2024, Volume 31, Supplement 1: Lipoprotein(a) – advances in understanding

Raised lipoprotein(a) (Lp[a]) cholesterol is highly prevalent affecting 1 in 5 individuals and is also frequently associated with the inherited condition familial hypercholesterolaemia (FH).1 It is associated with an increased risk of atherosclerotic cardiovascular disease, stroke and peripheral arterial disease, independent of traditional cardiovascular risk factors.2 Accurate measurement of circulating Lp(a) levels is currently a challenge3 and there are no licensed pharmacotherapies available for the management and treatment of elevated Lp(a).4...

Lipoprotein(a) (Lp[a]) can improve the accuracy of assessment of atherosclerotic cardiovascular disease and the risk of aortic valve stenosis. Currently, there is no specific treatment to lower its circulating concentration. Raised Lp(a) is a feature of familial hypercholesterolaemia. Management of high levels encourages rigorous attention to correction of other risk factors, such as blood pressure, smoking and low-density lipoprotein (LDL)....

Genome-wide association and Mendelian randomisation studies have identified lipoprotein(a) (Lp[a]) as an emerging risk factor for calcific aortic stenosis and a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) in different ethnicities. Given that Lp(a) is predominantly genetically determined, blood levels are relatively stable over time. The European Atherosclerosis Society recommends Lp(a) measurement in all adults at least once during their lifetime unless a secondary cause is suspected, or a specific treatment is instituted at lower levels. HEART UK recommends Lp(a) measurement in specific ‘at-risk’ cohorts. A new risk calculator introduced in association with the 2022 European Atherosclerosis Society guidelines calculates global ASCVD risk with and without Lp(a) concentrations alongside traditional risk factors; it highlights the importance of measuring Lp(a) in individuals to identify those with high or very high levels. Clinical laboratories therefore need to deliver timely, accurate and standardised measurements of Lp(a). The development of a reference material (WHO/IFCC SRM-2B) to assign molar values to calibrators alongside immunoassays that minimise sensitivity to the effect of isoform size (e.g., Denka reagent) offers a reliable and consistent assessment of graded Lp(a)-associated ASCVD risk based on particle number, which is endorsed by the European Atherosclerosis Society and HEART UK....

Large-scale observational data have demonstrated a robust, independent association of elevated lipoprotein(a) (Lp[a]) levels with atherosclerotic cardiovascular disease (CVD), stroke, and peripheral artery disease. Elevated Lp(a) concentrations in patients with ischaemic heart disease have been linked to higher rates of peri-procedural myocardial infarction (MI) during percutaneous coronary intervention (PCI). This association could be attributed to the proatherogenic, proinflammatory, and potentially antifibrinolytic properties of the Lp(a) particle. In addition, there is an increased prevalence of high-risk plaque features, such as heavy macrophage infiltration, large necrotic lipid core, and thin-cap fibroatheromas in patients with elevated Lp(a) concentrations presenting with acute coronary syndrome. Despite growing evidence linking elevated Lp(a) to incident CVD, its association with recurrent ischaemic cardiovascular (CV) events has been less clear. Multiple observational studies have assessed the effect of elevated Lp(a) levels on major adverse cardiovascular events (MACE) and rates of restenosis in patients with previous PCI. This review summarises the available data on the modulatory effect of Lp(a) on plaque morphology and recurrent ischaemic events....

A raised level of lipoprotein(a) (Lp[a]) is gaining recognition worldwide as a significant and prevalent risk factor that can predispose affected individuals to premature and progressive cardiovascular disease (CVD). However, challenges remain with regards to the identification of patients with raised Lp(a) levels, limited treatment options and a lack of prospective evidence to support the therapeutic reduction of Lp(a) levels to prevent CVD. We hereby present real-world examples of patients with elevated Lp(a) concentrations as the underlying aetiology for atherosclerotic cardiovascular disease (ASCVD), illustrating the key principles of diagnosis and management to date....