Increased cardiovascular risk associated with hyperlipoproteinemia (a) and the challenges of current and future therapeutic possibilities

Özet

Population, genetic, and clinical studies demonstrated a causative and continuous, from other plasma lipoproteins independent relationship betweenelevated plasma lipoprotein (a) [Lp(a)] concentration and the development of cardiovascular disease (CVD), mainly those related to atheroscleroticCVD, and calcific aortic stenosis. Currently, a strong international consensus is still lacking regarding the single value which wouldbe commonly used to define hyperlipoproteinemia (a). Its prevalence in the general population is estimated to be in the range of 10%–35% inaccordance with the most commonly used threshold levels (>30 or >50 mg/dL). Since elevated Lp(a) can be of special importance in patients withsome genetic disorders, as well as in individuals with otherwise controlled major risk factors, the identification and establishment of the propertherapeutic interventions that would lower Lp(a) levels and lead to CVD risk reduction could be very important. The majority of the classical lipidloweringagents (statins, ezetimibe, and fibrates), as well as nutraceuticals (CoQ10 and garlic), appear to have no significant effect on its plasmalevels, whereas for the drugs with the demonstrated Lp(a)-lowering effects (aspirin, niacin, and estrogens), their clinical efficacy in reducing cardiovascular(CV) events has not been unequivocally proven yet. Both Lp(a) apheresis and proprotein convertase subtilisin/kexin type 9 inhibitorscan reduce the plasma Lp(a) by approximately 20%–30% on average, in parallel with much larger reduction of low-density lipoprotein cholesterol(up to 70%), what puts us in a difficulty to conclude about the true contribution of lowered Lp(a) to the reduction of CV events. The most recentadvancement in the field is the introduction of the novel apolipoprotein (a) [apo(a)] antisense oligonucleotide therapy targeting apo(a), which hasalready proven itself as being very effective in decreasing plasma Lp(a) (by even >90%), but should be further tested in clinical trials. The aim ofthis review was to present some of the most important accessible scientific data, as well as dilemmas related to the currently and potentiallyin the near future more widely available therapeutic options for the management of hyperlipoproteinemia (a). (Anatol J Cardiol 2020; 23: 60-9)