Primary prevention

Primary prevention is the intervention against the modifiable risk factors of ischaemic events. Global risk scores such as the SCORE are recommended to combine individual risk factors into a single quantitative risk estimate.10–12

In Europe and USA, individuals with a 10-year risk of CVD death ≥5% qualify for lifestyle intervention and, when CVD death risk is ≥10%, drug treatment is frequently recommended. However, guideline-based recommendations for individuals ≥70 years are lacking despite the fact that >80% of CVD deaths occur in this age group.13 14

Nevertheless, population-based screening and intervention based on clinical risk scores does not reduce all causes or cardiovascular mortality.15 16 Although these trials were performed before or in the beginning of modern cardiovascular preventive treatment with statins, the conclusion from these trials was that screening was not needed due to the quality of the general practitioners. Thus, these studies do not address the potential of modern-day screening in primary prevention. Finally, the majority of these studies were in those aged <60 years, and the Cochrane review excluded studies targeting older patients, and from our point of view, those are the most relevant for in lesion-based pharmacological preventive strategy.15 16

Secondary prevention

Secondary prevention entails interventions that are specifically targeted against lesions, which can cause ischaemic events (eg, due to type IV lesions). Secondary prevention techniques require the visualisation of asymptomatic lesions whether by opportunistic, chance-based detection or by systematic screening. The rationale for screening has been discussed intensively.17 18 Overall, ultrasound-based screening for abdominal aortic aneurysm (AAA) of men has been found to reduce mortality in a cost-effective manner,19 although similar evidence supporting screening for CVD is lacking.12 13 20

Tertiary prevention

Tertiary prevention includes preventive actions that are taken to prevent new events after symptomatic disease, such as antithrombotic treatment after coronary revascularisation. Such preventative approaches are beyond the scope of this educational article.

Opportunistic screening

Opportunistic screening occurs when individuals, healthcare providers or the healthcare system take initiative to check for health conditions on an ad hoc basis, typically because of suspected risk. Unlike systematic, population-based screening, opportunistic screening is often not centrally managed, and thus has the advantage of little to no cost in regard to administration. The disadvantage is that the benefits and harms are usually unclear and not evaluated according to the same criteria that are used for systematic and centrally organised screening. A further issue is social inequality in regard to access to healthcare, because the initiative, at least at the first step of the process, is placed on the individual. As a result, if more informed, resourceful individuals are more likely to suspect and act on their risk, then opportunistic screening might lead to increased inequality in health, in addition to the overall, inferior effect of screening because individuals in the highest-risk category might not be reached at all.

Population-based screening

In population-based, systematic, screening programmes, everyone in the target population is invited. This implies the testing of asymptomatic, apparently healthy people, of which the majority will only be exposed to the negative effects of screening to identify the few who will enjoy a health benefit. Such screening is thus a distinct and complex public health strategy that requires additional resources, coordination and infrastructure. Consequently, a screening programme should be implemented only when its effectiveness has been proved; when human, financial and physical resources are present to cover nearly all the target groups; when facilities exist for the follow-up of abnormal results to confirm diagnoses and ensure treatment, as well as when the prevalence/health consequences of the disease are high enough to justify the efforts and costs of screening.22

In 1968, Wilson and Jungner proposed a number of still core criteria that should be satisfied for screening to be justified22 (table 1). In general, the condition for which the screening programme will be established must be an important health problem that can be detected and treated in an acceptable way for the target population, at costs that are reasonable.

In addition, according to WHO, a screening programme should entail21:

• Algorithms for systematic invitation and follow-up for screening positives.

• Participation rate ≥70% of the target population.

• Sufficient infrastructure and resources to offer the test and to adequately diagnose and treat those found to have the disease.

• Robust monitoring and evaluation framework to assure quality.

It should be noted that successful models from high-resource countries with advanced healthcare systems may not be adaptive to countries without the needed infrastructure and resources to cover the population. Ideology and policies on screening may differ significantly between countries due to culture, disease pattern, and healthcare organisation and finance. As a result, there is no one-size-fits-all approach, and local adaptations are typically needed.

Value proposition of screening to society

The Wilson-Jungner criterion regarding the benefits of a screening programme being ‘economically balanced in relation to possible expenditure’ (table 1) remains another pivotal element of decision-making with regard to screening.22 Since 1968, methods such as cost-effectiveness and cost utility evaluations that incorporate and synthesise evidence concerning the net benefit against the total costs from a healthcare, or even a societal, perspective have evolved and become an obligatory part of assessments by, for example, the USPSTF or the UK NSC. These methods essentially assess the additional cost required to achieve additional value, which can be compared with the equivalent cost of value gains elsewhere in healthcare, or even in society, to inform priority setting. If prevention is to be judged on similar terms as other healthcare activities (when competing for funding), then this evidence is necessary to prioritise according to the value obtained for the money spent.

In societies where equity is a key concern, the value-for-money perspective should be supplemented by the distributional consequences, that is, not only is it important whether screening offers a mean additional benefit but also who receives this benefit—or in other words, whether screening exacerbates health inequality.25 Although this is not a formal assessment criterion, it is often considered by both the USPSTF and the UK NSC in practice. More recently, methods to directly assess the citizens’ preferences for screening based on information concerning benefits and harms have been proposed for consistency with the idea of value-based healthcare.26

Hypertension

The USPSTF recommends annual screening for adults ≥40 years of age or who are at increased risk for high blood pressure (overweight or obese, and African-Americans). Adults between 18 and 39 years of age with normal blood pressure (<130/85 mm Hg) who do not have other risk factors should be screened every 3 to 5 years.

The evidence behind the recommendation is moderate-quality to high-quality RCTs, which have shown that the treatment of individuals ≥60 years of age toward a target blood pressure of 150/90 mm Hg reduces the incidence of stroke, heart failure and coronary heart disease events.27 Similarly, RCTs have demonstrated the efficacy of the treatment of younger adults to a target diastolic blood pressure of less than 90 mm Hg in reducing cerebrovascular events, heart failure and overall mortality.27

Diabetes

Population-based screening for diabetes is controversial. In the USA, this approach is recommended in asymptomatic adults every third year, if the sustained blood pressure is greater than 135/80 mm Hg. In the UK, it is not recommended due to insufficient evidence.28 29

The USPSTF found sufficient evidence that in adults who have hypertension and diabetes, lowering of the individual’s blood pressure below conventional target values reduces the incidence of cardiovascular events and cardiovascular mortality.

Dyslipidaemia

Although statin therapy is recommended for manifest CVD, nonetheless this treatment approach is more controversial as primary prevention. The USPSTF found level A evidence that men ≥35 years of age and women ≥45 years of age who are at increased risk for coronary heart disease ought to be screened for lipid disorders every fifth year. Population-based screening for familiar hypercholesterolaemia is neither recommended in the UK nor in the USA.

Risk of CVD assessment

In many countries, including the UK and the USA, as well as in the European Society for Cardiology,12 13 it is recommended that individuals ≥40 years of age have their CVD risk reviewed on a regular basis by means of assessment tools such as the SCORE or the QRISK2. Such risk assessments include the measurement of blood pressure and lipids.30 31

Atrial fibrillation

Screening for AF has been the subject of much debate due to the increasing prevalence of AF-related stroke and the potential to prevent this condition with appropriate anticoagulation. In a cohort study of 5555 asymptomatic patients with AF or with incidentally detected AF, antithrombotic therapy was compared with no antithrombotic therapy, showing an absolute 3% reduced risk of both stroke and death within 1.5 years.32 Several cost-effectiveness analyses have been published, which conclude that AF screening is cost-effective. Unfortunately, all these studies rely on critical assumptions regarding the natural history of AF as well as the treatment effect, which has yet to be established in a randomised setting. Several ongoing RCTs are currently underway internationally, the results of which will inform the effect of AF screening.

Abdominal aortic aneurysms

A meta-analysis of four randomised trials showed that screening halves the mortality from AAA and reduces total mortality by 1%–2%.33–35 One of the most recent health economic studies concluded that it is highly cost-effective to screen 65-year-old Danish men for AAA, as a QALY can be gained for approximately Danish Krone 5000 (£550/US$750).36 37 This cost is less than one-tenth of a QALY gained by colorectal cancer screening.38

Consequently, the USPSTF and the UK NSC recommend a one-time screening of men at the age of 65 years; in the USA, however, this screening is restricted to prior and current smokers. National screening programmes have been implemented in Sweden, England, Scotland, Wales, Northern Ireland, Ireland, the USA and Germany.

Coronary artery calcification

Solitary screening for coronary artery calcification using none-contrast CT (nCT) scanning have been suggested by many including recommendations in current guidelines weighing the non-trial evidence of improved risk prediction and could be used for opportunistic screening, but when considered by the USPSTF for systematic screening, they found the evidence of the balance between benefits and harms insufficient (table 3). The only way to clarify would be by randomised trials, but after the NLST and NELSON trials of screening lung cancer have proved its benefits, it is unlikely to be ethically acceptable only to examine the heart in a CT scan. Screening and treatment of increased CAC carries a risk of harm regarding screening-induced cancers by radiation, psychological distress, muscle pain by statins and intracerebral bleeding by antiplatelets. Consequently, RCTs are needed.

The Viborg Vascular (VIVA) screening trial

The first trial that testing multifaceted CVD screening was the Danish VIVA trial, which combined screening for AAA (by ultrasound scanning), peripheral artery disease (PAD) and hypertension (by measurement of ABI). More than 50 000 men aged 65–74 years were randomised 1:1. After 5 years, overall mortality was significantly reduced by 7%.37 The consequences to Qol were followed both overall and for individuals who tested positive, with no significant harm detected. The costs of an additional life year or QALY was well within what is considered acceptable, at approximately one-tenth of the cost of many cancer screening programmes.38

The VIVA study represents the first time that a reduction in overall mortality by a population-based screening offer has been demonstrated in a single trial. Thus, there is obvious academic interest in disentangling the effect of the three combined screening tests. In the UK, where screening for AAA is already implemented on a national scale, plans to inform this line of inquiry are already in place, where it has been suggested to randomise individuals who have already been invited to abdominal aortic screenings into groups that would or would not have supplementary ABI measurements.

The Danish Cardiovascular (DANCAVAS) screening trial

The most recent and sophisticated proposal for multiple CVD screening is another Danish trial, the DANCAVAS trial, in which nearly 50 000 men aged 65–74 years were randomised 1:2. The screening test included: (1) low-dose nCT scanning to detect and quantify CAC score and aortic/iliac aneurysms; (2) AF; (3) brachial and ankle blood pressure measurements to detect PAD and hypertension and (4) blood levels of cholesterol and haemoglobin A1c to detect diabetes and hypercholesterolaemia. Web-based self-booking and data management was used to enhance participant flexibility and to reduce the administrative burden. The complex digitalised algorithm used in this study is illustrated in figure 1, which includes the number of positive findings. In total, more than one-third of all screened initiated preventive medication (statins, aspirin, antidiabetics and anticoagulants) excluding hypertensives. The direct costs for screening and handling of the results were €80 per invited.39

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Figure 1

Flow chart of the DANCAVAS trial illustrating that complex multiple CVD screening is feasible with use of modern digital solutions. AAA, abdominal aortic aneurysm; ABI, ankle–brachial index; ALAT,alanineaminotransferase; Asc,ascending; CAC, coronary artery calcium; CVD, cardiovascular disease; DANCAVAS,Danish Cardiovascular; Diast., diastolic; Desc, descending; HgbA1c, haemoglobin A1c; LDH, lactatedehydrogenase; PAD, peripheral arterial disease; Syst, systolic.

Thus far, the trial shows that complex multiple cardiovascular general population-based screening programmes are feasible and that the programme cost is moderate relative to the health benefit potential. Only 3%–4% initiated similar prevention in the VIVA trial, which nonetheless demonstrated a relative reduction in overall mortality by 7%, and the DANCAVAS proposal provides a potential breakthrough for improving public health and life expectancy in men.