Data from the INTERHEART study, a case-control study involving participants from 52 countries, also indicate that nine traditional factors may account for as much as 90% of population-attributable risk for myocardial infarction in men and 94% in women.¹ However, these figures should be interpreted with care and considered as rough estimates of a preventative potential embedded in the listed risk factors, and do not necessarily say anything about causal relationships.^2,3 Furthermore, case-control studies tend to inflate the impact of risk. Still, we need further improvements in risk prediction techniques and a better understanding of the basic mechanisms behind occurrences of cardiovascular disease. Certain events cannot be explained by the common risk factors.

Genetic Markers of Cardiovascular Disease
The rapid advances within genetics and vascular cell biology and atherosclerosis research have directed recent research interest towards the clinical usefulness of genetic factors as well as measurable biochemical and immunological markers. The INTERHEART study did not provide data on familial factors or novel biomarkers. It is well known that cardiovascular disease (CVD) and particularly coronary heart disease (CHD) runs in families. Long-term follow-up studies on the Swedish Twin Registry indicate that genetic influences are particularly important for premature death from CHD,⁴ and furthermore that heritability estimates indicate that the risk of dying from CHD can partly be attributed to genetic factors, with a heritability of 57% for men and 38% for women.⁵ The genetic influences on death from CHD were mediated through common risk factors to a greater extent among women than men.⁵ During recent years, several potentially important genes for CHD and myocardial infarction (MI) have been identified, applying various candidate gene approaches⁶ for the genes stromelycin-1 (5A-1171/6A), a metalloproteinase of the arterial wall,⁷ ALOX5AP and LTA4 in the leukotriene pathways^8,9 and TNFSF4 of the Ox40L, a pro-inflammatory cytokine,¹⁰ to mention just a few of the most challenging genes. The problems have been to confirm and replicate initial findings, most likely due to variations in study designs, end-point classifications and difference in population structures. However, more recent replications have been more successful through large-scale genome-wide associations by which novel chromosomal regions such as 9p21 have been identified and also related to CHD without being linked to traditional risk factors.^11,12 The prospects for these huge undertakings look promising, particularly with regard to unravelling novel mechanistic pathways, creating data for analyses of gene–environmental interactions and exploring potential routes towards the development of prodrugs, but the clinical utility for risk prediction remains to be seen.