In the INTERHEART study roughly one quarter of the world’s countries provided between them some 15,000 cases of myocardial infarction and 15,000 controls. Questionnaires, physical examinations, and measurements on blood samples were used to elicit information which then went to Canada’s McMaster University in Hamilton, Ontario, for checking and analysis. The paper focuses on nine variables. Four were lifestyle factors (smoking, alcohol intake, [lack of] exercise and dietary fruit and vegetables); the other five were hypertension, diabetes, abdominal obesity, psychosocial factors, and lipid levels. Taken together, these nine factors accounted for 90.4% of the population attributable risk (PAR) for acute myocardial infarction. The PAR for lifestyle choices taken together was 54.6%. No family history, then? This did prove to be an independent risk factor, with a PAR of 10-12%, which puts it on a par with diabetes and not eating enough fruit and vegetables. However, family history made hardly any difference to the overall PAR because the burden it carried appears under other risk headings. For example, someone with a family history linked to one of the inherited lipid disorders would have that risk expressed in his or her own lipid levels, at least in part.

To label the INTERHEART results as merely confirmatory would be to neglect the reason behind the study. Professor Salim Yusuf, director of McMaster’s Population Health Research Institute, tells Science Watch that his interest in ethnicity and cardiovascular disease began about 15 years ago. People of South Asian origin but living in, say, North America or the U.K. had unexpectedly high heart-disease rates, while in Japan, where smoking is very popular, rates were low. Also there was the view "often unreferenced but claimed by many leading scientists, that currently known risk factors only explained 50% of the risk of heart disease." A key finding in INTERHEART, apart from the 90.4% PAR already mentioned, was the consistency of findings across very different regions of the world. The nine-factor PAR did slip to only 72.5% in Central and Eastern Europe but in the other nine world regions the range was remarkably narrow, 89.4-98.7%. Yusuf had expected greater ethnic variation in risk factors, "so the results truly surprised us."

Funding for a randomized trial of modifying all the INTERHEART factors (other than alcohol) is proving "a big challenge," Yusuf says, but he outlines for Science Watch readers ongoing work, prompted by the heart findings (#8), which is trying to look at what lies beneath the risks identified. There is FAMILY, a 10-year prospective study from birth of the interaction of genes and environment, which has as its endpoint atherosclerosis, a condition that can be detected in children. INTERHEART 2 looks at the gene/environment question too but via the families of patients and controls in the first study. The PURE study (Prospective Urban and Rural Epidemiology) is looking at societal transitions and health policies and has so far recruited 35,000 of the hoped-for 135,000 individuals in 15 countries. And, as if all that was not enough, the McMaster group and its international collaborators have now embarked on the pilot phase of INTERSTROKE, a study similar in design to INTERHEART.