Effect of Potentially Modifiable Risk Factors Associated with Myocardial Infarction in 52 Countries: The INTERHEART Study

INTERHEART enrolled 15,152 cases of first acute MI and 14,820 matched controls across 52 countries representing every inhabited continent, creating the largest global case-control study of myocardial infarction risk factors. The study was designed to determine which modifiable risk factors explain global MI risk — and by what magnitude.

Nine modifiable risk factors accounted for 90% of population attributable risk (PAR) for MI in men and 94% in women. In order of PAR: ApoB/ApoA1 ratio (49.2%), smoking (35.7%), psychosocial factors (32.5%), abdominal obesity (20.1%), hypertension (17.9%), fruits and vegetables (protective, 13.7%), physical activity (protective, 12.2%), diabetes (9.9%), and alcohol (protective, 6.7%). The ApoB/ApoA1 ratio was the single most potent risk factor, with an OR of 3.25 for the highest versus lowest tertile.

The INTERHEART finding that the ApoB/ApoA1 ratio carries the highest population-attributable MI risk — greater than smoking, hypertension, diabetes, or obesity — places the atherogenic particle burden at the center of global cardiovascular risk. This was among the first large-scale epidemiological datasets to confirm that lipid risk is best captured by the apolipoprotein ratio rather than LDL-C, consistent with the biological principle that particle concentration and function, not cholesterol mass, drive atherogenesis.

The consistency of these nine risk factors across 52 countries — in men and women, old and young, across geographic, ethnic, and socioeconomic contexts — establishes that cardiovascular prevention can be built on a universal set of modifiable targets. There is no such thing as a population where these risk factors don’t apply.

We rate the evidence strong. The landmark INTERHEART case-control study in 29,972 participants across 52 countries demonstrating that nine modifiable risk factors — led by the ApoB/ApoA1 ratio — account for 90%+ of global MI risk, with remarkable consistency across all populations studied.