SIGN guideline on cardiovascular disease outlines key factors to help with timely recognition and intervention by the primary care team, explains Dr James Grant

T he Scottish Intercollegiate Guidelines Network (SIGN) published guideline 97—Risk Estimation and the Prevention of Cardiovascular Disease — in February 2007.1 This guideline replaces SIGN 40 and 41,2,3 which were published in 1999 and 2000, respectively.

Primary and secondary prevention are important

The updated guideline addresses both the primary and secondary prevention of cardiovascular disease (CVD). However, as this disease is a continous process, primary and secondary terminology are essentially artificial. What is important is to understand the risk and to intervene appropriately, according to the evidence. Previous guidelines such as SIGN 40 and 41 have focused only on coronary heart disease (CHD), which has resulted in a substantial underestimation of the risk of stroke and, consequently, overall cardiovascular risk.2,3

There has been an inevitable expansion of the relevant literature on CVD, which has necessitated a reassessment of the evidence. The new guideline covers risk estimation and lifestyle modification, as well as the effect of reducing blood pressure, lipid lowering, and the use of antiplatelet therapy. For the first time, it also examines the evidence for the psychosocial and psychological aspects of CVD and how interventions may best be directed in order to maximise patient compliance.

Recommendations in the SIGN guideline are graded from A to D according to strength of evidence, with additional good practice points (Figure 1).

Figure 1: Key to evidence statements and grades of recommendations

Levels of Evidence
1++ High quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias.
1+ Well conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias.
1- Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias.
2++ High quality systematic reviews of case control or cohort studies.
High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal.
2+ Well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal.
2- Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal.
3 Non-analytic studies, e.g. case reports, case series.
4 Expert opinion.
Grades of Recommendation
Note: The grade of recommendation relates to the strength of the evidence on which the recommendation is based. It does not reflect the clinical importance of the recommendation.
A At least one meta-analysis, systematic review of RCTs, or RCT rated as 1++ and directly applicable to the target population; or
  A body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results.
B A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or
  Extrapolated evidence from studies rated as 1++ or 1+
C A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or
  Extrapolated evidence from studies rated as 2++.
D Evidence level 3 or 4; or
  Extrapolated evidence from studies rated as 2+.
Good practice points
? Recommended best practice based on the clinical experience of the guideline development group.
RCT=randomised controlled trials
Reproduced from Risk Estimation and the Prevention of Cardiovascular Disease by kind permission of SIGN

Why this guideline is important

Cardiovascular disease remains the major cause of premature death in the UK despite recent data on disease incidence, which indicate that rates are falling.4 Prevalence of CHD is highest among men, the elderly, and in deprived areas.5 The effects of socioeconomic status on the risk of developing CVD are particularly relevant in Scotland, where the incidence and mortality rates from acute myocardial infarction in people younger than 65 years old are higher in areas of deprivation than in more affluent areas.1

The aetiology of CVD involves a number of risk factors, including age, sex, cigarette smoking, blood pressure, total cholesterol, and high-density lipoprotein, which have proved to be consistent in every population study.6

General practitioners and their teams remain the first point of contact for the majority of patients who may present either with a disease episode or opportunistically. The importance of the primary care team in understanding the evidence for intervention, and their ability to carry out these interventions in a timely and appropriate way is crucial if continuing progress is to be made in reducing the mortality and morbidity rates from CVD.

The concept of risk

The moderate risk group comprises the largest number of individuals and, therefore, also contributes the most deaths from CVD. However, historically, the highest priority in clinical practice has been given to higher risk individuals, as this group has the most to gain from risk factor modification.7

The majority of risk scoring systems for CHD and CVD are based on the American Framingham study.8,9 These scoring systems tend to exaggerate risk in low and medium risk groups and undervalue it for certain other sub-groups10— these include British Asians, people with Type 1 diabetes, and people with Type 2 diabetes with nephropathy.11,12

Levels of CVD risk in men from lower socioeconomic groupings are also underestimated using the Framingham risk scores.10

Adjustments to the risk scoring system

Risk scoring systems have to allow for deprivation in order to ensure that those who are actually at high risk receive treatment, and those who are at relatively lower risk are not treated inappropriately. Under the auspices of SIGN, a new risk scoring system ASSIGN (ASsessing cardiovascular risk using SIGN guidelines to assign preventive treatment) has been developed.1 This incorporates standard risk factors but adds to these factors family history, the number of cigarettes smoked, and social deprivation, which is determined by postcode. It is hoped that this new system, which is currently available on the internet (, will be available on NHS desktops in Scotland in 2008.

Level of intervention

The basis of any preventive strategy is first to make an estimation of risk so that treatment can be assigned appropriately. Previously in Scotland it was recommended that preventive treatment for CHD was offered when an individual's risk was estimated to be greater than 30% over the next 10 years.13

In SIGN 97, it is now recommended that this intervention level be reduced to ?20% CVD risk over the next 10 years. It has been estimated that this will mean that, in Scotland alone, approximately half a million more adults will be eligible for treatment with statin therapy.14 This obviously has significant implications for primary care.

Lifestyle modification

The principal approach to CVD prevention is modification of lifestyle. It is crucial that patients look carefully at their dietary fat intake, their levels of physical exercise, and their consumption of alcohol. Strong recommendations to stop smoking and to avoid passive smoking are reinforced within the guideline. Key recommendations are given in Figure 2.

Figure 2: Key recommendations for lifestyle modification

A Diets low in total and saturated fats should be recommended to all for the reduction of cardiovascular risk.
? All individuals should eat at least two portions of fish per week, one of which should be a fatty fish.
A Antioxidant vitamin supplementation is not recommended for the prevention or treatment of CHD.
  Physical activity
B Physical activity of at least moderate intensity (e.g. makes person slightly out of breath) is recommended for the whole population (unless contraindicated by condition).
B Physical activity should include occupational and/or leisure time activity and incorporate accumulated bouts of moderate intensity activities such as brisk walking.
B Those who are moderately active and are able to increase their activity should be encouraged to do so. Activity can be increased through a combination of changes to intensity, duration, or frequency.
B Patients with no evidence of CHD may be advised that light to moderate alcohol consumption may be protective against the development of CHD.
C Patients with established CHD may be advised that light to moderate alcohol consumption may be protective against further coronary events.
A Brief multicontact interventions should be used to encourage patients to reduce their levels of drinking if their current intake is hazardous to their health
B All people who smoke should be advised to stop and offered support to help facilitate this in order to minimise cardiovascular and general health risks.
B Exposure to passive smoking increases cardiovascular risk and should be minimised.
A Nicotine replacement therapies or bupropion should be used as part of a smoking cessation programme to augment professional advice and increase long-term abstinence rates
B Smokers with CHD and comorbid clinical depression should have their depression treated both for alleviation of depressive symptoms and to increase the likelihood of stopping smoking.
  Antiplatelet therapy
A Individuals with established atherosclerotic disease should be treated with 75 mg aspirin daily.
A Individuals with a history of stroke or TIA and who are in sinus rhythm should be considered for low dose aspirin (75–300 mg daily) and dipyridamole (200 mg twice daily) to prevent stroke recurrence and other vascular events. If aspirin is contraindicated, or there are side effects, clopidogrel 75 mg daily is an alternative.
A Asymptomatic individuals without established atherosclerotic disease but with a calculated cardiovascular risk of ?20% over ten years should be considered for treatment with aspirin 75 mg daily.
  Psychological issues
B Depression and social isolation or lack of quality social support are risk factors for the development of and prognosis with CHD and should be taken into account when assessing individual risk.
A CBT should be considered for increasing physical function and improving mood in patients with CHD.
A Use of the stages of change model alone is not recommended as a method for changing the health behaviour of individuals with CHD.
B Motivational interviewing should be considered in patients with CVD who require to change health behaviours including diet, exercise, alcohol, and compliance with treatment.
CHD=coronary heart disease; TIA=transient ischaemic attack; CBT=cognitive behavioural therapy; CVD=cardiovascular disease
Reproduced from Risk Estimation and the Prevention of Cardiovascular Disease by kind permission of SIGN

Reducing blood pressure

Blood pressure and cardiovascular risk are related in an approximately linear way between the values of 115/70 and 170/100 mmHg. No matter what the baseline blood pressure measurement is within this range, the relative benefits of treatment are similar. Individuals who are more at risk of CVD will benefit the most from treatment, which will start for them at a lower intervention threshold.15

The risk of cardiovascular and total mortality is improved by reducing blood pressure, without affecting the quality of life detrimentally. A reduction in the relative risk of CHD of 15 to 25% was achieved during trials of antihypertensive drugs; the trials also reduced occurrence of a transient ischaemic attack (TIA) by 30 to 40%.16

Key recommendations from the guideline for blood pressure and lipid lowering are given in Figure 3.

Figure 3: Key recommendations for reducing blood pressure and lipid lowering

B Individuals with BP ?160/100 mmHg should have drug treatment and specific lifestyle advice to lower their BP and risk of CVD.
? All individuals with a persistent BP ?140/90 mmHg or a family history of hypertension should receive lifestyle advice to help reduce their BP and CVD risk. Lifestyle advice should continue even when drug therapy is initiated.
A Individuals with sustained systolic BP >140 mmHg systolic and/or diastolic BP >90 mmHg and clinical evidence of CVD should be considered for BP-lowering drug therapy.
A Individuals with established CVD, who also have chronic renal disease or diabetes with complications, or target organ damage may be considered for treatment at the lower threshold of systolic >130 mmHg and/or diastolic >80 mmHg.
? Asymptomatic individuals with sustained systolic blood pressures ?40 mmHg systolic and/or diastolic blood pressures ?90 mmHg and whose ten year risk of a first CVD event is calculated to be ?20% should be considered for blood pressure lowering drug therapy.
? Individuals with such BP levels whose ten year risk of a first CVD event is <20% should continue with lifestyle strategies and have their blood pressure and total CVD risk reassessed every one to five years, depending on clinical circumstances.
A All adults over the age of 40 years who are assessed as having a 10-year risk of having a first cardiovascular event ?20% should be considered for treatment with simvastatin 40 mg/day following an informed discussion of risks and benefits between the individual and responsible clinician.
B All patients with established symptomatic atherosclerotic CVD should be considered for more intensive statin therapy following an informed discussion of risks and benefits between the individual and responsible clinician.
BP=blood pressure; CVD=cardiovascular disease
Reproduced from Risk Estimation and the Prevention of Cardiovascular Disease by kind permission of SIGN

Lipid lowering

The main treatment for lipid lowering for prevention of initial and repeat CVD events is with statins.

The results from 14 large randomised trials of statin therapy found that a 1.0 mmol/l reduction in low density lipoprotein (LDL) cholesterol reduced the 5-year relative risk of a major vascular event by 21%, regardless of gender, age, blood pressure, pre-existing diabetes, or history of a previous CVD event.17 Statin therapy was found to be more beneficial for individuals judged to be at high risk of CVD. The resulting relative risk reduction for patients with established CHD was 48 per 1000 fewer individuals experiencing a major vascular event, compared with 25 per 1000 fewer cases among individuals without established CHD.17

The reduction in relative risk of CVD events after treatment with statin therapy is approximately constant across all baseline levels of total or LDL cholesterol and cardiovascular risk. Individuals such as those with established symptomatic CVD or those with familial hypercholesterolaemia, and who are at high risk of a CVD event, will benefit to a greater extent from more aggressive lipid lowering than those who are at lower absolute levels of risk.18

The Joint British Society guideline (JBS2) found that there are no clinical trials that have evaluated the relative and absolute benefits of cholesterol lowering to different total and LDL cholesterol targets in relation to clinical events.19

The lack of lifelong follow-up studies for statin therapy means that any target level for cholesterol can only be based on evidence of apparent benefits of lipid lowering, which have been established by major trials, while at the same time allowing adequate safety margins. The SIGN 97 guideline has, therefore, recommended that high-risk individuals, who are over 40 years of age and without a history of CVD, should be started on simvastatin 40 mg daily.

Although intensive statin therapy should be considered for patients with established symptomatic CVD, there is, as yet, no long-term evidence for the safety of this therapy and its cost-effectiveness.20

Antiplatelet therapy

In those with no history of CVD, questions still remain about the long-term use of aspirin. Each patient being considered for therapy should be made fully aware of the benefit to risk profile.

Aspirin reduces the risk of myocardial infarction (MI) by approximately 30%, but increases the risk of haemorrhagic strokes by 40% and the risk of major gastrointestinal bleeding by 70%.21

There is strong evidence for the use of aspirin, or its equivalent, for patients with established CVD. The Antithrombotic Trialists' Collaboration showed clear evidence of a reduction in all-cause mortality, vascular mortality, non-fatal reinfarction of the myocardium, and non-fatal stroke in people who had experienced acute coronary syndromes, stroke, TIA, or other vascular disease.22

Psychological issues

Although stress is often perceived by cardiac patients as being a significant cause of their heart disease, it has been a difficult area to research because of the lack of precise definitions and the difficulties of measurement. The INTERHEART study reported on risk factors, including subjective stress, which appeared to be associated with an increased risk of developing an acute MI independent of smoking and socio-economic status.23

The evidence has, therefore, been reviewed in SIGN 97 and recommendations on psychological interventions that may benefit patients with CVD have been made.

Implications for primary care

Using estimates from the Scottish Health Survey 2003, based on SIGN 40, one in 21 asymptomatic individuals aged 35–69 years fall within the risk thresholds for treatment, reducing to 1 in 13 if extended to asymptomatic individuals aged 40 years or over.24

Updating these statistics using criteria set out in SIGN 97 means that almost 1 in 3 asymptomatic individuals aged 40 years of age or over will fall within the risk schedules for treatment, and 1 in 4 will be identified as being at high risk of CVD and requiring lifestyle advice and drug therapy.14

There are obviously very significant implications in these figures for workloads of GPs and their teams. It will take some significant time, an increase in practice nursing resources and, for some practices, significant reorganisation of CVD clinics before SIGN 97 is fully implemented. Currently a SIGN implementation group is working closely with the management executive in Scotland to bring this about.


Although improvements in the prevalence of CVD have been seen over recent years, it remains the major cause of premature death in the UK.

The recommendations in SIGN 97 and their implementation represent a further significant step towards continuing the downward pressure on CVD prevalence rates.

The guideline emphasises the importance of risk estimation and social deprivation, and, for the first time, provides a useful tool to incorporate deprivation into CVD risk calculation.

The guideline makes strong recommendations in relation to behavioural and lifestyle modification (Figure 2) and BP and lipid lowering (Figure 3), while at the same time recognising that the evidence does not exist for recommending cholesterol targets. Important recommendations are also made in relation to behavioural modification.

  • Effective CVD prevention reduces morbidity and mortality and reduces secondary care costs (e.g. for bypass surgery)
  • CVD prevention, however, does increase medication costs from the indicative budget
  • The best evidence for primary prevention of CVD is using simvastatin 40mg daily which has a low acquisition cost25
  • There is no good evidence for using more expensive statins to treat to targets such as recommended by JBS219
  • PBC consortia should agree a low cost evidence based prescribing policy for CVD prevention
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  2. Scottish Intercollegiate Guidelines Network (SIGN 40). Lipids and the primary prevention of coronary heart disease. Edinburgh: SIGN, 1999.
  3. Scottish Intercollegiate Guidelines Network (SIGN 41). Secondary prevention of coronary heart disease following myocardial infarction. Edinburgh: SIGN, 2000.
  4. NHS National Services Scotland. Information and Statistics Division. CHD: practice consultations (statistical data) 28th Nov 2006. Available from
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  11. Cappuccio F, Oakeshott P, Strazzullo P, Kerry S. Framingham based scoring systems tend to overestimate risk in low and medium risk groups and underestimate risk for certain sub-groups including British Asians, people with Type 1 diabetes and people with Type 2 diabetes with neuropathy. Br Med J 2002; 325 (7375): 1271.
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  15. Lewington S, Clarke R, Qizilbash N et al. Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360 (9349): 1903–1913.
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  22. Antithromboic Trialists' Collaboration. Collaborative meta analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction and stroke in high-risk people. Br Med J 2002; 324 (7329): 71–86.
  23. Rosengren A, Hawken S, Ounpuu S et al. Association of psychological risk factors with risk of acute myocardial infarction in 11119 cases and 13648 controls from 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364 (9438): 953–962.
  24. Scottish Health Survey 2003. Edinburgh: Scottish Executive, 2003.
  25. Heart Protection Study Collaborative Group.MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360 (9326): 7–22.G