RNA therapeutics
Elevated Lp(a) above 30 mg/dL affects 20-30% of the global population, a review of emerging Lp(a)-lowering therapies (Curr Opin Endocrinol Diabetes Obes 2016)
Original title: Lipoprotein(a): novel target and emergence of novel therapies to lower cardiovascular disease risk
This review by Tsimikas summarises evidence establishing Lp(a) as a cardiovascular risk factor, noting Lp(a) above 30 mg/dL affects 20-30% of the global population, with no specific Lp(a)-lowering therapy yet available. Three lines of evidence, epidemiologic studies and meta-analyses, genome-wide association studies, and Mendelian randomisation studies, support elevated Lp(a) as a causal, independent, genetic cardiovascular risk factor. Recent studies also found low Lp(a) is associated with higher risk of incident type 2 diabetes and high Lp(a) with lower risk, though this association does not appear causal. Novel therapies including PCSK9 inhibitors and antisense oligonucleotides blocking apolipoprotein(a) mRNA translation are emerging as substantial Lp(a)-lowering options, with trials underway to determine whether they reduce Lp(a) cardiovascular contribution.
Original abstract
Purpose Of Review: This article summarizes recent observations on the role of lipoprotein(a) [Lp(a)] as a risk factor mediating cardiovascular disease.
Recent Findings: Lp(a) is a highly prevalent cardiovascular risk factor, with levels above 30 mg/dl affecting 20-30% of the global population. Up until now, no specific therapies have been developed to lower Lp(a) levels. Three major levels of evidence support the notion that elevated Lp(a) levels are a causal, independent, genetic risk factor for cardiovascular disease: epidemiologic studies and meta-analyses, genome-wide association studies and Mendelian randomization studies. Recent studies also have noted that individuals with low levels of Lp(a) are associated with a higher risk of incident type 2 diabetes mellitus, and conversely individuals with high levels have a lower risk, but this association does not appear to be causal. Novel therapies to lower Lp(a) include PCSK9 inhibitors and antisense oligonucleotides directly preventing translation of apolipoprotein(a) mRNA.
Summary: With this robust and expanding clinical database, a reawakening of interest in Lp(a) as clinical risk factor is taking place. Trials are underway with novel drugs that substantially lower Lp(a) and may reduce its contribution to cardiovascular disease.
diabetesgeneticsPCSK9 inhibitionRNA therapeutics
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.