Interheart Study

Prevention of cardiovascular disease: a worldwide core of nine risk factors for myocardial infarction

Yusuf S, Hawken S, Ounpuu S, et al, on behalf of the INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): casecontrol study. Lancet 2004;364:937-52.

Although more than 80% of the burden of cardiovascular disease occurs nowadays in lowand middle-income countries, knowledge about risk factors is mainly derived from developed
countries. INTERHEART was a large, international, standardised, case-control study of acute myocardial infarction (MI) that has been designed to assess the importance of risk factors for coronary heart disease worldwide. Participants were recruited in 52 countries representing all inhabited continents. The relation of nine risk factors (smoking, history of hypertension or diabetes, waist/hip ratio, dietary patterns, physical activity, alcohol consumption, blood apolipoproteins [Apo] and psychosocial factors) to first acute MI was determined for the overall study population and for subgroups defined by geographic region, ethnic origin, sex and age. Odds ratios for the association (risk factors to MI) and their population attributable risks (PAR) were calculated.

12 461 cases (patients admitted to hospital within 24 h of the onset of a first acute MI) and 14 637 controls (sex matched within 5 years of age with no previous diagnosis of heart disease or history of exertional chest pain), enrolled between February, 1999 and March, 2003, were included in the analysis. All factors taken individually were significantly (P<0.0001) related to acute MI, except alcohol which had a weaker association (P=0.03). After multivariate analysis, raised ApoB/ApoA1 ratio (odds ratio 3.25 for top vs lowest quintile, PAR 49.2% for top four quintiles vs lowest quintile) and smoking (2.87 for current vs never, PAR 35.7% for current and former vs never) were the two strongest risk factors (Table I).

Both showed a graded relation with the odds of MI, without a threshold or a plateau in the dose response. They were followed by psychosocial factors (2.67, PAR 32.5%), history of diabetes (2.37, PAR 9.9%), history of hypertension (1.91, PAR 17.9%) and abdominal obesity (1.62 for top vs lowest tertile, PAR 20.1% for top two tertiles vs lowest tertile). Addition of five risk factors, smoking, raised plasma
lipids, hypertension, diabetes, and abdominal obesity, presented by a large proportion of individuals, accounted for about 80% of the PAR. Collectively, all nine risk factors accounted for 90% of the PAR in men and 94% in women. Abnormal lipids had the highest PAR in both men (49.5%) and women (47.1%). In the subgroup analyses by age, abnormal lipids (as high ApoB/ApoA1 ratio >1 in the top quintile) presented the highest PAR in both young and old individuals. Strikingly, smoking, adverse lipid profile, hypertension and diabetes had a greater relative effect on risk of acute MI in younger than in older individuals, indicating that most
premature myocardial infarction is preventable. On the other hand, daily consumption of fruits and vegetables (odds ratio 0.70, PAR 13.7% for lack of daily consumption), alcohol consumption three or more times a week (0.91, PAR 6.7%) and regular moderate or strenuous exercise (0.86, PAR 12.2%) were protective. Together, daily consumption of fruits and vegetables, regular physical activity and avoidance of smoking conferred an odds ratio of 0.21 (0.17-0.25) suggesting that modification of these aspects of lifestyle could potentially reduce the risk of an acute MI by more than three-quarters compared with a smoker with a poor lifestyle.

The major risk factors (odds ratio of about 2 or greater on univariate analysis such as smoking,
abnormal lipids, psychosocial factors, hypertension, diabetes and abdominal obesity) were consistently adverse in all regions of the world and in all ethnic groups. The odds ratio for these risk factors were qualitatively similar despite variations in prevalence for risk factors in different subpopulations. Worldwide, the two most important risk factors were smoking and abnormal lipids, accounting for about two-thirds of the PAR of an acute MI. The nine risk factors together accounted for three-quarters to almost all the PAR for acute MI. It is noteworthy that in high-income countries, abdominal obesity was associated with a PAR greater than that associated with smoking (Table II).

These results suggest that the overall approach to prevention of coronary heart disease can be based on similar principles worldwide, with varying emphasis in different subgroups on the basis of the prevalence of individual risk factors and economic and cultural factors. Lifestyle modification is of substantial importance and has the potential to prevent most premature cases of MI.