Lipids module 2: cardiovascular risk

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Who is at risk?

Cardiovascular disease (CVD) remains the leading cause of death in England and Wales, accounting for almost one-third of deaths. While it is well accepted that following a heart attack or stroke patients should wherever possible receive “secondary prevention” treatment to reduce the likelihood of further cardiovascular events, “primary prevention” of a first cardiovascular event is increasingly considered as an important priority for the NHS. This is reflected in the CVD Outcomes Strategy1 which emphasises that “prevention is everybody’s business”. Accurate prediction of those at risk for CVD should ensure that there is a favourable balance between benefit and harm. This is a prerequisite for primary prevention strategies and is based on the assessment of cardiovascular risk factors, a concept generated from the Framingham Heart Study.

The Framingham Heart Study – where ‘risk factors’ came from

In 1948, the Framingham Heart Study ( embarked on an ambitious public health project. Coincidentally, this was the year in which the UK National Health Service (NHS) was founded. At the time, little was known about the general causes of heart disease and stroke, but death rates for CVD had been increasing and had become an American epidemic. The Framingham Heart Study became a joint project of the National Heart, Lung and Blood Institute and Boston University (see figure 1).

Figure 1. The Framingham Heart Study Primary Investigators (click for more)
Figure 1. The Framingham Heart Study Primary Investigators (click for more)
Table 1. Cardiovascular risk factors
Table 1. Cardiovascular risk factors

The researchers recruited 5,209 men and women between the ages of 30 and 62 from the town of Framingham (a dormitory town of Boston, Massachusetts), and began the first round of extensive physical examinations and lifestyle interviews that they would later analyse for common patterns related to CVD development. Since 1948, the subjects have continued to return to the study every two years for a detailed medical history, physical examination, and laboratory tests, and in 1971, the Study enrolled a second generation – 5,124 of the original participants’ adult children and their spouses – to participate in similar examinations.

In 1994, the need to establish a new study reflecting a more diverse community of Framingham was recognised, and the first Omni cohort of the Framingham Heart Study was enrolled.

In April 2002 the Study entered a new phase, the enrollment of a third generation of participants, the grandchildren of the Original Cohort. In 2003, a second group of Omni participants was enrolled.

Identifying major CVD risk factors

Over the years, careful monitoring of the Framingham Study population has led to the identification of the major CVD risk factors (see table 1) – hypertension, high blood cholesterol, smoking, obesity, diabetes, and physical inactivity – as well as a great deal of valuable information on the effects of related factors such as blood triglyceride and high-density lipoprotein (HDL) cholesterol levels, age, gender, and psychosocial influences.


Figure 2. Professor Salim Yusuf (McMaster University, Ontario, USA)
Figure 2. Professor Salim Yusuf (McMaster University, Ontario, USA)

The major Canadian-led global INTERHEART study2 has identified nine easily measured risk factors (smoking, lipids, hypertension, diabetes, obesity, diet, physical activity, alcohol consumption, and psychosocial factors) that account for over 90% of the risk of acute myocardial infarction (AMI). The INTERHEART investigators, led by Professor Salim Yusuf, from McMaster University (see figure 2) found that these risk factors are the same in almost every geographic region and every racial/ethnic group worldwide and are consistent in men and women.

Although the Framingham cohort is primarily Caucasian, the importance of the major CVD risk factors identified in this group have been shown in other studies to apply almost universally also, and among racial and ethnic groups, even though the patterns of distribution may vary from group to group.

The concept of CVD risk factors has become an integral part of modern medicine and has led to the development of effective treatment and preventive strategies in clinical practice. It led to the development of the first ‘risk engine’ where in the USA the Framingham Score was developed, and subsequently modified for use in other countries including the UK. Several other ‘risk engines’ have also been developed (see table 2).

Table 2. Cardiovascular ‘risk engine’ calculators
Table 2. Cardiovascular ‘risk engine’ calculators

Modifying risk factors, and optimising treatment for associated comorbidities, can reduce the risk of developing CVD. It is estimated that 60% of the decline in death rates in the UK in the 1980s and 1990s was attributable to reductions in risk factors, most notably a large reduction in smoking rates.

NHS vascular screening programme

Population-based screening has been introduced by the NHS Health Checks programme in 2009 (see figure 3).3 In the UK, adults aged 40 to 74 years without a diagnosis of vascular disease will be contacted by their primary care trust and offered a health check. From 2012–13, the first full year of implementation, 2.7 million offers were made and 1.26 million appointments were taken up. The aim is for 20% of the eligible population to be offered an NHS Health Check each year, with a take up rate of 75%.4

Figure 3. NHS Health Checks
Figure 3. NHS Health Checks (click to enlarge)

This programme targets those who have not yet been diagnosed with heart disease, stroke, diabetes or kidney disease. People older than 40 should have their estimate of CVD risk reviewed on an ongoing basis. Thus, every five years the individual’s risk of each disorder, along with advice on how to lower such risk, will be offered during consultation. Factors including blood pressure, body mass index (BMI), cholesterol (total [TC] and HDL), ethnicity and family history will be recorded, and the results and potential consequences discussed with a healthcare professional.

It is not the purpose of this module to ‘compare and contrast’ individual risk equations, these have been summarised elsewhere.5 However it is worth looking at some of the major calculators still in use.

Reynolds Risk Score

The Reynolds Risk Score is a relatively new method for calculating a woman’s risk for developing CVD. It is specifically designed for women, and some experts think it is a more accurate risk calculation method than the more standard risk calculators, such as the Framingham study.

The Reynolds score was developed because in recent years it has become apparent that the more standard risk models might not apply as accurately in women as in men. The risk equation includes C-reactive protein (CRP) measurement, which may be a stronger risk factor in women.


Risk equations have emerged from the PROCAM (Munster Heart Study). The PROCAM study showed that HDL cholesterol is an important driver of coronary heart disease (CHD) risk and provided evidence that HDL cholesterol levels exert a much stronger influence on CHD risk in individuals with elevated global cardiovascular risk.

Another important finding from PROCAM was that CHD risk factors do not act in isolation but rather in conjunction.

It also demonstrated that fasting triglyceride levels are an independent risk factor for CHD events, regardless of HDL or LDL cholesterol concentrations.


The Systematic COronary Risk Evaluation (SCORE): provides high and low cardiovascular risk charts (see figure 4)6 based on gender, age, TC, systolic blood pressure and smoking status, with relative risk chart, qualifiers and instructions, have been developed by the European Society of Cardiology (ESC). These are based on a large data set (database was derived from 12 European cohort studies of 250,000 patients) tested thoroughly on European data, operating with hard, reproducible end points (CVD death). Risk of CHD and stroke death can be derived separately.

Figure 4. SCORE Chart for Use in High-Risk European Regions
Figure 4. SCORE Chart for Use in High-Risk European Regions


In 2010 the National Institute for Health and Care Excellence (NICE) decided it could no longer recommend that the Framingham risk equation be used, as it tends to overestimate risk by approximately 5% in UK men. The decision also coincides with the emergence of the QRISK® calculator which has been shown to predict risk more accurately. The QRISK® calculator is available at (see figure 5).

Figure 5. QRISK calculator
Figure 5. QRISK calculator

The QRISK2 risk calculation algorithm is based on a large UK primary care observational database. It is updated annually each April, refitted to the latest data to remain as accurate as possible. It incorporates additional risk factors which improve overall accuracy of the risk estimates in adults up to 84 years. However weighting of lipid risk factors is reduced by imputation of data and the calculator is not recommended for use in older patients or those with chronic kidney disease, Type 1 diabetes or inherited lipid disorders. QRISK2 can however be used to assess CVD risk in those with type 2 diabetes.


The Joint British Societies (JBS3) risk calculator, is the new kid on the block. It has evolved from the proposals published in the JBS3 report7 which are consensus recommendations, and are a collaborative effort from the British cardiovascular societies who deal with cardiovascular disease prevention. The report was written for GPs and practitioners to help guide their work with patients, in preventing CVD.

QRISK® Lifetime has been chosen as the basis for the JBS3 risk calculator as it provides the option of a calculation of lifetime risk and is based on a UK population.

The JBS3 risk calculator (see figure 6) rejects the established method of 10-year risk assessment, for the lifetime risk score. It includes factors such as vascular age and time until first cardiovascular event, in an attempt to calculate a patient’s absolute risk of an event over the rest of their lifetime.

Figure 6. JBS3 risk calculator
Figure 6. JBS3 risk calculator

JBS3 risk calculator estimates both 10-year risk and lifetime risk of CVD in all individuals except for those with existing CVD or certain high risk diseases, i.e. diabetes age >40 years, patients with chronic kidney disease (CKD) stages 3–5, or familial hypercholesterolaemia (FH).

Practice points:

  • All of the risk engines reviewed only provide a score which is an estimate and needs to be used in conjunction with clinical judgment
  • Do not use a risk assessment tool for people with pre-existing CVD

Exclusions from risk equations

Table 3. Individuals to exclude from risk equation assessment
Table 3. Individuals to exclude from risk equation assessment

Formal risk assessment is not necessary for a number of individuals (see table 3) who are considered already to be at sufficiently high risk to justify lifestyle and pharmacological interventions, including statins.

NICE guidance

Further advice on cardiovascular risk assessment is anticipated from NICE in the Autumn of 2015. Presently this is encapsulated in NICE Clinical Guideline 1818 on lipid modification, which was issued in July 2014.

Key recommendations in this guidance include:

  • Identifying and assessing CVD risk using the QRISK2 assessment tool for the primary prevention of CVD in people up to the age of 84 years
  • Prioritising people for a full formal risk assessment if their estimated 10-year risk of CVD is 10% or more.
  • Taking a full lipid profile before starting lipid modification therapy for primary prevention. A fasting sample is not needed.

NICE notes that not everyone with a 10% or greater risk of CVD within 10 years will need to take a statin and the guideline advises that preventative lifestyle measures are adopted first.

The full guidance can be found at

Key learning messages

  • Accurate prediction of those at risk for CVD should ensure that there is a favourable balance between benefit and harm.
  • It is a prerequisite for primary prevention strategies
  • It is important to establish cardiovascular risk with a view to offsetting cardiovascular events in the population.
  • A number of ‘risk engines’ have been validated but QRISK2 is the choice with which to assess CVD risk for primary prevention.
  • Do not use QRISK2 to assess CVD risk for secondary prevention or in primary prevention in patients with CKD, Type 1 diabetes or FH.
  • Risk threshold for the consideration of statin therapy for primary prevention is now 10% or greater 10-year risk of developing CVD.

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1. Cardiovascular disease outcomes strategy: improving outcomes for people with or at risk of cardiovascular disease. Department of Health, March 2013.

2. Yusuf S, Hawken S, Ounpuu S et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004;364:937–52.

3. NHS Health Check best practice guidance. (Accessed June 2015)

4. NHS Health Check Programme: priorities for research. Public Health England. November 2014. Available at

5. Reiner Z, Catapano AL, De Backer G et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011;32:1769–818.

6. Perk J, De Backer G, Gohlke H, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). Euro Heart J 2012;33:1635–701.

7. JBS3 Board. Joint British Societies’ consensus recommendations for the prevention of cardiovascular disease (JBS3). Heart 2014;100:ii1–67.

8. NICE clinical guideline 181. 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 2014. Available from

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