• The enzyme PCSK9 binds to the hepatic LDL receptor and targets it for a intracellular degradation, leading to decreased number of LDL receptor on cells and reduced removal of circulating LDL cholesterol.

• The usefulness of circulating PCSK9 as a marker for risk of coronary heart disease in the general population remains unclear.

• In this large prospective population study, serum levels of PCSK9 were modestly associated with increased risk of myocardial infarction in age- and sex-adjusted analysis. However, after adjustment for LDL-C and other lipids, the strength of the association was largely attenuated.

• Our findings suggest that serum levels of PCSK9 do not contribute additional useful information in cardiovascular risk assessment beyond the information provided by lipid measurements.

• Moreover, our results are consistent with the biological understanding of PCSK9 and of its effect on atherosclerosis being mainly mediated by changes in LDL- receptor function.