Lipoprotein(a): Bridging the Gap Between Screening and Treatment—A Narrative Review

Atherosclerotic cardiovascular disease (ASCVD) has been screened for decades using the traditional lipid profile, with by far the most emphasis on low-density lipoprotein-cholesterol (LDL). Even though more recent studies have suggested that there might be more to atherosclerosis than LDL, with inflammation and immune processes being some of the possible culprits, solid recommendations still haven’t been made regarding the potential use of other biomarkers. Most of the research has focused on Lipoprotein(a) [Lp(a)], an independent cardiovascular (CV) risk factor, with involvement in the progression of atherosclerosis, yet dramatically underused in clinical practice. This review aims to highlight the reasons for the lack of Lp(a) screening in clinical practice and to address these potential limitations. The study also reviews current screening and treatment methods and explores the hypothesis that proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9-i) provide CV benefits due to a reduction in Lp(a), rather than LDL. A comprehensive review of the literature was conducted to assess the role of Lp(a) in cardiovascular disease risk, compare its predictive value to traditional lipid markers, and evaluate different measurement techniques, including mass spectrometry and immunoassays. Additionally, the review examined both current treatment strategies and emerging therapeutic approaches, such as gene-silencing therapies, that may offer new possibilities for managing elevated Lp(a) levels. One in four clinicians does not routinely check Lp(a) levels, which proves a lack of awareness amongst them. The reasons for that are implying that the cost is too high and that available treatments are scarce. The traditional lipid profile, including LDL, high-density lipoprotein (HDL) and triglycerides, continues to be the gold standard for CV risk assessment. However, Lp(a) has emerged as a potential biomarker for ASCVD, particularly in patients with high baseline levels or in patients who continue to develop CV events, despite having controlled LDL levels. One limitation of using Lp(a) in clinical practice is the significant variability in apo(a) sizes, which results from the presence of multiple isoforms determined by the number of kringle domains. This structural diversity poses challenges in standardizing measurement methods, affecting the accuracy and comparability of results. While statins have minimal impact on Lp(a), PCSK9-i lower its levels by 20-25%, although this class is not prescribed primarily for this reason. Lastly, gene-silencing therapies, which achieve the most reduction in Lp(a) levels, are still in phase III trials, and there is still a need to examine whether the reduction translates into CV benefits. Currently, there is more than one challenge that needs to be addressed when it comes to the use of Lp(a) as a reliable biomarker. Among them, the most mentioned in the literature are the lack of standardization and the absence of data to support a treatment. This should not discourage further research, because ASCVD’s complexity requires a more tailored approach. Current lipid-lowering therapy still fails in a minority of cases, as evidenced by new-onset cardiovascular events in patients with well-controlled LDL levels. There is a need for future interventional studies to assess whether the reduction in Lp(a) by PCSK9-i really translates into CV benefits, independent of LDL.