Lipoprotein(a) (Lp(a)) are LDL-like lipoprotein particles in which the lipids are bound to apolipoprotein(a)1. Approximately 5 percent of the population has a significantly elevated value of lipoprotein(a)2. Elevated Lp(a) levels are an independent, heritable risk factor for atherosclerotic cardiovascular disease as they are largely determined by variations in the Lp(a) gene encoding apo(a). Lp(a) has a negative impact on vascular inflammation, atherosclerotic lesions, endothelial function and thrombogenicity, which pathophysiologically leads to cardiovascular events.
Both Lp(a) and LDL contain 1 apolipoprotein B (apoB) per particle.
Standard antilipidemic therapies, such as statins, fibrates, and ezetimibe, have a modest effect on Lp(a) levels, although it is not yet clear whether such treatments may influence cardiovascular events and prognosis.
The purpose of the current genetic study published in Journal of the American College of Cardiology3 was to compare the atherogenic effect of Lp(a) with that of low-density lipoprotein (LDL), and then assess the risk of coronary heart disease in relation to the number of particles with apolipoprotein B. The study was based on data from a UK Biobank population .
The authors found that Lp(a) has a significantly higher atherogenic potential than LDL. For every 50 nmol/L increase in apolipoprotein B, the risk of cardiovascular disease was significantly higher for Lp(a) than for LDL, with an approximately sixfold higher atherogenicity observed for Lp(a) on a per-particle basis.
These findings highlight the relevance of monitoring Lp(a) levels as well as the importance of targeting Lp(a) in drug interventions. The authors write in their conclusion that Lp(a) represents a central target for drug-based intervention in a significant proportion of the risk population.
According to European guidelines, the Lp(a) value must be interpreted and treated in relation to other cardiovascular risk factors2. This means that lipoprotein(a) should not be measured alone without an assessment of total cardiovascular risk or other additional conditions.
According to a Norwegian article, the treatment of elevated Lp(a) is currently aimed at reducing modifiable cardiovascular risk factors, but Lp(a)-reducing drugs are being tested2. Studies of the effect of Lp(a) reduction on cardiovascular events are expected in 2024. Lp(a)-reducing treatment may then become relevant as additional treatment.