Lipoprotein(a) and Cardiovascular Risk in Asian Populations: A Comprehensive Review
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Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein particle that plays a causal role in atherosclerotic cardiovascular disease (ASCVD), ischemic stroke, and calcific aortic valve stenosis. Structurally similar to low-density lipoprotein, Lp(a) contains apolipoprotein(a) [apo(a)], which imparts unique atherogenic properties. Although Lp(a) levels vary significantly by ethnicity, East Asians generally have lower median concentrations, attributed to a higher frequency of large apo(a) isoforms and fewer high-risk LPA gene variants. However, even modest elevations in Lp(a) are associated with increased ASCVD risk in Asians, especially among high-risk populations. Observational studies from Asian populations have shown that elevated Lp(a) levels are linked to coronary artery calcification, myocardial infarction, stroke, and recurrent cardiovascular events. Novel therapeutic agents, including proprotein convertase subtilisin/kexin type 9 inhibitors, inclisiran, and antisense oligonucleotides such as pelacarsen, have demonstrated promising effects in lowering Lp(a). These therapies are currently under investigation in outcome trials, including Asian subgroups. Given the high burden of cardiovascular disease and ethnic variability in Lp(a) distribution and genetic determinants, routine measurement of Lp(a) could improve risk stratification and therapeutic decision-making. This review summarizes current evidence regarding the epidemiology, genetic background, clinical relevance, and emerging therapeutic strategies targeting Lp(a) in Asian populations, highlighting the need for population-specific thresholds and further research to guide clinical practice.
Abstract
Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein particle that plays a causal role in atherosclerotic cardiovascular disease (ASCVD), ischemic stroke, and calcific aortic valve stenosis. Structurally similar to low-density lipoprotein, Lp(a) contains apolipoprotein(a) [apo(a)], which imparts unique atherogenic properties. Although Lp(a) levels vary significantly by ethnicity, East Asians generally have lower median concentrations, attributed to a higher frequency of large apo(a) isoforms and fewer high-risk LPA gene variants. However, even modest elevations in Lp(a) are associated with increased ASCVD risk in Asians, especially among high-risk populations. Observational studies from Asian populations have shown that elevated Lp(a) levels are linked to coronary artery calcification, myocardial infarction, stroke, and recurrent cardiovascular events. Novel therapeutic agents, including proprotein convertase subtilisin/kexin type 9 inhibitors, inclisiran, and antisense oligonucleotides such as pelacarsen, have demonstrated promising effects in lowering Lp(a). These therapies are currently under investigation in outcome trials, including Asian subgroups. Given the high burden of cardiovascular disease and ethnic variability in Lp(a) distribution and genetic determinants, routine measurement of Lp(a) could improve risk stratification and therapeutic decision-making. This review summarizes current evidence regarding the epidemiology, genetic background, clinical relevance, and emerging therapeutic strategies targeting Lp(a) in Asian populations, highlighting the need for population-specific thresholds and further research to guide clinical practice.