Fast track — ArticlesEffect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study
Introduction
Worldwide, cardiovascular disease is estimated to be the leading cause of death and loss of disability-adjusted life years.1 Although age-adjusted cardiovascular death rates have declined in several developed countries in past decades, rates of cardiovascular disease have risen greatly in low-income and middle-income countries,1, 2 with about 80% of the burden now occurring in these countries. Effective prevention needs a global strategy based on knowledge of the importance of risk factors for cardiovascular disease in different geographic regions and among various ethnic groups.
Current knowledge about prevention of coronary heart disease and cardiovascular disease is mainly derived from studies done in populations of European origin.2 Researchers are unsure to what extent these findings apply worldwide. Some data suggest that risk factors for coronary heart disease vary between populations—eg, lipids are not associated with this disorder in south Asians,3 and increases in blood pressure might be more important in Chinese people.4 Even if the association of a risk factor with coronary heart disease is similar across populations, prevalence of this factor might vary, resulting in different population attributable risks (PAR)—eg, serum cholesterol might be lower in Chinese populations.4 On the other hand, these apparent variations between ethnic populations could be attributable to differences between studies in their design and analysis, information obtained, and small sample sizes.
To clarify whether the effects of risk factors vary in different countries or ethnic groups, a large study undertaken in many countries—representing different regions and ethnic groups and using standardised methods—is needed, with the aim to investigate the relation between risk factors and coronary heart disease. Such a study could also estimate the importance of known risk factors on the PAR for acute myocardial infarction. This aim, however, needs either very large cohort trials or case-control studies with many events—eg, several thousands of cases of myocardial infarction in whom all (or most) currently known risk factors are measured. We judged the latter most practical.
INTERHEART is a large, international, standardised, case-control study, designed as an initial step to assess the importance of risk factors for coronary heart disease worldwide (slides available at http://www.phri.ca/interheart).5 We aimed to include about 15000 cases and a similar number of controls from 52 countries, representing all inhabited continents. Specific objectives are to determine the strength of association between various risk factors and acute myocardial infarction in the overall study population and to ascertain if this association varies by geographic region, ethnic origin, sex, or age. A key secondary objective is to estimate the PAR for risk factors and their combinations in the overall population and in various subgroups. This report focuses on the association of nine easily measured protective or risk factors (smoking, lipids, self-reported hypertension or diabetes, obesity, diet, physical activity, alcohol consumption, and psychosocial factors) to first myocardial infarction.
Section snippets
Participants
Study participants were recruited from 262 centres from 52 countries in Asia, Europe, the Middle East, Africa, Australia, North America, and South America (webtable 1; http://image.thelancet.com/extras/04art8001webtable1.pdf). The national coordinator selected centres within every country on the basis of feasibility. To identify first cases of acute myocardial infarction, all patients (irrespective of age) admitted to the coronary care unit or equivalent cardiology ward, presenting within 24 h
Results
Between February, 1999, and March, 2003, 15152 cases and 14820 controls were enrolled. 1531 cases were diagnosed as having unstable angina, 260 had insufficient data, 205 did not have coronary artery disease, and 695 had a previous myocardial infarction. For 74 controls data were missing and 109 had previous coronary heart disease. Therefore, 12461 cases and 14637 controls are included in the analysis. Table 1 shows the distribution of participants by region and ethnic origin. 9459 cases (76%)
Overall effect of risk factors
Table 3 provides the overall odds ratios for individual risk factors adjusted for age, sex, smoking status, and region and by multivariate adjustment for all risk factors. All risk factors were significantly (p<0·0001) related to acute myocardial infarction, except alcohol, which had a weaker association (p=0·03). After multivariate analysis, current smoking and raised ApoB/ApoA1 ratio (top vs lowest quintile) were the two strongest risk factors, followed by history of diabetes, hypertension,
Cumulative effect of risk factors
Figure 2 shows the effect of multiple risk factors on increased risk of myocardial infarction. Together, current smoking, hypertension, and diabetes increased the odds ratio for acute myocardial infarction to 13·01 (99% CI 10·69–15·83) compared to those without these risk factors, and they accounted for 53% of the PAR of acute myocardial infarction. Addition of ApoB/ApoA1 ratio (top vs lowest quintile) increased the odds ratio to 42·3 (33·2–54·0), and the PAR for these four risk factors
Risk in men and women
Figure 4 presents odds ratios and PARs for risk of acute myocardial infarction in men and women. Similar odds ratios were recorded in women and men for the association of acute myocardial infarction with smoking, raised lipids, abdominal obesity, composite of psychosocial variables, and vegetable and fruit consumption. However, the increased risk associated with hypertension and diabetes, and the protective effect of exercise and alcohol, seemed to be greater in women then in men (figure 4).
Risk by age
Smoking, adverse lipid profile, hypertension, and diabetes had a greater relative effect on risk of acute myocardial infarction in younger than older individuals (table 5). Overall, abnormal lipids was the most important risk factor with respect to PAR in both young and old individuals (table 5). Collectively, the nine risk factors accounted for a significantly greater (p<0·0001) PAR in younger than older individuals; these patterns were consistent in males and females.
Regional and ethnic variations in importance of risk factors
When the odds ratio (adjusted for age, sex, smoking, and geographic region) for association of acute myocardial infarction with a risk factor is around 2 or more, eg, for smoking, lipids, hypertension, diabetes, abdominal obesity, and the combined psychosocial index, subgroup analyses are likely to be fairly robust. We recorded a clear, significant, and consistent excess risk of acute myocardial infarction associated with these risk factors in most regions of the world and in every ethnic group
Population attributable risk by geographic region
Table 4 also presents overall PARs and values by sex across different geographic regions. In all regions, the nine risk factors account for between three-quarters and virtually all the PAR for acute myocardial infarction. The relative importance of every risk factor varied, and was largely related to its prevalence. However, raised lipids, smoking, and psychosocial factors were the most important risk factors in all regions in the world. It is noteworthy that in western Europe, North America,
Consistency of results
Subgroup analyses with both types of controls (hospital-based and community-based) showed consistent odds ratios for current smoking (hospital-based 3·1 vs community-based 2·8), for the top quintile versus lowest quintile of lipids (4·2 vs3·9), for diabetes (2·7 vs3·4), for hypertension (2·1 vs3·0), for abdominal obesity (1·7 vs1·9), for psychosocial factors (1·6 vs1·5), for consumption of fruits (0·78 vs0·93) and vegetables (0·78 vs0·83), for regular physical activity (0·79 vs0·79), and for
Family history
Family history of coronary heart disease was associated with an odds ratio of 1·55 (99% CI 1·44–1·67), adjusted for age, sex, smoking, and geographic region. Adjustments for the nine previously described risk factors slightly reduced the odds ratio to 1·45 (1·31–1·60). The PAR was 12·0% (99% CI 9·2%–15·1%), which fell to 9·8% (7·6–12·5) after full adjustment. However, when family history is added to the information from other nine risk factors, the overall PAR rose from 90·4% to only 91·4%,
Repeat measures
Repeat measures of risk factors were made in 279 controls at a median interval of 409 days. The agreement rates for smoking (Cohen's kappa16 κ=0·94), history of diabetes (κ=0·90), ApoB/ApoA1 (intraclass correlation=0·74), hypertension (κ=0·82), depression (κ=0·44), abdominal obesity (intraclass correlation=0·68), regular physical activity (κ=0·56), and consumption of fruits (κ=0·66), vegetables (κ=0·52), and alcohol (κ=0·52) were high to moderate. These data suggest that the association of
Discussion
Our study shows that nine easily measured and potentially modifiable risk factors account for an overwhelmingly large (over 90%) proportion of the risk of an initial acute myocardial infarction. The effect of these risk factors is consistent in men and women, across different geographic regions, and by ethnic group, making the study applicable worldwide. The effect of the risk factors is particularly striking in young men (PAR about 93%) and women (about 96%), indicating that most premature
References (27)
- et al.
Risk factors for acute myocardial infarction in Indians: a case-control study
Lancet
(1996) - et al.
INTER-HEART: a global study of risk factors for acute myocardial infarction
Am Heart J
(2001) - et al.
Association of psychosocial risk factors with risk of acute myocardial infarction in 11119 cases and 13648 controls from 52 countries (the INTERHEART study): case-control study
Lancet
(2004) - et al.
High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study
Lancet
(2001) - et al.
Blood pressure, stroke, and coronary heart disease: part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias
Lancet
(1990) - et al.
Global burden of cardiovascular diseases, part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization
Circulation
(2001) - et al.
Global burden of cardiovascular diseases, part II: variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies
Circulation
(2001) - et al.
Coronary heart disease attack rate, incidence and mortality 1975–1994 in Gŝteborg, Sweden
Eur Heart J
(1997) - et al.
International Federation of Clinical Chemistry Standardization Project for Measurements of Apolipoproteins A-1 and B: IV comparability of apolipoprotein B values by use of International Reference Material
Clin Chem
(1994)
International Federation of Clinical Chemistry Standardization Project for Measurements of Apolipoprotein A-1 and B: III comparability of apolipoprotein A-1 values by use of International Reference Material
Clin Chem
The distribution of Levin's measure of attributable risk
Biometrika
Cited by (9168)
Sex differences in patients presenting with acute coronary syndrome: a state-of-the-art review
2024, Current Problems in CardiologyEffects of childhood obesity on heart failure and its associated risk factors in the European population: A Mendelian randomization study
2024, Nutrition, Metabolism and Cardiovascular DiseasesTraditional risk factors and premature acute coronary syndromes in South Eastern Europe: a multinational cohort study
2024, The Lancet Regional Health - EuropeHeartfelt living: Deciphering the link between lifestyle choices and cardiovascular vitality
2024, Current Problems in CardiologyAcute psychological stress-induced progenitor cell mobilization and cardiovascular events
2024, Journal of Psychosomatic Research
Listed at end of paper