Lipid Conundrum: Lp(a)-Not So Little in Lipid Therapeutics

With the discovery of low-density lipoprotein (LDL) receptor in 1980s much of the therapeutic developments have had a robust influence in LDL-c reduction and guidelines globally have documented targets for LDL-c and other lipoproteins. Despite the advances, the risk for atherosclerotic cardiovascular disease (ASCVD) remains high globally and the prevalence of ASCVD has increased since 1990 from 271 million to 523 million in 2019. With time it has become evident that at any level of LDL-c, ASCVD events rate are a 2-3 fold risk higher, when lipoprotein little a Lp(a) level is elevated. Furthermore, the ASCVD risk from elevated Lp(a) has been demonstrated to be similar in magnitude to each of the established major risk factors (hypercholesterolemia, smoking, hypertension, diabetes, etc.). It means unlike other established risk factors, but like homozygous familial hypercholesterolemia, Lp(a) levels influence atherogenicity from birth. Since 24% of the world's population (1.891 billion) is in South Asia (India, Pakistan, Afghanistan, Nepal, Bangladesh, and Sri Lanka) and Indians do tend to elicit ASCVD 5-10 years earlier than other populations; clinicians in this geography may be prudent to consider intervention without waiting given the early incidence of disease and the high burden of illness in this geography. There are no approved medications for lowering Lp(a), but medications have been demonstrated to modulate Lp(a). Except for statins most currently available hypolipidemic agents demonstrate mixed and perhaps ambiguous effects on Lp(a). Emerging nucleic acid-based therapies allow for selective gene silencing, thus preventing the production of proteins that may cause or enhance ASCVD. This review summarise available scientific knowledge and progress made in understanding Lp(a) and the current research that is in works of planned with newer therapeutics.