The genetics of heart attacks

What implications do genetic studies have for the practice of cardiovascular medicine? Here is a two-part summary of the current state of affairs.

Clinical experience shows that the risk of atherosclerosis and heart attack is substantially codetermined by genetic factors. Monogenetic causes of atherosclerosis such as familial hypercholesterolaemia have a high level of penetration and expressivity; in some cases they are very well characterised and have also become identifiable through molecular diagnosis.

The case is different for the complex, polygenic causes of coronary disease. Their effects are limited in individual cases and are overlaid by lifestyle and environmental factors. For this reason, until recently it was difficult to identify such factors with certainty.

Methodological advances in recent years have made it possible to scan the entire human genome without hypotheses for genes associated with diseases by determining frequent sequence variants. These genome-wide association studies, as they are referred to, have led to the identification of over 20 genetic locations in which frequent sequence variants affect the risk of coronary disease.

The findings collected in this way produced new insights into the pathogenesis of atherosclerosis and may contribute to the definition of new therapies and to the individualisation of treatment.