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.