About half of all patients with ischaemic heart disease do not exhibit traditional risk factors.1 Therefore further gains in the control of ischaemic heart disease will require concerted efforts, and the necessary allocation of resources, for current research to evaluate new possible risk factors and preventive interventions. These concerted efforts should proceed on several fronts simultaneously. Basic researchers provide biological mechanisms and answer the crucial question of why an agent or intervention reduces disease or death. Clinicians provide benefits to affected patients through advances in diagnosis and treatment, and formulate hypotheses from their clinical experience. Epidemiologists and statisticians formulate hypotheses from basic, clinical, and descriptive epidemiological studies and test these hypotheses in prospective studies and, where appropriate, in randomised trials.

The ultimate goal of epidemiological studies is to establish whether a cause–effect relation exists between a putative risk factor and disease. Making such a judgement involves several steps, the first being to establish whether there is in fact a valid statistical association. To conclude that an association is valid, the potential role of chance, bias, and confounding must be ruled out. If a valid statistical association is present, the question then becomes: is it one of cause and effect? To render this judgement, the totality of evidence from all sources must be considered, including the strength and consistency of the association and the plausible biological mechanisms to explain the findings.2