships. A meta-analysis confirmed that anger and hostility are associated with a small but significant increased riskfor CV events in both healthy and CVD populations (RR 1.2).
The type D (’distressed’) personality involves an enduring tendency to experience a broad spectrum of negative emotions (negative affectivity) and to inhibit self-expression in relation to others (social inhibition). The type D personality has been shown to predict poor prognosis in patients with CAD (RR 2.2).
In most situations, psychosocial risk factors cluster in individuals and groups. For example, both women and men of lower socio-economic status and/or with chronic stress are more likely to be depressed, hostile and socially isolated.
The INTERHEART study has shown that a cluster of psychosocial risk factors (i.e. social deprivation, stress at work or in family life and depression) is associated with increased risk for myocardial infarction (MI) (RR 3.5 for women and 2.3 for men). The population attributable risk was 40% in women and 25% in men.
Mechanisms that link psychosocial factors to increased CV risk include unhealthy lifestyle [more frequent smoking, unhealthy food choices and less physical activity (PA)] and low adherence to behaviour change recommendations or CV medication.
In addition, depression and/or chronic stress are associated with alterations in autonomic function, in the hypothalamic–pituitary axis and in other endocrine markers, which affect haemostatic and inflammatory processes, endothelial function and myocardial perfusion.
Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association.
Assessment of psychosocial factors in patients and persons with CV risk factors should be considered for use as risk modifiers in CV risk prediction, especially in individuals with SCORE risks near decisional thresholds. In addition, psychosocial factors can help identify possible barriers to lifestyle changes and adherence to medication. Standardized methods are available to assess psychosocial factors in many languages and countries.
Alternatively, a preliminary assessment of psychosocial factors can be made within the physicians’ clinical interview, as shown in Table 7.
Table 7Core questions for the assessment of psychosocial risk factors in clinical practice
Table 7Core questions for the assessment of psychosocial risk factors in clinical practice
No more than a minimum education according to the requirement of the country and/or a ’yes’ for one or more items indicate an increased CV risk and could be applied as a modifier of CV risk (see Chapter 2.3.6). The management of psychosocial risk factors should be addressed according to Chapter 3a.2.
Gap in evidence
•
It remains unknown whether routine screening for psychosocial risk factors contributes to fewer future cardiac events.
2.4.3 Circulating and urinary biomarkers
Key messages
•
CV circulating and urinary biomarkers have either no or only limited value when added to CVD risk assessment with the SCORE system.
•
There is evidence of publication bias in the field of novel biomarkers of CV risk, leading to inflated estimates of strength of association and potential added value.
Tabled
1Recommendation for assessment of circulating and urinary biomarkers
Recommendation for assessment of circulating and urinary biomarkers
aClass of recommendation.bLevel of evidence.cReference(s) supporting recommendations.
In general, biomarkers can be classified into inflammatory (e.g. high-sensitivity C-reactive protein (hsCRP, fibrinogen), thrombotic (e.g. homocysteine, lipoprotein-associated phospholipase A2), glucose- and lipid-related markers (e.g. apolipoproteins) and organ-specific markers (e.g. renal, cardiac). However, for the purpose of overall CV risk estimation, these distinctions are generally not relevant. Also, from the perspective of risk stratification (i.e. prediction of future CV events), the question of whether a biomarker is causally related to CVD or may be a marker of preclinical disease is equally irrelevant.
Among the most extensively studied and discussed biomarkers is hsCRP. This biomarker has shown consistency across large prospective studies as a risk factor integrating multiple metabolic and low-grade inflammatory factors, with RRs approaching those of classical CV risk factors. However, its contribution to the existing methods of CV risk assessment is probably small.
Meta-analyses and systematic reviews suggest that the vast majority of other circulating and urinary biomarkers have no or limited proven ability to improve risk classification. However, the extent to which they have been tested for their ability to add value to risk stratification varies considerably,
Organ-specific biomarkers may be useful to guide therapy in specific circumstances (e.g. albuminuria in hypertension or DM may predict kidney dysfunction and warrant renoprotective interventions) (see section 3a).
If, despite these recommendations, biomarkers are used as risk modifiers, it is important to note that having an unfavourable biomarker profile may be associated with a somewhat higher risk, but also that a favourable profile is associated with a lower risk than calculated. The degree to which the calculated risk is affected by biomarkers is generally unknown, but almost universally smaller than the (adjusted) RRs reported for these biomarkers in the literature.
Hence, in these patients, particularly with a moderate risk profile, only relatively small adjustments in calculated risk are justifiable, and patients who are clearly at high or low risk should not be reclassified based on biomarkers.
Not all potentially useful circulatory and urinary biomarkers have undergone state-of-the-art assessment of their added value in CV risk prediction on top of conventional risk factors.
•
Biomarkers may be useful in specific subgroups, but this has been addressed in only a limited number of studies.
•
The role of metabolomics as risk factors for CVD and to improve CV risk prediction beyond conventional risk factors should be further assessed.
2.4.4 Measurement of preclinical vascular damage
Key messages
•
Routine screening with imaging modalities to predict future CV events is generally not recommended in clinical practice.
•
Imaging methods may be considered as risk modifiers in CV risk assessment, i.e. in individuals with calculated CV risks based on the major conventional risk factors around the decisional thresholds.
Tabled
1Recommendations for imaging methods
Recommendations for imaging methods
ABI = ankle–brachial index; CV = cardiovascular; IMT = intima–media thickness.aClass of recommendation.bLevel of evidence.cReference(s) supporting recommendations.
Although most CVD can be explained by traditional risk factors, there is substantial variation in the amount of atherosclerosis. Thus interest has continued in the use of non-invasive imaging techniques to improve CV risk assessment. In individuals with calculated CV risks based on the major conventional risk factors near the decisional thresholds, some imaging techniques may be considered as risk modifiers to improve risk prediction and decision making.
2.4.4.1 Coronary artery calcium
Coronary artery calcium (CAC) is examined through electron beam or multislice CT. Calcifications indicate late-stage subclinical coronary atherosclerosis.
Atherosclerotic coronary arteries do not necessarily always show calcifications. The extent of the calcification correlates with the extent of total coronary plaque burden.
The value of the score can be further increased if the age and sex distribution within percentiles are taken into account. A CAC score ≥300 Agatston units or ≥75th percentile for age, sex and ethnicity is considered to indicate increased CV risk.
CAC has shown a very high negative predictive value, since an Agatston score of 0 has a negative predictive value of nearly 100% for ruling out significant coronary narrowing.
Correlation of coronary calcification and angiographically documented stenoses in patients with suspected coronary artery disease: results of 1,764 patients.
Clinical characteristics of patients with obstructive coronary lesions in the absence of coronary calcification: an evaluation by coronary CT angiography.
Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data.
Prevalence, vascular distribution, and multiterritorial extent of subclinical atherosclerosis in a middle-aged cohort: the PESA (Progression of Early Subclinical Atherosclerosis) study.
Implications of coronary artery calcium testing among statin candidates according to American College of Cardiology/American Heart Association cholesterol management guidelines: MESA (Multi-Ethnic Study of Atherosclerosis).
There are concerns regarding costs and radiation exposure. For CAC scoring, the radiation exposure with properly selected techniques is +1 mSv.
2.4.4.2 Carotid ultrasound
Population-based studies have shown correlations between the severity of atherosclerosis in one arterial territory and the involvement of other arteries.
Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group.
Therefore, early detection of arterial disease in apparently healthy individuals has focused on peripheral arteries, and in particular on the carotid arteries. Risk assessment using carotid ultrasound focuses on the measurement of the intima-media thickness (IMT) and the presence and characteristics of plaques.
The IMT is not only a measure of early atherosclerosis, but also of smooth muscle hypertrophy/hyperplasia. There is a graded increase in CV risk with increasing IMT,
Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group.
and a value >0.9 mm is considered abnormal. The risk of stroke associated with IMT is non-linear, with hazards increasing more rapidly at lower IMTs than at higher IMTs. The IMT-associated risk of cardiac events is also non-linear.
Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987–1993.
The extent of carotid IMT is an independent predictor of CVD, but seems to be more predictive in women than in men.
The lack of standardization regarding the definition and measurement of IMT, its high variability and low intra-individual reproducibility have raised concerns. A recent meta-analysis failed to demonstrate any added value of IMT compared to the Framingham Risk Score in predicting future CVD, even in the intermediate risk group.
Thus, the systematic use of carotid ultrasound IMT to improve risk assessment is not recommended.
Plaque is usually defined as the presence of a focal wall thickening that it is at least 50% greater than the surrounding vessel wall oras a focal region with an IMT measurement ≥1.5 mm that protrudes into the lumen.
30214-3&id=gr1.jpg){kind=link}
30214-3&id=gr2.jpg){kind=link}
30214-3&id=gr3.jpg){kind=link}
30214-3&id=gr4.jpg){kind=link}
