by G. G. De Backer,Belgium
Guy G. DE BACKER MD, PhD
Department of Cardiology – University Hospital Ghent and Department of Public Health – Ghent University – Ghent, BELGIUM
The coronary heart disease (CHD) epidemic has been extremely dynamic over the last half century, with marked variation in its characteristics among different regions of the world—both between neighboring nations and even regions within a country. In the USA and most countries of the European Union, the age-standardized CHD mortality rates have decreased significantly; this may lead paradoxically to an increase in the prevalence of CHD in these countries—indeed, better survival of CHD patients and demographic changes have resulted in more elderly people suffering from CHD. In other parts of the world, the incidence of CHD is still on the increase, and it is estimated that in the coming years the number of CHD patients will increase substantially, especially in developing and transitional countries. Recent developments in the epidemic in the USA and Europe additionally suggest that the spectacular decline in CHD in the last half of the 20th century may have halted, especially in younger subjects. CHD is also an important source of disability, which can be translated into disability-adjusted life years (DALYs). The CHD burden in terms of DALYs is also projected to rise in the coming years, especially in countries in transition. There are also important regional differences in CHD burden within countries. If these differences are well understood, lessons can be learned and the knowledge applied in order to reduce the burden in less well-off communities.
Medicographia. 2009;31:343-348 (see French abstract on page 348)
“Coronary heart disease (CHD) is now the leading cause of death worldwide; it is on the rise and has become a true pandemic that respects no borders.” This statement, made in 2009, can be found on the Web site of the World Health Organization,1 and is not that different from the warning issued in 1969 by the executive board of the World Health Organization: “Mankind’s greatest epidemic: coronary heart disease has reached enormous proportions striking more and more at younger subjects. It will result in coming years in the greatest epidemic mankind has faced unless we are able to reverse the trend by concentrated research into its cause and prevention.”2
This may give the wrong impression that nothing has changed over the last 40 years. On the contrary, the epidemic of CHD has been, and still is, extremely dynamic and influenced by environmental factors, resulting in rises and falls in morbidity and mortality over relatively short time periods. Furthermore, during the last 40 years, results from observational and intervention studies have clearly shown that CHD is partial- ly preventable. Knowledge of this has been implemented in some populations more than in others, which may explain the heterogeneous changes that have taken place in CHD incidence and mortality among different places around the world.
The underlying pathology of most clinical manifestations of CHD is atherosclerosis; this is a slowly progressive process that starts in the young. Despite the progress that has been made toward prevention and cure of CHD, it appears that our actual abilities are limited to a retardation of atherosclerosis and a postponement of CHD to older age; given the demographic changes that are taking place in most communities, one has to expect a further increase in the absolute number of people with CHD.
The purpose of this article is to describe aspects of the CHD epidemic in relation to time, place, age, and gender. From this, one can learn lessons about how to prevent CHD, or at least how to reduce the number of premature deaths and improve quality of life, thus prolonging life expectancy in good health and reducing the number of disability-adjusted life years (DALYs).
The burden of coronary heart disease at the global level
CHD has received great attention because its epidemic development after World War II initially struck the industrialized countries. Nowadays, however, the burden of CHD involves the whole world; the age-standardized death rates for CHD are declining in many developed countries but are increasing in developing and transitional countries—partly as a result of demographic changes, urbanization, and lifestyle changes. Today, approximately 3.8 million men and 3.4 million women worldwide die each year from CHD.1 According to the Global Burden of Disease Study,3 the developing countries contributed 3.5 million of the 6.2 million global deaths from CHD in 1990. The projections estimate that these countries will account for 7.8 million of the 11.1 million deaths due to CHD in 2020.
But there is more to these numbers when they are translated into health care and community costs. In 2003, the economic impact of cardiovascular disease (CVD) on health care costs in the enlarged European Union (EU) was estimated to be 169 billion euros,4 which is an average of 3724 euros per capita per year. A total of 62% of this sum was related to direct costs and 21% to productivity loss. The latter is particularly important in developing countries; indeed, given the demographic composition of the populations of developing countries and the changes that will take place in age distribution, not only is the increase in CVD alarming in itself, but also the fact that this increase in the coming decades will manifest itself mainly in the economically active part of societies.
In 1990, 47% of all CVD-related deaths in developing countries occurred before the age of 70 years, in contrast with only 23% in high-income industrialized countries. This has a consequence in that there is a difference in the number of DALYs resulting from CVD; the burden of CVD expressed in DALYs from 1990 to 2020 was estimated for different populations in the Global Burden of Disease Study.3 In India and China, a spectacular rise in the number of DALYs is expected in the coming years—from a figure of less than 25 million DALYs in each country in 1990, to 30 million and 35 million in India and China, respectively, in 2020. By contrast, a decline from around 20 million to 15 million DALYs is expected in established market economies. The gap between industrialized countries and developing countries will significantly increase, and the increasing burden of CVD in terms of DALYs will clearly mostly affect developing countries in the next two decades. In different parts of the world, the dynamics of the CHD epidemic are also very different in terms of pattern, magnitude, and timing.5
The burden of coronary heart disease in the USA
CHD mortality in the USA began to decline in the mid 1960s. Age-adjusted CHD mortality rates continued to fall throughout the 1990s, although crude mortality rates changed more modestly, with CHD being postponed and manifesting itself at an older age. Because of this, CHD remains the largest single cause of death and disability in the USA.6 In 2005, CHD caused approximately 1 of every 5 deaths in the USA.7 It is the largest major killer of both American men and women. Approximately 37% of people who develop a coronary event in a given year will die from it.
Results from the Framingham study8 based on observations from 1950 until 1999 demonstrate that CHD death rates decreased by 59% during this time period. This favorable trend was seen in men and women. From 1995 to 2005, the death rate from CHD declined by 34.3%. In 2005, the overall CHD death rate was 144.4 per 100 000 population. For white males it was 187.7 and for black males it was 213.9 per 100 000, and for white females the rate was 110.0 and for black females 140.9 per 100 000.9
According to data from the National Registry of Myocardial Infarction, the in-hospital mortality rate for an acute myocardial infarction declined from 11.2% in 1990 to 9.4% in 1999.10 Analysis of CHD mortality data among US adults aged 35 to 54 years showed that the annual percentage change in (age-adjusted) mortality rates slowed markedly from 1980 to 2002 in both men and women. Particularly noteworthy is that the mortality rate among women aged 34 to 44 years of age has been increasing on average by 1.3% per year since 1997.11
With regard to incidence, data from the Atherosclerosis Risk In Communities (ARIC) and Cardiovascular Health Study indicate that annually, 785 000 Americans have a new coronary attack and 470 000 have a recurrent attack; in addition, approximately 195 000 silent myocardial infarctions occur each year. This assumes that 21% of the 935 000 first and recurrent myocardial infarctions are silent.12,13 On the basis of results from the Framingham study, it is estimated that CHD accounts for more than half of all cardiovascular events in men and women under 75 years of age.12 The lifetime risk of developing CHD after the age of 40 years is 49% in men and 32% in women.14 The total incidence of CHD in women lags behind men by 10 years.3
The burden of coronary heart disease in Europe
_ Mortality burden
CHD by itself is the single most common cause of death in Europe and the EU. Between 1 in 5 and 1 in 7 women die from CHD in Europe and the EU, and in men, it accounts for between 1 in 4 and 1 in 6 of all deaths.15 One could argue that this is the fate of communities that are growing to very old ages. This may be part of the explanation. In 2005, the mean life expectancy at the age of 50 years for men and women in all 25 EU countries was 28.6 and 33.5 years, respectively.16 Therefore, dying before the age of 75 years in an EU country may be considered as premature. In Figure 1, EU deaths under the age of 75 years are given by cause for men and women. CHD was the cause of 15% and 10% of all premature deaths in men and women, respectively.15 In other parts of Europe, CHD strikes even more: in Europe as a whole, CHD causes 20% of all male deaths before the age of 75 years and 18% of all female deaths before the same age.15
In the economically active work force of Europe (ie, those below the age of 65 years), CHD was found to be the cause of death in 16% and 12% of men and women, respectively. Age-standardized and gender-specific CHD mortality rates have significantly decreased during recent decades in many countries in the north, west, and south of Europe. However, the decline has been less apparent, or indeed absent, in Central and Eastern Europe. So based on the mortality statistics, one may conclude that the epidemic of CHD in Europe has been extremely diverse in pattern, magnitude, and timing. The decreases in the standardized CHD mortality rates are the result of great efforts made in preventive cardiology, but there are limitations: in fact, the crude CHD mortality rates remain stable or are even on the increase because of aging of the population. Therefore the total CHD burden remains high, and it may appear paradoxical that as a result of prevention, the total number of CHD deaths could even increase. New therapeutic options for prevention and treatment of CVD have resulted in an increasing number of patients who survive a cardiovascular event; in developed countries, the burden has shifted from the middle aged to the elderly, and the prevalence of CVD increases exponentially with age.
Figure 1. Causes of death in the European Union in males and
females under the age of 75 years.
disease. Based on data from reference 15.
At present there is no standardized source of worldwide or Europe-wide coronary artery disease (CAD) morbidity data. Hospital discharge data can be used, but this provides only part of the picture and the validity of such data in some countries is open to question. The results from the multinational MONItoring of trends and determinants in CArdiovascular disease (MONICA) project17 are still the best available source of information, although they are now more than 15 years old. Some MONICA centers have continued their registers and have reported more recent results.
The cross-sectional data from MONICA revealed age-standardized annual event rates for fatal and nonfatal coronary events in men aged 35 to 64 years covering a 12-fold range; from 915 per 100 000 for North Karelia, Finland to 76 per 100 000 for Beijing, China. For women, rates covered an 8.5- fold range, from 256 per 100 000 for Glasgow, UK to 30 per 100 000 for Catalonia, Spain.18
Twenty-eight-day case fatality rates ranged in men from 37% to 81% and in women from 31% to 91%. From1985 to 1990, overall 28-day case fatality was halved for hospitalized events (compared with all events), and was nearly halved for hospitalized 24-hour survivors. Because approximately twothirds of 28-day CHD deaths occurred before individuals reached the hospital, opportunities for reducing case fatalities through improved in-hospital care are limited.
Figure 2. Rates of acute coronary events in Ghent, Belgium, in
the male population aged 25-69 years during the periods 1983-
1987, 1988-1992, and 1996-2001.
Over the decade studied, CHD mortality rates as defined by MONICA criteria fell annually by an average 2.7% in men (range –8.0% to +4.2%) and by an average 2.1% in women (range –8.5% to +4.1%). Changes in nonfatal rates were smaller (–2.1%; range –6.5% to +2.8%).19 There were, however, important regional differences in all of these changes; countries from the same geographical area have experienced very different time trends in terms of the CHD epidemic. For example, incidence rates for men living in North Karelia, Finland, fell by 6.5% per year from 1983 to 1996, but rose by 1.2% per year for men of the same age living in Kaunas, Lithuania. For women, the incidence fell by 5.1% per year in North Karelia, but rose by 2.7% per year in Kaunas in women of similar age.17
MONICA was partly established to investigate how much of the reported decline in CHD mortality is attributable to improvements in case fatality, and how much is attributable to declines in CHD incidence. The project concluded that, “contribution to changing CHD mortality varied, but in populations in which mortality decreased, coronary event rates contributed two thirds and case fatality one third.”17
Patterns of CHD incidence and case fatality across Europe may have changed since the mid 1990s. Some MONICA centers have been able to continue their registers until now, but in comparing time trends over a longer time period, one has to consider possible differences in the definition of coronary events following the introduction of troponin estimations. In Ghent, Belgium, the register continued, and the MONICA methodology to identify and define acute coronary events was kept identical. In Figure 2, results are given from the register of acute myocardial infarction in the population aged less than 70 years in the city of Ghent. Attack rates are presented for the male population; when comparing the period 1983-1986 with the period 1996-2001, a decline of almost 40% was observed.
In Figure 3, the most recent results from the register up to 2005 are given; since 1999, the study population has been extended up to the age of 74 years. In the figure, attack rates are given for the male and female populations; results are given both for all events and only nonfatal events, the latter meaning only those patients who survived for at least 28 days. The curves have now become very flat; statistically there was no change observed from 1999 to 2005.
This confirms results published from the US, where agespecific mortality rates for CHD have been found to be leveling off in younger adults.11 These observations are also consistent with results from a population-based autopsy study of non-natural deaths, suggesting that temporal declines in the grade of CHD at autopsy have ended.20 All this necessitates continuous and careful monitoring of an epidemic that continues to change over relatively short time periods—indicating the importance of environmental influences—with the use of valid and comparable methods that allow accurate surveillance of the epidemic dynamics.
_ Quality of life
CHD is not only the leading cause of death, but is also an important source of disability that translates into DALYs. In 2002, CHD was the cause of 11% of all DALYs in Europe, comparable to that caused by all cancers. All CVD taken together was, however, responsible for 23% of all DALYs, and was thus the most important cause.15 CVD is responsible for 10% of DALYs lost in low and middle income countries, and 18% in high income countries. The CHD burden is projected to rise from around 47 million DALYs globally in 1990 to 82 million DALYs in 2020.1
Figure 3. Age-standardized rates (per 10 000 patients) of acute
myocardial infarction in men and women in Ghent, Belgium.
The burden of coronary heart disease at the national level
Looking solely at the burden of CHD at the international level may hide important regional differences. In 2005, male life expectancy at the age of 50 years in the 25 countries of the EU varied from 21.3 years in Latvia to 30.4 years in Italy16; for women, the variation between countries was 6.1 years. The healthy life expectancy (HLY) varied even more: the range in HLY at age 50 years was 14.5 years in men and 13.7 years in women. Death rates from CAD are generally higher in Central and Eastern Europe than in Northern, Western, and Southern Europe. For example, the death rate for men aged less than 65 years living in Ukraine is 14 times higher than in France, and for women it is 25 times higher. Likewise, Western Europe has generally higher death rates than Southern Europe: for example, in Ireland, the death rate for men aged less than 65 years is 1.6 times higher than in Italy, and for women it is 1.8 times higher. In Figure 4, the age-standardized mortality rates for CHD in the year 2000 are given for populations aged 45 to 74 years in different European countries; the figures vary from 0.65 to 4.61 per 1000, illustrating that there is still a clear North-East to South-West gradient in CHD mortality within Europe.21
The Institut des Sciences de la Santé carried out a study examining CHD mortality changes in the EU population in individuals less than 75 years of age between 1990/91 and 2000/02. Age-standardized CHD mortality fell in all countries, but not equally across the EU. CHD mortality declined by almost a half in the Czech Republic, the UK, Ireland, and Finland. Elsewhere, rates fell by about one fifth to one third; the only exceptions were Latvian men and Polish women, in whom the improvements were just over 10%.22
But even within countries, significant regional variation in CHD mortality has been observed. In Germany, for example, there was found to be an East-West gradient, with a twofold increased risk of dying from CHD in the state with the highest mortality rate compared with the lowest mortality.23 In Great Britain, a North-South gradient has been observed, with CHD mortality rates being higher in the north.24 In France, the mortality from CHD also shows a North-South gradient, with very low figures in the south-west region.25 In Belgium, large differences in CHD incidence and mortality have been observed, with higher rates in Wallonia compared with Flanders.26 All these regional differences are partly explained by variations in classical risk factors and in socioeconomic factors.
The burden of CHD remains high across Europe and the rest of the world. CHD continues to be the main cause of death and a major cause of morbidity and loss of quality of life. The decline in age-standardized mortality rates and in the incidence of CHD in many countries illustrates the potential for prevention of premature deaths and for prolonging healthy life expectancy. However, one should realize that this will paradoxically increase the prevalence of patients with CHD, especially in old age. This is a challenge for modern cardiology; specific attention needs to be given to the development of guidelines in elderly patients. For policy makers, it is also important to know whether major contributors to morbidity and mortality such as CHD are tracking up or down. A valid and actual description of the epidemic by place, by time, and by personal characteristics is continuously needed to guide and support appropriate health policies. _
1. World Health OrganizationWeb site. http://www.WHO.int. AccessedMarch 26, 2009.
2. World Health Organization Regional Office for Europe. The prevention and control of major cardiovascular diseases: report on a conference. Euro 8214. Brussels: WHO Regional Office for Europe. 1973.
3. Murray CJL, Lopez AD. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Disease, Injuries and Risk Factors in 1990 and Projected to 2020. Boston, Ma: Harvard University Press; 1996.
4. Leal J, Luengo-Fernandez R, Gray A, Petersen SQ, Rayner N. Economic burden of cardiovascular diseases in the enlarged European Union. Eur Heart J. 2006;27:1610-1619.
5. Mirzaei M, Truswell S, Taylor R, Leeder SR. Coronary heart disease (CHD) epidemics: not all the same. Heart. 2008, December 18. Epub ahead of print.
6. Lloyd-Jones D, Adams R, Carnethon M, et al; American Heart Association Statistics Committee and the Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics 2009 Update. A report from the American Heart Association Statistics Committee and the Stroke Statistics subcommittee. Circulation. 2008;119:480-486.
7. Heron MP, Hoyert DL, Xu J, Scott C, Tejada-Vera B. Deaths: preliminary data for 2006. Natl Vital Stat Rep. 2008;56:1-52.
8. Fox CS, Evans JC, Larson MG, Kannel WB, Levy D. Temporal trends in coronary heart disease mortality and sudden cardiac death from 1950-1999: the Framingham Heart Study. Circulation. 2004;110:522-527.
9. Rea TD, Pearce RM, Raghunathan TE, et al. Incidence of out-of-hospital cardiac arrest. Am J Cardiol. 2004;93:1455-1460.
10. National Registry of Myocardial Infarction Web site. http://www.nrmi.org/ nrmi_data.html. Accessed February 20, 2008.
11. Ford ES, Capewell S. Coronary heart disease mortality among young adults in the U.S. from 1980 through 2002: concealed leveling of mortality rates. J Am Coll Cardiol. 2007;50:2128-2132.
12. Thom TJ, Kannel WB, Silbershatz H, D’Agostino RB. Cardiovascular disease in the United States and preventive approaches. In: Fuster V, Alexander RW, O’Rourke RA, eds. Hurst’s The Heart, Arteries and Veins. 10th ed. New York, NY: McGraw-Hill; 2001:3-7.
13. Boland LL, Folsom AR, Sorlie PD, et al. Occurrence of unrecognized myocardial infarction in subjects aged 45 to 65 years: the ARIC Study. Am J Cardiol. 2002;90:927-931.
14. Lloyd-Jones DM, Larson MG, Beiser A, Levy D. Lifetime risk of developing coronary heart disease. Lancet. 1999;353:89-92.
15. European Cardiovascular Disease Statistics 2008. European Heart Network Web site. http://www.ehnheart.org. Accessed April 29, 2009.
16. Jagger C, Gillies C, Moscone F, et al. Inequalities in healthy life years in the 25 countries of the European Union in 2005: a cross-national meta-regression analysis. Lancet. 2008;372:2124-2131.
17. Tunstall Pedoe H. MONICA Monograph and Multimedia Sourcebook. Geneva, Switzerland: World Health Organization; 2003.
18. Tunstall Pedoe H, Kuulasmaa K, Amouyel P, Arveiler D, Rajakangas AM, Pajak A. Myocardial infarction and coronary deaths in the WHO MONICA project. Circulation. 1994;90:583-612.
19. Tunstall Pedoe H, Kuulasmaa K, Mahonen M, Tolonen H, Ruokokoski E, Amouyel P. Contribution of trends in survival and coronary event rates to changes in CHD mortality: 10 year results from 37 WHO MONICA project populations. Lancet. 1999;353:1547-1557.
20. Nemetz P, Roger VL, Ransom JE, Bailey KR, EdwardsWD, Leibson CL. Recent trends in the prevalence of coronary disease. A population-based autopsy study of nonnatural deaths. Arch Intern Med. 2008;168:264-270.
21. Muller-Nordhorn J, Binting S, Roll S, Willich SN. An update on regional variation in cardiovascular mortality within Europe. Eur Heart J. 2008;29:1316-1326.
22. Newey C, Nolte E, McKee M, Mossialos E. Avoidable mortality in the enlarged European Union. Institut des Sciences de la Santé (Paris). http://www.euractiv. com. Accessed 29 April, 2009.
23. Muller-Nordhorn J, Rossnagel K, Mey W, Willich SN. Regional variation and time trends in mortality from ischaemic heart disease: East and West Germany 10 years after reunification. J Epidem Community Health. 2004;58: 481-485.
24. Morris RW, Whincup PH, Emberson JR, Lampe FC, Walker M, Shaper AG. North-South gradients in Britain for stroke and CHD: are they explained by the same factors? Stroke. 2003;34:2604-2609.
25. Lang T, Ducimetiere P, Arveiler D, et al. Trends and geographical disparities in CHD in France: are results concordant when different definitions of events are used? Int J Epidemiol. 1999;28:1050-1058.
26. De Henauw S, De Bacquer D, De Smet P, Kornitzer M, De Backer G. Trends in coronary heart disease in two Belgian areas: results from the MONICA Ghent- Charleroi study. J Epid Comm Health. 1999;53:89-98.