From the Research
Introduction to Lipoprotein(a) [Lp(a)]
Lipoprotein(a) [Lp(a)] is a complex molecule with unique biological functions, playing a significant role in the inflammatory process and contributing to endothelial dysfunction, activation of monocytes, macrophages, and proliferation of smooth muscle cells, which promotes the development of atherosclerotic cardiovascular disease (ASCVD) 1.
Clinical Significance of Lp(a)
The clinical significance of Lp(a) lies in its role as a risk factor for ASCVD and its potential as a therapeutic target 2. Lp(a) has been found to have a causal and independent relationship with cardiovascular risk, and its levels are associated with calcific aortic valve stenosis 2, 3.
Mechanisms of Lp(a) in ASCVD
Lp(a) exerts its atherogenic effects through several mechanisms, including proinflammatory effects mediated by oxidized phospholipids, and its role in cholesterol accumulation in the arterial wall 2, 4. The atherogenicity of Lp(a) is considered to be higher than that of low-density lipoprotein (LDL) on a per-particle basis 4.
Measurement and Interpretation of Lp(a) Levels
Measurement of Lp(a) levels poses challenges due to the absence of a definitive reference method, and different assays report Lp(a) values as molar or mass concentrations 2. Despite these challenges, Lp(a) measurement is recommended to refine cardiovascular risk in specific clinical settings, such as in individuals with a family history of premature ASCVD or in patients with ASCVD not explained by standard risk factors 2.
Management of High Lp(a) Levels
Patients with high Lp(a) levels should be managed with more intensive approaches to treat other modifiable cardiovascular risk factors 2. Available lipid-lowering agents have a moderate impact on Lp(a) levels, and potent Lp(a)-lowering treatments that target LPA expression are under development 2, 3.
Treatment and Therapies
Among available therapies, antibody proprotein convertase subtilisin/kexin type 9 inhibitors are the most effective in reducing Lp(a) levels 2. However, there are still no specific approved therapies that reduce Lp(a) levels, and further research is needed to develop effective treatments for managing Lp(a)-associated risk 1, 5.
Caveats and Considerations
It is essential to consider the complex bidirectional relationship between Lp(a) and inflammation, as well as the genetic character of Lp(a) levels, which persist largely unchanged throughout life 1. The identification of high Lp(a) levels offers the opportunity to screen family members and develop more personalized approaches to managing cardiovascular risk 1.
Differential Diagnosis
In differential diagnosis, it is crucial to consider other risk factors for ASCVD and aortic valve stenosis, and to evaluate Lp(a) levels in the context of overall cardiovascular risk assessment 2, 3.
Conclusion
In conclusion, Lp(a) is a significant risk factor for ASCVD and aortic valve stenosis, and its measurement and management are crucial for refining cardiovascular risk assessment and developing personalized treatment strategies 1, 2, 3, 5, 4.