Dear Editor,
We were intrigued by the study conducted by Björnson et al. Reference Björnson, Adiels and Taskinen1 which highlighted the considerably higher atherogenicity of lipoprotein[a] (Lp[a]) compared to low-density lipoprotein. The researchers employed a unique technique to measure the concentration of Lp[a] in patients, addressing the challenge of accurately measuring Lp[a] due to the repetitive structure of its component, apolipoprotein[a] (apo[a]). Each apo[a] is covalently bound to an apo[B] molecule on low-density lipoprotein particles to form Lp[a]; therefore, quantifying the contained apo[B] enabled them to measure Lp[a] indirectly. This approach allowed them to determine the relative atherogenicity of apo[B] in Lp[a] versus low-density lipoprotein. The results revealed a significant disparity in atherogenicity between Lp[a] and low-density lipoprotein, with Lp[a] being 6.6 times more atherogenic per particle compared to low-density lipoprotein. Reference Björnson, Adiels and Taskinen1
Lp[a] is a complex plasma lipoprotein like low-density lipoprotein, but with the addition of apo[a]. Apo[a] is a protein like plasminogen that is covalently bonded to the apolipoprotein B-100 (apoB-100) of an low-density lipoprotein particle. Reference Ugovšek and Šebeštjen2 The serum levels of Lp[a] are primarily determined by genetic factors rather than lifestyle choices. Understanding the relative atherogenicity of Lp[a] and low-density lipoprotein holds crucial implications for risk assessment and therapeutic interventions in coronary heart disease. Studies have shown that elevated Lp[a] levels are independently linked to an increased risk of cardiovascular disease regardless of traditional risk factors. Reference Wang, Li, Li and Liu3,Reference Ellis, Pang and Chieng4 This establishes Lp[a] as a significant risk factor for multiple cardiovascular endpoints, each with varying levels of association. Additionally, individuals with high levels of both Lp[a] and low-density lipoprotein, such as those with familial hypercholesterolaemia, are at an even greater risk of cardiovascular events. Reference Wang, Li, Li and Liu3 This highlights the importance of comprehensive risk assessment in clinical practice. A study conducted by Wohlfahrt et al. Reference Wohlfahrt, Jenča and Melenovský5 found an association between mortality and recurrent cardiovascular events after myocardial infarction, both in individuals with high and very low levels of Lp[a]. The association of low Lp[a] levels with increased mortality raises interesting questions that warrant further research. Reference Wohlfahrt, Jenča and Melenovský5 Apart from its role in atherosclerosis, Lp[a] also has prothrombotic effects.
Traditional lipid-lowering therapies, such as statins, ezetimibe, nicotinic acid, and lipoprotein apheresis, have limited effectiveness in lowering Lp[a] levels. In fact, statin therapy is associated with increased Lp[a] levels, making Lp[a] an even stronger predictor of cardiovascular events in patients on this therapy. Reference Feng, Li and Xue6 Therefore, there is a pressing need for more effective and safer treatments. Recently, emerging therapies specifically aimed at lowering Lp[a] levels have garnered significant attention. One such approach involves using antisense apo[a] and/or apo[B] inhibitors to suppress the production of atherogenic proteins in the liver. Reference Lippi, Favaloro and Sanchis-Gomar7 This novel approach has the potential to significantly lower Lp[a] levels by 35–80%, with the added decrease if low-density lipoprotein levels by 6–16%. Reference Lippi, Favaloro and Sanchis-Gomar7 thereby mitigating cardiovascular risk.
In conclusion, recent evidence emphasises the importance of addressing elevated levels of Lp[a] as a major target for managing cardiovascular disease. Since Lp[a] levels remain stable throughout life and are primarily determined by genetics, it is advisable to measure Lp[a] at least once in the lifetime of all individuals. This can provide a more accurate evaluation of cardiovascular disease risk, enabling the initiation of a more effective therapeutic approach. This would be a significant stride towards preventing the estimated 29% of global deaths caused by cardiovascular disease.
