Many epidemiological projects and clinical trials on determinants of atherosclerotic cardiovascular diseases (CVDs) have been conducted to identify risk factors and demonstrate the reversibility of risk through actions directed at their reduction, both in healthy subjects and in patients with established CVDs.
At the international level, the Seven Countries Study identified risk factors common to different cultures, consistent for their importance, predictive power, and frequency among the general population.1 Smoking habit, and a rich diet with consequent high levels of total cholesterol and high blood pressure, were ascertained to be partly responsible for differences in the incidence of stroke and coronary heart disease (CHD) between countries.2,3 The WHO's European Collaborative Trial of the multifactorial prevention of CHD demonstrated the reversibility of risk among European populations, through healthier lifestyles and treatment of high risk subjects.4 To this extent the North Karelia Project represents the best example of community-based primary prevention.5
In all these studies, risk factors were carefully standardized and CVD incident events and deaths validated. The scenario may be different when evaluating whole countries. In fact in most industrialized countries CHD mortality has decreased since 1960, but in others it has increased. Time trends have been described for total cholesterol, smoking habit, blood pressure, and body mass index. However, the comparability of mortality and risk factors data was poor. The MONICA-WHO Project (Monitoring Trends and Determinants in Cardiovascular Disease) was the first multinational large-scale study specifically designed to understand the wide variations in CHD and stroke mortality among different countries, and to assess whether the mortality changes were real, and whether they were related to changes in CHD incidence, case fatality/survival, trends in classical risk factors, or advances in coronary care.6 MONICA monitored 37 populations in 21 countries and collected data on >166 000 coronary events in men and women between the ages of 35 and 64 years. According to MONICA data, in men CHD mortality rates decreased in 25 populations and increased in 11 populations while in women CHD mortality rates decreased in 22 populations and increased in 13 populations. In percentage terms, the decrease in mortality rates in the MONICA data was less than that recorded in official mortality rates based on death certificate data.7 The MONICA Project demonstrated the substantial contribution of both decreased incidence and increased survival, as well as the spontaneous changes in the prevalence of risk factors, to the declining trend of mortality: one-third of the decline in mortality was explained by changes in case fatality rates related to advances in coronary care and two-thirds by declining incidence in coronary events as partly explained by the reduction of classical risk factors.7,8 Endeavours such as the MONICA Project are not sustainable in the long term, because of costs and evolving concepts in the classification of CHD non-fatal events.9
The IMPACT model10 may be an important way to overcome those problems, because it relies on CHD mortality and published data on risk factors and treatments. With this approach, several papers have been published recently,11 including that by Björck et al.12
The authors report that between 1986 and 2002, CHD mortality rates in Sweden decreased by 53% in men and 52% in women, aged 25–84 years. During the same period, all-cause mortality declined by 400/100 000 in men (–27%) and 186/100 000 (–18%) in women. The contribution of CHD to all-cause mortality thus declined from 36.7 and 28.6% in 1986 to 23.4 and 16.8% in 2002 in men and women, respectively.
Evidence from the study of Björck et al., 12 from a recent IMPACT-Italy model,13 and from previous studies (Figure 1) consistently suggests that 50–75% of the decrease in cardiac deaths can be attributed to population-wide improvements in the major risk factors, particularly smoking, total cholesterol (dramatically, in the present study a 10.4% level of reduction accounted for a reduction of 39% in total CHD mortality), and blood pressure. The remaining 25–50% of the decreased mortality is generally explained by modern cardiology treatments for known CHD patients, such as thrombolysis, angiotensin-converting enzyme (ACE) inhibitors, statins, and perhaps revascularization procedures (coronary artery bypass surgery and coronary angioplasty). Among treatments, a major role (∼35%) is played by pharmacological treatments, both in the acute phase and for secondary prevention, whereas coronary artery bypass surgery and angioplasty accounted for <1% of deaths prevented or postponed. It is somewhat disappointing to read that primary percutaneous coronary intervention (PCI) prevented or postponed only 40 deaths among 20 955 patients suffering from acute myocardial infarction in Sweden in 2002. This well known paradox is based on the fact that primary angioplasty is applied to a minority of patients admitted to hospital (8% in the study of Björck et al.12), and that the vast majority of patients dying of acute myocardial infarction did not reach the hospital alive.
Even if reduction of risk factors in CHD patients (secondary prevention) is more rewarding in terms of efficacy, the study of Björck et al.12 confirms the great epidemiological potential of wider non-pharmacological interventions yielding a larger reduction in CHD deaths.
The IMPACT model does not include data on socio-economic status, which is known to be an independent risk factor for total and CHD mortality. However, it is likely that most of the socio-economic differences in CHD mortality can be eliminated by current best-practice interventions directed to classic coronary risk factors, if successfully implemented in both high and low socio-economic classes.14
However, modelling analyses should be interpreted with caution due to several limitations: (i) the assumption that randomized controlled trial (RCT) efficacy is equal to effectiveness; (ii) the use of up-to-date and robust RCTs or meta-analyses when modelling different treatments; and (iii) modelling analysis requires the gathering of data from numerous sources, each with recognized limitations. One way to implement the model could be to develop a sustainable way to collect a minimal data set of standardized comparable data on risk factors and treatments in primary and secondary prevention and acute coronary care throughout Europe.
We believe that this is the case for the Swedish IMPACT model. Data sources used for the modelling are derived from integrated clinical and administrative registries, all maintained by the public health system. A long-standing and validated data set and the use of disease descriptors (e.g. myocardial necrosis biomarkers) helps in standardizing hospital cardiovascular events and treatments, largely independently from the physician discharge classification and from changes in disease definition.
The EUROASPIRE project,15 quoted in the Swedish experience,12 especially with the recent extension to the high risk subjects of EUROASPIRE III, could be reshaped, extended also to incident event validation, and adapted to continuous registration in many centres in Europe, with appropriate quality controls. Probably the availability of very large natural cohorts could overcome the limits of non-randomization. In this way, a meaningful surveillance could address cardiovascular prevention in Europe.
Ultimately, this and similar studies are the final step in the virtuous cycle of evidence-based medicine, and finalize the effort for maintaining registries and conducting surveys. Although primary and secondary prevention interventions are probably both necessary to maximize population health, quantifying their relative contributions is important for regulatory health authorities in designing effective interventions based on actual data and future prevision modelling, and therefore it is also important to invest in continuous cardiovascular surveillance.
Conflict of interest: none declared.