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European Heart Journal Advance Access published online on February 5, 2008
European Heart Journal, doi:10.1093/eurheartj/ehm604
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org.

An update on regional variation in cardiovascular mortality within Europe

Jacqueline Müller-Nordhorn*, Sylvia Binting, Stephanie Roll and Stefan N. Willich

Institute of Social Medicine, Epidemiology and Health Economics, Charité University Medical Center, Luisenstr. 57, D-10117 Berlin, Germany

Received 25 May 2007; revised 22 November 2007; accepted 6 December 2007.

* Corresponding author. Tel: +49 30 450 529026, Fax: +49 30 450 529902. Email: jacqueline.mueller-nordhorn{at}charite.de


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Acknowledgements
 References
 
Aims: For risk assessment in primary prevention of cardiovascular disease, different risk charts are used for high-risk and low-risk countries. The objective of the present study was to analyse the current regional variation in cardiovascular mortality within Europe.

Methods and results: Age-standardized mortality rates were calculated for ischaemic heart disease (IHD) and cerebrovascular disease (CVD) from data provided by Eurostat and the National Statistical Offices of the respective countries (2000). For age-standardization, the European standard population (1976) was taken. Rates were calculated both on a national and on a regional level. There is still a clear north–east to south–west gradient in mortality from IHD. With regard to CVD, there appears to be a ‘green’ circle of reduced mortality in the centre of Western Europe including countries such as France or the northern regions of Italy and Spain. Countries with higher mortality rates, such as the Central and East European countries as well as some Mediterranean countries including Greece, Portugal, and certain regions in Southern Spain and Italy, surround this circle.

Conclusion: There is a changing pattern of cardiovascular mortality within Europe, which needs to be taken into account in the definition of high- and low-risk countries in the primary prevention of cardiovascular disease.

Key Words: Regional variation • Cardiovascular mortality • Europe • Prevention


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Acknowledgements
 References
 
Regional variations in cardiovascular mortality have been observed both between and within countries in Europe.1–3 Sans et al.1 reported a clear north–east to south–west gradient in cardiovascular disease mortality (1990–1992; 45–74 years age-adjusted) with the lowest rates for both men and women in France, Spain, Switzerland, and Italy. The highest rates were observed in Central and East European countries such as Ukraine, Bulgaria, or the Russian Federation. When dividing cardiovascular mortality into mortality due to ischaemic heart disease (IHD) and cerebrovascular disease (CVD), some differences in the regional distribution became apparent. For IHD, the north–east to south–west gradient was similar to that observed for cardiovascular diseases as a whole. For CVD, however, there appeared to be a predominantly east to west gradient in mortality. Regional variation within countries, similarly, can be huge.2,4,5 In Germany, for example, there was an east–west gradient in mortality with a two-fold increased risk of dying from IHD in the state with the highest compared with the state with the lowest mortality.2 A north–south gradient has been observed for Britain with higher cardiovascular mortality rates in the north compared with the south.4 In France, similarly, mortality due to IHD showed a north–south gradient.5

There are many reasons for the observed regional variations in cardiovascular diseases. They include differences between populations in ‘classic’ coronary risk factors such as smoking, hypertension, hyperlipidaemia, diabetes, or overweight as well as socio-economic factors, lifestyle variables such as diet, alcohol use, physical activity, medical care, genetic factors, and environmental conditions. The current European Guidelines on Cardiovascular Disease Prevention in Clinical Practice take national variation in cardiovascular mortality into account.6 In the primary prevention setting, the overall 10-year cardiovascular risk is estimated for different risk factor combinations. The assessment of cardiovascular risk takes into account the following risk factors: age, sex, smoking, systolic blood pressure, and cholesterol. An increased risk ≥5% of a fatal cardiovascular event in the next 10 years should lead to increased preventive efforts, both with regard to lifestyle changes and medication. In the guidelines, the use of two different risk assessment charts is recommended: one for countries with high risk and one for countries with low risk. On the basis of a number of cohort studies assessing cardiovascular risk, countries with a low risk include Belgium, France, Greece, Italy, Luxembourg, Spain, Switzerland, and Portugal and countries with a high risk include all other European regions.

The objective of the present study was to analyse the current variation in cardiovascular mortality within Europe, both on a national and on a regional level.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Acknowledgements
 References
 
Data sources
For cardiovascular mortality rates on a regional level, we contacted the National Statistical Offices of the respective European countries for the year 2000. For IHD and CVD, we used the International Classification of Diseases (ICD)-10 codes I20–I25 and I60–I69. For the assessment of cardiovascular mortality, i.e. IHD and CVD, we combined the respective ICD codes. We excluded countries such as Liechtenstein, Luxembourg, Iceland, and Malta from the analysis, because the year-to-year variation in small countries is too large. For Belgium, no data were available for the year 2000, neither on the regional nor the national level. For Italy, no data were available for the region of Bolzano.

Age-standardization
The statistical offices provided either number of deaths from IHD and CVD as well as population data per 5-year age group, or crude standardized mortality rates per 100 000 per 5-year age group. In case of absolute numbers of death, we calculated the standardized rates by dividing the number of deaths in the respective age group by the population number in this age group. Crude standardized rates were assessed for all, and separately for men and women; age-standardization was performed subsequently. As mortality in younger age groups is very low and may, therefore, dilute differences in mortality, we restricted the age-standardization to the age groups 45–74 years. For age-standardization using the direct method, the European standard population (1976) was taken. The weights used for standardization by 5-year age groups were 7 (45–54 years), 6 (55–59 years), 5 (60–64 years), 4 (65–69 years), and 3 (70–74 years).7 The same weights were used for all, men, and women. All-cause mortality rates were calculated for comparison.

Cartographic and statistical analyses
We analysed the data from the corresponding regional level of each country. Age-standardized mortality rates were divided into five regular quintiles and displayed accordingly by different shades of colours.8 In addition, rate ratios with the respective 95% confidence intervals (95% CIs) were calculated for men and women between the state with the highest mortality rate and the state with the lowest mortality rate. For the cartographic analyses and the calculation of age-standardized mortality rates as described above, EasyMap, Version 8.0, and SAS for Windows, Version 9.1, were used.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Acknowledgements
 References
 
Within Europe, there is a considerable variation in cardiovascular and all-cause mortality both on a national and on a regional level (Figures 1GoGoGoGo–6, Tables 1Go–3). Tables 1–3 summarize national mortality rates for IHD, CVD, and all-cause mortality for all, men, and women. Figures 1–6 show mortality rates from IHD, CVD and cardiovascular disease, i.e. IHD and CVD combined, for both men and women in European regions in 2000. The rate ratio of dying from IHD between the countries with the highest mortality compared with the lowest mortality is 7.1 (95% CI, 6.6–7.6) for men (Latvia vs. France) and 9.9 (95% CI, 8.5–11.5) for women (Estonia vs. France). For CVD, the rate ratio is 14.5 (95% CI, 12.7–16.4) for men (Estonia vs. Switzerland) and 12.0 (95% CI, 10.2–14.1) for women (Estonia vs. Switzerland).


Figure 1
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  		Figure 1 Age-standardized mortality from ischaemic heart disease in European regions (men; age group 45–74 years; year 2000)

 

Figure 2
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  		Figure 2 Age-standardized mortality from ischaemic heart disease in European regions (women; age group 45–74 years; year 2000)

 

Figure 3
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  		Figure 3 Age-standardized mortality from cerebrovascular disease in European regions (men; age group 45–74 years; year 2000)

 

Figure 4
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  		Figure 4 Age-standardized mortality from cerebrovascular disease in European regions (women; age group 45–74 years; year 2000)

 

Figure 5
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  		Figure 5 Age-standardized mortality from cardiovascular disease, i.e. ischaemic heart disease and cerebrovascular disease combined, in European regions (men; age group 45–74 years; year 2000)

 

Figure 6
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  		Figure 6 Age-standardized mortality from cardiovascular disease, i.e. ischaemic heart disease and cerebrovascular disease combined, in European regions (women; age group 45–74 years; year 2000)

 

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  		Table 1 Age-standardized mortality rates (45–74 years) from ischaemic heart disease in Europe (2000)

 

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  		Table 2 Age-standardized mortality rates (45–74 years) from cerebrovascular disease in Europe (2000)

 

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  		Table 3 Age-standardized mortality rates (45–74 years) from all-cause mortality in Europe (2000)

 
With regard to IHD, there is a clear north–east to south–west gradient in age-standardized mortality within Europe (Figures 1 and 2). Particularly, countries from Central and Eastern Europe have high mortality rates compared with other European countries. For IHD, the lowest mortality rates are found in France, Portugal, Italy, Spain, Switzerland, and the Netherlands. There is a considerable within-country variation in IHD in Germany, the UK, and Poland. With regard to cerebrovascular mortality rates (Figures 3 and 4), there is a different pattern of regional variation compared with IHD. Cerebrovascular mortality is reduced in the centre of Western Europe with the lowest national mortality rates in Switzerland, France, Norway, Spain, the Netherlands, and Italy. Countries and regions with higher mortality rates surround this circle of reduced mortality, such as the Central and East European countries as well as some Mediterranean countries including Greece, Portugal, and certain regions in Southern Spain and Italy. There is a considerable within-country variation in cerebrovascular mortality in Italy, Spain, Portugal, and the UK. Cardiovascular disease (Figures 5 and 6) shows a similar north–east to south–west gradient compared with IHD.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Acknowledgements
 References
 
Within Europe, there is still a clear north–east to south–west gradient in mortality from cardiovascular disease and IHD. With regard to CVD, the pattern, however, is less clear. There appears to be a ‘green’ circle of reduced mortality in the centre of Western Europe with regard to countries such as France or the northern regions of Italy and Spain. Countries with higher mortality rates surround this circle, such as the Central and East European countries as well as some Mediterranean countries including Greece, Portugal, and certain regions in Southern Spain and Italy.

When analysing the regional variation in Europe, it has to be kept in mind that mortality from both IHD and CVD has continuously been decreasing in most West European countries over the last decades.9,10 Kesteloot et al.9 showed an age-adjusted annual percentage change in cardiovascular mortality rates in Western Europe of –1.8 in men and –2.1 in women, aged 45–75 years. In some West European countries such as Finland, efforts in reducing the risk factors with public health interventions on a population level have been enormous.11 In most Central and East European countries, on the other hand, cardiovascular mortality increased during the 1970s and 1980s and started to decline in the early to mid-1990s.9,10 Despite the recent decrease, mortality rates are still considerable higher in most Central and East European countries compared with West European countries. Some countries such as the Ukraine reach almost top levels in a worldwide comparison.10 Although most Central and East European countries appear to have reached their peak in cardiovascular mortality, the majority of them can clearly still be classified as high-risk countries.

A number of risk factors can be responsible for the variation on both the national and the regional level. Risk factors include socio-economic variables such as income or employment status, psychosocial factors such as stress or the prevalence of depression, the ‘classic’ cardiovascular risk factors such as hypertension, hyperlipidaemia, and overweight, lifestyle variables such as physical activity, nutritional pattern, and smoking, environmental factors, or medical care. Studies such as the WHO Monica (monitoring of trends and determinants in cardiovascular diseases) Project or the Seven Countries Study allow the comparison of certain risk factors in European countries.12,13 With regard to the east–west gradient in Europe, dietary fat intake appears to play a major role.9,14,15 In Eastern Europe, a higher consumption of saturated fat has been reported compared with West European countries during the 1980s and early 1990s. In Poland, changes in dietary fat intake during the 1990s, leading to a more favourable ratio of polyunsaturated to saturated fat, were associated with a drop in mortality from IHD by approximately one quarter.15 Other factors such as the consumption of fruit and vegetables, smoking, or alcohol consumption have been linked to the east–west gradient in mortality.2

The attribution of single risk factors to regional variation may also vary depending on the geographical location of the area of interest. For example, regional differences between Israel, Bavaria (Germany), and the Czech Republic were found to be associated particularly with differences in blood pressure levels.16 Within England, on the other hand, the regional variation was associated to a large extent with differences in smoking prevalence.4 In addition, secondary prevention in IHD may vary considerable between European countries as shown by the EUROASPIRE I and II surveys.17 The EUROCISS Project (European Cardiovascular Indicators Surveillance Set) listed the existing population-based registers of acute myocardial infarction and stroke in Europe.18 Whereas a number of countries such as Belgium, Denmark, Finland, France, Germany, Italy, Norway, Spain, and Sweden have registers for cardiovascular morbidity, there is a lack in other countries.

The analysis of regional variation in cardiovascular mortality is important for the classification of countries into high- and low-risk countries and the recommendations provided by current guidelines. Misclassification may have a huge impact at the population level with regard to the number of people over-(or under-)treated. Regular updates on the complex pattern of regional variation within Europe are needed to make efficient prevention possible. Although the SCORE model allows the insertion of national mortality data and data on prevalence of risk factor to produce national risk charts,19,20 there is, of course, no substitute for risk assessment based on actual population data. The baseline survival curves in the SCORE project are based on the selected cohort studies from the respective countries.21 For the high-risk model, cohorts from Denmark, Finland, and Norway are used, whereas for the low-risk model, cohorts from Belgium, Italy, and Spain are used. Most of these cohort studies were conducted during the 1980s and 1990s. When analysing time trends in cardiovascular mortality, it seems that former high-risk West European countries now have similar mortality rates compared with those of the low-risk countries at the time of the cohort studies.22–24 It is, therefore, indicated to reconsider the classification of countries into high-risk and low-risk countries for risk assessment in primary prevention of cardiovascular disease. For example, it may be more appropriate and practical to generally classify West European countries as low-risk countries and Central and East European countries as high-risk countries. Otherwise, there may be an overestimation of current cardiovascular risk in certain populations leading to unnecessary therapies and costs.

Further research into the underlying reasons of the observed differences in cardiovascular mortality in Europe both between and within countries is indicated. Multilevel analyses combining individual patient data if available with aggregate data may be a feasible approach to identify those risk factors attributing the most to the regional variation. Preventive strategies may then focus on specific risk factors. In addition, the monitoring of cardiovascular disease and risk in Europe may become more manageable when focusing on those risk factors with the highest attributable risk.


   Acknowledgements
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Acknowledgements
References
 
We thank the European Statistical Office (Eurostat) and the respective National Statistical Offices for kindly providing crude and/or standardized mortality rates from ischaemic heart disease and cerebrovascular disease for the year 2000.

Conflict of interest: none declared.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Acknowledgements
 References
 

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