Ischaemic heart disease

Ischaemic heart disease (IHD) and stroke are the most frequently occurring among cardiovascular diseases

Cardiovascular disease (CVD) is the leading cause of death and hospitalisation in both sexes in nearly all EU countries. More than 1.9 million people die every year in the EU-25 countries, accounting for nearly half of all deaths (47% of deaths in women and 39% deaths in men; see Death by main cause). From the total group of cardiovascular diseases, ischaemic heart disease and stroke occur the most frequently. Both are of an atherosclerotic origin. This EUphact deals exclusively with IHD. The topic of stroke will be discussed in a separate EUphact.

Ischaemic heart disease

According to the International Classification of Diseases, as shown in the table below, IHD includes acute myocardial infarction (AMI), commonly known as heart attack, acute coronary syndrome (ACS), angina pectoris and other forms of coronary heart disease (CHD). IHD is caused by atherosclerosis, i.e. the accumulation of plaque on the walls of the coronary arteries. This causes an oxygen shortage (ischaemia) in the heart muscle. Chest pain, biochemical markers of myocardial necrosis, and ECG findings are important for diagnosis.

Table 1: Division of Ischaemic Heart Disease according to the International Classification of Diseases (ICD; source; EUROCISS, 2003)

AMI/ACS: sudden and complete closure of a coronary artery

An AMI/ACS occurs when a blood clot suddenly blocks a coronary artery. Through this blockage a part of the heart muscle no longer receives any oxygen and dies. At the site of the infarction a scar develops (old myocardial infarction), which eventually turns into connective tissue leading to a loss of function in the heart muscle. Major complications will result in heart failure. An AMI/ACS can be associated with serious cardiac arrhythmia and can lead to death.

The clinical and cardiac marker manifestations are determined by the volume of heart muscle affected and the severity of ischaemia. Despite the similarities in disease mechanism, the time course and severity of cardiac complications vary substantially across the spectrum of AMI/ACS. Similarly, treatment patterns differ. AMI/ACS should be classified as either:

• ACS with unstable angina; or
• ACS with myocardial necrosis; or
• ACS with clinical AMI.

Angina pectoris

Angina pectoris, literally pain in the chest, is almost always caused by one or more constrictions in the coronary arteries, leading to a temporary shortage in the blood flow and available oxygen in part of the heart muscle. This oxygen shortage is often associated with physical effort, when the heart muscle needs more oxygen than the constricted blood vessel can supply. The symptoms of angina pectoris disappear shortly after the physical exertion has ended. Angina pectoris causes a typical oppressive, pressing chest pain.

Angina pectoris can be separated into stable and unstable angina pectoris. There are differences in symptoms, in the pathophysiological state and probably also in the prognosis. In stable angina pectoris the symptoms do not progress in intensity over time. They usually occur in response to provocative influences, such as physical exertion or a change from colder to warmer temperatures. Pathologically, an atherosclerotic constriction is present in the coronary arteries. Unstable angina pectoris is diagnosed where the same symptoms are newly occurring or increasing in relatively short time, without preceding provocative influences. Pathologically, it can be associated with a clot developing in the coronary artery where an atherosclerotic lesion or plaque has formed.

ECG specifies location and severity of acute events

An electrocardiogram (ECG) provides important information about the location and seriousness of the vessel blockage in patients suffering from an acute AMI/ACS. In the case of stable angina pectoris, abnormalities are only visible on the ECG when the patient is actually experiencing the symptoms. Therefore patients with (suspected) angina pectoris are subjected to an examination, such as a running/biking test, in which their heart is put under strain. An eventual oxygen shortage can then be identified.

The course of disease depends on various factors

The prognosis of patients with IHD is dependent on the seriousness of the atherosclerotic abnormalities of the heart and other eventual affected organs (brain, kidney, large blood vessels), the remaining functions of the heart and the presence and scope of the known risk factors for atherosclerosis.

The MONICA project as a pioneer in cardiovascular epidemiology

At present, comparable data on morbidity from ischaemic heart disease are not collected on a country-wide basis across Europe. Over 10 years of surveillance (between the mid-1980s and the mid-1990s), the WHO MONICA project (MONItoring trends and determinants in CArdiovascular disease) examined the incidence of coronary events in 37 different populations in 21 countries (including 29 populations in 16 European countries). These populations were not necessarily representative of the countries in which they were located. However, MONICA data were collected through standardized methodologies. Therefore these data are comparable across Europe and are to this day recognised as the golden standard.

The Rates of coronary events and case-fatality in 13 European countries, over a 10-year period around 1990, as derived from the MONICA project (Tunstall-Pedoe et al., 1999) showed that attack rates for coronary events (myocardial infarction - heart attack) were higher in MONICA project populations in Northern, Central and Eastern Europe than in Southern and Western Europe (with the exception of the United Kingdom). During the project period, attack rates have been falling rapidly in Northern and Western Europe but not as fast in Southern, Central and Eastern Europe and in some countries, such as Lithuania (Kaunas), East Germany and Spain (Catalonia) they have even risen.

Contributions to changing IHD mortality varied, but in populations with decreasing mortality, the decrease in coronary events contributed two thirds and improved case fatality one third (Tunstall-Pedoe et al., 1999). Of all patients who died within 28 days after the onset of symptoms, about two thirds died before reaching the hospital. Therefore, primary prevention seems more effective in preventing IHD mortality than improving care (Chambless et al., 1997).

Current population-based registers are mostly regional

Data collection by the MONICA project ended in 1994-95. After that, some countries continued to collect data, sometimes using simplified procedures, but ensuring the validation of coronary events. An updated inventory of population characteristics and case definitions of AMI/ACS registers in 14 countries or regions was performed by the EUROCISS project (EUROCISS, 2003; Madsen et al., 2007). It appears that these registers cover different age groups (ranging between 25 and 74 years) and use different procedures for event definition. Therefore, data comparison between countries is difficult.

See as an example, data on attack rates and case fatality of coronary events are given from the Italian register. These recent Italian data cannot be directly compared to the MONICA data since the upper age limit was extended to 74, and since not all cases have been validated (the Italian registry validates cases on a sample basis).

IHD is the largest single cause of death in the EU

IHD by itself is the most common single cause of death in the EU, accounting for 744.000 deaths each year. Around one in six men (17%) and over one in seven women (16%) die from the disease, as shown by the figure Death by main cause.

IHD mortality shows a clear East-West gradient

Recently, an analysis was performed on Eurostat mortality data following the recommendations by the EUROCISS project (EUROCISS, 2003). According to these recommendations, data were selected for the age range 35-74, since below 35 events are rare and above 74 the age structure differs a lot between countries. Data were age-standardised according to the European Standard population.

In the age range 35-74, IHD mortality accounts for 15% of deaths, and this percentage increases with age. IHD mortality patterns show a clear-cut East-West gradient, with the highest rates being reported from the Baltic countries and from Eastern Europe. When observed per country, the rates vary between 42.7 deaths per 100,000 population in France to 327 per 100,000 in Latvia. This 8-fold difference applies both to men andwomen (men: 72 deaths per 100,000 in France and 555 per 100,000 in Latvia; in women these numbers are 16 and 167, respectively).

Mortality decreases in all regions, but more slowly in the East

Over the past ten years, the data for the 35-74 age range show a decreasing IHD mortality in each of the six regions (see Trends in IHD mortality for men in six European regions and Trends in IHD mortality for women in six European regions). The decrease is strongest, in relative terms, in Central Eastern Europe (Czech and Slovak Republics, Poland), followed by the North (Scandinavian countries, Ireland and the United Kindom) and Central Europe (Belgium, The Netherland, Luxembourg, Germany, Austria and Slovenia).

The actual percentage decreases are, for men and women, respectively: Central Eastern Europe: 45%, 51%; Northern Europe: 38%, 41%; Central Europe: 37%, 40%; Southern Europe: 34%, 41%; Baltic states: 27%, 36%; Balkan Eastern: 27%, 23%. In all regions except Balkan Eastern, not only the rates themselves, but also the percentage decrease seems to be more favourable for women than for men. For more details, see Trends in IHD mortality for men in six European regions and Trends in IHD mortality for women in six European regions.

In the time range covered by the MONICA project (mid-1980s to mid-1990s), around two-thirds of the decline in IHD mortality was due to a decline in IHD incidence rates; the remaining one-third of the decline was due to improvements in survival because of better treatments (Tunstall-Pedoe et al., 1999; Kuulasmaa et al., 2000; Tunstall-Pedoe et al., 2000).

In addition to the EUROCISS compilation, trend data on IHD mortality by country (standardised death rates) are also available from the WHO mortality database: see Mortality (SDR) from IHD in men, all ages, Mortality (SDR) from IHD in men, ages 25-64, Mortality (SDR) from IHD in women, all ages and Mortality (SDR) from IHD in women, ages 25-64. When compared to the figures shown for the six European regions for 1994-2003, these trends show the same steady decrease also from 1980. The numbers are not directly comparable because of different age windows being used.

IHD has far-reaching consequences

A heart attack can lead to arrhythmias and heart failure. It can also cause angina pectoris. When patients experience severe complaints, an operation can be performed on the coronary arteries (coronary by-pass surgery) or a percutaneous intervention can be carried out (Percutaneous Transluminal Coronary Angioplasty). Continuing symptoms can result in a patient being limited in his/her physical activities and being forced to give up employment. Some patients develop depressions or anxieties, disorders that cannot always be identified.

High death toll from acute heart attack

According to the Euro Heart Survey 2001, 11% of patients admitted to hospital with an acute infarction die within 30 days. For patients with unstable angina pectoris this figure is 2% (Hasdai et al., 2002). Patients diagnosed with (stable) angina pectoris have a much better prognosis. Only 2 to 3% of these patients suffer from serious complications such as death or an acute heart attack per year (Daly et al., 2006).

See the table on rates of coronary events and case-fatality in 13 European countries which shows the case-fatality as recorded in the MONICA project for all coronary events, thus including deaths occurring before arrival in the hospital. These case-fatality rates shown in this table range from 35% in Northern Sweden and Iceland to over 80% in the Polish region of Tarnobrzeg.

Prognosis for coronary heart disease has improved over time

The prognosis for coronary heart disease has improved in the past decades. The two-year death rates for Swedish patients with unstable angina pectoris, for example, dropped from 30% in 1988 to 19% in 1995 (Abrahamsson et al., 2000). Research in the United States has shown that a positive outcome is now more common for heart attack patients (Hellermann et al., 2002).

Diverging risk factors exist for cardiovascular disease

Longitudinal studies, such as the Seven Country and Framingham studies identified major risk factors for cardiovascular disease (CVD): smoking and a rich diet, with consequent high levels of total cholesterol and high blood pressure. Differences in the prevalence of these risk factors among participating countries have been ascertained to be responsible for differences in the incidence of stroke and IHD (Keys et al., 1980; Keys et al., 1981; Mariotti et al., 1982). For more detailed information about the prevalence, causes and consequences of (high) blood pressure, see the EUphact Blood Pressure.

Other studies have contributed to the knowledge of CVD risk factors and demonstrate that low socio-economic status, physical inactivity, obesity and diabetes are also associated with an increased CVD risk (Marmot et al., 1978a; Marmot et al., 1978b; Morris et al., 1980; Barrett-Connor et al., 1991).

More recently, a standardized case-control study of acute myocardial infarction conducted in 52 countries has demonstrated that abnormal lipids, smoking, hypertension, diabetes, abdominal obesity, psychosocial factors, unfavourable patterns of fruit, vegetable and alcohol consumption and of physical activity account for most of the risk of myocardial infarction worldwide. See Association of risk factors with acute myocardial infarction .

Finally there are other factors such as infections, personal such as the ability to cope with stress (Rosengren et al., 2004) and exposure to air polluting particles (Hoek et al., 2002, Brook et al., 2004) that can play a role. More detailed research is needed to identify the precise contribution of these individual factors.

Alongside these observational studies that have demonstrated the predictive role of risk factors, there are other studies, which have highlighted the risk reversibility (reducing disease incidence by reducing the risk factors) and the substantial decrease of CVD and other chronic degenerative diseases through preventive action at both individual and population levels (Puska et al., 1995).

Although priorities can differ between geographic regions because of variations in the prevalence of risk factors, disease occurrence and socio-economic status, the effective prevention of well-known risk factors has the potential to prevent most premature cases of myocardial infarction.

In recent years, an important conceptual advance has been introduced. The focus is now no longer exclusively on adverse effects of risk factors, but also on protective effects of favourable levels of all readily measured modifiable major risk factors. Low-risk persons are rare in the general population and therefore research on the impact of low risk requires following large cohorts on a long-term basis. Available data indicate that for low risk substrata, CVD, and particularly IHD, is rare and endemic, not epidemic, throughout adulthood (Palmieri et al., 2006).

Quantitative risk assessment is possible

The global absolute cardiovascular risk is the best way to assess cardiovascular risk in persons who have no recognized clinical manifestations of atherosclerotic disease. The use of this indicator takes into account the multifactorial aetiology of CVD. Knowing some risk factors (sex, age, cholesterol, systolic blood pressure, smoking) it is possible to estimate the probability to experience a major cardiovascular event in the following ten years. Furthermore, the global absolute CVD risk makes the assessment objective, accurate and comparable over time.

To carry out this risk assessment, the 2007 European Guidelines on CVD Prevention (Fourth Joint Task Force, 2007) used the SCORE system (Conroy et al., 2003). See The SCORE risk chart as an example.

Primary prevention is aimed at lifestyle interventions and health-promoting environments

Primary prevention of IHD focuses on lifestyle issues, notably smoking, nutrition and physical exercise.

Concerning smoking, there are three issues: stimulating smokers to stop, preventing young people to start, and protecting non-smokers against exposure to tobacco smoke. Raising taxes, media campaigns and individual support have been shown effective as interventions to reduce smoking. For the latter, the primary care setting as well as the school setting are important. In the Tobacco control scale, countries are rated according to their accomplishment on the following five elements of tobacco control policies:

• Warnings on tobacco packages
• Price increases by increasing taxes
• Smoke-free working areas, public places and restaurants
• Information and public campaigns
• Advertising bans

See also the EUphacts Smoking and Smoking policies.

In the area of nutrition, effective interventions include information and education, measures related to the availability of certain food items in schools, etc., and challenges towards industry to develop healthier food products. The core issue is making the healthy choice the easy choice.

Also for physical exercise, interventions combine campaigns to enhance physical exercise with measures that create an environment which stimulates people to be more physically active. See also the EUphact on Physical activity.

Successful campaigns aimed at neighborhoods (e.g. of low average educational level), schools or in primary care, often combine the focus on the various lifestyle issues.

Secondary prevention targets cholesterol, hypertension, and overweight

For high cholesterol and hypertension (high blood pressure), secondary prevention includes the detection of cases, either in the general population or in high-risk groups. The latter would include those with a familial history of CVD, persons having diabetes or overweight, or smokers above a certain age. Treatment of the condition should consider the entire spectrum of CVD risk factors. Medication can lower (total) cholesterol by 20-50%, resulting a decrease in IHD incidence up to 30%. See also the EUphact Blood pressure.

The ‘European Guidelines on cardiovascular disease prevention in clinical practice’ emphasizes the importance of healthy lifestyles in people with an enhanced risk of developing CVD. It indicates cholesterol-lowering medication when lifestyle changes are not sufficiently effective (De Backer et al., 2003). It also advises medication when a risk assessment based on the risk factor profile calculation in SCORE indicates a more than 5% increased risk of developing CVD during the coming 10 years.

Interventions in overweight and obese people focus on improving dietary habits and physical exercise. Since short-term effects are often not consolidated, long-term strategies are advocated, as well as an integrated approach. See also EUphact Overweight.

Many diagnostic possibilities exist

A doctor can make use of the following tools when diagnosing coronary heart disease:

• Anamnesia (disease history)
• Irregularities on the (physical exertion-)electrocardiogram (ECG)
• Echocardiography or other picture-forming examination
• Heart-catheterisation (coronary angiogram)
• Coronary angiography: to determine the location of the blockage
• Blood test when a heart attack is suspected: the presence of enzymes such as creatinine kinase and/or lactate dehydrogenase in serum are indicative of an acute heart attack. Currently testing for the presence of the protein troponin in serum is the standard method to identify death (necrosis) of heart tissue.

Surgical treatment is either declining or stabilising in most of Europe

For both heart attack and angina pectoris the most common treatments are:

• PTCA (percutaneous transluminal coronary angioplasty), to dilate the arterial constriction
• Medication, by thrombolytics (to dissolve the blood clots), beta-blocking agents, ACE (angiotensin-converting enzyme)-inhibitors, aspirin and cholesterol-lowering medication especially statins.
• Surgery: bypass surgery or coronary artery bypass grafting (CABG).

PTCA and bypass operations (CABG) are the most common types of invasive operations carried out (Boersma et al., 2002). It is estimated that almost 80% of patients with an acute heart attack require an invasive operation. Of those patients (figures for Western Europe in 2002), 57% received a PTCA treatment, 21% a bypass operation, and 21% exclusively a medicinal treatment. Trends in the volume of surgical and percutaneous procedures show that the growth of coronary surgery in 12 European countries subsided in the mid 1990s, whereas percutaneous (non-surgical) intervention rates are rising in all countries (Simoons, 2003).

Treatment of IHD has contributed to improved survival

The prognosis for coronary heart disease has improved in the past decades. The two-year death rates for Swedish patients with unstable angina pectoris, for example, dropped from 30% in 1988 to 19% in 1995 (Abrahamsson et al., 2000). Research in the United States has shown that a positive outcome is now more common for heart attack patients (Hellermann et al., 2002).

There are remarkable differences between countries in the numbers and proportions of medical procedures carried out in relation to coronary heart disease (Boersma et al., 2002). There is, on the other hand, no clear relationship between the number of medical procedures performed and the death rate for coronary heart disease. On the whole, however, the recent decline in the death rate in Western Europe and the United States appears to be substantially (around 40%) attributable to improvements in the treatment of coronary heart disease (Kesteloot et al., 2006).

A similar observation comes from the MONICA project: around two-thirds of the decline in CHD mortality during the MONICA period was ascribed to a decline in CHD incidence rates and the remaining one-third of the decline was ascribed to improvements in survival because of better treatments (Tunstall-Pedoe et al., 1999; Kuulasmaa et al., 2000; Tunstall-Pedoe et al., 2000).

Similar results were found in England and Wales between 1981 and 2000 (Unal et al., 2005) where approximately half the falls in IHD deaths could be attributed to primary prevention: reductions in the three major risk factors in people without recognized IHD. Primary prevention had a bigger impact on mortality that did secondary prevention.

New developments in diagnostics and treatment

In recent years there have been many developments in the diagnostics and treatments for coronary heart disease, including faster diagnosis and treatment without hospitalisation:

• Extension of equipment of ambulances with e.g. an ECG monitor.
• Increasing availability of defibrillators in public places (shopping centres, airports, football stadiums).
• Improved treatment in acute state of the disease: increasing numbers of patients receive percutaneous treatment in the acute stage of an infarction

Smoking

Physical activity

Blood pressure

Diabetes

Alcohol use

Alcohol policies

Overweight

Smoking policies

Diabetes prevention and care

EHN European cardiovascular disease statistics

HFA-DB European health for all database

EHN European Heart Network

Escardio European Society of Cardiology

Attack rates and case fatality of coronary events in Italy for men and women, 1998-1999, ages 35-74 years

Rates of coronary events and case-fatality in a number of European countries, for men and women, over a 10-year period around 1990

Population characteristics of AMI/ACS registers in 14 European countries or regions

Case definitions of AMIC/ACS registers in 12 European countries or regions

Death by main cause for men and women in the EU-25, 2003

Trends in IHD mortality in six European regions, men aged 35-74 years, 1994-2003

Trend in IHD mortality in six European regions, women aged 35-74 years, 1994-2003

Trends in mortality from ischaemic heart disease for men, all ages, in selected countries, 1980-2006 (interactive)

Trends in mortality from ischaemic heart disease for women, all ages, in selected countries, 1980-2006 (interactive)

Trends in mortality from ischaemic heart disease for men, aged 25-64 years, in selected countries, 1980-2006 (interactive)

Trends in mortality from ischaemic heart disease for women, aged 25-64 years, in selected countries, 1980-2006 (interactive)

Association of risk factors with acute myocardial infarction for men and women

Ten-year risk of fatal cardiovascular disease in population at varying cardiovascular risk factor levels, for men and women

The data are collected by the Italian registry on cardiovascular diseases. Age-specific rates were calculated as estimated on each range divided by correspondent population per 10,000, where the estimated number of events was the result of the sum of estimated events for each single cause of death or hospital discharge.